With the rapid evolution of SARS-CoV-2, the emergence of new strains is an intriguing question. This paper presents an evolutionary theory to analyze the mutations of the virus and identify the conditions that lead to the generation of new strains. We represent the virus variants using a 4-letter sequence based on amino acid mutations on the spike protein and employ an n-distance algorithm to derive a variant phylogenetic tree. We show that the theoretically-derived tree aligns with experimental data on virus evolution. Additionally, we propose an A-X model, utilizing the set of existing mutation sites (A) and a set of randomly generated sites (X), to calculate the emergence of new strains. Our findings demonstrate that a sufficient number of random iterations can predict the generation of new macro-lineages when the number of sites in X is large enough. These results provide a crucial theoretical basis for understanding the evolution of SARS-CoV-2.

Ammonium sulfate has been utilized in agriculture; however, there is a dearth of research on its application in maize cultivation subsequent to the implementation of nitrification inhibitors or coating. This study aims to analyze the impacts of various combinations of ammonium sulfate fertilizers on soil nutrients, plant nutrient uptake, yield, and fertilizer utilization efficiency in maize cultivation to ascertain the optimal and stabilized disposal method for ammonium sulfate. A completely randomized design was employed with five treatments (AU, the control using urea; AS, treatment using ammonium sulfate; ASN, treatment using ammonium sulfate with a nitrification inhibitor; ASG, treatment using oil-coated ammonium sulfate; ASD, treatment using oil-humic acid-coated ammonium sulfate). Results showed that: (1) Compared with AU and AS, ASN, ASG and ASD decreased the leaching rates of TN, NH4+-N and NO3-N to the 10-20 cm soil layer, and more residual N was obtained in 0-10 cm soil layer. The first-order kinetic equation Nt=N0(1-e-kt) can better fit the process of nitrogen accumulation and release, and the N release rate constant is AU>CK>AS>ASH>ASN>ASD; (2) Compared with AU and AS treatments, the plant dry weight, grain dry weight, spike width, spike length, and yields of maize increased by 8.85-11.08%, 12.98-14.15%, 2.95-3.52%, 5.50-5.65%, and 43.21-51.10% under ASG treatment respectively. The impact of effective spike number on maize yield was found to be significant, as demonstrated by the path analysis conducted in this study. Furthermore, the accumulation levels of nitrogen, phosphorus, and potassium within above-ground plants significantly increased under the ASG treatment compared to the AU and AS treatments. The partial productivity of nitrogen, phosphorus, and potassium increased by 1.43-1.51-fold under ASG treatment, while grain nitrogen balance, grain phosphorus balance, and grain potassium balance increased by 1.41-1.58-fold, 1.51-1.95-fold, and 1.15-l.96-fold respectively. The oil-coated ammonium sulfate, therefore, exhibited the optimal slow-release effect of nutrients, thereby achieving superior performance in enhancing maize production and efficiency.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

In this paper, we identify several relative ordering properties of the modified proportional hazard rate and modified proportional reversed hazard rate models. For this purpose, we use two well-known relative orderings, namely the relative hazard rate ordering and the relative reversed hazard rate ordering. The investigation is to see how a relative ordering between two possible base distributions for the response distributions in these models is preserved when the parameters of the underlying models are changed. We will give some examples to illustrate the results and the conditions under which they are obtained.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Culex quinquefasciatus is an important target for vector control because of its ability to transmit pathogens that cause disease. Most populations are resistant to pyrethroids and often to organophosphates, the two most common classes of active ingredients used by public health agencies. A knockdown resistance (kdr) mutation, resulting in a change from a leucine to phenylalanine in the voltage gated sodium channel, is one mechanism contributing to the pyrethroid resistant phenotype. Enzymatic resistance has also been shown to play a very important role. Recent studies have shown strong resistance in populations even when kdr is relatively low which indicates factors other than kdr may be larger contributors to resistance. In this study, we examined on a statewide scale (over 70 populations), the strength of the correlation between resistance in the CDC bottle bioassay and the kdr genotypes and allele frequencies. Spearman correlation analysis showed only moderate (-0.51) and weak (-0.29) correlation between the kdr genotype and permethrin and deltamethrin respectively. The frequency of the kdr allele was an even weaker correlate. These results indicate, in contrast to Aedes aegypti, assessing kdr in populations of Culex quinquefasciatus is not a good surrogate for phenotypic resistance testing.

This paper examines certain implications from the literature on Tiebout’s model of local gov-ernment service provision, particularly Hamilton’s extension of the model to include local control of land use and property taxation. Our empirical analysis focuses on the use of fiscal zoning to lower property tax rates, a topic that has not been addressed in the extensive Tiebout literature. Using data for over 100 municipalities in the Miami, Florida, metropolitan area, we specify property tax rates as a function of fiscal zoning measures, other municipal characteristics, and tax mimicking. We conclude that single-family zoning is by far the most important variable ex-plaining municipal property tax rates.

Phylogeny construction can help to reveal evolutionary relatedness among molecular sequences. The spike (S) gene of SARS-CoV-2 is the subject of an immune selective pressure which increases the variability in such region. This study aimed to identify mutations in the S gene among SARS-CoV-2 sequences collected in the Middle East and North Africa (MENA), focusing on the D614G mutation, that has a presumed fitness advantage. Another aim was to analyze the S gene sequences phylogenetically. The SARS-CoV-2 S gene sequences collected in the MENA were retrieved from the GISAID public database, together with its metadata. Mutation analysis was conducted in Molecular Evolutionary Genetics Analysis software. Phylogenetic analysis was done using maximum likelihood (ML) and Bayesian methods. A total of 553 MENA sequences were analyzed and the most frequent S gene mutations included: D614G=435, Q677H=8, and V6F=5. A significant increase in the proportion of D614G was noticed from (63.0%) in February 2020, to (98.5%) in June 2020 (p<0.001). Two large phylogenetic clusters were identified via ML analysis, which showed an evidence of inter-country mixing of sequences, which dated back to February 8, 2020 and March 15, 2020 (median estimates). The mean evolutionary rate for SARS-CoV-2 was about 6.5 × 10^-3 substitutions/site/year based on large clusters’ Bayesian analyses. The D614G mutation appeared to be taking over the COVID-19 infections in the MENA. Bayesian analysis suggested that SARS-CoV-2 might have been circulating in MENA earlier than previously reported.

Outbreaks of the crown-of-thorns seastar (CoTS) represent a major cause of coral loss on the Great Barrier Reef. Outbreaks might be explained by enhanced larval survival supported by higher phytoplankton availability after flood events, yet little is known about CoTS larvae feeding behaviour, in particular their potential for selective feeding. Here, single- and mixed-species feeding experiments were conducted on CoTS bipinnaria larvae using five algae (Phaeodactylum tricornutum, Pavlova lutheri, Tisochrysis lutea , Dunaliella sp. and Chaetoceros sp.) and two algal concentrations (1000 and 2500 algae mL^-1). Cell counts using flow-cytometry at the beginning and end of each incubation experiment allowed us to calculate the filtration and ingestion rates of each species by CoTS larvae. In line with previous studies, CoTS larvae ingested more algae when initial algal concentration was higher. We found evidence for the selective ingestion of some species (Chaetoceros sp., Dunaliella sp.) over others (P. lutheri, P. tricornutum). The preferred algal species had the highest energy content, suggesting that CoTS selectively ingested the most energetic algae. Ultimately, combining these results with spatio-temporal patterns in phytoplankton communities will help elucidate the role of larval feeding behaviour in determining the frequency and magnitude of CoTS outbreaks.

The Foreign Exchange rate is very much crucial for determining the economic health level of the country. The foreign exchange rate provides financial stability, enhances purchasing power and allows global trades. This rate usually fluctuates due to the market forces which control the supply and demand of the currency. Nominal and relative inflation and income level have a substantial effect on determining the exchange rates. Government measures, international situations, natural disasters or any unexpected situation like Covid-19, Rohingya crisis etc. can affect the exchange rates. Besides this, the interaction between the factors can create different reasoning to affect the market. This study tries to identify some factors with relevant examples.

This is an article or technical note which is intended to provides an insight journey of Machine Learning Systems (MLS) testing, its evolution, current paradigm and future work. Machine Learning Models, used in critical applications such as healthcare industry[1], Automobile [2], [3] and Air Traffic control, Share Trading etc., and failure of ML Model can lead to severe consequences in terms of loss of life or property. To remediate this, developers, scientists, and ML community around the world, must build a highly reliable test architecture for critical ML application. At the very foundation layer, any test model must satisfy the core testing attributes such as test properties and its components. This attribute comes from the software engineering [5], [6], but the same cannot be applied in as-is form to the ML testing and we will tell you “why”.

The mutation databases have vital importance in detecting genetic mutation and their corresponding phenotypes. The emergence of next generation sequencing genetic technologies has accelerated this process, and the growth of genetic disease identification has created a need for quality control and documentation of mutation-related information. Ethnic-specific mutation databases offer valuable information for researchers, and the article evaluates the homogeneity and effectiveness of these databases. The aim to raise awareness of NEMDBs to healthcare professionals, the general public, and researchers studying genetic disorders. The article also recommendations to improve the effectiveness of these databases.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA Hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed pre-COVID-19 pandemic (2015 to 2019) and during the pandemic (2020 - 2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from 10/2019 – 3/2022. CDI case numbers declined 43.2% in 2020 – 2021 compared to the annual mean over the previous 5 years. Stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; P = 0.013). Although inpatient volume declined, rates of CDI among inpatients were reduced by 34.2% in 2020 – 2021. Mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89 – 3.87) vs. 1.92 (95% CI: 1.27 – 2.56); P = &lt;0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic from March 8, 2020, through June 30, 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%. After adjusting for CDI risk factors, a multivariable logistic regression model revealed that odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03 – 39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the initial waves of the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain and frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic.

Innovative interventions in the planning and design of stair and escalator facilities call for understanding their effects on stair use. This study considers five planning variables for the twinned stair and escalator facilities–stair pitch and width, angle of deviation, height and separating distance. Public sites were identified in 8 commercial districts in Beijing. Facilities (n=21) presenting heterogeneously across variables were sampled for simultaneous up and down pedestrian counts in 18 5-minute video segments middays, for a total of 1464 counts. Stair width accounts for 20% of the variance in ascending rate and 10% in descending. Plan angle accounts for 2% in ascending and 5% in descending, while pitch accounts for 1% in ascending and 5% in descending. The study confirms the effects of layout and design of stairway and escalator facilities on facility choice. The results point directly to interventions in support of higher stair-climbing rates.

Based on a rich data set of recoveries donated by a debt collection business, recovery rates for non-performing loans taken from a single European country are modelled using linear regression, linear regression with Lasso, beta regression and inflated beta regression. We also propose a two-stage model: beta mixture model combined with a logistic regression model. The proposed model allows us to model the multimodal distribution we find for these recovery rates. All models are built using loan characteristics, default data and collections data prior to purchase by the debt collection business. The intended use of the models is to estimate future recovery rates for improved risk assessment, capital requirement calculations and bad debt management. They are compared using a range of quantitative performance measures under K-fold cross validation. Among all the models, we find that the proposed two-stage beta mixture model performs best.

Since 2019, the SARS-CoV-2 virus has caused a global pandemic, resulting in widespread infections and ongoing mutations. Analysing these mutations is essential for predicting future impacts. Unlike influenza mutations, SARS-CoV-2 mutations displayed distinct selective patterns that were concentrated in the spike protein and small ORFs. In contrast to the gradual accumulation seen in influenza mutations, SARS-CoV-2 mutations lead to the abrupt emergence of new variants and subsequent outbreaks. This phenomenon may be attributed to their targeted cellular substances; unlike the influenza virus, which has mutated to evade acquired immunity, SARS-CoV-2 appeared to mutate to target individuals who have not been previously infected. The Omicron variant, which emerged in late 2021, demonstrates significant mutations that set it apart from previous variants. The rapid mutation rate of SARS-CoV-2 has now reached a level comparable to 30 years of influenza variation. The most recent variant, JN.1, exhibits a discernible trajectory of change distinct from previous Omicron variants.

The objective of the study was to evaluate the risk factors associated with lower COVID-19 vaccination rates in the United States. The study evaluated the effect of red-blue political affiliation and the effect of the US state's average educational aptitude score and per capita income on states' vaccination rates. The study found that states with concomitantly lower income along with lower educational aptitude scores are less vaccinated while the states with higher income have higher vaccination rates even among those with lower educational aptitude scores. These findings stayed significant after adjusting for red-blue political affiliation where states with red political affiliation have lower vaccination rates. Further study is needed to evaluate how to stop online misinformation among states with low income and low educational aptitude scores; and whether such an effort will increase overall vaccination rates in the United States.

(1) Background: In nervous system information is conveyed by a sequence of action potentials, called spikes-trains. As MacKay and McCulloch proposed, spike-trains can be represented as bits sequences coming from Information Sources. Previously, we studied relations between Information Transmission Rates (ITR) carried out by the spikes, their correlations, and frequencies. Here, we concentrate on the problem of how spikes fluctuations affect ITR. (2) Methods: The Information Theory Method developed by Shannon is applied. Information Sources are modeled as stationary stochastic processes. We assume such sources as two states Markov processes. As a spike-trains' fluctuation measure, we consider the Standard Deviation sigma, which, in fact, measures average fluctuation of spikes around the average spike frequency. (3) Results: We found that character of ITR and signal fluctuations relation strongly depends on the parameter s which is a sum of transitions probabilities from no spike state to spike state and vice versa. It turned out that for smaller s (s<1) the quotient ITR\sigma has a maximum and can tend to zero depending on transition probabilities. While for s large enough (1<s) the ITR\sigma is separated from 0 for each s. Similar behavior was observed also when we replaced Shannon entropy terms in Markov entropy formula by their approximation with polynomials. We also show that the ITR quotient by Variance behaves in a completely different way. (4) Conclusions: Our results show that for large transition parameter s the Information Transmission Rate by sigma will never decrease to zero. Specifically, for 1<s<1.7 the ITR will be always, independently on transition probabilities which form this s, above the level of fluctuations, i.e. in this case we have sigma<ITR. Thus, we conclude that in a more noisy environment, to get appropriate reliability and efficiency of transmission, Information Sources with higher tendency of transition from the state no spike to spike state and vice versa should be applied.

This review article delves into the multifaceted nature of primary ovarian insufficiency (POI), a condition marked by diminished ovarian function before age 40, underscoring the complexity of its aetiology encompassing genetic, autoimmune, infectious, and environmental factors. A significant focus is placed on the potential role of single-gene mutations, such as those in FMR1, BMP15, and GDF9, in the pathogenesis of POI, highlighting the intricate interplay between genetics and ovarian health. The article also explores innovative therapeutic avenues, including the activation of dormant follicles in vitro, offering hope for fertility restoration in affected individuals. Despite the prevalence of traditional treatments, such as Chinese medicine and hormone therapy, in China, these approaches often need to meet therapeutic needs, underscoring the urgency for advanced research and tailored treatment strategies. The discovery of a pituitary tumour-associated POI case further complicates the diagnostic landscape, suggesting a broader diagnostic lens and more in-depth research to unravel the complex underpinnings of POI and enhance patient care.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

Somerateofmutationisinevitable,eveningenesthatthemselvesdeterminethemutation rate. Because mutation in these genes can alter the mutation rate, variation in the mutation rate is inevitable. This simple line of reasoning is corroborated by a handful of empirical studies that found mutation-rate variation in natural and laboratory populations. The evolutionary consequences of mutation-rate variation in natural populations can be many and can be difficult to predict, as selection on such variation can be both direct and indirect. For example, lineages with increased mutation rate will have increased adaptability in the long term but decreased overall fitness in the short term because most fitness mutations are immediately deleterious. In spite of its great relevance to basic and applied science, the rate of mutation to mutator phenotype continues to be essentially unknown. The reasons for this gap in our knowledge are largely methodological; in general, a mutator phenotype cannot be observed directly but must instead be inferred from numbers of some neutral “marker” mutation that can be observed directly: different mutation-rate variants will produce this marker mutation at different rates. Here, we derive the expected distribution of numbers of the marker mutants observed, accounting for the fact that some of the mutants will have been produced by a mutator phenotype that itself arose by mutation during the growth of the culture. This development makes possible a novel experimental protocol for estimating the rate of mutation to mutator phenotype. Simulated experiments using biologically-reasonable parameters that employ this protocol show that such experiments in the lab can give us fairly accurate estimates of the rate of mutation to mutator phenotype. Although our ability to estimate mutation-to-mutator rates from simulated experiments is promising, we view this study as a proof-of-concept study and only a first step towards practical empirical estimation.

Left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy (HCM) commonly occur as separate disorders with distinct clinical and pathoanatomical features. However, these cardiomyopathies may have a similar genetic origin with mutations encoding sarcomeric proteins. The described case demonstrates an example, in which phenotypic expression of both diseases occurs in the same patient.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

Spike (S) protein of Coronaviruses help in receptor attachment and virus entry into the host cells. While S protein is required for virus entry, it is also important as an immunogen as it is the most accessible part of the virus architecture. S protein form knob like structures (viral spikes) protruding outwards in the form of homotrimers containing an S1 and S2 as monomers. Mutations in structural proteins of virus play crucial role in determining virulence and also in many instances influencing emergence of antibody escape variants and cellular tropism. In this paper we have performed in depth analyses of spike protein sequences from various parts of the world and tried to correlate the data with possible functional relevance of such mutations.

The temporal evolution of pandemics described by the susceptible-infectious-recovered (SIR)-compartment model is sensitively determined by the time dependence of the infection (a(t)) and recovery (u(t)) rates regulating the transitions from the susceptible to the infected and from the infected to the recovered compartment, respectively. Here approximated SIR-solutions for different time dependencies of the infection and recovery rates are derived which are based on the adiabatic approximation assuming time-dependent ratios k(t)=u(t)/a(t) varying slowly in comparison to the typical time characteristics of the pandemic wave. For such slow variations the available analytical approximations from the KSSIR-model, valid for a stationary value of the ratio k, are used to insert a-posteriori the adopted time-dependent ratio of the two rates. Instead of investigating endless different combinations of the time dependencies of the two rates a(t) and u(t) a suitably parameterized reduced time dependence of the ratio k(tau) is adopted. Together with the definition of the reduced time this parameterized ratio k(tau) allows us to cover a great variety of different time dependencies of the infection and recovery rates. The agreement between the solutions from the adiabatic approximation in its four different studied variants and the exact numerical solutions of the SIR-equations is remarkably good providing strong confidence in the accuracy of the proposed adiabatic approximation.

Currently available data are consistent with increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at temperatures encountered in the upper airways (25–33°C when breathing room temperature air, 25°C) compared to those in the lower airways (37°C). One factor that may contribute to more rapid viral growth in the upper airways is the exponential increase in SARS-CoV-2 stability that occurs with reductions in temperature, as measured in vitro. Because SARS-CoV-2 frequently initiates infection in the upper airways before spreading through the body, increased upper airway viral growth early in the disease course may result in more rapid progression of disease and potentially contribute to more severe outcomes. Similarly, higher SARS-CoV-2 viral titer in the upper airways likely supports more efficient transmission. Conversely, the possible significance of air temperature to upper airway viral growth suggests that prolonged delivery of heated air might represent a preventative measure and prophylactic treatment for coronavirus disease 2019.

Studies have shown that STK11 mutation plays a critical role in affecting the lung adenocarcinoma (LUAD) tumor immune environment. By training an Inception-Resnet-v2 deep convolutional neural network model, we were able to classify STK11-mutated and wild type LUAD tumor histopathology images with a promising accuracy (per slide AUROC=0.795). Dimensional reduction of the activation maps before the output layer of the test set images revealed that fewer immune cells were accumulated around cancer cells in STK11-mutation cases. Our study demonstrated that deep convolutional network model can automatically identify STK11 mutations based on histopathology slides and confirmed that the immune cell density was the main feature used by the model to distinguish STK11-mutated cases.

Papillary thyroid carcinoma (PTC) accounts for approximately 85%-90% of all thyroid cancers. BRAFV600E mutation is a highly specific target for papillary thyroid carcinoma (PTC) and may have a reciprocal causative relationship with iodide-metabolizing genes. Here, we performed a review of studies published in the past 10 years to determine the relationship between iodine intake and BRAFV600E mutation in patients with PTC. We searched the MEDLINE, PubMed, and EMBASE databases for studies published from 2009 to 2019; seven partially matched the selection criteria and were suitable for review, and five passed all selection criteria. We divided the patients into three groups by iodine intake: low (urinary iodine concentration [UIC] &lt;100 μg/L), adequate (UIC 100–200 μg/L), and high iodine intake groups (UIC ≥200 μg/L). Between-group analysis revealed no significant differences in the odds ratio of the prevalence of BRAFV600E mutation between the high and adequate/low iodine intake groups and between the adequate and low iodine intake groups. To further analyzed the results of studies, they exhibited U-shaped curves in the relation of deficient and excessive dietary iodine intake in BRAFV600E mutation. The results might suggest that iodine intake slightly influences the prevalence of BRAFV600E mutation in patients with PTC despite the heterogeneity of studies. Further research should explore potential mechanisms underlying the associations between iodine intake and BRAF mutation in PTC. The systematic review was registered in PROSPERO (CRD42021279462).

Data on the KIT mutation rate in skin melanoma in the central European region is missing. Accordingly, in a cohort of 79 double wild type (BRAF/NRAS) skin melanoma KIT mutation was assessed by Sanger sequencing of exons 9,11,13,17 and 18. In this skin melanoma cohort KIT mutation frequency was found to be 34/79 (43%) with a significantly higher rate in acrolentiginous melanoma (ALM) as compared to UV-induced common variants (20/34, 58.8% versus 14/45, 31.1%, p=0.014). Exon 11 was the most frequent mutation site (44.7%) followed by exon 9 (21.1%) equally characterizing UV-induced common histotypes and ALM tumors. KIT mutation hotspots were identified in exon 9 (c491/492), in exon 11 (c559,c572, c570), in exon 13 (c642), in exon 17 (c822) and in exon 18 (c853). The relatively high KIT mutation rate in skin melanoma in this central-European cohort justifies regular testing of this molecular target.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

This study examines the causal relationships between interest rates in the Korean financial market using a vector error correction model (VECM) and a Bayesian network. The Bayesian network, a novel approach in this context, identifies two distinct transmission channels: one led by call rates (reflecting monetary policy) and another by 10-year Treasury bond yields (reflecting fiscal policy). While the call rate channel aligns with traditional views, affecting bank lending rates, corporate bond spreads, and commercial paper rates, the 10-year Treasury yield channel highlights a separate fiscal policy transmission mechanism, influencing commercial paper rates indirectly through 30-year Treasury yields and directly impacting merchant bank lending rates. This finding suggests that fiscal intervention could potentially interfere with monetary policy, emphasizing the need for coordinated macroeconomic policy measures. The study also emphasizes the role of 10-year Treasury bonds as a benchmark in the Korean bond market, reflecting medium- to long-term economic outlooks and serving as the underlying asset for various derivatives.

Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

Analysis of SARS-CoV-2 spike protein sequences of over 19 countries from biological databases submitted around the globe was carried out with help of bioinformatics tools and structure prediction databases. Initial data analysis showed entry of virus into different geographic regions started in the month of January 2020. Meanwhile, alignment of spike protein sequences of SARS-CoV-2 isolates from China and other countries revealed a critical mutation of D614G. Surprisingly, mutation D614G was not seen in early samples submitted in the month of January but gradually it started appearing globally from the month of March 2020. However, the mutations of amino acids in the spike protein other than D614G exhibiting similar pI and altered polarity were found to be specific to geographical regions. Besides, prediction of homology model for interaction of spike protein showed predominant role of chain C of trimeric spike protein in adhering receptor binding domain (RBD) of human ACE2 receptor. Furthermore, the prediction of glycosylation points has revealed that there are about 20 N-glycosylation potential sites on spike protein. We believe that the information present here would not only help in thorough understanding of infectivity but also enhance the knowledge of the scientific community in developing prophylactics and/or therapeutics for SARS-CoV19-2 virus.

In flowering plants with dry stigmas, pollen hydration involves water movement, which may be facilitated by aquaporins. To explore the possibility underlying this biological process, we identified and characterized a mutant with a T-DNA insertion in PIP2;5, which encodes an aquaporin with water channel activity in the PIP2 subfamily. We monitored the pollination process (pollen hydration, germination, and pollen tube growth) of wild type pollen on stigmas of the mutant and wild type. Pollen hydration was postponed on the stigmas of the mutant, compared with that on wild type stigmas. However, pollen tube germination and growth was unaffected in the mutant. The PIP2;5 protein was located in the cell plasma membrane and was preferentially expressed in the stigma. Based on our results, we concluded that PIP2;5 might play an important role in water movement during pollen hydration.

Our investigations show that electrochemical corrosion of copper is faster than electrochemical corrosion of aluminium at temperatures below 100oC. Literature data analysis shows that the Al atoms diffuse faster than the Cu atoms at temperatures higher than 475oC, Al rich intermetallic compounds (IMCs) are formed faster in the Cu-Al system, and the Kirkendall plane shifts toward Al side. Electrochemical corrosion occurs due to electric current and due to diffusion. An electronic devise working time, for example, depends on initial copper cover thickness on aluminium wire, connected to the electronic devise, temperature, and volume and dislocation pipe diffusion coefficients, so copper, iron, and aluminium electrochemical corrosion rates are investigated experimentally at room temperature and at temperature 100oC. Intrinsic diffusivities ratios of copper and aluminium at different temperatures and diffusion activation energies in the Cu-Al system are calculated by proposed here methods using literature experimental data. Dislocation pipe and volume diffusion activation energies of pure iron are calculated separately by earlier proposed method using literature experimental data. Aluminium dissolved into NaCl solution as the Al3+ ions at room temperature and at temperature 100oC, iron dissolved into NaCl solution as the Fe2+ (not Fe3+) ions at room temperature and at temperature 100oC, copper dissolved into NaCl solution as the Cu+ ions at room temperature and as the Cu+ and the Cu2+ ions at temperature 100oC. It is founded experimentally that copper corrosion is higher than aluminium corrosion, and ratio of electrochemical corrosion rates, kCu/kAl>1, decreases with temperature increasing, although iron electrochemical corrosion rate doesn’t depend on temperature below 100oC. It is obvious, because melting point of iron is more higher then melting point of copper or aluminium. It is calculated that copper electrochemical corrosion rate is approximately equal to aluminium electrochemical corrosion at temperature about 300oC, so copper can dissolve into NaCl solution mostly as the Cu2+ ions at temperature about 300oC. Ratio of intrinsic diffusivities, DCu/DAl <1, increases with temperature increasing, and intrinsic diffusivity of aluminium could be approximately equal to intrinsic diffusivity of copper at temperature about 460oC.

The aims of study was to evaluate the effects of rates, sources and timing of nitrogen application under cover of transgenic corn yield cultivated in Amazon Biome. The experiments were conducted in Parauapebas city, State of Pará, Brazil, in two years (2016/2017 and 2017/2018). The experimental design was randomized blocks, in a 5x2x2 factorial scheme, consisting of five rates of N (0; 45; 90; 135; and 180 kg ha-1), two nitrogen sources (urea and ammonium sulfate) and two application times of N (phenological stages V4 and V8), with four replications. The factor N rates promoted adjustment of linear equation (leaf area index, mass of thousand grains, and yield) and quadratic equation (dry mass of leaf index). Nitrogen fertilization promoted significant increases in mass of thousand grains and yield, obtaining the best results with 180 kg ha-1 of N applied at V4 phenological stage. Based on results obtained in two years of corn cultivated under conditions of Amazon Biome, the application of N at V4 phenological stage at rates of 121 to 131.39 kg ha-1 of N showed the best results for vegetative growth, while 180 kg ha-1 of N, regardless of source used, urea or ammonium sulfate, promoted greater grain weight and greater yield.

Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Purpose: To investigate the molecular basis of congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome. Methods: We report ocular features of 3 girls with GAPO syndrome born of consanguineous marriage in a multi- generation consanguineous family. The proband (4year old girl) and her younger sibling (1 year old girl) were operated for bilateral congenital glaucoma in both eyes. The elder sibling (10year old female) had features of GAPO syndrome but did not manifest features of glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a homozygous ANTXR1 mutation in all 3 affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense mutation in TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome.Conclusions: Mutations in TGFBI gene could have a role in the pathogenesis of congenital glaucoma.

It has been more than a year since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found. This coronavirus has infected more than 110 million people worldwide by the end of February, 2021, and several virulent as well as more spreadable mutant forms of SARS-CoV-2 have emerged subsequently. In the latter group, three variants B.1.1.7, B.1.351, and P1 lineages, have been reported. Using computer simulation, the present paper investigates the structural differences between the wild type SARS-CoV-2 spike protein and its Asn501Tyr (N501Y) mutant variant. Time-based structural changes between the receptor binding domains of these two species are also examined. The N501Y mutation is common to all the three aforesaid mutant variants.

Mutations in the calcium channel gene Transient Receptor Potential cation channel subfamily V member 4 (TRPV4) cause autosomal dominant skeletal dysplasia, with phenotypes ranging from mild to perinatal lethality. A recent report detailed murine thrombocytosis in the absence of functional TRPV4, but no prior reports have described platelet count abnormalities in the context of human TRPV4 disease. Here, we report a case of prolonged thrombocytosis in the context of TRPV4-associated metatropic dysplasia that was lethal in the infantile period.

Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LEM-domain, emerin interacts with the DNA-binding protein Barrier-to-Autointegration (BAF). Emerin also binds to members of the Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss Muscular Dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, ∆K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas DK37 mutation impairs correct folding of the LEM-domain, P22L and T43I have no impact on the 3D structure of emerin. Surprisingly, all three mutants bind to BAF, albeit with a weaker affinity in the case of DK37. In human myofibroblasts derived from a patient’s fibroblasts, emerin ∆K37 is correctly localized at the inner nuclear membrane, but is present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 is reduced, and cells are defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation DK37 is to perturb emerin function within the LINC complex in response to a mechanical stress.

Although evolutionary theory has yet to furnish a comprehensive rationale for the underlying mechanism of natural selection, it is pertinent to note that the phenomenon transcends the confines of biological systems, exhibiting analogous patterns in physical systems as well. Specifically, isolated and closed systems tend to evolve towards states of progressively increasing entropy. In scenarios where multiple paths for entropy increase are accessible, such systems tend to favor combinations of paths that exhibit the most rapid entropy increase rates. Among the various processes in nature, life activities constitute a salient means of achieving entropy increase. Genetic variation within organisms generates individuals that vary in their rates of entropy increase. As these organisms interact, compete and combine, they form diverse combinations of entropy-increasing pathways. Nature, in turn, selects among these combinations, favoring those that culminate in the fastest entropy increase, thereby propelling the evolution of life. Essentially, the evolution of life is an ongoing exploration of diverse combinations of pathways that maximize entropy increase across various energy pools. Amidst continuous genetic variation and the selective pressure imposed by nature for maximum entropy production rates, information accumulates, leading to a corresponding acceleration in the rate of entropy increase. This natural selection, which favors maximizing the entropy at the fastest possible rate, serves as the ultimate driving force for the origin and evolution of life.

This research article examines the state-wise literacy rates in India, with a focus on male and female literacy, as well as the disparities between them. The data was sourced from a survey conducted by the National Statistical Office (NSO), with a special emphasis on Union Territories and Northeastern states based on the 2011 Census. Kerala boasts the highest literacy rate at 96.2%, while Andhra Pradesh reports the lowest at 66.4%. Notably, the national male-female literacy gap stands at 12.9%. Kerala also demonstrates the smallest gender gap at 2.2%, while Rajasthan exhibits the highest at 23.3%. Through descriptive and explorative analysis, this article provides a comprehensive overview of literacy rates across various Indian states and Union Territories, highlighting the significant disparities that exist.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Glioma accounts for 80% of all malignant brain tumors and is the most common adult primary brain tumor. Age is an important factor affecting the development of cancer as somatic mutations accumulate with age. In this study, we aimed to analyze the significance of age-related non-silent somatic mutations in glioma prognosis. Histological tumor grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wildtype counterpart. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. In conclusion, among the many somatic mutations, those in IDH1, TP53, ATRX, and EGFR are important for glioma classification based on histological grade. Patients with EGFR mutation had the poorest prognosis, whereas those with only IDH1 mutation showed the best prognosis.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

Changes in crude oil price affect the shipping freight market in three different channels. This study explores the dependence structure between oil prices and maritime freight rates to identify the strongest channel. Therefore, it investigates the relationship between oil prices and three major maritime freight rates; the Baltic Dry Index (BDI), the Baltic Dirty Tanker Index (BDTI), and the Baltic Clean Tanker Index (BCTI). We employ the decomposition method, not studied in the existing literature. The copula approach identifies the time-varying effects and asymmetry in the tail dependence structure between oil prices and freight rates. The main results of this analysis are as follows. The decomposed components display different conditional dependence patterns, and asymmetry is revealed in the upper and lower tail dependence. In the long run, we find more dependence in extreme periods like the financial crises. In short-run fluctuations, we find the dependence increases in an economic boom. The implications of the results suggest that dependence can vary over time and may change depending on extreme events, implying that the complementary strategies of the long run and short run should be different.

Genus Clematis is one of the largest within Ranunculaceae. Here we report the chloroplast genome of two Clematis species, C. brachyura and C. trichotoma endemic to Korea. The chloroplast genome lengths of C. brachyura and C. trichotoma are 159,532 bp and 159,170 bp, respectively. Gene contents in the complete chloroplast genomes of these two Clematis species are identical to that of most Ranunculaceae and other angiosperms. However, our data results demonstrated that genus Clematis has inversion and rearrangement events concerning gene rps4 gene, rps16 to trnH region, and trnL to ndhC region, and IR regions expansion. Comparison of IR regions among Ranunculaceae species revealed that Clematis species contained six protein coding genes (infA, rps8, rpl14, rpl16, rps3, and rpl22) usually found in the long single copy (LSC) region of other species. Phylogenetic analysis demonstrated that genus Clematis is closely related to genus Ranunculus. Differences in repeat structure, substitution rates, and IR expansion in genera Clematis and Ranunculus, explained their relationship. Clematis species showed slightly higher tandem repeats content than Ranunculus species. The six protein-coding genes showed lower synonymous substitution rates in the IR of Clematis species than in the LSC of Ranunculus species. Overall, the chloroplast genomes and results presented here provide important information on the evolution of Ranunculaceae.

Organisms in the wild have cryptic life stages that are sensitive to changing environmental conditions and can be difficult to survey. In this study, I used mark-recapture methods to repeatedly survey Anaea aidea (Nymphalidae) caterpillars in nature, then modeled caterpillar demography as a hidden Markov process to assess if temporal variability in temperature and density influence the survival and growth of A. aidea over time. Individual encounter histories result from the joint likelihood of being alive and observed in a particular stage, and I included hidden states by separating demography and observations into parallel and independent processes. I constructed a demographic matrix containing the probabilities of all possible fates for each stage, including hidden states, e.g., eggs and pupae. I observed both dead and live caterpillars with high probability. Peak caterpillar abundance attracted multiple predators, and survival of fifth instars declined as per capita predation rate increased through spring. A time lag between predator and prey abundance was likely the cause of improved fifth instar survival estimated at high density. Growth rates showed an increase with temperature, but the most likely model did not include temperature. This work illustrates how state-space models can include unobservable stages and hidden state processes to evaluate how environmental factors influence vital rates of cryptic life stages in the wild.

As the fast growth of information technology (IT), the safety of image transmission and the storing of images are increasingly concerned. Traditional image encryption algorithms have certain limitations in transmission and security, so there is an urgent need for a secure and reliable image encryption algorithm. A universal compression sensing (CS) image encryption (IE) algorithm based on DNA-triploid mutation (DTM) is presented in this paper. Firstly, by using CS algorithm an image is compressed while obtaining a range of chaotic sequences by iteration of chaotic map. Then DNA sequences are generated by encoding the image, and based on the DTM, new mutant DNA sequences are generated according to specific rules. Next, the chaotic sequences are operated at the DNA level to do confusion and diffusion operations on the image to ensure the security of the data. At last, DNA decoding is carried out to obtain the compressed-encrypted image. Both simulation experiments and performance tests fully show that a high level of security and reliability of the proposed algorithm in protecting image privacy is achieved.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

BRCA-associated hereditary breast and ovarian cancer syndrome (HBOC) implies increased absolute risk also for other malignancies such as cholangiocarcinoma (CCA). However, even if somatic mutations in CCA have been reported, there are no data on its utilization as predisposing genetic factor in a family. For the first time, we utilized CCA somatic BRCA mutation to individualize a family with HBOC. A 47-year-old woman (daughter of a patient died for CCA) accessed to our Genetic Councelling to evaluate her personal cancer risk. We performed a somatic BRCA1/2 NGS analysis on DNA extracted from formalin-fixed, paraffin-embedded CCA-tissue of her mother. After demonstration of pathogenic variant c.6468_6469delTC in BRCA2 gene mutation, the same germline pathogenic variant was found in DNA blood of one of two daugthers. So far, CCA tissue can be utilized, in addition to patient’s selection to specific therapeutic strategies, also to individualize families belonging to HBOC syndrome.

Potassium inwardly-rectifying channel, subfamily J, member 12 (KCNJ12) gene is one promising candidate for economic traits because of its crucial roles in myoblast development. Here, a missense mutation (Cys>Arg), was firstly detected to locate in exon 3 of KCNJ12 from three Chinese cattle breeds by DNA-pool sequencing. Then, we performed the association analysis of this SNP with stature in three Chinese cattle populations (n = 820). Significantly positive correlation was revealed by reduced animal general linear model and the genotype of CC is the most excellent genotype in three breeds. Further, we measured the expression profiling of the KCNJ12 gene in various cattle tissues and primary bovine skeletal muscle cells. Ubiquitous expression with high abundance in muscle was observed. Further, in primary bovine skeletal muscle cells, the KCNJ12 mRNA expression was gradually up-regulated in differentiation medium (DM) compared with that in growth medium (GM), suggesting that KCNJ12 gene is involved in bovine myocyte differentiation. Conclusively, KCNJ12 gene is a functional candidate gene which can be used as molecular marker for beef cattle breeding.

The G-NUMEN array is the future gamma spectrometer of the NUMEN experiment (Nuclear Matrix Element for the Neutrinoless double beta decay), to be installed around the object point of the MAGNEX magnetic spectrometer at the INFN-LNS laboratory.. This project aims at exploring Double Charge Exchange (DCE) reactions in order to obtain crucial information about the neutrinoless double beta decay (0νββ). The primary objective of the G-NUMEN array is to detect the gamma rays emitted from the de-excitation of the excited states populated via DCE reactions with good energy resolution and detection efficiency, amidst a background composed of transitions from competingreaction channels with far higher cross-sections. To achieve this, the G-NUMEN signalswill be processed in coincidence with those generated by the detection of the reaction ejectiles in the MAGNEX Focal Plane Detector(FPD). Under the expected experimental conditions, G-NUMEN detectors will operate at high counting rates, of the order of hundreds of kHz per detector, while maintaining excellent energy and timing resolutions. The complete array will consist of over 100 LaBr3(Ce) scintillators. Initial tests have been conducted on the first detectors of the array, allowing for the determination of their performance at high rates.

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10^-5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10^-4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.

it has been just over three years since SARS-CoV-2 viral infection was first known as causing severe acute and highly transmissible respiratory syndrome coronavirus. During one of the worst global pandemics of the last century, caused by the COVID-19 disease, under the persistent immune pressure exerted by the newest vaccines, the SARS-CoV-2 virus is fastly mutating and becoming less severe, but more contagious. On the other hand, some studies [1,2,3] indicate that the elderly COVID-19 patients or those who have reported a virulent episode of this infection, experience some long-lasting neurological complications, including encephalopathy, encephalitis, cerebrovascular disease, Parkinson’s disease (PD), Alzheimer’s disease (AD) and prion disease (PrD). So, there are several recent reports of patients [4,5] developing PrD following the SARS-CoV-2 infection, but, to the best of our knowledge, this is the first case reported in Italy on an association of the PRNP E200K somatic mutation with gCJD. The rising global prevalence neurodegenerative complications following COVID-19 disease adds urgency to the study of this potential relationship.

The length of time it takes to experimentally make one-sided choppers, as found in the fossil record, bears a linear relationship to the knapping process of fabricating them. In addition, this temporal frame appears to be related to human heart rates measured as beats per minute, which act as a physiological metronome. We achieved these observations assuming that any paleolithic one-sided chopper has the information needed to estimate quantitatively the number of strikes on it. The experimental data allow us to establish the total timing needed for the standard fabricating of any one-sided chopper. We discuss issues derived from these experimental results, showing the evolution of human neurological abilities from 2.4 million years ago to the Modern period through the duration of time needed for making one chopper to that needed to play a 19th-century music score on a piano. Given that the neuronal and physiological distance between both actions differs by a factor of 6, we propose the concept of “technome” to measure human evolution by using methodological homogeneous metrics applied to these two human technologic objects, the chopper and the piano.

This work explored and contrasted the effect of microstructure on the tensile properties of AlSi10Mg alloys generated by transient directional solidification depending on variations in cooling rate and Magnesium (Mg) content (i.e., 0.45 and 1wt.% Mg), with a focus on understanding the dendritic growth and phases constitution. Optical and Scanning electron (SEM) microscopies, CALPHAD and thermal analysis were used to describe the microstructure, forming phases and resulting tensile properties. The findings showed that the experimental evolution of the primary dendritic spacing is very similar when both directionally solidified (DS) Al-10wt.% Si-0.45wt.% Mg and Al-10wt.% Si-1wt.% Mg alloys samples are compared. The secondary dendritic spacing was lower for the alloy with more Mg, especially considering the range of high growth velocities. Moreover, a greater fraction of (Al+Si+Mg2Si) ternary eutectic islands surrounding the -Al dendritic matrix was noted for the alloy with 1wt.% Mg. As a result of primary dendritic spacings greater than 180 m related to lower cooling rates, slightly higher tensile properties were attained for the Al-10wt.% Si-0.45wt.% Mg alloy. In contrast, combining dendritic refining (< 150 m) and larger Mg2Si fraction, fast solidified DS Al-10wt.% Si-1wt.% Mg samples exhibited higher tensile strength and elongation. The control of cooling rate and fineness of the dendritic array provided a new insight related to the addition of Mg in slightly higher levels than conventional ones, capable of achieving a better balance of tensile properties in AlSi10Mg alloys.

The coronavirus disease pandemic 2019 (COVID-19) has emerged in Wuhan province, China in December 2019 and has spread over all countries. The current study was carried out to predict active, death and cured rate of COVID 19 in Algeria for a future period of 35 days using FB prophet model. Results shoed that the active rate and the death rate decrease for the next days while the cured rate increase. The active, cured and death rates are estimated at 19.7% 78.85% and 2.55% respectively. These results highlight the importance of FB prophet model in COVID-19 prediction which could help national authorities in adopting the best preventive measures.

While obesity is a serious chronic condition, its prevalence and documentation as a diagnosis has not been extensively studied in hospitalized patients. We conducted a retrospective chart review to investigate the prevalence and documentation of obesity as a diagnosis among patients admitted to our medical center. IRB approval was obtained for this retrospective study. Body mass index as per CDC, admission and discharge diagnosis of obesity and common comorbidities including hypertension, diabetes, hyperlipidemia and others, were recorded. Length of hospital stay was calculated. We also investigated whether counselling for weight loss was provided to obese patients. A total of 540 consecutive patients with mean age of 66 ± 6 years, were investigated, of which 182(34%) had normal weight, 188(35%) patients were overweight and 170(31%) patients were obese. Obese group included 55% female and 45% male. 100 (59%) had class I obesity, 43(25%) had class II obesity and 27(16%) class III obesity. Of the obese patients 40/170(23.5%) patients had obesity documented on the admission problem list and only 21(12%) had obesity documented as a discharge diagnosis. Only 3(2%) patients received appropriate counseling and referral for obesity management during the hospitalization. Comorbidities included hypertension (68%), diabetes (35%), hyperlipidemia (36%), coronary artery disease (18%), chronic kidney disease (17%), congestive heart failure (18%) and COPD (24%). The average length of stay in normal weight, overweight and obese patients was similar (4.5 ± 0.5 days). An overwhelming percentage never had weight status documented despite significant prevalence of obesity. Hospitalization offers health care providers a window of opportunity to identify obesity, communicate risks and initiate weight management interventions.

Crop production in Afghanistan suffers from limited phosphorus (P) availability, which severely hinders national agriculture sustainability. This present study hypothesized that deep fertilizer placement could significantly enhance uptake of immobile P and thus tissue P accumulation and crop yield. A two-year pot experiment growing two maize (Zea mays) hybrid cultivars (Xida-789 and Xida-211) was therefore conducted to test these hypotheses under three contrasting fertilizer placement methods (broadcast, side band, and deep band). In doing so, P concentrations in both maize tissues and soils were compared at 45, 60, and 115 days after sowing (DAS) under nine combinations of nitrogen (N) and P fertilizer rates (kg ha-1: N112P45, N112P60, N112P75, N150P45, N150P60, N150P75, N187P45, N187P60, N187P75). Results have shown that deep band placement significantly increased P uptake efficiency, leading to greater P concentration and accumulation in maize tissues compared to other two fertilization methods. This improved P uptake was attributed to several factors associated with deep placement, including reduced P fixation, enhanced root access to P, and moisture availability for P uptake. Additionally, deep band placement combined with higher N application rates (N187 and N150) further enhanced plant P uptake by promoting P availability and utilization mechanisms. Deep band placement also resulted in significantly higher total soil P, Olsen-P, and P use efficiency than broadcast and side band methods, indicating a more efficient P fertilization strategy for maize that can improve growth and yield. This present study also found positive correlations between P concentration in plant organs and soil Olsen-P, highlighting the importance of adequate soil P levels for optimal plant growth. Overall, our results have showed that deep band fertilizer placement emerged as a superior strategy for enhancing P uptake efficiency, utilization, and maize productivity compared to broadcast and side band placement. This approach can potentially optimize P fertilizer utilization, improve maize growth and yield, while minimizing environmental P losses associated with broadcast applications.

This study presents an analysis of subsidence rates and their effects on Mexico City. Mexico City is well known for its subsidence as a result of excess water withdrawal for many years. This study focuses on this problem utilizing the integration of Interferometric Synthetic Aperture Radar (InSAR), Continuous Global Positioning Systems (CGPS), and optical remote sensing data. Fifty-two ENVISAT-ASAR, nine GPS stations, and one Landsat ETM+ image from Mexico City area have been analyzed to prepare a better understanding of the subsidence rates and its effects on Mexico City’s commune. This study has utilized InSAR methods. It includes differential interferometry and Persistent Scatter Interferometry (PSI) to monitor the existing subsidence in the Mexico City area. The InSAR data covers the temporal baseline between 2002 until June 2010, and the GPS data include temporal baseline from 1998 until 2012. Maximum of 352 mm annually change in Line Of Sight (LOS) direction is in agreement with the previous geodetic studies. InSAR data have been compared with CGPS data at the same time interval. The finding of this study reveals a high amount of correlation (up to 0.98) between two independent geodetic methods. We also implemented the Support Vector Machine (SVM) analysis method based on Landsat ETM+ image to classify Mexico City’s populated density area. This method performed comparing the subsidence rates with populated area buildings. This integrated study shows that the fastest subsidence zone (i.e., areas greater than 100 mm/yr) in the over mentioned temporal baseline occurs in the high and sparsely populated areas

BA.2, a sublineage of Omicron BA.1, is now prominent in many parts of the world. Early reports indicate that BA.2 is more infectious than BA.1. To gain insight into BA.2 mutation profile and the resulting impact of mutations on interaction with receptor and/or monoclonal antibodies, we analyzed available se-quences, structures of Spike/receptor, and Spike/antibody complexes, and conducted molecular dynamics simulations. The results showed that BA.2 has 50 high-prevalent mutations compared to 48 in BA.1. Seventeen BA.1 mutations are not present in BA.2. Instead, BA.2 has 19 unique mutations and a signature Delta variant mutation (G142D). Intriguingly, the BA.2 has 28 signature mutations in Spike, compared to 30 in BA.1. This is due to two revertant mutations S446G and S496G in the receptor-binding domain (RBD), making BA.2 somewhat similar to Wuhan-Hu-1 (WT), which has G446 and G496. The molecular dynamics simulations showed that the RBD consisting of G446/G496 is more stable than S446/S496 containing RBD. Thus, our analyses suggest that BA.2 has evolved with novel mutations (i) to maintain receptor binding similar to WT, (ii) evade the antibody binding greater than BA.1, and (iii) acquire mutation of the Delta variant that may be associated with the high infectivity.

Weathering and erosion transport minerals and organics toward the sea or lake bottoms over geologic time. The finest solids are deposited in lower, less turbulent areas, such as lake bottoms and continental shelves. They sometimes stack up to thicknesses of kilometers, and begin compacting. These sediment sections are called shales, and as initially deposited in water, shales can have porosities up to 50-80{\%} water, As they are buried, many alteration products from oil to slate are produced due to overburden and temperature increasess, making them important to study. A preceeding paper \cite{1} showed that pressure solution is the primary mechanism for porosity reduction, with possible mechanical compaction at shallow depths. Without naming the mineral(s) involved, it postulated that the greater the product of the water and pore interfaces, the faster the reaction would proceed. This term is $ \varphi^{4m/3}(1-\varphi)^{4n/3}$ , where $\varphi$ is porosity and m and n are numbers close to unity. The large exponents, {\em 4/3}, recognize that the reaction occurs at the molecular scale at which the surfaces are rough. A second term, $\exp^{(-E/RT)}$ , indicates that the reaction is impeded by a quantum energy barrier, E, with diminished impeding power as increased available thermal energy, represented by the absolute temperature, T, becomes available at greater depths in the Earth. These two factors combine to allow porosity $\varphi$ to reduce with time, or equivalently for the fraction of solids, $(1-\varphi)$, to increase with time,$\left. \frac{\partial(ln(1-\varphi) ) }{\partial t } \right |_{\sigma} = (\varphi )^{4m/3}( 1-\varphi )^{4n/3}Ae^{-E/(RT)}$. { \em Here it is shown that this equation can cover quantitatively any actual deposition rates which may have been experienced by the six sections studied, the actual deposition rates being unknown for these cases. Hence a time-depth depositional history for any new shale section, known in detail, would allow determination of the parameters m, n, E and a lumped proportionality constant A. This was accomplished by showing that, for a wide range of depositional rates, r, the range of E for any of the studied sections is small compared to laboratory measurements of quartz solution\cite{2}, 24+-15kJ/mol. Results were obtained over this range of r's using the previously determined m and n, and porosity and temperature profiles. The presently existing porosity profiles necessarily incorporate any overpressure or underpressure conditions that may have existed in the past or currently, as the net difference between overburden and pore pressure is a primary driving force for pressure solution. $SiO_2$ usually comprises 20-50{\%} of shales. In conclusion, pressure solution of quartz can account for vertical compaction of shales quantitatively in the studied examples. Separately, a quasi-eqivalent method for discussing reduced porosities in Macron 2 versus Macron 1 as increased vertical stress, rather than additional horizontal stress, is illustrated. Experiments are suggested to clarify the pressure solution mechanism. The role of horizontal forces is discussed. From a global point of view, shale compaction by pressure solution is a quantified step in the cycling of continental rocks, beginning with rifting.

Hypertension stands as the foremost modifiable risk factor for cardiovascular disorders in South Asia. This research demonstrates the superiority of statistical models over traditional approaches in identifying clinical risks related to hypertension. Leveraging individual-level data from the Bangladesh Demographic and Health Survey (2017-18), a unified dataset was created. Adhering to JNC7 and ACC/AHA guidelines for hypertension classification, two prominent regression models were employed to estimate the prevalence of undiagnosed hypertension. A substantial 16% of hypertension cases in Bangladesh remain undetected. The study identifies undiagnosed hypertension as a heightened risk, particularly among the youth and residents of Sylhet and Rangpur divisions. Statistical models exhibit efficacy in discerning undiagnosed hypertension and associated factors in South Asia. Subsequent investigations should incorporate biological markers to enhance statistical models and ascertain their practicality.

Utility of vaccine campaigns to control coronavirus disease 2019 (COVID-19) is not merely dependent on vaccine efficacy and safety. Vaccine acceptance among the general public and the healthcare workers, appears to have a decisive role for successful control of the pandemic. The aim of this review was to provide an up-to-date assessment of COVID-19 vaccination acceptance rates worldwide. A systematic search of the peer-reviewed English survey literature indexed in PubMed was done on December 25, 2020. Results from 30 studies, met the inclusion criteria and formed the basis for final COVID-19 vaccine acceptance estimates. Results of an additional recent survey from Jordan and Kuwait was considered in this review as well. Survey studies on COVID-19 vaccine acceptance rates were found from 33 different countries. Among adults representing the general public, the highest COVID-19 vaccine acceptance rates were found in Ecuador (97.0%), Malaysia (94.3%), Indonesia (93.3%) and China (91.3%). On the other hand, the lowest COVID-19 vaccine acceptance rates were found in Kuwait (23.6%), Jordan (28.4%), Italy (53.7), Russia (54.9%), Poland (56.3%), US (56.9%), and France (58.9%). Only eight surveys among healthcare workers (doctors, nurses) were found, with vaccine acceptance rates ranging from 27.7% in the Democratic Republic of the Congo to 78.1% in Israel. In a majority of survey studies among the general public (62%), the acceptance of COVID-19 vaccination showed a level of ≥ 70%. Low rates of COVID-19 vaccine acceptance were reported in the Middle East, Russia, Africa and several European countries. This could represent a major problem in the global efforts that aim to control the current COVID-19 pandemic. More studies are recommended to address the scope of COVID-19 vaccine hesitancy. Such studies are particularly needed in the Middle East Africa, Eastern Europe, Central Asia, Middle and Latin America.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

Sterile alpha motif domain-containing protein 9 (SAMD9) is a regulatory protein centrally involved in cell proliferation and apoptosis. Mapped to 7p21.1, variants in SAMD9 have been reported in &lt;50 pediatric cases worldwide, typically with early lethality. Germline gain-of-function SAMD9 variants are associated with MIRAGE Syndrome (myelodysplasia, infection, restricted growth, adrenal hypoplasia, genital anomalies, and enteropathy). Spalt like transcription factor 1 (SALL1) is a zinc finger transcriptional repressor located at 16q12.1 where only two transcript variants in SALL1 are known. RUNX2 (6p21.1) encodes a nuclear protein with a Runt DNA-binding domain critical for osteoblastic differentiation, skeletal morphogenesis, and serves as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. RUNX2 and SALL1 are thus both ‘master regulators’ of tissue organization and embryo development. Here, we describe exome sequencing and copy number variants in two previously unknown mutations—R824Q in SAMD9, and Q253H in SALL1. A new multiexon 3’ terminal duplication in RUNX2 is also reported. This is the first known phenotype characterization for the intersection of all three variants in a healthy 46,XX adult. Focusing on developmental progress, ultrastructural renal anatomy, and selected reproductive aspects, we describe this unique genotype diagnosed incidentally during Covid-19 illness. Individual disruption in SAMD9, RUNX2, or SALL1 would be expected to give a bleak prognosis. However, the convergence discovered here appears to dampen severe pathology, perhaps by cross-gene silencing of effects normally deleterious when such changes occur alone.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an outbreak of COVID-19 disease in humans with the aid of spike protein. It consists of a receptor-binding domain (RBD) that recognizes and binds to the host receptor angiotensin-converting enzyme 2 (ACE2). The aim of this study was to examine the mutational effect of spike protein on the sequence through an interaction study of the mutant spike protein and the human ACE2 protein at the structural level. A total of 17,227 spike proteins from Asia, Africa, Europe, Oceania, South America, and North America were compared to the Wuhan spike protein reference sequence (Wuhan-Hu-1). The structural and stability implications of D614G, N501Y, and S477N mutations were evaluated. The binding affinity between mutated RBD and human ACE2 protein was also studied. The D614G mutation may have originated in Germany, Europe based on the date of the first sample collection report. It is now widely circulated all over the world with most occurrences in North America. The mutations N501Y and S477N may have originated from Oceania based on the date of the first sample collection report and also have the highest occurrences in Oceania. Based on the computational analysis of mutational effects, the D614G, N501Y, and S477N mutations decreased stability and were tolerated. For disease propensity prediction, N501Y was more prone to disease compared to D614G, while S477N was not prone to disease. The mutation of D to G at position 614 and S to N at position 477 for secondary structure prediction shows no changes in secondary structure while remaining in the coil region, whereas the mutation of N to Y at position 501 changes from coil structure to extended strand. N501Y mutation has a higher affinity to human ACE2 protein compared to D614G and S477N based on a docking study. D614G spike mutation was identified to exist between the two hosts based on a comparison of SARS-CoV-2 derived between the mink and human. Further research is needed on the link between the mink mutation N501T and the mutation N501Y in humans, which has evolved as a separate variant.

Background: Infantile haemangiomas (IH) may require treatment with propranolol. Sleep disturbances are the most fre-quently reported side effects. Monitoring drug adverse events necessitates repeated hospital visits, despite the SARS-CoV-2 pandemic. Objectives: To explore the effectiveness of a new electronic questionnaire in identifying sleep disturbances as adverse events to treatment and potential confounders. To evaluate the response rate to the questionnaire. To report the propor-tion of patients on propranolol with sleep disturbances. Methods: In an observational, prospective cohort study, caregivers provided clinical information at office visits and via an electronic questionnaire after an 8-week treatment course and at treatment interruption. Adverse drug reaction (ADR) reporting forms were evaluated for causality assessment. Results: The questionnaire response rate was 91%, and the completion rate was 100%. The prevalence of sleep disturb-ances as adverse reactions was 59%. Sleep disorders were more frequent during sleep regression phases and in subjects who fell asleep with physical contact with caregivers or bed-sharing with parents. Conclusion: The application of this questionnaire allows for identifying sleep-adverse events associated with propranolol in IH and potential confounders. Counselling on sleep hygiene is recommended before treatment onset

Tree pruning is a management tool in agroforestry systems for reducing shade, enhancing nutrient cycling or providing fodder. However, little information is available on the effect of pruning management on plant growth, non-structural carbohydrate (NSC) levels in the roots and N2 fixation of Sesbania sesban. A glasshouse experiment was conducted to assess the effect of pruning frequency on biomass production, NSC levels and N2 fixation of Sesbania sesban. Treatments included pruning at (i) 3 months only, (ii) 3 and 6 months, and (iii) 3, 6 and 9 months, with each pruning removing shoot biomass above 50% of the initial height. Increased pruning frequency decreased above- and belowground dry matter (DM), and root NSC levels. The decrease in aboveground DM correlated with reduced levels of starch, sugar and total non-structural carbohydrates. Pruning more frequently significantly decreased nodulation, the percentage N derived from the atmosphere and N2 fixed. It could be concluded that more frequent prunings decreases biomass and NSC levels which could reduce the regeneration capacity of trees since they rely on NSCs to regrow. The suppressive effects of increased pruning frequency on N2 fixation could decrease the desirable benefits of legume trees on soil N fertility improvement.

The powder bed fusion (PBF) metal additive manufacturing (AM) method uses an energy source like a laser to melt the metal powders. The laser can locally melt the metal powders and creates a solid structure as it moves. The complexity of the heat distribution in laser PBF metal AM is one of the main features that need to be accurately addressed and understood to design and manage an optimized printing process. In this research, the dependency of local thermal rates and gradients on print after solidification (in the heat-affected zone) was numerically simulated and studied to provide information for designing the print process. The simulation results were validated by independent experimental results. The simulation shows that the local thermal rates are higher at higher laser power and scan speed. Also, the local thermal gradients increase if the laser power increases. The effect of scan speed on the thermal gradients is opposite during heating versus cooling times. Increasing the scan speed increases the local thermal gradients in the cooling times and decreases the local thermal gradients during the heating. In addition, these simulation results could be used in artificial intelligence (AI) and machine learning for developing digital additive manufacturing.

This study investigated the trends of registered Death and Birth in Nigeria using Generalized Linear Models. Annual data on Death and Birth was collected from National Population Commission for the period of 2004 to 2017. The Natural increase calculated revealed a positive trend in the natural increase in Nigeria from 2004 to 2017. Evidence from summary statistics revealed some level of over dispersion (variance > mean). This study explored Poisson Regression Models and Negative Binomial Regression Models using two links (identity and log). The results revealed a positive increase in registration of birth and death rates in Nigeria and among the competing the models, Negative Binomial regression model with identity link emerged as the best model for modeling birth and death rates registration in Nigeria. Data on numbers of deaths and causes of death are essential if countries are to determine priorities, formulate and monitor policies for public health care as well as other government policies that may be based on such data

The work proposes a backtesting analysis in comparison between the Lee-Carter and the Cairns-Blake-Dowd mortality models, employing Italian data. The mortality data come from the Italian National Statistics Institute (ISTAT) database and span the period 1975-2014, over which we computed back-projections evaluating the performances of the models in comparisons with real data. We propose three different backtest approaches, evaluating the goodness of short-run forecast versus medium-length ones. We find that both models were not able to capture the improving shock on the mortality observed for the male population on the analyzed period. Moreover, the results suggest that CBD forecast are reliable prevalently for ages above 75, and that LC forecast are basically more accurate for this data.

Hepatitis B and C are major health issues in developing countries such as Pakistan and Afghan-istan. The aim of this study was to determine the prevalence and effectiveness of a screening program for hepatitis B and C in a region with no existing programs, and to estimate their prev-alence in the general population in Khyber Pakhtunkhwa Province, Pakistan, as well as in Afghan refugees or migrants. A prospective cohort study was done in the general population of Peshawar and its adjacent districts, as well as migrants from neighboring provinces of Afghani-stan, who presented to our tertiary-care health facility. A Microsoft Excel registry was created for data collection, which were analyzed using IBM SPSS via descriptive analysis, normal distribution curve histograms, and chi-squared tests. A total of 9563 individuals were screened for hepatitis (5894 males and 3669 females), including Afghan migrants in Peshawar and surrounding districts. 876 individuals tested positive for hepatitis, with 538 positive for hepatitis B (383 males and 155 females) and 330 positive for hepatitis C (198 males and 134 females). Eight individuals had a hepatitis B and C co-infection. Among the study population, the prevalence rates were 2.2% for hepatitis B and 2.3% for hepatitis C, of which the Afghan migrants accounted for 2.7% and 0.5%, respectively. According to the gender-based distribution, hepatitis B was more prevalent in males, whereas there was no significant gender-based difference for hepatitis C. Our results highlight the need for a comprehensive approach to control hepatitis B and C in Pakistan and Afghanistan. Increased awareness, improved healthcare, and preventive measures such as screening and elimination programs to prevent severe liver diseases and eradicate hepatitis are necessary.

This study aligns with the 2030 United Nations Sustainable Development Goals- 3 which aim to “ensure healthy lives and promote well-being for all at all ages”. It contributes to the nascent literature stream on energy-health dynamics by introducing a holistic theoretical model to empirically examine the mediation effect of carbon emissions on the relationship between nonrenewable energy and infant mortality rates. Using an unbalanced panel data on 42 Asia and the Pacific countries from 2005 to 2015 and deploying the structural equation modeling approach, the empirical results are surmised as follows: (i) in regard to the full sample of countries, nonrenewable energy indirectly increases infant mortality rates through increasing carbon emissions. In other words, carbon emissions play a partial mediation role between nonrenewable energy and infant mortality rates; and (ii) for the different income groups, carbon emissions show varying mediation effects. For example, the mediation effects of carbon emissions in lower-middle and upper-middle income countries are found to be similar to those of the full sample of countries. Therefore, based on these findings, we conclude that nonrenewable energy is an essential determinant of infant mortality rates. Policy recommendations are put forward.

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. The KRAS mutation is present in 30-50% of CRC patients. This mutation confers resistance to treatment with anti-EGFR therapy. This article aims at proving that Computer Tomography (CT)-based Radiomics can predict the KRAS mutation in CRC patients. The piece is a retrospective study with 56 CRC patients from the Hospital of Santiago de Compostela, Spain. All patients had a confirmatory pathological analysis of the KRAS status. Radiomics features were obtained from the abdominal contrast enhancement CT (CECT), before applying any treatments. We used several classifiers, including adaboost, neural network, decision tree, support vector machine and random forest, to predict the presence or absence of KRAS mutation. The most reliable prediction was achieved using the adaboost ensemble on clinical patient data, with a kappa and accuracy of 53.7% and 76.8%, respectively. The sensitivity and specific were of 73.3% and 80.8%. Using texture descriptors, the best accuracy and kappa were 73.2% and 46%, respectively, with sensitivity and specificity of 76.7% and 69.2%, showing also a correlation between texture patterns on CT images and KRAS mutation. Radiomics could help manage CRC patients, and in the future, it could have a crucial role in diagnosing CRC patients ahead of invasive methods.

Rabson-Mendenhall syndrome is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We are reporting the first case of Rabson-Mendenhall syndrome in a Paraguayan patient. The patient is a 5-year-old girl who presented with hypertrichosis, acanthosis nigricans, and nephrocalcinosis. Genetic testing by NGS revealed two pathogenic variants in exons 2 and 18 of the INSR gene; c.332G&gt;T (p. Gly111Val) and c.3485C&gt;T (p. Ala1162Val), in combined heterozygosis. The novel INSR c. 332G&gt;T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software predicted it as pathogenic. The c. 3485C&gt;T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and Rabson-Mendenhall syndrome. The management of Rabson-Mendenhall syndrome is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of Rabson-Mendenhall syndrome to the Paraguayan population and adds a novel pathogenic variant to the existing literature.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to the cell receptor angiotensin-converting enzyme-2 (ACE2) as the first step in viral cell entry. SARS-CoV-2 spike protein expression in ACE2-expressing cell surface induces cell–cell membrane fusion, thus forming syncytia. To exert its fusiogenic activity, the spike protein is typically processed at a specific site (S1/S2 site) by cellular proteases such as furin. The C488 residue, located at the spike–ACE2 interacting surface, is critical for the fusiogenic and infectious roles of the SARS-CoV-2 spike protein. We further demonstrated that the C488 residue of spike protein is involved in subcellular targeting and S1/S2 processing. C488 mutant spike localization to the Golgi apparatus and cell surface were impaired. Consequently, the S1/S2 processing of the spike protein, probed by anti-Ser-686-cleaved spike antibody, markedly decreased in C488 mutant spike proteins. Moreover, brefeldin A-mediated endoplasmic reticulum-to-Golgi traffic suppression also suppressed spike protein S1/S2 processing. As brefeldin A treatment and C488 mutation inhibited S1/S2 processing and syncytia formation, the C488 residue of spike protein is required for functional spike protein processing.

SARS-CoV-2, the novel coronavirus behind COVID-19 pandemic is acquiring new mutations in its genome. Although some mutations provide benefits to the virus against human immune response, a number of them may result in their reduced pathogenicity and virulence. By analyzing more than 3000 high-coverage, complete genome sequences deposited in the GISAID database, here I report a unique 28881-28883:GGG>AAC trinucleotide-bloc mutation in the SARS-CoV-2 genome that results in two sub-strains, described here as SARS-CoV-2g (28881-28883:GGG genotype) and SARS-CoV-2a (28881-28883:AAC genotype). Computational analysis and literature review suggest that this bloc mutation would bring 203-204:RG(arginine-glycine)>KR(lysine-arginine) amino acid changes in the nucleocapsid (N) protein affecting the SR (serine-arginine)-rich motif of the protein, a critical region for the transcription of viral RNA and replication of the virus. Thus, 28881-28883:GGG>AAC bloc-mutation is expected to modulate the pathogenicity of the SARS-CoV-2. Remarkably, SARS-CoV-2g and SARS-CoV-2a strains can be linked with the heterogeneity of COVID-19 cases across different regions within and between countries by analyzing existing data. Sequence analysis suggests that severely affected cities, such as Milan, Lombardy, New York, Paris have the predominant presence of SARS-CoV-2g strains, whereas less affected places like Abruzzo, Lyon, Valencia have a relatively higher presence of SARS-CoV-2a, an indication that the latter strain may contribute to the reduced cases of COVID-19. A similar relationship is observed when Netherlands, Portugal are compared with Spain, France and Germany. These analyses suggest that the SARS-CoV-2 has already evolved into a less infective SARS-CoV-2a affecting COVID-19 cases in different regions. The time a country or region needs to acquire SARS-CoV-2a strains may be indicative to the time it would need to overcome the peak of the COVID-19 cases. To confirm these assumptions, prompt retrospective and prospective epidemiological studies should be conducted in different countries to understand the course of pathogenicity of the SARS-CoV-2a and SARS-CoV-2g. Potential drugs can be designed targeting 28881-28883 region of the N protein to modulate virus pathogenicity.

The high mutation rate of human immunodeficiency virus type 1 (HIV-1) plays a major role in treatment resistance from the development of vaccines to long-lasting drugs. In addressing the crux of the issue, various attempts to estimate the mutation rate of HIV-1 resulted in a large range of 10-5 - 10-3 errors/bp/cycle due to the use of different types of investigation methods. In this review, we discuss the different assay methods, their findings on the mutation rates of HIV-1 and how the location of these mutations can be further analyzed for their potential allosteric effects to reveal potentially new inhibitors with different pharmacodynamics that can be used to circumvent fast occurring HIV drug resistance. Given that HIV is one of the fastest mutating viruses, it is a good model for comprehensive study of its mutations that can give rise to much horizontal understanding towards overall viral drug resistance as well as emerging viral diseases.

This study concerns calculation and comparison of Fe, Co, Ni and Cu deposition rates in tungsten codeposition process based on electrodeposition of numerous tungsten alloys. 8 different tungsten alloys containing from 2 to 5 metals were electrodeposited in constant conditions in order to compare exact reduction rates. Calculated rates enabled control of the alloy composition precise enough to obtain a high-entropy WFeCoNiCu alloy with well-balanced composition. Introduction of copper to form the quinternary alloy was found to catalyze the whole process, increasing deposition rates of all components of the high-entropy alloy.

Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n=67) were sequenced for clarithromycin and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples that amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C the most common mutation, 90%. While prevalence of metronidazole resistance-associated mutations was higher, 93.9%, mutations were more variable, with D95N the most common, followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider the resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed.

$\beta$-decay is one of the key factors to understand the $r$-process and evolution of massive stars. The Gamow-Teller (GT) transitions drive the $\beta$-decay process. We employ the proton-neutron quasiparticle random phase approximation (pn-QRPA) model to calculate terrestrial and stellar $\beta$-decay rates for 50 top-ranked nuclei possessing astrophysical significance according to a recent survey \cite{Nab21}. The model parameters of the pn-QRPA model effect the predicated results of $\beta$-decay. The current study investigates the effect of nucleon-nucleon pairing gaps on charge-changing transitions and the associated $\beta$ decay rates. Three different values of pairing gaps, namely TF, 3TF and 5TF, were used in our investigation. It was concluded that both GT strength distributions and half-lives are sensitive to pairing gap values. The 3TF pairing gap scheme, in our chosen nuclear model, resulted in best prediction with around 80$\%$ of the calculated half-lives within a factor 10 of the measured ones. The 3TF pairing scheme also led to calculation of biggest $\beta$-decay rates in stellar matter.

In this paper, we constructed and analyzed a modified SIR-type model for the epidemic problem which considering waning-immunity class in the population, with the nonlinear incidence and recovery rates. Depending on the basic reproduction ratio, we investigated conditions for both non-endemic and co-existing cases. The RouthHurwitz criteria is used to verify the local stability of equilibria, whereas for the global stability, the suitable Lyapunov function is selected to analyze the behavioral stability for each equilibria. Moreover, we studied the optimal control problem for this case. Numerically, we give some simulations to support our analitycal findings.

Semantic rules link purely theoretical terms like “price” and “electron” to things we can measure. Without them, theories cannot be tested empirically. When inappropriate, they produce false rejections. Economists routinely ignore semantic rules. Empirical journal articles essentially never mention them. More to the point, the conventional tests that reject the Law of One Price and Purchasing Power Parity never consider them. As a result, those rejections are unwarranted because such tests use inappropriate semantic rules. Both theories should be restored to not rejected and then retested using the more appropriate semantic rules described here. By using appropriate semantic rules, this paper is able to combine Covered Interest Parity and Purchasing Power Parity into a single theory that links auction markets for financial assets and commodities to auction markets for exchange rates. Using appropriate semantic rules for both theories also explains several puzzles in open economy macroeconomics and opens up broad new vistas for research.

A recent study by the Wall Street Journal reveals that the hydrofractured horizontal wells in shales have been producing less than forecasted by the industry with the empirical hyperbolic decline curve analysis (DCA). As an alternative to DCA, we introduce a simple, fast and accurate method of estimating ultimate recovery (EUR) in oil shales. We adopt a physics-based scaling approach to analyze oil rates and ultimate recovery from 14,888 active horizontal oil wells in the Bakken shale. To predict EUR, we collapse production records from individual horizontal shale oil wells onto two segments of a master curve: (1) We find that cumulative oil production from 4,845 wells is still growing linearly with the square root of time; and (2) 6,401 wells are already in exponential decline after approximately seven years on production. In addition, 2,363 wells have discontinuous production records, because of refracturing or changes in downhole flowing pressure, and are matched with a linear combination of scaling curves superposed in time. The remaining 1,279 new wells with less than 12 months on production have too few production records to allow for robust matches. These wells are scaled with the slopes of other comparable wells in the square-root-of-time flow regime. In the end, we predict that total ultimate recovery from all existing horizontal wells in Bakken will be some 4.5 billion barrels of oil. We also find that wells completed in the Middle Bakken formation, in general, produce more oil than those completed in the Upper Three Forks formation. The newly completed longer wells with larger hydrofractures have higher initial production rates, but they decline faster and have EURs similar to the cheaper old wells. There is little correlation among EUR, lateral length, and the number and size of hydrofractures. Therefore, technology may not help much in boosting production of new wells completed in the poor immature areas along the edges of the Williston Basin. Operators and policy-makers may use our findings to optimize the possible futures of the Bakken shale and other plays. More importantly, petroleum industry may adopt our physics-based method as an alternative to the overly-optimistic hyperbolic DCA that yields an "illusory picture" of shale oil resources.

Loess was deposited in the Negev during the Pleistocene, but such sediments seem to be missing for the Holocene. This could be due to erosion unless structures such as ruins offered protection. We studied soils developed on archaeological hilltop ruins in the Negev and the Petra region and compared them with local soils, paleosols, geological outcrops, and current dust. The ruin soils in both regions were found to consist of similarly complex mixtures of local and remote sediment sources. They differ from sediments deposited during current dust storms. This seems due to fixation processes: average accretion rates are estimated to ~0.14 mm/a, suggesting that only ~3% of the current dust that can be trapped with dry marble dust collectors is stored in the soils. Vegetation, biocrusts, and/or clast pavements associated with vesicular layers seem to act as sediment-fixing agents. As well, climate might play a role: rain, and in particular one snowstorm in the Petra region brought a high amount of sediment that was more similar to the ruin soils. Wet deposition and snow might catalyze dust deposition and enhance fixation by fostering vegetation and crust formation. Frequent snow during the Pleistocene might be one explanation of enhanced loess deposition.

The extrinsic and intrinsic factors are essential in glioma initiation. Many extrinsic factors (UV, radiation, food, etc.) and intrinsic factors (proteins, hormones, ageing, DNA and RNA damages, etc.) was reported to being responsible for glioma initiation and progression. However, the cell responsible for glioma origin is still unknown. Many research papers have reported that glioma stem cells, senescent cells, injured cells, and death neurons are the cells of glioma origin. However, gene mutation and oncogene protein overexpression doesn’t occur only in cancer but during life evolution. The source of genetic mutations has become a fundamental issue in understanding its role in the initiation of glioma. The glioma is the precise coordination of several distant factors that work together in the initiation and development of glioma. However, the role and effects of the genes (GDNF and SOX1) on cancer cells are well known, but their gene mutation origin is controversial. Several models and theories have been proposed to explain the origins of GDNF and SOX1 genetic mutations and epigenetic modification related to cancer. Our aim in this review is to clear that incertitude about glioma origin (gene mutation and epigenetic modifications) and those factors involved in glioma initiation and recurrence.

Balanced nitrogen (N) and phosphorus (P) rates coupling with rational fertilization methodology could promote crop N accumulation, N use efficiency and yield production, particularly in semi-arid and arid regions. To test these characteristics, a two-year (2018 and 2019) pot experiment was therefore performed by growing summer maize in a rain-proof glass greenhouse, under 9 combined N (112, 150 and 187 kg ha-1, urea) and P (45, 60, 75 kg ha-1, calcium superphosphate) rates and three contrasting fertilizer placements. The fertilizers were placed by broadcast on soil surface (Broadcast), side band on 4 cm strip soil surface within 7 cm from sowing line (Side band) and deep band on 4 cm strip below 7 cm soil depth within 7 cm from sowing line (Deep band). Results from three maize growth stages (eight-leaf, 45 days after sowing, DAS; tasseling, 60 DAS; and harvest, 115 DAS) showed that leaf, stem, root N accumulation and total soil N were significantly increased under Deep band than under both Side band and Broadcast at N150P60, N187P60, N150P75 and N187P75, but not at N112P45, N150P45, N187P45, N112P60 and N112P75. Significantly greater leaf, stem, and root N accumulations were also displayed at N150 and N187 than at N112 for the same P60 or P75 under Deep band at 60 DAS and 115 DAS, while were for leaf and stem N accumulations at P75 and P60 than at P45 for the same N150 under Deep band at 45 DAS, 60 DAS and 115 DAS. Significantly greater agronomy N use efficiency, partial factor productivity and N use efficiency exhibited under Deep band than under Side band and Broadcast at N150P75 and N187P75, but at N150P60 and N187P60 for NUE only. In addition, leaf, stem, seed, root N concentrations positively correlated with their own N accumulations or soil N concentration at tasseling and harvest stages. Our results demonstrate that a synchronized N150P60, N187P60, N150P75 or N187P75 fertilization rate with Deep band placement can improve soil N availability and root N uptake, and hereby greater aboveground N accumulation, N use efficiency and yield production of maize particularly practical for small-holder farmers globally.

Despite polycarbonate (PC) being a widely used engineering plastic, its notch and crack sensitivity pose challenges in critical applications. To address this, PC was blended with elastomeric polymers to explore the improvement in toughness. This study systematically investigates the toughening mechanisms of PC blended with acrylonitrile-butadiene-styrene (ABS), copolyether ester elas-tomer (COPE), and ABS and styrene-ethylene-butylene-styrene (SEBS) copolymer grafted with maleic anhydride (MA). The morphology and mechanical behavior were evaluated under qua-si-static and high-speed tensile tests and Charpy impact tests using optical, electronic, and atomic force microscopy and Raman spectroscopy. The morphological analysis reveals cavitation and crazing phenomena for COPE and SEBS-g-MA systems, and mostly debonding for ABS, indicating an improvement in toughening. While the addition of ABS improves the PC plastic deformation, modifying ABS with maleic anhydride enhances the elastic modulus. Blending PC with SEBS-g-MA increases the strain at break, and the addition of COPE significantly improves the deformation behavior of PC (by around 115%). This comparative study provides valuable insights into the performance of different PC-elastomer blends under similar conditions, supporting the selection of appropriate materials for given applications.

Brugada syndrome (BrS) is an inherited disease characterized by right precordial ST-segment elevation on electrocardiograms (ECGs), and a high risk of life-threatening ventricular arrhyth-mia and sudden cardiac death. In BrS patients, except for SCN5A, mutations in other responsible genes are poorly elucidated. We identified a new missense mutation, c.1189C>T (p.R397C), in the KCNH2 gene in asymptomatic male proband with diagnosed BrS. We performed patch-clamp analysis on I(Kr) reconstituted with this KCNH2 mutation in Chinese hamster ovary cells and compared the phenotype with the wild type. We found that the R397C mutation increased the I(Kr) density. In silico modeling demonstrated that this missense mutation potentially leads to the shortening of action potential in the heart.

Data-Flow and Higher-Order Mutation are white-box testing techniques. To our knowledge, no work has been proposed to compare data flow and higher-order mutation. This paper compares all def-uses data-flow and second-order mutation criteria. This compassion investigates the subsumption relation between these two criteria and evaluates the effectiveness of test data developed for each. To compare the two criteria, a set of test data satisfying each criterion is generated, which is used to explore whether one criterion subsumes the other criterion and assess the effectiveness of the test set that was developed for one methodology in terms of the other. The results showed that the mean mutation coverage ratio of the all du-pairs adequate test cover is 80.9%, and the mean data flow coverage ratio of the 2nd-order mutant adequate test cover is 98.7%. Consequently, 2nd-order mutation “ProbSubsumes” the all du-pairs data flow. The failure detection efficiency of the mutation (98%) is significantly better than the failure detection efficiency of data flow (86%). Consequently, 2nd-order mutation testing is “ProbBetter” than all du-pairs data flow testing. In contrast, the size of the test suite of 2nd-order mutation is more significant than the size of the test suite of all du-pairs.

Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

Our study explores the genetic mechanisms underlying the spotted leaf phenotype in rice, focusing on the rpt5a mutant characterized by persistent reddish-brown leaf spots from seedling stage to maturity, leading to extensive leaf necrosis. Through map-based cloning, we localized the responsible locus to a 330Kb region on chromosome 2 and identified LOC_Os02g56000 (named OsRPT5A) as the causative gene. A point mutation in OsRPT5A, substituting valine for glutamic acid, was identified as the critical factor for the phenotype. Functional complementation and generation of knockout lines in the IR64 background confirmed the central role of OsRPT5A in controlling this trait. Our study also revealed that OsRPT5A is constitutively expressed across various tissues, with its subcellular localization unaffected by mutations. Notably, we observed an abnormal accumulation of reactive oxygen species (ROS) in rpt5a mutants, suggesting a disruption in the ROS system. Complementation studies indicated OsRPT5A's involvement in ROS homeostasis and catalase activity regulation. Moreover, the rpt5a mutant exhibited enhanced resistance to Xanthomonas oryzae pv. oryzae (Xoo), highlighting OsRPT5A's role in rice's pathogen resistance mechanisms. These findings elucidate the genetic basis of the spotted leaf phenotype and emphasize the intricate interplay between plant defense responses and developmental pathways.

In 1984, Susumu Ohno hypothesized that the nylon-degrading enzyme NylB arose de novo via a frameshift mutation within a hypothetical precursor protein (PR.C). However, Ohno never tested his hypothesis or provided supporting biological evidence. For decades, Ohno’s famous frame-shift hypothesis has been uncritically accepted as the correct explanation for the origin of NylB and has been used to illustrate how simple it is for a totally new enzyme to arise spontaneously. In this paper we test Ohno’s hypothesis in light of data not available in 1984. We searched multiple protein databases and found that the NylB protein is widely occurring, has thousands of homologs, and is found in diverse organisms and diverse habitats. Conserved domain searches showed that the NylB sequence is homologous to beta lactamases - a family of highly conserved enzymes. However, our searches showed that there is no evidence for the existence of Ohno’s hypothetical PR.C protein, nor any credible homolog. Our results effectively falsify Ohno's frameshift hypothesis. We extended this analysis to other nylonases and found all the nylonases we examined had large numbers of homologs throughout the biosphere. This falsifies the long-held assumption that all nylonases evolved after the invention of nylon in 1935.

To date, uncertainty remains about how long the protective immune responses against SARS-CoV-2 persists and reports of suspected reinfection began to be described in recovered patients months after the first episode. Viral evolution may favor reinfections, and the recently described spike mutations, particularly in the receptor binding domain (RBD) in SARS-CoV-2 lineages circulating in the UK, South Africa, and most recently in Brazil, have raised concern on their potential impact in infectivity, immune escape and reinfection. We report a case of reinfection from distinct SARS-CoV-2 lineages presenting the E484K mutation in Brazil, a variant associated with escape from neutralizing antibodies.

Using smartphone especially android platform has already got eighty percent market shares, due to aforementioned report, it becomes attacker’s primary goal. There is a growing number of private data onto smart phones and low safety defense measure, attackers can use multiple way to launch and to attack user’s smartphones.(e.g. Using different coding style to confuse the software of detecting malware). Existing android malware detection methods use multiple features, like safety sensor API, system call, control flow structure and data information flow, then using machine learning to check whether its malware or not. These feature provide app’s unique property and limitation, that is to say, from some perspectives it might suit for some specific attack, but wouldn’t suit for others. Nowadays most malware detection methods use only one aforementioned feature, and these methods mostly analysis to detect code, but facing the influence of malware’s code confusion and zero-day attack, aforementioned feature extraction method may cause wrong judge. So, it’s necessary to design an effective technique analysis to prevent malware. In this paper, we use the importance of word from apk, because of code confusion, some malware attackers only rename variables, if using general static analysis wouldn’t judge correctly, then use these importance value to go through our proposed method to generate picture, finally using convolutional neural network to see whether the apk file is malware or not.

Multilayered metallic sheets fabricated by hot metal forming processes are attractive structural components in the aerospace and automobile industry. The strength of the mechanical bond between the different layers is critical to the applicability of such components in load bearing applications. While it is well understood that the process conditions such as temperature, deformation and rate of deformation influence the bond strength, a clear functional relationship between these conditions and the bond strength has yet to be established. The objective of the current study is to investigate the joining of Aluminum-6061 alloy specimens by hot compression bonding. Hot compression tests of beam specimen pairs were conducted at different temperatures (300-500℃), with different strains and strain rates (10-2-10-1 [1sec]). Coupled thermo-mechanical finite element models were utilized to compute the time dependent thermo-mechanical fields that develop along the specimen interface. The computed values were used to map the spatial distribution of a scalar parameter J which is hypothesized to govern bond formation. Mechanical tensile tests were used to determine the bond strength and expose the bonded surfaces. It is demonstrated that the computed J distribution can be correlated well with SEM observations of the debonded surface. It is also shown that the actual bonded area can be predicted from the computations for a certain range of critical J values.