Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological evaluation of RBx-0128, a potent and selective dipeptidyl peptidase-IV inhibitor in type 2 diabetes genetic model

Aim: Dipeptidyl peptidase IV (DPP-IV) inhibition to modulate the incretin effect is a proven strategy to treat type 2 diabetes mellitus. The present study describes the pharmacological profile of a novel DPP-IV inhibitor RBx-0128, as an antidiabetic agent. Material and Methods: DPP-IV assay was carried out to evaluate in vitro potency of RBx-0128 using human, mouse, and rat plasma as an enzyme source. Selectivity was assessed with various serine proteases. In vivo efficacy was assessed in ob/ob mice. The pharmacokinetic (PK) profile was performed in Wistar rats. Results: RBx-0128 inhibited human, mouse, and rat plasma DPP-IV activity with IC50 values of 10.6, 18.1, and 56.0 nM respectively, selective over various serine proteases (900–9000-fold). The inhibition was reversible and competitive in nature. In ob/ob mice, RBx-0128 significantly (P < 0.05) inhibited plasma DPP-IV and stimulated GLP-1 and insulin at 10 mg/kg. In the oral glucose tolerance test (OGTT), glucose lowering effect was better than sitagliptin (23 vs. 17%) at 10 mg/kg. The effect was sustained till 8 hours (30-35%) at 10 mg/kg with favorable PK profile (plasma clearance: 39.3 ml/min/kg; Cmax 790 ng/ml; t1/2 1.6 hours; tmax 4.8 hours, Vss 3.24 l/kg and Foral 55%) in Wistar rats. Conclusions: The present study showed that RBx-0128 is a novel, DPP-IV inhibitor with an antihyperglycemic effect. It can be a promising candidate for the treatment of type 2 diabetes mellitus.
Differences in the protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils following transient global cerebral ischemia

The thioredoxin (Trx) and peroxiredoxin (Prx) redox system is associated with neuronal damage and neuroprotective effects via the regulation of oxidative stress in brain ischemia. In the present study, ischemia-induced changes in the protein expression levels of Trx2 and Prx3 in the stratum pyramidale (SP) of the hippocampal CA1 region were investigated in adult and aged gerbils, subjected to 5 min of transient global cerebral ischemia, using immunohistochemistry and western blot analysis. In the adult ischemia-group, minimal Trx2 immunoreactivity was detected in the SP 2 days after ischemia-reperfusion. In the aged animals, the Trx2 immunoreactivity in the sham-group was marginally lower compared with that in the adult sham-group. In the aged ischemia-group, Trx2 immunoreactivity in the SP was significantly higher 1, 2 and 4 days post-ischemia, compared with that in the adult ischemia-group and, in the 5 days post-ischemia group, Trx2 immunoreactivity was significantly decreased in the SP. Prx3 immunoreactivity in the SP of the adult ischemia-group was significantly decreased from 4 days after ischemia-reperfusion. In the aged animals, Prx3 immunoreactivity in the sham-group was also marginally lower compared with that in the adult sham-group. Prx3 immunoreactivity in the aged ischemia-group was also significantly higher 1, 2 and 4 days post-ischemia, compared with the adult ischemia-group; however, the Prx3 immunoreactivity was significantly decreased 5 days post-ischemia. The western blot analyses revealed that the pattern of changes in the protein levels of Trx2 and Prx3 in the adult and aged hippocampal CA1 region following ischemic damage were similar to the results obtained in the immunohistochemical data. These findings indicated that cerebral ischemia lead to different protein expression levels of Trx2 and Prx3 in the hippocampal CA1 region between adult and aged gerbils, and these differences may be associated with more delayed neuronal death in the aged gerbil hippocampus following transient global cerebral ischemia.
Vitamin D/VDR signaling attenuates lipopolysaccharide-induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier

Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)-induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild-type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS-treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P<0.001), increased alveolar permeability [demonstrated by a higher wet-dry ratio of lung weight (P<0.05), greater expression levels of BALF protein (P<0.001) and fluorescein isothiocyanate-conjugated 4 kDa dextran (P<0.001) leakage into the alveolar space], elevated proinflammatory cytokine and chemokine mRNA levels, as demonstrated by reverse transcription-quantitative polymerase chain reaction (P<0.05), and decreased protein and mRNA expression levels of occludin (P<0.01) and zonula occludens-1 (ZO-1; P<0.01) compared with WT mice. Paricalcitol treatment partially inhibited these pathological changes in WT mice by maintaining the mRNA and protein expression levels of occludin (P<0.01) and ZO-1 (P<0.05). A lack of VDRs in the pulmonary epithelial barrier appeared to compromise its defense, leading to more severe LPS-induced lung injury. Furthermore, vitamin D treatment alleviated LPS-induced lung injury and preserved alveolar barrier function. Therefore vitamin D treatment may present as a potential therapeutic strategy in ALI and acute respiratory distress syndrome.
Internet of Things and Edge Cloud Computing Roadmap for Manufacturing

The manufacturing industry is exploring the use of Internet of Things and cloud computing to enhance the efficiency of manufacturing plant operations, improve product quality, increase manufacturers' ability to respond to changing customer demands, and expand to new markets. Productivity, quality, safety, and the ability to respond quickly to changing conditions are essential to maintaining the industry's competitiveness.
New signal features for robust identification of isolated vowels

Current signal processing techniques do not match the astonishing ability of the Human Auditory System in recognizing isolated vowels, particularly in the case of female or child speech. As didactic and clinical interactive applications are needed using sound as the main medium of interaction, new signal features must be used that capture important perceptual cues more effectively than popular features such as formants. In this paper we propose the new concept of Perceptual Spectral Cluster (PSC) and describe its implementation. Test results are presented for child and adult speech, and indicate that features elicited by the PSC concept permit reliable and robust identification of vowels, even at high pitches.
Analyzing Involvements of Reviewers through Mining a Code Review Repository

In order to assure the quality of software, early detection of defects is highly recommended. Code review is one of effective way for such early detection of defects in software. Code review activities must contain various useful insights for software quality. However, especially in open source software developments, records of code review merely exist. In this study, we try to analyze a code review repository of an open source software, Chromium, which adopts a code review tool in its development.Before analyzing the code review data, we address 7 research questions. We can find interesting answers for these questions by repositories mining.
Structural Behavior of Composite Materials.

Abstract : This study is concerned with the analysis of the structural behavior of composite materials. It is shown that composite materials can be designed to produce a wide range of mechanical properties. Thus, a structural designer now has at his disposal an added dimension in optimum design - the materials optimization. Two types of composite materials are investigated: the unidirectional fiber reinforced composite and the laminated anisotropic composite. Analytical relations are derived between the composite material coefficients and the geometric and material parameters of the constituents. Test specimens made of filament-wound materials are used. The experimental results show that the relations derived in this study are more accurate than existing theories, which include the netting analysis. Reliable data on filament-wound materials, which are now available for the first time, can be used for future investigations of the behavior of filament-wound structures.
An architecture for multi-user software development environments

We present an architecture for multi-user software development environments, covering general, process-centered and rule-based MUSDEs. Our architecture is founded on componentization, with particular concern for the capability to replace the synchronization component–to allow experimentation with novel concurrency control mechanisms–with minimal effects on other components while still suporting integration. The architecture has been implemented for the MARVEL SDE.
Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3–Mediated Calcium Handling in the Vasculature From Hypertensive Rats

Background Mitochondrial Ca2+ homeostasis is fundamental to the regulation of mitochondrial reactive oxygen species (ROS) generation and adenosine triphosphate production. Recently, transient receptor potential channel, canonical type 3 (TRPC3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. Inhibition of TRPC3 attenuates vascular calcium influx in spontaneously hypertensive rats (SHRs). However, it remains elusive whether mitochondrial TRPC3 participates in hypertension by increasing mitochondrial calcium handling and ROS production. Methods and Results In this study we demonstrated increased TRPC3 expression in purified mitochondria in the vasculature from SHRs, which facilitates enhanced mitochondrial calcium uptake and ROS generation compared with Wistar‐Kyoto rats. Furthermore, inhibition of TRPC3 by its specific inhibitor, Pyr3, significantly decreased the vascular mitochondrial ROS production and H2O2 synthesis and increased adenosine triphosphate content. Administration of telmisartan can improve these abnormalities. This beneficial effect was associated with improvement of the mitochondrial respiratory function through recovering the activity of pyruvate dehydrogenase in the vasculature of SHRs. In vivo, chronic administration of telmisartan suppressed TRPC3‐mediated excessive mitochondrial ROS generation and vasoconstriction in the vasculature of SHRs. More importantly, TRPC3 knockout mice exhibited significantly ameliorated hypertension through reduction of angiotensin II–induced mitochondrial ROS generation. Conclusions Together, we give experimental evidence for a potential mechanism by which enhanced TRPC3 activity at the cytoplasmic and mitochondrial levels contributes to redox signaling and calcium dysregulation in the vasculature from SHRs. Angiotensin II or telmisartan can regulate [Ca2+]mito, ROS production, and mitochondrial energy metabolism through targeting TRPC3.
Fathers and work‐life balance in France and the UK: policy and practice

Purpose – This paper seeks to focus on the role of organizations in mediating the impact of national work‐life balance (WLB) policy on employees, in particular fathers.Design/methodology/approach – It presents existing research about WLB policy implementation in organizations as well as the findings of empirical work in insurance and social work in France and the UK (questionnaire survey, case study analysis, interviews with national and sector‐level trade union officials). Findings – These indicate that fathers' take‐up of WLB policies is the outcome of a complex dynamic between national fatherhood regimes, organizational and sector characteristics and the individual employee. They suggest that fathers tend to use WLB measures to spend time with their families where measures increase their sense of entitlement (state policies of paternity leave) or where measures offer non‐gendered flexibility (reduced working time/organizational systems of flexi‐time). In line with other studies it also finds that father.
Inorganic materials and coatings produced by EBPVD

Abstract The present paper describes the process of high speed electron beam evaporation of inorganic substances under vacuum and process parameters controlling the deposition, structure and properties of thick condensates (films). Considered are examples of single phase and multiphase metal, metal–ceramic, cermet and ceramic condensates of the thickness from several micrometres to several millimetres with dispersed, multilayer, porous and graded structures in a broad range of structural element dimensions. Dimensional effects in the structure and mechanical properties of thick condensates are noted. Areas of practical application of inorganic materials deposited from the vapour phase are described.
S5-H7: GaN-HEMT technology for high power millimeter-wave amplifier

In this work, we developed (1) an offset-overhanging Y-shaped gate structure to reduce the electric field at gate-edge, and demonstrated (2) low current collapse of InGaN back barrier structure that improved off-state breakdown voltage. In addition, we adopted (3) an InAlN electron-supplying layer to enhance the drain current. The fabricated InAlN/GaN HEMTs with 80-nm gates showed a high off-state breakdown of 73 V, a high drain current of 1.2 A/mm and a high Pout density of 1 W/mm at 90 GHz.
Distributed strategies for average consensus in directed graphs

We address the average consensus problem for a distributed system whose components (nodes) can exchange information via interconnections (links) that form an arbitrary, strongly connected but possibly directed, topology (graph). Specifically, we discuss how the nodes can asymptotically reach average consensus (i.e., obtain the average of their initial values) with linear-iterative algorithms in which each node updates its value using a weighted linear combination of its own value and the values of neighboring nodes. In the process, the strategies we develop allow the nodes to adapt their weights in a distributed fashion, so that asymptotically they obtain a doubly stochastic weight matrix, which is useful for many algorithms that utilize linear- or nonlinear-iterative schemes to perform various estimation and optimization tasks.
Injectin molding of short fiber reinforced thermoplastics in a center‐gated mold

We have studied injection molding of a rectangular box using short fiber reinforced polypropylene. The fiber orientation distribution and the local stiffness properties in radial and transverse directions have been measured in the bottom plane. The deduced orientation tensors are compared with predictions of a commercial computer code. Discrepancies are related to approximations made in the calculations and effects not accounted for by the present modeling approach. In the calculations the fiber interaction coefficient was varied seeking to fit experiments. We comment on the out-of-plane components of the orientation tensor, the relative thickness of skin and core layers, and the radial dependence of the fiber orientation in each layer. Values of the components of the 4 th -order orientation tensor calculated from the measured orientation distribution are used to compare different closure approximations referred in the literature. Anisotropy in the stiffness properties, calculated from the measured fiber orientation, agree well with measurements.
UvA-DARE ( Digital Academic Repository ) Abnormal blood flow in the sublingual microcirculation at high altitude

We report the first direct observations of deranged microcirculatory blood flow at high altitude, using sidestream dark-field imaging. Images of the sublingual microcirculation were obtained from a group of 12 volunteers during a climbing expedition to Cho Oyu (8,201 m) in the Himalayas. Microcirculatory flow index (MFI) was calculated from the moving images of microcirculatory red blood cell flow, and comparison was made between the baseline and high altitude measurements. Peripheral oxygen saturation (SpO2) and Lake Louise scores (LLS) were recorded along with MFI. Our data demonstrate that there was a significant reduction in MFI from baseline to 4,900 m in small (less than 25 lm) and medium (26–50 lm) sized blood vessels (P = 0.025 and P = 0.046, respectively). There was no significant correlation between MFI and SpO2 or MFI and LLS. Disruption of blood flow within microcirculatory may explain persistent abnormal oxygen flux to tissues following the normalisation of systemic oxygen delivery that accompanies acclimatisation to high altitude.
Sp1‐dependent regulation of the tissue inhibitor of metalloproteinases‐1 promoter

Extracellular matrix (ECM) remodeling is involved in many cellular properties such as division, migration, differentiation, and death. The turnover of ECM is regulated by matrix metalloproteinases (MMPs) and the MMPs are inhibited by the tissue inhibitors of metalloproteinases (TIMPs). In this study, the transcriptional regulation of the TIMP‐1 promoter was investigated. The 5′‐deletion assay showed that the region between −1,200 and −1,101 was responsible for the TIMP‐1 promoter activity. The mutations of the two Sp1 sites in this region reduced the transcription activity. In addition, the co‐transfection with antisense Sp1 oligonucleotide decreased the promoter activity, suggesting that the transcription of the TIMP‐1 promoter is mediated by Sp1. Previously, it was reported that the TIMP‐1 expression was enhanced under hypoxia. Therefore, the TIMP‐1 promoter activity was investigated with or without cobalt ion, which elicits the same physiological effect as hypoxia. The results showed that the TIMP‐1 promoter was induced in the presence of cobalt ion and that the promoter activity was regulated by Sp1 as well as HIF‐1. Therefore, this study suggests that Sp1 is involved in the regulation of the TIMP‐1 promoter in the presence of cobalt ion as well as in the basal level transcription. © 2004 Wiley‐Liss, Inc.
Active Epilepsy as Indicator of Neurocysticercosis in Rural Northwest India

Objective. To determine the contribution of neurocysticercosis as a cause for active epilepsy and to establish Neurocysticercosis as major definable risk of epilepsy in our setup. Methods. We conducted a door-to-door survey of 2,209 individuals of Bhore Pind and Bhore Kullian villages in Chattah zone of district Jammu (Jumma and Kashmir, Northwest India) to identify patients with symptomatic epilepsy. Patients with active epilepsy were investigated with neuroimaging techniques to establish diagnosis of NCC (neurocysticercosis). Results. Among 25 patients with epilepsy 10(40%) had CT/MR evidence of past or recent NCC infection. This gave us the point prevalence of 4.5/1000 for Neurocysticercosis in our study population. Interpretation. The study shows a high prevalence of NCC accounting for symptomatic epilepsy in our part of India.
Popular channel concentration schemes for efficient channel navigation in internet protocol televisions

Internet Protocol Television (IPTV) is becoming increasingly popular as an emerging Internet application due to its variety of contents and services. However, hundreds of IPTV channels make it difficult to find one¿s desired channel. To relieve this problem, this paper presents a popular channel concentration scheme for efficient channel navigation in IPTV. Based on the property that TV channel selections concentrate on several frequently selected channels, the proposed scheme reorganizes channel sequences by clustering popular channels. Specifically, channels are rearranged in a frequency interleaved way to minimize the seek distance. Simulation studies show that the proposed scheme reduces the seek time of IPTV channel navigation significantly when up-down channel selection interfaces are used.
Hypermethylation of the GATA gene family in esophageal cancer

The GATA family of transcription factors promotes the normal development of the gastrointestinal tract during embryogenesis and determines tissue differentiation in adult gut epithelium. Loss of GATA‐4 and GATA‐5 has been reported in human gastric and colon cancer. We examined GATA‐4,‐5 and ‐6 gene expression in established esophageal squamous cancer cell lines and the relationship to DNA methylation in the promoter region of these genes. GATA‐4 and GATA‐5 expression was absent in most esophageal cancer cell lines, but was restored upon treatment with the demethylating agent 5‐aza‐2′‐deoxycytidine. For each of the cell lines without detectable GATA gene expression, aberrant methylation of the promoter region CpG‐island was detected by methylation specific PCR. We confirmed these results with genomic bisulfite sequencing. GATA‐6 expression was found in each of the cell lines. GATA‐4/‐5 promoter methylation was not detected in normal esophageal mucosa, but GATA‐4 methylation was present in 27 of 44 (61%) squamous carcinomas and 31 of 44 (71%) adenocarcinoma of the esophagus, while GATA‐5 methylation was present in 14 of 44 (32%) squamous carcinomas and 24 of 44 (55%) adenocarcinoma of the esophagus. Our studies demonstrate frequent silencing of GATA‐4 and GATA‐5, but not GATA‐6, in human esophageal neoplasia associated with gene promoter hypermethylation. © 2006 Wiley‐Liss, Inc.
Thermal Expansion Coefficients of Unidirectional Composites

An analytical and experimental investigation on thermal expansion coef ficients of unidirectional composites (UD) is carried out. The fiber aniso tropy and temperature dependency of the constituent material properties are considered in the formulation of the problem. The solving technique used here is constructed by a slight modification of the one which was once developed and employed by the authors for calculating elastic moduli of UD. It is shown that α z of UD is approximately given by the modulus modified law of mixture, and that α x 's based on the hexagonal and square array models are almost identical. Some relationships between α's of UD and the constituent material properties are graphically indicated. The first point of the main purpose of the experiments is to reveal certain tempera ture dependent behavior of α's of the constituents of the Carbon-Epoxy. The second is a comparison between the experimental and theoretical re sults of an influence of αm on α x and α z. The third is to estimate unknown αfr and αfz of the carbon fibers. A testing apparatus used here is an interferometric dilatometer using gas Laser which is sensitive enough to measure temperature dependent α's.
Healthy places: exploring the evidence.

"Sense of place" is a widely discussed concept in fields as diverse as geography, environmental psychology, and art, but it has little traction in the field of public health. The health impact of place includes physical, psychological, social, spiritual, and aesthetic outcomes. In this article, the author introduces sense of place as a public health construct. While many recommendations for "good places" are available, few are based on empirical evidence, and thus they are incompatible with current public health practice. Evidence-based recommendations for healthy place making could have important public health implications. Four aspects of the built environment, at different spatial scales-nature contact, buildings, public spaces, and urban form-are identified as offering promising opportunities for public health research, and potential research agendas for each are discussed.