This review seeks to explain four features of viral respiratory illnesses that have perplexed many generations of microbiologists: (1) the seasonal occurrence of viral respiratory illness; (2) the occurrence of respiratory illness year-round in the Tropics; (3) the rapid response of illness to temperature drops in temperate regions; (4) the explosive arrival and rapid termination of epidemics caused by influenza and other respiratory viruses. I discuss the inadequacy of the popular explanations of seasonality, and propose a simple hypothesis, called Temperature Dependent Viral Tropism (TD-VT), that is compatible with the above and other features of respiratory illness. TD-VT notes that viruses can often transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining the mobility of their hosts) and suggests that most endemic respiratory viruses accomplish this by developing thermal sensitivity, in the sense that they normally replicate rapidly only at temperatures below normal body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. I review biochemical and tissue-culture studies that found that “wild” respiratory viruses often show natural thermal sensitivity within a range that supports organ-specific tropism within the human body, and I discuss the evident tendency for viral strains to adapt their thermal sensitivity to their local climate and season. I also explore the possible misinterpretation of early experiments where volunteers were inoculated nasally with viral samples and then chilled. Next, I discuss the practical implications of the TD-VT hypothesis for preventing and treating respiratory illness. Finally, I note that the hypothesis is very testable and make suggestions for the most important experiments to increase our understanding of the seasonality and pathogenicity of viral respiratory illness.

The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of ‘checkpoint blockade’ and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient’s own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function. The production of extracellular adenosine is mediated by the cell surface ectoenzymes CD73, CD39 and CD38 and therapeutic agents have been developed to target these as well as the downstream adenosine receptors (A₁R, A_2AR, A_2BR, A₃R) to enhance anti-tumor immune responses. This review will discuss the role of adenosine and adenosine receptor signaling in tumor and immune cells with a focus on their cell-specific function and their potential as targets in cancer immunotherapy.

This review seeks to explain four features of viral respiratory illnesses that have perplexed generations of virologists: (1) the seasonal timing of respiratory illness; (2) the common viruses causing respiratory illness worldwide, including year-round disease in the Tropics; (3) the rapid response of outbreaks to weather, specifically temperature; (4) the rapid arrival and termination of epidemics caused by influenza and other viruses. The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called Temperature Dependent Viral Tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can transmit themselves more effectively if they moderate their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ-specific viral tropism within the human body, whereby they replicate most rapidly at temperatures below body temperature. This allows them to confine themselves to the upper respiratory tract and to avoid infecting the lungs, heart, gut etc. Biochemical and tissue-culture studies show that “wild” respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the existence of respiratory illness in the Tropics year-round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. The TDVT hypothesis has important practical implications for preventing and treating respiratory illness including Covid-19. TVDT is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

Nickel nitrate diammine, Ni(NH₃)₂(NO₃)₂, can be synthesised from the thermal decomposition of the nickel nitrate hexammine, Ni[(NH₃)₆](NO₃)₂. The hexammine decomposes in 2 distinct steps; the first releases 4 equivalents of ammonia while the second involves the release of NO_x, N₂ and H₂O to yield NiO. The intermediate diammine compound can be isolated following the first deammoniation step or synthesised as a single phase from the hexammine under vacuum. Powder X-ray diffraction (PXD) experiments have allowed the structure of Ni(NH₃)₂(NO₃)₂ to be solved for the first time. The compound crystallises in orthorhombic space group Pca2₁ (a = 11.0628 (5) Å, b = 6.0454 (3) Å, c = 9.3526 (4) Å; Z = 4) and contains 11 non-hydrogen atoms in the asymmetric unit. Fourier Transform Infrared (FTIR) spectroscopy demonstrates that the bonding in the ammine is consistent with the structure determined by PXD.

In the present paper we introduce three new classes of bi-univalent functions connected with Gregory coefficients. For functions in each of these three bi-univalent function classes we have derived the estimates of the Taylor--Maclaurin coefficients $\left|a_{2}\right|$ and $\left|a_{3}\right|$ and Fekete-Szeg\H{o} functional problems for functions belonging to these new subclasses. We defined three subclasses of the class of the bi-univalent functions $\Sigma$, namely $\mathfrak{HG}_{\Sigma}$, $\mathfrak{GM}_{\Sigma}(\mu)$ and $\mathfrak{G}_{\Sigma}(\lambda)$ by using the subordinations with the function whose coefficients are Gregory's numbers. First, we proved that these classes are not empty, i.e. contains other functions than the identity one. Using the well-known Carath\'eodory Lemma for the functions with real positive parts in the open unit disk, together with an estimation due to P. Zaprawa (see https://doi.org/10.1155/2014/357480) and another one of Libera and Zlotkiewicz, we gave upper bounds for the above mentioned initial coefficients and for the Fekete-Szeg\H{o} functionals. The main results are followed by some particular cases, and the novelty of the definitions and the proofs could involve further studies for such type of similarly defined subclasses.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

We aimed to test the hypothesis that serum 25-hydroxyvitamin D3 [25(OH)D] concentration is associated with mental health and life stress measures in young adults, and investigate sex and racial disparities in these associations. This study comprised 327 black and white participants. Depression, trait anxiety, perceived stress, and hostility were measured by validated instruments: Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS), and Cook-Medley Hostility Scale (CMHS). Linear regression was used to estimate correlations between serum 25(OH)D concentration and mental health measurements in total population and in subgroups stratified by sex and race. In this sample (28.2 ± 3.1 years, 48% male, 53% black), serum 25(OH)D concentration was negatively related to BDI, STAI, PSS, total CMHS score and the majority of CMHS subscale scores (p-values < 0.05). Stratified by sex, most of these associations remained significant only in women (p-values < 0.05). Stratified by race, higher 25(OH)D concentrations in the whites were significantly related to lower BDI, STAI, PSS, and CMHS-cynicism subscale (p-values < 0.05); 25(OH)D concentrations in the blacks were only inversely associated with CMHS and most CMHS subscales (p-values < 0.05), but not with BDI, STAI and PSS. We present novel findings of consistent inverse relationships between serum 25(OH)D concentration and various measures of mental health and life stress. Long-term interventional studies are warranted to investigate the roles of vitamin D supplementation in prevention and mitigation of depression, anxiety and psychological stress in young adults.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

Surface temperature influences human health directly and alters the biodiversity and productivity of the environment. While previous research has identified that the composition of urban landscapes influences the physical properties of the environment such as surface temperature, a generalizable and flexible framework is needed that can be used to compare cities across time and space. This study employs the Structure of Urban Landscapes (STURLA) classification combined with remote sensing of New York City’s (NYC) surface temperature. These are then linked using machine learning and statistical modeling to identify how greenspace and the built environment influence urban surface temperature. It was observed that areas with urban units composed of largely the built environment hosted the hottest temperatures while those with vegetation and water were coolest. Likewise, this is reinforced by borough-level spatial differences in both urban structure and heat. Comparison of these relationships over the period between2008 and 2017 identified changes in surface temperature that are likely due to the changes in prevalence in water, lowrise buildings, and pavement across the city. This research reinforces how human alteration of the environment changes ecosystem function and offers units of analysis that can be used for research and urban planning.

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality; we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle, and improving health, life and financial costs.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Cadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze dried bone allografts and xenografts. In the case of freeze dried bone allograft transplants, it was theorized that these materials mineralize by way of osteoinduction and stimulating osteogenesis. However, these theories have been proven false. It has been proposed that these materials mineralize via osteoconduction however, there are no studies to support this hypothesis. This study was undertaken to determine how these transplants mineralize and what type of bone they produce. Materials and Methods: This study is a histological analysis of human cadaver bone graft healing from the incipient stages of mineralization through completed mineralization. All cadaver bone grafts used for evaluation in this study were particulate bone graft materials in the maxilla or mandible. No block grafts were evaluated. Results: The mineralization of cadaver bone transplants was produced by an inflammatory response to the transplanted tissue. The histologic findings of the mineralized bone produced by this process was sclerotic bone. No resorption of cadaver bone graft particles was found. When loaded the sclerotic bone was found to fail through an accumulation of microfractures.Conclusions: Particulate freeze-dried bone allografts and xenografts do not heal via the normal processes of mineralization. Cadaver bone grafts produce significant inflammation and are hypothesized to mineralize by a process termed antigenic ossification. The process of antigenic ossification produces sclerotic bone that is not capable of self-repair which can ultimately lead to bone failure.

The paper examines common elements between Lévai’s and Milson’s potentials obtained by Liouville transformations of two rational canonical Sturm-Liouville equations (RCSLEs) with even density functions which are exactly solvable via Jacobi polynomials in a real or accordingly imaginary argument. We refer to the polynomial numerators of the given rational density function as ‘tangent polynomial’ (TP) and thereby term the aforementioned potentials as ‘e-TP’ A special attention is given to the overlap between the two potentials along symmetric curves which represent two different forms of the Ginocchio potential exactly quantized via Gegenbauer and Masjed-Jamei polynomials respectively. Our analysis reveals that the actual interconnection between Lévai’s parameters for these two rational realizations of the Ginocchio potential is much more complicated than one could expect based on the striking resemblance between two quartic equations derived by Lévai for ‘averaged’ Jacobi indexes.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

There is a need for versatile in vivo nuclear imaging reporter systems to foster preclinical and clinical research. We explore the applicability of the SNAPTag and novel radiolabeled small-molecule ligands as a versatile reporter gene system for in vivo nuclear imaging. SNAPTag is a high-affinity protein tag used in a variety of biochemical research areas and based on the suicide DNA repair enzyme O6-methylguanine methyl transferase (MGMT). Its ligands are well suited for reporter gene imaging as the benzyl guanine core scaffold can be derivatized with fluorescent or radiolabeled moieties for various applications. Three guanine-based SNAPTag ligands ([18F]FBBG, [18F]pFBG and [18F]mFBG) were synthesized in high yields and were (radio)chemically characterized. HEK293 cells were engineered to express the SNAPTag on the cell surface and served as cell model to assess target affinity by radiotracer uptake assays, Western blotting and SDS-PAGE autoradiography. A subcutaneous HEK293-SNAPTag xenograft model in immunodeficient mice was used for in vivo evaluation of [18F]FBBG amd [18F]pFBG while the biodistribution of [18F]mFBG was characterized in naïve animals. The results were validated by ex vivo biodistribution studies and immunofluorescence staining of the xenografts. All three radiotracers were produced in high radiochemical purity, molar activity and good yields. Western blot analysis revealed successful SNAPTag expression by the transfected HEK293 cells. In vitro testing revealed high target affinity of all three tracers with an up to 191-fold higher signal in the HEK293-SNAPTag cells compared to untransfected cells. This was further supported by a prominent radioactive protein band at the expected size in the SDS-PAGE autoradiograph of cells incubated with [18F]FBBG or [18F]pFBG. The in vivo studies demonstrated high uptake in HEK293-SNAP xenografts compared to HEK293 xenografts with excellent tumor-to-muscle ratios (7.5 ± 4.2 for [18F]FBBG and 10.6 ± 6.2 for [18F]pFBG). In contrast to [18F]pFBG and its chemical analogue [18F]mFBG, [18F]FBBG showed no signs of unspecific bone uptake and defluorination in vivo. Radiolabeled SNAPTag ligands bear great potential for clinical applications such as in vivo tracking of cell populations, antibody fragments and targeted radiotherapy. With excellent target affinity, good stability, and low non-specific binding, [18F]FBBG is a highly promising candidate for further preclinical evaluation.

Enteropathogens, namely Salmonella and Campylobacter, are a concern in global public health and have been attributed in numerous risk assessments to a poultry source. During the last decade a large body of research addressing this problem has been published. The literature reviewed contains review articles on certain aspects of poultry production chain, however in the past decade there hasn’t been a review on the through production chain, farm to fork, production of poultry. This review, a pool of 514 articles were selected for relevance via a systematic screening process (from >7500 original search articles). These studies identified a diversity of management and intervention strategies for the elimination or reduction of enteropathogens in poultry production. Many studies were laboratory or limited field trials with implementation in true commercial operations being problematic. Entities considering using commercial anti-enteropathogen products and interventions are advised to perform an internal validation and fit for purpose trial as Salmonella and Campylobacter serovars and biovars may have regional diversity. Future research should focus on non-chemical application within the processing plant and how synergistic through chain intervention may contribute to reducing the overall carcass burden of enteropathogen, coupled with increased consumer education on safe handling and cooking of poultry.

There is increasing interdisciplinary interest in phytoplankton community dynamics as the growing environmental problems of water quality (particularly eutrophication) and climate change demand attention. This has led to a pressing need for improved biophysical and causal understanding of Phytoplankton Functional Type (PFT) optical signals, in order that satellite radiometry may be used to detect ecologically relevant phytoplankton assemblage changes. This understanding can best be achieved with biophysically and biogeochemically consistent phytoplankton Inherent Optical Property (IOP) models, as it is only via modelling that phytoplankton assemblage characteristics can be examined systematically in relation to the bulk optical waterleaving signal. The Equivalent Algal Populations (EAP) model is used here to investigate the source and magnitude of size- and pigment- driven PFT signals in the water-leaving reflectance, as well as the potential to detect these using satellite radiometry. This model places emphasis on explicit biophysical modelling of the phytoplankton population as a holistic determinant of IOPs, and a distinctive attribute is its comprehensive handling of the spectral and angular character of phytoplankton scattering. Selected case studies and sensitivity analyses reveal that phytoplankton spectral scattering is the primary driver of the PFT-related signal. Key findings are that the backscattering-driven signal in the 520 to 600 nm region is the critical PFT identifier at marginal biomass, and that while PFT information does appear at blue and red wavelengths, it is compromised by biomass/gelbstoff ambiguity in the blue and low signal in the red, due primarily to absorption by water. These findings are hoped to provide considerable insight into the next generation of PFT algorithms.

Optical power splitters play a crucial role as the fundamental building blocks for many integrated optical devices. They should have low losses, broad bandwidth, and a high tolerance to fabrication errors. Adiabatic optical power splitters inherently possess these qualities while being compatible with foundry processes well-suited for mass-production. The long device lengths of adiabatic power splitters, however, are a limiting factor to achieve compact device sizes, which must be reduced. Here, we use a polynomial taper profile optimization algorithm to design 1×2 and 2×2 adiabatic power splitters with significantly shorter lengths than their adiabatic counterparts. The best performing 1×2 and 2×2 power splitters have 20 μm and 16 μm coupling lengths, respectively. Our designs have minimum feature sizes ranging from 140 nm to 200 nm, and our measurements averaged across 9 different chips show excellent consistency in performance for devices with 180 nm and 200 nm minimum features. Both the 1×2 and 2×2 adiabatic optical power splitters have excess losses less than 0.7 dB over a 100 nm bandwidth, with a standard deviation lower than 0.3 dB. Furthermore, our measurements show greater than 20 dB extinction ratios over 130 nm bandwidth. We also demonstrate the design of 1×2 power splitters with arbitrary splitting ratios, where splitting ratios ranging from 50:50 to 94:6 were achieved with standard deviations between 2% and 6%.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Many ecosystems are being severely degraded, leading the United Nations to deem 2021-2030 as the Decade on Ecosystem Restoration. To be successful, this effort requires robust monitoring tools to assess land reclamation practices. Our study aimed to evaluate the quality of recovery efforts in mined areas by developing a Recovery Quality Index (RQI) based on soil and vegetation indicators. Using the heavily mined Iron Quadrangle region of Brazil as an example, we selected four local, undisturbed reference areas as restoration goals: Atlantic Forest (AF); ferruginous rupestrian grassland with dense vegetation (FRGD); ferruginous rupestrian grassland with sparse vegetation (FRGS); and quartzite rupestrian grassland (QRG). We also selected four areas that were directly or indirectly affected by mining, including an environmental compensation area set aside 5 years prior to the study (COMP-5), two sterile piles that had undergone recovery for 15 and 20 years (SP-20 and SP-15), and a cave area with 15 years of recovery (CAVE-15). The four recovery areas were grouped together with each individual reference area (making four combinations of sites), and measurements of 2 vegetation parameters and 34 soil attributes were used in a Principal Component Analysis (PCA) for each grouping. We determined the RQI for each group by summing weighted PCA scores for responsive indicators. Vegetative parameters had the lowest RQI weights in all four groups. Soil physical indicators tended to be the most important, except in AF, where chemical indicators were most relevant. RQI values were also lowest when AF was used as the reference, showing that the forest was a unique ecosystem, and the CAVE-15 site had lower RQI scores than the other restored sites, indicating the high degree of disturbance that occurred in that low-lying area. The SP-20 site tended to have higher RQI values than the SP-15, and similar values to the less disturbed COMP-5 areas, potentially indicating greater recovery of native soil properties during the longer recovery period. This RQI-based approach has excellent potential for robust assessment of the recovery of areas degraded by mining and can support decision-making during monitoring.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

The paper examines rational Darboux-Crum transforms (RDCTs) of the Jacobi-reference (JRef) potential on the line, with an emphasis on the transformations using only normalizable seed solutions. The Cooper-Ginocchio-Khare (CGK) potential constitutes the simplest example of this rich family of exactly solvable one-dimensional (1D) potentials. It was explicitly confirmed that that an arbitrary Darboux-Crum transformation (DCT) of the given Sturm-Liouville equation (SLE) can be represented as a chain of sequential Darboux deformations of the associated Liouville potentials. If the rational SLE (RSLE) under consideration is exactly solvable and the transformation function (TF) used at each step is nodeless then each RSLE constructed in such a way was proven being exactly solvable itself. The exact solvability of RDCTs of the JRef canonical SLE (CSLE) was also confirmed for the DCTs using pairs of juxtaposed eigenfunctions (an extension of the renowned Adler theorem to the RCSLEs of our interest). By re-expressing the reference polynomial fraction (RefPF) of the transformed CSLE in terms of the Krein determinant (KD), instead of Crum Wronskian (CW), it was shown that the eigenfunctions under consideration are expressible in terms of polynomial solutions of a generalized Heun equation with positions of the most poles dependent on the exponent parameters. The outlined technique was extended to two isospectral SUSY partners of the JRef potential (as well as to its third sibling with the inserted new lowest-energy level) which, by analogy with the CGK potential, are quantized by polynomial solutions of the 2-Heun equation with all four poles at some fixed positions on the real axis.

AbstractCadaver bone is possibly the most common transplant material used today. Common types of cadaver bone transplants are freeze-dried bone allografts and xenografts. Studies have shown that mineralized freeze-dried bone allografts have the same percentage of retained bone graft particles at different time points, indicating that these materials are never resorbed. However, it is commonly accepted by clinicians that these materials are resorbed and convert the graft site into normal bone. This histologic study was undertaken to determine the fate of mineralized freeze-dried bone allograft particles grafted into human extraction sockets. Materials and Methods:This study is a photographic, radiologic, and histological analysis of mineralized freeze-dried bone allograft healing in human sockets after mineralization at different time points. The mineralized freeze-dried bone allografts used for evaluation in this study were particulate bone graft materials in maxillary or mandibular extraction sockets. Patient selection was random, based on the following time periods: 6 months, 2 years, 5 years, 7 years, 10 years and 15 years. No block bone grafts were evaluated. Results:No resorption of cadaver bone graft particles was found at any time point. No osteoclasts were found in any of the histology at any time point. At different time points from 6 months through 15 years, mineralized freeze-dried bone allograft particles were found to be exfoliated out of the alveolar crest as a result of the formation of a hypervascular zone surrounding the grafted site. The embedded graft particles remain embedded in sclerotic bone until the particles reach the alveolar crest at which time the sclerotic bone and graft particles break up and are released into the gingiva. All histologic samples from 6 months to 15 years contained residual graft particles. The sclerotic bone formed around graft particles did not integrate to the graft particles or the implant surface. Conclusions:Mineralized freeze-dried bone allograft particles are not resorbed after mineralization. A hypervascular zone forms around the grafted site and exfoliates the bone graft particles into the gingiva. The mineralization process produces sclerotic bone which never remodels into normal bone. Sclerotic bone covers but does not integrate to the retained bone graft particles or implant surface resulting in a weakened structure with an increased likelihood of bone failure and implant loss.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

A classical origin for the Bohmian quantum potential, as that potential term arises in the quantum mechanical treatment of black holes and Einstein-Rosen (ER) bridges, can be based on 4th-order extensions of Einstein's equations. In Bohm's ontological interpretation, black hole radiation, and the analogous tunneling process of quantum transmission through an ER bridge, are classically allowed if the dynamics are modified to include such a quantum potential. The 4th-order extension of general relativity required to generate the quantum potential is given by adding quadratic curvature terms with coefficients that maintain a fixed ratio, as their magnitudes approach zero. Quantum transmission through the classically non-traversable bridge is replaced by classical transmission through a traversable wormhole. If entangled particles are connected by a Planck-width ER bridge, as conjectured by Maldacena and Susskind, then the classical wormhole transmission effect gives the ontological nonlocal connection between the particles posited in Bohm's interpretation of their entanglement. It is hypothesized that higher-derivative extensions of classical gravity can account for the nonlocal part of the quantum potential generally.

Targeted cancer therapy has grown exponentially in the last decade, representing the largest frontier in the modern concept of precision medicine. This renaissance is largely due to our rapidly evolving ability to biochemically harness our immune systems to target cancer-specific antigens. Combined with an increasing armamentarium of surgical and non-invasive techniques for cancer mitigation we have upgraded cancer therapy from a non-specific assault on cell-division to a multi-modal, targeted approach. This renaissance has resulted in an increase in the perioperative footprint of patients with advanced cancer. The scope of the perioperative clinician has evolved from one of passive/reactive management of complications to a proactive approach that starts in the preoperative optimization phase and continues into the postoperative period. The perioperative world should not exist in a silo, and thus involvement of the oncology team is paramount. To provide safe oncologic care, it is essential to be up to date in newer cancer therapies, lest we act on erroneous and/or outdated information. Oncologists should weigh in on immune status, recent chemotherapeutic exposures, and potentially evolving toxicities. These might involve critical changes to perioperative infectious prophylaxis, steroid administration, and coagulopathy management. First, patients living beyond the typical life-expectancy for their cancer will carry a high burden of cancer-related downstream effects. General metabolic issues will include malnutrition, cachexia, and gastric outlet obstruction. Severe protein-calorie malnutrition, as well as hepatic and renal dysfunction can impact the metabolism and clearance of drugs. The cardiovascular, endocrinologic, pulmonary, and central nervous system implications of new cancer therapies will be discussed extensively below. Second, we have to enhance our ability to manage a cancer population who may be experiencing increasing novel chemotherapeutic toxicities. Newer agents differ from historical agents, which were blunt-force tools aimed at nonspecific destruction of cell-division. These drugs are efficacious but physiologically costly. Newer immunogenic therapies have a slightly improved acute safety profile, and a more complex chronic toxicity profile that may be overt or insidious. Chronic toxicities can present overtly or as a smoldering undertone to other active medical conditions such as sepsis, pneumonia, failure to thrive, or renal failure. The new therapies discussed in this review occur in the context of an overall increasingly multi-faceted cancer care machine. An example is screening for esophageal cancer in patients with Barrett's esophagus, or periodic chest CTs for patients with a strong history of tobacco use. These interventions are more likely to detect disease while it is still resectable, and resections will commonly accompany neo-adjuvant therapy. These approaches commonly involve new immunotherapies whose efficacy is higher-yield with a lower disease burden. In a recent example, the immune-checkpoint inhibitors (ICIs) ipilimumab plus nivolumab have significantly increased survival rate for squamous cell esophageal cancer when combined with standard chemotherapy. Surgical resection has evolved to one that often accompanies neoadjuvant chemo and radiation. The increasing efficacy of this approach may de-necessitate many major resections, and increase the number of sub-anatomic resections and minimally invasive procedures. Improved techniques - notably for hepatectomy, whipple procedure, prostatectomy, nephrectomy - have increased the safety profile and decreased the perioperative physiologic burden. This has enabled a broader subset of patients (due to cancer burden or due to medical comorbidities) to qualify for the operation, and increased the involvement of anesthesia and their perioperative services. With an increase in surgical candidacy comes an increase in post-surgical complications, and post-surgical maintenance such as drains, embolizations, imaging studies, etc. In the non-OR anesthesia realm, there have been considerable advancements in cancer “micro-treatments” such as hepatic metastasis embolization, tumor ablation, and peri-tumor vascular embolization. There are an ever-increasing number of IR-guided embolizations for bleeding tumors, aspiration of malignant effusions, and drainage of abscesses. This review serves to provide insight into new categories of chemotherapy and their perioperative implications.

The importance of knowing the advance time in drip irrigation lines lies in its precision, as this influences the proper management of water and nutrients delivery. The mathematical calculation to determine the advance time is based on the general hydraulic flow equation, which relates the fluid velocity and the cross-sectional area of the pipe to the volume of water flowing through it. However, in irrigation pipes, where the flow is a mixture of dripper properties, its pressure, the approach to solving the advance time is different, as it is the sum of individual advance times for each segment. To address this issue, Python 3.11 was used along with various libraries such as Pandas, NumPy, Matplotlib, Seaborn, and Scikit-learn to create a modeling environment and run algorithms that could predict outcomes. A program was developed that calculates the advance time for each segment of the drip line using partial velocities, and a dataset was generated that was used to train and test machine learning models. Several machine learning algorithms such as Linear Regression, Support Vector Machines (SVM), K-Nearest Neighbors (KNN), Decision Trees, and Random Forests were implemented to predict the advance time. Additionally, SciPy optimize was used to obtain multivariable equations that describe the advance time in drip irrigation lines. Results showed that the dripper flow has the greatest influence on the advance time, followed by the diameter and distance. Decision Tree and SVM models had the best accuracy with scores above 98%. Equations were found to calculate the advance time in the complete drip line and in 95% of its length, with coefficients of determination close to 99.33%. This study demonstrated the importance of understanding the relationship between dripper parameters and travel time in drip irrigation, as well as the utility of machine learning and optimization tools for predicting and modeling this phenomenon.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

Understanding the relationships between land cover/urban structure patterns and air pollutants is key to sustainable urban planning and development. In this study, we employ a mobile monitoring method to collect PM_2.5 and BC data in the city of Philadelphia, PA during the summer of 2019 and apply the Structure of Urban Landscapes (STURLA) methodology to examine relationships between urban structure and atmospheric pollution. We find that, while PM_2.5 and BC vary by STURLA class, many of the differences in pollutant concentrations between classes are not significant. However, we also find that the proportions in which STURLA components are present throughout the urban landscape can be used to predict urban air pollution. Among frequently sampled STURLA classes, gpl hosted the highest PM_2.5 concentrations on average (16.60 _± 4.29 µg/m³), while tgbwp hosted the highest BC concentrations (2.31 _± 1.94 µg/m³). Furthermore, STURLA combined with machine learning modeling was able to correlate PM_2.5 (R²= 0.68, RMSE 2.82 µg/m³) and BC (R² = 0.64, RMSE 0.75 µg/m³) concentrations with the urban landscape and spatially interpolate concentrations where sampling did not take place. These results demonstrate the efficacy of the STURLA methodology in modeling relationships between air pollution and land cover/urban structure patterns.

Ion channels are integral membrane proteins that facilitate the movement of ions across cell membranes, playing a key role in a range of biological processes. The high cost and time required for wet lab experiments to characterize ion channels has spurred the development of computational methods for this purpose. In our previous work, we demonstrated the effectiveness of protein language models for ion channel prediction, using a logistic regression classifier to distinguish ion channels from non-ion channels (TooT-BERT-C) and transporters from non-transporters (TooT-BERT-T). In this study, we build upon this approach by using a combination of classical machine learning classifiers and a Convolutional Neural Network (CNN) with fine-tuned representations from ProtBERT, ProtBERT-BFD, and MembraneBERT to discriminate ion channels from non-ion channels. The results of our experiments demonstrate that TooT-BERT-CNN-C, a combination of the representations from ProtBERT-BFD and a CNN, outperforms existing state-of-the-art methods for predicting ion channels, with a Matthews Correlation Coefficient (MCC) of 0.86 and an accuracy of 98.35% on an independent test set.

Four discrete models using the exact spectral derivative discretization finite difference (ESDDFD) method are proposed for a chaotic five-dimensional, conformable fractional derivative financial system incorporating ethics and market confidence. Since the system considered was recently studied using the conformable Euler finite difference (CEFD) method and found to be hyperchaotic, and the CEFD method was recently shown to be valid only at fractional index , the source of the hyperchaos is in question. Through numerical experiments, illustration is presented that the hyperchaos previously detected is in part an artifact of the CEFD method as it is absent from the ESDDFD models.

As brachycephalic dog breed ownership increases, there is a growing concern for the welfare of these breeds due to extreme brachycephalism. Understanding the motivations and behaviours of those choosing to own these breeds is important if we wish to address these concerns. The aim of this study was to investigate how owners of brachycephalic and non-brachycephalic dog breeds use social media dog breed groups to discuss common health issues. The purpose of Facebook posts in relation to common health issues, owner awareness of health issues, and the role of Facebook facilitated social support were explored between brachycephalic and non-brachycephalic dog owners. Twelve Facebook breed groups were selected (brachycephalic breed groups, n=6, non-brachycephalic breed groups, n=6). Using key word searches we extracted the first twenty posts from each group. Thematic analysis revealed three overarching themes: advice seeking, advice giving and community bonding mechanisms. Whilst the purpose of posting did not differ between groups, non-brachycephalic owners appeared to display greater awareness of breed-specific health issues, whilst social support played a more prominent role in brachycephalic groups. This research highlights that social media groups can act as platforms for knowledge exchange and emotional support. These could be utilised by owners, veterinarians and welfare organisations to more effectively enhance dog health and wellbeing.

Eating disorder (ED) symptoms often co-occur with nonsuicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. One hundred and five community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI.

The Social-Ecological Systems (SES) framework serves as a valuable framework to explore and understand social and ecological interactions, and pathways in water governance. Yet, it lacks a robust understanding of change. We argue an analytical and methodological approach to engaging global changes in SES is critical to strengthening the scope and relevance of the SES framework. Relying on SES and resilience thinking, we propose an institutional and cognitive model of change that institutions and natural resources systems co-evolve to provide a dynamic understanding of SES that stands on three causal mechanisms: institutional complexity trap, rigidity trap, and learning processes. We illustrate how Data Cube technology could overcome current limitations and offer reliable avenues to test hypothesis about the dynamics of social-ecological systems and water security by offering to combine spatial and time data with no major technical requirements for users.

Quantitative research on positive aspects of work-life integration and the well-being of families with children with disabilities is scarce, especially in the national context. The aim of this study was to examine the contributions of some personal and environmental resources in explaining work-to-family (WFF) and family-to-work (FWF) facilitation and mental health of parents of children with disabilities residing in Croatia. The mediational role of WFF and FWF in the relationship between the resources and mental health was tested, while controlling for some general socio-demographic variables. A total of 571 employed parents of a child/children with disabilities completed an online self-assessment questionnaire. The results showed higher WFF (19%) was predicted by higher levels of social support at work, a higher level of education, posttraumatic growth (PTG) of personal strength, and recovery management. Higher FWF (46%) was predicted by higher levels of social support in the family, PTG of personal strength, the emotional regulation strategy of reorienting to planning, optimism, a lower age, the male gender, a greater number of children, and a higher level of education. A higher level of mental health (47%) was predicted directly by higher levels of optimism, recovery management, FWF, emotional regulation strategies of positive refocusing and planning, and a greater number of children, and indirectly by all the predictors of FWF, through a higher level of FWF (but not WFF).

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

Heat shock proteins (HSPs) are a family of molecular chaperones that regulate essential protein refolding and triage decisions to maintaining protein homeostasis. Numerous co-chaperone proteins directly interact and modify the function of HSPs, and these interactions impact the outcome of protein triage, impacting everything from structural proteins to cell signaling mediators. The chaperone/co-chaperone machinery protects against various stressors to ensuring cellular function in the face of stress. However, coding mutations, expression changes, and post-translational modifications of the chaperone/co-chaperone machinery can alter the cellular stress response. Importantly, these dysfunctions appear to contribute to numerous human diseases. Therapeutic targeting of chaperones is an attractive but challenging approach due to the vast functions of HSPs, likely contributing to the off-target effects of these therapies. Current efforts focus on targeting co-chaperones to develop precise treatments for numerous diseases caused by defects in protein quality control. This review focuses on the recent developments regarding selected HSP70/HSP90 co-chaperones, focusing on cardioprotection, neuroprotection, and cancer. We also discuss therapeutic approaches that highlight both the utility and challenges of targeting co-chaperones.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases a cause, with a mechanistic basis). Clots are, of course, a well-known consequence of atrial fibrillation. We here ask the question as to whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known ‘risk factors’ for AF, and in particular exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots are cytotoxic by inducing hypoxia/reperfusion and other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.

We revisit the argument that link the efficiency of a solar cell to its reverse operation as a LED, in the case where the material is organic. In organic cells, exciton transport is an intermediate process between sunlight absorption and the generation of electric current. We show that quenching exciton radiation can be beneficial to cell efficiency, without contradicting the general rule prevailing for semiconductor cells. Our treatment allows us to discuss both bulk heterojunction and planar junctions.

Acoustic emission (AE) has proven to be a very useful technique for determining damage in ceramic matrix composites (CMCs). CMCs rely on various cracking mechanisms which enable non-linear stress-strain behavior with ultimate failure of the composite due to fiber failure. Since these damage mechanisms are all micro-fracture mechanisms, they emit stress waves ideal for AE monitoring. These are typically plate waves since for most specimens or applications one dimension is significantly smaller than the wavelength of the sound waves emitted. By utilizing the information of the sound waveforms captured on multiple channels from individual events, the location and identity of the sources can often be elucidated. The keys to the technique are the use of wide-band frequency sensors, digitization of the waveforms (modal AE), strategic placement of sensors to sort the data and acquire important contents of the waveforms pertinent for identification, and familiarity with the material as to the damage mechanisms occurring at prescribed points of the stress history. The AE information informs the damage progression in a unique way which adds to the understanding of the process of failure for these composites. The AE methodology was applied to composites tested in fatigue at different frequencies where identification of when and where AE occurred coupled with waveform analysis leads to source identification and failure progression.

1) Background: We analyzed the corpus of three geoscientific journals to investigate if there are enough locational references in research articles to apply a geographical search method, on the example of New Zealand. 2) Methods: Based on all available abstracts and all freely available papers of the New Zealand Journal of Geology and Geophysics, the New Zealand Journal of Marine and Freshwater Research, and the Journal of Hydrology, New Zealand, we searched title, abstracts and full texts for place name occurrences that match records from the official Land Information New Zealand (LINZ) gazetteer. We generated ISO standard compliant metadata records for each article including the spatial references and make them available in a public catalogue service. This catalogue can be queried for articles based on authors, titles, keywords, topics as well as by spatial reference. We visualize the results in a map to show which area the research articles are about. 3) Results: We outline the methodology and technical framework for the geo-referencing of the journal articles and the platform design for this knowledge inventory. The results indicate that the use of well-crafted abstracts for journal articles with carefully chosen place names of relevance for the article provides a guideline for geographically referencing unstructured information like journal articles and reports in order to make such resources discoverable through geographical queries. 4) Conclusion: This approach can actively support integrated holistic assessment of water resources and support decision making.

In this review, we provide an overview of the current knowledge on the different sexual systems and sex determining mechanisms in bivalves, with a focus on the various epigenetic and genetic factors that may be involved. The final section of the review provides recent discoveries on sex-specific mitochondrial genes in bivalves possessing the unconventional system of doubly uniparental inheritance of mitochondria (which is found in several members of the orders Mytiloida, Unionoida, Veneroida and Nuculanoida). The genes involved in this developmental pathway could represent the first sex determination system in animals in which mitochondrially-encoded genes are directly involved.

On the occasion of Kynouria and in order to achieve the protection and projection of antiquities, a web-based model is proposed for highlighting individual monuments and archaeological sites, having in mind the historical and archaeological evidence of the region, the topography, the demographic profile and the tourist infrastructure, and combining them with the development programs for cultural routes. Therefore, creating suitable databases and mapping the monuments in the area are key prerequisites of the process, as they contribute to an objective assessment of the current situation and then to make rational decisions. In this frame, modern technology provides some important planning tools (GIS, GPS, and OMS) which allow recording and mapping of data, viewing the relationships between them in the area where they appear and managing their projection. The complete study of Kynouria’s archaeological routes contains the implementation of a website using free or open-source software, which should include all the necessary procedures and the historical and archaeological information material (text, maps, and photographs).

Important first phases in the process of implementing CO2 subsurface and ocean storage projects include selecting of best possible location(s) for CO2 storage, site selection evaluation. Sites must fulfil a number of criteria that boil down to the following basics: they must be able to accept the desired volume of CO2 at the rate at which it is supplied from the CO2 source(s); they must as well be safe and reliable; and must comply with regulatory and other societal requirements. They also must have at least public acceptance and be based on sound financial analysis. Site geology; hydrogeological, pressure, and geothermal regimes; land features; location, climate, and access, etc. can all be refined from these basic criteria. In addition to aiding in site selection, site characterization is essential for other purposes, such as foreseeing the fate and impacts of the injected CO2, and informing subsequent phases of site development, including design, permitting, operation, monitoring, and eventual abandonment. According to data from the IEA, in 2022, emissions from Africa and Asia's emerging markets and developing economies, excluding China's, increased by 4.2%, which is equivalent to 206 million tonnes of CO2 and were higher than those from developed economies. Coal-fired power generation was responsible for more than half of the rise in emissions that were recorded in the region. The difficulty of achieving sustainable socio-economic progress in the developing countries is entwined with the work of reducing CO2 emissions, which is a demanding project for the economy. Organisations from developing countries, such as Bangladesh, Cameroon, India, and Nigeria, have formed partnerships with organisations in other countries for lessons learn and investment within the climate change arena. The basaltic rocks, coal seams, depleted oil and gas reservoirs, soils, deep saline aquifers, and sedimentary basins that developing countries (Bangladesh, Cameroon, India, and Nigeria etc) possesses all contribute to the individual country's significant geological sequestration potential. There are limited or no carbon capture and storage or clean development mechanism projects running in these countries at this time. The site selection and characterization procedure are not complete without an estimate of the storage capacity of a storage location. Estimating storage capacity relies on volumetric estimates because a site must accept the planned volume of CO2 during the active injection period. As more and more applications make use of site characterization, so too does the body of written material on the topic. As the science of CO2 storage develops, regulatory requirements are implemented, field experience grows, and the economics of CO2 capture and storage improve, so too will site selection and characterisation change.

MIGAL – Galilee Research Institute is a regional R&amp;D center in the northeast peripheral region of Israel. An internationally recognized applied research institute, MIGAL specializes in biotechnology and computational sciences, plant sciences, precision agriculture and environmental sciences, as well as food, nutrition and health. Most of MIGAL’s researchers serve as the core faculty at Tel Hai Academic College (TH). Despite the country’s small surface area, socioeconomic inequality in Israel is high by OECD standards, with wage differences between rich and poor regions reaching up to 400%. The aims of this study are to identify possible socioeconomic impacts of MIGAL–TH on the peripheral northeast’s development. We discuss the effects of academic research and institutions of higher education on mitigating differences between the center and periphery of the country. Data for MIGAL, TH and the northeastern peripheral region were collected from the yearly reports of the two institutions and the Israel Central Bureau of Statistics. MIGAL was found to serve as a link between research, academic teaching and socioeconomic development in the northeast periphery. Several variables related to this link and describing MIGAL–TH and northeastern periphery development were analyzed over time: MIGAL’s budget, total number of employees and number of employees with PhDs; number of TH graduate students; socioeconomic index (SEI) of the northeastern periphery and its position on the Israeli list of regional SEIs. The signs and significance levels of their trends indicate a potential socioeconomic impact of academic research and higher education on peripheral development in the northeast of the country. Research budgets and the creation of jobs for academics living in the region are just a few examples of this impact.

We investigate the flow structure and dynamics of moderate-Rayleigh-number ($Ra$) thermal convection in a two-dimensional inclined porous layer. Direct numerical simulations (DNS) confirm the emergence of $\mathit{O}(1)$ aspect-ratio large-scale convective rolls, with one `natural' roll rotating in the counterclockwise direction and one `antinatural' roll rotating in the clockwise direction. As the inclination angle $\phi$ is increased, the background mean shear flow intensifies the natural-roll motion, while suppressing the antinatural-roll motion. Moreover, our DNS reveal---for the first time in single-species porous medium convection---the existence of \emph{spatially-localized} convective states at large $\phi$, which we suggest are enabled by subcritical instability of the base state at sufficiently large inclination angles. To better understand the physics of inclined porous medium convection at different $\phi$, we numerically compute steady convective solutions using Newton iteration and then perform secondary stability analysis of these nonlinear states using Floquet theory. Our analysis indicates that the inclination of the porous layer stabilizes the boundary layers of the natural roll, but intensifies the boundary-layer instability of the antinatural roll. These results facilitate physical understanding of the large-scale cellular flows observed in the DNS at different values of $\phi$.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

The studied Khanbogd pluton of peralkaline granite is located in southern Mongolia and occupies an area of ~1000 sq. km. Previously, two ring-shaped bodies were constructed in a flattened shape pluton. However, this shape was not used for the genesis of this pluton. A recent study of Landsat image showed a several elliptical intrusions in two bodies. Chemistry interpretation shows that each intrusion differs in ASI, CIPW norms, 87Sr/86Sri and δ18O isotopes. Elliptical intrusions, uplifted country rocks between them, and roof pendants suggest magma penetration along fractured country rocks. Furthermore, two adjacent intrusive bodies and undeformed host rocks at the front part of the pluton are consistent with underplating magmatic factors during duplex-type thrusting. This magma event is also supported by low of Sr, Ba, Eu and high of Th, U, Pb anomalies and a few amount of garnet crystals in the granites, implying vapor absent melt crystallization associated with underplating. Multiple melt sources, as well as from mantle and recycled sea floor rocks, are identified by ratio of 87Sr /86Sri and δ18O values. The low isotope values, the thrust nature and 295–286 Ma ages of the alkali granites, indicate an underplate magma evidenced during Permian rifting.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

In the present work we revise and extend the Characteristic Crystallographic Element (CCE) norm, an algorithm used to simultaneously detect radial and orientational similarity of computer-generated structures with respect to specific reference crystals and local symmetries. Based on the identification of point group symmetry elements, the CCE descriptor is able to gauge local structure with high precision and finely distinguish between competing morphologies. As test cases we use computer-generated monomeric and polymer systems of spherical particles interacting with the hard-sphere and square-well attractive potentials. We demonstrate that the CCE norm is able to detect and differentiate, between others, among: hexagonal close packed (HCP), face centered cubic (FCC), hexagonal (HEX) and body centered cubic (BCC) crystals as well as non-crystallographic fivefold (FIV) local symmetry in bulk 3-D systems; triangular (TRI), square (SQU) and honeycomb (HON) crystals, as well as pentagonal (PEN) local symmetry in thin films of one-layer thickness (2-D systems). The descriptor is general and can be applied to identify the symmetry elements of any point group for arbitrary atomic or particulate system in two or three dimensions, in the bulk or under confinement.

Disruption of epigenetic regulation by environmental toxins is an emerging point of focus for understanding the latter’s impact on human health. Polybrominated diphenyl ethers (PBDEs), one such toxin, are an environmentally pervasive class of brominated flame retardants that have been extensively used as coatings on a wide range of consumer products. Their environmental stability, propensity for bioaccumulation, and known links to adverse health effects have evoked extensive research to characterize underlying biological mechanisms of toxicity. Of particular concern is the growing body of evidence correlating human exposure levels to behavioral deficits related to neurodevelopmental disorders. The developing nervous system is particularly sensitive to influence by environmental signals, including dysregulation by toxins. Several major modes of actions have been identified, but a clear understanding of how observed effects relate to negative impacts on human health has not been established. Here we review the growing body of evidence for epigenetic disruptions induced by PBDEs, including DNA methylation, chromatin dynamics, and non-coding RNA expression while discussing potential relationship between PBDEs and neurodevelopmental disorders.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

(1) Background: This report examines the unique demands of off-road triathlon (XT) by presenting physiological, field, and race data from a national champion off-road triathlete using several years of laboratory and field data to detail training and race intensity. (2) Methods: Laboratory and field data were collected when the athlete was at near peak fitness and included oxygen consumption (VO2), heart rate (HR), power output (W), and blood lactate (BLC) during cycling and running, while HR, cycling W, and running metrics were obtained from training and race data files over a period of seven years. Intensity was described using % HR max zones (Z) 1 &lt; 75%, 2 = 75 - 87%, and Zone 3 &gt; 87%, and W. An ordinary least squares analysis was used to model differences between event types. (3) Results: Weather conditions were not different across events. XT events had twice the elevation change (p&lt;0.01) and two-three times greater W’ (p&lt; 0.001) than road triathlon (ROAD), but similar HR intensity profiles (max, avg, and zones); both events are predominately performed at &gt; Z2 or higher intensity. Championship XT events were longer (p&lt;0.01) , with higher kJ expenditure (p&lt;0.001). OLS modelling suggested three variables were strongly related (R2 = 0.84; p &lt; 0.0001) to cycling performance: event type (XT vs ROAD), total meters climbed, and total bike duration. Championship XT runs were slower than either regional (p&lt;0.05) or ROAD (p&lt;0.01) runs, but HR intensity profiles similar. OLS modelling indicates that slower running is linked to either greater total bike kJ expenditure (R2 = 0.57; p&lt;0.001), or total meters gained (R2 = 0.52; p&lt;0.001). Race simulation data support these findings but failed to produce meaningful differences in running. Conclusions: XT race demands are unique and mirror MTB and trail running demands. XT athletes must be mindful of developing anaerobic fitness, technical ability, and aerobic fitness, all of which contribute to off-road cycling economy. It is unclear whether XT cycling affects subsequent running performance different from ROAD cycling.

Hospitalizations for patients with diabetes and dementia take a significant health and economic toll on older adults in the United States. The present study sought to examine the differences in hospitalization characteristics and outcomes associated with diabetes and dementia separately and together using discharge record data of Los Angeles County residents aged 50+ from the California Department of Health Care Access and Information for the period 2019-2021. Results from multiple linear regression analyses indicated that when compared to those with no diabetes or dementia, patients with diabetes alone exhibited the highest total charges, while those with comorbid diabetes and dementia exhibited lower charges (p≤.05). Results of a multinomial logistic regression found that patients with comorbid diabetes and dementia had the highest odds of having a length of stay of 7+ days (AOR=1.49; 95% CI=1.44-1.53). A matched-case control analysis found that comorbid diabetes and dementia was associated with significantly lower odds of hypertensive disease than diabetes alone (MOR=0.81; 95% CI=0.67-0.97). These results highlight the complexity of factors affecting variation in hospitalization outcomes across these distinct disease profiles. Findings suggest a need to carefully consider this complexity when developing health policies or strategies to improve hospitalization outcomes involving these disease conditions.

We have previously reported that a single test measuring oVEMP n10 to 4000Hz stimuli (either bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients with a sensitivity of 1.0 and specificity of 1.0. Such a single short screening test has great advantages of speed, minimizing testing time and the exposure of patients to stimulation. However some studies of the 4000Hz test for SCD have reported sensitivity and sensitivity values somewhat less that what we reported.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

The past two decades has seen a growing demand for high-power, high-voltage utility scale inverters mostly fueled by the integration of large solar PV and wind farms. Multilevel inverters have emerged as the industry choice for these megawatt range inverters because their reduced voltage stress, capable of generating an almost sinusoidal voltage, in-built redundancy, among others. This paper present a new Switched-Source Multilevel Inverter (SS MLI) architecture. The new inverter show superior over existing topologies. It has reduced voltage stress on the semiconductor, uses less number of switches –reduced size/weight/cost and increased efficiency. The new SSMLI is comprised of two voltage sources (V₁, V₂) and 6 switches. It is capable of generating 5-level output voltage in symmetric modes (i.e., V₁ = V₂), and 7-level output voltage in asymmetric modes (i.e., V₁ ≠ V₂). To demonstrate the validity of the proposed inverter, simulations results using MATLAB^® /Simulink^® for 5- and 7-level output voltages are presented . The simulations are also verified experimentally using a laboratory prototype.

This work presents a novel approach for the study of the movement of droplets on inclined surfaces under the influence of gravity and chemical heterogeneities. The developed numerical methodology uses data-driven modeling to extend the applicability limits of an analytically derived reduced-order model for the contact line velocity. More specifically, while the reduced-order model is able to capture the effects of the chemical heterogeneities to a satisfactory degree, it does not account for gravity. To alleviate this shortcoming, datasets generated from direct numerical simulations are used to train a data-driven model for the contact line velocity, which is based on the Fourier neural operator and corrects the reduced-order model predictions to match the reference solutions. This hybrid surrogate model, which comprises of both analytical and data-driven components, is then integrated in time to simulate the droplet movement, offering a speedup of five orders of magnitude compared to direct numerical simulations. The performance of this hybrid model is quantified and assessed in different wetting scenarios, by considering various inclination angles and values for the Bond number, demonstrating the accuracy of the predictions as long as the adopted parameters lie within the ranges considered in the training dataset.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

We provide a comprehensive framework for forecasting five minute load using Gaussian processes with a positive definite kernel specifically designed for load forecasts. Gaussian processes are probabilistic, enabling us to draw samples from a posterior distribution and provide rigorous uncertainty estimates to complement the point forecast, an important benefit for forecast consumers. As part of the modeling process, we discuss various methods for dimension reduction and explore their use in effectively incorporating weather data to the load forecast. We provide guidance for every step of the modeling process, from model construction through optimization and model combination. We provide results on data from the PJMISO for various periods in 2018. The process is transparent, mathematically motivated, and reproducible. The resulting model provides a probability density of five-minute forecasts for 24 hours.

Performing optimisation and scale-up studies of crystallisation systems requires accurate and computationally efficient mathematical models. The assumption of the ideal mixing conditions in batch reactors typically produce inaccurate results while the computational expense of CFD models is still prohibitively high. Therefore, in this work, a new intermediary approach is proposed that takes into account the non-ideal mixing conditions in the reactor and requires less computational resources than full CFD simulations. Starting with the Danckwerts concept of the intensity of segregation, an analogy between its application to chemical reactions and the kinetics of the crystallisation phenomena (such as nucleation and growth) has been made. As a result, the modified kinetics expressions have been derived which incorporate the effect of non-idealities present in stirred reactors. This way, based on the experimental measurements of the mixing time using the Laser Induced Fluorescence (LIF) technique, computationally more efficient mathematical models can be developed in two ways: (1) the accurate semi-empirical correlations are available for standard mixing configurations with the most often used types of impellers, (2) CFD simulations can be utilised for estimation of the mixing time; in this case it is necessary to simulate only the mixing process. The benefits offered by the LIF experimental technique have been demonstrated and some frequent problems in its application analysed. The mixing time results for configurations with and without baffles for three types of impellers and four different rotational speeds have been presented. The false shorter mixing times in the non-baffled configurations have been observed and this phenomena explained by the existence of two segregated zones in the reactor and confirmed by additional experiments. The precise measurements in these cases have been shown as difficult using the LIF technique, particularly for higher rpms. The experimental data has been compared to the preliminary simulation results obtained from the Smoothed Particle Hydrodynamics method and the standard k-ε turbulence model with the modest success. The shortcomings of the SPH model have been recognized and the directions for the future work discussed.

Background: Distance to a health facility for inpatient care in developing countries has been a huge hindrance towards the achievement of the Sustainable Development Goal three. The United Nation encourages countries to research on access to inpatient care, so as to form health policies based on data. Methods: Data on four hundred and eighty-one participants of all ages from forty-seven counties in Kenya who sought inpatient care in Kenya in 2018 were analyzed. Distance to a health facility was captured as a continuous variable and was self-reported by the respondent. The response exhibited a discrete mass at zero and continuous characteristic, therefore a Tweedie distribution was adopted for modelling. Due to the correlation nature of clustered data, we embraced the Generalized Estimating Equations approach with an exchangeable correlation. Since no standard software was available to analyze this problem, we developed an R functions. We assessed the best model fit using the QICu and criteria, in which the lowest value for the former and the highest for the later are preferred.Findings: Differences in employment, ability to pay for the service and household size are associated with the distance covered to access government facilities. Interpretation: Poor people tend to have large households and are more likely to live in rural areas and slums, thus are forced to travel for long distance to access inpatient care. Compared to unemployed, the employed could have better socio-economic status and possibly live within reach of the inpatient health facilities, therefore travel less distances to access. Longer distances are associated with high payments, signifying some form of specialized treatment care due to the complexity of the medical cases, that are expensive to treat.

The aim of this study was to develop a valid and reliable questionnaire to assess vitamin D-related knowledge, attitude and practice (KAP) in Iranian adults who may be at increased risk of vitamin D deficiency. This study was conducted on 527 subjects, aged ≥20 years from Public health care centers in Tehran, Iran. Based on results of literature review and in-depth interviews, the 38-item vitamin D-related KAP questionnaire with four subscale was developed: 1) general knowledge; 2) nutritional knowledge; 3) attitudes; 4) behaviors. Validity of the developed vitamin D-KAP questionnaire was assessed, utilizing face, content, and construct validity methods. Internal consistency was calculated to assess reliability of the current developed questionnaire. A total of 572 (54.1% female) adults, aged 30.2±7.9 years, participated in the study. All items were perceived as relevant and comprehendible by participants. Content validity was confirmed by the panel of experts. The internal consistency, as measured by Cronbach’s alpha coefficients, exceeded the minimum reliability standard of 0.60 for four subscales. The EFA suggested a four-factor construct and the results of the CFA indicated acceptable fit indices for the proposed model. No ceiling effects were observed except for general knowledge (1.2%). Floor effects detected were 0, 1.1, 2.4, and 8.7% for practice, attitude, general knowledge, and nutrition knowledge, respectively. General knowledge had the highest score (79.59±14.52) and nutrition knowledge, the lowest score (42.58±20.40) among the four sub-scales. Results confirm the initial validity and reliability of the vitamin D-related knowledge, attitude and practice questionnaire. Further investigations in different urban and rural population are recommended.

Freezing of gait (FOG), a debilitating symptom of Parkinson’s disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (AUC = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

Given the persistence of microplastics in the environment and their potential toxicity to ecosystems, understanding of likely microplastic accumulation ‘hotspots’ in rivers is urgently needed. To contribute to this challenge, this paper reports results of a microplastic survey from a heavily urbanised catchment, the River Tame, which flows through the city of Birmingham, UK. All sediment sampled was found to contain microplastics with an average abundance of 165 particles kg-1. While urban areas generally have a greater abundance of microplastics as compared with rural, there is no simple relationship between microplastic numbers and population density or proximity to wastewater treatment sites. The greatest change in microplastic abundance was due to the presence of a lake along the course of the River Tame i.e. on entering the lake flow velocities are reduced which promotes the deposition of fine sediment and potentially microplastics. This suggests that the greatest concentrations of microplastics will not be found in-channel but rather on the floodplain and other low velocity environments such as meander cutoffs. We also identified a new mechanism of microplastic fixation in freshwater environments through ecological engineers, specifically caddisfly that incorporated microplastics into their casing. These results highlight the need to explore further hydrodynamic and ecological impacts on microplastics fate and transport in rivers.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

A primary challenge facing conservationists is reconciling the human needs of forest adjacent communities with the needs of conserving forest biodiversity, especially in tropical regions with growing populations of rural poor. Agroforestry has the potential to simultaneously provide for human needs and enhance forest biodiversity, but the complex interactions and feedbacks between the social and natural dimensions are relatively undescribed and thus systematic implementation is rare. The attributes of trees on farms required for human needs and conservation value may conflict. For example, exotic species in monoculture may provide the most economic value for farmers, while relic or planted indigenous tree mixtures may be more valuable for biological conservation. The objective of this study was to explore whether agroforestry practices in a moist tropical forest ecosystem in Kenya can simultaneously provide timber and fuelwood value to small-holder farmers while extending forest tree biodiversity. We described the agroforestry attributes on farms around a tropical forest, assessed the relationship between number and biomass of timber/fuelwood trees and tree biodiversity, and explored the relationships between forest tree diversity attributes and farm tree diversity attributes on a landscape scale using spatial analysis. We found that the diversity and number of trees on farms in this area are extensive yet variable, but that no significant relationship exists between the number of timber/fuelwood trees and tree diversity. This suggests that the two values of agroforestry may not be in conflict, due mainly to the high diversity of trees used for fuelwood. We also found that trees on farms in the larger landscape add to the conservation value of forest tree biodiversity and could be important components in conservation management. If agroforestry is to play an increasingly active role in conserving biodiversity in human-dominated landscapes, particularly in areas of dense subsistence farmer populations, increase recognition needs to be given to farmer’s perception of the value of trees and their selection of what trees to plant or maintain.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Chitosan is a copolymer of β-glucosamine and N-acetylglucosamine. Recent experiments showed that the degree and pattern of acetylation along the chitosan chain modulate the biological and physicochemical properties; however, the molecular mechanism is unknown. Here we apply the de novo all-atom molecular dynamics (MD) simulations to study chitosan’s self-assembly process at different degrees of acetylation and two different acetylation patterns. The simulations revealed that the 10-mer chitosan chains with 50% acetylation in either block or alternating patterns associate to form ordered nanofibrils comprised of mainly antiparallel chains in agreement with the fiber diffraction data of deacetylated chitosan. Surprisingly, regardless of the acetylation pattern, the same intermolecular hydrogen bonds mediate the fibril sheet formation while water-mediated interactions stabilize the sheet-sheet stacking. Moreover, the acetylated units are involved in forming the strong intermolecular hydrogen bonds (NH–O6 and O6H–O7), which offers an explanation for the experimental observation that increased acetylation lowers chitosan’s solubility. Taken together, the present study provides the atomic-level understanding the role of acetylation plays in modulating chitosan’s physiochemical properties, contributing to the rational design of chitosan-based materials with the ability to tune by its degree and pattern of acetylation. Additionally, we disseminate the improved molecular mechanics parameters that can be applied in MD studies to further understand chitosan-based materials.

Capturing and storing CO2 (CCS) was once regarded as a significant, urgent, and required option for reducing the emissions of CO2 from coal and oil and gas industries and mitigating the serious impacts of CO2 on the atmosphere and the environment. This recognition came about as a result of extensive research conducted in the past. The CCS cycle comes to a close with the last phase of CO2 storage, which is accomplished primarily by the adsorption of CO2 in the ocean and injection of CO2 subsurface reservoir formation, in addition to the formation of limestone by the process of CO2 reactivity with reservoir formation minerals through injectivities. CCS is the last stage in the carbon capture and storage (CCS) cycle and is accomplished chiefly via oceanic and subterranean geological sequestration, as well as mineral carbonation. The injection of supercritical CO2 into geological formations disrupts the sub-surface's existing physical and chemical conditions; changes can occur in the pore fluid pressure, temperature state, chemical reactivity, and stress distribution of the reservoir rock. This paper aims at advancing our current knowledge in CO2 injection and storage systems particularly CO2 storage methods and the challenges encountered during the implementation of each method and analyses on how key uncertainties in CCS can be reduced. CCS sites are essentially unified systems; yet, given the scientific context, these storage systems are typically split during scientific investigations based on the physics and spatial scales involved. Separating the physics by using the chosen system as a boundary condition is a strategy that works effectively for a wide variety of physical applications. Unfortunately, the separation technique does not accurately capture the behaviour of the larger important system in the case of water and gas flow in porous media. This is due to the complexity of geological subsurface systems, which prevents the approach from being able to effectively capture the behaviour of the larger relevant system. This consequently gives rise to different CCS technology with different applications, costs and social and environmental impacts. The findings of this study can help improve understanding of selecting a suitable CCS application method and can further improve the efficiency of greenhouse gas emissions and their environmental impact, promoting the process sustainability and helping to tackle some of the most important issues that human being is currently accounting global climate change. Though this technology has already had large-scale development for the last decade, some issues and uncertainties are identified. Special attention was focused on the basic findings achieved in CO2 storage operational projects to date. The study has demonstrated that though a number of CCS technology has been researched and implemented to date, choosing a suitable and acceptable CCS technology is still daunting in terms of its technological application, cost-effectiveness and socio-environmental acceptance.

Carbon subsurface storage (CSS) has already been recognised as a critical, urgent, and essential method for reducing anthropogenic CO2 emissions and mitigating the severe effects of climate change. CSS is the last stage in the carbon capture and storage (CCS) cycle and is accomplished chiefly via oceanic and subterranean geological sequestration, as well as mineral carbonation. The injection of supercritical CO2 into geological formations causes a disruption in the subsurface's existing physical and chemical conditions; changes can occur in the pore fluid pressure, temperature state, chemical reactivity, and stress distribution of the reservoir rock. This paper aims to present a comprehensive review on the current advances in CSS, particularly CO2 storage methods and the challenges encountered during the implementation of each methods and analyses on how key uncertainties in CSS can be reduce. CSS sites are essentially unified systems; yet, given the scientific context, these systems are typically split during scientific investigations based on the physics and temporal/spatial scales involved. Separating the physics by using the system as a boundary condition is a strategy that works effectively for a wide variety of physical applications. Unfortunately, the separation technique does not accurately capture the behaviour of the larger important system in the case of water and gas flow in porous media. This is due to the complexity of geological subsurface systems, which prevents the approach from being able to effectively capture the behaviour of the larger relevant system. This consequently give rise to different CSS methods. A good CSS application method can further improve the efficiency of greenhouse gas emission and their environmental impact, promoting the process sustainability and helping to tackle some of the most important issues that human being is currently accounting, global climate change. Though this technology is already large-scale development for the last decade, some issues and uncertainties are identified. Special attention was focused on the basic findings achieved in CO2 storage operational projects to date.

Plant-based diets are increasingly popular for health as well as financial, ethical, and religious reasons. The medical literature clearly demonstrates that plant-based diets can be both nutritionally sufficient and medically beneficial. However, any person on an intentionally restrictive but poorly-informed diet may predispose themselves to clinically-relevant nutritional deficiencies. For persons on a poorly-informed plant-based diet, deficiencies are possible in both macronutrients (protein, essential fatty acids) and micronutrients (vitamin B12, iron, calcium, zinc and vitamin D). Practitioner evaluation of symptomatic patients on a plant-based diet requires special consideration of 7 key nutrient concerns for plant-based diets. This article translates these concerns into 7 practical questions that all practitioners can introduce into their patient assessments and clinical reasoning. Ideally, persons on plant-based diets should be able to answer these 7 questions. Each serves as a heuristic prompt for both clinician and patient attentiveness to a complete diet. As such, these 7 questions support increased patient nutrition knowledge and practitioner capacity to counsel, refer, and appropriately focus clinical resources.

Graphene-based Field-Effect Transistors (FETs) integrated with microstrip patch antennas offer a promising approach for Terahertz signal radiation. In this study, a dual-stage simulation methodology is employed to comprehensively investigate the device’s performance. The initial stage, executed in MATLAB, delves into charge transport dynamics within a FET under asymmetric boundary conditions, employing hydrodynamic equations for electron transport in the graphene channel. Electromagnetic field interactions are modeled via Finite-Difference Time-Domain (FDTD) techniques. The second stage, conducted in COMSOL Multiphysics, focuses on the microstrip patch antenna’s radiative characteristics. Notably, analysis of the S11 curve reveals minimal reflections at the FET’s resonant frequency of 1.34672 THz, indicating efficient impedance matching. Examination of the radiation pattern demonstrates the antenna’s favorable directional properties. This research underscores the potential of graphene-based FETs for Terahertz applications, offering tunable impedance matching and high radiation efficiency for future Terahertz devices.

The ability of S. aureus to infect humans and cause a wide range of infections so efficiently is a consequence of the many variant virulence factors that it can produce. Superantigens (SAgs) make up a group of them and include staphylococcal enterotoxins (SE). The main objective of this study was to detect enterotoxin gene cluster (EGC) in S. aureus isolates that caused infections in Paraguayan children in the year 2017, through an observational and cross-sectional study. The detection of the EGC including the seg, sei, sem, sen, seo, and seu genes, was carried out by end-point PCR. 181 S. aureus isolates were collected, most of them caused skin and soft tissue infections (SSTI, n=140, 77%) and came from children under 6 years 50% (n=90). At least one SE gene was detected in 96% (174/181) of isolates and 24% (44/181) carried the entire EGC. An association between methicillin resistance and seg, sei, seo, and seu gene carriage (p ≤0.05) was observed. A high prevalence of EGC was detected in S. aureus isolates collected from infected children attending the main health care centers in Paraguay, its importance is due to the potential of these toxins to aggravate staphylococcal infections.

Cells respond to DNA double-strand breaks by initiating DSB repair and ensuing a cell cycle checkpoint. The primary responder to DSB repair is non-homologous end joining, an error prone repair pathway. However, when DSBs are generated after DNA replication in the G2 phase of the cell cycle, a second DSB repair pathway, homologous recombination, can come into action. Both ATM and ATR are important for DSB-induced DSB repair and checkpoint responses. One method of ATM and ATR working together is through the DNA end-resection of DSBs. As a readout and marker of DNA end-resection, RPA is phosphorylated at Ser4/Ser8 of the N-terminus of RPA32 in response to DSBs. Here, the significance of RPA32 Ser4/Ser8 phosphorylation in response to DNA damage, specifically in S phase to G2 phase of the cell cycle is examined. RPA32 Ser4/Ser8 phosphorylation in G2 synchronized cells is necessary for increases in TopBP1 and Rad9 accumulation on chromatin and full activation of the ATR-dependent G2 checkpoint. In addition, our data suggest RPA Ser4/Ser8 phosphorylation modulates ATM-dependent KAP-1 phosphorylation and Rad51 chromatin loading in G2 cells.

Minirhizotron tubes were installed to monitor root growth dynamics of mature Shiraz grapevines in a rootstock trial established in the hot climate Riverina region of New South Wales, Australia. The vertical root distribution and seasonal root growth dynamics of Shiraz on own-roots and Shiraz grafted on the rootstocks Ramsey, 140 Ruggeri and Schwarzmann was studied for five seasons across a seven-year period to a depth of 60 cm. New root production was significantly influenced by genotype, soil depth, season, growth stage and year. Soil moisture and soil tem-perature were monitored at 10, 30 and 60 cm in the last two seasons. Soil moisture at 30 cm and soil temperature at all three depths were significant predictors of root growth. New root numbers were significantly higher in 140 Ruggeri than the other rootstocks. To the depth studied, 140 Ruggeri roots were evenly distributed from the topsoil down, whereas the majority of roots of Schwarzmann and Shiraz were located at intermediate depths in the 10-40 cm ad 20-40 cm zones respectively, while Ramsey roots were found at 20 cm or below. Depending on genotype, root growth occurred across several phenological stages but tended to peak at flowering. In some years we observed root growth in early and late winter at rates exceeding that of autumn, and this was associated with warmer temperatures during this period. Overall, seasonal rooting dynamics were responsive to abiotic factors but dominated by genotype.

Microbes have evolved many fascinating and complex ways of interacting with conspecifics. Perhaps one of the most interesting is aggregative multicellularity, wherein independent cells come together and adhere to one another in order to form a larger entity. The fundamental benefits of active aggregation into multicellular groups generally remain unclear, and there are many open questions about what selective pressures led to the evolution of this behavior in various eukaryotic and prokaryotic taxa, most notably the dictyostelids and the myxobacteria. Aggregative multicellularity can be partitioned into three main phases: coming together, staying together as a group, and disaggregation. Different selective pressures may have led to adaptations unique to each phase. While aggregative microbial systems generally form elevated multicellular structures such as fruiting bodies, these can vary in complexity and morphology even among closely related species. What evolutionary forces shaped such morphological diversification remains unknown. Strains that are not genetically identical can coaggregate, which can impact group-level function either positively through functional synergy or negatively through harmful exploitation. Such chimerism within aggregates is likely to have played important roles in shaping the evolution of microbial multicellularity. Much further research is needed into the evolutionary forces and processes leading to and shaping the many forms of microbial aggregation.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

In atomic GdFe$_2$ films capped by 4$d$ and 5$d$ transition metals, we show that skyrmions with diameters smaller than 12 nm can emerge. The Dzyaloshinskii--Moriya interaction (DMI), exchange energy, and the magnetocrystalline anisotropy (MCA) energy were investigated based on density functional theory. Since DMI and MCA are caused by spin--orbit coupling (SOC), they are increased with 5$d$ capping layers which exhibit strong SOC strength. We discover a skyrmion phase by using atomistic spin dynamic simulations at small magnetic fields of $\sim$1 T. In addition, a ground state that a spin spiral phase is remained even at zero magnetic field for both films with 4$d$ and 5$d$ capping layers.

The greater Wellington region, New Zealand, is highly vulnerable to large earthquakes because it is cut by active faults. Bulk water supply pipelines cross the Wellington Fault at several different locations, and there is considerable concern about severe disruption of the provision of reticulated water supplies to households and businesses in the aftermath of a large earthquake. A number of policy initiatives have been launched encouraging householders to install rainwater tanks to increase post-disaster resilience. However, little attention has been paid to potential health hazards associated with consumption of these supplies. To assess health hazards for householders in emergency situations, six 200-litre emergency water tanks were installed at properties across the Wellington region, with five tanks being allowed to fill with roof-collected rainwater and one tank being filled with municipal tapwater as a control. Such tanks are predominantly set aside for water storage, and once filled, feature limited drawdown and recharge. Sampling from these tanks was carried out fortnightly for one year, and samples analysed for E. coli, pH, conductivity, a range of major and trace elements, and organic compounds, enabling an assessment of the evolution of water chemistry in water storage tanks over time. Key findings were that the overall rate of E.coli detections in the rain-fed tanks was 17.7%, which is low in relation to other studies. We propose that low incidences of E.coli may be due to biocidal effects of high zinc concentrations in tanks, originating from unpainted galvanised steel roof cladding. Lead concentrations were high compared to other studies, with 69% of rain-fed tank samples exceeding the World Health Organisation’s health-based guideline of 0.01 mg/L. Further work is required to determine risks of short-term consumption of this water in emergency situations.

The objective of this study was to assess the impact of different inoculation technologies on the aerobic biological semi-decomposition process of bokashi-type biofertilizer formulations. We examined their effects on the chemical and biological quality of the product, as well as their influence on the agronomic and nutritional characteristics of red-beet and cabbage crops in the field. The highest yields of field-grown beet crops were obtained from seedlings produced using the following treatments: bokashi biofertilizer + biodynamic preparations 502-507 BPB (62.6 Mg ha-1), bokashi + Chamomilla 12CH (60.2 Mg ha-1), and bokashi + Carbo vegetabilis 12 CH (56.3 Mg ha-1). These results corresponded to an increase of 60.9%, 54.7%, and 44.7%, respectively, compared to the yield of the control treatment (38.9 Mg ha-1). The increase in productivity of cabbage plants was higher in the treatment bokashi + Calcarea carbônica 12 CH (35.8 Mg ha-1), being 148.6% higher than the control (14.4 Mg ha-1).The content of moisture, carbon, nitrogen, C/N ratio, and pH H2O in the majority of the evaluated formulations, comply with the standards outlined in IN Nº 61, 2020, by Ministry of Agriculture, Fisheries and Supply, qualifying them as class "A" solid organic compound fertilizers.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

This paper reviews state of the art Additive Manufactured (AM) IN718 alloy intended for high temperature applications. AM processes have been around for decades and have gained traction in the past five years due to the huge economic benefit it brings to manufacturers. It is crucial for the scientific community to look into AM IN718 applicability in order to see a step-change in the production. Microstructural studies reveal that the grain structure plays a significant role in determining the fatigue lifespan of the material. Controlling IN718 respective phases such as the ϒ’', δ and Laves phase is seen to be crucial. Literature reviews have shown that the mechanical properties of AM IN718 were very close to its wrought counterpart when treated appropriately. Higher homogenization temperature and longer ageing were recommended to dissolve the damaging phases. Various surface enhancement techniques were examined to find out their compatibility to AM IN718 alloy that is intended for high temperature application. Laser shock peening (LSP) technology stands out due to the ability to impart low cold work which helps in containing the beneficial compressive residual stress it brings in high temperature fatigue environment.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Organic light-emitting diodes (OLEDs) have ushered in a technological revolution with their remarkable impact on diverse sectors of our daily lives. These versatile devices known for their outstanding display and lighting capabilities, have become indispensable components in various industries including smartphones, tablets, televisions, and automotive applications. This paper delves into the development of a group of twisted donor-acceptor-donor (D-A-D) derivatives incorporating bicarbazole and benzophenone structures for potential use as blue emitters in OLEDs. The synthesized compounds, namely DB14, DB23 and DB29, were designed with various alkyl side chains to enhance their film forming properties as for blue emitters. Characterization and evaluation of these derivatives included photophysical, electrochemical, thermal, and electroluminescent analysis. Some of the OLED devices incorporating these emitters demonstrated promising performance with maximum current efficiency (CEmax) of 2.6 cd/A and external quantum efficiency (EQEmax) of 5.3%. Notably, the DB23 emitter exhibited the highest EQE among all devices. The study also emphasizes the influence of host-guest energy transfer, optimal doping concentrations, and molecular structures on device performance. This research not only contributes to the understanding of advanced OLED materials but also provides insights into designing efficient blue emitters for future display and lighting applications, thereby advancing the field of organic electronics.

It is unclear whether military shoes (combat boots and sports shoes) attenuate loading rate or affect force transfer during walking. Therefore, this study compared ground reaction forces (GRF) related to impact and force transfer between combat boots, military sports shoes and running shoes. Ten army recruits walked over a walkway with two force plates embedded. GRF were measured when walking barefoot (for data normalization) and with combat boots, military sports shoes and running shoes. Loading rate, first and second peak forces and push-off rate of force were computed along with temporal analysis of waveforms. Reduced loading rate was observed for the running shoe compared to the combat boot (p = 0.02 and d = 0.98) and to the military sports shoe (p = 0.04 and d = 0.92). The running shoe elicited a smaller second peak force than the combat boot (p < 0.01 and d = 0.83). Walking with military shoes and combat boots led to larger force transfer then running shoes potentially due to harder material used in midsole composition (i.e. styrene-butadiene rubber). These results could lead to a potentially larger risk of injuries while long duration walking in military shoes and boots compared to traditional running shoes.

With proper processing and utilization, biofortified cassava may contribute to the nutritional status of the consumers, thus, the need for this study. High-quality cassava flour from white- (TME 419) and biofortified (TMS 01/1368) cassava varieties were produced at a commercial processing factory, after which the flour is composite with wheat flour to produce bread. The nutritional composition, physical properties and sensory quality of the composite bread were analyzed using standard methods. Results showed that composite bread from 20% biofortified cassava flour (20-YCF) had a higher value of total β-carotene (0.74 μg/g), moisture (37.83%) and ash (2.29%) contents. The fat (3.72%) and protein (12.83%) contents were higher in 20% white cassava flour (20-WCF) composite bread. The 20-YCF composite bread had the highest loaf volume (3286.2 cm3), elasticity (6.32), chewiness (40.51 N) and gumminess (6.41), 20-WCF composite bread had higher specific volume (3.59 cm3/g) and hardness (176.50 N). The 100% wheat bread had higher cohesiveness (0.10) and loaf weight (932.35 g). A significant negative correlation (r = - 0.98, p≤0.05) exist between bread hardness and protein content. The composite bread compared favourably with the 100% wheat bread in terms of weight and aroma, but, the 100% wheat bread was more acceptable.

Loss-of-function mutations of the spermine synthase gene (SMS) result in Snyder-Robinson Syndrome (SRS), a recessive X-linked syndrome characterized by intellectual disability, osteoporosis, hypotonia, speech abnormalities, kyphoscoliosis, and seizures. As SMS catalyzes the biosynthesis of the polyamine spermine from its precursor spermidine, SMS deficiency causes a lack of spermine with an accumulation of spermidine. As polyamines, spermine and spermidine play essential cellular roles that require tight homeostatic control to ensure normal cell growth, differentiation, and survival. Using patient-derived lymphoblast cell lines, we sought to comprehensively investigate the effects of SMS deficiency on polyamine homeostatic mechanisms including polyamine biosynthetic and catabolic enzymes, derivatives of the natural polyamines, and polyamine transport activity. In addition to decreased spermine and increased spermidine in SRS cells, ornithine decarboxylase activity and its product putrescine were significantly decreased. Treatment of SRS cells with exogenous spermine revealed that polyamine transport was active, as the cells accumulated spermine, decreased their spermidine level, and established a spermidine-to-spermine ratio within the range of wild type cells. SRS cells also demonstrated elevated levels of tissue transglutaminase, a change associated with certain neurodegenerative diseases. These studies form a basis for further investigations into the leading biochemical changes and properties of SMS-mutant cells that potentially represent therapeutic targets for the treatment of Snyder-Robinson Syndrome.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.