gebhart/patrepeval huggingface dataset:
The effect of the laparoscopic insemination technique on the oestrous cycle of the ewe (1991)

This investigation was designed to determine whether or not the technique of intrauterine insemination affects the length of the subsequent oestrous cycle. Dorper ewes (n = 31) were divided into treatment and control groups. All the ewes were synchronised using 40 mg fluorogestone acetate intravaginal sponges for 14 d and 300 IU pregnant mare serum gonadotrophin on the day of sponge removal. A standard semen diluent was deposited laparoscopically in each uterine horn of ewes in the treatment group. Teaser rams were used to detect oestrus. Progesterone profiles were used to confirm oestrus. The mean oestrous cycle length of 17.83 +/- 0.69 d for the group in which the diluent was deposited by laparoscopy did not differ significantly (P less than 0.1) from the 18.36 +/- 2.11 d of the control group. The technique of laparoscopic insemination did not influence the length of subsequent oestrous cycles.
Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis (2012)

The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity.
FstSNP-HapMap3: a database of SNPs with high population differentiation for HapMap3 (2008)

http://FstSNP-hapmap3.googlecode.com/
Chemical tools to discover and target bacterial glycoproteins (2010)

Bacterial protein glycosylation is an important post-translational modification that can distinguish pathogenic bacteria from human cells. This review discusses recent findings in the field of bacterial glycobiology, with a particular focus on the unusual structures of bacterial glycans and their link to pathogenesis. We then describe how chemical tools can augment the study of this class of biomolecules, offering the potential to unveil novel pathogen-associated targets. Finally, this article highlights recent advances in targeting bacteria with therapeutics based on their unique glycans.
Early embryonic lethality in Bmp5;Bmp7 double mutant mice suggests functional redundancy within the 60A subgroup (1999)

Members of the BMP family of signaling molecules display a high conservation of structure and function, and multiple BMPs are often coexpressed in a variety of tissues during development. Moreover, distinct BMP ligands are capable of activating common pathways. Here we describe the coexpression of two members of the 60A subfamily of BMPs, Bmp5 and Bmp7, at a number of different sites in the embryo from gastrulation onwards. Previous studies demonstrate that loss of either Bmp5 or Bmp7 has negligible effects on development, suggesting these molecules functionally compensate for each other at early stages of embryonic development. Here we show this is indeed the case. Thus we find that Bmp5;Bmp7 double mutants die at 10.5 dpc and display striking defects primarily affecting the tissues where these factors are coexpressed. The present analysis also uncovers novel roles for BMP signaling during the development of the allantois, heart, branchial arches, somites and forebrain. Bmp5 and Bmp7 do not appear to be involved in establishing pattern in these tissues, but are instead necessary for the proliferation and maintenance of specific cell populations. These findings are discussed with respect to potential mechanisms underlying cooperative signaling by multiple members of the TGF-beta superfamily.
Effect of nordihydroguaiaretic acid on cultured rat and human glioma cell proliferation (1989)

When cultured malignant cells derived from rat gliomas (C6 and 9L) and human gliomas (A-172 and T98G) were treated for 4 hours with 1 to 80 microns nordihydroguaiaretic acid (NDGA) or 5,8,11,14-eicosatetraynoic acid (ETYA), a dose-dependent inhibition of deoxyribonucleic acid (DNA) synthesis occurred. In a series of three experiments for each cell line, 40 microM NDGA suppressed 3H-thymidine incorporation in the rat and human glioma lines to an average of less than 3.1% and 5.6% of control uptake (counts per minute), respectively. Incubation with a higher concentration of ETYA (80 microM) resulted in inhibition of rat and human DNA synthesis to less than 53% and 62% of control levels, respectively. This inhibition was not associated with any loss of cell viability, as judged by trypan blue exclusion studies. Prolonged incubation (for 72 hours) of the rat and human glioma cells with NDGA markedly decreased cell proliferation with no loss of cell viability. The inhibition of human glioma cell division by NDGA was rapidly reversible after incubation for 24 hours and at least partially reversible after incubation for 96 hours. It is concluded that the inhibitors of eicosanoid biosynthesis, NDGA and (to a lesser extent) ETYA, reduce in vitro cell proliferation in two glioma lines from both the rat and human. Since neither indomethacin nor acetylsalicylic acid altered DNA synthesis in these cell lines, this implicates the lipoxygenase products of arachidonic acid metabolism as important positive modulators in glioma cell division. These findings warrant further study in an in vivo system.
Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo (2018)

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited <i>in vitro</i> expansion, absence of a full phenotypic characterization, few insights on their <i>in vivo</i> fate). Standardized MSCs derived <i>in vitro</i> from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4<sup>+</sup> FoxP3<sup>+</sup> regulatory T (Treg) cells. Further tested <i>in vivo</i> in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3<sup>+</sup>-Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells <i>in vivo</i>. They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.
对,就敲一下(上) (2003)

一个罹难者打来电话,他面临着致命的危险,但他是谁?他现在何处? 去年2月5日刚过中午,密歇根州圣克莱尔海岸57岁的市参议员卡斯·弗里德里克独自坐在厨房的桌旁,准备吃块三明治,再喝杯牛奶,突然他感到左臂特别麻木。不到一年前,他曾因一次中风住了几个星期的医院。恐怖一下子向他袭来,是
The Chip Is the Network: Toward a Science of Network-on-Chip Design (2008)

In this survey, we address the concept of network in three different contexts representing the deterministic, probabilistic, and statistical physics-inspired design paradigms. More precisely, we start by considering the natural representation of networks as graphs and discuss the main deterministic approaches to Network-on-Chip (NoC) design. Next, we introduce a probabilistic framework for network representation and optimization and present a few major approaches for NoC design proposed to date. Last but not least, we model the network as a thermodynamic system and discuss a statistical physics-based approach to characterize the network traffic. This formalism allows us to address the network concept in the most general context, point out the main limitations of the proposed solutions, and suggest a few open-ended problems.
Human endothelial stem/progenitor cells, angiogenic factors and vascular repair (2010)

Neovascularization or new blood vessel formation is of utmost importance not only for tissue and organ development and for tissue repair and regeneration, but also for pathological processes, such as tumour development. Despite this, the endothelial lineage, its origin, and the regulation of endothelial development and function either intrinsically from stem cells or extrinsically by proangiogenic supporting cells and other elements within local and specific microenvironmental niches are still not fully understood. There can be no doubt that for most tissues and organs, revascularization represents the holy grail for tissue repair, with autologous endothelial stem/progenitor cells, their proangiogenic counterparts and the products of these cells all being attractive targets for therapeutic intervention. Historically, a great deal of controversy has surrounded the identification and origin of cells and factors that contribute to revascularization, the use of such cells or their products as biomarkers to predict and monitor tissue damage and repair or tumour progression and therapeutic responses, and indeed their efficacy in revascularizing and repairing damaged tissues. Here, we will review the role of endothelial progenitor cells and of supporting proangiogenic cells and their products, principally in humans, as diagnostic and therapeutic agents for wound repair and tissue regeneration.
Brown adipose tissue thermogenesis: interdisciplinary studies (1990)

Energy expenditure for thermogenesis in brown adipose tissue (BAT) serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT can grow or atrophy; it is usually atrophied in obese animals. Control of BAT thermogenesis and growth is by the sympathetic nervous system, with integration of signals in the hypothalamus. Sensory nerves may also be involved. Understanding the control of growth and differentiation of BAT is important for discovering how to reactivate it is obesity. Studies on control of gene expression in BAT are concentrating on thermogenically important components such as the uncoupling protein (which allows BAT mitochondria to operate in a thermogenic uncoupled mode), lipoprotein lipase (which allows BAT to compete with white adipose tissue for dietary lipid), and thyroxine 5'-deiodinase (which allows endogenous triiodothyronine generation, part of the control of differentiation and growth of BAT). Differentiation of BAT cell precursors in culture has recently been achieved. BAT is present in adult humans and some anti-obesity drugs are targeted to stimulation of BAT thermogenesis. However, extrapolation to humans of results of studies of BAT requires the development of novel approaches to the noninvasive assessment of amount and function of human BAT.
High Resolution Structure of Deinococcus Bacteriophytochrome Yields New Insights into Phytochrome Architecture and Evolution (2007)

Phytochromes are red/far red light photochromic photoreceptors that direct many photosensory behaviors in the bacterial, fungal, and plant kingdoms. They consist of an N-terminal domain that covalently binds a bilin chromophore and a C-terminal region that transmits the light signal, often through a histidine kinase relay. Using x-ray crystallography, we recently solved the first three-dimensional structure of a phytochrome, using the chromophore-binding domain of Deinococcus radiodurans bacterial phytochrome assembled with its chromophore, biliverdin IXalpha. Now, by engineering the crystallization interface, we have achieved a significantly higher resolution model. This 1.45A resolution structure helps identify an extensive buried surface between crystal symmetry mates that may promote dimerization in vivo. It also reveals that upon ligation of the C3(2) carbon of biliverdin to Cys(24), the chromophore A-ring assumes a chiral center at C2, thus becoming 2(R),3(E)-phytochromobilin, a chemistry more similar to that proposed for the attached chromophores of cyanobacterial and plant phytochromes than previously appreciated. The evolution of bacterial phytochromes to those found in cyanobacteria and higher plants must have involved greater fitness using more reduced bilins, such as phycocyanobilin, combined with a switch of the attachment site from a cysteine near the N terminus to one conserved within the cGMP phosphodiesterase/adenyl cyclase/FhlA domain. From analysis of site-directed mutants in the D. radiodurans phytochrome, we show that this bilin preference was partially driven by the change in binding site, which ultimately may have helped photosynthetic organisms optimize shade detection. Collectively, these three-dimensional structural results better clarify bilin/protein interactions and help explain how higher plant phytochromes evolved from prokaryotic progenitors.
Randomized, Double-Blind, Placebo-Controlled, Pilot Trial of Infliximab, a Chimeric Monoclonal Antibody to Tumor Necrosis Factor-α, in Patients With Moderate-to-Severe Heart Failure (2003)

Short-term TNFalpha antagonism with infliximab did not improve and high doses (10 mg/kg) adversely affected the clinical condition of patients with moderate-to-severe chronic heart failure.
Imidazo[1,2‐b]pyridazines: Syntheses and interaction with central and peripheral‐type (mitochondrial) benzodiazepine receptors (1998)

Abstract The fundamental chemistry of pyridazines, the syntheses of substituted irnidazo[1,2‐ b ]pyridazines (1) (and some related compounds) and the interaction of the products with central benzodiazepine receptors (CBR) and peripheral‐type (mitochondrial) benzodiazepine receptors (PBR) are described. Some of these imidazo[1,2‐ b ]pyridazines had high selective affinity for the central benzodiazepine receptors and others had high selectivity for the peripheral‐type (mitochondrial) benzodiazepine receptors. The results of structure‐activity studies and molecular modeling will be reported. In vivo tests of some compounds which interacted strongly with the central benzodiazepine receptors revealed reasonably potent anticonvulsant/anticonflict activity, and some of those which bind selectively to the peripheral‐type (mitochondrial) benzodiazepine receptors are being examined as possible radiopharmaceuticals for imaging of tumors (and other disease states).
Upregulation of Glutathione-Related Genes and Enzyme Activities in Cultured Human Cells by Sublethal Concentrations of Inorganic Arsenic (2002)

Inorganic arsenic (iAs), a known human carcinogen, acts as a tumor promoter in part by inducing a rapid burst of reactive oxygen species (ROS) in mammalian cells. This causes oxidative stress and a subsequent increase in the level of cellular glutathione (GSH). Glutathione, a ubiquitous reducing sulfhydryl tripeptide, is involved in ROS detoxification and its increase may be part of an adaptive response to the oxidative stress. Glutathione related enzymes including glutathione reductase (GR) and glutathioneS-transferase (GST) also play key roles in these processes. In this study the regulatory effects of inorganic arsenite (As(III)) on the activities of GSH-related enzymes were investigated in cultured human keratinocytes. Substantial increases in GR enzyme activity and mRNA levels were shown in keratinocytes and other human cell lines after exposure to low, subtoxic, micromolar concentrations of As(III) for 24 h. Upregulation of GSH synthesis paralleled the upregulation of GR as shown by increases in glutamate-cysteine lyase (GCL) enzyme activity and mRNA levels, cystine uptake, and intracellular GSH levels. Glutathione S-transferase activity was also shown to increase slightly in keratinocytes, but not in fibroblasts or breast tumor cells. Overall the results show that sublethal arsenic induces a multicomponent response in human keratinocytes that involves upregulation of parts, but not all of the GSH system and counteracts the acute toxic effects of iAs. The upregulation of GR has not previously been shown to be an integral part of this response, although GR is critical for maintaining levels of reduced GSH.
Determination of cyclosporine concentrations with monoclonal antibodies. (1987)

We measured cyclosporine in whole blood from normal volunteers administered single oral doses of the drug and from two renal-transplant patients on immunosuppressive maintenance therapy, by liquid chromatography (I) and by radioimmunoassay with use of nonspecific polyclonal (II), specific monoclonal (III), and nonspecific monoclonal (IV) antibodies. Concentrations determined by III were equivalent to I, irrespective of cyclosporine dose, concentration, time after dose, or time after transplant. Concentrations determined by II and IV were consistently higher than those by I, owing to cross reactivity with metabolites. Ratios of values by II and IV to those by I increased from less than 1.5 to about 3-4 between 0.5 and 12 h after a single cyclosporine dose, owing to differences in rates of appearance and disappearance of cyclosporine and cross-reacting metabolites, though for the constant 12-h dose intervals in the two renal-transplant patients at steady state these ratios (most within the range 3-4) were relatively stable. Ratios of concentrations measured by IV to those by II (mean of 1.2 for single-dose data, most within the range of 1.2 to 1.5 at steady state) were unaffected by time after dose or time after transplant, suggesting that, despite certain cross-reactivity differences between the two nonspecific antibodies, results are proportional throughout therapy. We therefore propose that III and IV offer alternatives, respectively, to the currently used I and II for cyclosporine monitoring.
Salt tolerance of desorption electrospray ionization (DESI) (2007)

The salt tolerance of desorption electrospray ionization (DESI) was systematically investigated by examining three different drug mixtures in the presence of 0, 0.2, 2, 5, 10, and 20% NaCl:KCl (1:1) from different surfaces. At physiological salt concentrations, the individual drugs in each mixture were observed in each experiment. Even at salt concentrations significantly above physiological levels, particular surfaces were effective in providing spectra that allowed the ready identification of the compounds of interest in low nanogram amounts. Salt adducts, which are observed even in the absence of added salt, could be eliminated by adding 0.1% 7 M ammonium acetate to the standard methanol:water (1:1) spray solvent. Comparison of the salt tolerance of DESI with that of electrospray ionization (ESI) demonstrated better signal/noise characteristics for DESI. The already high salt tolerance of DESI can be optimized further by appropriate choices of surface and spray solution.
A Simple and Efficient Approach to the Synthesis of 2-Phenylquinazolines via sp3 C−H Functionalization (2010)

A facile and novel approach to the synthesis of 2-phenylquinazolines was developed via a tandem reaction following sp(3) C-H functionalization. Twenty-five examples of 2-phenylquinazolines were obtained from easily available 2-aminobenzophenones and benzylic amines with good to excellent yields.
The Cytoplasmic Tails of Protease-activated Receptor-1 and Substance P Receptor Specify Sorting to Lysosomes versusRecycling (1999)

The G protein-coupled receptor (GPCR) for thrombin, protease-activated receptor-1 (PAR1), is activated when thrombin cleaves its amino-terminal exodomain. The irreversibility of this proteolytic mechanism raises the question of how desensitization and resensitization are accomplished for thrombin signaling. PAR1 is phosphorylated, uncoupled from signaling, and internalized after activation like classic GPCRs. However, unlike classic GPCRs, which internalize and recycle, activated PAR1 is sorted to lysosomes. To identify the signals that specify the distinct sorting of PAR1, we constructed chimeras between PAR1 and the substance P receptor. Wild-type substance P receptor internalized and recycled after activation; PAR1 bearing the cytoplasmic tail of the substance P receptor (P/S) behaved similarly. By contrast, wild-type PAR1 and a substance P receptor bearing the cytoplasmic tail of PAR1 (S/P) sorted to lysosomes after activation. Consistent with these observations, PAR1 and the S/P chimera were effectively down-regulated by their respective agonists as assessed by both receptor protein levels and signaling. Substance P receptor and the P/S chimera showed little down-regulation. These data suggest that the cytoplasmic tails of PAR1 and substance P receptor specify their distinct intracellular sorting patterns after activation and internalization. Moreover, by altering the trafficking fates of PAR1 and substance P receptor, one can dictate the efficiency with which a cell maintains responsiveness to PAR1 or substance P receptor agonists over time.
Thiophosphate interference experiments locate phosphates important for the hammerhead RNA self-cleavage reaction (1990)

A hammerhead domain of less than 50 nucleotides is responsible for a self-cleavage reaction in the replication of plant RNA pathogens. The hammerhead is composed of three helices joining at a central conserved core of 11 single stranded nucleotides. The core is believed to fold into a tertiary structure that provides functional groups for catalysis and to coordinate one or more divalent metal ions. In this study we use a phosphorothioate substitution interference assay to identify four phosphates in the conserved core which also play a role in the self-cleavage reaction.
Efficient pure-white organic light-emitting diodes with a solution-processed, binary-host employing single emission layer (2006)

Efficient white light-emitting diodes were fabricated with a solution-processed single emission layer composing a molecular and polymeric materials mixed binary host. The main host used was a molecule of 4,4′-bis-(carbazol-9-yl) biphenyl and the assisting host used was a blue light-emitting polyfluorene-derived copolymer of poly[(9,9-dioctylfluo-renyl-2,7-diyl)-alt-co-(9-hexyl-3,6-carbazole)]. The hosts were doped via solution-mixing a green dye of tris(2-phenylpyridine) iridium (III) and a red dye of bis[2-(2′-benzo-thienyl)-pyridi-nato-N,C3,](acetylacetonate) iridium (III). One resultant device having a pure white emission of Commission Internationale de l’Eclairage (0.33, 0.33) has a maximum power efficiency of 4.2lm∕W at 802cd∕m2 and a maximum brightness of 11800cd∕m2. The better efficiency performance may be attributed to the addition of the assisting host, which halves the energy barrier for holes to inject into the light-emitting zone.