Simplified inelastic electron tunneling spectroscopy based on low-noise derivatives.

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 ([Formula: see text]) 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. [Formula: see text] 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.

Review on long afterglow nanophosphors, their mechanism and its application in round-the-clock working photocatalysis.

Semiconductor assisted photocatalysis is one of the most efficient methods for the degradation of complex organic dyes. A major limiting factor of semiconductor assisted photocatalysis is the requirement of a continuous source of light to perform a redox reaction. One of the upcoming solutions is photon energy-storing long afterglow/persistent phosphors. They are an unusual kind of rechargeable, photon energy capturing/trapping phosphors that can trap charge carriers (electrons/holes) in their meta-stable energy levels, thereby resulting in persistent luminescence. Persistence luminescence from such materials can range from minutes to hours. The coupling of long afterglow phosphors (LAP) with the conventional semiconductor is a promising way to support the photocatalytic process even in dark. In addition, dissimilar band structures of LAPs and semiconductor results in formation of heterojunction which further suppresses the recombination of charge. Such an encouraging idea of LAP for round-the-clock working photocatalytic system is in its premature stage; which is required to be investigated fully. Thus, we present a state-of-art review on the potential materials for assisting round-the-clock photocatalysis, trapping-detrapping mechanism in LAP materials, fabrication strategies and their associated characterization tools. Review also covers LAP materials and their photocatalytic mechanism briefly.

Correction in Active Cases Data of COVID-19 for the US States by Analytical Study.

The total coronavirus disease (COVID-19) cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have reached 139 million worldwide and nearing 3 million deaths on April 16, 2021. The availability of accurate data is crucial as it makes it possible to analyze correctly the infection trends and make better forecasts. The reported recovered cases for many US states are surprisingly low. This could be due to difficulties in keeping track of recoveries, which resulted in higher numbers for the reported active cases than the actual numbers on the ground. In this work, based on the typical range of recovery rate for COVID-19, we estimate the active data from the total cases and death cases and bring out a correction for the data for all the US states reported on Worldometer.

Estimation of undetected symptomatic and asymptomatic cases of COVID-19 infection and prediction of its spread in the USA.

The reported COVID-19 cases in the United States of America have crossed over 10 million and a large number of infected cases are undetected whose estimation can be done if country-wide antibody testing is performed. In this study, we estimate this undetected fraction of the population by a modeling and simulation approach. We employ an epidemic model SIPHERD in which three categories of infection carriers, symptomatic, purely asymptomatic, and exposed are considered with different transmission rates that are taken dependent on the social distancing conditions, and the detection rate of the infected carriers is taken dependent on the tests done per day. The model is first validated for Germany and South Korea and then applied for prediction of the total number of confirmed, active and dead, and daily new positive cases in the United States. Our study predicts the possible outcomes of the infection if social distancing conditions are relaxed or kept stringent. We estimate that around 30.1 million people are already infected, and in the absence of any vaccine, 66.2 million (range: 64.3-68.0) people, or 20% (range: 19.4-20.5) of the population will be infected by mid-February 21 if social distancing conditions are not made stringent. We find the infection-to-fatality ratio to be 0.65% (range: 0.63-0.67).

An epidemic model SIPHERD and its application for prediction of the spread of COVID-19 infection in India.

Originating from Wuhan, China, in late 2019, and with a gradual spread in the last few months, COVID-19 has become a pandemic crossing 9 million confirmed positive cases and 450 thousand deaths. India is not only an overpopulated country but has a high population density as well, and at present, a high-risk nation where COVID-19 infection can go out of control. In this paper, we employ a compartmental epidemic model SIPHERD for COVID-19 and predict the total number of confirmed, active and death cases, and daily new cases. We analyze the impact of lockdown and the number of tests conducted per day on the prediction and bring out the scenarios in which the infection can be controlled faster. Our findings indicate that increasing the tests per day at a rapid pace (10k per day increase), stringent measures on social-distancing for the coming months and strict lockdown in the month of July all have a significant impact on the disease spread.

Sequential computation of elementary modes and minimal cut sets in genome-scale metabolic networks using alternate integer linear programming.

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. AVAILABILITY AND IMPLEMENTATION: The software is implemented in Matlab, and is provided as supplementary information . CONTACT: hyunseob.song@pnnl.gov. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Endothelial cell transforming growth factor-ß receptor activation causes tacrolimus-induced renal arteriolar hyalinosis.

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)-ß levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-ß receptor activation. Here we tested whether tacrolimus binding to FKBP12 removes an inhibition of the TGF-ß 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-ß 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-ß 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-ß 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-ß receptor inhibitor SB-505124. Thus, endothelial cell TGF-ß receptor activation is sufficient to cause vascular remodeling and renal arteriolar hyalinosis.

Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy.

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.

Toll-like receptor 3 activation during pregnancy elicits preeclampsia-like symptoms in rats.

BACKGROUND: Preeclampsia (PE), a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. There is strong evidence that maternal immune system activation, of which Toll-like receptors (TLRs) play a major role, contributes to the development of PE. Viral infections, sensed by TLR3, are associated with hypertensive disorders of pregnancy. We tested the hypothesis that TLR3 activation during pregnancy would cause hypertension, endothelial dysfunction, proteinuria, and intrauterine growth restriction in normal pregnant rats. METHODS: We treated pregnant and nonpregnant rats with the viral mimetic polyinosinic:polycytidylic acid (poly I:C) or vehicle every other day beginning at day 10 of gestation and measured systolic blood pressure, aortic vasodilation, urinary protein concentration, fetal growth, and serum and placental cytokine levels. RESULTS: Pregnant rats treated with poly I:C displayed significantly elevated systolic blood pressures compared to pregnant rats and nonpregnant rats treated with poly I:C on day 18 of gestation. Poly I:C-treated pregnant rats also exhibited significantly decreased aortic vasodilation, significantly increased urinary protein concentrations, and had more malformed pups/litter. Additionally, poly I:C-treated rats exhibited a significant increase in placental TLR3 expression and proinflammatory/anti-inflammatory cytokine ratio compared to vehicle-treated rats. Poly I:C treatment of nonpregnant control rats had no effect on systolic blood pressure, aortic vasodilation, or urinary protein concentrations. CONCLUSION: These findings demonstrate that sustained maternal immune system activation via TLR3 during pregnancy causes PE-like symptoms in rats and suggest that viral infection during pregnancy may contribute to the development of PE.

Immunosuppression improves blood pressure and endothelial function in a rat model of pregnancy-induced hypertension.

BACKGROUND: Hypertensive disorders of pregnancy, including preeclampsia (PE), affect approximately 7-10% of pregnancies in the US. Clinical and experimental studies strongly suggest that the maternal immune system plays a role in the development of these disorders; however, few therapeutic options exist aside from delivery. METHODS: Using a deoxycorticosterone acetate (DOCA)/salt-low renin rat model, which exhibits hypertension, proteinuria, endothelial dysfunction, and intrauterine growth restriction (IUGR), we measured serum cytokine levels as an indication of immune system activation. In addition, we suppressed the immune system with either azathioprine (Aza) or mycophenolate mofetil (MMF) during the second half of pregnancy to determine whether the these symptoms could be ameliorated. RESULTS: Our results demonstrate that serum T helper-1 (Th1)-type inflammatory cytokines interleukin (IL)-2, IL-12, interferon-gamma (IFNgamma), and RANTES were significantly elevated in hypertensive pregnant rats while the Th2-type cytokine IL-4 was elevated in normal pregnant animals. Either Aza or MMF significantly attenuated the hypertension, proteinuria, and endothelial dysfunction as well as the increased proinflammatory Th1 cytokine profile in pregnant rats treated with DOCA/salt, and had no effect on these parameters in normal pregnant rats. CONCLUSION: These data strongly suggest that maternal immune system activation plays a role in the development of pregnancy-induced hypertension (PIH).

Hypoparathyroidism associated with severe mineral bone disease postrenal transplantation, treated successfully with recombinant PTH.

Chronic kidney disease (CKD) is commonly, if not universally, associated with derangements in bone and mineral metabolism, characterized by hyperphosphatemia, low calcitriol levels, and secondary hyperparathyroidism. The spectrum of these disorders is termed renal osteodystrophy or chronic kidney disease-mineral bone disease complex. Aggressive phosphorus control is the cornerstone of management to prevent debilitating complications. Dietary control, phosphate binders, and administration of active vitamin D analogues is the most common initial therapy. Frequently parathyroidectomy is required to reverse or slow the pathological changes when medical management fails. The most common adverse effect of parathyroidectomy is hypocalcemia. We describe a case report of severe hypocalcemia (secondary to surgical hypoparathyroidism) and "hungry bone syndrome," treated successfully with teriparatide (Forteo) in a patient who underwent renal transplantation following subtotal parathyroidectomy.