Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucose Effects on Beta-Cell Growth and Survival Require Activation of Insulin Receptors and Insulin Receptor Substrate 2

ABSTRACT Insulin and insulin-like growth factor I (IGF-I) are ubiquitous hormones that regulate growth and metabolism of most mammalian cells, including pancreatic β-cells. In addition to being an insulin secretagogue, glucose regulates proliferation and survival of β-cells. However, it is unclear whether the latter effects of glucose occur secondary to autocrine activation of insulin signaling proteins by secreted insulin. To examine this possibility we studied the effects of exogenous glucose or insulin in β-cell lines completely lacking either insulin receptors (βIRKO) or insulin receptor substrate 2 (βIRS2KO). Exogenous addition of either insulin or glucose activated proteins in the insulin signaling pathway in control β-cell lines with the effects of insulin peaking earlier than glucose. Insulin stimulation of βIRKO and βIRS2KO cells led to blunted activation of phosphatidylinositol 3-kinase and Akt kinase, while surprisingly, glucose failed to activate either kinase but phosphorylated extracellular signal-regulated kinase. Control β-cells exhibited low expression of IGF-1 receptors compared to compensatory upregulation in βIRKO cells. The signaling data support the slow growth and reduced DNA and protein synthesis in βIRKO and βIRS2KO cells in response to glucose stimulation. Together, these studies provide compelling evidence that the growth and survival effects of glucose on β-cells require activation of proteins in the insulin signaling pathway.
Orthogonal Magnetic Field Analysis of a Double-Stator Linear-Rotary Permanent Magnet Motor With Orthogonally Arrayed Permanent Magnets

In this paper, a double-stator linear-rotary permanent magnet motor (DSLRPMM) for linear and/or rotary movement is presented. Since the two types of permanent magnets are orthogonally arrayed on the inner and outer surfaces of the mover core, respectively, the influences of the orthogonal magnetic field (OMF) on the motor electromagnetic characteristics cannot be ignored. Based on the 3-D finite-element method (FEM), the OMF in the motor and the iron core magnetization characteristics are investigated, and a test device is constructed to verify the results obtained by the theoretical analysis and 3-D finite-element analysis (FEA). On the basis of the measured data, the 2-D FEM is employed to analyze the electromagnetic characteristics of the DSLRPMM, including flux density, flux linkage, back-electromotive force, detent force, and cogging torque. The results are compared with that obtained by the 3-D FEA, and they are in agreement. Moreover, a prototype is built and tested. The experimental results verify the correctness of the predictions.
Predicting answer types for question-answering

We tackle the problem of answer type prediction, applying a transition-based neural network parser to understand the syntactic structure of a query and infer the focus word or phrase that contains the correct type. To achive this, we first come up with a framework to combine a dataset of labeled question-answer pairs and a type inventory into a dataset to learn types. Second, we fit a sigmoid prediction layer on top of query words and the inferred syntactic structure of a query to predict the correct answer types. Our model outperforms a logistic regression baseline that does not take into account the syntactic structure of the query.
Online concentration by field‐amplified sample injection in acidic buffer for analysis of fangchinoline and tetrandrine in herbal medicine by flow injection‐micellar electrokinetic capillary chromatography

A novel, rapid, and continuous online concentration approach based on field‐amplified sample injection for the analysis of fangchinoline and tetrandrine was developed in this paper by combination of flow injection‐MEKC. The BGE used was a solution composed of 75 mM H3PO4–triethylamine–2.5% v/v polyoxyethylene sorbitan monolaurate–20% v/v methanol buffer (pH* 5.0). The analytes prepared in 50% v/v aqueous ethanol were used as the test analytes. Sample was injected electrokinetically between plugs of water. When the cations reached the boundary between the water plug and BGE, they slowed down and became concentrated. Thereafter, MEKC was initiated for the separation. This results in 6.8–8.9‐fold improvement in concentration sensitivity relative to conventional CE methods. The separation could be achieved within 10 min and sample throughput rate can reach up to 50/h. The repeatability (defined as RSD) was 4.8, 4.4% with peak height evaluation and 3.6, 0.94% with peak area evaluation for TET and FAN, respectively.
Expression of IL-24, an Activator of the JAK1/STAT3/SOCS3 Cascade, Is Enhanced in Inflammatory Bowel Disease

IL-24 is a member of the IL-10 family of cytokines. In this study, we investigated IL-24 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-24 expression in human colonic subepithelial myofibroblasts (SEMFs). IL-24 expression in the IBD mucosa was evaluated by immunohistochemical methods. IL-24 mRNA and protein expression was determined by real-time PCR and ELISA, respectively. AP-1 and C/EBP DNA-binding activity and IL-24 promoter activity were assessed by EMSA analysis and a reporter gene assay, respectively. IL-24 mRNA expression was significantly elevated in active lesions from patients who have ulcerative colitis and Crohn’s disease. Colonic SEMFs were identified as a major source of IL-24 in the mucosa. IL-1β, but not IL-17A, TNF-α, or IFN-γ, significantly enhanced IL-24 mRNA and protein expression in isolated colonic SEMFs. The IL-1β-induced IL-24 mRNA expression was mediated by the activation of the transcription factors, AP-1 and C/EBP-β. Induction of IL-24 mRNA stabilization was also involved in the effects of IL-1β. IL-24 induced JAK1/STAT-3 phosphorylation and SOCS3 expression in HT-29 colonic epithelial cells. IL-24 did not modulate the proliferation of HT-29 cells, but significantly increased the mRNA expression of membrane-bound mucins (MUC1, MUC3, and MUC4). IL-24 derived from colonic SEMFs acts on colonic epithelial cells to elicit JAK1/STAT-3 activation and the expression of SOCS3 and mucins, supporting their suppressive effects on mucosal inflammation in IBD.
Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci

Degenerate oligonucleotides based on the published Escherichia coli glutamate decarboxylase (GAD) protein sequence were used in a polymerase chain reaction to generate a DNA probe for the E. coli GAD structural gene. Southern blots showed that there were two cross-hybridizing GAD genes, and both of these were cloned and sequenced. The two GAD structural genes, designated gadA and gadB, were found to be 98% similar at the nucleotide level. Each gene encoded a 466-residue polypeptide, named, respectively, GAD alpha and GAD beta, and these differed by only five amino acids. Both GAD alpha and GAD beta contain amino acid residues which are highly conserved among pyridoxal-dependent decarboxylases, but otherwise the protein sequences were not homologous to any other known proteins. By restriction mapping and hybridization to the Kohara miniset library, the two GAD genes were located on the E. coli chromosome. gadA maps at 4046 kb and gadB at 1588 kb. Neither of these positions is in agreement with the current map position for gadS as determined by genetic means. Analysis of Southern blots indicated that two GAD genes were present in all E. coli strains examined, including representatives from the ECOR collection. However, no significant cross-hybridizing gene was found in Salmonella species. Information about the DNA sequences and map positions of gadA and gadB should facilitate a genetic approach to elucidate the role of GAD in E. coli metabolism.
Decentralized resilient H∞ filtering for large-scale systems with delayed interactions under communication constraints

This paper is concerned with the decentralized resilient H∞ filtering problem for a class of large-scale discrete-time systems with delayed interactions under communication constraints. A switched time-delay system with randomly occurring uncertainties is employed to model the network-based filtering system where measurement quantization and data missing phenomena are taken into account. The main purpose of this paper is to design decentralized resilient filters with randomly occurring gain variations such that filtering error system is exponentially stable in the mean square and satisfied a prescribed H∞ disturbance attenuation. Sufficient condition are first established in virtue of the switched system method for the existence of the desired decentralized resilient filters. By utilizing the conditions, the filter gains are then designed. Finally, a numerical example is illustrated to show the efficacy of the results proposed.
Active Form of Notch Imposes T Cell Fate in Human Progenitor Cells1

The crucial role of Notch signaling in cell fate decisions in hematopoietic lineage and T lymphocyte development has been well established in mice. Overexpression of the intracellular domain of Notch mediates signal transduction of the protein. By retroviral transduction of this constitutively active truncated intracellular domain in human CD34+ umbilical cord blood progenitor cells, we were able to show that, in coculture with the stromal MS-5 cell line, depending on the cytokines added, the differentiation toward CD19+ B lymphocytes was blocked, the differentiation toward CD14+ monocytes was inhibited, and the differentiation toward CD56+ NK cells was favored. The number of CD7+cyCD3+ cells, a phenotype similar to T/NK progenitor cells, was also markedly increased. In fetal thymus organ culture, transduced CD34+ progenitor cells from umbilical cord blood cells or from thymus consistently generated more TCR-γδ T cells, whereas the other T cell subpopulations were largely unaffected. Interestingly, when injected in vivo in SCID-nonobese diabetic mice, the transduced cells generated ectopically human CD4+CD8+ TCR-αβ cells in the bone marrow, cells that are normally only present in the thymus, and lacked B cell differentiation potential. Our results show unequivocally that, in human, Notch signaling inhibits the monocyte and B cell fate, promotes the T cell fate, and alters the normal T cell differentiation pathway compatible with a pretumoral state.
A Novel Method for Survivability Test Based on End Nodes in Large Scale Network

Survivability is a necessary property of network system in disturbed environment. Recovery ability is a key actor of survivability. This paper concludes network survivability into a novel composite metric, i.e. Network Recovery Degree (NRD). In order to measure this metric in quantity, a concept of Source-Destination Pair (SD Pair), is created to abstract end-to-end activity based on end nodes in network, and the quality of SD Pair is also used to describe network performance, such as connectivity, quality of service, link degree, and so on. After that, a Survivability Test method in large scale Network based on SD pairs, called STNSD, is provided. How to select SD Pairs effectively in large scale network is also provided. We set up simulation environment to validate the test method in a severe destroy scenario and evaluate the method scalability in different large scale network scenarios. Experiment and analysis shows that the metric NRD correctly reflects the effort of different survivability strategy, and the proposed test method STNSD has good scalability and can be used to test and evaluate quantitative survivability in large scale network.
Selective Mechanism-Based Inactivation of CYP3A4 by CYP3cide (PF-04981517) and Its Utility as an In Vitro Tool for Delineating the Relative Roles of CYP3A4 versus CYP3A5 in the Metabolism of Drugs

CYP3cide (PF-4981517; 1-methyl-3-[1-methyl-5-(4-methylphenyl)-1H-pyrazol-4-yl]-4-[(3S)-3-piperidin-1-ylpyrrolidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine) is a potent, efficient, and specific time-dependent inactivator of human CYP3A4. When investigating its inhibitory properties, an extreme metabolic inactivation efficiency (kinact/KI) of 3300 to 3800 ml · min−1 · μmol−1 was observed using human liver microsomes from donors of nonfunctioning CYP3A5 (CYP3A5 *3/*3). This observed efficiency equated to an apparent KI between 420 and 480 nM with a maximal inactivation rate (kinact) equal to 1.6 min−1. Similar results were achieved with testosterone, another CYP3A substrate, and other sources of the CYP3A4 enzyme. To further illustrate the abilities of CYP3cide, its partition ratio of inactivation was determined with recombinant CYP3A4. These studies produced a partition ratio approaching unity, thus underscoring the inactivation capacity of CYP3cide. When CYP3cide was tested at a concentration and preincubation time to completely inhibit CYP3A4 in a library of genotyped polymorphic CYP3A5 microsomes, the correlation of the remaining midazolam 1′-hydroxylase activity to CYP3A5 abundance was significant (R2 value equal to 0.51, p value of <0.0001). The work presented here supports these findings by fully characterizing the inhibitory properties and exploring CYP3cide's mechanism of action. To aid the researcher, multiple commercially available sources of CYP3cide were established, and a protocol was developed to quantitatively determine CYP3A4 contribution to the metabolism of an investigational compound. Through the establishment of this protocol and the evidence provided here, we believe that CYP3cide is a very useful tool for understanding the relative roles of CYP3A4 versus CYP3A5 and the impact of CYP3A5 genetic polymorphism on a compound's pharmacokinetics.
Biochemical Analysis of a Mutant Tetrahymena Lacking Outer Dynein Arms

ABSTRACT. Tetrahymena thermophila mutants homozygous for the oad mutation become nonmotile when grown at the restrictive temperature, and axonemes isolated from nonmotile mutants lack approximately 90% of their outer dynein arms. Electrophoretic analyses of axonemes isolated from nonmotile mutants (oad axonemes) indicate they contain significantly fewer of the 22 S dynein heavy chains that axonemes isolated from wild‐type cells (wild‐type axonemes) contain. The 22 S dynein heavy chains that remain in axonemes isolated from nonmotile, oad mutants are assembled into 22 S dynein particles that exhibit wild‐type levels of ATPase activity. Two‐dimensional gel electrophoresis of oad axonemes show that they are deficient in no proteins other than those proteins thought to be components of 22 S dynein. This report is the first formal proof that outer dynein arms in Tetrahymena cilia are composed of 22 S dynein.
A Historical Study of an Implementation Methodology: A Morphogenetic Analysis

To improve the results of Enterprise Systems (ES) implementation projects, new or revised implementation methodologies are introduced by ES vendors. Yet, the innovation and adoption of implementation methodologies (IM), which are computer-based and incorporate both project management and functional components, can be problematic. The purpose of this paper is to describe and explain the adoption of an implementation methodology. We recount for the adoption of an implementation methodology through the lens of a realist theory of social change. Our qualitative study provides insight into IM instantiation as manifestation of IM adoption configuration generated by the interplay between structure and agency over time, and suggests four implementation methodology adoption configurations: Fragmented, aggregated, integrated, and infrastructural. This study also offers a foundation for future work that may contribute to a more coherent view on the instantiation of IMs and adoption configurations. (Less)
West Nile Virus Infection in Eastern Fox Squirrels (Sciurus niger)

Since the initial outbreak of West Nile virus (WNV) in the northeastern United States in 1999, the virus has rapidly spread westward and southward across the USA, causing high mortality in crows as well as sporadic mortality in horses, humans, and a wide variety of birds. In 2002 the epidemic widened as hundreds of equine and human cases and sporadic cases in other mammalian species were reported. This is the first report of WNV infection in three Eastern fox squirrels (Sciurus niger). Neurologic signs included head tilt, uncoordinated movement, paralysis, and tremors. Gross lesions were absent. Microscopic lesions consisted of lymphoplasmacytic inflammation involving the brain, heart, kidney, and liver. Formalin-fixed tissues from the three squirrels were tested for WNV antigen by immunohistochemical staining and for WNV-specific RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). The kidneys of all three squirrels stained positive with immunohistochemistry for WNV, whereas the brain and heart were positive in only one animal. Two of the three squirrels were positive for WNV by RT-PCR.
Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

OBJECTIVE To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. METHODS In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. RESULT Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P<0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). CONCLUSION Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.
Multilayer approach to cost-efficient home automation

This paper describes an approach to a full vertical smart building solution. The concept relies on identification of distinct layers, selection of optimal technologies for each, and their seamless integration into a unified service. The solution uses low-cost, energy efficient Zigbee for the most massive device layer, embedded solution for the layer local intelligence resides in, and enterprise technologies for the cloud. The experiments and measurements show that the selected technologies ensure adequate feature distribution and responsiveness across all layers. User test proves the interactivity is maintained across the full vertical.
Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention

Objective Restenosis after percutaneous coronary intervention (PCI) remains an issue even in the drug-eluting stent era. Genetic polymorphisms may provide insight in the pathogenesis of restenosis and may help in the stratification of patients at risk for restenosis. The aim of this study was to examine whether polymorphisms at the toll-like receptor 4 (TLR4) locus, that are associated with impaired innate immune system and with an increased risk of cardiovascular events, were associated with clinical and/or angiographic restenosis after PCI. Methods The GENetic Determinants of Restenosis (GENDER) project was a prospective, multicenter study that enrolled 3146 consecutive patients after successful PCI. Frequencies of the TLR4 896A/G (Asp299Gly; rs4986790) and 1196C/T (Thr399Ile; rs4986791) polymorphisms and haplotypes were assessed. Patients were followed up for 1 year and in a subgroup of 406 patients angiographic follow-up was obtained. Results We included a total of 2682 patients that underwent successful PCI. There was no association between genotypes and the risk of target vessel revascularization at 1-year or late luminal loss at 6-months angiographic follow-up (P=0.53 and 0.44, respectively). Absence of association with target lesion revascularization and late luminal loss was replicated in the GEnetic risk factors for In-Stent Hyperplasia study Amsterdam (GEISHA) cohort study of 674 patients and in a subgroup of 550 patients with angiographic follow-up available (P=0.26, and 0.86, respectively). Moreover, in both the studies, no significant differences between haplotypes A/C and G/T were observed for target vessel revascularization at late luminal loss. Conclusion Although inflammation has been implicated in the pathophysiology of restenosis, the 896A/G and 1196C/T polymorphisms or haplotypes based on these polymorphisms at the TLR4 locus are not associated with an increased risk of target vessel revascularization or angiographic restenosis after PCI. These polymorphisms are not useful for pre-PCI identification of patients at risk for restenosis.
Influence of mineral, olive or sunflower oils on male reproductive parameters in vitro – the wild rodent Calomys laucha

The aim of this study was to evaluate the influence of oils on male reproductive parameters in Calomys laucha. Twenty‐four animals were distributed into four groups and given the following substances by gavage: water, mineral oil, olive oil and sunflower oil. After 10 days of gavage, the animals were euthanised and the semen was collected from them for assessing acrosome integrity and carrying out in vitro penetration (IVP) test. Acrosome was significantly reduced (P < 0.05) for the vehicles in relation to control. In vitro penetration was reduced in all vehicles in relation to control, but only sunflower oil had statistically lower levels of reduction (P < 0.05). Oily vehicles are able to influence in vitro reproductive tests negatively, interfering in reproductive toxicological studies.
Wake-Up Oscillators with pW Power Consumption in Dynamic Leakage Suppression Logic

In this paper, two circuit topologies of pW-power Hz-range wake-up oscillators for sensor node applications are presented. The proposed circuits are based on standard cells utilizing the Dynamic Leakage Suppression logic style [4]–[5]. The proposed oscillators exhibit low supply voltage sensitivity over a wide supply voltage range, from nominal voltage down to the deep sub-threshold region (i.e., 0.3 V). This enables direct powering from energy harvesters or batteries through their whole discharge cycle, suppressing the need for voltage regulation. Post-layout time-domain simulations of the proposed oscillators in 180nm show a power consumption of 1.4–1.7pW, a supply-sensitivity of 55–40%/V over the 0.3V–1.8V supply voltage range, and a compact area down to 1,500µm2. The very low power consumption makes the proposed circuits very well suited for energy-harvested systems-on-chip for Internet of Things applications.