Searching for an Environmental Kuznets Curve in Carbon Dioxide Pollutant in Latin American Countries

This study utilized a semiparametric panel model to estimate environmental Kuznets curves (EKC) for carbon dioxide (CO2) in 15 Latin American countries, using hitherto unused data on forestry acreage in each country. Results showed an N-shaped curve for the region; however, the shape of the curve is sensitive to the removal of some groups of countries. Specification tests support a semiparametric panel model over a parametric quadratic specification.CO2, forest acreage, environmental Kuznets curve, Latin American countries, semiparametric regression model, Agribusiness, Environmental Economics and Policy, Research and Development/Tech Change/Emerging Technologies, C14, C33, Q23, Q53,

Selective Breeding to Improve Productive and Reproductive Performances and Survivability of Indigenous Sakini Chicken

Indigenous chickens are quite popular in Family Poultry Production System (FPPS) in Nepal, but are constrained with their low productive performance. The present study evaluated the productive and reproductive performance of Sakini chicken in different filial generations and sexes. In addition, research also aimed at understanding the effect of generations on above performances. Initially, base populations (G-0) of Sakini were maintained by collecting eight weeks old birds from different agro-ecologial zones of Nepal. Performance of the birds of G-0 was evaluated based on weekly body weight (12-24 weeks), laying performance, fertility, hatchability, hatch weight and survivability. Selected birds of base population (G-0) were used to produce first (G-1), second (G-2) and third (G-3) generations through selective breeding in each generation. Similarly, body weights at hatching, 12 weeks, 16 weeks, 20 week and 24 weeks were significantly (p<0.001) improved from G0 to G3 and were also significantly (p<0.001) differ for sex (males were always heavier than females). Likewise, there was significant (p<0.05) improvement in egg production (per hen per year), age at first lay (days), body weight at sexual maturity, egg number and egg weight at 90 days of laying in progressive generations. Fertility, hatchability and survivability significantly (p<0.05) improved in selected generations in comparison to base population, whereas, no significant difference was obtained within the different selected population. Thus, indigenous Sakini chicken under this experiment performed better with respect to survivability, fertility and hatchability in later generations that provides ample scope of advancing selective breeding activities within the indigenous population in order to bring significant improvement in the overall productive performance of Sakini chicken in Nepal

GLOW: A Workflow Integrating Gaussian-Accelerated Molecular Dynamics and Deep Learning for Free Energy Profiling

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, Copyright © 2022 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jctc.1c01055.We introduce a Gaussian-accelerated molecular dynamics (GaMD), deep learning (DL), and free energy profiling workflow (GLOW) to predict molecular determinants and map free energy landscapes of biomolecules. All-atom GaMD-enhanced sampling simulations are first performed on biomolecules of interest. Structural contact maps are then calculated from GaMD simulation frames and transformed into images for building DL models using a convolutional neural network. Important structural contacts are further determined from DL models of attention maps of the structural contact gradients, which allow us to identify the system reaction coordinates. Finally, free energy profiles are calculated for the selected reaction coordinates through energetic reweighting of the GaMD simulations. We have also successfully demonstrated GLOW for the characterization of activation and allosteric modulation of a G protein-coupled receptor, using the adenosine A1 receptor (A1AR) as a model system. GLOW findings are highly consistent with previous experimental and computational studies of the A1AR, while also providing further mechanistic insights into the receptor function. In summary, GLOW provides a systematic approach to mapping free energy landscapes of biomolecules. The GLOW workflow and its user manual can be downloaded at http://miaolab.org/GLOW

Metabolic health and vascular complications in type 1 diabetes

AIMS: Optimal glycaemic control benefits risk of microvascular and macrovascular complications in type 1 diabetes (T1DM) but the importance of other components of metabolic health is less certain, particularly in the context of routine clinical practice. METHODS: Data for this cross-sectional analysis derived from a database covering inner North West London adult diabetes clinics. People with T1DM and with complete information for height, weight, blood pressure and serum high and low-density lipoprotein cholesterol (HDL-c and LDL-c) and triglyceride concentration measurements were included. RESULTS: Among the 920 participants, those with complications were older and had longer duration of diabetes but had similar HbA1c to people without complications. Systolic hypertension and low HDL-c were independently associated with complications. From having 0 risk factors, the prevalence of micro and macrovascular disease increased with increasing number of risk factors. Relative to those with ≥1 risk factor, those with 0 risk factors (n = 179) were at lower risk of retinopathy (OR 0.6 (0.4-0.9), p = 0.01) and nephropathy [OR 0.1 (0.04-0.3), p = 0.002], independent of individual characteristics. CONCLUSIONS: In routine clinical management of T1DM, associations between lipid and blood pressure risk factors and prevalent micro and macrovascular disease remain, implying that more intensive risk factor management may be beneficial

Effects of presenilin-1 familial Alzheimer’s disease mutations on γ-secretase activation for cleavage of amyloid precursor protein

Presenilin-1 (PS1) is the catalytic subunit of γ-secretase which cleaves within the transmembrane domain of over 150 peptide substrates. Dominant missense mutations in PS1 cause early-onset familial Alzheimer’s disease (FAD); however, the exact pathogenic mechanism remains unknown. Here we combined Gaussian accelerated molecular dynamics (GaMD) simulations and biochemical experiments to determine the effects of six representative PS1 FAD mutations (P117L, I143T, L166P, G384A, L435F, and L286V) on the enzyme-substrate interactions between γ-secretase and amyloid precursor protein (APP). Biochemical experiments showed that all six PS1 FAD mutations rendered γ-secretase less active for the endoproteolytic (ε) cleavage of APP. Distinct low-energy conformational states were identified from the free energy profiles of wildtype and PS1 FAD-mutant γ-secretase. The P117L and L286V FAD mutants could still sample the “Active” state for substrate cleavage, but with noticeably reduced conformational space compared with the wildtype. The other mutants hardly visited the “Active” state. The PS1 FAD mutants were found to reduce γ-secretase proteolytic activity by hindering APP residue L49 from proper orientation in the active site and/or disrupting the distance between the catalytic aspartates. Therefore, our findings provide mechanistic insights into how PS1 FAD mutations affect structural dynamics and enzyme-substrate interactions of γ-secretase and APP

Structural Basis for Binding of Allosteric Drug Leads in the Adenosine A1 Receptor

This work is licensed under a Creative Commons Attribution 4.0 International License.Despite intense interest in designing positive allosteric modulators (PAMs) as selective drugs of the adenosine A1 receptor (A1AR), structural binding modes of the receptor PAMs remain unknown. Using the first X-ray structure of the A1AR, we have performed all-atom simulations using a robust Gaussian accelerated molecular dynamics (GaMD) technique to determine binding modes of the A1AR allosteric drug leads. Two prototypical PAMs, PD81723 and VCP171, were selected. Each PAM was initially placed at least 20 Å away from the receptor. Extensive GaMD simulations using the AMBER and NAMD simulation packages at different acceleration levels captured spontaneous binding of PAMs to the A1AR. The simulations allowed us to identify low-energy binding modes of the PAMs at an allosteric site formed by the receptor extracellular loop 2 (ECL2), which are highly consistent with mutagenesis experimental data. Furthermore, the PAMs stabilized agonist binding in the receptor. In the absence of PAMs at the ECL2 allosteric site, the agonist sampled a significantly larger conformational space and even dissociated from the A1AR alone. In summary, the GaMD simulations elucidated structural binding modes of the PAMs and provided important insights into allostery in the A1AR, which will greatly facilitate the receptor structure-based drug design.Extreme Science and Engineering Discovery Environment award TG-MCB170129National Energy Research Scientific Computing Center project M2874American Heart Association (Award 17SDG33370094)College of Liberal Arts and Sciences at the University of KansasNHMRC Senior Principal Research FellowAustralian Heart Foundation Future Leader Fello

Matrix Diagonalization as a Board Game: Teaching an Eigensolver the Fastest Path to Solution

Matrix diagonalization is at the cornerstone of numerous fields of scientific computing. Diagonalizing a matrix to solve an eigenvalue problem requires a sequential path of iterations that eventually reaches a sufficiently converged and accurate solution for all the eigenvalues and eigenvectors. This typically translates into a high computational cost. Here we demonstrate how reinforcement learning, using the AlphaZero framework, can accelerate Jacobi matrix diagonalizations by viewing the selection of the fastest path to solution as a board game. To demonstrate the viability of our approach we apply the Jacobi diagonalization algorithm to symmetric Hamiltonian matrices that appear in quantum chemistry calculations. We find that a significant acceleration can often be achieved. Our findings highlight the opportunity to use machine learning as a promising tool to improve the performance of numerical linear algebra.Comment: 14 page

Social Safety Net Programmes in Selected Villages of Andhra Pradesh. SaciWATER Working Paper 02/2014

Social Protection Programmes are those programmes instituted by governments or society that help protect citizens from “risks, vulnerabilities and deprivations”. Social Protection can be considered like an insurance against poverty, this can be instituted by governments (official social protection) or otherwise (unofficial social protection). Social Safety Nets are subsets of such programmes Such protection is needed as poverty is a major issue in rural India, 72 percent of the population lives in rural areas. It is estimated that 42 percent of the rural population lives below the poverty line. This is especially true in the semi-arid tropics of India, where 40.5% of India’s rural poor lives, despite only covering 37% of the country’s area. The rural poor in SAT India are faced with the shocks and seasonalities that increase vulnerability, such as the issues of water scarcity under increasingly variable climatic conditions, food security and issues of livelihood security. SAT Andhra Pradesh is no different. This paper examines the issues that had an influence on vulnerability in four selected villages in Andhra Pradesh in India and examines how, if at all, social safety net programmes alleviate these issues. To this end focus group discussions and informal interviews were carried out among landless and landowning inhabitants of the village. The findings of the study are as follows. Though issues differ slightly from village to village, a common thread was seen in the form of lack of access to water resources for farming which has far reaching impacts, on migration, labour availability and even food security. Additional issues reported were of sanitation and fluctuating prices, both in terms of selling agricultural produce, as well as purchasing essential commodities. A large number of safety nets function in these villages, among these, the major programmes include the Mahatma Gandhi National Rural Employment Guarantee Scheme, Public Distribution Systems, Self Help Groups, health insurance schemes, housing schemes, agricultural subsidies, loan waivers and so on. It was found that though official social safety nets were functional in all villages to varying degrees, their reception and impacts have been mixed. Of the official formal safety net programmes, only self help groups were reported as functioning excellently, and not many complaints were raised about it. With respect to the other official safety nets, there were gaps identified in the implementation on the ground, mostly due to lack of monitoring. Thus there is room for improvement in this regard. Respondents state that even when fully functional, these programmes often do not help them with the problems faced in the village. People often resort to unofficial safety nets, due to urgent need, or even due to official safety nets not being effective in that case. Among the unofficial safety nets, it was found that borrowing from friends and relatives is the most common and preferred method of obtaining money in times of need, as is credit at local village stores. Thus, it was seen that the social safety net programmes do not fully address the issues that are faced in the village, in order to get better results, it is important to increase transparency in the implementation process, additionally, even though there is existing convergence between government schemes, more convergence and streamlining would be beneficial. Another issue is the lack of ownership among the beneficiaries, where community led initiatives to solve problems are lacking. This could be addressed through advocacy and capacity building, through a rights based approach

Major Social Safety Net Programmes in the Context of Dryland Farming: Review and Synthesis. Working Paper, (SaciWater WP- 01/2014).

Poverty is a major issue in rural India, especially in the semiarid tropic region of India. In order to alleviate poverty the Government of India, and state governments, like governments world over, have instituted social protection and social safety net programmes. This paper seeks to review and synthesize implementation of the major social safety net programmes in India and globally and document various social safety net programmes that area commonly being implemented in the semiarid tropical regions of Andhra Pradesh. In order to do this, this paper investigates the existing definitions of poverty, and vulnerability with a special focus on the semiarid tropics of India and examines the need for social assistance in this region. The concepts of social protection in terms of social protection programmes and social safety nets are also investigated. A review of social protection programmes from all over the world is carried out – examining the different programmes in developed nations such as Germany, United States and United Kingdom; developing nations, with a focus on Latin America; and least developed nations in Africa. In this range of studies, it is possible to see how social protection programmes vary, from the more affluent nations, where these programmes are more contributory in nature, dealing more with health and temporary relief in cases of unemployment. Whereas in the less developed nations, where SPPs are a more non-contributory in nature, and form a much more essential part in ensuring livelihood security. The paper then examines the most important social protection programmes in India, in great detail providing a history of development of important schemes meant to ensure food, nutritional and livelihood security, such as the PDS and NREGA among other import programmes, and talks about the criticisms and shortcomings of the programmes. The various SPPs in Andhra Pradesh are examined, with a special focus on Self- Help Groups which are mostly comprised of women have been instrumental in improving well being, not just of women but also of families. There have been reports of issues with many social protection programmes in India, in terms of access, leakages, benefits not being received, the cost effectiveness of these programmes , lack of gender sensitivity in the programmes and so on. Despite all the flaws and gaps in implementation, the way now is forward. There is an urgent need to study how access or lack thereof to the various official and non official social safety net programmes have affected not just the intended direct and indirect beneficiaries, but also those in rural India who are not beneficiaries of the programmes, but who may directly or indirectly be affected by them, either positively or negatively