Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of oral vitamin D(3) and calcifediol.

AIM Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens. METHODS In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitamin D(3) daily, 140 μg calcifediol or vitamin D(3) weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitamin D(3), or both. 25(OH)D3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants. RESULTS For daily (weekly) dosing, the area under the concentration–time curve (AUC0–24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D3. After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D3 AUC0–96h values than 140 μg vitamin D3, while the simultaneous intake of both did not further increase exposure. CONCLUSIONS Calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.
How to improve tourism energy efficiency to achieve sustainable tourism: evidence from China

ABSTRACT This study constructs the biennial Malmquist index, including undesirable outputs, to evaluate tourism energy efficiency and decompose its changes using a sample of 30 provinces in China over the period of 9 years from 2005 to 2013. The changes in tourism energy efficiency can be attributed to five factors, including total factor productivity, capital-energy ratio, labour-energy ratio, energy supply composition and output composition. The study results show that the energy efficiency of the tourism industry is much lower than that of the industry as a whole and not greener. Total factor productivity is a key positive driving force to boost tourism energy efficiency. Capital-labour ratio gradually overtook the total factor productivity as the tourism energy efficiency change’s largest contribution since 2010 and thus became the biggest inhibitor for increasing tourism energy efficiency. The rational utilization of capital and new capital investment should accompany energy-saving technology and is essential for sustainable tourism.
The Cytoplasmic Tail of Large Conductance, Voltage- and Ca2+-activated K+ (MaxiK) Channel Is Necessary for Its Cell Surface Expression*

The large conductance, voltage- and Ca2+-activated K+ channel (MaxiK) is expressed in several renal segments and functions in cell volume regulation and flow-mediated K+ secretion. Previously, we cloned two MaxiK channel isoforms, named rbslo1 and rbslo2, from rabbit renal cells. rbslo1 has a 58-amino acid insertion after the S8 hydrophobic domain, whereas rbslo2 is truncated and cannot be activated. Here we use the sequence differences between the two variants to examine their plasma membrane processing. Plasma membrane localization of rbslo1 and 2 expressed in HEK293 cells was assayed by electrophysiology, immunocytochemistry, and biochemistry studies. Consistent with its functional silence, rbslo2 localized primarily within the cytoplasm, presumably in the endoplasmic reticulum and Golgi region. Coexpression with MaxiK β subunits did not alter the cellular localization of either rbslo1 or rbslo2. When rbslo1 and 2 are cotransfected in non-polarized cells, they colocalized primarily within the cell with only rbslo1 detected at the plasma membrane. When transfected into polarized, medullary-thick ascending limb (mTAL) cells, rbslo1 is expressed at the apical membrane whereas the majority of rbslo2 localized throughout the cytoplasm. Given the high degree of similarity between the two isoforms, we conclude that the cytoplasmic tail of rbslo1 is important for the cell surface expression of MaxiK channels.
Reference Command Tracking for a Linearized Model of an Air-breathing Hypersonic Vehicle

The focus of this paper is on control design and simulation for an air-breathing hypersonic vehicle. The challenges for control design in this class of vehicles lie in the inherent coupling between the propulsion system, and the airframe dynamics, and the presence of strong exibilit y eects. Working from a highly nonlinear, dynamically-coupled simulation model, control designs are presented for velocity, angle-of-attack, and altitude command input tracking for a linearized version of a generic air-breathing hypersonic vehicle model linearized about a specic trim condition. Control inputs for this study include elevator deection, total temperature change across the combustor, and the diuser area ratio. Two control design methods are presented, both using linear quadratic techniques with integral augmentation, and are implemented in tracking control studies. The rst approach focuses on setpoint tracking control, whereas in the second, a regulator design approach is taken. The eectiv eness of each control design is demonstrated in simulation on the full nonlinear model of the generic vehicle.
The experiences of treatment from other people as narrated by people with moderate or severe traumatic brain injury and their close relatives

Purpose. The aim of this study was to describe the treatment from other people as experienced by people with moderate or severe traumatic brain injury (TBI) and their close relatives. Method. Twelve people with moderate or severe TBI and eight of their close relatives were interviewed. The interviews were analysed using thematic content analysis. Results. The results were described by the means of two themes: being excluded and missing confirmation. People with TBI and their close relatives had experiences of being avoided, being ruled by the authorities, being met with distrustfulness and being misjudged. They also searched for answers and longed for the right kind of help. People who listened to them, believed them and tried to understand and help them were appreciated. Conclusions. This study showed a lack of treatment which promotes well-being of the people with TBI and their close relatives. They experienced bad treatment also from authorities. Therefore, we emphasize that authorities should continuously reflect on how to make their practice a place which promotes dignity. Treatment of people with TBI and close relatives may be improved by increased knowledge about TBI, living with it and being a close relative to a person with TBI. This is a challenge to health care and rehabilitation professionals.
Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes

Background Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. Methods Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. Results Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. Conclusions Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.
The secretome of bone marrow mesenchymal stem cells‐conditioned media varies with time and drives a distinct effect on mature neurons and glial cells (primary cultures)

Transplantation of bone marrow mesenchymal stem cells (BM‐MSCs) has been shown to ameliorate the injured central nervous system (CNS). Although these effects were initially attributed to the putative differentiation of MSCs towards the neural lineage, it is now known that most of them are mediated by the secretome. Up to now most in vitro reports have dealt with the effects of the secretome on neural stem cells and their differentiation. Consequently, there is a lack of information regarding the role of the secretome on the viability and survival of pre‐existent matured differentiated cell populations. Moreover, it is also not known how the time points of conditioned media (CM) collection affect such parameters. In the present study, primary cultures of hippocampal neurons and glial cells were incubated with CM obtained from MSCs. To determine how the temporal profiles of CM collection impact on post‐natal neurons and glial cells, we collected MSCs CM at 24, 48, 72 and 96 h of conditioning. MTS test revealed that for the hippocampal cultures the incubation with CM increased cell viability for all time points, with significant increases in the percentage of neurons in culture incubated with CM 24 h. For glial cells only the later time point of CM collection (96 h) increased cell viability. Fluorescence microscopy observations also revealed that CM 48 h and 72 h increased astrocytes percentages, while CM 24 h decreased microglial cell and oligodendrocytes values. These results revealed that post‐natal neuronal and glial cells respond differently to MSCs CM; moreover, there are specific temporal variations in the composition of the CM of MSCs collected at different time points that trigger different effects on mature neurons and the distinct glial cell populations (astrocytes, oligodendrocytes and microglial cells). Copyright © 2011 John Wiley & Sons, Ltd.
Screening of tumor necrosis factor receptor-associated factor 6 as a candidate gene for inflammatory bowel disease

Objective. The two forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of unfavorable genetic and exogenous factors. During a genome-wide linkage study of IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further confirmed upon fine density mapping. This chromosomal region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6 (TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis. Material and methods. Using denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon-intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially screened; this material comprised 20 CD, 39 UC and 36 mixed families. Results. No nucleotide changes in the coding sequence of TRAF6 were detected, but a single-base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7 thymines, respectively) in intron 3 was identified. However, examination of an extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy blood donors failed to show any association with this 7T/8T variation and IBD, nor was this polymorphism related to specific clinical features in IBD. Conclusions. Our study tends to exclude a good positional and functional candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea that the function of TRAF6 is important enough not to permit structural alterations of this mediator.
E$^2$BoWs: An End-to-End Bag-of-Words Model via Deep Convolutional Neural Network

Traditional Bag-of-visual Words (BoWs) model is commonly generated with many steps including local feature extraction, codebook generation, and feature quantization, etc. Those steps are relatively independent with each other and are hard to be jointly optimized. Moreover, the dependency on hand-crafted local feature makes BoWs model not effective in conveying high-level semantics. These issues largely hinder the performance of BoWs model in large-scale image applications. To conquer these issues, we propose an End-to-End BoWs (E$^2$BoWs) model based on Deep Convolutional Neural Network (DCNN). Our model takes an image as input, then identifies and separates the semantic objects in it, and finally outputs the visual words with high semantic discriminative power. Specifically, our model firstly generates Semantic Feature Maps (SFMs) corresponding to different object categories through convolutional layers, then introduces Bag-of-Words Layers (BoWL) to generate visual words for each individual feature map. We also introduce a novel learning algorithm to reinforce the sparsity of the generated E$^2$BoWs model, which further ensures the time and memory efficiency. We evaluate the proposed E$^2$BoWs model on several image search datasets including CIFAR-10, CIFAR-100, MIRFLICKR-25K and NUS-WIDE. Experimental results show that our method achieves promising accuracy and efficiency compared with recent deep learning based retrieval works.
Evidence for isofunctional enzymes in the degradation of phenol, m- and p-toluate, and p-cresol via catechol meta-cleavage pathways in Alcaligenes eutrophus

A study of the degradation of phenol, p-cresol, and m- and p-toluate by Alcaligenes eutrophus 345 has provided evidence that these compounds are metabolized via separate catechol meta-cleavage pathways. Analysis of the enzymes synthesized by wild-type and mutant strains and by strains cured of the plasmid pRA1000, which encodes m- and p-toluate degradation, indicated that two or more isofunctional enzymes mediated several steps in the pathway. The formation of three catechol 2,3-oxygenases and two 2-hydroxymuconic semialdehyde hydrolases was indicated from an examination of the ratio of the specific activities of these enzymes against various substrates. Evidence for two 2-hydroxymuconic semialdehyde dehydrogenases, two 4-oxalocrotonate isomerases and decarboxylases, and three 2-ketopent-4-enoate hydratases was derived from the induction of these enzymes under different growth conditions. Each activity was detected when the wild type was grown in the presence of m-toluate, but not when grown with phenol (except for a hydratase) or p-cresol, whereas in strains cured of pRA1000, growth with phenol or p-cresol, but not with m-toluate, induced these enzymes. Hydroxylation of phenol and p-cresol appears to be mediated by the same enzyme.
Stabilized helical peptides: overview of the technologies and therapeutic promises

Introduction: Helical structures in proteins and naturally occurring peptides play a major role in a variety of biological processes by mediating interactions with proteins and other macromolecules such as nucleic acids and lipid membranes. The use of short synthetic peptides encompassing helical segments to modulate or disrupt such interactions, when associated with human diseases, represents great pharmacological interest. Areas covered: Multiple chemical approaches have been developed to increase the conformational and metabolic stabilities of helical peptides and to improve their biomedical potential. After a brief overview of these technologies and the most recent developments, this review will focus on the main therapeutic areas and targets and will discuss their promise. Expert opinion: Potential benefits associated with increased helix stability extend beyond simple affinity enhancement. Some peptidomimetic helices are being endowed with features desirable for cellular activity such as increased resistance to proteolysis and/or cell permeability. Recent advances in the field of peptide and related peptidomimetic helices are not just conceptual, but are likely to be of practical utility in the process of optimizing peptides as clinical candidates, and developing medium-size therapeutics.
Systemic Inflammatory Response during Cardiac Surgery: A Pilot Study

Objective There is a growing body of evidence indicating that perioperative fluid management during cardiac surgery influences patient care and outcome. The choice of fluid therapy and the degree of systemic inflammatory response triggered during surgery control the effects of tissue edema formation and end-organ function. As such, “goal-directed” fluid resuscitation protocols that measure colloid osmotic pressure (COP) may promote improvements in patient morbidity and mortality. Methods Thirty patients scheduled for primary coronary artery bypass grafting were prospectively randomized for perioperative fluid treatment under COP guidance [albumin (ALB), n = 17] or conventional fluid protocols without COP support (control, n = 13). Whole-blood samples were drawn at four different time intervals including (A) anesthesia induction, (B) 10 minutes after the initiation of cardiopulmonary bypass, (C) at the completion of sternal skin approximation, and (D) 3 hours after admission to the cardiac intensive care unit. Interleukin 6 (IL-6) and IL-8 were measured by immunometric, enzyme-linked immunosorbent assays as well as C-reactive protein. Colloid osmotic pressure values were measured using a colloid osmometer. Results As compared with conventional fluid protocols, the patients treated in the intervention (ALB) group received significantly less total perioperative fluid [7893.6 (1874.5) vs 10,754.8 (2403.9), P = 0.001], and this relationship remained after controlling for age, sex, and The Society of Thoracic Surgeons risk score (β = −0.5, t = −3.1, P = 0.005). Colloid osmotic pressure values were significantly higher in the ALB group at time point D after surgery (P= 0.03). There were no significant differences in IL-6, IL-8, and C-reactive protein values between the groups at any of the time blood draw intervals. Perioperative outcomes were evaluated by treatment group. For both groups, the incidence of perioperative morbidity was low and did not differ by treatment group. Conclusions The use of COP-guided fluid resuscitation was associated with a significant reduction in perioperative fluid demand. However, patients prescribed to COP-guided fluid therapy did not experience a reduction in whole-body inflammation or improved surgical outcome as compared with conventional fluid management techniques.
Endoplasmic Reticulum-bound Ribosomes Reside in Stable Association with the Translocon following Termination of Protein Synthesis*

In current views, translation-coupled ribosome binding to the endoplasmic reticulum (ER) membrane is transient, with association occurring via the signal recognition particle pathway and dissociation occurring upon the termination of protein synthesis. Recent studies indicate, however, that ribosomal subunits remain membrane-bound following the termination of protein synthesis. To define the mechanism of post-termination ribosome association with the ER membrane, membrane-bound ribosomes were detergent-solubilized from tissue culture cells at different stages of the protein synthesis cycle, and the composition of the ribosome-associated membrane protein fraction was determined. We report that ribosomes reside in stable association with the Sec61α-translocon following the termination stage of protein synthesis. Additionally, in vitro experiments revealed that solubilized, gradient-purified ribosome-translocon complexes were able to initiate the translation of secretory and cytosolic proteins and were functional in assays of signal sequence recognition. Using this experimental system, synthesis of signal sequence-bearing polypeptides yielded a tight ribosome-translocon junction; synthesis of nascent polypeptides lacking a signal sequence resulted in a disruption of this junction. On the basis of these data, we propose that in situ, ribosomes reside in association with the translocon throughout the cycle of protein synthesis, with membrane release occurring upon translation of proteins lacking topogenic signals.
Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement

The present work aimed to investigate the effect of different concentrations of poloxamer 188, a surfactant, on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles (SLNs) for oral bioavailability enhancement. Microemulsion technique was employed to prepare the SLN formulations having varying concentrations of poloxamer 188, which were subsequently subjected to various in vitro and in vivo evaluations to study their release pattern. On increasing the percentage concentration of poloxamer 188, the bioavailability decreased from 4.91- to 2.84-fold after intraduodenal administration in the male Wister rat. It could be attributed to the increase in particle size as well as reduction in hydrophobicity of SLNs. As indicated by pharmacokinetic data, the AUC(0–t) of all three (SLN) formulations (6.27 ± 0.24 μgh/mL with FZ-1, 4.13 ± 0.11 μgh/mL with FZ-2, and 3.63 ± 0.10 μgh/mL with FZ-3) were significantly higher (p < 0.05) than that of carvedilol suspension (1.27 ± 0.23 μgh/mL). These findings augur well with the possibility of enhancement of the oral bioavailability of drug, via the lymphatic system bypassing hepatic first pass metabolism.
[Detection for severe acute respiratory syndrome (SARS) coronavirus RNA in stool of SARS patients].

OBJECTIVE To investigate excretion of severe acute respiratory syndrome coronavirus RNA (SARS-CoV) in stool of SARS patients. METHODS SARS-CoV RNA was detected in stool specimens with fluorescent quantitative polymerase chain reactions (FQ-PCR) in 101 SARS patients on the 10 to 55 days after onset, 27 non-SARS patients and 400 individuals with health check-up. RESULTS SARS-CoV RNA was positive in stool specimens by FQ-PCR in 58 of 101 SARS patients (57.4%), and all negative in 27 non-SARS patients and 400 healthy individuals. Positive rate of SARS-CoV RNA was 100% (8/8), 67.7% (21/31), 47.4% (27/57) and 40.0% (2/5) on the 10 - 19, 20 - 29, 30 - 39 and 40 - 55 days after onset of fever, respectively, with values of logarithm of SARS-CoV RNA load of 6.06 +/- 2.05, 4.51 +/- 1.23, 3.82 +/- 1.44 and 3.57 +/- 1.25, respectively. CONCLUSION Positive rate and load of SARS-CoV RNA in stool of SARS patients was the highest at their acute phase, and decreased with the extension of its course.