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The design of rural drinking water schemes consists of optimization of several network components like pipes, tanks, pumps and valves. The sizing and configuration of these network configurations need to be such that the water requirements are met while at the same time being cost efficient so as to be within government norms. We developed the JalTantra system to design such water distribution networks. The Integer Linear Program (ILP) model used in JalTantra and described in our previous work solved the problem optimally, but took a significant amount of time for larger networks—an hour for a network with 100 nodes. In this current work, we describe a series of three improvements of the model. We prove that these improvements result in tighter models, i.e. the set of points of linear relaxation is strictly smaller than the linear relaxation for the initial model. We test the series of three improved models along with the initial model over eight networks of various sizes and show a distinct improvement in performance. The 100-node network now takes only 49 s to solve. These changes have been implemented in JalTantra, resulting in a system that can solve the optimization of real world rural drinking water networks in a matter of seconds. The JalTantra system is free for use, and is available at https://www.cse.iitb.ac.in/jaltantra/. [ABSTRACT FROM AUTHOR]

The analysis of retention characteristics is essential for reliability assessment of any type of flash memory. A high-k (HK) material in the Interpoly dielectric (IPD) stack is known to improve the program-erase characteristics and makes the control oxide thicker for better retention time; however, it also brings-in defects along with it, creating undesirable charge loss path that plays a significant role in retention. Accurate modeling of this leakage process is important for optimizing the architecture that is less prone to oxide defects and exhibiting improved charge retention. In this paper, we present a physical model considering all possible charge leakage mechanisms that include inelastic tunneling through multiple traps in addition to direct tunneling (DT). The trap capture process is modeled as an inelastic process from nanocrystal (NC) to trap state, while the trap-to-trap tunneling is calculated by Bardeen's Transfer Hamiltonian approach. The trap emission process and DT from the spherical NC are modeled by computing the lifetime of quasi-bound states with very small decay widths in the finite-element setup. We show that a single trap model in HK cannot explain the retention characteristics. We propose a new asymmetric IPD structure that show significant improvement in retention time. [ABSTRACT FROM AUTHOR]

The program/erase process in floating gate (FG) flash memory devices is modeled by considering sequential quantum tunneling of electrons and taking into account quantum confinement in the channel and FG. We precisely determine location of quasi-bound or decaying quantum states in the inversion layer and in FG comprising a nanocrystal (NC) layer, and compute their lifetime by finding the complex eigenenergy of the resonance transmission problem. Self-consistent solutions to Poisson and Schrödinger equations are obtained for the quantum states of electrons in the inversion layer of MOS devices, and subsequently, sequential Fowler–Nordheim tunneling current to the spherical NCs is obtained using finite-element method considering open boundary conditions. The method described here is capable of determining the tunneling current accurately for arbitrary potential profiles, and can be applied for composite tunnel dielectric stacks. Our results show good agreement with the experimental data for high- $k$ interpoly dielectric flash memory devices. [ABSTRACT FROM PUBLISHER]

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition. [ABSTRACT FROM AUTHOR]

Motivation: Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. To alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Results: Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP-derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome-scale networks, but also improves the understanding of the linkage between EMs and MCSs. [ABSTRACT FROM AUTHOR]

A standard experimental setup for Inelastic Electron Tunneling Spectroscopy (IETS) performs the measurement of the second derivative of the current with respect to the voltage ( d 2 I / d V 2 ) using a small AC signal and a lock-in based second harmonic detection. This avoids noise arising from direct differentiation of the current-voltage characteristics (I–V) by standard numerical methods. Here we demonstrate a noise-filtering algorithm based on Tikhonov Regularization to obtain IET spectra (i.e. d 2 I / d V 2 vs. V) from measured DC I–V curves. This leads to a simple and effective numerical method for IETS extraction. We apply the algorithm to I–V data from a molecular junction and a metal-insulator-semiconductor tunneling device, demonstrating that the computed first/second derivatives have a workable match with those obtained from our lock-in measurements; the computed IET spectral peaks also correlate well with reported experimental ones. Finally, we present a scheme for automated tuning of the algorithm parameters well-suited for the use of this numerical protocol in real applications. [ABSTRACT FROM AUTHOR]

Arteriolar hyalinosis is a common histological finding in renal transplant recipients treated with the calcineurin inhibitor tacrolimus; however, the pathophysiologic mechanisms remain unknown. In addition to increasing transforming growth factor (TGF)-β levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-β receptor activation. Here we tested whether tacrolimus binding to FKBP12 removes an inhibition of the TGF-β receptor, allowing ligand binding, ultimately leading to receptor activation and arteriolar hyalinosis. We found that specific deletion of FKBP12 from endothelial cells was sufficient to activate endothelial TGF-β receptors and induce renal arteriolar hyalinosis in these knockout mice, similar to that induced by tacrolimus. Tacrolimus-treated and knockout mice exhibited significantly increased levels of aortic TGF-β receptor activation as evidenced by SMAD2/3 phosphorylation, along with increased collagen and fibronectin expression compared to controls. Treatment of isolated mouse aortas with tacrolimus increased TGF-β receptor activation and collagen and fibronectin expression. These effects were independent of calcineurin, absent in endothelial denuded aortic rings, and could be prevented by the small molecule TGF-β receptor inhibitor SB-505124. Thus, endothelial cell TGF-β receptor activation is sufficient to cause vascular remodeling and renal arteriolar hyalinosis. [ABSTRACT FROM AUTHOR]

Arteriolar hyalinosis is a common histological finding in renal transplant recipients treated with the calcineurin inhibitor tacrolimus; however, the pathophysiologic mechanisms remain unknown. In addition to increasing transforming growth factor (TGF)-β levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-β receptor activation. Here we tested whether tacrolimus binding to FKBP12 removes an inhibition of the TGF-β receptor, allowing ligand binding, ultimately leading to receptor activation and arteriolar hyalinosis. We found that specific deletion of FKBP12 from endothelial cells was sufficient to activate endothelial TGF-β receptors and induce renal arteriolar hyalinosis in these knockout mice, similar to that induced by tacrolimus. Tacrolimus-treated and knockout mice exhibited significantly increased levels of aortic TGF-β receptor activation as evidenced by SMAD2/3 phosphorylation, along with increased collagen and fibronectin expression compared to controls. Treatment of isolated mouse aortas with tacrolimus increased TGF-β receptor activation and collagen and fibronectin expression. These effects were independent of calcineurin, absent in endothelial denuded aortic rings, and could be prevented by the small molecule TGF-β receptor inhibitor SB-505124. Thus, endothelial cell TGF-β receptor activation is sufficient to cause vascular remodeling and renal arteriolar hyalinosis. [ABSTRACT FROM AUTHOR]