bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of formulation and route of administration on the systemic availability of Ex‐RAD®, a new radioprotectant, in preclinical species
Authors: Chun Amy W. , Freshwater Robert E. , Taft David R. , Gillum Amanda M. , Maniar Manoj 
Published: January 2011

AbstractON 01210.Na (Ex‐RAD®) is a novel small molecule under development by Onconova Therapeutics, Inc. as a radiation protection agent. The purpose of this investigation was to evaluate the effect of various formulation approaches on the systemic exposure of ON 01210.Na.In vitroexperiments were used to characterize the plasma binding and metabolic stability of ON 01210.Na using hepatocytes from several animal species (mouse, rat, rabbit, dog, monkey and human).In vivostudies were performed in rats, rabbits, dogs and monkeys, and involved several routes of administration (intravenous, subcutaneous, oral). Plasma protein binding was high across species (>83%), and the rate of ON 01210.Na metabolism was highest in rat and mouse hepatocytes. After intravenous administration, ON 01210.Na demonstrated biphasic elimination from the plasma. Systemic exposure parameters (Cmax,AUC) were dose‐proportional up to 100 mg/kg. Following subcutaneous dosing, ON 01210.Na showed relatively low bioavailability upon administration of the suspension formulation. Developing a solution formulation significantly increased the bioavailability of the drug. This solution formulation demonstrated significant oral bioavailability in rabbit (70%) and monkey (30%). The findings from these preclinical studies provide an overview of the systemic disposition of ON 01210.Na, aiding in the development of optimal formulations and routes of administration for pivotal animal efficacy and clinical safety studies. A solution formulation of ON 01210.Na for s.c. administration is being developed, in addition to an oral dosage form for potential use of the compound as a radioprotectant and a radiation‐mitigating agent in wider military and civilian populations. Copyright © 2011 John Wiley & Sons, Ltd.
Detecting and adjusting for small‐study effects in meta‐analysis
Authors: Rücker Gerta , Carpenter James R. , Schwarzer Guido 
Published: January 2011

AbstractPublication bias and related types of small‐study effects threaten the validity of systematic reviews. The existence of small‐study effects has been demonstrated in empirical studies. Small‐study effects are graphically diagnosed by inspection of the funnel plot. Though observed funnel plot asymmetry cannot be easily linked to a specific reason, tests based on funnel plot asymmetry have been proposed. Beyond a vast range of funnel plot tests, there exist several methods for adjusting treatment effect estimates for these biases. In this article, we consider the trim‐and‐fill method, the Copas selection model, and more recent regression‐based approaches. The methods are exemplified using a meta‐analysis from the literature and compared in a simulation study, based on binary response data. They are also applied to a large set of meta‐analyses. Some fundamental differences between the approaches are discussed. An assumption common to the trim‐and‐fill method and the Copas selection model is that the small‐study effect is caused by selection. The trim‐and‐fill method corresponds to an unknown implicit model generated by the symmetry assumption, whereas the Copas selection model is a parametric statistical model. However, it requires a sensitivity analysis. Regression‐based approaches are easier to implement and not based on a specific selection model. Both simulations and applications suggest that in the presence of strong selection both the trim‐and‐fill method and the Copas selection model may not fully eliminate bias, while regression‐based approaches seem to be a promising alternative.
How to quantify protein diffusion in the bacterial membrane
Authors: van den Wildenberg Siet M. J. L. , Bollen Yves J. M. , Peterman Erwin J. G. 
Published: January 2011

AbstractLateral diffusion of proteins in the plane of a biological membrane is important for many vital processes, including energy conversion, signaling, chemotaxis, cell division, protein insertion, and secretion. In bacteria, all these functions are located in a single membrane. Therefore, quantitative measurements of protein diffusion in bacterial membranes can provide insight into many important processes. Diffusion of membrane proteins in eukaryotes has been studied in detail using various experimental techniques, including fluorescence correlation spectroscopy (FCS), fluorescence recovery after photobleaching (FRAP), and particle tracking using single‐molecule fluorescence (SMF) microscopy. In case of bacteria, such experiments are intrinsically difficult due to the small size of the cells. Here, we review these experimental approaches to quantify diffusion in general and their strengths and weaknesses when applied to bacteria. In addition, we propose a method to extract multiple diffusion coefficients from trajectories obtained from SMF data, using cumulative probability distributions (CPDs). We demonstrate the power of this approach by quantifying the heterogeneous diffusion of the bacterial membrane protein TatA, which forms a pore for the translocation of folded proteins. Using computer simulations, we study the effect of cell dimensions and membrane curvature on measured CPDs. We find that at least two mobile populations with distinct diffusion coefficients (of 7 and 169 nm2 ms−1, respectively) are necessary to explain the experimental data. The approach described here should be widely applicable for the quantification of membrane‐protein diffusion in living bacteria. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 312–321, 2011.
Chain‐to‐chain inventory transshipment model and robust switch control in CSC networks
Authors: Li Jizi , Xiong Naixue , Park Jong Hyuk , Liu Chunling , Ma Shihua , Sun Linfu 
Published: January 2011

SUMMARYOn the basis of CSC (Cluster Supply Chain) networks with two four‐echelon single supply chains, chain‐to‐chain inventory transshipment between two retailers is taken into account in the context of the two single chains cooperation. The uncertain robust switched control system model is built. Meanwhile, the methodology of robust optimization is introduced to minimize the bullwhip effect, and the solution of optimal decision serials is explored utilizing H‐infinity switched control algorithm. The online decision‐making simulation framework structure is developed to demonstrate the switching procedure. The simulation example proves that chain‐to‐chain inventory transshipment in CSC networks and robust switch control method can effectively weaken the bullwhip effect, reduce stock, dwindle fluctuation of order, and improve response to cluster market. Copyright © 2011 John Wiley & Sons, Ltd.
Nitric Oxide Transport in Blood: A Third Gas in the Respiratory Cycle
Authors: Doctor Allan , Stamler Jonathan S. 
Published: January 2011

AbstractThe trapping, processing, and delivery of nitric oxide (NO) bioactivity by red blood cells (RBCs) have emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We present here an expanded paradigm for the human respiratory cycle based on the coordinated transport of three gases: NO, O2, and CO2. By linking O2and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2availability in the lung and to O2need in the periphery. The elements required for regulated O2‐based signal transduction via controlled NO processing within RBCs are presented herein, includingS‐nitrosothiol (SNO) synthesis by hemoglobin and O2‐regulated delivery of NO bioactivity (capture, activation, and delivery of NO groups at sites remote from NO synthesis by NO synthase). The role of NO transport in the respiratory cycle at molecular, microcirculatory, and system levels is reviewed. We elucidate the mechanism through which regulated NO transport in blood supports O2homeostasis, not only through adaptive regulation of regional systemic blood flow but also by optimizing ventilation‐perfusion matching in the lung. Furthermore, we discuss the role of NO transport in the central control of breathing and in baroreceptor control of blood pressure, which subserve O2supply to tissue. Additionally, malfunctions of this transport and signaling system that are implicated in a wide array of human pathophysiologies are described. Understanding the (dys)function of NO processing in blood is a prerequisite for the development of novel therapies that target the vasoactive capacities of RBCs. © 2011 American Physiological Society.Compr Physiol1:541‐568, 2011.
Carbon Monoxide Transport and Actions in Blood and Tissues
Authors: Thom Stephen R. 
Published: January 2011

AbstractThis chapter will discuss the transport of carbon monoxide (CO) from the environment to the tissues of the body and physiological effects on blood‐borne cells and perivascular tissues. It will review the physiology of CO exchange between alveolar gas and pulmonary capillary blood, dynamics of hemoglobin transport, the effects of CO on blood elements, and the effects of CO on extravascular tissues at the capillary bed. Effects of CO from exogenous and endogenous sources on the activities of different proteins will be reviewed. Because CO binds competitively to heme‐containing proteins its effects depend on CO concentration relative to alternative ligands. Therefore, some discussion is devoted to how nitric oxide and hydrogen sulfide influence CO effects. © 2011 American Physiological Society.Compr Physiol1:421‐446, 2011.
A novel theory on parallel repeater‐insertion methodologies for long on‐chip interconnects
Authors: Awwad Falah R. , Nekili Mohamed , Sawan Mohamad 
Published: January 2011

SUMMARYRepeaters are now widely used to enhance the performance of long on‐chip interconnects in CMOS devices. For RC‐as well as RLC‐modeled interconnects, parallel repeaters (PRs) have proved to be superior to serial ones. In a previous work, a new regeneration technique, named variable‐segment, was proven to outperform other existing regeneration techniques including variable‐repeater techniques. In this paper, an approximate analytical delay model is presented for both the variable‐repeater and variable‐segment parallel regeneration techniques. This model is used to confirm the optimality of our design and is built based on first and second‐moment transfer functions, which take into account the inductive effects of interconnects. HSpice electrical and C + +/MATLAB simulations are conducted to assess the performance of the proposed optimization methodology using 0.25‐µm CMOS technology. The mathematical simulation results are remarkably in agreement with those obtained from electrically simulated variable‐repeater and variable‐segment structures which are used in this work to regenerate interconnect lengths ranging from 0.1 to 10 cm. This work is part of a first‐of‐its‐kind global theory on PRs in repeater‐insertion methodologies for long on‐chip interconnects. This theory aims at exploring the different degrees of freedom in interconnect modeling as well as repeater type and design parameters. Copyright © 2011 John Wiley & Sons, Ltd.
Current‐fed isolated PFC pre‐regulator for multiple LED lamps with extended lifetime
Authors: Qu Xiaohui , Wong Siu‐Chung , Tse Chi K. 
Published: January 2011

SUMMARYTo emit high‐quality LED light, one or a bin of LED lamp(s) is normally driven by a PWM‐controlled constant current source to minimize device variation and achieve accurate brightness control. Powered from offline AC mains, the front‐end power converters should provide a relatively low DC voltage bus for the inputs of post‐end LED current regulators. To match the long lifetime of LEDs, the whole LED driver (ballast) should work as durably as the LEDs. However, the lifetime of the driver is usually limited by the high‐voltage electrolytic charge storage capacitors used in conventional PFC pre‐regulators. In this paper, our previously proposed resonant current‐fed isolated PFC pre‐regulator is extended to operate in discontinuous conduction mode (DCM). It allows the use of the low‐voltage storage capacitors on the transformer secondary, and therefore extends the overall lifetime of the LED lighting system. A detailed procedure for finding the expected lifetime of the low‐voltage electrolytic capacitor is given. As before, the high‐voltage stress on the main switches, which is typical in current‐fed isolated converters, is reduced substantially by taking advantage of the transformer leakage inductance necessary for resonance. Additionally, high efficiency is ensured by the use of dual non‐cascading structures. Steady‐state state‐space averaging analysis is performed for designing the converter in DCM operation. A prototype converter is built to verify performance of the proposed PFC LED pre‐regulator. Copyright © 2011 John Wiley & Sons, Ltd.
Critical factors of indirect determination of 3‐chloropropane‐1,2‐diol esters
Authors: Hrncirik Karel , Zelinkova Zuzana , Ermacora Alessia 
Published: January 2011

AbstractSeveral indirect methods have been developed for the determination of 3‐chloropropane‐1,2‐diol (3‐MCPD) esters in fat matrices, but the variation between these methods leads to an uncertainty about the comparison of the results. All the indirect methods are based on the conversion of 3‐MCPD esters into free 3‐MCPD upon transesterification (either in acid or alkaline solution), its purification, derivatisation and instrumental analysis. In this study, major critical factors of the methodology, particularly transesterification, salting out and the choice of internal standard, were evaluated. 3‐MCPD showed low stability under the conditions of alkaline transesterification (only around 40% recovery) affecting the sensitivity of the method. Furthermore, the results obtained within the first 1–2 min were 10–20% higher than those obtained at longer (5–10 min) transesterification time. A comparison of results obtained by using two different internal standards (free or esterified form of deuterated 3‐MCPD) revealed a slight overestimation (7–15%) when free deuterated 3‐MCPD was used, which may be possibly explained by the different behaviour of the both forms during alkaline transesterification. The use of different salts and pH values of the reaction medium during salting out step had a major impact on the results due to the formation of additional 3‐MCPD. Other compounds, like glycidyl esters, present in oil samples may be converted to 3‐MCPD during this step, however, the conversion was not complete and varied substantially (12–93%) in dependence on the pH value of the medium. The method based on acid transesterification showed better selectivity and robustness.
Survey of US academic hospitalist leaders about mentorship and academic activities in hospitalist groups
Authors: Harrison Rebecca , Hunter Alan J. , Sharpe Bradley , Auerbach Andrew D. 
Published: January 2011

AbstractBACKGROUND:Few data describe the structure, activities, and goals of academic hospital medicine groups.METHODS:We carried out a cross sectional email survey of academic hospitalist leaders. Our survey asked about group resources, services, recruitment and growth, as well as mentoring of faculty, future priorities, and general impressions of group stability.RESULTS:A total of 57 of 142 (40%) potential hospitalist leaders responded to our email survey. Hospitalist groups were generally young (<5 years old). Hospitalist group leaders worried about adequate mentorship and burnout while placing a high priority on avoiding physician turnover. However, most groups also placed a high priority on expanding nonclinical activities (teaching, research, etc.). Leaders felt financially and philosophically unsupported, a sentiment which seemed to stem from being viewed primarily as a clinical rather than an academic service.CONCLUSION:Academic hospital medicine groups have an acute need for mentoring and career development programs. These programs should target both individual hospitalists and their leaders while also helping to enhance scholarly work. Journal of Hospital Medicine 2011;6:5–9. © 2011 Society of Hospital Medicine.
Production of biodiesel with glycerol carbonate by non‐catalytic supercritical dimethyl carbonate
Authors: Ilham Zul , Saka Shiro 
Published: January 2011

AbstractNew biodiesel production processes comprising one‐step and two‐step supercritical dimethyl carbonate methods have been pioneered. The use of dimethyl carbonate allows the reaction conditions to be mild and thus avoid unwanted deterioration of substrates during reaction. In this process, without any catalyst applied, supercritical dimethyl carbonate converts triglycerides (rapeseed oil) into fatty acid methyl esters (FAME) along with glycerol carbonate as a value‐added by‐product, instead of glycerol. Free fatty acids could be also converted into FAME so that the total yield of biodiesel for both methods resulted in over 96 wt%. In addition, the produced FAME satisfy the fuel requirements for the international standards of biodiesel specification.
Reversed‐phase analysis of triacylglycerols by ultra performance liquid chromatography‐evaporative light scattering detection (UPLC‐ELSD)
Authors: Ross Keri L. , Hansen Steven L. , Tu Travis 
Published: January 2011

AbstractAn improved reversed‐phase (RP) method has been developed for the analysis of triacylglycerols (TAG) in fats and oils. This method has shown superior performance over traditional reversed‐phase liquid chromatographic (LC) methods in speed and resolution, and equivalent to superior performance in quantitation accuracy (101%–109%) and reproducibility (1.3%–5.8% RSD). The method can easily be adjusted for use with different oils by simple modification of the gradient and run time. Additionally, a mobile phase is used that is compatible with liquid chromatography/mass spectrometry (LC/MS) that when required, can aid in identification of TAG, for which many standards do not exist. This method is suited to a broad number of applications including (but not limited to) research and development of new oils, quality control, production of industrial or edible oils, and seed strain selection.
Pharmacological postconditioning protects against hepatic ischemia/reperfusion injury a
Authors: Dal Ponte Caterina , Alchera Elisa , Follenzi Antonia , Imarisio Chiara , Prat Maria , Albano Emanuele , Carini Rita 
Published: January 2011

Abstract
Postconditioning is a procedure based on the induction of intracellular protective reactions immediately after the onset of reperfusion. Because of the growing need to prevent ischemia/reperfusion (I/R) injury during liver surgery and transplantation, we investigated the possibility of pharmacologically inducing hepatic postconditioning. The effects of the adenosine A2A receptor agonist 2p-(2-carboxyethyl)-phenyl-amino-5′-N-ethylcarboxyamido-adenosine (CGS21680; 5 μmol/L) and the phosphatase and tensin homologue deleted from chromosome 10 (PTEN) inhibitor dipotassium bisperoxo-(5-hydroxypyridine-2-carboxyl)-oxovanadate [bpV(HOpic); 250 nmol/L] were investigated in primary rat hepatocytes during reoxygenation after 24 hours of cold storage and in an in vivo model of rat liver warm I/R. The addition of CGS21680 at reoxygenation significantly reduced hepatocyte death through the activation of the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB)/Akt signal pathway and through the reduction of the intracellular level of PTEN. PTEN lowering was associated with the increased generation of reactive oxygen species after A2A receptor-mediated stimulation of β-nicotinamide adenine dinucleotide phosphate oxidase (NOX). The inhibition of PI3K or NOX with wortmannin or diphenyleneiodonium chloride, respectively, and the addition of the antioxidant N,N′-diphenyl-p-phenylenediamine reversed the effects of CGS21680. The PTEN inhibitor bpV(HOpic) mimicked the protection provided by CGS21680 against reoxygenation damage. An in vivo rat treatment with CGS21680 or bpV(HOpic) during reperfusion after 1 hour of partial hepatic ischemia also promoted PKB/Akt activation and ameliorated alanine aminotransferase release and histological lesions induced by 2 hours of reperfusion. We conclude that adenosine A2A receptor agonists and PTEN inhibitors are possibly useful agents for the pharmacological induction of postconditioning in the liver.
Liver Transpl, 2011. © 2011 AASLD.
Transplantation for liver failure in patients with sickle cell disease
Authors: Hurtova Monika , Bachir Dora , Lee Ketty , Calderaro Julien , Decaens Thomas , Kluger Michael D. , Zafrani Elie Serge , Cherqui Daniel , Mallat Ariane , Galactéros Frédéric , Duvoux Christophe 
Published: January 2011

Abstract
Sickle cell disease (SCD) frequently affects the liver; if acute liver failure (ALF) develops, the only potentially effective therapeutic option is liver transplantation (LT). Only 12 patients for whom LT was performed for SCD-related ALF have been described so far. We report a retrospective series of 6 adult patients with SCD (3 men and 3 women, median age = 40.1 years) who underwent emergency LT. The indication for LT was ALF complicating cirrhosis in 5 patients (hepatitis C/iron overload-induced cirrhosis in 3 and iron overload-induced cirrhosis in 2); one patient had autoimmune hepatitis. The median follow-up was 52.7 months (0.5-123 months). The 1-, 3-, 5-, and 10-year survival rates were 83.3%, 66.7%, 44.4%, and 44.4%, respectively. One patient died of hepatocellular failure precipitated by hyperacute allograft rejection on post-LT day 10. Soon after LT, 2 patients developed seizures; in 1 case, the seizures were a complication of early calcineurin inhibitor-induced leukoencephalopathy. Four long-term survivors benefited from specific management of SCD; specifically, the hemoglobin S fraction was maintained below 30% and the total hemoglobin level was maintained between 8 and 10 g/dL. Two patients had mild vaso-occlusive crises. Three patients experienced a recurrence of hepatitis C virus (HCV) infection; 2 of these patients experienced reversible neurological complications while they were receiving antiviral treatment. Carefully selected patients with SCD may benefit from emergency LT. However, such patients seem to be particularly susceptible to neurological complications after LT. In contrast, severe SCD-related crises do not seem to recur if specific management is provided. Outcomes may be improved if the neurological complications can be minimized; for example, the administration of a calcineurin inhibitor can be delayed, and the management of HCV infection recurrence can be improved.
Liver Transpl, 2011. © 2011 AASLD.