The purpose of this work was to evaluate the suitability of recent US Food and Drug Administration (US-FDA) approved and marketed oral liquid, powder, or granule products for children in North America, to identify the next group of Active Pharmaceutical Ingredients (APIs) that have high potential for development as commercially available FDA-approved finished liquid dosage forms , and to propose lists of compounded nonsterile preparations (CNSPs) that should developed as commercially available FDA-approved finished liquid dosage forms as well as those that pharmacists should continue to compound extemporaneously. Through this identification and categorization process, the pharmaceutical industry, government, and the professions are encouraged to continue to work together to improve the likelihood that patients will receive high quality standardized extemporaneous CNSPs and US-FDA-approved products.

Abstract: A primary action of vitamin D is regulation of gene transcription. Many cell types possess genes that make antimicrobial peptides (AMPS) (endogenous antibiotics), recently discovered to be regulated by vitamin D. Two examples are cathelicidin and beta defensins, both bioactive against many different bacteria, fungi, mycobacteria, parasites and viruses. The signal transduction pathway is triggered by sensing microorganisms via cell surface receptors, causing intracellular production of calcitriol (1,25(OH)2D) and vitamin D receptors, leading to upregulation of AMP production. Serum 25(OH)D concentrations required to sustain adequate AMP production to eradicate infections are unknown. Vitamin D3 is photosynthesized in skin in amounts ranging from 10,000 (250 mcg) to 25,000 (625 mcg) International Units (IU) from 7-dehydrocholesterol after whole-body exposure to one minimal erythemal dose (MED) of ultraviolet B (UVB) radiation, and is impacted by many factors including geographic localities, seasonal changes and skin pigmentation. We and others have reported extended daily oral dosing with these amounts of vitamin D3 safe. We routinely observe serum 25(OH)D concentrations below 20ng/ml on new admissions, which have been reported insufficient to sustain AMP production. In contrast serum 25(OH)D concentrations above 100ng/ml have been reported after serial UVB treatments for psoriasis. Little vitamin D naturally occurs in food, and insufficient sun exposure may be causing worldwide deficiency. We review evidence suggesting that higher daily intakes of vitamin D3 than the currently recommended 600 (15 mcg) IU/day may be necessary to sustain AMP production in the face of an overwhelming infection, particularly in non-Hispanic blacks, a high risk population suffering the worst outcomes from COVID-19. We propose that increased vitamin D supplementation could provide a safe and cost-effective way to protect all populations from infections, in particular those from pandemic COVID-19.

Bidirectional gene promoters affect the transcription of two genes, leading to the hypothesis that they should exhibit protection against genetic or epigenetic changes in cancer. Therefore, they provide an excellent opportunity to learn about promoter susceptibility to somatic alteration in tumors. We tested this hypothesis using data from genome-scale DNA methylation (14 cancer types), simple somatic mutation (10 cancer types), and copy number variation profiling (14 cancer types). For DNA methylation, the difference in rank differential methylation between tumor and tumor-adjacent normal matched samples based on promoter type was tested by Wilcoxon rank sum test. Logistic regression was used to compare differences in simple somatic mutations. For copy number alteration, a mixed effects logistic regression model was used. The change in methylation between non-diseased tissues and their tumor counterparts was significantly greater in single compared to bidirectional promoters across all 14 cancer types examined. Similarly, the extent of copy number alteration was greater in single gene compared to bidirectional promoters for all 14 cancer types. Furthermore, among 10 cancer types with available simple somatic mutation data, bidirectional promoters were slightly more susceptible. These results suggest that selective pressures related with specific functional impacts during carcinogenesis drive the susceptibility of promoter regions to somatic alteration.

Responses to water stress were measured for sugar maple (Acer saccharum subsp. saccharum Marshall) sources from Oklahoma (Caddo sugar maple), Missouri, Tennessee, Ontario and a black maple (Acer saccharum subsp. nigrum F. Michx.) source from Iowa. Seedling sources were selected for differences in temperature and precipitation of their geographic origins. Seedlings were preconditioned through moist (watered daily) or dry (watered every 4-7 days) cycles and then exposed to prolonged water stress. Dry preconditioned sugar maple seedlings from Oklahoma, Missouri, and Tennessee, sources from warmer and/or drier climates with greater relative evapotranspiration potentials, declined less rapidly in net photosynthesis, stomatal conductance, and water use efficiency (WUE) as water stress increased than dry preconditioned seedlings from Ontario and Iowa having origins in cooler, moister climates. Under imposed water stress the Ontario and Iowa sourced seedlings increased their root to shoot ratios and decreased their specific leaf area, mechanisms for drought avoidance. However, no corresponding changes in these values occurred for Oklahoma, Missouri, and Tennessee sources. Results from this study suggest greater tolerance of water stress in the Oklahoma, Missouri and Tennessee ecotypes from the western and southern range of sugar maple resulted primarily with WUE rather than other water stress coping mechanisms.

In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) have led to the development of biologically-driven targeted therapies. Hypoxia inducible factors (HIFs), angiogenic growth factors, von Hippel-Lindau (VHL) gene mutations and oncogenic miRNAs play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of VEGF inhibitors, mTOR inhibitors and immunotherapeutic agents which have significantly improved outcomes of patients with advanced RCC. HIF inhibitors will be a valuable asset in the growing therapeutic armamentarium of RCC. Various histone deacetylase (HDAC)inhibitors, including selenium and agents such as PT2385 and PT2977, are being explored in various clinical trials as potential HIF inhibitors to ameliorate the outcomes of RCC patients. In this article, we will review the current treatment options and highlight the potential role of selenium in the modulation of drug resistance biomarkers expressed in ccRCC tumors.

Charcot-Marie-Tooth (CMT) syndrome is the most common progressive human motor and sensory peripheral neuropathy. CMT type 1E is a demyelinating neuropathy affecting Schwann cells due to pmp22 mutations, modelized by Trembler-J mice. Curcumin, a natural polyphenol com-pound obtained from turmeric (Curcuma longa), exhibits dose- and time-varying antitumor, antioxidant and neuroprotective properties, however, the neurotherapeutic actions of curcumin still remain elusive. Here, we propose curcumin as a possible natural treatment capable of enhancing cellular detoxification mechanisms, resulting in an improvement of the neurodegenerative Trembler-J phenotype. Using a refined method for obtaining enriched Schwann cell cultures, we evaluated the neurotherapeutic action of low dose curcumin treatment on the PMP22 expression, and on the chaperones (HSF1 and Hsp27) and autophagy/mTOR (HDAC6 and ribosomes) pathways in Trembler-J and wild-type genotypes. In wild-type Schwann cells, the action of cur-cumin resulted in strong stimulation of the chaperone and macroautophagy pathway, whereas the modulation of ribophagy showed a mild effect. However, despite the promising neuroprotective effects for the treatment of neurological diseases, we report (demonstrate?) that the action of cur-cumin in Trembler-J Schwann cells could be impaired due to the irreversible impact of ethanol used as a common curcumin vehicle necessary for administration. These results contribute to expand our still limited understanding of PMP22 biology in neurobiology, and expose the intrinsic lability of the neurodegenerative Trembler-J genotype. Furthermore, they unravel interesting physiological mechanisms of cellular resilience relevant for to the pharmacological treatment of the neurodegenerative Tremble J phenotype with curcumin and ethanol. We conclude that the analysis of the effects of the vehicle itself is an essential and in-escapable step to comprehensibly assess the own effects and full potential of curcumin treatment for therapeutic purposes.

We know that the classical Mittag-Leffler function play an important role as solution of fractional order differential and integral equations. We introduce the j-generalized p - k Mittag-Leffler function. We evaluate the second order differential recurrence relation and four different integral representations and introduce a homogeneous linear differential equation whose one of the solution is the j-generalized p-k Mittag-Leffler function. Also we evaluate the certain relations that exist between j-generalized p - k Mittag-Leffler function and Riemann-Liouville fractional integrals and derivatives. We evaluate Mellin-Barnes integral representation of j-generalized p-k Mittag-Le er Function. The relationship of j-generalized p-k Mittag-Leffler Function with Fox H-Function and Wright hypergeometric function is also establish. we obtained its Euler transform, Laplace Transform and Mellin transform. Finally we derive some particular cases.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

Sechium compositum (Cucurbitaceae) is a wild species that is distributed in the Soconusco region, Chiapas, Mexico, and the border with Guatemala. This species has an intangible biochemical value resulting from the pharmacological relevance of its secondary metabolites. However, as a consequence of the lack of knowledge about its importance, it is being displaced from its habitat at an accelerated rate, incurring the risk of genetic loss. Therefore, an in vitro culture protocol with two experimental phases was evaluated to propagate, conserve, and regenerate this species. The first phases considered the multiplication of seedlings, adding seven concentrations (0.1, 0.2, 0.4, 0.6, 0.8, 1.0, 1.2 mg mL-1) of 6-benzylaminopurine (BA) and thidiazuron (TDZ) and evaluating the number of buds, shoots, and seedling height. The best multiplication response was recorded with 0.1, 0.2, 0.4, and 1.0 mg L-1 of BA and 0.1 mg L-1 of TDZ, as well as the MS base culture medium. With 0.1 mg L-1 of BA, 52-mm height, 1.36 shoots, and 9.22 buds were obtained, surpassing the MS control (MS culture medium alone); likewise, twice more roots (80%) and a 14% reduction in the bud structure were packed in 50 repetitions. The second phase consisted of inducing callus formation from stem and leaf explants through the addition of 0.5, 1.0, and 2.0 mg L-1 of TDZ and 2,4-Dichlorophenoxyacetic acid (2,4-D) to the medium. The results demonstrated that the induction of callogenesis in S. compositum has a better start from the stem in a medium with 2.0 mg L-1 of 2,4-D, whose value was 4.89 —equivalent to 97.8% callus formation around the explant. The addition of 500 mg L-1 of polyvinylpyrrolidone (PVP) is also suggested to reduce oxidation. This protocol represents a significant advance in the conservation, multiplication, and callogenesis of S. compositum and contributes to its rescue and revaluation in the face of the danger of extinction.

In this research paper, design and development of pyramidal horn antenna for J-band application is reported. It is particularly designed for 17 dB gain and half beam width about 25 degrees at 6.93 GHz. Horn aperture, horn axial length and distance from the throat of the antenna to aperture are the main design constraints which are calculated and used for the antenna design and simulation. Beam width in E-plane and H-plane horn is calculated and it is 19.18 dB and 22.86 dB respectively. The reported antenna design shows good performance for J-band in radiometry, satellite, and radar applications.

Despite the increasing popularity of liquid chromatography-mass spectrometry (LC-MS)-based lipidomics, there is a lack of accepted and validated method for lipid extract quality and quantity assessment prior to LC-MS. Fourier-Transform Infrared Spectroscopy (FTIR) has been reported for quantification of pure lipids, however, the sample complexity and purity complex lipid extract quantification in lipidomics experiments could be impact quantification accuracy. Here, we report comprehensive assessment of the sample matrix on the accuracy of lipid quantification using Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). Pure lipids are characterized by CH-and C=O-stretching vibrations on FTIR, with quantitative range of 40–3000 ng and a limit of detection of 12 ng. Sample extraction method and local baseline subtraction during FTIR spectral processing significantly impact lipid quantification by CH-stretching. To facilitate sample quality screening, we developed the Lipid Quality (LiQ) score from a spectral library of common contaminants, using a ratio of peak heights between CH-stretching vibrations maxima and the collective vibrations from amide/amine, CH-stretching minima and sugar moieties. We evaluated LiQ score as a rapid sample quality control method by comparing to total LC-MS intensity of targeted lipidomics of 107 human plasma lipid extracts. Exclusion of poor-quality samples based on LiQ score improved the correlation between FTIR and LC-MS quantification. Finally, the uncertainty of absolute quantification by FTIR was estimated using a 795 ng SPLASH LipidoMix standard to be <10%. In summary, this study identified key parameters for accurate FTIR-based quantification of complex lipid mixture, and developed a rapid workflow requiring only 1 µL of MS-ready sample and < 5 minutes for routine lipidomics sample quality and quantity assessment.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

This cross-sectional study evaluated the validity of three alternative methods compared to the gold standard 24-h urine collection for estimating dietary sodium intake, a modifiable risk factor for hypertension, among middle-aged and older adults with elevated blood pressure. These included spot urine collection (using Kawasaki, Tanaka, and INTERSALT equations), 24-h dietary recall, and food frequency questionnaire responses, compared against 24-h urine collection in a subset of 65 participants (aged 50–75 years, 58.5 % women, 61.6 % hypertensive) from the DePEC-Nutrition trial. The validity of the methods was assessed using bias, Spearman correlation coefficient (SCC), intraclass correlation coefficient (ICC), and Bland-Altman analysis. Among the alternative methods, spot urine collection using the Kawasaki equation showed the strongest correlation (SCC 0.238; ICC 0.119, 95 % CI -0.079 to 0.323) but it exhibited a significant bias (1414 mg/day, p-value < 0.001) relative to 24-h urine collection. Conversely, dietary surveys had a smaller bias but wider limits of agreement. These findings underscore the complexities of accurately estimating dietary sodium intake using spot urine collection or dietary surveys in this specific population, suggesting that a combination or refinement of existing methodologies might improve accuracy. Further research with larger samples is necessary to develop more reliable methods for assessing sodium intake in this high-risk group.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

In 2016–2017, we conducted and published a systematic review on caffeine safety [1] that set out to determine whether conclusions presented in the heavily cited Health Canada assessment, Nawrot et al. [2], remain supported by more recent data. To that end, we reviewed data from 380 studies published between June 2001 and June 2015, which were identified from an initial batch of over 5,000 articles through a stringent search and evaluation process [1]. In the current paper, we use plain language to summarize our process and findings, with the intent of sharing additional context for broader reach to the general public. We addressed whether caffeine doses previously determined not to be associated with adverse effects by Health Canada (400 mg/day for healthy adults, 300 mg/day for pregnant women, 2. 5 mg/kg body weight/day for adolescents and children, and 10 g/day for acute effects) remain appropriate for five outcome areas (acute toxicity, cardiovascular toxicity, bone & calcium effects, behavior, and development and reproduction) in healthy adults, pregnant women, adolescents, and children. We used a weight-of-evidence approach to draw conclusions for each of the five outcomes, as well as more specific endpoints within those outcomes, which considered study quality, consistency, level of adversity, and magnitude of response. In general, updated evidence confirms the levels of intake put forth by Nawrot et al., as not being associated with any adverse health effects, and our results support a shift in caffeine research from healthy to sensitive populations.

Many corporations aspire to become Net Zero Carbon Dioxide by 2030-2050. This paper examines what it will take. It requires understanding where energy is produced and consumed, the magnitude of CO2 generation, and the Carbon Cycle. Reviews are provided for prior technologies for reducing CO2 emissions from fossil to focus on their limitations and to show that none offer a complete solution. Both biofuels and CO2 sequestration reduce future CO2 emissions from fossil fuels. They will not remove CO2 already in the atmosphere. Planting trees has been proposed as one solution. Trees are a temporary solution. When they die, they decompose and release their carbon as CO2 to the atmosphere. The only way to permanently remove CO2 already in the atmosphere is to break the Carbon Cycle by growing biomass from atmospheric CO2 and sequestering biomass carbon. Permanent sequestration of leaves is proposed as a solution. Leaves have a short Carbon Cycle time constant. They renew and decompose every year. Theoretically, sequestrating a fraction of the world’s tree leaves can get the world to Net Zero without disturbing the underlying forests. This would be CO2 capture in its simplest and most natural form. Permanent sequestration may be achieved by redesigning landfills to discourage decomposition. In traditional landfills, waste undergoes several stages of decomposition, including rapid initial aerobic decomposition to CO2, followed by slow anaerobic decomposition to methane and CO2. The latter can take hundreds to thousands of years. Understanding landfill chemistry provides clues to disrupting decomposition at each phase.

It is standard to identify and compare predicted protein sequence of the Drosha and Pasha genes subsidiary to detection and identification of novel microRNAs in newly sequenced taxa or review of previous deep sequencing data. Drosha and Pasha proteins are the key, conserved members of the ‘microprocessor’ protein complex which facilitates nuclear nuclear localized, pri to pre miRNA processing miRNAs of the canonical eumetazoan complement. Because of the necessity of the microprocessor for production of c anonical eumetazoan miRNA, the detection of both (1) bona fide microRNAs and (2) presence of Drosha/Pasha orthologs (or homologs) is often presented as sufficient to represent a functional canonical eumetazoan microRNA biogenesis pathway. However, the fun ctional role of the Drosha and Pasha homologs sometimes, though not always experimentally validated in non model taxa. Differentiation of ‘bona fide miRNAs’, opposed to ‘non bona fide’ small RNAs of similar size, are also necessary for miRNA identificatio n projects. Recent rubrics are based on structural and sequence elements of the miRNAs themselves, however these inclusion criteria include paraphyletic groupings of miRNAs, for example eumetazoan miRNAs and S treptophyte (green plant) miRNAs which are not produced by the Drosha/Pasha microprocessor mechanism. Therefore, a dichotomy exists between the structural definitions for miRNAs and understanding of the evolutionarily conserved function of the microprocessor and its components. In this article, I re view literature in the context of this topic and discuss philosophical significance for understanding the importance of the microprocessor in understanding the evolutionary and molecular origins of miRNA.

In this report, we establish a straightforward method for estimating the equilibrium constant for the CK reaction over wide but physiologically and experimentally relevant ranges of pH, Mg2+ and temperature. Our empirical formula for CK Keq” is based on experimental measurements. It can be used to estimate [ADP] when [ADP] is below the resolution of experimental measurements, a typical situation because [ADP] is on the order of micromolar concentrations in living cells, and may be much lower in many in vitro experiments. Accurate prediction of [ADP] is essential for in vivo studies of cellular energetics and metabolism, and for in vitro studies of ATP-dependent enzyme function under near-physiological conditions. With [ADP], we could estimate ΔGATP. Application to actomyosin force generation in muscle provides support for the hypothesis that, when [Pi] varies but not when pH is altered, maximum Ca2+-activated isometric force depends on ΔGATP in both living and permeabilized muscle preparations. Further analysis of the pH studies introduces a novel hypothesis for the role of submicromolar ADP in force generation.

Under suitable continuity and uniqueness conditions, solutions of an α order Caputo fractional boundary value problem are differentiated with respect to boundary values and boundary points. This extends well-known results for nth order boundary value problems. The approach used is a standard technique and makes heavy use of recent results for differentiation of solutions of Caputo fractional intial value problems with respect to initial conditions and continuous dependence for Caputo fractional boundary value problems.

A new model of gravity is presented here similar to the earlier work of Verlinde on Emergent Gravity but without the use of Verlinde's main assumption on the nature of gravity as an entropic force using the First Law of Thermodynamics. Instead, the model will be shown to be consistent with the Second Law of Thermodynamics as used in Black Hole Physics. Moreover, it does not use the Equipartition Theorem such that there is no need to define a thermal bath enclosed within a holographic screen. The theory uses $E=NE_{p}$, for the total energy of a massive object where $E_{p}$ is the Planck Energy while $N$ is the number of Planck Energy to represent the maximum possible density of information that can reside in matter. The theory uses also the Holographic Principle as the basis for an information-theoretic approach to the nature of gravity. It is shown here that gravity emerges whenever there is an updating of the information within a given volume of space by the presence of matter.

Decision tables have been used for many years in data processing and business applications to simulate complex rule sets. Several computer languages have been developed based on rule systems and they are easily programmed in several current languages. Land management and river-reservoir models simulate complex land management operations and reservoir management in highly regulated river systems. Decision tables are a precise yet compact way to model the rule sets and corresponding actions found in these models. In this study, we discuss the suitability of decision tables to simulate management in the river basin scale Soil and Water Assessment Tool (SWAT+) model. Decision tables are developed to simulate automated irrigation and reservoir releases. A simple auto irrigation application of decision tables was developed using plant water stress as a condition for irrigating corn in Texas. Sensitivity of the water stress trigger and irrigation application amounts were shown on soil moisture and corn yields. In addition, the Grapevine Reservoir near Dallas, Texas was used to illustrate the use of decision tables to simulate reservoir releases. The releases were conditioned on reservoir volumes and flood season. The release rules as implemented by the decision table realistically simulated flood releases as evidenced by a daily NSE (Nash-Sutcliffe Efficiency) of 0.52 and a percent bias of -1.1%. Using decision tables to simulate management in land, river and reservoir models was shown to have several advantages over current approaches including: 1) mature technology with considerable literature and applications, 2) ability to accurately represent complex, real world decision making, 3) code that is efficient, modular and easy to maintain, and 4) tables that are easy to maintain, support, and modify.

Heterotopic ossification (HO) is most dramatically manifested in the rare and severely debilitating disease, fibrodysplasia ossificans progressiva (FOP), in which heterotopic bone progressively accumulates in skeletal muscles and associated soft tissues. The great majority of FOP cases are caused by a single amino acid substitution in the type 1 bone morphogenetic protein (BMP) receptor ACVR1, a mutation that imparts responsiveness to activin A. Although it is well-established that biological sex is a critical variable in a range of physiological and disease processes, the impact of sex on HO in animal models of FOP has not been explored. We show that female FOP mice exhibit both significantly greater and more variable HO responses after muscle injury. Additionally, the incidence of spontaneous HO was significantly greater in female mice. This sex dimorphism is not dependent on gonadally-derived sex hormones, and reciprocal cell transplantations indicate that apparent differences in osteogenic activity are intrinsic to the sex of the transplanted cells. By circumventing the absolute requirement for activin A using an agonist of mutant ACVR1, we show that the female-specific response to muscle injury or BMP2 implantation is dependent on activin A. These data identify sex as a critical variable in basic and preclinical studies of FOP.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

Many corporations and governments aspire to become Net Zero Carbon Dioxide by 2030-2050. Achieving this goal requires understanding where energy is produced and consumed, the magnitude of CO₂ generation, and the Carbon Cycle. Many prior proposed solutions focus on reducing future CO₂ emissions from continued use of fossil fuels. Examination of these technologies exposes their limitations and shows that none offer a complete solution. For example, bioethanol is shown to be both carbon and energy inefficient. Direct Air Capture technologies are needed to reduce CO₂ already in the air. The most natural form of Direct Air Capture involves letting nature do the work of creating biomass via photosynthesis. However, it is necessary to break the Carbon Cycle by permanently sequestering that biomass carbon in “landfills” modified to discourage decomposition to CO₂ and methane. Tree leaves and biomass grown on-purpose, such as high yield switchgrass, are proposed as good biomass sources for this purpose. Left unsequestered, leaves decompose with a short Carbon Cycle time constant releasing CO₂ back to the atmosphere. While in any given year, leaves represent a small fraction of a tree’s above ground biomass, leaves can represent a substantial fraction of the total biomass generated by a tree when integrated over a tree’s lifetime. Understanding the chemistry of the distinct phases landfills undergo is the key to minimizing or eliminating decomposition. First, the compact cross-linked structure of cellulose and keeping water out will make it difficult for initial depolymerization to release sugars. Air ingress should be minimized to minimize Phase I aerobic decomposition. pH manipulation can discourage acid formation during Phase II. Lignocellulose is low in nutrients needed for anaerobic decomposition. Inhibitors can be added if needed. The goal is to move quickly to the dormant phase where decomposition stops. The cost for Carbon Capture and Storage (CCS) for growing and sequestering high yield switchgrass is estimated to be lower than CCS for steam reforming of methane hydrogen plants (SRM) and supercritical or combined cycle coal power plants. Thus, sequestration of biomass is a natural, carbon efficient, and low-cost method of Direct Capture. Biomass sequestration can provide CO₂ removal on giga tonnes per year scale and can be implemented in the needed timeframe (2030-2050).

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

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

Polymethyl methacrylate (PMMA) polymer is widely used in various fields today. In order to thoroughly reveal the structural impact performance of PMMA materials, this paper is based on the comprehensive Johnson-Cook constitutive model and damage failure model, and accurately confirm the J-C constitutive and damage failure model parameters of PMMA through material test data, The dynamic process of steel bullet impacting PMMA plate structure is analyzed by finite element software ABAQUS. The calculation results show that the numerical simulation results in this paper are in good agreement with the experimental test data. Therefore, the feasibility and accuracy of the impact analysis of PMMA structures based on J-C constitutive and damage failure models in this paper are studied. Finally, based on the J-C constitutive model and damage failure model, the variation of the residual velocity of the bullet with the PMMA plate thickness is analyzed in depth, that is, the results show that the residual velocity of the bullet has a certain linear relationship with the plate thickness.

We reviewed various physical and biological manifestations of an unprecedented large-scale water temperature anomaly that emerged in the Northeast Pacific in late 2013. The anomaly dubbed “The Blob” persisted through 2014-2016, with some signs of its persistence through 2017-2018 and a possible reemergence in 2019. The tentative timeline of The Blob’s successive appearances around the Northeast Pacific is suggestive of its advection by currents around the Gulf of Alaska, along the Aleutians, into the Bering Sea, and eventually to the Bering Strait. During the initial phase of The Blob’s development in 2013-2014, advection along the Polar Front might have played a certain role. The extreme persistence and magnitude of The Blob resulted in numerous and sometimes dramatic ecosystem responses in the eastern Bering Sea. The multi-year duration of The Blob might have preconditioned the Bering Sea for the record low seasonal sea ice extent during the winter of 2017-2018 and disappearance of the cold pool in 2016 and 2018 that profoundly affected zooplankton, invertebrates, fishes, sea birds, and marine mammals. Comparison of time-series of population responses across trophic levels suggests that The Blob lowered primary production during spring, increasing small copepod production and jellyfish, and reducing energy transfer efficiently to higher trophic levels. While the Bering Sea’s water temperature, seasonal sea ice, and cold pool seem to return to the long-term mean state in 2022, it remains to be seen if the Bering Sea ecosystem will completely recover. The two most likely alternative scenarios envision either irreversible changes or hysteresis recovery.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

The transverse momentum distribution of J/ψ mesons produced in pp collisions at the center-of-mass energy 5 TeV, 7 TeV，and 13 TeV is described by the modified Hagedorn function which is based on the Tsallis function and Hagedorn function. The calculated results by the modified Hagedorn function are in accord with experimental data measured by the LHCb Collaboration at LHC. The related parameters are obtained and analyzed.

Considered one of the finest first-generation Nigerian writers, John Pepper Clark-Bekederemo, who passed away on 13th October, 2020, had been categorised as a Eurocentric writer. This work assesses the authenticity or otherwise of this critics’ perception of Clark by critiquing his America, their America. By analysing this autobiography vis-à-vis the notion of self and other which is a theoretical concern in contemporary travel writing, it was established, among other things, that every culture has its dark sides which it must not feel too proud to change as time and situation demand; that Clark vehemently rejects the Americans’ claim of sophistication and superiority of their culture over African culture. The paper concludes that contemporary travel writing should be a rightful site for negotiating cultural, political and diplomatic compromises between the Self and the Other since the gulf may be difficult to close altogether.

Molecular therapies exploiting mRNA vectors embody enormous potential, as evidenced by the utility of this technology for the context of the COVID-19 pandemic. None-the-less, broad implementation of these promising strategies has been restricted by the limited repertoires of delivery vehicles capable of mRNA transport. On this basis, we explored a strategy based on exploiting the well characterized entry biology of adenovirus. To this end, we studied an adenovirus-polylysine (AdpL) that embodied “piggyback” transport of the mRNA on the capsid exterior of adenovirus. We hypothesized that the efficient steps of Ad binding, receptor-mediated entry, and capsid-mediated endosome escape could provide an effective pathway for transport of mRNA to the cellular cytosol for transgene expression. Our studies confirmed that AdpL could mediate effective gene transfer of mRNA vectors in vitro and in vivo. Facets of this method may offer key utilities to feasibilize the promise of mRNA-based therapeutics.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

Proper treatment of infectious air could potentially mitigate the spread of airborne viruses such as porcine reproductive and respiratory syndrome virus (PRRSV). The objective of this research is to test the effectiveness of ultraviolet (UV) in inactivating aerosolized PRRSV, specifically, four UV lamps, UV-A (365 nm, both fluorescent and LED-based), "excimer" UV-C (222 nm), and germicidal UV-C (254 nm), were tested. The two UV-C lamps effectively irradiated fast-moving PRRSV aerosols with short treatment times (<2 s). One-stage and two-stage UV inactivation models estimated the UV doses needed for target percentage (%) reductions on PRRSV titer. UV-C (254 nm) dose needed for 3-log (99.9%) reduction was 0.521 and 0.0943 mJ/cm2, respectively, based on one-stage and two-stage models. An order of magnitude lower UV-C (222 nm) doses were needed for a 3-log reduction, i.e., 0.0882 and 0.048 mJ/cm2, based on one-stage and two-stage models, respectively. However, the cost of 222-nm excimer lamps is still economically prohibitive for scaling-up trials. The UV-A (365 nm) lamps could not reduce PRRSV titers for tested doses up to 4.11 mJ/cm2. Pilot-scale or farm-scale testing of UV-C on PRRSV aerosols simulating barn ventilation rates are recommended based on its effectiveness and reasonable costs comparable to HEPA filtration.

: Belize is located within the Mesoamerican biodiversity hotspot and is an important link between critical biodiverse habitats in Central America. Despite considerable research on biodiversity in marine environments of Belize, research in freshwater environments is limited, with the most recent checklists having been published in obscure, mostly unavailable references more than 20 years ago.Belize is currently experiencing serious degradation of some of its major freshwater resources such as the New River in the northern part of the country. These unique habitats are increasingly threatened by agro-urban development, invasive species and erratic climatic events. The economically important barrier coral reef is also experiencing impacts from the degraded freshwater watersheds that empty into the sea near the reefs. This work addresses the paucity of documentation of the freshwater fishes of Belize, particularly for the Shipstern Peninsula area. The Shipstern Peninsula is a unique region in northern Belize, adjacent to the southern border of Mexico and the northeastern end of the Corozal Bay Wildlife Sanctuary. This paper reports on fish collected in 2015, with comparisons to historical data in surveys published in 1990, 1993, and 1997. We report on 12 genera/species collected in 2015 and provide molecular barcode data on several, which was not available in previous publications. Floridichthys polyommus, a new observation for the Shipstern Lagoon, and Dajaus monticola, a revised name and new observation for the Inland Blue Hole, were confirmed by barcodes. This update is vital to the continued management of freshwater environments in Belize, and especially for the Shipstern Peninsula and its important habitats held in trust for perpetuity for the Belizean people.

Within this paper, a machine learning algorithm is used to investigate the importance of certain setpoints and parameters in the filtration processes of a large-scale water treatment facility. Previously, a model for the filtration process based on Run-to-Run Control was proposed and tested against sample data from the treatment plant, but it was quickly found that such a model was incompatible for successfully computing setpoints of operation which minimize the energy cost of running the filtration systems. The machine learning model described herein is an attempt to elucidate the importance of the available data on the filtration systems and to identify the most important variables that influence the filtration run time.

Since their identification over twenty-five years ago, the plethora of cell penetrating peptides (CPP) and their applications has skyrocketed. These 5 to 30 amino acid long peptides have the unique property of breaching the cell membrane barrier while carrying cargoes larger then themselves into cells in an intact, functional form. CPPs can be conjugated to fluorophores, activatable probes, radioisotopes or contrast agents for imaging tissues, such as tumors. There is no singular mechanism for translocation of CPPs into a cell, and therefore, many CPPs are taken up by a multitude of cell types, creating the challenge of tumor specific translocation and hindering clinical effectiveness. Varying strategies have been developed to combat this issue and enhance their diagnostic potential by derivatizing CPPs for better targeting by constructing specific cell activated forms. These methods are currently being used to image integrin expressing tumors, breast cancer cells, human histiocytic lymphoma and protease secreting fibrosarcoma cells, to name a few. Additionally, identifying safe, effective therapeutics for malignant tumors has long been an active area of research. CPPs can circumvent many of the complications found in treating cancer with conventional therapeutics by targeted delivery of drugs into tumors, thereby decreasing off-target side effects, a feat not achievable by currently employed conventional chemotherapeutics. Myriad types of chemotherapeutics such as tyrosine kinase inhibitors, anti-tumor antibodies and nanoparticles can be functionally attached to these peptides leading to the possibility of delivering established and novel cancer therapeutics directly to tumor tissue. While much research is needed to overcome potential issues with these peptides, they offer a significant advancement over current mechanisms to treat cancer. In this review, we present a brief overview of the research leading to identification of CPPs with a comprehensive state of the art review on the role of these novel peptides in both cancer diagnostics as well as therapeutics.

There are two generic approaches to curing any medical condition. The first treats every patient for all of the known possible causes that contribute to pathogenesis; the second individualizes potentially curative therapy by identifying in each separate patient only those components of pathogenesis that are actually operative, and treating those. This article adopts the second approach for formulating a cure of Alzheimer’s dementia (AD). Components of AD’s pathogenesis are, in alphabetical order: circadian rhythm disturbances, depression, diabetes and insulin resistance, dyslipidemia, hypertension, inflammation, metabolic syndrome, mitochondrial dysfunction, nutritional deficiencies, TGF-β deficiency, underweight, vascular abnormalities, and Wnt/β-catenin deficiency. For each component, data are described that show the degree by which its prevalence is more in the patients with mild cognitive impairment (MCI) who did not revert to having normal cognition than in those who did, because the former group is the pool of patients from among which future AD may develop. Addressing only those components that are present in a particular individual, is potentially a curative strategy. Published data indicate that curative therapy requires that the number of such components to address should be ≥3. Although structural brain changes cannot be directly addressed, the impaired neural tracts result from many of the reversible causal elements, so correcting them will benefit those tract

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16α-carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes mostly xenobiotic metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor α (PPARα) signature. Comparison of this signature with a list of fasting-induced PPARα target genes confirmed that PXR activation decreased the expression of more than 25 PPARα target genes, among which the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPARα activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

COVID-19 affects many organs in our body, including the heart and lungs. COVID-19 cases that require hospitalization often exhibit pulmonary hypertension (PH) due to changes in the lung microvasculature in which the blood vessels become stiff, damaged, or narrow, causing increased pulmonary arterial pressure. This review examines the hypothesis that PH can lead to right ventricular hypertrophy (RVH) as a long-lasting aftereffect of COVID-19. Recent studies have shown that significant percentages of hospitalized patients develop right ventricular hypertension and right ventricular dilatation (RVD), which may lead to right ventricular failure and death. Despite recommendations for echocardiogram reports to include right ventricular wall thickness to assess RVH, few published reports have reported this parameter. Relevant studies on animal models of PH in which the timing of PH can be precisely controlled suggest that one to three weeks of PH can cause RVH. Thus, according to the hypothesis proposed here COVID-19 patients who have long-lasting severe disease (e.g., needed to be on a ventilator for one or more weeks) accompanied by PH and RVD may develop RVH as a long-lasting sequela outlasting the infection itself. Echocardiogram studies of recovered COVID-19 patients may determine whether oft-reported cardiovascular sequelae include RVH.

The rapid spread of African swine fever virus (ASFV), causing severe and often lethal disease in domestic pigs and Eurasian wild boar, continues to be a threat for pig populations and dependent industries. Despite scientific achievements that deepen our understanding of ASFV pathogenesis, alternative transmission routes for ASFV remain to be elucidated. We previously demonstrated the efficient transmission of ASFV from infected boars to naïve recipient gilts via artificial insemination, thereby highlighting the importance of surveillance in boar semen prior to shipment. Since accurate and reliable detection of even low amounts of ASFV in boar semen is key for disease prevention and control, we established a suitable diagnostic pipeline to efficiently detect ASFV genome in boar semen. Here, we assessed sensitivity, specificity and overall performance of various routine nucleic acid extraction kits as well as qPCR protocols in detecting ASFV genome in blood and semen of boars. Feasibility of respective kits and methods for future use in boar studs was also considered. Variability in sensitivity mostly concerned samples with low to very low amounts of ASFV genome. Ultimately, we defined a well-suited pipeline to precisely detect ASFV genome in boar semen, as early as 2 days post ASFV infection.

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 (&gt;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.

Mitochondria are semiautonomous organelles, which are pivotal for the energy metabolism of eukaryotic cells. These organelles contain their own genetic system (mtDNA, mitogenome) that encodes to some structural RNAs and organellar proteins. The biogenesis and function of mitochondria is tightly regulated by nuclear-encoded protein cofactors. The mtDNAs of land plants are characteristically large, with a complex mode of gene organization and expression, in particularly at the post-transcriptional level. To become functional, the primary organellar transcripts undergo extensive maturation steps, which include endo- and exo-nucleolytic cleavage, RNA-base editing, and both ‘cis’- and ‘trans’-splicing events. These essential processing steps rely on the activities of a large set of nuclear-encoded factors. Among these, the RNA helicases serve as key players in organellar (mt-)RNA metabolism. This review summarizes the important roles played by these factors in regulating the highly dynamic processes of transcription, RNA processing, and translation within the mitochondria of land plants. We further discuss recent advancements in understanding how dysregulation of mitochondrial RNA helicases affects the organellar gene expression, respiratory functions, and hence the growth, development and physiology of land plants.

People wore clothes for warmth, survival and necessity in modern life as well but in modern era, eco-friendliness, shorten production time, design, and intelligence also matters. The seamless bonding technology strengthen the bond between fabrics in textiles, while Grey relational analysis (GRA) can be applied to fabrics to measure the relationship between data series and determine the closeness of each data series. In this study, polyurethane prepolymer, 2-Hydroxyethyl acrylate (2-HEA) as an end-capping agent, and n-octyl acrylate (ODA) as a photo-initiator were used to synthesize dual-curing polyurethane hot-melt adhesive. The Taguchi quality engineering and grey relational analysis used to discuss the influence of different mole ratio of NCO:OH, and the effect of the molar ratio of addition of octyl decyl acrylate on the mechanical strength. The Fourier transform infrared spectroscopy (FTIR) results showed the termination of prepolymer's polymerization reaction and the C=O peak intensity at 1730 cm-1 indicating the efficient bonding to main chain. The high molecular weight polymer (20,000-30,000) described by advanced polymer chromatography (APC) confirmed the polyurethane polymer bonded with octyl decyl acrylate to achieve the photo-thermosetting effect. The thermogravimetric analysis (TGA) results showed the thermal decomposition temperature of polyurethane hot melt adhesive also increased and highest pyrolysis temperature (349.89℃) for the polyhydric alcohols. The high value of shear strength (34.94 kg/cm2) as well as peel strength (1.68 kg/cm) were also observed in dual-cure photo-thermosetting polyurethane hot melt adhesive. The signal-to-noise ratio also used to generate the grey relational degree. It was observed that the best parameter ration of NCO: OH was 4:1 with 5 moles of monomer. The Taguchi quality engineering method was used to find the parameters of single quality optimization, and then the grey relation calculation was used to obtain the parameter combination of multi-quality optimization for thermosetting polyurethane hot melt adhesive. The study aims to meet the requirements of seamless bonding in textile factories and optimized experimental parameter design by setting target values can effectively increase production speed, reduce processing time and costs as well.

During speciation-with-gene-flow, a transition from single-locus to multi-locus processes can occur, as strong coupling of multiple loci creates a barrier to gene flow. Testing predictions about such transitions with empirical data requires building upon past theoretical work and the continued development of quantitative approaches. We simulated genomes under different evolutionary scenarios of gene flow and divergent selection, extending previous work with the additions of neutral sites and coupling statistics, allowing us to investigate if and how selected and neutral sites differ in the conditions they require for transitions during speciation. As the per-locus strength of selection grew and/or migration decreased, it became easier for selected sites to show divergence – and thus to rise in linkage disequilibrium (LD) with each other as a statistical consequence – farther in advance of the conditions under which neutral sites could diverge. Indeed, even very low rates of gene flow were sufficient to prevent differentiation at neutral sites. However, once strong enough, coupling among selected sites eventually reduced gene flow at neutral sites as well. To explore whether similar transitions might be detectable in empirical data, we used published genome resequencing data from three taxa of Heliconius butterflies. We found that allele-frequency outliers and F ST outliers exhibited stronger patterns of LD than the genomic background, as expected. The statistical characteristics of LD – likely indicative of the strength of coupling of barrier loci – varied between chromosomes and taxonomic comparisons. Broad qualitative agreement between the patterns we observed in the empirical data and our simulations suggests that selection drives rapid genome-wide transitions to multi-locus coupling, illustrating how divergence and gene flow interact along the speciation continuum.

We describe the innate and adaptive immune system trajectory in Multi-system inflammatory syndrome of childhood (MIS-C), at acute(within 72 hours of hospitalization), resolution (at clinical improvement) and convalescent phase. In our cohort, in the acute phase, 68% of the children were SARS-CoV-2 seropositive, with hypercytokinenemia (high interleukin(IL)-1beta,IL-6,IL-8,IL-10,IL-17, interferon gamma), procoagulant state, myocardial dysfunction, activated neutrophils and monocytes; differential T and B cell subset lymphopenia; activated chemokine receptor type-7 positive and gamma-delta T cell subsets; antigen presenting cells had reduced HLA-DR expression; and B-cell class-switch responses occurred with illness resolution. MIS-C is an immunopathogenic illness associated with SARS-CoV-2 infections in children.

In this data deposit, I describe a dataset that is the result of content mining 167,318 published articles for statistical test results. As a result of this content mining, 688,112 results from 50,845 articles were extracted. In order to provide a comprehensive set of data, the statistical results are supplemented with metadata from the article they originate from. The dataset is provided in a comma separated file (CSV) in long-format. For each of the 688,112 results, 20 variables are included, of which seven are article metadata and 13 pertain to the individual statistical results (e.g., reported and recalculated p-value). A five-pronged approach was taken to generate the dataset: (i) collect journal lists, (ii) spider journal pages for articles, (iii) download articles, (iv) add article metadata, and (v) mine articles for statistical results.

DNA double-strand breaks (DSBs) trigger the Ataxia telangiectasia mutated (ATM)-dependent DNA damage response (DDR), which consists of histone H2AX, MDC1, RNF168, 53BP1, PTIP, RIF1, Rev7, and Shieldin. Early stages of B and T lymphocyte development are dependent on recombination activating gene (RAG)-induced DSBs that form the basis for further V(D)J recombination. Non-homologous end joining (NHEJ) pathway factors recognize, process, and ligate DSBs. Based on numerous loss-of-function studies, DDR factors were thought to be dispensable for the V(D)J recombination. In particular, mice lacking Mediator of DNA Damage Checkpoint Protein 1(MDC1) possessed nearly wild-type levels of mature B and T lymphocytes in the spleen, thymus, and bone marrow. NHEJ factor XRCC4-like factor (XLF)/Cernunnos is functionally redundant with ATM, histone H2AX, and p53-binding protein 1 (53BP1) during the lymphocyte development in mice. Here, we genetically inactivated MDC1, XLF, or both MDC1 and XLF in murine vAbl pro-B cell lines and, using chromosomally integrated substrates, demonstrated that MDC1 stimulates the V(D)J recombination in cells lacking XLF. Moreover, combined inactivation of MDC1 and XLF in mice resulted in synthetic lethality. Together, these findings suggest that MDC1 and XLF are functionally redundant during the mouse development, in general, and the V(D)J recombination, in particular.

Sediment cores were collected from a mudflow lobe (80 m water depth) offshore of the Mississippi River’s Southwest Pass in 2017 to better understand the sedimentology near the lobe entraining the SS Virginia shipwreck (sunk by a German U-Boat in 1942) and surrounding Mississippi River Delta Front. Core analyses included 210Pb/137Cs geochronology, granulometry, and X-radiography. Sediment accumulation rates (SAR) calculated from excess 210Pb activity in multicores are 0.22–0.29 cm/yr at seabed depths less than 20 cm and 0.29–0.51 cm/year at depths greater than 20 cm. 137Cs accumulation rates are ~0.15 to ~ 0.37 cm/year since 1954 and 1963 respectively. Sediment accumulation rates from 210Pb and 137Cs geochronology and indicators of relative sedimentation and bioturbation from X-radiographs suggest that rates of sediment accumulation near Virginia have declined since ca. the mid-20th century. This may be explained by the multi-decade downslope mass transport of the mudflow lobe in which the shipwreck is embedded, and decreases in sediment supply delivered offshore from the Mississippi River. Mass-transport calculations of the Virginia lobe derived from core properties and published lobe advection rates suggest downslope mass transport is far higher than sediment resupply from the Mississippi River, consistent with recent studies of delta retreat.

This study describes the AMD impacted environments and critically discusses the effects of AMD, current prediction and prevention methods and treatment technologies. The study further, crit-ically analyses the case studies, gaps in AMD research and the challenges and opportunities of-fered by AMD. The study outlined future technological intervention aiming at a paradigm shift towards reducing the volume of sludge generated as well as the operating cost and improving AMD treatment efficiency. The integrated AMD treatment technologies that result in a holistic approach toward sustainable AMD treatment are a current need. As a result, a sustainable AMD treatment strategy has been made possible due to water reuse and rich resource recoveries such sulphuric acid, rare earth elements, and metals. The cost of AMD treatment can be decreased with the use of recovered water and resources, which is essential for developing a sustainable AMD treatment process.

Atomic state preparation can benefit from a compact and uniform magnetic field source. Simulations and experimental measurements have been used to design, build, and test such a source as shown by optical pumping of atomic Helium. This source is a 9.5 mm (3/8") OD x 6.7 mm (1/4") ID x 9.5 mm (3/8") long, NdFeB-N42 assembly of 1.6 mm (1/16") thick customized annular magnets. It has octopole decay with a residual dipole far field from imperfect dipole cancelations. It has greater than 50% clear aperture with uniform and collimated magnetic field consistent with the prediction of several models. Octopole roll-off localizes the field minimizing the need for shielding in applications. The device is applied to a high precision 3,4He laser spectroscopy experiment using σ+ or σ- optical pumping currently resulting in a measured 99.3% preparation efficiency and in accordance with a rate-equation model.

The aim of the present study was to evaluate the association between television viewing/physical activity (TVV/PA) interactions and cardiometabolic risk in an adult European population. A total of 2,155 subjects (25-64 years) (45.2% males), a random population-based sample were evaluated in Brno, Czechia. TVV was classified as low (&lt;2hours/day), moderate (2-4), and high (≥4). PA was classified as insufficient, moderate, and high. To assess the independent association of TVV/PA categories with cardiometabolic variables, multiple linear regression was used. After adjustments, significant associations were: high TVV/insufficient PA with body mass index (BMI) (β=2.61,SE=0.63), waist circumference (WC) (β=7.52,SE=1.58), body fat percent (%BF) (β=6.24,SE=1.02), glucose (β=0.25,SE=0.12), triglycerides (β=0.18,SE=0.05), and HDL-C (β=-0.10,SE=0.04); high TVV/moderate PA with BMI (β=1.98,SE=0.45), WC (β=5.43,SE=1.12), %BF (β =5.15,SE=0.72), triglycerides (β =0.08,SE=0.04), total cholesterol (β=0.21,SE=0.10), LDL-c (β=0.19,SE=0.08), and HDL-c (β=-0.07,SE=0.03); and moderate TVV/insufficient PA with WC (β=2.68,SE=1.25), %BF (β=3.80,SE=0.81), LDL-c (β=0.18,SE=0.09), and HDL-c (β=-0.07,SE=0.03). Independent of PA levels, higher TVV was associated with higher amounts of adipose tissue. Higher blood glucose and triglycerides were present in subjects with high TVV and insufficient PA, but not in those with high PA alone. These results affirm the independent cardiometabolic risk of sedentary routines even in subjects with high-levels of PA.

Abstract: The baculovirus expression vector (BEV) system is an efficient, cost effective and scalable method to produce recombinant adeno-associated virus (rAAV) gene therapy vectors. Most BEV designs emulate the wild type AAV transcriptome and translate the AAV capsid proteins, VP1, VP2 and VP3 from a single mRNA transcript with three overlapping open reading frames (ORFs). Non-canonical translation initiation codons for VP1 and VP2 reduce their abundances relative to VP3. Changing capsid ratios to improve rAAV vector efficacy requires theoretical modification of translational context. We have made a Lac repressor inducible system to empirically regulate expression of VP1 and VP2 proteins relative to VP3 in the context of the BEV. We demonstrate the use of this system to tune the abundance, titer and potency of a neurospecific rAAV9 serotype derivative. VP1:VP2:VP3 ratios of 1:1:8 gave optimal potency for this rAAV. It was discovered that ratios of capsid proteins expressed were different than ratios that ultimately were in purified capsids. Over expressed VP1 did not become incorporated into capsids while over expressed VP2 did. Overabundance of VP2 correlated with reduced rAAV titers. This work demonstrates a novel technology for controlling production of rAAV in the BEV system and shows a new perspective on the biology of rAAV capsid assembly.

J/ψ, a charmonium bound state made of a charm and an anti-charm quark, has been discovered in the 1970s and confirmed the quark model. Because the mass of charms quarks is significantly above the Quantum Chromodynamics (QCD) scale ΛQCD, charmonia are considered as excellent probes to test perturbative Quantum Chromodynamics (pQCD) calculations. Over the past decades, they have been studied extensively at different high energy colliders. However, their production mechanisms, which involves multiple scales, are still not very well understood. Recently, in high multiplicity p+p collisions at RHIC and at the LHC, a significant enhancement of J/ψ production yield has been observed, which suggests a strong contribution from the Multi-Parton Interaction (MPI). This is different from the traditional pQCD picture where charm quark pairs are produced from a single hard scattering between partons in p+p collisions. In this work, we will report the J/ψ normalized production yield as a function of normalized charged particle multiplicity over a board range of rapidity and event multiplicity in the J/ψ→μ+μ− channel with PHENIX Run 15 p+p data at \sqrt{s}=200 GeV. The results are compared with PYTHIA 8 simulations with the MPI option on and off. Finally, the outlooks of J/ψ in p+Au and Au+p collisions along with Color Glass Condensate (CGC) predictions and of multiplicity dependent ψ(2S)/J/ψ ratio in p+p data will be briefly discussed.

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

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

In this study, we examine the relationship of bank level lending and borrowing decisions and the risk preferences on the dynamics of the interbank lending We develop an agent-based model that incorporates individual bank decisions using the temporal difference reinforcement learning algorithm with empirical data of 6600 S. banks. The model can successfully replicate the key characteristics of interbank lending and borrowing relationships documented in the recent literatur A key finding of this study is that risk preferences at individual bank level can lead to unique interbank market structures which are suggestive of the capacity that the market responds to surprising

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorders in children and is frequently associated with Epstein-Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or NK-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with vesiculopapules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory therapy is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated, overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.

In the transition towards sustainable energy sources, hydrogen has emerged as the predominant alternative after fossil fuels. This comprehensive literature review delves into the evolving landscape of hydrogen launching strategies within the energy market. Numerous countries have strategically initiated efforts to introduce products based on hydrogen, underscoring the global acknowledgment of the potential inherent in hydrogen. Despite witnessing significant growth in the adoption of hydrogen energy worldwide, impediments to its widespread commercialization persist. This review identifies key barriers, including cost structures, technical complexities, and marketing challenges, hindering the establishment of a robust hydrogen energy market. The article critically examines the actions already undertaken to harness hydrogen energy for commercial purposes, leveraging scientific insights and statistical data. By carefully examining the current state of hydrogen energy initiatives, the review highlights gaps in existing strategies that require thoughtful consideration. Insights derived from scientific and statistical analyses inform the identification of barriers and contribute to a nuanced understanding of the challenges faced in the journey towards hydrogen energy commercialization. Ultimately, the article presents a strategic proposal outlining marketing actions geared towards expediting the commercialization and widespread adoption of hydrogen energy. Grounded in a thorough review of existing literature and supported by scientific and statistical evidence, this comprehensive analysis offers valuable insights for stakeholders seeking to navigate the intricate landscape of hydrogen energy in the global energy market.

It is not established whether SARS-CoV-2 (COVID-19) patients with movement disorders, are at greater risk for more serious outcomes than the larger COVID-19 population beyond the susceptibility associated with greater age. We reviewed electronic health records and conducted telephone interviews to collect the demographics and clinical outcomes of patients seen at our Movement Disorders Center who tested positive for COVID-19 from 8 March 2020 through 6 June 2020. Thirty-six patients were identified, 23 men and 13 women, median age of 74.5 years. They primarily carried diagnoses of idiopathic Parkinson disease (n=22; 61%) and atypical parkinsonism (n=7; 19%) with the balance having other diagnoses. Twenty-seven patients (75%) exhibited alteration in mental status and fifteen (42%) had abnormalities of movement as common manifestations of COVID-19; in 61% and 31%, these were the presenting symptoms of the disease. 67% of patients in our cohort required hospitalization, and the mortality rate was 39%.. These data demonstrate that in patients with movement disorders, the likelihood of hospitalization and death after contracting COVID-19 was substantially greater than in the general population. Patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility but not anosmia.

At 12:28 UTC (8:28 PM, local time) on 15 January 2023, a shallow, moderate earthquake with a magnitude (Mw) of 4.7 and a depth of one (1) kilometer shook the northern part of Leyte Island in the central part of the Philippines. The ground shaking was felt at PHIVOLCS Earthquake Intensity Scale (PEIS) VI, (very strong) equivalent to Modified Mercalli Intensity (MMI) VI in areas along the strike of the Leyte segment of the Philippine Fault. Even though this earthquake is classified as moderate in size, significant geologic, structural, and socio-economic impacts were documented. Most of the earthquake impacts that include surface rupture, liquefaction, and mass movements are limited near the epicentral area. The earthquake produced an 8-km-long surface rupture, the first documented rupture generated by a magnitude &lt;6 along the Philippine Fault, and is unusual in other surface rupturing earthquakes worldwide. It injured 18 persons and damaged 434 residential buildings and 26 public infrastructures which amounts to about 500 thousand US dollars. Structural damages were caused by surface rupture and/or poor engineering construction practices. Analysis of the seismic waveform and recorded peak ground acceleration (PGA) suggests that the subsurface geology influenced the ground motion amplification in an area near the epicenter. Based on the hypocenter, focal mechanism solution, aftershock distribution, and actual field observation, the causative fault for this event is the northern end of the Philippine Fault – Leyte segment. Moderate in size, this earthquake emphasizes the need and importance of documenting moderate-sized earthquakes as a tool and guide for medium and long-term earthquake risk assessment and resiliency.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Loneliness is becoming prevalent across Japan in spite of its a dense population and communal culture. Surveys show 40% of adults report isolation across demographics. The contradiction emerges due to deteriorating social structure with modernization, economic parity, urbanization, and fading conventional setup. The continually social withdrawals, called “hikikomori." Relief seekers have embraced AI based emotive robots, digital avatars, and immersive VR as low-stakes social surrogates despite limited capacity to cultivate human intimacy. To stabilise government attempts awareness through reforms, scheme and support services. But a concrete transformation can be brough in with work-life balance, gender equality and rewire the metrics for self-esteem. Even a perfectly personalized AI cannot replace the human affection lacking in the society. Lasting solutions demand technological aids be balanced by confronting and reinventing community purpose and bring in structural change. Overall Japan’s endemic isolation reveals the societal fraying when modernization privileges independence over interdependence. The path forward rests on restoring cultural foundations to reverse loneliness and social isolation.

Contaminants of Emerging Concern (CECs), a new category of contaminants in limelight, is a major issue of global concern. The pervasive nature of CECs and its harmful effects, such as cancer, reproductive disorders, neurotoxicity etc., make the situation alarming. The perilous nature of CECs lies in the fact that even very small concentration of CECs can cause great impacts on living beings. It also has a nature of bioaccumulation. Thus, it is the ultimate need to have efficient sensors for detection of CECs to ensure safe living environment. Electrochemical sensors are an efficient platform for CEC detection as they are highly selective, sensitive, stable, reproducible, and prompt, and can detect very low concentrations of analyte. Major classes of CECs are pharmaceuticals, illicit drugs, personal care products, endocrine disruptors, newly registered pesticides, and disinfection by-products. This review focusses on CECs, including their sources and pathways, health effects caused by them, and electrochemical sensors as reported in literatures under each category for the detection of major CECs.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

Attempts to use computers to aid in the detection of breast malignancies date back more than 20 years. Despite significant interest and investment, this has historically led to minimal or no significant improvement in performance and outcomes with traditional computer aided detection. However, recent advances in artificial intelligence and machine learning are now starting to deliver on the promise of improved performance. There are at present more than 20 FDA approved AI applications for breast imaging, but adoption and utilization are widely variable and overall low. Breast imaging is unique and has aspects that create both opportunities and challenges for AI development and implementation. Breast cancer screening programs worldwide rely on screening mammography to reduce the morbidity and mortality of breast cancer and many of the most exciting research and available AI applications focus on cancer detection for mammography. There are however multiple additional potential applications for AI in breast imaging including decision support, risk assessment, breast density quantitation, workflow and triage, quality evaluation, response to neoadjuvant chemotherapy assessment, and image enhancement. In this review the current status, availability, and future directions of investigation of these applications are discussed, as well as the opportunities and barriers to more widespread utilization.

: Image guided superficial radiation therapy (IGSRT) combines superficial radiation therapy (SRT) with full dermal visualization (FDV) via high resolution dermal ultrasound (HRDUS) for the treatment of non-melanoma skin cancer (NMSC). The gold standard for IGSRT delivery includes a comprehensive cancer care model with support for the dermatologists by a multidisciplinary team. When delivered in this model, IGSRT can achieve cure rates of 99% for treatment of NMSC. This paper focuses on the benefits of IGSRT during therapy. Medical records from 7 dermatology clinics of 883 patients with 1,507 cases of NMSC treated with IGSRT be-tween 2017 and 2018 were retrospectively reviewed. 92% of the NMSC lesions showed daily depth fluctuations, 60.32% of lesions did not require changes during therapy, and nearly 40% of lesions required at least one compensatory change during therapy. 83% of NMSC lesions were labeled high-risk based on the 2024 NCCN guidelines. Increasing and decreasing tumor depth measurements during IGSRT inform dermatologists when adaptive changes in energy (kV), TDF and dose will result in more efficacy and less toxicity, respectively.

Active ageing is defined as the process of optimizing opportunities for physical, social and mental health to enable older people to take an active part in society without discrimination and to enjoy an independent and good quality of life. The World Health Organization assumed this as a process for increasing and maintaining an individual’s participation in activities to enhance his/her quality of life. In this survey, the authors addressed the following question: “Is assistive technology (AT) for mobility contributing to enhancement of lifelong capacity and performance?”. From June 2015 until February 2016, 96 community dwelling adults, AT users for mobility (powered wheelchairs, manual wheelchairs, lower limb prostheses, walkers, crutches and canes), aged 45-97, mean 67.02 +/- 14.24 years old, 56.3% female, were interviewed using the Psychosocial Impact of Assistive Devices Scale (P-PIADS), the Activities and Participation Profile related to Mobility (APPM) and demographics, clinical and questions about AT use and training. The participants’ profiles revealed moderate limitation and restrictions in participation, measured by the APPM (2.03). Most participants showed positive impact of AT; average scores obtained from the P-PIADS subscales were: Self-esteem 0.62, Competency 1.11 and Adaptability 1.10. P-PIADS total was 0.96, with the powered wheelchair users scoring the highest (1.53) and the walker users scoring the lowest (0.73). All subscales and P-PIADS total were positively correlated with the activities and participation profile. There was no relation between age and the psychosocial impact of AT or activities and participation profile. These results encourage the authors to follow these participants up for a lifelong intervention. To accomplish that aim, currently, the protocol is implemented at the AT prescribing centers in Coimbra, Portugal in order to assess the impact of AT on participation in society, one of the domains of the Active Ageing Index, a new analytical tool to help policy makers in developing policies for active and healthy ageing.

For older adults, approaching end-of-life (EOL) brings unique transitions related to family relationships. Unfortunately, most families greatly underestimate the need to discuss these difficult issues. For example, parents approaching EOL issues often struggle with receiving assistance from others, avoiding family conflict, and maintaining their sense of personhood. In addition, discussions of EOL issues force family members to face their parents’ mortality, which can be particularly difficult for the adult children to process emotionally. This study explored aging issues identified by aging parents and their families as they traverse these impending EOL changes. Ten focus groups of seniors (n = 65) were conducted. Focus groups were organized according to race (African American/Caucasian), gender, and whether the older adult was living independently or in an assisted care facility. When asked open-ended questions about discussing aging and EOL issues with family members, participants revealed tensions that led us to consider Relational Dialectics Theory as a framework for analysis. The predominant tension highlighted in this report was certainty versus uncertainty, with the two sub-themes of sustained life versus sustained personhood and confronting versus avoiding EOL issues. For these data, there were more similarities than differences as a result of gender, race, or living situation than one might expect, although culture and financial status were found to be influential in the avoidance of EOL discussions. The results of this study help to provide additional insight into relational dialectics related to aging, EOL, and the importance of communication in facilitating family coping.

Due to the impacts from climate change, the allocation of water resources must urgently be optimized worldwide to ensure that the needs of both water managers and farmers are balanced. In this study, manager-oriented and farmer-oriented assessment models were developed for irrigation water optimization and allocation. The distance from water sources and hydraulic head were the main factors in the manager-oriented assessment model; crop value, water demand of crops, and soil type were additional factors in the farmer-oriented assessment model. The developed assessment models were used to assess irrigation water allocation in five villages in Neimen District. Cadasters at high elevation were discovered to not be suitable for cultivation of crops because of the difficulties in constructing irrigation facilities and the loss of irrigation water during transportation. The result obtained from the manager-oriented assessment system was related to the costs involved in the construction and maintenance of irrigation facilities, which indicated that cadasters located at long distances from water sources and at high elevation are unsuitable for cultivation. By contrast, the result obtained from the farmer-oriented assessment system was related to the profits of farmers and revealed that more cadasters would be suitable for cultivation if suitable crops were chosen.

High-throughput screening technologies continues to produce large amounts of multiomics data from different populations and cell types for various diseases, such as cancer. However, analysis of such data encounters difficulties due to cancer heterogeneity, further exacerbated by human biological complexity and genomic variability. There is a need to redefine the drug discovery development pipeline, bringing an Artificial Intelligence (AI)-powered informational view that integrates relevant biological information and explores new ways to develop effective anticancer approaches. Here, we show SynPred, an interdisciplinary approach that leverages specifically designed ensembles of AI-algorithms, links omics and biophysical traits to predict synergistic anticancer drug synergy. SynPred exhibits state-of-the-art performance metrics: accuracy – 0.85, precision – 0.77, recall – 0.75, AUROC – 0.82, and F1-score - 0.76 in an independent test set. Moreover, data interpretability was achieved by deploying the most current and robust feature importance approaches. A simple web-based application available online at http://www.moreiralab.com/resources/synpred/ was constructed to predict synergistic anticancer drug combinations requiring only the upload of the two drug SMILES to be tested, allowing easy access by non-expert researchers.

Based on surveys of winter roost sites, the eastern migratory population of the monarch butterfly (Danaus plexippus) in North America appears to have declined in the last 20 years and this has prompted the implementation of numerous conservation strategies. However, there is little information on the survivorship of first-generation monarchs in the core area of occupancy in Texas, Oklahoma, and Louisiana where overwinter population recovery begins. The purpose of this study was to determine the survivorship of first-generation eggs to third instars at a site in north Texas and to evaluate host plant arthropods for their effect on survivorship. Survivorship to third instar averaged 13.4% and varied from 11.7% to 15.6% over three years. The host plants harbored 77 arthropod taxa, including 27 predatory taxa. Despite their abundance, neither predator abundance nor predator richness predicted monarch survival. However, host plants upon which monarchs survived often harbored higher numbers of non-predatory arthropod taxa and more individuals of non-predatory taxa. These results suggest that ecological processes may have buffered the effects of predators and improved monarch survival in our study. The creation of diverse functional arthropod communities should be considered for effective monarch conservation, particularly in southern latitudes.

Cell free systems are a widely used research tool in systems and synthetic biology and a promising platform for manufacturing of proteins and chemicals. In the past, cell free biology was primarily used to better understand fundamental biochemical processes. Notably, E. coli cell free extracts were used in the 1960s to decipher the sequencing of the genetic code. Since then, the transcription and translation capabilities of cell free systems have been repeatedly optimized to improve energy efficiency and protein yield. Today, cell free systems, in combination with the rise of synthetic biology, have taken on a new role as a promising technology for just in time manufacturing of therapeutically important biologics and high-value small molecules. They have also been implemented in an industrial scale for the production of antibodies and cytokines. In this review, we discuss the evolution of cell free systems, advancements in cell free protein synthesis, and cell free metabolic engineering, and conclude with discussing the importance and feasibility of mathematical modeling in cell free systems.

Ferrite body is the origin of crack and corrosion initiation of steels. Distribution and density of ferrite in seven steel ingots were examined by light optical microscopy and computational modeling in the study to explore the correlation of ferrite formation to chemical composition and mushy zone temperature in ingot forming. The central segregation phenomenon in ferrite distribution was observed in all the examined steel specimens except 0Cr17Ni4Cu4Nb stainless steel. No significant difference was found in distribution and density of ferrite amongst zones of the surface, ½ radius and core in neither risers nor tails of 0Cr17Ni4Cu4Nb ingots. Additionally, fewer ferrite was found in 0Cr17Ni4Cu4Nb compared to other examined steels. The difference of ferrite formation in 0Cr17Ni4Cu4Nb elicited a debate on the traditional models explicating ferrite formation. Considering the compelling advantages in mechanical strength, plasticity and corrosion resistance, further investigation on the unusual ferrite formation in 0Cr17Ni4Cu4Nb would help understand the mechanism to improve steel quality. In summary, we observed that ferrite formation in steel was correlated with mushy zone temperature. The advantages of 0Crl7Ni4Cu4Nb in corrosion resistance and mechanical stability could be resulted from that fewer ferrites formed and distributed in a scattered manner in microstructure of the steel.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

The advent of the era of big data will bring more convenience to people and greater development to society. But at the same time, it will also bring people the problem of 'information overload', i.e., when people are faced with huge information data, there are many redundant and worthless data. The redundant and worthless data information seriously interferes with the accurate selection of information data. Even though people can use Internet search engines to access information data, they cannot meet the individual needs of specific users in specific contexts. The personalized needs of a particular user in a particular context. Therefore, how to find useful and valuable information quickly has become one of the key issues in the development of big data. With the advent of the era of big data, recommendation systems, as an important technology to alleviate information overload, have been widely used in the field of e-commerce. Recommender systems suffer from a key problem: data sparsity. The sparsity of user history rating data causes insufficient training of collaborative filtering recommendation models, which leads to a significant decrease in the accuracy of recommendations. In fact, traditional recommendation systems tend to focus on scoring information and ignore the contextual context in which users interact. There are various contextual modal information in people's real life, which also plays an important role in the recommendation process. In this paper we achieve data degradation and feature extraction, solving the problem of sparse data in the recommendation process. An interaction context-aware sub-model is constructed based on a tensor decomposition model with interaction context information to model the specific influence of interaction context in the recommendation process. Then an attribute context-aware sub-model is constructed based on the matrix decomposition model and using attribute context information to model the influence of user attribute contexts and item attribute contexts on recommendations. In the process of building the model, the method not only utilizes the explicit feedback rating information of users in the original dataset, but also utilizes the interaction context and attribute context information of the implicit feedback and the unlabeled rating data. We evaluate our model by extensive experiments. The results illustrate the effectiveness of our recommender model.

Arctic sea ice characteristics have been changing rapidly and significantly in the last few decades. Using a long-term time series of sea ice products from satellite observations - the extended AVHRR Polar Pathfinder (APP-x), trends in sea ice concentration, ice extent, ice thickness, and ice volume in the Arctic from 1982 to 2020 are investigated. Results show that the Arctic has become less ice-covered in all seasons, especially in summer and autumn. Arctic sea ice thickness has been decreasing at the rate of -3.24 cm per year, resulting in about a 52% reduction in thickness from 2.35 m in 1982 to 1.13 m in 2020. Arctic sea ice volume has been decreasing at the rate of -467.7 km³ per year, resulting in about a 63% reduction in volume, from 27590.4 km³ in 1982 to 10305.5 km³ in 2020. These trends are further examined from a new perspective, where the Arctic Ocean is classified into open water, perennial, and seasonal sea ice-covered areas based on the sea ice persistence. The loss of the perennial sea ice-covered area is the major factor in the total sea ice loss in all seasons. If the current rates of sea ice changes in extent, concentration, and thickness continue, the Arctic is expected to have ice-free summer by the early 2060s.

Purpose: Prostate cancer remains the 2nd leading cancer killer of men, yet it is also a disease with a high rate of overtreatment. Diffusion weighted imaging (DWI) has shown promise as a reliable, grade-sensitive imaging method, but it is limited by low image quality. Currently, DWI image quality is directly related to low gradient ampli-tudes, since weak gradients must be compensated with long echo times. Methods: We propose a new type of MRl accessory, an "inside-out" and nonlinear gradient, whose sole purpose is to deliver diffusion encoding to a region of interest. Performance was simulated in OPERA and the resulting fields were used to simulate DWI with two compartment and kurtosis models. Experiments with a nonlinear head gradient prove the accuracy of DWI and ADC maps diffusion encoded with nonlinear gradients. Results: Simulations validated thermal and mechanical safety while showing a 5 to 10-fold increase in gradient strength over prostate. With these strengths, lesion CNR in ADC maps approximately doubled for a range of anatomical positions. Proof-of-principle experiments show that spatially varying b-values can be corrected for accurate DWI and ADC. Conclusions: Dedicated nonlinear diffusion encoding hardware could improve prostate DWI.

Angiogenesis is a critical physiological response to ischemia but becomes pathological when dysregulated and driven excessively by inflammation. We recently identified a novel angiogenic role for tripartite-motif-containing protein 2 (TRIM2) whereby lentiviral shRNA-mediated TRIM2 knockdown impaired endothelial angiogenic functions in vitro. This study sought to determine whether these effects could be translated in vivo and to determine the molecular mechanisms involved. CRISPR/Cas9-generated Trim2–/– mice that underwent a periarterial collar model of inflammation-induced angiogenesis exhibited significantly less adventitial macrophage infiltration relative to wildtype (WT) littermates, concomitant with decreased mRNA expression of macrophage marker Cd68 and reduced adventitial proliferating neovessels. Mechanistically, TRIM2 knockdown in endothelial cells in vitro attenuated inflammation-driven induction of critical angiogenic mediators, including nuclear HIF-1α, and curbed the phosphorylation of downstream effector eNOS. Conversely, in a hindlimb ischemia model of hypoxia-mediated angiogenesis, there were no differences in blood flow reperfusion to the ischemic hindlimbs of Trim2–/– and WT mice despite a decrease in proliferating neovessels and arterioles. TRIM2 knockdown in vitro attenuated hypoxia-driven induction of nuclear HIF-1α but had no further downstream effects on other angiogenic proteins. Our study has implications for understanding the role of TRIM2 in the regulation of angiogenesis in both pathophysiological contexts.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

Little is known about public knowledge of meat chicken production and how it influences attitudes to birds’ welfare and consumer behaviour. We interviewed 506 members of the public in SE Queensland, Australia, to investigate this. Knowledge was assessed from 15 questions, and low scores were supported by respondents’ self-assessed report of low knowledge levels and agreement that their knowledge was insufficient to form an opinion about which chicken products to purchase. Older respondents and single people without children were most knowledgeable. There was uncertainty about whether chicken welfare was adequate, particularly in those with little knowledge. There was also evidence that lack of empathy towards chickens related to lack of knowledge, since those that thought it very acceptable that some birds are inadequately stunned at slaughter had low knowledge scores. More knowledgeable respondents ate chicken more frequently and were less likely to buy products with accredited labelling. Approximately half of the respondents thought the welfare of the chicken to be more important than the cost. It is concluded that the public’s knowledge has an important connection to their attitudes and consumption of meat chickens. Respondents with little knowledge demonstrated that they had both lack of empathy and intolerance to religious slaughter practices.

We confirm that energy dissipation weighting provides the most accurate approach to determining the effective hydraulic conductivity (Keff) of a binary K grid. A deep learning algorithm (UNET) can infer Keff with extremely high accuracy (R2 > 0.99). The UNET architecture could be trained to infer the energy dissipation weighting pattern from an image of the K distribution with high fidelity, although it was less accurate for cases with highly localized structures that controlled flow. Furthermore, the UNET architecture learned to infer the energy dissipation weighting even if it was not trained on this information directly. However, the weights were represented within the UNET in a way that was not immediately interpretable by a human user. This reiterates the idea that even if ML/DL algorithms are trained to make some hydrologic predictions accurately, they must be designed and trained to provide each user-required output if their results are to be used to improve our understanding of hydrologic systems most effectively.

Sustainable agricultural production is endangered by several ecological factors such as drought, extreme temperatures, excessive salts, parasitic ailments, and insect pest infestation. These challenging environmental factors may have adverse effects on future agriculture production in many countries. In modern agriculture, conventional crop breeding techniques alone are inadequate for achieving the increasing population’s food demand on a sustainable basis. The advancement of molecular genetics and related technologies are promising tools for the selection of new crop species. Gene pyramiding through marker assisted selection (MAS) and other techniques have accelerated the development of durable resistant/tolerant lines with high accuracy in the shortest possible period of time for agricultural sustainability. Gene stacking has not been fully utilized for biotic stress resistance development and quality improvement in most of the major cultivated crops. This review emphasizes on gene pyramiding techniques that are being successfully deployed in modern agriculture for improving crop tolerance to abiotic and biotic stresses for sustainable crop improvement.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions including diet and exercise to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively-normal older adults (N = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

Lead-acid batteries utilised in electrical substations release hydrogen and oxygen when these are charged. These gases could be dangerous and cause a risk of fire if they are not properly ventilated. Therefore, this research seeks to design and implement a network control panel for heating, ventilation, and air-conditioning systems (HVACS). This is done using a specific range of controllers, which have more than thirty loops of proportional, integral and derivative (PID) control to achieve a cost-effective design. It performs the required function of extracting hydrogen, oxygen, and maintaining the desired temperature of the battery storage room within the recommended limits (i.e. 25°C ±1°C tolerance) without compromising quality as set out in the user requirement specification in Appendix-A. The system control panel allows the user to access control parameters such as changing temperature set-points, fan-speed, sensor database amongst others. The hardware is configured to detect extreme hydrogen and oxygen gas content in the battery room and ensure that the HVACS extract the gas content to the outside environment. The results of the system show that the network control panel effectively operates as per the recommended system requirements. Therefore, the effective operation of the HVACS ensures sufficient gas ventilation, thus mitigating the risk of fire in a typical battery storage room. Furthermore, the effective operation of HVACS enhances battery lifespan because of regulated operating temperature, which is conducive to minimise the effect of sulfation in lead acid Batteries (LABs).

Objective: The goal of this review is to provide a succinct, yet comprehensive, guide to the an-tepartum management of multiple gestations. Methods: This narrative review on twins and multiple gestation provides a concise guide for providers with this ever-growing patient population. PubMED was utilized for literature search. Each reference was evaluated and graded for quality of evidence by US Preventative Services Task Force and Cochrane Review guidelines. Screening, surveillance, and management strategies are delineated succinctly and organized by type of multiple gestation being managed from the lowest risk dichorionic twin pair to the increasingly escalating risks of twins and higher order multiples sharing a placenta and/or amniotic sac. Results: The incidence of twin pregnancies has grown over the past several years, due in large part to delayed reproductive timing and surge in assisted reproductive technologies. Twin pregnancies are associated with higher morbidity for both gravidas and offspring, warranting evidence-based approach in counseling and management. Conclusions: We note the important differences among multiples in chorionicity and amnionicity, in the importance of close surveillance and early delivery. Graded clinical pearls and evi-dence-based recommendations are presented to guide obstetric providers.

In the past decade, RNA fragments derived from full length small nucleolar RNAs (snoRNAs) have been shown to be specifically excised and functional. These sno-derived RNAs (sdRNAs) have been implicated as gene regulators in a multitude of cancers, controlling a variety of genes post-transcriptionally via association with the RNA-induced silencing complex (RISC). In this review, we have summarized the literature connecting sdRNAs to cancer gene regulation. SdRNAs possess miRNA-like functions, and are able to fill the role of tumor-suppressor or tumor-promoter in a tissue context-dependent manner. Indeed, there are many miRNAs that are actually derived from snoRNA transcripts, meaning that they are truly sdRNAs and as such are included in this review. As sdRNAs are frequently discarded from ncRNA analyses, we emphasize that sdRNAs are functionally relevant gene regulators and likely represent an overlooked subclass of miRNAs. Based on the evidence provided by the papers reviewed here, we propose that sdRNAs deserve more extensive study to better understand their underlying biology and to identify previously overlooked biomarkers and therapeutic targets for a multitude of human cancers.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

This study aimed at testing the effectiveness of novel combinations of chemical and physical methods to control Prosopis juliflora, an invasive weed in the Moshi and Simanjiro districts of Nothern Tan-zania. Six different treatments including manual uprooting, glyphosate, bark chop with chemical application, two separate chemical mixtures and control were tested in a total of 32 plots, which represented two land use types (grazing land and farmland) found in the two districts. Each plot covered 20m×30m plot area. Two response variables (stem count and tree volume) were recorded to compare weed population density before and after treatment six months later. An analysis of the untreated control plots, showed that the inherent growth potential of P. juliflora was higher in Moshi than in Simanjiro district. The number of stems increased during the experiment for all six treatments showing that the P. juliflora population had not yet reached the local carrying capacity. For the manual control treatment, the increase was reduced compared to the untreated control. For all other treatments, the increase in stem count was on par with that in the untreated control or even higher. Thus, we conclude that only manual uprooting had a controlling effect but not to the extent that it eradicated P. juliflora. Thus, it is for P. juliflora as for weed control in general: weed control must be an ongoing effort.

Predictive numerical models in the study of ground-borne vibrations generated by railway sys-tems have traditionally relied on the segmented approach of subsystems. In this approach, loads are individually applied, and the cumulative effect of rolling stock is obtained through superposi-tion. While this method serves to mitigate computational costs, it may not fully capture the com-plex interactions involved in ground-borne vibrations. Recent advancements in computational and software tools have enabled the development of more sophisticated vibrational pollution models. These advanced models encompass the entire dynamic system, from the rolling stock to the terrain, allowing for continuous simulations with a defined time step. Furthermore, the incorporation of computational contact tools between various ele-ments not only ensures temporal accuracy but also extends the analysis to the frequency domain. This paper explores the evolution of predictive numerical models in the context of ground-borne vibrations generated by trains on ballasted tracks. It highlights the shift from segmented models to continuous simulations, demonstrating the progressive advancement towards more comprehen-sive and accurate representations of railway-induced and generated vibrations in the track sur-roundings as an additional way of evaluate sustainability of infrastructures. In particular, this development of a numerical model from its inception aimed to expand upon ex-isting emission - prediction models by enriching the data with frequency-domain information. This approach has been driven by the aspiration to bridge the gap between numerical predictions and measured signals, striving for a higher level of accuracy in our obtained results. This model can predict the impact of a high-speed rail (HSR) vehicle passing on its own track. It possesses sufficient information in both the time and frequency domains to precisely characterize vibrations. This initiative marks a pivotal advancement, enabling us to more effectively capture the intricacies of ground-borne vibrations and their impact on the surrounding environment due to a deeper comprehension of the occurrences in the frequency domain, there's a heightened ca-pability to accurately characterize vibrations.

Fires are complex multi-physics problems that span wide spatial scale ranges. Capturing this complexity in computationally affordable numerical simulations for process studies and “outer-loop” techniques (e.g., optimization and uncertainty quantification) is a fundamental challenge in reacting flow research. Further complications arise for propagating fires where a priori knowledge of the fire spread rate and direction is typically not available. In such cases, static mesh refinement at all possible fire locations is a computationally inefficient approach to bridging the wide range of spatial scales relevant to fire behavior. In the present study, we address this challenge by incorporating adaptive mesh refinement (AMR) in fireFoam, an OpenFOAM solver for simulations of complex fire phenomena involving pyrolyzing solid surfaces. The AMR functionality in the extended solver, called fireDyMFoam, is load balanced, models gas, solid, and liquid phases, and allows us to dynamically track regions of interest, thus avoiding inefficient over-resolution of areas far from a propagating flame. We demonstrate the AMR capability and computational efficiency for fire spread on vertical panels, showing that the AMR solver reproduces results obtained using much larger statically refined meshes, but at a substantially reduced computational cost. We then leverage the computational efficiency of the AMR solver to demonstrate an optimization framework for fire suppression based on the open-source Dakota toolkit.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Urban lakes, especially those of natural origin, provide ecosystem services, recreation being one of the most important and highly valued by the city dwellers. Fulfilling the needs of city residents to relax and have contact with nature has become a priority in urbanized areas and has been proved to positively affect people’s health and well-being. The recreational potential of water bodies was identified to be most important aspect of ecosystem services to the residents of the neighboring areas. An assessment of recreational ecosystem services (RES) provisioning to society based on the real time spent by the citizens and housing values in the rural-urban gradient revealed that the economic benefits of lakes differ in urbanized, suburban and rural landscapes. The growth of cities has led to an increased population density in the surroundings of ecologically valuable areas, resulting in higher pressure from visitors seeking recreational areas. Along with urbanization, the impoverishment of ecosystem functions takes place, limiting their capability to provide ecosystem services. In this work provisioning of recreational ecosystem services of 28 floodplain lakes located along the urban-rural gradient of the Warsaw agglomeration was assessed. The relationship between the ecological value of the water bodies, measured using naturalness indices, and the recreational ecosystem services they can provide was assessed. The results showed that the floodplain lakes located along the urban-rural gradient are of a great importance to the citizens due to their recreational potential. The provisioning of recreational ecosystem services is poorly connected with the ecological characteristics of the floodplain lakes. Only hemeroby, was significantly correlated with provisioning, and there was no relationship with factors such as naturalness of vegetation or water quality, demonstrating that public preference was not generally influenced by high ecological quality. These data should be available to potential buyers and be integrated in spatial planning management plans in order to shape future housing policy.

Traditional photodynamic therapy (PDT), a clinical cancer therapeutic approach using light in killing cancer cells, is often limited by insufficient light penetration, inefficient photosensitizer energy transfer, and inadequate oxygen in hypoxic tumors. Employing X-ray to activate photosensitizer in PDT can potentially overcome these limitations. Here, we compared protocols to synthesize a novel nano-photosensitizer composed of a europium-doped yttrium oxide core with a silica shell (Y₂O₃:Eu@SiO₂) which can be utilized in such therapeutic method, i.e., X-ray activated PDT (XPDT). Transmission electron microscopy (TEM) and dihydroethidium (DHE) were utilized to evaluate the effects of various synthesis conditions on the characteristics of Y₂O₃:Eu@SiO₂ and their ability to generate reactive oxygen species (ROS). The in vivo tumor suppression effects of the Y₂O₃:Eu@SiO₂ were assessed by ¹⁸F-fluorothymidine position emission tomography (¹⁸F-FLT PET) in human ovarian cancer xenografts using radiation sensitive CAOV3 and radiation resistant SKOV3 cell lines. Our data revealed a positive correlation between nanoparticle condensation time and core size as well as a negative correlation between urea concentrations and core size. Addition of cetyltrimethylammonium bromide (CTAB) during core synthesis enhanced particle dispersion. Two silica coating conditions showed the greatest efficiency in the enhancement of ROS generation. Furthermore, our in vivo study revealed suppression of tumor growth by Y₂O₃:Eu@SiO₂ administration when compared to non-treated control. Silica shell provides flexibility to conjugate moieties that specifically target to cancers. This nano-photosensitizer demonstrates the significant promise for overcoming limitations of conventional PDT and combating various cancers in clinical applications.

Ambulatory heart rate (HR) monitors that acquire electrocardiogram (ECG) or/and photoplethysmographm (PPG) signals from the torso, wrists, or ears are notably less accurate in tasks associated with high levels of movement compared to clinical measurements. However, reliable estimation of HR can be obtained through data fusion from different sensors. These methods are especially suitable for multimodal hearable devices, where heart rate can be tracked from different modalities, including electrical ECG, optical PPG, and sounds (heart tones). Combined information from different modalities can compensate for single source limitations. In this paper, we evaluate the possible application of data fusion methods in hearables. We assess data fusion for heart rate estimation from simultaneous in-ear ECG and in-ear PPG, recorded on eight subjects while performing 5-minute sitting and walking tasks. Our findings show that data fusion methods provide a similar level of mean absolute error as the best single-source heart rate estimation but with much lower intra-subject variability, especially during walking activities. We conclude that data fusion methods provide more robust HR estimation than a single cardiovascular signal. These methods can enhance the performance of wearable devices, especially multimodal hearables, in heart rate tracking during physical activity.

We evaluated the potential of using fish species and functional traits as indicators of land use impacts to fish assemblages. We used environmental data collected at multiple spatial scales (local, reach, and upstream catchment) for 19 tributary and main stem sites in the Nolichucky River watershed in Tennessee. Canonical correspondence analyses showed that temperature, elevation, specific conductivity, sediment yield, impervious surfaces, and row crop cover at the catchment scale were strongly associated with fish assemblage structure, as well as forest cover from all three spatial scales. Blocked indicator species analysis, with stream size as the block, showed that significantly strong indicators of the least-impacted riparian land use condition (≥60% forest cover) were Saffron Shiner (Notropis rubricroceus), Rainbow Trout (Oncorhyncus mykiss), Longnose Dace (Rhynichthys cataractae), Creek Chub (Semotilus atromaculatus), and Mottled Sculpin (Cottus bairdi). Traits indicative of the least-impacted sites were the herbivorous trophic guild, mean female age-at-maturity, longevity, rock-gravel spawners, montane geology and pelagic swimmers. Specific conductivity was strongly related to multiple catchment-scale land use variables, and was a strong local-scale influence on fish assemblage structure. Our results show promise for using a relatively common but endemic southern Appalachian fish species, the Saffron Shiner, as an indicator for land-use related impacts to these streams.

This study was conducted to investigate the effect of supplementing different types of methionine (L and D-type) and its precursor (HMBi) on milk protein synthesis using immortalized bovine mammary epithelial cell line (MAC-T Cell); D-methionine (D-Met), L-methionine (L-met) and 2-hydroxy-4-methylthiobutanoic acid I (HMBi), an isopropyl ester of the hydroxy analogue precursor of methionine. The underlying mechanism of milk protein synthesis by adding D- and L-type amino acid as well as HMBi was elucidated through omics analysis to verify the metabolism pathway. Results showed that HMBi group showed the highest beta casein mRNA expression levels compared to D- and L-Met groups and highest medium protein although not different with the L-Met treatment. The observed upregulated (>2 protein expression vs. control) and downregulated (<0.5 protein expression vs. control) proteins in L-Met, D-Met and HMBi treated groups were: 39, 77; 46, 68; and 40, 78, respectively. Interestingly, based on protein pathway analysis, L-Met treated group stimulated the ATP synthesis, PI3 kinase and pyruvate metabolism. On the other hand, the D-Met group stimulated fructose-galactose metabolism, glycolysis pathway, PI3 kinase and pyruvate metabolism. And lastly HMBi-treated group stimulated pentose phosphate pathway and glycolysis pathway. Metabolite analysis revealed that L-Met treated group resulted in the increase in 11 metabolites. On the other hand, D-Met treated group showed increase in 7 metabolites and decreased of uridine monophosphate (UMP). HMBi supplementation caused increases of 3 metabolites and decreased of UMP and N-acetyl-L-glutamate Addition of different isoforms of Met stimulated the production of intermediate metabolites for energy production. Addition of L-Met stimulated the production of energy metabolites such as pyruvate, malate, and fumarate, well-known as intermediates of Krebs cycle. On the other hand, HMBi supplementation resulted in increases of energy metabolite glucose 1-phosphate and 6-phosphogluconate. Results showed that HMBi-treated group exhibited highest expression of β-casein mRNA expression by stimulating proteins and metabolites as well as protein and metabolic pathways involved in protein and energy synthesis. As a result, HMBi-treated group resulted in highest protein concentration but not significantly different with L-Met. Both the D- and L-isoforms has considerably the same medium protein concentration and β-casein mRNA expression higher than the control. So, D- and L-Met isoforms can be used alternatively without any significant change in protein synthesis efficiency in bovine mammary epithelial cells.