Electrogenic amino acid exchange via the rBAT transporter

AbstractA cDNA clone was isolated from rabbit renal cortex using DNA-mediated expression cloning, which caused alanine-dependent outward currents when expressed in Xenopus oocytes. The cDNA encodes rBAT, a Na-independent amino acid transporter previously cloned elsewhere. Exposure of cDNA-injected oocytes to neutral amino acids led to voltage-dependent outward currents, but inward currents were seen upon exposure to basic amino acids. Assuming one charge/alanine, the outward current represented 38% of the rate of uptake of radiolabelled alanine, and was significantly reduced by prolonged preincubation of oocytes in 5 mM alanine. The currents were shown to be due to countertransport of basic amino acids for external amino acids using the cut-open oocyte system. This transport represents a major mode of action of this protein, and may help in defining a physiological role for rBAT in the apical membrane of renal and intestinal cells

Prevalence and predictors of polypharmacy prescription among type 2 diabetes patients at a tertiary care department in Ningbo, China: A retrospective database study

ObjectivesTo determine the prevalence of polypharmacy prescription among type 2 diabetes (T2DM) patients at a tertiary care department in Ningbo, China, and to determine factors that independently predict this polypharmacy prescription.MethodsA retrospective cross-sectional study was conducted using an existing computerised medical records database. This database was screened from 2012 to 2017 for adult patients with T2DM and parameters like prescribed medicines and socio-demographic, behavioural and other medical information. Polypharmacy prescription was defined as the simultaneous prescription of ≥5 medicines by the clinician at the time of discharge for daily usage by the patient as part of his/her long-term treatment plan.ResultsThe study inclusion criteria were satisfied by 3370 T2DM patients. Over a 5-year period, 72.2% (n = 2432) of T2DM patients were prescribed polypharmacy. On an average, eight medicines were prescribed to them. The odds of polypharmacy prescription increased with patients’ age (18–39 years: 1; 40–59 years: OR 1.86, 95% CI 1.28–2.71; and ≥60 years: 2.42, 1.65–3.55), duration of T2DM (≤1 year: 1; >5–10 years: 1.70, 1.10–2.62; and >10 years: 2.55, 1.68–3.89), and length of hospital stay (≤5 days: 1; >5–10 days: 2.43, 1.86–3.17; and >10 days: 2.99, 2.24–3.99), and were higher in those with poor blood glucose level (2.09, 1.67–2.62) and with comorbidities like other endocrine, nutritional and metabolic diseases (2.24, 1.76–2.85), circulatory system diseases (4.35, 3.62–5.23), skin and subcutaneous tissue diseases (1.64, 1.04–2.59), and musculoskeletal system and connective tissue diseases (1.61, 1.27–2.03). The odds of polypharmacy prescription were lower in those with comorbidities like neoplasms (0.51, 0.36–0.70) and during pregnancy, childbirth and the puerperium (0.06, 0.01–0.49).ConclusionsAround three fourth of T2DM patients at the tertiary care department were prescribed polypharmacy, and the predictors were identified. The study findings could be taken into consideration in future interventional studies aimed at supporting medicines optimisation (and deprescribing) among these patients

Micro grid fault diagnosis based on redundant embedding Petri net

On account of the variable topology and multi-terminal power supply in micro-grid, the fault diagnosis faces more and more challenges. Traditional fault location criteria are unsuitable and fault diagnosis modelling is complex or poor versatility. Further on, the fault reasoning operation is time-consuming. A high transplantable fault diagnosis model aiming at the fault features in micro-grid is established in this paper, and a simple inference algorithm with good error-detecting capability is proposed. Firstly, the fault location criterion based on current magnitude, current phase and Distributed Generation’s current direction information is proposed, and the fault transient component is adopted as a supplementary criterion. Secondly, a hierarchical Petri net model utilizing the electrical information, relays’ and circuit breakers’ state information is accomplished. The model consists of fault location layer and fault clearance layer. In order to increase the portability of the model, the collective processing for the breakers is implemented. Moreover, ‘bidirectional arrowhead arc’ is introduced to reduce the number of places to optimize the Petri net model well. An improved redundant coding Petri net reasoning algorithm is proposed based on the fault clearance layer of the Petri net model. Finally, the validity of the method is verified through case analysis and comparison

A generalized alarm delay-timer’s performance indices computing method

With the rapid development of the modern process industry, the importance of the alarm system has become significant. In general, too many nuisance alarms exist in alarm systems and distract operators’ attention from paying attention to the real abnormal situation. As an effective technique to remove nuisance alarms, the alarm delay-timer is applied extensively in practice. Due to the defects of the alarm delay-timer, the generalized alarm delay-timer is proposed recently as an improvement. But the alarm performance indices alarm rate (FAR), missed alarm rate (MAR), and average alarm delay (AAD) for the generalized alarm delay-timer are not obtained easily so far. In view of this fact; first, a generalization computing method is proposed in the form of three formulas based on the Markov models. Second, the application range of the generalized alarm delay-timer and conventional alarm delay-timer are compared through a numerical simulation. Finally, the procedures of applying the generalized alarm delay-timer are illustrated by a simulation example

A tumor-penetrating peptide modification enhances the antitumor activity of thymosin alpha 1.

A serious limitation of numerous antitumor drugs is the incapacity to penetrate solid tumors. However, addition of an RGD fragment to peptide drugs might solve this problem. In this study, we explored whether the introduction of a permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would enhance the activity of thymosin alpha 1 (Tα1). The modified Tα1 (Tα1-iRGD) was successfully expressed and purified, and the in vitro assay showed that Tα1-iRGD presented a similar activity as Tα1 in promoting proliferation of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Tα1-iRGD exhibited more specific and greater binding with tumor cells compared with Tα1. Furthermore, the iRGD fragment evidently enhanced the basal ability of Tα1 to inhibit proliferation of cancer cells in vitro, particularly of mouse melanoma cell line B16F10 and human lung cancer cell line H460. Our findings indicated that the addition of an iRGD fragment increased the anti-proliferative activity of Tα1 against cancer cells by improving the ability of Tα1 to penetrate the tumor cells. This study highlighted the important roles of an iRGD sequence in the therapeutic strategy of Tα1-iRGD. Thus, Tα1-iRGD could be a novel drug candidate for cancer treatment

Unbalanced power flow algorithm for AC&DC hybrid distribution network with diverse-controlled VSC-MTDC converts

The paper aims to propose an algorithm to calculate the power flow of an AC&DC hybrid distribution system. AC&DC distribution networks have recently attracted increasing attention, for the distributed generations (DGs) and DC loads can be integrated in DC networks in more simple and flexible ways than AC networks. Many efforts have been made to deal with the power flow problem of hybrid networks, however, the DC-side power flow's effect on three-phase unbalanced AC side and the influence to entire distribution system which DG directly connected in the DC side are both not considered. Therefore, this paper discusses the grid architecture with multiple AC&DC feeders. Then, models of VSC-MTDC, DC/DC converters, DGs, and other elements are formulated for power flow calculation. Furthermore, power flow equations of DC distribution and VSC converters are deduced in detail. As for converters under different control strategies and diverse forms of linking combinations between AC&DC grids, calculating approaches are considered to be of partial differences. Considering these distinct cases, a specific and improved sequential method is employed to compute distribution network's power flow. Simulation results on a modified IEEE 13 Node Test Feeder demonstrate the rapidity, accuracy, and easy-convergence of the algorithm

Study on Optimal Loading of Zero Load Cargo

In recent years, thanks to the transformation and upgrading of domestic consumption and the continuous improvement of logistics network, the total freight volume of China’s part-load logistics market is also increasing, among which urban logistics network plays an important role in part-load logistics enterprises. Reasonable and perfect urban network is helpful to reduce the total cost of market logistics and improve distribution efficiency. This paper introduces the problems existing in part-load logistics, studies the urban logistics model of part-load logistics enterprises, introduces three ways of part-load transportation, and analyzes the urban logistics model of part-load logistics enterprises. At the end of this paper, the above contents are briefly summarized

“English Disease”: Historical Notes on Rickets, the Bone–Lung Link and Child Neglect Issues

Nutritional or classical rickets (here labeled as “rickets”) is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule’s important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region

Probing the effect of the non-active-site mutation Y229W in New Delhi metallo-β-lactamase-1 by site-directed mutagenesis, kinetic studies, and molecular dynamics simulations.

New Delhi metallo-β-lactamase-1 (NDM-1) has attracted extensive attention for its high catalytic activities of hydrolyzing almost all β-lactam antibiotics. NDM-1 shows relatively higher similarity to subclass B1 metallo-β-lactamases (MβLs), but its residue at position 229 is identical to that of B2/B3 MβLs, which is a Tyr instead of a B1-MβL-conserved Trp. To elucidate the possible role of Y229 in the bioactivity of NDM-1, we performed mutagenesis study and molecular dynamics (MD) simulations. Although residue Y229 is spatially distant from the active site and not contacting directly with the substrate or zinc ions, the Y229W mutant was found to have higher kcat and Km values than those of wild-type NDM-1, resulting in 1 ∼ 7 fold increases in k(cat) /K(m) values against tested antibiotics. In addition, our MD simulations illustrated the enhanced flexibility of Loop 2 upon Y229W mutation, which could increase the kinetics of both substrate entrance (kon) and product egress (koff). The enhanced flexibility of Loop 2 might allow the enzyme to adjust the geometry of its active site to accommodate substrates with different structures, broadening its substrate spectrum. This study indicated the possible role of the residue at position 229 in the evolution of NDM-1