Miracle-dz/UniFAR-FTUs huggingface dataset:
Bile acid formation in primary human hepatocytes.

AIM:To evaluate a culture system for bile acid formation in primary human hepatocytes in comparison with HepG2 cells.METHODS:Hepatocytes were isolated from normal human liver tissue and we re cultured in serum-free William's E medium.The medium was collected and re newed every 24 h. Bile acids and their precursors in media were finally analysed by gas chromatography mass spectrometry.RESULTS:Cholic acid (CA) and chenodeoxycholic acid (CDCA) conjugated with glycine or taurine accounted for 70% and 25% of total steroids. A third of CDC A was also conjugated with sulphuric acid. Dexamethasone and thyroid hormone alone or in combination did not significantly effect bile acid formation. The addition of cyclosporin A (10&mgr;mol/L) inhibited the synthesis of CA and CDCA by about 13% and 30%, respectively.CONCLUSION:Isolated human hepatocytes in primary culture behave as in the intact liver by converting cholesterol to conjugated CA and CDCA.This is in contrast to cultured HepG2 cells, which release large amounts of bile acid precursors and unconjugated bile acids into the medium.
Understanding the X chromosome inactivation cycle in mice

During mouse development, imprinted X chromosome inactivation (XCI) is observed in preimplantation embryos and is inherited to the placental lineage, whereas random XCI is initiated in the embryonic proper. Xist RNA, which triggers XCI, is expressed ectopically in cloned embryos produced by somatic cell nuclear transfer (SCNT). To understand these mechanisms, we undertook a large-scale nuclear transfer study using different donor cells throughout the life cycle. The Xist expression patterns in the reconstructed embryos suggested that the nature of imprinted XCI is the maternal Xist-repressing imprint established at the last stage of oogenesis. Contrary to the prevailing model, this maternal imprint is erased in both the embryonic and extraembryonic lineages. The lack of the Xist-repressing imprint in the postimplantation somatic cells clearly explains how the SCNT embryos undergo ectopic Xist expression. Our data provide a comprehensive view of the XCI cycle in mice, which is essential information for future investigations of XCI mechanisms.
Delegation and the Regulation of U.S. Financial Markets

We explore the determinants of U.S. financial market regulation with a formal model of the policy-making process in which government regulates financial risk at both the firm and systemic levels, and test these predictions with a novel, comprehensive data set of financial regulatory laws enacted since 1950. We find that political factors impact Congress' decision to delegate regulatory authority to executive agencies, which in turn impacts the stringency of financial market regulation. In particular, Congress delegates authority to regulators when: 1) policy preferences between Congress and executive officials become more similar; 2) Firms' investment risks become more uncertain; and 3) Congress' concerns about a bailout are greater. As a result, financial markets are more heavily regulated when firm-specific and systemic risks are uncertain. However, when inter-branch preferences differ or perceived systemic risk is low, Congress may allow risky investments to be made that, ex post, it wished it had regulated.
On-line optimal ion conductivity control of Li-ion battery

The battery charging control strategies with considering battery characteristics in the high power battery energy storage applications are limited, because it is difficult to obtain the overall electrochemical characteristics. However, this information is important, because they are related on life cycle, charging speed, and efficiency. In order to improve these factors, this paper proposes to control the ion conductivity, which is one of the electrochemical characteristics as an optimal charging control strategy. It results in reducing polarization impact. This control scheme needs to measure on-line battery impedance and track its saturation points. This control scheme enhanced the charging efficiency and moderate temperature rising rate. Experimental results based on a 14.6V 40Ah LiFeMgPO4 battery are used to validate and to demonstrate the performance of the proposed control scheme.
HIV-associated kidney glomerular diseases: changes with time and HAART.

BACKGROUND Treatment and co-morbidities of human immunodeficiency virus (HIV)-infected individuals have changed dramatically in the last 20 years with a potential impact on renal complications. Our objective was to assess the change in distribution of the glomerular diseases in HIV patients. METHODS We retrospectively analysed demographic, clinical, laboratory and renal histopathological data of 88 HIV-infected patients presenting with a biopsy-proven glomerular disease between 1995 and 2007. RESULTS In our study including 66% Black patients, HIV-associated nephropathy (HIVAN) was observed in 26 cases, classic focal segmental glomerulosclerosis (FSGS) in 23 cases, immune complex glomerulonephritis in 20 cases and other glomerulopathies in 19 patients. HIVAN decreased over time, while FSGS emerged as the most common cause of glomerular diseases (46.9%) in HIV-infected individuals undergoing kidney biopsy in the last 2004-07 period. Patients with HIVAN were usually Black (97%), with CD4 <200/mL (P = 0.01) and glomerular filtration rate <30 mL/min/1.73 m(2) (P < 0.01). Compared to HIVAN, patients with classic FSGS were less often Black (P < 0.01), have been infected for longer (P = 0.03), were more often co-infected with hepatitis C virus (P = 0.05), showed more often cardiovascular (CV) risk factors (P < 0.01), had less often CD4 <200/mL (P = 0.01), lower HIV viral load (P = 0.01) and tended to be older (P = 0.06). CONCLUSIONS Classic FSGS associated with metabolic and CV risk factors has overcome HIVAN in HIV-infected patients. Compared with other glomerulopathies, HIVAN remains strongly associated with severe renal failure, Black origin and CD4 lower than 200/mL at presentation.
Adaptive optimal PI controller for high-precision low-temperature experiments

In this paper, we describe an adaptive optimal PI controller for high-precision low-temperature experiments. We used a modified LQR algorithm to obtain the optimal parameters for the PI controller. Since the plant is nonlinear, a gain scheduling method is applied to modify the optimal parameters under different operating conditions. The simulation results show that this controller has good transient response, disturbance rejection ability, and robustness. Furthermore, the controller can accommodate a variety of first-order nonlinear systems. At last, we discuss the design of the optimal PID controller for a class of second order system using the modified LQR algorithm.
The cleavage site of C5 from man and animals as a common target for neutralizing human monoclonal antibodies: in vitro and in vivo studies

The isolation of an anti‐C5 single‐chain fragment variable (scFv) antibody, TS‐A12/22, from a human phage display library, is described. This antibody inhibits the activation of C5 and the assembly of the terminal complement complex implicated in cell and tissue damage. Using antibody‐sensitized sheep erythrocytes and rabbit red cells as target cells in hemolytic assays, we found that TS‐A12/22 inhibited the activation of C5 by the convertases of both classical and alternative pathways. Western blot analysis and competition experiments with synthetic peptides showed that TS‐A12/22 reacted with the α chain of C5 and recognized the cleavage site of this complement component by the C5 convertase. As a result, the antibody prevented splitting of C5 and inhibited the generation of C5a and of the terminal complement complex. The identification of the TS‐A12/22 recognition site as a conserved sequence in man, mouse, rat and rabbit enabled the demonstration of in vitro inhibition of complement activity in these species. The scFv TS‐A12/22 was tested in a rat model of antigen‐induced arthritis and proved to be effective in preventing influx of polymorphonuclear cells into the knee joint and C9 deposition on synovial tissue.
Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome*

Objectives: Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis. Design: A prospective, multicenter, observational, descriptive, and validation study. Setting: A network of multidisciplinary ICUs. Patients: Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation. Interventions: None. Measurements and Main Results: Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an independent cohort of 300 acute respiratory distress syndrome patients. Primary outcome was in-hospital mortality. We found that a 9-point score based on patient’s age, PaO2/FIO2 ratio, and plateau pressure at 24 hours after acute respiratory distress syndrome diagnosis was associated with death. Patients with a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0–11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p < 0.0000001). We confirmed the predictive validity of the score in a validation cohort. Conclusions: A simple 9-point score based on the values of age, PaO2/FIO2 ratio, and plateau pressure calculated at 24 hours on protective ventilation after acute respiratory distress syndrome diagnosis could be used in real time for rating prognosis of acute respiratory distress syndrome patients with high probability.
Effects of Aerobic Exercise Training on Psychosocial Status and Serum Uric Acid in Men with Essential Hypertension: A Randomized Controlled Trial

Background: Chronic psychosocial stress and serum uric acid (SUA) level have been implicated in the etiology and cardiovascular events risk factors in hypertension. Studies have reported significant benefit of exercise in the overall management of hypertension. However, studies on the effect of exercise on psychosocial stress and SUA in the management of hypertension seem scanty. Aim: The aim of this study was to determine the effect of continuous training program on SUA and psychosocial status of black African (Nigerian) population with hypertension. Subjects and Methods: Age-matched randomized controlled trial was used; subjects with diagnosis of hypertension attending the hypertensive clinic of Murtala Muhammed Specialist Hospital (MMSH), Kano, Nigeria form the population for the study. Two hundred and seventeen subjects with mild to moderate (systolic blood pressure (SBP) between 140 and180 and diastolic blood pressure (DBP) between 90 and 109 mmHg) essential hypertension were grouped into continuous (112) and control groups (105). The continuous group involved in an 8 weeks continuous training (60%-79% HR max) of between 45 and 60 min, 3 times per week, while the controls group remain sedentary. SBP, DBP, SUA, VO2 max and psychosocial status were assessed. Student t-test and Pearson correlation test were used in data analysis. Results: The study revealed significant beneficial effect of continuous training programs on VO2 max, SBP, DBP, SUA, and psychosocial status (P < 0.05). Psychosocial status and SUA was significantly and positively and negatively correlated respectively with VO2 max at P < 0.01. Conclusions: This study concludes and supports the recommendations of moderate intensity (continuous) training program in blood pressure reduction, SUA and psychosocial stress management in hypertension.
Clopidogrel Before Elective Percutaneous Coronary Intervention

The introduction of percutaneous coronary intervention (PCI) substantially changed the treatment of patients with coronary artery disease. Stent thrombosis is the most worrisome early complication in patients undergoing PCI. Therefore, antiplatelet therapy forms an integral component of treatment with intracoronary stent implantation. A multitude of randomized and observational studies have helped identify and define the role of clopidogrel in today's PCI patient. Although much is known about its use, a number of questions still remain.
Mobility Improvement and Microwave Characterization of a Graphene Field Effect Transistor With Silicon Nitride Gate Dielectrics

We report on the influence of a silicon nitride gate dielectric in graphene-based field-effect transistors (FETs). The silicon nitride is formed by a plasma-enhanced chemical vapor deposition method. The process is based on a low-density plasma at a high pressure (1 torr), which results in a low degradation of the graphene lattice during the top-gate formation process. Microwave measurements of the graphene FET show a cutoff frequency of 8.8 GHz for a gate length of 1.3 μm. A carrier mobility of 3800 cm2/V·s at room temperature was extracted from the dc characteristic.
Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the beta 2-microglobulin gene

Mice infected intracerebrally with lymphocytic choriomeningitis virus (LCM virus) develop a characteristic central nervous system disease and usually die. If the intravenous or intraperitoneal route is used, the infection leads to less severe clinical signs and the virus is eliminated. Illness and virus clearance are immunological phenomena, which are assumed to be caused exclusively by CD8+ T lymphocytes. In contrast, of the two phases of a delayed-type hypersensitivity reaction caused by inoculation of the virus into the mouse's foot, only the first is mediated by CD8+ cells, whereas the second is mediated by CD4+ cells. We have examined LCM virus-specific immune responses in mice devoid of CD8+ T lymphocytes as a result of disruption of the beta 2-microglobulin gene. As expected, the virus persisted but footpad swelling did not occur, although intracerebral infection resulted in CD4+ T-lymphocyte-mediated illness and antiviral antibodies were produced. Different results had been obtained by Fung-Leung et al. (W.-P. Fung-Leung, T. M. Kündig, R. M. Zinkernagel, and T. W. Mak, J. Exp. Med. 174:1425-1429, 1991), who, is essentially identical experiments but with mice lacking CD8+ T lymphocytes as a result of disruption of the Lyt-2-encoding gene, recorded control of the infection and development of a local delayed-type hypersensitivity reaction. We consider these differences important, because they provide us with clues that may help to understand the mode of action of the CD8+ T cells in cell-mediated antiviral immunity.
Spike-Based Plasticity Circuits for Always-on On-Line Learning in Neuromorphic Systems

Event-driven neuromorphic hardware with on-line learning capabilities enables the low-power local processing of signals on the edge sensors. Implementing such hardware requires having an always-on online learning operation in order to continuously adapt to the changes in the environment. Therefore, as the data is continuously streaming, there cannot be a separation between the training and the testing phase. Such constraint thus asks for a continuous time learning strategy which includes a mechanism to stop changing the weights when the system has reached an optimal operating point, so that it does not over-fit the input data and it generalizes to unseen patterns of the learned class. In this paper we propose spike-based circuits based on a local gradient-descent based learning rule that comprise also this additional “stop-learning” feature and that have a wide range of configurability options over the learning parameters. We describe the circuit behavior and present simulation results for a standard CMOS 180 nm process, showing how the width of the stop-learning region can be controlled along with the learning rate of the system. Such system represents a hardware implementation of a feature which has shown to improves the stability of the learning process and the convergence properties of the network.
A Data-Intensive FLAC3D Computation Model: Application of Geospatial Big Data to Predict Mining Induced Subsidence

Big data are widely used in various fields. However, the application of big data is rare in the study of predicting surface subsidence caused by underground mining. Traditional research has the problem of oversimplifying geological mining conditions. In the context of geospatial big data, a data-intensive FLAC3D (Fast Lagrangian Analysis of a Continua in 3 Dimensions) model is proposed in this paper based on CAD software (Rhinoceros) and borehole logs. The data-intensive FLAC3D model was developed using Rhinoceros software to visualize borehole logs in three dimensions. In the three dimensional modeling process, based on the characteristics of the FLAC3D model and borehole logs, we developed a method to handle geospatial big data and were able to make full use of borehole logs. The effectiveness of the proposed method was verified by comparing the results of the traditional method, proposed method and 70 observation points on the surface. This study shows that the proposed method has obvious advantages over the traditional prediction results. Compared with the traditional prediction results, the relative error of the surface maximum subsidence predicted by the proposed method decreased by 93.7% and the standard deviation of the prediction results (which was 70 points) decreased by 39.4%, on average. The proposed method is the first method to geospatial big data into the mining subsidence prediction research, which is of great significance for improving the accuracy of mining subsidence predictions.
Antimicrobial Tolerance of Pseudomonas aeruginosa Biofilms Is Activated during an Early Developmental Stage and Requires the Two-Component Hybrid SagS

ABSTRACT A hallmark characteristic of biofilms is their extraordinary tolerance to antimicrobial agents. While multiple factors are thought to contribute to the high level of antimicrobial tolerance of biofilms, little is known about the timing of induction of biofilm tolerance. Here, we asked when over the course of their development do biofilms gain their tolerance to antimicrobial agents? We demonstrate that in Pseudomonas aeruginosa, biofilm tolerance is linked to biofilm development, with transition to the irreversible attachment stage regulated by the two-component hybrid SagS, marking the timing when biofilms switch to the high-level tolerance phenotype. Inactivation of sagS rendered biofilms but not planktonic cells more susceptible to tobramycin, norfloxacin, and hydrogen peroxide. Moreover, inactivation of sagS also eliminated the recalcitrance of biofilms to killing by bactericidal antimicrobial agents, a phenotype comparable to that observed upon inactivation of brlR, which encodes a MerR-like transcriptional regulator required for biofilm tolerance. Multicopy expression of brlR in a ΔsagS mutant restored biofilm resistance and recalcitrance to killing by bactericidal antibiotics to wild-type levels. In contrast, expression of sagS did not restore the susceptibility phenotype of ΔbrlR mutant biofilms to wild-type levels, indicating that BrlR functions downstream of SagS. Inactivation of sagS correlated with reduced BrlR levels in biofilms, with the produced BrlR being impaired in binding to the previously described BrlR-activated promoters of the two multidrug efflux pump operons mexAB-oprM and mexEF-oprN. Our findings demonstrate that biofilm tolerance is linked to early biofilm development and SagS, with SagS contributing indirectly to BrlR activation.
Novel Charge-Metering Stimulus Amplifier for Biomimetic Implantable Prosthesis

A novel charge-metering stimulus amplifier is proposed for high performance neural prosthesis stimulation. The new charge-based approach with feedback has low charge error 0.5%, low charge imbalance 0.2%, and high power efficiency. Charge-metering stimulus amplifier can be implemented using advanced 0.18mum CMOS technology and is compatible with mixed-signal system-on-a-chip (SoC) implantable devices. It also has the capability to monitor the electrode-tissue contact quality and estimate the interface impedance in real-time for robust stimulation.
CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Hypertension Is Harmful to Dialysis Patients and Should Be Controlled

Managing hypertension is among the commonest and most challenging features of end‐stage renal disease and many clinical trials have shown the benefit of treating hypertension in the general population. If associations between blood pressure levels and cardiovascular outcomes in dialysis patients mirrored those seen in general population studies, one could argue that dialysis population‐specific antihypertensive trials are unnecessary. Associations between blood pressure levels and outcomes are complex in this population. Naturally, comparisons of observational and experimental findings within intervention in patients with chronic kidney disease often show a surprising degree of disparity. In addition, the possibility of serious unmeasured co‐morbid illnesses masking the true causal relationship between blood pressure and outcomes in this population looms large. Unfortunately, therefore, observational studies appear to be highly unreliable guides to identifying the truth regarding optimal management of hypertension. It appears, then, that controlled trials, alone, can inform appropriate treatment. Of late, intervention trials of antihypertensives in dialysis patients have begun to emerge. Though mostly small, less than definitive, and heterogeneous regarding patient selection, interventions and outcomes, several suggest net benefit and none suggests net harm. As dialysis patients are at vast cardiovascular risk, these findings suggest that aggressive treatment of hypertension should be the default approach, until large clinical trials show otherwise.