Selection Of Variants Research Articles

A genome-wide association study of the racing performance traits in Yili horses based on Blink and FarmCPU models.

Racing performance traits are the main indicators for evaluating the performance and value of sport horses. The aim of this study was to identify the key genes for racing performance traits in Yili horses by performing a genome-wide association study (GWAS). Breeding values for racing performance traits were calculated for Yili horses (n = 827) using an animal model. Genome-wide association analysis of racing performance traits in horses (n = 236) was carried out using the Blink, and FarmCPU models in GAPIT software, and genes within the significant regions were functionally annotated. The results of GWAS showed that a total of 24 significant SNP markers (P < 6.05 × 10- 9) and 22 suggestive SNP markers (P < 1.21 × 10- 7) were identified. Among them, the Blink associated 16 significant SNP loci and FarmCPU associated 12 significant SNP loci. A total of 127 candidate genes (50 significant) were annotated. Among these, CNTN6 (motor coordination), NIPA1 (neuronal development), and DCC (dopamine pathway maturation) may be the main candidate genes affecting speed traits. SHANK2 (neuronal synaptic regulation), ISCA1 (mitochondrial protein assembly), and KCNIP4 (neuronal excitability) may be the main candidate genes affecting ranking score traits. A common locus (ECA1: 22698579) was significantly associated with racing performance traits, and the function of the genes at this locus needs to be studied in depth. These findings will provide new insights into the detection and selection of genetic variants for racing performance and will help to accelerate the genetic improvement of Yili horses.

Genome-wide local ancestry and the functional consequences of admixture in African and European cattle populations.

Bos taurus (taurine) and Bos indicus (indicine) cattle diverged at least 150,000 years ago and, since that time, substantial genomic differences have evolved between the two lineages. During the last two millennia, genetic exchange in Africa has resulted in a complex tapestry of taurine-indicine ancestry, with most cattle populations exhibiting varying levels of admixture. Similarly, there are several Southern European cattle populations that also show evidence for historical gene flow from indicine cattle, the highest levels of which are found in the Central Italian White breeds. Here we use two different software tools (MOSAIC and ELAI) for local ancestry inference (LAI) with genome-wide high- and low-density SNP array data sets in hybrid African and residually admixed Southern European cattle populations and obtained broadly similar results despite critical differences in the two LAI methodologies used. Our analyses identified genomic regions with elevated levels of retained or introgressed ancestry from the African taurine, European taurine, and Asian indicine lineages. Functional enrichment of genes underlying these ancestry peaks highlighted biological processes relating to immunobiology and olfaction, some of which may relate to differing susceptibilities to infectious diseases, including bovine tuberculosis, East Coast fever, and tropical theileriosis. Notably, for retained African taurine ancestry in admixed trypanotolerant cattle we observed enrichment of genes associated with haemoglobin and oxygen transport. This may reflect positive selection of genomic variants that enhance control of severe anaemia, a debilitating feature of trypanosomiasis disease, which severely constrains cattle agriculture across much of sub-Saharan Africa.

Pharmacogenetics of colorectal cancer in a third-level hospital in Valencia

Abstract Objectives Genetic variants with associated pharmacokinetic and pharmacodynamic effects have an impact on the development of adverse drug reactions and survival of patients with colorectal cancer. Methods A selection of genetic variants was performed according to the established chemotherapy and the pharmacogenetic databases. Genotyping was performed using MassArray technology (Agena Bioscience). Variant-toxicity and survival-genotype correlations were assessed using logistic regression (SPSS v.28.0.1.1). Results Genotyping of 25 SNPs was performed in 96 patients. In relation to the DPYD gene, 3.5 % had the rs75017182 mutation; 4.7 % the rs1801158 mutation and 7.1 % the rs1801160 mutation. Genotypic frequencies in the UGT1A1 gene were 39.4 % (*1/*1); 37.9 % (*1/*28); 19.7 % (*28/*28); and 3 % (*1/*36). The genotypes CT of the rs1801160 variant, AT of the rs67376798 variant (DPYD) and *1/*36 (UGT1A1) were associated with low survival (p-value: 0.006, &lt;0.001, and 0.052, respectively). The most frequent adverse reactions were gastrointestinal disorders, followed by neurotoxicity. The CC genotype (rs1801160, DPYD) was associated with a lower risk for developing severe gastrointestinal events, whereas CC (rs1801158, DPYD) was associated with a lower risk of developing severe general hematologic toxicity. Conclusions The population frequencies obtained in our study for rs1801160 and rs75017182 (DPYD); and for *1/*28, *28/*, and *1/*36 (UGT1A1) were inconsistent with the frequencies reported for the Spanish population in the literature. The genotypes CT of rs1801160, AT of rs67376798 (DPYD), and 1/*36 (UGT1A1) were associated with lower survival rates.

Variant selection and macrozone in Ti-6Al-4V walls during laser hot wire direct energy deposition

Variant selection and macrozone in Ti-6Al-4V walls during laser hot wire direct energy deposition

Design and control the selection of martensitic variant to simultaneously improve strength and toughness of low-carbon martensitic steel

In this paper, the microstructure evolution and mechanical properties of low carbon steels during direct quenched and rolling followed by water-cooled processes were studied. Two experimental steels, which were directly quenched at 900 °C (Q900) and 1000 °C (Q1000), were compared with steels that were water-cooled after rolling at the same temperatures (R900 and R1000). Microstructural analyses using EBSD and TEM revealed that rolling reduced the size of prior austenite grains (PAGs), resulting in an average width of 3.6 μm, which influenced grain boundary distributions and variant selection. The best combination of strength, ductility and toughness was obtained in R900 steel, including tensile (with the yield strength of 1304 MPa, the total elongation of 22.95 %), Charpy impact (with the impact energy at 20 °C is 182 J), and fracture toughness evaluations (with the J1c is 326.28 KJ/m2), this demonstrates that R900 steel exhibited significantly enhanced strength and ductility compared to Q900 steel. Moreover, EBSD analysis of crack propagation paths highlighted the role of high-angle grain boundaries (HAGBs) in enhancing fracture toughness by deflecting cracks. These findings underscore the critical role of PAGs size in tailoring microstructures to achieve superior mechanical properties in low carbon martensitic steels, offering insights for advanced material design and application in demanding structural and industrial contexts.Keyworks.low-carbon martensitic steel; strength and toughness; martensitic transformation; ductile-to-brittle transition phenomenon; selection of martensitic variants.

Interface compatibility and hysteresis in shape memory materials are affected by lattice distortions from applied stresses

Significant effort has been put into designing shape-memory materials that can survive many cycles without functional or structural fatigue. A component of the design process is the condition defining perfect interface compatibility between the austenite and martensite lattices (λ2=1). In this paper, we evaluate the traditional mathematical theories of martensite under applied stresses, which distort the lattice compatibility through elastic strains. In NiTi we find that elastic distortions resulting from applied stresses influence the interface compatibility to a degree of impacting the material's functional abilities. Combining our results with empirical relationships connecting interface compatibility to transformation hysteresis we show that the model matches reasonably to a number of experimental results in the literature in which hysteresis changes under applied loads. We also apply these theories to a shape-memory ceramic (zirconia), which suggests a large orientation-dependence and asymmetric behavior in tension and compression. In both systems, we find that variant selection plays a large role in whether interface compatibility will improve or worsen under stress.

Unravelling the impact of Al-Ti content on the microstructure-toughness relationship in the coarse-grained heated-affected zone of super-high-strength pipeline steels

This study aims to investigate the role of Al-Ti addition on particle modification in super-high-strength pipeline steels, and its following effect on microstructural evolution and impact toughness in the coarse-grained heated-affected zone (CGHAZ) is also explored. The steel plates with low and high Al-Ti content (0.009 wt-% Al + 0.006 wt-% Ti vs. 0.033 wt-% Al + 0.025 wt-% Ti), respectively, are subjected to gas metal arc welding with 6–7 kJ/cm heat input. The results reveal that the second-phase particles including micron-scale inclusion of Al-Mg oxide covered with CaS and nano-scale precipitate of titanium nitride are obtained in low Al-Ti steel, which are modified to the Al-Mg-Ti oxide core surrounded by CaS and TiN precipitate in high Al-Ti steel. The nano-scale TiN precipitate and micron-scale inclusion can restrict the austenite grain growth at high temperatures and induce acicular ferrite nucleation at medium temperatures, respectively, leading to the fine-grained mixed microstructure of bainite and acicular ferrite in CGHAZ of both steels. Because of the variant selection during the decomposition of austenite to bainite and acicular ferrite, those fine-grain structures with amounts of high-angle grain boundaries exhibit excellent CGHAZ toughness in both specimens. Compared with low Al-Ti steel, more precipitates induce smaller austenite grains, and the inclusions containing titanium increase the ability of inclusion to promote acicular ferrite nucleation in CGHAZ of high Al-Ti steel. Both of them resulted in smaller crystallographic grain and toughness improvement in CGHAZ of high Al-Ti steel than that in low Al-Ti steel.

Polymorphic insertions of DcSto miniature inverted-repeat transposable elements reveal genetic diversity structure within the cultivated carrot.

Miniature inverted-repeat transposable elements (MITEs) are a potent source of polymorphisms in plant genomes. A genotyping system, named DcS-ILP, based on polymorphic insertions of Stowaway MITEs (DcStos) localized in introns and identified in the reference genome DH1, has been developed for carrot. Here, we report an extension of the DcS-ILP genotyping system by incorporation of non-reference insertions identified in resequenced genomes representing the eastern gene pool. We genotyped 52 carrot accessions representing the eastern and western carrot gene pools with 92 markers developed previously (western DcS-ILP panel) together with 84 newly developed markers (eastern DcS-ILP panel). Overall, the DcS-ILP markers revealed a highly structured genetic diversity separating the eastern and the western carrot accessions at K = 2 and differentiating Indian breeding lines from the eastern accessions at K = 3. The eastern DcS-ILP panel proved to be more robust with respect to the eastern carrot gene pool, while it provided little information on the western accessions, as many of the DcSto insertions present in the eastern gene pool were absent in the western gene pool. As the western carrot accessions represent improved cultivars, DcSto insertional polymorphisms allowed detection of a selection-driven bottleneck at the improvement stage. Selection in the course of the improvement stage generally operated on standing variation, as the subset of DcSto insertions present in the western carrot likely originated from transposition events preceding the separation of both gene pools. However, occasional frequency shifts in the opposite direction were also revealed, possibly indicating selection for favorable variants associated with DcSto insertions.

Analysis of genetic characteristics associated with reduced bedaquiline susceptibility in multidrug-resistant Mycobacterium tuberculosis

Bedaquiline (BDQ) has shown efficacy in shortening treatment duration and enhancing treatment success rates for multidrug-resistant tuberculosis (MDR-TB), thereby prompting widespread adoption. However, resistance to BDQ has emerged. This study aimed to identify genetic characteristics associated with decreased susceptibility to BDQ, using a public database to aid in the detection of resistant strains. Seventy-one BDQ-resistant and 929 BDQ-susceptible isolates from the open-source CRyPTIC database were selected for analysis. Variant calling was conducted via the clockwork pipeline. Univariate logistic regression was performed for each gene mutation, followed by LASSO regression for further variant selection. Ultimately, a multiple linear regression model was developed using log2-transformed Minimum Inhibitory Concentration values as the dependent variable, with variant selection refined through stepwise regression based on the Akaike Information Criterion. Ten gene mutations were significantly associated with reduced BDQ susceptibility, including two key gene mutations: Rv0678_141_ins_1 and Rv1979c_D249E, with effect estimates of 1.76 (95 % CI: 0.67–2.84) and 1.69 (95 % CI: 0.22–3.17), respectively. Other implicated genes included Rv2699c_-84_del_1, hsaB_I179T, mmpL9_T241A, pncA_C14R, Rv0373c_G621S, Rv0893c_L27F, Rv1770_A4D, and Rv3428c_S327C. This study identified ten gene mutations linked to decreased susceptibility to BDQ, providing a reference for developing a comprehensive catalog of BDQ-resistant genes.

The acquisition of sociolinguistic variation by multilingual merchants: the case of seventeenth-century Spanish

Abstract This article analyzes an unpublished corpus of 131 letters written in Spanish by four Dutch merchants during the seventeenth-century (1669–1677). The aim of the investigation is to determine whether the variation found in these letters was internal, external, or both, and to study the factors that favored each source. To do so, I will look at vowel variation in this corpus. Since standard vowel variants were being selected in seventeenth-century Spanish, the research questions addressed in this work are the following: Did multilingual merchants acquire the emerging standard of the moment? Did multilingual merchants contribute to the selection of standard variants? Did multilingual merchants acquire the sociolinguistic variation of that period? How did multilingual merchants differ from L1 speakers and why? How did linguistic and social factors influence this variation? The results revealed a great amount of intra- and inter-speaker vowel variation, and this variability was a matter of both internal and external factors. Therefore, this study argues that, while multilingual merchants acquired some of the standard variants that were being selected in the emerging standard Spanish of the seventeenth century, they reported linguistic variation that can be explained considering the context of use and the socio-economic conditions underlying their acquisition of linguistic repertoires.

Effect of Cooling Rate on α Variant Selection and Microstructure Evolution in TB17 Titanium Alloy

The α variant selection and microstructure evolution in a new metastable β titanium alloy TB17 were studied in depth by DTA, microhardness, XRD, SEM, and EBSD characterization methods. Under the rapid cooling rate conditions (150 °C/min–400 °C/min), only a very small amount of granular αWM (α Widmanstatten precipitates within the grains) precipitated within the grains. The secondary α phase precipitated in the alloy changed from granular to fine needle-like at moderate cooling rates (15 °C/min–20 °C/min). When continuing to slow down the cooling rates (10 °C/min and 1 °C/min), the αGB (α precipitates along the β grain boundaries), αWGB (α Widmanstatten precipitates that developed from β grain boundaries or αGB) and αWM grew rapidly. Moreover, the continuous cooling transformation (CCT) diagram illustrated the effect of cooling rate on the β/α phase transition. EBSD analysis revealed that the variants selection of α near the original β grain boundary is mainly divided into three categories. (i) The double-BOR (Burgers orientation relationship) αWGB colonies within neighboring β grains grow in different directions but have the same crystallographic orientation. (ii) The double-BOR αWGB colonies within neighboring β grains have different growth directions and different crystallographic orientations. (iii) The double-BOR αWGB colonies within the same grain have the same growth direction, but different crystallographic directions. And these double-BOR αWGB colonies correspond to two variants of the given {0001}α//{110}β.

Effect of austenitizing temperature on variant selection of martensite transformation in a 2 GPa grade steel

The correlation of prior austenite grain (PAG) size, mechanical properties, and the variant selection in martensite transformation of a 2 GPa grade automobile steel has been systematically investigated by using a combination of scaning electron microscopy (SEM), electron backscatter diffraction (EBSD), and uniaxial tesile tests. As the austenitizing temperature decreases from 970 °C to 870 °C, the as-quenched microstructure of the studied steel is fully lath martensite. Meanwhile, the average size of PAG is refined from 7.2 ± 3.9 μm to 2.1 ± 1.2 μm, and the volume fraction of high angle grain boundaries (HAGB) is increased from 59.8% to 72.3%, accompanied with an increased number fraction of grains belonging to closely spaced planes (CP) group. With the refinement of the PAGs, the martensitic variant selectivity becomes strong, and the Bain group variant selection discretely transites to the CP group, resulting in a dominate CP group. Consequently, a tensile strength of 2014 ± 33 MPa, a tensile elongtation of 12.9 ± 0.5% and a maximum strength × ductility production of 26.0 ± 1.4 GPa·%, are obtained when the austenitization temperature is at 920 °C.

Prevalence of Drug Resistance Associated Substitutions in Persons With Chronic Hepatitis C Infection and Virological Failure Following Initial or Re-treatment With Pan-genotypic Direct-Acting Antivirals: A Systematic Review and Meta-analysis.

The advent of short-course, curative treatment with direct-acting antivirals (DAA) has given promise for the global elimination of hepatitis C virus (HCV) infections by 2030. Virological failure occurs in 2%-12% of persons receiving curative DAA treatment and may be presaged by pre-existing polymorphisms or result from selection of drug resistant variants during therapy. We conducted a systematic review to assess the prevalence of HCV resistance associated substitutions (RAS) among individuals with chronic hepatitis C infection who had virological failure following initial or re-treatment with pan-genotypic DAA regimens. We included 34 and 22 studies assessing RAS in people with virological failure published between January 2014 and July 2023. Pooled RAS prevalence was estimated using random-effects meta-analysis. The pooled prevalence of RAS in people with virological failure following initial DAA treatment was 78.0% (95% confidence interval [CI]: 62.0-92.0) for sofosbuvir/velpatasvir, 81.0% (95% CI: 67.0-93.0) for sofosbuvir/daclatasvir, and 79.0% (95% CI: 70.0-87.0) for glecaprevir/pibrentasvir, with a high prevalence of resistance to the NS5A inhibitors. Among those with virological failure following re-treatment regimens, RAS were present in 93.0% (95% CI: 83.0-99.0) for sofosbuvir/velpatasvir/voxilepravir and in 100% (95% CI: 92.0-100) for glecaprevir/pibrentasvir, with resistance driven by RAS to NS5A inhibitors. At least 1 RAS is present in a high proportion of the few individuals with virological failure following initial or re-treatment with pan-genotypic DAA regimens. There is a need for ongoing surveillance for DAA-associated resistance, to assess risk factors for their development and clinical impact to inform best practice strategies for re-treatment.

Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study

Nirsevimab, a long-acting monoclonal antibody, has been approved for the prevention of respiratory syncytial virus (RSV) infection in infants. In France, more than 210 000 single doses were administered in infants younger than 1 year during the 2023-24 season. In this context, the selection and spread of escape variants might be a concern. Here, we aimed to characterise RSV associated with breakthrough infection. We did a multicentre, national, observational study in France during the 2023-24 RSV season in RSV-infected infants (aged <1 year) who either received or did not receive a dose of nirsevimab before their first RSV season. We excluded infants with insufficient information about nirsevimab treatment or without parental consent. We used respiratory samples collected in each laboratory for full-length RSV RNA sequencing to analyse changes in the nirsevimab binding site Ø. We tested clinical RSV isolates for neutralisation by nirsevimab. We analysed F candidate substitutions by fusion-inhibition assay. Of the 695 RSV infected infants, we analysed 545 (78%) full-length RSV genome sequences: 260 (48%) from nirsevimab-treated breakthrough infections (236 [91%] RSV-A and 24 [9%] RSV-B) and 285 (52%) from untreated RSV-infected infants (236 [83%] RSV-A and 49 [17%] RSV-B). Analysis of RSV-A did not reveal any substitution in site Ø known to be associated with resistance to nirsevimab. Two (8%) of 24 RSV-B breakthrough infections had resistance-associated substitutions: F:N208D (dominant resistance-associated substitution) and a newly described F:I64M plus F:K65R combination (minority resistance-associated substitution), both of which induced high levels of resistance in the fusion-inhibition assay. This study is, to the best of our knowledge, the largest genotypic and phenotypic surveillance study of nirsevimab breakthrough infections to date. Nirsevimab breakthrough variants remain very rare despite the drug's widespread use. The detection of resistance-associated substitutions in the RSV-B F protein highlights the importance of active molecular surveillance. ANRS Maladies Infectieuses Emergentes and the French Ministry of Health and Prevention.

Human IL-22 receptor-targeted small protein antagonist suppress murine DSS-induced colitis

BackgroundHuman interleukin-22 (IL-22) is known as a “dual function” cytokine that acts as a master regulator to maintain homeostasis, structural integrity of the intestinal epithelial barrier, and shielding against bacterial pathogens. On the other hand, the overexpression of IL-22 is associated with hyper-proliferation and recruitment of pathologic effector cells, leading to tissue damage and chronic inflammation in specific diseases including inflammatory bowel disease (IBD). To study a role of IL-22-mediated signaling axis during intestinal inflammation, we generated a set of small protein blockers of IL-22R1 and verified their inhibitory potential on murine model of colitis.MethodsWe used directed evolution of proteins to identify binders of human IL-22 receptor alpha (IL-22R1), designated as ABR ligands. This approach combines the assembly of a highly complex combinatorial protein library derived from small albumin-binding domain scaffold and selection of promising protein variants using ribosome display followed by large-scale ELISA screening. The binding affinity and specificity of ABR variants were analyzed on transfected HEK293T cells by flow cytometry and LigandTracer. Inhibitory function was further verified by competition ELISA, HEK-Blue IL-22 reporter cells, and murine dextran sulfate sodium (DSS)-induced colitis.ResultsWe demonstrate that ABR specifically recognizes transgenic IL-22R1 expressed on HEK293T cells and IL-22R1 on TNFα/IFNγ-activated HaCaT cells. Moreover, some ABR binders compete with the IL-22 cytokine and function as IL-22R1 antagonists in HEK-Blue IL22 reporter cells. In a murine model of DSS-induced acute intestinal inflammation, daily intraperitoneal administration of the best IL-22R1 antagonist, ABR167, suppressed the development of clinical and histological markers of colitis including prevention of mucosal inflammation and architecture deterioration. In addition, ABR167 reduces the DSS-induced increase in mRNA transcript levels of inflammatory cytokines such as IL-1β, IL-6, IL-10, and IL-17A.ConclusionsWe developed small anti-human IL-22R1 blockers with antagonistic properties that ascertain a substantial role of IL-22-mediated signaling in the development of intestinal inflammation. The developed ABR blockers can be useful as a molecular clue for further IBD drug development.

Crystallographic Study of Transformation Products of Heat-Affected Zone and Correlation with Properties of FH690 Heavy-Gauge Marine Steel by Multi-Pass Submerged Arc Welding

In this work, the microstructure–property relationship of the heat-affected zone (HAZ) of a FH690 ultra-heavy marine steel plate was investigated based on insight of microstructure and crystallographic features. After multi-pass welding with a heat input of ~30 kJ/cm, an ~8 mm wide HAZ was obtained with a coarse grain HAZ (CGHAZ) of ~3.8 mm, fine grain HAZ (FGHAZ) of ~3.4 mm, and intercritical HAZ (ICHAZ) of ~1 mm. High impact toughness values of ~120 and 140 J at -60 °C were obtained for coarse grain HAZ and fine grain HAZ, respectively. The microstructure of the CGHAZ and FGHAZ was fine lath bainite. Although the average prior austenite grain size for the CGHAZ was ~75 μm, which was five times that of the FGHAZ (15 μm), a high density of high-angle grain boundaries (HAGBs) with misorientation higher than 45° was obtained in the CGHAZ. This is the underlying reason for the excellent low-temperature toughness of the HAZ. Thermo-dynamic calculations indicated that the high density of HAGBs in the CGHAZ was attributed to the decreased bainitic transformation temperature due to the reduced phase transformation driving force via the high nickel addition, leading to weak variant selection. In addition, the high nickel addition offered high hardenability for high hardness in the FGHAZ. The outcome of this study could provide an experimental and fundamental basis for designing high-strength ultra-heavy steel plates with excellent weldability.

Biosensor-Guided Engineering of a Baeyer-Villiger Monooxygenase for Aliphatic Ester Production.

Esters are valuable aroma compounds and can be produced enzymatically by Baeyer-Villiger monooxygenases (BVMOs) from (aliphatic) ketone precursors. However, a genetically encoded biosensor system for the assessment of BVMO activity and the detection of reaction products is missing. In this work, we assembled a synthetic enzyme cascade - featuring an esterase, an alcohol dehydrogenase, and LuxAB - in the heterologous host Escherichia coli. Target esters are produced by a BVMO, subsequently cleaved, and the corresponding alcohol oxidized through the artificial pathway. Ultimately, aldehyde products are detected in vivo by LuxAB, a luciferase from Photorhabdus luminescens that emits bioluminescence upon the oxidation of aldehydes to the corresponding carboxylates. This biosensor system greatly accelerated the screening and selection of active BVMO variants from a focused library, omitting commonly used low-throughput chromatographic analysis. Engineered enzymes accepted linear aliphatic ketones such as 2-undecanone and 2-dodecanone and exhibited improved ester formation.

Quantitative evaluation of local strain distribution induced by deformation twins and triggering effect of deformation twinning on neighboring grains in polycrystalline AZ31 magnesium alloys

{101‾2}<1‾011> deformation twinning commonly occurs in Mg/Mg alloys. In their polycrystals, however, twinning is not always activated at locations with high Schmid factor for {101‾2}<1‾011> twinning. It is believed that twinning behavior in polycrystalline Mg/Mg alloys can be understood with a consideration of interaction between adjacent twins as well as local deformation behavior on a micro- and meso‑structural scale. In this study, we theoretically estimate local plastic strain within twins by transforming coordinates and then compare it with that experimentally obtained from digital image correlation (DIC) analysis for understanding the reason for non-Schmid twinning in polycrystalline-Mg alloys. The theoretically estimated strain of twins was found to be in good agreement with the DIC-strain value. Furthermore, it was observed that the variant selection of twin can be explained by the compatibility parameter m’, rather than Schmid factor, suggesting that twin activation in polycrystalline-Mg is strongly influenced by adjacently appeared twins.

Elimination of pores and microstructural characterization in Ti-6Al-4V alloy welds using fast-frequency double pulse TIG welding

This study utilizes a fast-frequency double pulse tungsten inert gas (FFDP TIG) process to weld 2 mm thick Ti-6Al-4V alloy, with the objective of investigating the influence of a large fast-frequency current amplitude on porosity, microstructure, and tensile properties of the weld joint. Unlike conventional TIG welding, the FFDP TIG welding process led to a reduction and elimination of porosity, and refined the prior β grain and α phase by 34.3 % and 33.3 %, respectively, while also refining the martensitic α′ structure. Stirring of the molten pool resulted in improved uniformity of grain orientation distribution, accompanied by decreased variant selection of the α phase and reduced texture strength of the α phases. Moreover, three-variant clusters of α/α′ phases with triangular morphology and micro- and nanoscale recrystallized α grains appear in the FFDP TIG weld. Concurrently, the FFDP TIG process significantly enhanced the tensile strength and ductility by 14.5 % and 114 %, respectively, compared to the conventional TIG process.

From the "One-Molecule, One-Target, One-Disease" Concept towards Looking for Multi-Target Therapeutics for Treating Non-Polio Enterovirus (NPEV) Infections.

Non-polio enteroviruses (NPEVs), namely coxsackieviruses (CV), echoviruses (E), enteroviruses (EV), and rhinoviruses (RV), are responsible for a wide variety of illnesses. Some infections can progress to life-threatening conditions in children or immunocompromised patients. To date, no treatments have been approved. Several molecules have been evaluated through clinical trials without success. To overcome these failures, the multi-target directed ligand (MTDL) strategy could be applied to tackle enterovirus infections. This work analyzes registered clinical trials involving antiviral drugs to highlight the best candidates and develops filters to apply to a selection for MTDL synthesis. We explicitly stated the methods used to answer the question: which solution can fight NPEVs effectively? We note the originality and relevance of this proposal in relation to the state of the art in the enterovirus-inhibitors field. Several combinations are possible to broaden the antiviral spectrum and potency. We discuss data related to the virus and data related to each LEAD compound identified so far. Overall, this study proposes a perspective on different strategies to overcome issues identified in clinical trials and evaluate the "MTDL" potential to improve the efficacy of drugs, broaden the antiviral targets, possibly reduce the adverse effects, drug design costs and limit the selection of drug-resistant virus variants.