Approaches of Analysis of Ogee Shaped Barrage Raft Floor on Varying Foundation Media

The analysis of ogee shaped barrage raft floor is a challenging task for the designers because of varying heterogeneous strata disposition, worst combination of loading conditions and functional requirements. A typical Indian barrage bay 3 and 4 has been chosen for analytical comparison between conventional and numerical approach. The behavior of ogee shaped barrage raft floor under representative load cases highlighted that conventional analytical approach i.e. Hetenyi’s method may prove to be inadequate for varying foundation media, which has been recommended by Indian standard code. Unlike the analytical approach, the numerical approach of analysis especially the finite element method with the help of digital computers is capable of accounting for the variation in foundation media, which is a pointer to the advantage of numerical modeling approach of analysis of a typical barrage structure especially the ogee shaped barrage raft floor. The conventional and numerical approaches have been compared to show the limitations of conventional approach and their implication on design estimates

Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms

Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyllysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways. We show that higher protein concentrations of both TFAM mimics are required to compact DNA to a similar extent as the wild-type. Compaction is thought to be crucial for regulating mtDNA segregation and expression. Moreover, we reveal that the reduced DNA binding affinity of the acetyl-lysine mimic arises from a lower on-rate, whereas the phosphoserine mimic displays both a decreased on-rate and an increased off-rate. Strikingly, the increased off-rate of the phosphoserine mimic is coupled to a significantly faster diffusion of TFAM on DNA. These findings indicate that acetylation and phosphorylation of TFAM can fine-tune TFAM-DNA binding affinity, to permit the discrete regulation of mtDNA dynamics. Furthermore, our results suggest that phosphorylation could additionally regulate transcription by altering the ability of TFAM to locate promoter sites

Nitrogen uptake and remobilization from pre‑ and post‑anthesis stages contribute towards grain yield and grain protein concentration in wheat grown in limited nitrogen conditions

Background In wheat, nitrogen (N) remobilization from vegetative tissues to developing grains largely depends on genetic and environmental factors. The evaluation of genetic potential of crops under limited resource inputs such as limited N supply would provide an opportunity to identify N-efficient lines with improved N utilisation efficiency and yield potential. We assessed the genetic variation in wheat recombinant inbred lines (RILs) for uptake, partitioning, and remobilization of N towards grain, its association with grain protein concentration (GPC) and grain yield. Methods We used the nested association mapping (NAM) population (195 lines) derived by crossing Paragon (P) with CIMMYT core germplasm (P × Cim), Baj (P × Baj), Watkins (P × Wat), and Wyalkatchem (P × Wya). These lines were evaluated in the field for two seasons under limited N supply. The plant sampling was done at anthesis and physiological maturity stages. Various physiological traits were recorded and total N uptake and other N related indices were calculated. The grain protein deviation (GPD) was calculated from the regression of grain yield on GPC. These lines were grouped into different clusters by hierarchical cluster analysis based on grain yield and N-remobilization efficiency (NRE). Results The genetic variation in accumulation of biomass at both pre- and post-anthesis stages were correlated with grain-yield. The NRE significantly correlated with aboveground N uptake at anthesis (AGNa) and grain yield but negatively associated with AGN at post-anthesis (AGNpa) suggesting higher N uptake till anthesis favours high N remobilization during grain filling. Hierarchical cluster analysis of these RILs based on NRE and yield resulted in four clusters, efficient (31), moderately efficient (59), moderately inefficient (58), and inefficient (47). In the N-efficient lines, AGNa contributed to 77% of total N accumulated in grains, while it was 63% in N-inefficient lines. Several N-efficient lines also exhibited positive grain protein deviation (GPD), combining high grain yield and GPC. Among crosses, the P × Cim were superior and N-efficient, while P × Wya responded poorly to low N input

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Nitrogen Challenges and Opportunities for Agricultural and Environmental Science in India

In the last six decades, the consumption of reactive nitrogen (Nr) in the form of fertilizer in India has been growing rapidly, whilst the nitrogen use efficiency (NUE) of cropping systems has been decreasing. These trends have led to increasing environmental losses of Nr, threatening the quality of air, soils, and fresh waters, and thereby endangering climate-stability, ecosystems, and human-health. Since it has been suggested that the fertilizer consumption of India may double by 2050, there is an urgent need for scientific research to support better nitrogen management in Indian agriculture. In order to share knowledge and to develop a joint vision, experts from the UK and India came together for a conference and workshop on “Challenges and Opportunities for Agricultural Nitrogen Science in India.” The meeting concluded with three core messages: (1) Soil stewardship is essential and legumes need to be planted in rotation with cereals to increase nitrogen fixation in areas of limited Nr availability. Synthetic symbioses and plastidic nitrogen fixation are possibly disruptive technologies, but their potential and implications must be considered. (2) Genetic diversity of crops and new technologies need to be shared and exploited to reduce N losses and support productive, sustainable agriculture livelihoods. Móring et al. Nitrogen Challenges and Opportunities (3) The use of leaf color sensing shows great potential to reduce nitrogen fertilizer use (by 10–15%). This, together with the usage of urease inhibitors in neem-coated urea, and better management of manure, urine, and crop residues, could result in a 20–25% improvement in NUE of India by 2030

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21

Meta-AnalysisThis is the final version of the article. Available from the American Diabetes Association via the DOI in this record.Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.The major funding for this work comes from Council for Scientific and Industrial Research, Government of India, in the form of the grant “Diabetes mellitus—New drug discovery R&D, molecular mechanisms, and genetic and epidemiological factors” (NWP0032-19). R.T. received a postdoctoral fellowship from the Fogarty International Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health (D43-HD-065249)

“So what if ChatGPT wrote it?” Multidisciplinary perspectives on opportunities, challenges and implications of generative conversational AI for research, practice and policy

Transformative artificially intelligent tools, such as ChatGPT, designed to generate sophisticated text indistinguishable from that produced by a human, are applicable across a wide range of contexts. The technology presents opportunities as well as, often ethical and legal, challenges, and has the potential for both positive and negative impacts for organisations, society, and individuals. Offering multi-disciplinary insight into some of these, this article brings together 43 contributions from experts in fields such as computer science, marketing, information systems, education, policy, hospitality and tourism, management, publishing, and nursing. The contributors acknowledge ChatGPT's capabilities to enhance productivity and suggest that it is likely to offer significant gains in the banking, hospitality and tourism, and information technology industries, and enhance business activities, such as management and marketing. Nevertheless, they also consider its limitations, disruptions to practices, threats to privacy and security, and consequences of biases, misuse, and misinformation. However, opinion is split on whether ChatGPT's use should be restricted or legislated. Drawing on these contributions, the article identifies questions requiring further research across three thematic areas: knowledge, transparency, and ethics; digital transformation of organisations and societies; and teaching, learning, and scholarly research. The avenues for further research include: identifying skills, resources, and capabilities needed to handle generative AI; examining biases of generative AI attributable to training datasets and processes; exploring business and societal contexts best suited for generative AI implementation; determining optimal combinations of human and generative AI for various tasks; identifying ways to assess accuracy of text produced by generative AI; and uncovering the ethical and legal issues in using generative AI across different contexts

Genome-Wide Association Study for Type 2 Diabetes in Indians Identifies a New Susceptibility Locus at 2q21

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 3 1029 ). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 3 10212) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P , 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019