gebhart/patrepeval huggingface dataset:
A pig model of the human gastrointestinal tract (2013)

Easy access to next generation sequencing has enabled the rapid analysis of complex microbial populations. To take full advantage of these technologies, animal models enabling the manipulation of human microbiomes and the study of the impact of such perturbations on the host are needed. To this aim we are developing experimentally tractable and clinically relevant pig models of the human adult and infant gastro-intestinal tract. The intestine of germ-free piglets was populated with human adult or infant fecal microbial populations, and the piglets were maintained on solid or milk diet, respectively. Amplicons of 16S rRNA V6 region were deep-sequenced to monitor to what extent the transplanted human microbiomes changed in the pig. Within 24 h of transfer of human fecal microbiome to pigs, bacterial microbiomes rich in Proteobacteria emerged. These populations evolved toward a more diverse composition rich in Bacteroidetes and Firmicutes. In the experiment where infant microbiome was used, the phylogenetic composition of the transplanted bacterial population converged toward that of the human inoculum. A majority of sequences belonged to a relatively small number of operational taxonomic units, whereas at the other end of the abundance spectrum, a large number of rare and transient OTUs were detected. Analysis of fecal and colonic microbiomes originating from the same animal indicate that feces closely replicate the colonic microbiome. We conclude that the pig intestine can be colonized with human fecal microbiomes to generate a realistic model of the human GI tract.
The Basic Helix-Loop-Helix Transcription Factor Family in Plants: A Genome-Wide Study of Protein Structure and Functional Diversity (2003)

Basic helix-loop-helix (bHLH) transcription factors (TFs) belong to a family of transcriptional regulators present in three eukaryotic kingdoms. Many different functions have been identified for these proteins in animals, including the control of cell proliferation and development of specific cell lineages. Their mechanism for controlling gene transcription often involves homodimerization or heterodimerization. In plants, little is known about the bHLH family, but we have determined that there are 133 bHLH genes in Arabidopsis thaliana and have confirmed that at least 113 of them are expressed. The AtbHLH genes constitute one of the largest families of transcription factors in A. thaliana with significantly more members than are found in most animal species and about an equivalent number to those in vertebrates. Comparisons with animal sequences suggest that the majority of plant bHLH genes have evolved from the ancestral group B class of bHLH genes. By studying the AtbHLH genes collectively, twelve subfamilies have been identified. Within each of these main groups, there are conserved amino acid sequence motifs outside the DNA binding domain. Potential gene redundancy among members of smaller subgroups has been analyzed, and the resulting information is presented to provide a simplified visual interpretation of the gene family, identifying related genes that are likely to share similar functions. Based on the current characterization of a limited number of plant bHLH proteins, we predict that this family of TFs has a range of different roles in plant cell and tissue development as well as plant metabolism.
Poly(glycerol sebacate) Nanofiber Scaffolds by Core/Shell Electrospinning (2008)

The novel biomaterial poly(glycerol sebacate) (PGS) holds great promise for tissue engineering and regenerative medicine. PGS is a rubbery, degradable polymer much like elastin; however, it has been limited to cast structures. This work reports on the formation of PGS nanofibers in random non-woven mats for use as tissue engineering scaffolds by coaxial core/shell electrospinning. PGS nanofibers are an inexpensive and synthetic material that mimics the chemical and mechanical environment provided by elastin fibers. Poly(lactide) was used as the shell material to constrain the PGS during the curing process and was removed before cell seeding. Human microvascular endothelial cells from skin (HDMEC) were used to evaluate the in-vitro cellular compatibility of the PGS nanofiber scaffolds. [Figure: see text].
Marrow Stromal Cells, Mitosis, and Neuronal Differentiation: Stem Cell and Precursor Functions (2003)

To define relationships among marrow stromal cells (MSCs), multipotential progenitors, committed precursors, and derived neurons, we examined differentiation, mitosis, and apoptosis in vitro. Neural induction medium morphologically converted over 70% of MSCs to typical neurons, which expressed tau, neuronal nuclear antigen, neuron-specific enolase, and TUC-4 within 24 hours. A subset decreased fibronectin expression, consistent with mesenchymal to neuroectodermal conversion. More than 35% of differentiating neurons incorporated bromodeoxyuridine (BrdU) and divided, increasing cell number by 60%, while another subpopulation differentiated without incorporating BrdU or dividing. Inhibition of mitosis and DNA synthesis did not prevent neural differentiation, with 70% of blocked cells expressing tau and displaying neuronal morphologies. By deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, less than 1% of cells underwent apoptosis at 36 and 72 hours, suggesting differentiation without cell-selective mechanisms. Apparently, MSCs may directly differentiate into neurons without passing through a mitotic stage, suggesting that distinctions among stem cells, progenitors, and precursors are more flexible than formerly recognized.
Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3 (1998)

The propagation of embryonic stem (ES) cells in an undifferentiated pluripotent state is dependent on leukemia inhibitory factor (LIF) or related cytokines. These factors act through receptor complexes containing the signal transducer gp130. The downstream mechanisms that lead to ES cell self-renewal have not been delineated, however. In this study, chimeric receptors were introduced into ES cells. Biochemical and functional studies of transfected cells demonstrated a requirement for engagement and activation of the latent trancription factor STAT3. Detailed mutational analyses unexpectedly revealed that the four STAT3 docking sites in gp130 are not functionally equivalent. The role of STAT3 was then investigated using the dominant interfering mutant, STAT3F. ES cells that expressed this molecule constitutively could not be isolated. An episomal supertransfection strategy was therefore used to enable the consequences of STAT3F expression to be examined. In addition, an inducible STAT3F transgene was generated. In both cases, expression of STAT3F in ES cells growing in the presence of LIF specifically abrogated self-renewal and promoted differentiation. These complementary approaches establish that STAT3 plays a central role in the maintenance of the pluripotential stem cell phenotype. This contrasts with the involvement of STAT3 in the induction of differentiation in somatic cell types. Cell type-specific interpretation of STAT3 activation thus appears to be pivotal to the diverse developmental effects of the LIF family of cytokines. Identification of STAT3 as a key transcriptional determinant of ES cell self-renewal represents a first step in the molecular characterization of pluripotency.
TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Detection in Living Cells of Ca2+-dependent Changes in the Fluorescence Emission of an Indicator Composed of Two Green Fluorescent Protein Variants Linked by a Calmodulin-binding Sequence (1997)

We have designed a novel fluorescent indicator composed of two green fluorescent protein variants joined by the calmodulin-binding domain from smooth muscle myosin light chain kinase. When (Ca2+)4-calmodulin is bound to the indicator (Kd = 0.4 nM), fluorescence resonance energy transfer between the two fluorophores is attenuated; the ratio of the fluorescence intensity measured at 505 nm to the intensity measured at 440 nm decreases 6-fold. Images of microinjected living cells demonstrate that emission ratios can be used to monitor spatio-temporal changes in the fluorescence of the indicator. Changes in indicator fluorescence in these cells are coupled with no discernible lag (<1 s) to changes in the cytosolic free Ca2+ ion concentration, ranging from below 50 nM to approximately 1 microM. This observation suggests that the activity of a calmodulin target with a typical 1 nM affinity for (Ca2+)4-calmodulin is responsive to changes in the intracellular Ca2+ concentration over the physiological range. It is likely that the indicator we describe can be modified to detect the levels of ligands and proteins in the cell other than calmodulin.
Quantifying Selection against Synonymous Mutations in HIV-1 env Evolution (2013)

Intrapatient evolution of human immunodeficiency virus type 1 (HIV-1) is driven by the adaptive immune system resulting in rapid change of HIV-1 proteins. When cytotoxic CD8(+) T cells or neutralizing antibodies target a new epitope, the virus often escapes via nonsynonymous mutations that impair recognition. Synonymous mutations do not affect this interplay and are often assumed to be neutral. We test this assumption by tracking synonymous mutations in longitudinal intrapatient data from the C2-V5 part of the env gene. We find that most synonymous variants are lost even though they often reach high frequencies in the viral population, suggesting a cost to the virus. Using published data from SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) assays, we find that synonymous mutations that disrupt base pairs in RNA stems flanking the variable loops of gp120 are more likely to be lost than other synonymous changes: these RNA hairpins might be important for HIV-1. Computational modeling indicates that, to be consistent with the data, a large fraction of synonymous mutations in this genomic region need to be deleterious with a cost on the order of 0.002 per day. This weak selection against synonymous substitutions does not result in a strong pattern of conservation in cross-sectional data but slows down the rate of evolution considerably. Our findings are consistent with the notion that large-scale patterns of RNA structure are functionally relevant, whereas the precise base pairing pattern is not.
Pedestrian Crossing Behavior at Signalized Crosswalks (2017)

This study investigated pedestrian jaywalking at signalized crosswalks. Observational surveys were conducted at seven crosswalks in different areas in Hong Kong, after which pedestrian information and site condition data were incorporated into a database. A binary logit model was used to identify possible factors that determine the probability of pedestrian jaywalking. To address the variation in the effects of the explanatory variables among pedestrians and the unobserved heterogeneity across sites, a random parameter model and a random effect model were used, respectively. The results showed that the random parameter model performed the best in terms of goodness of fit. It was found that the signal when a pedestrian arrives at the crosswalk is critical for decision making, and the jaywalking of surrounding pedestrians also influences the pedestrian’s decision to cross. The gender and walking speed of the pedestrian, vehicle flow, and site location and condition of the crosswalk were also found to significantly determine the probability of pedestrian jaywalking.
Alkoxides as nucleophiles in (.pi.-allyl)palladium chemistry. Synthetic and mechanistic studies (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlkoxides as nucleophiles in (.pi.-allyl)palladium chemistry. Synthetic and mechanistic studiesSusan A. Stanton, Steven W. Felman, Carol S. Parkhurst, and Stephen A. GodleskiCite this: J. Am. Chem. Soc. 1983, 105, 7, 1964–1969Publication Date (Print):April 1, 1983Publication History Published online1 May 2002Published inissue 1 April 1983https://pubs.acs.org/doi/10.1021/ja00345a050https://doi.org/10.1021/ja00345a050research-articleACS PublicationsRequest reuse permissionsArticle Views800Altmetric-Citations58LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Screening for Hemochromatosis (1993)

In the United States the average daily intake of dietary iron ranges from 10 to 30 mg, but only about 1 mg is absorbed, to balance precisely the loss due to the sloughing of intact cells containing iron. Iron absorption can be increased if iron stores are depleted (usually through blood loss), and in genetically normal people absorption decreases with iron overload1,2 (usually from multiple transfusions). Iron balance is regulated at the absorptive step, but the mechanism by which the intestinal mucosa accomplishes this has not been defined. The defect responsible for hereditary hemochromatosis is malregulation of intestinal iron . . .
Effect of leukocytic endogenous mediators on endocrine pancreas secretory responses. (1977)

Crude mediators from stimulated rabbit peritoneal leukocytes (LEM) engender numerous physiologic alterations in rats, which are similar to those observed during infection. One hour after the intraperitoneal injection of crude LEM, plasma insulin and glucagon concentrations are elevated; at 2 h the hormonal alterations are manifested by a 30% increase in hepatic cyclic adenosine 3',5'-monophosphate (cAMP), glycogen depression, and uptake of 14C-labeled nonmetabolizable amino acid analogues (AA). Plasma hormone concentrations reach maximum levels by 5 h and decline by 24 h. The hepatic concentrations of AA parallel the insulin and glucagon responses and correlate with the inverse of insulin/glucagon molar ratio. In spite of mobilization of hepatic glycogen evident at 5 h, plasma glucose concentrations were transiently depressed. Plasma insulin, glucagon, and hepatic AA concentrations were dose dependent. Plasma insulin and glucagon responses to crude LEM may explain increases in hepatic cAMP, uptake of AA, and glycogenolysis as well as hypoglycemia. These data partially characterize the role of crude LEM, provide an explanation for the stimuli-inducing hyperglucagonemia and hyperinsulinemia during infection. They implicate the endocrine pancreas as a factor regulating the host's metabolic response to infection.
Microbial Pathogenesis in Cystic Fibrosis: Pulmonary Clearance of MucoidPseudomonas aeruginosaand Inflammation in a Mouse Model of Repeated Respiratory Challenge (1998)

Chronic endobronchiolitis compounded by recurring Pseudomonas aeruginosa infections is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). In this study, a mouse model of repeated respiratory exposure to P. aeruginosa was established to facilitate investigations of factors contributing to P. aeruginosa persistence and associated inflammatory processes in the lung. While a single exposure to P. aeruginosa aerosols resulted in only mild histopathological changes, repeated exposure caused significant lung pathology in C57BL/6J mice. The peak of histopathological changes and inflammation in C57BL/6J mice was characterized by subacute lymphohistiocytic bronchopneumonia and persistent elevation of tumor necrosis factor alpha and macrophage inflammatory protein 2 in the lung but not in the serum. When isogenic nonmucoid (mucA+) and mucoid (mucA22) P. aeruginosa strains were compared, the mucoid cells were cleared several-fold less efficiently than the parental nonmucoid strain during the initial stages of the aerosol exposure regimen. However, the microscopic pathology findings and proinflammatory cytokine levels were similar in mice exposed to nonmucoid and mucoid P. aeruginosa throughout the infection. We also tested lung histopathology and proinflammatory cytokines in interleukin 10 (IL-10)-deficient transgenic (IL-10T) mice. Significant mortality was seen in IL-10T mice on initial challenge with P. aeruginosa, although no histopathological differences could be observed in the lungs of C57BL/6J and surviving IL-10T mice after a single exposure. However, increased pathology was detected in IL-10T mice relative to C57BL/6J after repeated challenge with P. aeruginosa. This observation supports the proposals that anti-inflammatory cytokines may play a role in suppressing P. aeruginosa-induced tissue damage during chronic infection.
Engineering molecular recognition in alkane oxidation catalysed by cytochrome P450cam (1998)

The activity, selectivity and coupling efficiency of alkane oxidation by the monooxygenase enzyme cytochrome P450cam can be enhanced by engineering the active site topology to accommodate different alkanes: reducing the active site volume by the Y96F–V247L double mutations resulted in four-fold higher activity for the oxidation of hexane (1) than 3-methylpentane (2) while the larger active site of the Y96A–V247A double mutant gave rise to a two-fold preference for 2 over 1.
The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection (2004)

Viral infection and stimulation with lipopolysaccharide (LPS) or double stranded RNA (dsRNA) induce phosphorylation of interferon (IFN) regulatory factor (IRF)-3 and its translocation to the nucleus, thereby leading to the IFN-beta gene induction. Recently, two IkappaB kinase (IKK)-related kinases, inducible IkappaB kinase (IKK-i) and TANK-binding kinase 1 (TBK1), were suggested to act as IRF-3 kinases and be involved in IFN-beta production in Toll-like receptor (TLR) signaling and viral infection. In this work, we investigated the physiological roles of these kinases by gene targeting. TBK1-deficient embryonic fibroblasts (EFs) showed dramatic decrease in induction of IFN-beta and IFN-inducible genes in response to LPS or dsRNA as well as after viral infection. However, dsRNA-induced expression of these genes was residually detected in TBK1-deficient cells and intact in IKK-i-deficient cells, but completely abolished in IKK-i/TBK1 doubly deficient cells. IRF-3 activation, in response not only to dsRNA but also to viral infection, was impaired in TBK1-deficient cells. Together, these results demonstrate that TBK1 as well as, albeit to a lesser extent, IKK-i play a crucial role in the induction of IFN-beta and IFN-inducible genes in both TLR-stimulated and virus-infected EFs.
Induced pluripotent stem cells from GMP-grade hematopoietic progenitor cells and mononuclear myeloid cells (2011)

Because the use of blood cells allows minimally invasive tissue procurement under GMP conditions and rapid cellular reprogramming, mobilized HPCs and unmobilized PBMCs would be ideal somatic cell sources for clinical-grade iPSC derivation, especially from diabetes patients complicated by slow-healing wounds.
A 48-Core IA-32 Processor in 45 nm CMOS Using On-Die Message-Passing and DVFS for Performance and Power Scaling (2010)

This paper describes a multi-core processor that integrates 48 cores, 4 DDR3 memory channels, and a voltage regulator controller in a 64 2D-mesh network-on-chip architecture. Located at each mesh node is a five-port virtual cut-through packet-switched router shared between two IA-32 cores. Core-to-core communication uses message passing while exploiting 384 KB of on-die shared memory. Fine grain power management takes advantage of 8 voltage and 28 frequency islands to allow independent DVFS of cores and mesh. At the nominal 1.1 V supply, the cores operate at 1 GHz while the 2D-mesh operates at 2 GHz. As performance and voltage scales, the processor dissipates between 25 W and 125 W. The processor is implemented in 45 nm Hi-K CMOS and has 1.3 billion transistors.
Combined local ischemic postconditioning and remote perconditioning recapitulate cardioprotective effects of local ischemic preconditioning (2010)

Ischemic postconditioning (PostC) and perconditioning (PerC) provide practical methods for protecting the heart against ischemia-reperfusion (I/R) injury, but their combined effects have not been studied in detail. Using an in vivo rat I/R model, we tested 1) whether additive effects were produced when local PostC was preceded by varying doses of remote PerC, and whether the optimal PostC+PerC regime is additive to local ischemic preconditioning (IPC), and 2) how combined PostC+PerC alters the activity of the reperfusion injury salvage kinase pathway. The optimal combination of PerC and PostC therapy was produced by PerC delivered with four cycles of 5 min of limb ischemia followed by 5-min reperfusion. This resulted in lower infarct size (22.56 +/- 4.45%) compared with rats with PostC alone (29.39 +/- 3.66%) and PerC alone (33.49 +/- 5.81%) and complementary differences in the generation of reactive oxygen species and apoptotic signaling. However, this optimal combination of PostC+PerC resulted in protection similar to local IPC alone (18.8 +/- 2.54%, P = 0.13), and when added to IPC there was no additional protection (19.62 +/- 2.89%, P = 0.675). Akt and ERK1/2 phosphorylation was induced by PostC and PerC and maximally by combined PostC+PerC treatment, and protection was abolished by phosphatidylinositol 3-kinase or ERK1/2 inhibitors. This study shows that neither PostC nor a maximized "dose" of PerC leads to optimal kinase signaling or cardioprotection compared with IPC alone. However, combined PostC+PerC may result in complementary effects on kinase signaling to recapitulate the effects of local IPC. Finally, combined PostC+PerC is not additive to IPC, suggesting that each works via a common pathway.