The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Physiological storage disorders continue to cause sizable economic losses in a range of commercially important pomefruit cultivars. Given similar storage regimes, the incidence and severity of browning disorders in the apple cultivar ‘Braeburn’ can vary in different years in a way that can be explained by the interaction of preharvest seasonal and orchard factors. Over a three-year period (2016 to 2019) at the Kompetenzzentrum Obstbau-Bodensee (KOB) in Southwest Germany a range of orchard and storage treatments were conducted for: air temperature during cell division for three weeks post petalfall or during four weeks preharvest, calcium orchard sprays, crop load and harvest timings. Following controlled atmosphere (CA) storage, the disorder incidence for internal browning and cavity formation varied markedly over the three different growing seasons. Crop load treatments strongly influenced the expression of browning disorders in all years. Differences in air temperatures (△ +/- 2 °C compared to ambient) during the cell division period showed little effect on browning incidence. Warm night temperatures (>10 °C) prior to harvest can reduce internal browning in ‘Braeburn’ apples during CA storage and shelf-life.

It is well known that a sequence of two non-collinear Lorentz boosts (pure Lorentz transformations) does not correspond to a Lorentz boost, but involves a spatial rotation, the Wigner or Thomas-Wigner rotation. We visualize the interrelation between this rotation and the relativity of distant simultaneity by moving a Born-rigid object on a closed trajectory in several steps of uniform proper acceleration. Born-rigidity implies that the stern of the boosted object accelerates faster than its bow. It is shown that at least five boost steps are required to return the object's center to its starting position, if in each step the center is assumed to accelerate uniformly and for the same proper time duration. With these assumptions, the Thomas-Wigner rotation angle depends on a single parameter only. Furthermore, it is illustrated that accelerated motion implies the formation of an event horizon. The event horizons associated with the five boosts constitute a natural boundary to the rotated Born-rigid object and ensure its finite size.

Optical sensor data can be used to determine changes in anthocyanins, chlorophyll and soluble solids content (SSC) in apple production. In this study, visible and near-infrared spectra (729 to 975 nm) were transformed to SSC values by advanced multivariate calibration models i.e. partial least square regression (PLSR) in order to test the substitution of destructive chemical analyses through non-destructive optical measurements. Spectral field scans were carried out from 2016 to 2018 on marked ’Braeburn’ apples in Southwest Germany. The study combines an in-depth statistical analyses of longitudinal SSC values with horticultural knowledge to set guidelines for further applied use of SSC predictions in the orchard to gain insights into apple carbohydrate physiology. The PLSR models were investigated with respect to sample size, seasonal variation, laboratory errors and the explanatory power of PLSR models when applied to independent samples. As a result of Monte Carlo simulations, PLSR modelled SSC only depended to a minor extent on the absolute number and accuracy of the wet chemistry laboratory calibration measurements. The comparison between non-destructive SSC determinations in the orchard with standard destructive lab testing at harvest on an independent sample showed mean differences of 0.5 % SSC over all study years. SSC modelling with longitudinal linear mixed-effect (LME) models linked high crop loads to lower SSC values at harvest and higher SSC values for fruit from the top part of a tree.

Herpesviruses usurp cellular stress responses to avoid immune detection while simultaneously promoting viral replication and spread. The unfolded protein response (UPR) is an evolutionarily conserved stress response that is activated when the protein load in the ER saturates its chaperone folding capacity causing an accrual of misfolded proteins. Through translational and transcriptional reprogramming, the UPR aims to restore protein homeostasis; however, if this fails the cell undergoes apoptosis. It is commonly thought that many enveloped viruses, including herpesviruses, may activate the UPR due to saturation of the ER with nascent glycoproteins and thus these viruses may have evolved mechanisms to evade the potentially negative effects of UPR signaling. Over the past fifteen years there has been considerable effort to provide evidence that different viruses may reprogram the UPR to promote viral replication. Here we provide an overview of the molecular events of UPR activation, signaling and transcriptional outputs, and highlight key findings that demonstrate that the UPR is an important cellular stress response that herpesviruses have hijacked to facilitate persistent infection.

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study; real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)₂D₃. Frist; a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10nM but not at 100nM of 1,25(OH)₂D₃ treatment; suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation; gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1; SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1; no changes in gene expression were observed. However; a concomitant decrease in CAT and SOD1 mRNA; and increase in SOD2 mRNA after 24 hours of 10nM 1,25(OH)₂D₃ treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 hours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

Soil CO2 efflux (FCO2) plays a dominant role in the terrestrial carbon (C) cycle but interpreting constraints on local observations is impeded by challenges in disentangling belowground CO2 sources. Trees contribute most C to forest soils, so linking aboveground properties to FCO2 could open new avenues to study plant-soil feedbacks and facilitate scaling; furthermore, FCO2 responds dynamically to meteorological conditions, complicating predictions of total FCO2 and forest C balance. We tested for proximity effects of individual Acer saccharum Marsh. trees on FCO2, comparing FCO2 within 1 m of mature stems to background fluxes before and after an intense rainfall event. Wetting significantly increased background FCO2 (6.4±0.3 vs. 8.6±0.6 s.e. μmol CO2 m-2s-1), with a much larger enhancement near tree stems (6.3±0.3 vs. 10.8±0.4 μmol CO2 m-2s-1). FCO2 varied significantly among individual trees and post-rain values increased with tree diameter (with a slope of 0.058 μmol CO2 m-2s-1 cm-1). Post-wetting amplification of FCO2 (the ‘Birch effect’) in root zones often results from the improved mobility of labile carbohydrates and further metabolization of recalcitrant organic matter, which may both occur at higher densities near larger trees. Our results indicate that plant-soil feedbacks change through tree ontogeny and provide evidence for a novel link between whole-system carbon fluxes and forest structure.

Ebola virus (EBOV) is a zoonotic pathogen causing severe hemorrhagic fevers in humans and non-human primates with high case fatality rates. In recent years, the number and extent of outbreaks has increased, highlighting the importance of better understanding the molecular aspects of EBOV infection and host cell interactions to control this virus more efficiently. Many viruses, including EBOV, have been shown to recruit host proteins for different viral processes. Based on a genome-wide siRNA screen, we recently identified the cellular host factor carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) to be involved in EBOV RNA synthesis. However, mechanistic details of how this host factor plays a role in the EBOV life cycle remain elusive. In this study, we analyzed the functional and molecular interactions between EBOV and CAD. To this end, we used siRNA knockdowns in combination with various reverse-genetics based lifecycle-modelling systems and additionally performed co-immunoprecipitation and co immunofluorescence assays to investigate the influence of CAD on individual aspects of the EBOV life cycle and to characterize the interactions of CAD with viral proteins. Following this approach, we could demonstrate that CAD directly interacts with the EBOV nucleoprotein NP, and that NP is sufficient to recruit CAD into inclusion bodies dependent on the GLN-domain of CAD. Further, siRNA knockdown experiments indicated that CAD is important for both viral genome replication and transcription, while substrate rescue experiments showed that the function of CAD in pyrimidine synthesis is indeed required for those processes. Together this suggests that NP recruits CAD into inclusion bodies via its GLN domain in order to provide pyrimidines for EBOV genome replication and transcription. These results define a novel mechanism by which EBOV hijacks host cell pathways in order to facilitate genome replication and transcription, and provide further basis for the development of host directed broad spectrum antivirals.

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles compared to previously reported protocols.

Drought events are predicted to become more prevalent in the future. Evaluating the performance of herbicide-resistant and susceptible weed ecotypes to progressive drought can provide insights into whether resistance trait(s) increased or reduced the fitness of a resistant population. Two experiments were conducted in the greenhouse between January and May 2021 to evaluate drought tolerance differences between Palmer amaranth accessions resistant to S-metolachlor or glyphosate and their susceptible counterparts. The accessions used were: S-metolachlor-resistant (17TUN-A), a susceptible standard (09CRW-A), and glyphosate-resistant (22 to 165 EPSPS copies) and glyphosate-susceptible (3 to 10 EPSPS copies) plants from accession 16CRW-D. Daily transpiration of each plant was measured. The daily transpiration rate was converted to normalized transpiration ratio (NTR) using a double-normalization procedure. The daily soil water content was expressed as a fraction of transpirable soil water (FTSW). The threshold FTSW (FTSWcr), after which NTR decreases linearly, was estimated using a two-segment linear regression analysis. The data showed differences between S-metolachlor- resistant and -susceptible accessions (P ≤ 0.05). The FTSW remaining in the soil at the breakpoint for the S-metolachlor-susceptible accession (09CRW-A) was 0.17±0.007. The FTSW remaining in the soil at the breakpoint for the S-metolachlor-resistant accession (17TUN-A) was 0.23±0.004. Although the mechanism endowing resistance to S-metolachlor might have contributed to increased drought tolerance, follow-up experiments are needed to verify this finding. Increased EPSPS copy number did not improve drought tolerance of Palmer amaranth.

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (>12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Human endogenous retroviruses (HERV) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV promoting pathological conditions including the development of autoimmunity, neurodegenerative disease and cancer. What infections then trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases Crohn’s, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis and autoimmune thyroiditis. MAP is also associated with Parkinson’s disease. Autoimmune diabetes, multiple sclerosis and rheumatoid arthritis are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via unsilencing of HERV. We examine the link between the ever-increasing number of MAP- associated diseases, the MAP/HERV intersection with these diverse medical conditions and propose treatment opportunities based upon this association.

Topological indices have been used to modeling biological and chemical properties of molecules in quantitive structure property relationship studies and quantitive structure activity studies. All the degree based topological indices have been defined via classical degree concept. In this paper we define a novel degree concept for a vertex of a simple connected graph: S degree. And also we define S indices of a simple connected graph by using the S degree concept. We compute the S indices for well-known simple connected graphs such as paths, stars, complete graphs and cycles.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

MicroRNA-155 (miR-155) expression promotes inflammatory responses in macrophages. Activation of macrophages with lipopolysaccharide (LPS) elevates miR-155, while the anti-inflammatory cytokine interleukin-10 (IL10) reduces miR-155 levels. MiR-155 exists in two forms, miR-155-5p and miR-155-3p, produced from the precursor of miR-155 (pre-miR-155). MiR-155-5p is the most abundant strand in activated macrophages, but in response to LPS, the miR-155-3p level is upregulated first, followed by miR-155-5p later. We have previously identified CELF2 protein which interacts with pre-miR-155 and impairs miR-155-5p expression. We now show that CELF2 only regulates the miR-155-5p expression and that another protein FUBP1 controls miR-155-3p levels in response to LPS and IL10.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

Despite well-documented health benefits of probiotics Saccharomyces, its application in oral health has not been comprehensively assessed. Dental caries is a transmissible disease initiated by acid production of cariogenic bacteria and yeast, such as Streptococcus mutans and Candida albicans, on tooth enamel and followed by subsequent enamel demineralization. Here, we investigated the effect of two Saccharomyces strains (Saccharomyces boulardii, Saccharomyces cerevisiae) on S. mutans-C. albicans cross-kingdom interactions using a cariogenic planktonic model. Viable cells, pH changes and gene expression were measured. S. cerevisiae and S. boulardii inhibited the growth of C. albicans either in dual-, or multi-species conditions. Saccharomyces also inhibited C. albicans hyphal formation. Furthermore, Saccharomyces reduced the acidity of the culture medium which usually plummeted below pH 5 when S. mutans and C. albicans were present in the model. The presence of Saccharomyces maintained the culture medium above 6 even after overnight incubation, demonstrating a protective potential against dental enamel demineralization. S. boulardii significantly downregulated S. mutans atpD and eno genes expression. Overall, our results shed light on a new promising candidate, Saccharomyces, for dental caries prevention due to its potential to create a less cariogenic environment marked by a neutral pH and reduced growth of C. albicans.

Prime numbers are the atoms of mathematics and mathematics is needed to make sense of the real world. Finding the Prime number structure and eventually being able to crack their code is the ultimate goal in what is called Number Theory. From the evolution of species to cryptography, Nature finds help in Prime numbers. One of the most important advances in the study of Prime numbers was the paper by Bernhard Riemann in November 1859 called “Ueber die Anzahl der Primzahlen unter einer gegebenen Grösse” (On the number of primes less than a given quantity). In that paper, Riemann gave a formula for the number of primes less than x in terms the integral of 1/log(x) and the roots (zeros) of the zeta function defined by: Where ζ(z) is a function of a complex variable z that analytically continues the Dirichlet series. Riemann also formulated a conjecture about the location of the zeros of RZF, which fall into two classes: the "trivial zeros" -2, -4, -6, etc., and those whose real part lies between 0 and 1. Riemann's conjecture Riemann hypothesis [RH] was formulated as this: [RH] The real part of every nontrivial zero z* of the RZF is 1/2. Proving the RH is, as of today, one of the most important problems in mathematics. In this paper we will provide a proof of the RH. The proof of the RH will be built following these five parts: PART 1: Description of the RZF PART 2: The C-transformation PART 3: Application of the C-transformation to in Re(z) 0 to obtain ζ(z)=X(z)-Y(z) PART 4: Analysis of the values of z such that X(z)=Y(z), and |X(z)|=|Y(z)|, that equates to ζ(z)=0 Proof that |X(z)|=|Y(z)| only if Re(z)=1/2 Conclude that ζ(z)=0 only if Re(z)=1/2 for Re(z) 0 PART 5: We will also prove that all non-trivial zeros of ζ(z) in the critical line of the form are not distributed randomly. There is a relationship between the values of those zeros and the Harmonic function that leads to an algebraic relationship between any two zeros.

Introduction: The choice of Cardiac Preservation Solution (CPS) for myocardial protection at the time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm Heart Transplantation (HTx) outcomes. Thus, we retrospectively analyzed our adult HTx performed with two different CPS, during a period of 12 years, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. Methods: From January 2009 to December 2020, 154 adult HT were performed in our hospital. Patients were divided in two groups according to the CPS used: St. Thomas (n=75, group P 1) and HTK-Custodiol (n=79, group P 2). The choice of CPS was related to an institutional policy; from 2009 to 2015, St. Thomas solution was exclusively used, and after that, HTK-Custodiol alone. Results: There was no significant difference between the two groups in terms of preoperative and intraoperative features. Postoperatively, the Custodiol group showed significantly lower inotropic score (p&lt;0.0001), mean rejection score (p= 0.036) and 30 days mortality (p=0.0068). The use of HTK-Custodiol was the only variable that improved midterm survival (HTK-Custodiol vs St Thomas, HR= 0.20 (95% CI: 0.069 -0.6) p=0.0039). Conclusion: In our single center experience, using HTK-Custodiol as myocardial protection during heart procurement leads to improved outcomes after HTx, including postoperative inotropic score, rejection score, 30-days mortality and midterm survival.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

Herpes simplex virus (HSV) infections can be treated with direct acting antivirals like acyclovir and foscarnet, but long-term use can lead to drug resistance, which motivates research into broadly-acting antivirals that can provide a greater genetic barrier to resistance. Photodynamic inactivation (PDI) employs a photosensitizer, light, and oxygen to create a local burst of reactive oxygen species that inactivate microorganisms. The botanical plant extract Orthoquin^TM is a powerful photosensitizer with antimicrobial properties. Here we report that Orthoquin also has antiviral properties. Photoactivated Orthoquin inhibited herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) infection of target cells in a dose-dependent manner, across a broad range of sub-cytotoxic concentrations. HSV inactivation required direct contact between Orthoquin and the inoculum, whereas pre-treatment of target cells had no effect. Orthoquin did not cause appreciable damage to viral capsids or pre-mature release of viral genomes as measured by qPCR for the HSV-1 genome. By contrast, immunoblotting for HSV-1 antigens in purified virion preparations suggested that higher doses of Orthoquin had a physical impact on certain HSV-1 proteins that altered protein mobility or antigen detection. Orthoquin PDI also inhibited the non-enveloped adenovirus (AdV) in a dose-dependent manner, whereas Orthoquin-mediated inhibition of the enveloped vesicular stomatitis virus (VSV) was light-independent. Together, these findings suggest that broad antiviral effects of Orthoquin-mediated PDI may stem from damage to viral attachment proteins.

The retina is a complex and fragile photosensitive part of the central nervous system which is prone to degenerative diseases leading to permanent vision loss. No proven treatment strategies exist to treat or reverse the degenerative conditions. Recent investigations demonstrate that cell transplantation therapies to replace the dysfunctional retinal pigment epithelial (RPE) cells and or the degenerating photoreceptors (PRs) are viable options to restore vision. Pluripotent stem cells, retinal progenitor cells and somatic stem cells are the main cell sources used for cell transplantation therapies. The success of retinal transplantation based on cell suspension injection is hindered by limited cell survival and lack of cellular integration. Recent advances in material science helped to develop strategies to grow cells as intact monolayers or as sheets on biomaterial scaffolds for transplantation into the eyes. Such implants are found to be more promising than the bolus injection approach. Tissue engineering techniques are specifically designed to construct biodegradable or non-degradable polymer scaffolds to grow cells as a monolayer and construct implantable grafts. The engineered cell construct along with the extracellular matrix formed, can hold the cells in place to enable easy survival, better integration and improved visual function. This article reviews the advances in the use of scaffolds for transplantation studies in animal models and its application in current clinical trials.

The implementation of management systems has become a strategic advantage in achieving business goals, especially in industrial organizations, but the implementation of social responsibility requirements is especially ethical. Large multinational companies have long been developing and, in particular, implementing their own codes of conduct, which include their suppliers, to demonstrate their commitment to Corporate Social Responsibility (CSR). The compliance with CSR requirements from stakeholders is thus extended or intertwined with requirements in established management systems (MSs). The objectives of the study were to (1) analyze the different approaches to CSR in internationally recognized cross-industry and industry-specific standards and codes in different industries; (2) select the most appropriate framework for assessing the degree of applicability of CSR in the selected management systems and develop a methodology for its assessment; (3) apply the proposed methodology (referred to as SRIMS) in the selected areas: automotive industry, research organization, and metallurgical industry; (4) through ANOVA, validate its use for assessing the overall level of CSR applicability in an organization's established management systems. The application of the Bonferroni method confirmed the hypotheses that the developed SRIMS model is a sufficiently appropriate tool for assessing the overall level of applicability of CSR requirements to established MSs.

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

Globally, groundwater is the largest distributed storage of freshwater and plays an important role in an ecosystem’s sustainability in addition to aiding human adaptation to both climatic change and variability. However, groundwater resources are dynamic and often change as a result of land usage, abstraction, as well as variation in climate. To solve these challenges, many conventional solutions, such as certain numerical techniques, have been proffered for groundwater modelling. The global evolution of the Internet of Things (IoT) has enhanced the culture of data gathering for the management of groundwater resources. In addition, efficient data-driven groundwater resource management relies hugely on information relating to changes in groundwater resources as well as their availability. At the moment, some studies in the literature reveal that groundwater managers lack an efficient and real-time groundwater management system that is needed to gather the required data. Additionally, the literature reveals that the existing methods of collecting data lack the required efficiency to meet computational model requirements and meet management objectives. Unlike previous surveys, which solely focussed on particular groundwater issues related to simulation and optimisation management methods, this paper seeks to highlight the current groundwater management models as well as the IoT contributions.

Historical forest management practices in the southwestern US have left forests prone to high intensity, stand-replacement fires. Effective management to reduce the cost and impact of forest-fire management and allow fires to burn freely without negative impact depends on detailed knowledge of stand composition, in particular, above-ground biomass (AGB). Lidar-based modeling techniques provide opportunities to reduce costs and increase ability of managers to monitor AGB and other forest metrics. Using Bayesian Model Averaging (BMA), we develop a regionally applicable lidar-based statistical model for Ponderosa pine and mixed conifer forest systems of the southwestern USA, using previously collected field data. The selected regional model includes a mid and low canopy height metric, a canopy cover, and height distribution term. It explains 72% of the variability in field estimates of AGB, and the RMSE of the two independent validation data sets are 23.25 and 32.82 Mg/ha. The regional model developed is structured in accordance with previously described models fit to local data, and performs equivalently to models designed for smaller scale application. Developing regional models for broad scale application provides a cost-effective, robust approach for managers to monitor and plan adaptively at the landscape scale.

There is increased concern that the quality, generalizability, and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host immune reaction, and responses to antifungal therapy. We used diabetic ketoacidotic (DKA) or neutropenic mice infected with either Rhizopus delemar or Mucor circinelloides. The only difference detected was that when DKA mice were infected with M. circinelloides, female mice were more resistant to infection than male mice (median survival time of 5 vs. 2 days for female and male mice, respectively). However, a 100% lethality was detected among infected animals of both sexes. Treatment with either liposomal amphotericin B (L-AMB) or posaconazole (POSA) protected mice from infection and eliminated the difference seen between infected but untreated female and male mice. Treatment with L-AMB consistently outperformed POSA in prolonging survival and reducing tissue fungal burden of DKA and neutropenic mice infected with R. delemar or M. circinelloides, in both mouse sexes. Although little difference was detected in cytokine levels among both sexes, mucormycosis infection in the DKA mouse model induced more inflammatory cytokines/chemokines involved in neutrophil (CXCL1) and macrophage (CXCL2) recruitment vs. uninfected mice. As expected, this inflammatory response was reduced in the neutropenic mouse model. Our studies show that there are few differences between female and male DKA or neutropenic mice infected with mucormycosis with no effect on the outcome of treatment or host immune response.

This study investigates proximate drivers of cropland and forest degradation in Kloto district (Togo, West Africa) as, way of, exploring integrated sustainable landscape approaches in respect to socio-economic and environmental needs and requirements. Net change analysis of major cash and food crops based on three time steps Landsat data (1985–2002, 2002–2017 and 1985–2017) and quantitative analysis from participatory survey data with farmers and landowners are used. Study underlines poor agricultural systems and cassava farming as major impediments to alarming forest losses between 1985–2017. Significant net loss in forests cover by 23.6% and surface areas under cultivation of cocoa agroforestry and maize by 12.99 and 10.1% from 1985 to 2017, due to, intensive cassava cropping (38.78%) and settlement expansions (7.84%). Meanwhile, loss in forest cover between 2017 and 2002 was marginal (8.36%) compared to the period 1985–2002 for which the loss was considerable (15.24%). Based on participatory surveys, majority of agricultural lands are threatened by erosion or physical deterioration (67.5%), land degradation or salt deposits and loss of micro/macro fauna and flora at 56.7%, declining in soil fertility (32.5%), soil water holding capacity (11.7%) and changes in soil texture (3.3%). Majority of farmers adhere to the adoption of the proposed climate smart practices with emphasis on cost effective drip irrigation systems (45.83%), soil mulching (35%) and adoption of drought resilient varieties (29.17%) to anticipate drought spells adverse. The study concludes that low adoption of improved soil conservation, integrated water management and harvesting systems and low productive and adaptive cultivars entail extreme degradation of croplands and crops productivity decline. Therefore, farmers are forced to clear more forests in search of stable and healthy soils for production and extraction of forest products to meet their food demands and improve their livelihoods conditions. Capacity building on integrated pathways of soil and land management practices are therefore needed to ensure sustainable and viable socio-ecological systems at local scale.

Bovine tuberculosis surveillance in Northern Ireland includes Multiple-Locus Variable number tandem repeat Analysis (MLVA) to determine the Mycobacterium bovis genetic type present in both cattle, and the predominant wildlife host, the European badger (Meles meles). These data are informative for investigating clusters of infection and understanding the scale at which interspecific transmission may occur. We utilised a comprehensive dataset of routinely sampled isolates from infected cattle and from badgers killed in road-traffic accidents to investigate the spatial co-location of MLVA types in, and between, the badger and cattle populations. Furthermore, we investigate the hypothesis that the farming enterprise type might explain some variation in this relationship. MLVA types were spatially co-localised in cattle and RTA badger hosts, indicative of a shared epidemic. Dairy herds were more likely to have at least one MLVA type in common with nearby RTA badgers, compared to non-dairy herd types. Marginally more MLVA spatial clustering was observed in non-dairy herds, which may be a consequence relatively more between-herd movements. For the cattle population, local transmission mechanisms such as infection from contiguous herds, infectious wildlife and short-range between-herd cattle movements appear primarily to drive the epidemic: there appears to be a more limited role for long-range movements. Animal management practices are likely the driving force behind this observation, as beef rearing is associated with elevated numbers of animal movements compared to dairy herds.

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of C. tropicalis and C. albicans co-infection on dextran sodium sulfate (DSS)-induced colitis in mice. Colitis severity was evaluated using histology and colonoscopy. Mice were mono-inoculated with C. albicans, C. tropicalis or co-challenged with both species. Mice were administered 3% DSS to induce acute colitis. Biofilm activity was assessed using (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl] 2H-tetrazoliumhydroxide (XTT) assay. Abundance of C. albicans in the colon tissues was assessed by immunohistochemistry. Co-challenged mice showed decreased colitis severity compared to mono-inoculated mice. The XTT assay demonstrated a marked decrease of C. albicans biofilm production in a C. albicans culture incubated with C. tropicalis supernatant. Immunohistochemical staining showed that C. albicans was more abundant in the mucosa of C. albicans mono-inoculated mice compared to the co-inoculated group. These data indicate an antagonistic microbial interaction between the two Candida species, where C. tropicalis may produce molecules capable of limiting the ability of C. albicans to adhere to the host intestinal surface leading to a reduction in biofilm formation.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

The viewpoint and reaction of a country towards climate change are shaped by its political, cultural, and scientific backgrounds, in addition to the distinct characteristics of its evolving climate and the anticipated and actual consequences of the phenomenon in the times ahead. A region's climate has a significant impact on how water is managed and used, mostly in the primary sector (agroforestry systems, livestock, and agriculture), and both the distribution of ecosystem types and the amount and spreading of species on Earth. As a result, the environment and agricultural practices are affected by climate, so evaluating both distribution and evolution is extremely pertinent. Towards this aim, the climate distribution and evolution in the S. Francisco River basin (SFRB) is assessed in three periods (1970−2000, 1981−2022) in the past and 20412060 in the future from an ensemble of GCMs under two SSPs (Shared Socioeconomic Pathways), SSP2-4.5 and SSP5-8.5. The Köppen-Geiger (KG) climate classification system is analyzed, and climate change impacts are inferred for this watershed located in central-eastern Brazil, covering an area equivalent to 8% of the country. Results predict the disappearance of the hot-summer (Csa) and warm-summer (Csb) Mediterranean climates, and a reduction/increase in the tropical savanna with dry winter (Aw)/dry summer (As). A striking increase in the semi-arid hot (BSh-steppe) climate is predicted with a higher percentage (10%) under SSP5-8.5. The Source and the mouth of SFRB are projected to endure the major impacts of climate change that is followed by a predicted increase/decrease in temperature/precipitation. Future freshwater resource availability, and quality for human use will all be impacted. Consequences on ecosystems, agricultural and for the socioeconomic sectors within the SFRB might deepen the current contrasts between regions, urban and rural areas, and even between population groups, thus translating to a larger extent, the inequality that still characterizes Brazilian society. Maps depicting land use and cover changes in the São Francisco River basin from 1985 to 2022 highlight tendencies such as urbanization, agricultural expansion, deforestation, and changes in shrubland and water bodies. Urban areas fluctuated slightly, while cropland significantly increased from 33.57% to 45.45%, and forest areas decreased from 3.88% to 3.50%. Socioeconomic data reveals disparities among municipalities: 74.46% with medium Human Development Index (HDI), 0.59% with very high HDI, and 9.11% with low HDI. Most municipalities have a Gross Domestic Product (GDP) per capita below US$ 6,000. Population distribution maps show a predominance of small to medium-sized urban and rural communities, reflecting the basin's dispersed demographic and economic profile. To build routes towards a shared sustainable goal—namely, to adapt and reduce the expected climate change impacts in SFRB—it is imperative that integrated measures be conducted with the cooperation of stakeholders, local population, and decision-makers.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

In this systematic review, the PRISMA method was applied to examine publications from the last two decades that have investigated the noxious gaseous emissions from dairy barns. The aim was to analyse the outcomes from literature studies estimating the quantities of polluting gases produced in dairy barns, with specific focus on ammonia (NH₃) emissions. The review also explores proposed methods to reduce the associated effects through mitigation strategies. Estimation of NH₃ emissions is significantly influenced by the complex interactions among several factors, including animal management practices, such as controlling animal behavioral activities; manure management, like utilising practices for floor manure removal; the type of structure housing the animals, whether it is naturally or mechanically ventilated; and environmental conditions, such as the effects of temperature, wind speed, relative humidity, and ventilation rate on NH₃ release in the barn. These influential components have been considered by researchers, identifying targeted mitigation strategies. Despite growing attention to the issue, gaps in the scientific literature were identified and discussed, particularly regarding the analysis of mitigation strategies and their long-term impacts (i.e., environmental, economic and productivity-wise).

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

Micro-combs [1-4] - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts [5,6], but in an integrated footprint. The discovery of temporal soliton states (DKS – dissipative Kerr solitons) [4,7-11] as a means of mode-locking micro-combs has enabled breakthroughs in many fields including spectroscopy [12,13], microwave photonics [14], frequency synthesis [15], optical ranging [16,17], quantum sources [18,19], metrology [20,21] and more. One of their most promising applications has been optical fibre communications where they have enabled massively parallel ultrahigh capacity multiplexed data transmission [22,23]. Here, by using a new and powerful class of micro-comb called “soliton crystals” [11], we achieve unprecedented data transmission over standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits per second (Tb/s) using the telecommunications C-band at 1550nm with a spectral efficiency – a critically important performance metric - of 10.4 bits/s/Hz. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with a low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format of 64 QAM (quadrature amplitude modulated). We demonstrate error free transmission over 75 km of standard optical fibre in the laboratory as well as in a field trial over an installed metropolitan optical fibre network. These experiments were greatly aided by the ability of the soliton crystals to operate without stabilization or feedback control. This work demonstrates the capability of optical soliton crystal micro-combs to perform in demanding and practical optical communications networks.

Vertically aligned Fe, S, and Fe-S doped anatase TiO₂ nanotube arrays are prepared by electrochemical anodization process using an organic electrolyte in which lactic acid is added as an additive. In the electrolyte, nanotube layers of greater length (12 μm) and high order with inner diameter of approx. 90 nm and outer diameter of approx. 170 nm are achieved. Doping of Fe, S, and Fe-S via simple wet impregnation method substituted Ti and O sites with Fe and S, which leads to enhance the rate performance at high discharge current densities. Discharge capacities of TiO₂ tubes increased from 82 mAh g-1 (bare) to 165 mAh g-1 for Fe-S doped TiO₂ at high current densities of 0.3 mAcm-2 after 100 cycles with exceptional capacity retention of 85% after 100 cycles. Owing to the enhancement of thermodynamic and kinetic properties by doping of Fe-S, Li-diffusion increas2ed resulting in remarkable discharge capacities of 143 mAh g-1 and 89 mAh g-1 at a current density of 7.4 mA cm-2 and 19 mA cm-2, respectively.

Planning and implementation of construction projects are difficult processes and are burdened with many risk elements. The budget spread over time, which is developed on the basis of the schedule, presents the expected distribution of costs throughout the duration of the works, which during the implementation of the project is subject to constant changes resulting from time, cost and organizational factors. Managing construction contracts requires managers to be able to analyze on an ongoing basis the variances of production costs - from the values calculated in the offer cost estimate and assumed in the Budgeted Cost of Work Scheduled. The article attempts to analyze the emerging time and cost variances using proprietary C-S and S-C monitoring, based on simple indicators of the EVM method. An example of construction of a multi-family housing development was used to study the variances of planned and incurred costs.

For many engineering applications it is sufficient to use the concept of simple materials. However, higher gradients of the kinematic variables are taken into account to model materials with internal length scales as well as to describe localization effects using gradient theories in finite plasticity or fluid mechanics. In many approaches length scale parameter have been introduced that are related to a specific micro structure. An alternative approach is possible, if a thermodynamically consistent framework is used for material modelling as shown in the present contribution. However, even if sophisticated and thermodynamically consistent material models can be established there are still not yet standard experiments to determine higher order material constants. In order to contribute to this ongoing discussion system identification based on the method of self-adaptive filtering is proposed in this paper. To evaluate the effectiveness of this approach it has been applied to second-order gradient materials considering longitudinal vibrations. Based on thermodynamically consistent models that have been solved numerically it has been possible to prove that system identification based on self-adaptive filtering can be used effectively for both narrow-band and broadband signals in the field of second-order gradient materials. It has also been found that the differences identified for simple materials and gradient materials allow for condition monitoring and detection of gradient effects in the material behavior.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

Retrospective information about the climate system and plant ecophysiology are key inputs in climate and Earth system modelling. Dendrochronology provides such information with large spatiotemporal coverage, and stable carbon isotope (¹³C/¹²C) analysis across tree-ring series is among the most advanced dendrochronological tools. For the past seventy years, this analysis was performed on whole molecules, and, to this day, ¹³C/¹²C variation is attributed to ¹³C discrimination during CO₂ diffusion into leaves and assimilation by rubisco. By contrast, ¹³C discrimination by post-rubisco processes is presumed constant. Here, recently reported results on the first dataset of intramolecular ¹³C discrimination in tree rings were synthesised by variance component analysis. The emerging picture is not consistent with the classical (DR-discrimination-centred) concepts and practices of carbon-isotope dendrochronology. Specifically, leaf and stem post-rubisco discrimination each account for more variation in the data than diffusion-rubisco discrimination, i.e., post-rubisco discrimination is not constant. Furthermore, diffusion-rubisco discrimination is used widely as proxy of leaf intrinsic water-use efficiency (iWUE), a key determinant in the responses of global biogeochemical cycles to climate change. However, since diffusion-rubisco discrimination is a small component of the total data variance, whole-molecule analysis yields confounded iWUE estimates, yet intramolecular analysis will likely offer solutions. Lastly, all currently observed ¹³C/¹²C-climate relationships are attributed to diffusion-rubisco discrimination. However, here, relationships with temperature and radiation derive from leaf-level post-rubisco discrimination while relationships with precipitation derive from stem-level post-rubisco discrimination. That said, advances in mass spectrometry may soon make intramolecular ¹³C/¹²C analysis broadly available taking carbon-isotope dendrochronology to the next level.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

Kaposi’s sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first in vivo model for a virally-induced lymphoma in zebrafish, whereby KSHV-infected PEL tumour cells engraft and proliferate in the yolk sac of zebrafish larvae. Using a PEL cell line engineered to produce the viral lytic switch protein RTA in the presence of doxycycline, we demonstrate drug-inducible reactivation from KSHV latency in vivo, which enabled real-time observation and evaluation of latent and lytic phases of KSHV infection. In addition, we developed a sensitive droplet digital PCR method to monitor latent and lytic viral gene expression and host cell gene expression in xenografts. The zebrafish yolk sac is not well-vascularized and using fluorogenic assays we confirmed that this site provides a hypoxic environment that may mimic the microenvironment of some human tumors. We found that PEL cell proliferation in xenografts was dependent on the host hypoxia-dependent translation initiation factor, eukaryotic initiation factor 4E2 (eIF4E2). This demonstrates that the zebrafish yolk sac is a functionally hypoxic environment and xenografted cells must switch to dedicated hypoxic gene expression machinery to survive and proliferate. The establishment of the PEL xenograft model enables future studies that exploit the innate advantages of the zebrafish as a model for genetic and pharmacologic screens.

This note first summarizes the history of the manuscript "On a Continuum Model for Avalanche Flow and Its Simplified Variants" by Grigorian and Ostroumov―published in the Special Issue on snow avalanche dynamics of Geosciences―since the early 1990s and explains the guiding principles in editing it for publication. The changes are then detailed and some explanatory notes given for the benefit of readers who are not familiar with the early Russian work on snow avalanche dynamics. Finally, the editor's personal views as to why he still considers this paper of relevance for avalanche dynamics research today are presented in brief essays on key aspects of the paper, namely the role of simple and complex models in avalanche research and mitigation work, the status and possible applications of Grigorian's stress-limited friction law, and non-monotonicity of the dynamics of the Grigorian–Ostroumov model in the friction coefficient. A comparison of the erosion model proposed by those authors with two other models suggests to enhance it with an additional equation for the balance of tangential momentum across the shock front. A preliminary analysis indicates that continuous scouring entrainment is possible only in a restricted parameter range and that there is a second erosion regime with delayed entrainment.

The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

Retinal pigment epithelium (RPE) replacement therapy is evolving as a feasible approach to treat age-related macular degeneration (AMD). In majority of the preclinical studies, RPE cells are transplanted as cell suspension into immunosuppressed animal eyes and transplant effects were monitored only short-term. We investigated long-term effects of human iPSC derived RPE transplants in immunodeficient Royal College of Surgeons (RCS) rat model, in which RPE dysfunction lead to photoreceptor degeneration. iPSC-RPE cultured as polarized monolayer on nanoengineered ultrathin parylene C scaffold was transplanted into the subretinal space of 28-day old immunodeficient RCS rat pups and evaluated after 1, 4 and 11 months. Assessment at early time points showed good iPSC-RPE survival. The transplants remained as a monolayer, expressed RPE specific markers, performed phagocytic function and contributed to vision preservation. At 11-month post-implantation, RPE survival was observed only in 50% of the eyes that were concomitant with vision preservation. Loss of RPE monolayer characteristics at the 11month time point was associated with peri-membrane fibrosis, immune reaction through activation of macrophages (CD 68 expression) and transition of cell fate (expression of mesenchymal markers). The overall study outcome supports the therapeutic potential of RPE grafts despite the loss of some transplant benefits during long-term observations.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

Gastric outlet obstruction (GOO) poses a common and challenging clinical scenario, characterized by mechanical blockage in the pylorus, distal stomach, or duodenum, resulting in symptoms such as nausea, vomiting, abdominal pain, and early satiety. Its diverse etiology encompasses both benign and malignant disorders. The spectrum of current treatment modalities extends from conservative approaches to more invasive interventions, incorporating procedures like surgical gastroenterostomy (SGE), self-expandable metallic stents (SEMS) placement, and the advanced technique of endoscopic ultrasound-guided gastroenterostomy (EUS-GE). While surgery is favored for longer life expectancy, stents are preferred in malignant gastric outlet stenosis. The novel EUS-GE technique, employing a lumen-apposing self-expandable metal stent (LAMS), combines the immediate efficacy of stents with the enduring benefits of gastroenterostomy. Despite its promising outcomes, EUS-GE is a technically demanding procedure requiring specialized expertise and facilities.

Nowadays, the identification and characterization of grapevine cultivars resilient to climate and water stress while preserving quality traits is crucial for the wine industry. Therefore, the objective of this work was to characterize according to their aromatic potential 9 white and 6 red minority cultivars recently recovered from Castilla-La Mancha region (Spain), subjected at two different water deficit regimes: rainfed, with subsistence irrigation, and irrigated. For this, the varietal aromatic potential index (IPAv) and the detailed aromatic composition were analyzed by HS-SBSE-GC/MS, in extracts of two different ph. For IPAv values, red varieties did not show a clear trend with respect to irrigation. However, in white minority varieties, higher values were obtained under irrigation conditions. Thus, a clear differentiation of the minority varieties in comparison to the references was observed, primarily attributed to the content of esters and acids, in both white and red varieties. A notable contrast was observed at different pH, indicating a greater extractability of certain compounds like linalool, under more acidic conditions. This suggests that some recovered minority cultivars could be promising for cultivation in semi-arid regions with limited water, contributing to the wine sector sustainability in the future.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

This study investigates the petroleum potential of the Middle Jurassic Khatatba Formation (Fm) in the Matruh Basin, northwestern Egypt. This formation shows in situ dual source and reservoir characteristics, where alternations of fine and coarse clastics were deposited during semi-arid and semi-humid conditions due to climate changes and Tethyan sea level fluctuations. The organic-rich shales and argillaceous siltstones are fair to very good/excellent (TOCm wt%: 0.91–3.07) source rocks. They are rich in late mature to early postmature mostly gas-prone organic facies C, which sourced the juxtaposing intraformational coarse clastics of the Lower Safa Member with gas and condensates. The source rocks show poor to fair gas generation potential (S2: 0.38–1.96, mg HC/g rock). The middle part of the Lower Safa Member shows excellent organic richness (TOCm wt%: 5.39 and 22.90) of early postmature gas-prone carbonaceous material and coal deposits. These coaly shale layers exhibit fair to excellent wet gas and condensate generation potential (S2: 4.51–27.43, mg HC/g rock). Maturation of the source rocks was related to the Late Jurassic–Early Cretaceous Tethyan rifting. The onset of oil generation occurred in the Early Cretaceous (~ 116 Ma ago), while the onset of gas generation occurred in the Oligocene (~ 24 Ma ago). Shales of the Lower Cretaceous Alam El Bueib Fm are primary sealing rocks, while carbonates and shales of the Khatatba Fm are secondary sealing rocks. Trap types are structural, formed during the Late Jurassic and Early Cretaceous rifting of the Matruh Basin. Sandstones of the Upper Safa Member show upward increases in kaolinite and exhibit low-quality tight sandstone reservoirs. The Lower Safa Member sandstones show better gas reservoir quality with lower shale volumes. Operationally, the Lower Safa sandstone reservoirs in the Imhotep W-1X well are not suitable for gas production because they are ductile and show a high decline in production and pressure. Overall, the petroleum system of the Khatatba Fm shows mainly fair hydrocarbon potential in the study area.

EIMIs face the challenge of adapting to the Paris Agreement and the European Green Deal to achieve carbon neutrality. This change is being driven by consumer interest in low-carbon products, regulatory requirements from climate agreements and investors prioritizing sustainability. This pressure is pushing companies to go beyond short-term financial gains and integrate sustainability into their business. The growing awareness of the environmental impact of business models (BM) has fueled the development of Sustainable Business Models (SBMs). This study aims to link the discussion on the role of SBMs in the drivers of decarbonization, to improve the understanding of how the drivers can be integrated and enable new BMs for EIMIs. Based on a structured literature review, semi-structured interviews were conducted in the EIMIs. The study identifies BM-components that are influenced by these drivers and require sustainable business model innovation (SBMI). The results show that decarbonization drivers have a significant impact on all BM components. Experts emphasize the importance of collaborative approaches and cooperation throughout the value chain. This research elaborates on the importance of systematic analysis to understand how companies can effectively manage decarbonization drivers and suggests in-depth exploration within BM-research to uncover potential SBM design options.

By using a systems biological perspective and available literature on human social interaction, grouping, and cohesiveness, a new coherent model is proposed that integrates existing social integration and neurobiological research into a theoretical neurobiological framework of personality and social interaction. This model allows for the coherent analysis of complex social systems and interactions within them, and proposes a framework for estimating group cohesiveness and evaluating group structures in order to build and organize optimized social groups. This „Neurobiological-Associative“ model proposes two primary feedback loops, with environmental conditioning (learning) being sorted into an associative model that modulates interaction with the social environment, and which impacts the second feedback loop involving the individuals' neurobiological capacity. In this paper, the concept of neurobiological capacity is developed and based upon contemporary research on intelligence, personality, and social behavior with a focus on the oxytocin, serotonin, and dopamine systems. The basis of social exclusion and group structure is thus, expressed in the very most simple terms, neurobiological compatibility and risk assessment modulated by an internal associative model.

Let R be a commutative graded ring with unity, S be a multiplicative subset of homogeneous elements of R and P be a graded ideal of R such that P\bigcap S=\emptyset In this article, we introduce several results concerning graded S-prime ideals. Then we introduce the concept of graded weakly S-prime ideals which is a generalization of graded weakly prime ideals. We say that P is a graded weakly S-prime ideal of R if there exists s\in S such that for all x, y\in h(R), if 0\neq xy\in P, then sx\in P or sy\in P. We show that graded weakly S-prime ideals have many acquaintance properties to these of graded weakly prime ideals.

Twice-exceptional learners face a unique set of challenges arising from the intersection of extraordinary talent and disability. Neurobiology research has the capacity to complement pedagogical research and provide support for twice-exceptional learners. Very few studies have attempted to specifically address the neurobiological underpinnings of twice-exceptionality. However, neurobiologists have built a broad base of knowledge in nervous system function spanning from the level of neural circuits to the molecular basis of behavior. It is known that distinct neural circuits mediate different neural functions, which suggests that 2e learning may result from enhancement in one circuit and disruption in another. Neural circuits are known to adapt and change in response to experience, a cellular process known as neuroplasticity. Plasticity is controlled by a bidirectional connection between the synapse, where neural signals are received, and the nucleus, where regulated gene expression can return to alter synaptic function. Complex molecular mechanisms compose this connection in distinct neural circuits, and genetic alterations in these mechanisms are associated with both memory enhancements and psychiatric disorder. Understanding the consequences of these changes at the molecular, cellular, and circuit levels will provide critical insights into the neurobiological bases of twice-exceptional learning.

We have carried out a systematic review of the scientific literature published on PM and, more specifically, on its presence in fish and seafood of interest to the population from Mediterranean area. Given its preference and wide acceptability in the scientific community, we followed the PRISMA. The potential functional and clinical toxicity in humans due to MP in fish must be considered by the chemical composition of the microplastics the presence of PM and its additives, associated contaminants and pathogens in fish and shellfish, as well as the possible effects on human health, requires improving legislation on evaluation and providing a basis for consumer protection.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

Mice are not natural hosts for influenza A viruses (IAVs), but they are useful models for studying antiviral immune responses and pathogenesis. Serial passage of IAV in mice invariably causes the emergence of adaptive mutations and increased virulence. Typically, mouse-adaptation studies are conducted in inbred laboratory strains BALB/c and C57BL/6, which have defects in the antiviral Mx1 gene that results in increased susceptibility to infection and disease severity. Here, we report the adaptation of IAV reference strain A/California/07/2009(H1N1) (a.k.a. CA/07) in outbred Swiss Webster mice. Serial passage led to increased virulence and lung titers, and dissemination of the virus to brains. We adapted a deep-sequencing protocol to identify and enumerate adaptive mutations across all genome segments. Among mutations that emerged during mouse-adaptation, we focused on amino acid substitutions in polymerase subunits: polymerase basic-1 (PB1) T156A and F740L, and polymerase acidic (PA) E349G. These mutations were evaluated singly and in combination in minigenome replicon assays, which revealed that PA E349G increased polymerase activity. By selectively engineering these three adaptive PB1 and PA mutations into the parental CA/07 strain, we demonstrated that adaptive mutations in polymerase subunits decreased the production of defective viral genome segments with internal deletions, and dramatically increased the release of infectious virions from mouse cells. Together, these findings increase our understanding of the contribution of polymerase subunits to successful host adaptation.

Abstract: Theoretical and non-dimensional investigations have been performed to study the vibration control potential of approaches that can be based on viscoelastic but also on endochronic elements. The latter are known from the endochronic theory of plasticity and provide the possibility to establish rate-independent schemes for vibration control. The main question that has to be answered is: Can rate-independent damping be efficiently used to reduce mechanical vibrations? To answer this question non-dimensional models for dynamical systems are derived and analyzed numerically in time-domain as well as in frequency-domain. The results are used to compare the performance of an optimally tuned endochronic absorber to the performance of an optimally tuned dynamic absorber with viscoelastic damping. Based on a novel closed form representation for non-linear systems with endochronic elements, it has been possible to prove that rate-independent control of vibration results in an overall control profit that is close to the control profit obtained by the application of well-established approaches. It has also been found that the new concept is advantageous if anti-resonances have to be considered in broadband vibration control. Based on these novel findings, a practical realization in the context of active vibration control is proposed in which the rate-independent control law is implemented on an appropriate signal processing hardware.

The structures of a number of dimers of sulphur dioxide and ozone have been optimized by means of a series of ab initio calculations. The dimer species have been classified as either genuine energy minima or transition states of first or higher order, and the most probable structures consistent with the experimental data have been confirmed. The molecular orbitals engaged in the interactions resulting in adduct formation have been identified and relations between the orbitals of the dimers of the valence isoelectronic monomer species examined. The vibrational spectra of the most probable structures have been computed, and compared with those reported in the literature, particularly with spectra observed in cryogenic matrices. The calculations have been extended to predict the properties of a number of possible heterodimers formed between sulphur dioxide and ozone.

We suggest progress regarding the following six physics opportunities. List all elementary particles. Describe dark matter. Explain ratios of dark matter to ordinary matter. Explain eras in the history of the universe. Link properties of objects. Interrelate physics models. We use models based on Diophantine equations.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

We try to solve three decades-old physics challenges. List all elementary particles. Describe dark matter. Describe mechanisms that govern the rate of expansion of the universe. We propose new modeling. The modeling uses extensions to harmonic oscillator mathematics. The modeling points to all known elementary particles. The modeling suggests new particles. Based on those results, we do the following. We explain observed ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. We interrelate the masses of some elementary particles. We interrelate the strengths of electromagnetism and gravity. Our work seems to offer new insight regarding applications of harmonic oscillator mathematics. Our work seems to offer new insight regarding three branches of physics. The branches are elementary particles, astrophysics, and cosmology.

We develop and apply new physics theory. The theory suggests specific unfound elementary particles. The theory suggests specific constituents of dark matter. We apply those results. We explain ratios of dark matter amounts to ordinary matter amounts. We suggest details about galaxy formation. We suggest details about inflation. We suggest aspects regarding changes in the rate of expansion of the universe. The theory points to relationships between masses of elementary particles. We show a relationship between the strength of electromagnetism and the strength of gravity. The mathematics basis for matching known and suggesting new elementary particles extends mathematics for harmonic oscillators.

Duke University was founded in 1930 primarily due to funds generated from James B. Duke’s tobacco business. Duke achieved great financial wealth primarily due to the early application of machine rolled cigarettes, as opposed to hand rolled. This early adoption of technology allowed Duke Tobacco to out-produce other companies still selling hand rolled cigarettes. By making smoking more inexpensive and easier than pipe smoking, the cigarette formed the foundation for nicotine addiction in the 1900s, generating huge profits for the tobacco industry. At the time Duke University was founded, little was known about the connection between nicotine, cigarettes, and respiratory diseases such as emphysema and lung cancer. Through James Duke’s philanthropy, the devastating harm from cigarettes has been mitigated in part through the founding of one of the world’s most prominent medical centers and research universities.

Some physicists surmise that gravity lies outside of quantum mechanics. Thus theories like the standard semiclassical theory of quantum to gravity coupling (that of Rosenfeld and Møller) are possible real models of interaction, rather than a mere approximation of a theory of quantum gravity. Unfortunately, semiclassical gravity creates inconsistencies such as superluminal communication. Alternatives by authors such as Diósi, Martin, Penrose, and Wang often use the term 'stochastic' to set themselves apart from the standard semiclassical theory. These theories couple to fluctuations caused by for instance continuous spontaneous localization, hence the term 'stochastic'. This paper looks at stochastic gravity in the framework of a class of emergent or ontological quantum theories, such as those by Bohm, Cetto, and de Broglie. It is found that much or all of the trouble in connecting gravity with a microscopic system falls away, as Einstein's general relativity is free to react directly with the microscopic beables. The resulting continuous gravitational wave radiation by atomic and nuclear systems does not, in contrast to Einstein's speculation, cause catastrophic problems. The small amount of energy exchanged by gravitational waves may have measurable experimental consequences. A very recent experiment by Vinante et al. performed on a small cantilever at mK temperatures shows a surprising non-thermal noise component, the magnitude of which is consistent with the stochastic gravity coupling explored here.

Milk is a complex liquid, and the concentrations of many of its components are under genetic control. Many genes and pathways are known to regulate milk compositon, and the purpose of this review is to highlight how the discoveries of quantitative trait loci (QTL) for milk phenotypes can elucidate these pathways. The main body of this review focusses primarily on QTL discovered in cattle (Bos taurus) as a model species for lactation biology, with occasional references to other ruminant species, and some comparisons with human milk composition are also presented. The following section describes a range of techniques that can be used to help identify the causative genes underlying QTL when the underlying mechanism involves the regulation of gene expression. As genotype and phenotype data bases continue to grow and diversify, new QTL will continue to be discovered, and, although proving the causality of underlying genes and variants remains difficult, these new data sets will further enhance our understanding of lactation biology.

Astrocytes perform a wide variety of essential functions defining normal operation of the nervous system, and are active contributors to the pathogenesis of neurodegenerative disorders such as Alzheimer among others. Recent data provide compelling evidence that distinct reactive astrocyte states are associated with specific stages of Alzheimer´s disease. The advent of transcriptomics technologies enables rapid progress in the characterisation of such pathological astrocyte states. In this review, we provide an overview of the origin, main functions, molecular and morphological features of astrocytes in physiological as well as pathological conditions related to Alzheimer´s disease. We will also explore the main roles of astrocytes in the pathogenesis of Alzheimer´s disease and summarize main transcriptional changes and altered molecular pathways observed in astrocytes during the course of the disease.

Physics theory has yet to settle on specific descriptions for new elementary particles, for dark matter, and for dark energy forces. Our work extrapolates from the known elementary particles. The work suggests well-specified candidate descriptions for new elementary particles, dark matter, and dark energy forces. This part of the work does not depend on theories of motion. This work embraces symmetries that correlate with motion-centric conservation laws. The candidate descriptions seem to explain data that prior physics theory seems not to explain. Some of that data pertains to elementary particles. Our theory suggests relationships between masses of elementary particles. Our theory suggests a relationship between the strengths of electromagnetism and gravity. Some of that data pertains to astrophysics. Our theory seems to explain ratios of dark matter effects to ordinary matter effects. Our theory seems to explain aspects of galaxy formation. Some of that data pertains to cosmology. Our theory suggests bases for inflation and for changes in the rate of expansion of the universe. Generally, our work proposes extensions to theory in three fields. The fields are elementary particles, astrophysics, and cosmology. Our work suggests new elementary particles and seems to explain otherwise unexplained data.

Rice has become the second major food among rural people. It is one of the most nutrient and low-cost food available in Asia. Rice is composed of two major subspecies as Japonica and Indica and it belongs to the Poaceae family. The World Bank predicts that rice demand will grow 51% faster than population growth in 2025. It is high time to develop a model which predicts the type of infected paddy leaf and avoids the loss of grains. In this paper, the proposed hybrid CNN model, three CNN networks with different layer properties are trained parallel. The extracted feature from these CNN networks is combined to provide the classification of the type of infected leaf. Fieldwork was carried and about 340 samples are collected from five different types of classes. The proposed hybrid model was tested with both the fieldwork dataset and also with an available dataset on the internet. The experimental results show that the proposed model outperforms the other CNN network and yields an accuracy value of 98%, a precision value of 95%, and a misclassification rate of 4% respectively.

DNA Topoisomerase IIa (Top2A) is a nuclear enzyme that is a cancer drug target, and there is interest in identifying novel sites on the enzyme to inhibit cancer cells more selectively and to reduce off-target toxicity. The C-terminal domain (CTD) is one potential target, but it is an intrinsically disordered domain, which prevents structural analysis. Therefore, we set out to analyze the sequence of Top2A from 105 species using bioinformatic analysis including the PSICalc algorithm, entropy analysis, and other approaches. Our results demonstrate that large (10th-order) interdependent clusters are found including non-proximal positions across the major domains of Top2A. Further, CTD-specific clusters of 3rd, 4th, and 5th-order were identified that included positions that had been previously analyzed via mutation and biochemical assays. Some of these clusters coincided with positions that when mutated either increased or decreased relaxation activity. Finally, sites of low entropy (i.e., high information content) were identified and mapped as key positions in the CTD. Included in the low entropy sites are phosphorylation sites and charged positions. Together, these results help to build a clearer picture of the critical positions in the CTD and provide potential sites/regions for further analysis.

Pigs are a social species and they stablish hierarchies for a better use of resources and to reduce conflicts. However, in pig production, the opportunities for growing can differ in dominant and subordinate animals. In the present study a system was tested to perform a Dominance versus Subordinate test in growing pigs to investigate how the hierarchy affects feeding behaviour, growth and gut microbiota assessed in faeces. 64 animals housed in eight different pens were used, with four castrated males and four females in each one, weighing 18kg at arrival and maintained during the whole growing period, until 140 kg. Three stool samplings were obtained from the animals directly from the anus to avoid contamination of the faeces on 58, 100 and 133 days after the start of the study to investigate the microbiota composition. The dominant animals had higher gains during the growing period that the subordinate. In addition, they were performing more visits to the feeder throughout the day. Differential abundance patterns were observed in five bacterial genera, Oliverpabstia, Peptococcus, and Faecalbacterium being more abundant in dominant animals and Holdemanella and Acetitomaculum being overrepresented in subordinate ones. This microbial biomarker accurately classified dominant versus subordinate groups of samples with an AUC of 0.92.

Accurate forest reference and emission level (FRL, FREL) with related policies and regulations are the key determinants in establishing sustainable forest ecosystem management programmes (e.g. REDD+). This fundamental is for promoting and sustaining climate smart agricultural practices in a changing climate. With the aim to deliver better knowledge to the scientific community and policy makers on regulations and existing tools for more rigorous scientific communication when it comes to FRL and FREL accountability and policies. Thus, this review investigates forest in the changing climate and policies and underlines the performance of land use transition and intensity analysis towards deforestation with some key examples and achievements (e.g. Togo). Simply put, (i) forest as break of greenhouse gas (GHGs) and ecosystem regulator, (ii) policies and REDD+ actions, (iii) potential drivers and (iv) transition and intensity analysis approach for their accountability are discussed. In sum, impressive studies, policies and regulations are under initiations and implementations regarding the role, place and evaluation of forest losses and its ecosystem functions and services. However, there are still some gaps when it comes to: the choice of the evaluation methods in the real context of a specific ecosystem as well as the firm implementations of formulating policies in developing countries. This paper concludes with some policy measures for forest sustainability, carbon enhancement and accountability.

Quantum chaos is presented as a paradigm of information processing by dynamical systems at the bottom of the range of phase-space scales. Starting with a brief review of classical chaos as entropy flow from micro- to macro-scales, I argue that quantum chaos came as an indispensable rectification, removing inconsistencies related to entropy in classical chaos: Bottom-up information currents require an inexhaustible entropy production and a diverging information density in phase space, reminiscent of Gibbs' paradox in Statistical Mechanics. It is shown how a mere discretization of the state space of classical models already entails phenomena similar to hallmarks of quantum chaos, and how the unitary time evolution in a closed system directly implies the “quantum death” of classical chaos. As complementary evidence, I discuss quantum chaos under continuous measurement. Here, the two-way exchange of information with a macroscopic apparatus opens an inexhaustible source of entropy and lifts the limitations implied by unitary quantum dynamics in closed systems. The infiltration of fresh entropy restores permanent chaotic dynamics in observed quantum systems. Could other instances of stochasticity in quantum mechanics be interpreted in a similar guise? Where observed quantum systems generate randomness, that is, produce entropy without discernible source, could it have infiltrated from the macroscopic meter? This speculation is worked out for the case of spin measurement.

In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.

The topic of this paper is the airborne evaluation of ICESat-2 Advanced Topographic Laser Altimeter System (ATLAS) measurement capabilities and surface-height-determination over crevassed glacial terrain, with a focus on the geodetical accuracy of geophysical data collected from a helicopter. To obtain surface heights over crevassed and otherwise complex ice surface, ICESat-2 data are analyzed using the density-dimension algorithm for ice surfaces (DDA-ice), which yields surface heights at the nominal 0.7~m along-track spacing of ATLAS data. As the result of an ongoing surge, Negribreen, Svalbard, provided an ideal situation for the validation objectives in 2018 and 2019, because many different crevasse types and morphologically complex ice surfaces existed in close proximity. Airborne geophysical data, including laser altimeter data (profilometer data at 905~nm frequency), differential Global Positioning System (GPS), Inertial Measurement Unit (IMU) data, on-board-time-lapse imagery and photographs, were collected during two campaigns in summers of 2018 and 2019. Airborne experiment setup, geodetical correction and data processing steps are described here. To date, there is relatively little knowledge of the geodetical accuracy that can be obtained from kinematic data collection from a helicopter. Our study finds that (1)~Kinematic GPS data collection with correction in post-processing yields higher accuracies than Real-Time-Kinematic (RTK) data collection. (2)~Processing of only the rover data using the Natural Resources Canada Spatial Reference System Precise Point Positioning (CSRS-PPP) software is sufficiently accurate for the sub-satellite validation purpose. (3)~Distances between ICESat-2 ground tracks and airborne ground tracks were generally better than 25~m, while distance between predicted and actual ICESat-2 ground track was on the order of 9~m, which allows direct comparison of ice-surface heights and spatial statistical characteristics of crevasses from the satellite and airborne measurements. (4)~The Lasertech Universal Laser System (ULS), operated at up to 300~m above ground level, yields full return frequency (400~Hz) and 0.06-0.08~m on-ice along-track spacing of height measurements. (5)~Cross-over differences of airborne laser altimeter data are 0.1918 $\pm$ 2.385~m along straight paths over generally crevassed terrain, which implies a precision of approximately 2.4~m for ICESat-2 validation experiments. (6)~In summary, the comparatively light-weight experiment setup of a suite of small survey equipment mounted on a Eurocopter (Helicopter AS-350) and kinematic GPS data analyzed in post-processing using CSRS-PPP leads to high accuracy repeats of the ICESat-2 tracks. The technical results (1)-(6) indicate that direct comparison of ice-surface heights and crevasse depths from the ICESat-2 and airborne laser altimeter data is warranted. The final result of the validation is that ICESat-2 ATLAS data, analyzed with the DDA-ice, facilitate surface-height determination over crevassed terrain, in good agreement with airborne data, including spatial characteristics, such as surface roughness, crevasse spacing and depth, which are key informants on the deformation and dynamics of a glacier during surge.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

The performance of 5 forecasting models was investigated for predicting nursery mortality using the master table built for 3,242 groups of pigs (~ 13 million animals) and 42 variables, which concerned the pre-weaning phase of production and conditions at placement in growing sites. After training and testing each model’s performance through cross-validation, the model with the best overall prediction results was the Support Vector Machine model in terms of Root Mean Squared Error (RMSE=0.406), Mean Absolute Error (MAE=0.284), and Coefficient of Determination (R2=0.731). Subsequently, the forecasting performance of the SVM model was tested on a new dataset containing 72 new groups, simulating ongoing and near real-time forecasting analysis. Despite a decrease in R2 values on the new dataset (R2=0.554), the model demonstrated high accuracy (77.78%) for predicting groups with high (5&gt;%) or low (5&lt;%) nursery mortality. This study demonstrated the capability of forecasting models to predict the nursery mortality of commercial groups of pigs using pre-weaning information and stocking conditions variables collected post-placement in nursery sites.

Photovoltaic (PV) systems, which are renewable energy sources, are increasingly being utilized in distributed generation. To maintain a stable energy balance, energy storage systems such as batteries (BAT) play a vital role. Electric vehicles (EVs) offer a promising solution with rechargeable battery systems for operation. The BATs must maintain their state of charge within design boundaries, despite intermittent PV and load power fluctuations, and advanced power control and management techniques are essential for their effective operation. The article evaluates an intelligent controller that uses a Sliding Mode Control adaptive deep learning algorithm Convolutional Neural Networks (SMC-CNN) and a unique Strategy for managing supervisory power. (SPMS) for photovoltaic systems with battery energy storage for better regulation of DC bus voltage. SMC-CNN offers exceptional resilience and seamless functionality, minimizing fluctuations in DC bus voltage in the control strategy design requirements. The primary goals are maintaining a consistent power supply and ensuring continuous service by preventing system components from exceeding capacity. This study aims to enhance the control of DC bus voltage in the PV and battery system, with the primary significance focusing on the following aspects. The advanced SPMS has been created, incorporating control system constraints to enhance SOC balancing speed and reduce fluctuations in DC bus voltage. Power flow management involves optimizing energy flow between the PV system, battery system, and load while minimizing battery capacity requirements. The proposed SMC-CNN and SPMS are demonstrated through real-time simulation using Matlab/Simulink, as demonstrated in comprehensive case studies.

Through history, particular attention has been paid of the study of the relationship between the energy use and the city structure. Improving energy efficiency in modern agglomerations is the most promising means to mitigate climate change and its impacts. In this current context of globalisation, European Union proposes initiatives and policy targets to rethink the urban development strategies towards the ‘zero energy objectives’. Providing a methodological approach with a simulation district analysis, the present article summarizes how the ‘zero energy’ challenge is analyzed in an existing district (Epinlieu) to articulate the users’ requirements in energy. This study contributes to the scientific discussion of the districts’ urban structure and energy planning by establishing a linkage among the beneficial influence of the KPIs of the districts’ form to increase their energy efficiency and its application in a real case study in Belgium.

Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO®) has been approved by the US Food & Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of introduction of JEV in the US, the need to integrate planning for such an event in public health policy and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.

Shea tree (Vitellaria paradoxa) is an important fruit tree crop because of its oil used for cooking and industrial manufacture of cosmetics. Despite its many benefits, quantitative trait loci linked to the economic traits have not yet been studied. In this study, we performed association mapping on a panel of 374 shea tree accessions using 7,530 single-nucleotide polymorphisms (SNPs) markers for oil yield and seed related traits. Twenty three markers that were significantly (–log10 (p) = 4.87) associated to kernel oil content, kernel length; width and weight were identified. The kernel dry matter oil content and kernel width had the most significant Marker Trait Association (MTA) on chromosomes 1 and 8 respectively. Sixteen candidate genes that condition early induction of flower buds and somatic embryos, seed growth and development, substrate binding, transport, lipid biosynthesis, metabolic processes during seed germination and disease resistance and abiotic stress adaptation were identified. The presence of these genes suggest their role in promoting shea bioactive functions that condition high oil synthesis. This study provides insights into the important marker-linked seed traits with genes controlling them, useful for molecular breeding for improving oil yield in the species.

As the embedded device and internet of things (IoTs) concept prevalent in today's world, there is an increasing demand for the security and performance requirements on deploying these devices to private and public sectors. The crucial part of it is to protect privacy, confidentiality and integrity, meanwhile, maintain an adequate level of performance during transmission, storage and access of critical information. While the conventional cryptography methods, such as the Advanced Encryption Standard (AES), SHA$-$2 hashing method and RSA and Diffie Hellman for message authentication and identification, work well on systems which have reasonable processing power and memory capabilities. These do not scale well into a world with embedded systems and sensor networks, in conjunction with their nature of smaller size and lower cost. Thus, in the context of resource constrained device, lightweight cryptography methods are proposed to overcome many of the problems of conventional cryptography possessed. This includes constraints related to physical size, processing requirement, memory limitation, energy drain and production cost. This paper provides a survey of the architectures that are defined as replacements for conventional ciphers within an IoTs space and discuss some trends in the design of future lightweight algorithms. The performance metrics are carefully chosen to reflect and assess the suitability for embedded devices. The aim of this research is to identify the various performance metrics applied on different types of symmetric block ciphers especially lightweight ciphers and compare the results on versatile platforms with stream ciphers and public key methods. The comparative analysis on efficient LW cipher will be tested against other similar block ciphers on both MacBook Pro with Intel core and resource constrained device Raspberry Pi with ARM processor.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Recent pollinator declines have focused efforts on their conservation which require clear estimates of pollination value to agriculture. Our socio-economic producer surveys and agronomic field research data were used to present a new way of estimating ecosystem service value of native pollinators. Using two regionally important U.S.A. crops, Maine wild blueberry and Massachusetts cranberry as models, we present perceived values of native bee pollinators from both consumer and producers. Wild blueberry’s Replacement Cost (RC) was greater than Attributable Net Income (ANI), since greater rented honey bee stocking densities are required. Attributable Net Income for native bees were similar for wild blueberry ($613/ha) and cranberry ($689/ha). Marginal Net Farm Income (MNFI) from incrementally adding more hives per ha was greater from stocking a third/fourth hive per ha for cranberry ($6,206) than stocking a ninth/tenth hive per ha for wild blueberry ($556), given greater responsiveness of yield, revenue, and profit to using rented honey bee hives in cranberry compared to wild blueberry. Both crops’ producers were only willing to annually invest $140–188/ha in native pollination enhancements on their farms, justifying government support. Consumers are willing to pay ~6.7 times more to support native bees than producers, supporting market-based support for invertebrate conservation.

Physics lacks a confirmed description of dark matter, has yet to develop an adequate understanding of dark energy, and includes unverified conjectures regarding new elementary particles. This essay features modeling that addresses those problems and explains otherwise unexplained data. Our modeling starts from five bases – multipole expansions for the electromagnetic and gravitational fields associated with an object, the list of known elementary particles, some aspects of mathematics for isotropic harmonic oscillators, concordance cosmology, and a conjecture that the universe includes six isomers of most elementary particles. The multipole expansions – which have use in conjunction with Newtonian kinematics modeling, special relativity, and general relativity – lead to a catalog of kinematics properties such as charge, magnetic moment, mass, and repulsive gravitational pressure. The multipole expansions also point to all known elementary particles, some properties of those particles, and properties of some would-be elementary bosons and elementary fermions. The harmonic-oscillator mathematics points to Gauge symmetries regarding some elementary bosons. The would-be elementary fermions lack charge and would measure as dark matter. The conjecture regarding six isomers of most elementary particles rounds out and dominates our specification for dark matter. Five of the isomers form the basis for most dark matter. Our modeling explains ranges of observed ratios of dark matter effects to ordinary matter effects – for the universe, galaxy clusters, two sets of galaxies observed at high redshifts, three sets of galaxies observed at modest redshifts, and one type of depletion of cosmic microwave background radiation. Our description of repulsive gravitational pressure points toward resolution for tensions – between data and modeling – regarding the recent rate of expansion of the universe, resolution for possible tensions regarding large-scale clumping, and resolution for possible tensions regarding interactions between neighboring galaxies. Our work regarding gravity, dark matter, and elementary particles suggests characterizations for eras that might precede the inflationary epoch, a mechanism that might have produced baryon asymmetry, mechanisms that govern the rate of expansion of the universe, and insight about galaxy formation and evolution.

The gauge field equation for fluid mechanics established in Part 1 is developed into a first-order scattering theory in the simplified case of a two-dimensional incompressible flow over a flat plate. This is used to present a model for the origin of Tollmien-Schlichting (TS) waves based on scattering between fluid particles. As a result, analytical formulae for the maximum amplification factor and the transition point from laminar to turbulent flow in the boundary layer are obtained. The mathematical transformations from the stationary field equations in Part 1 to a scattering theory with time evolution along the flow axis using Wick rotation are elaborated in detail.

Brittle fracture of iron and steel above twinning temperatures are caused by cementite grain boundary wall cracks. These were revealed by an Atomic Force Microscope. At temperatures below the Ductile-Brittle Transition, cracks must propagate longitudinally within the cementite walls until the stress is sufficient high for the cracks to propagate across ferrite grains. Calculations using these concepts correctly predict the stress and temperature at the Ductile-Brittle Transition required for fracture to occur. At temperatures above the Ductile-Brittle Transition for hypoeutectoid ferritic steels, dislocations must fracture these walls transversely for plastic deformation to continue. This is responsible for the upper yield point at the elastic limit in these steels followed by a large drop in stress to the lower yield point. Here the walls surround completely all of the grains. Where the walls are segmented such as in iron, dislocations can pass around the walls resulting in a gradual change from elastic to plastic deformation. The Cottrell atmosphere theory of yielding is not supported experimentally. It was the best available until later experiments including those using the Atomic Force Microscope were obtained. Methods are presented here giving yield strength versus temperature and also the parameters for the Hall-Petch and Griffith equations.

The rapid expansion of social media and instant messaging applications, such as WhatsApp, has transformed how individuals and organizations communicate and engage. This think piece explores the potential of integrating WhatsApp as a customer relationship management (w-CRM) tool within the education sector to foster and sustain long-term relationships among students, teaching staff, and non-teaching staff. By leveraging real-time features and the widespread use of WhatsApp, educational institutions can create a more interactive and dynamic learning environment, benefiting all stakeholders involved. The literature highlights the importance of establishing clear frameworks for mutual engagement and interaction and the potential of w-CRM to improve communication between students' families and educational institutions. There are potential risks associated with the pervasive use of WhatsApp, and call for future research to explore strategies for mitigating these risks while maximizing the benefits of w-CRM in the education sector. Longitudinal studies are recommended to evaluate the long-term impact of w-CRM on stakeholder relationships, student outcomes, and overall institutional performance.

(1) Background: The diagnosis of lumbosacral radiculopathy involves anamnesis, assessment of sensitivity and strength, diagnostic imaging—usually magnetic resonance imaging (MRI)—and electrodiagnostic testing (EDX), typically electromyography (EMG) and electroneurography (ENG). MRI evaluates the structures supporting the spinal cord, while EDX evaluates root functionality. The present study aimed to analyze the concordance of MRI and EDX findings in patients with clinically suspected radiculopathy. Additionally, we investigated the comparison between these two reference tests and various clinical variables and questionnaires. (2) Methods: We designed a prospective epidemiological study of consecutive cases with an observational, descriptive, cross-sectional, and double-blind nature following the STROBE guidelines, encompassing 142 patients with clinical suspicion of lumbosacral radiculopathy. (3) Results: Of the sample, 58.5% tested positive for radiculopathy using EDX as the reference test, while 45.8% tested positive using MRI. The comparison between MRI and EDX in the diagnosis of radiculopathy in patients with clinical suspicion was not significant; the overall agreement was 40.8%. Only the years with symptoms were comparatively significant between the positive and negative radiculopathy groups as determined by EDX. (4) Conclusion: The comparison between lumbar radiculopathy diagnoses in patients with clinically suspected pathology using MRI and EDX as diagnostic modalities did not yield statistically significant findings. MRI and EDX are complementary tests assessing different aspects in patients with suspected radiculopathy; degeneration of the structures supporting the spinal cord does not necessarily imply root dysfunction.