gebhart/patrepeval huggingface dataset:
Differentiation of New Insulin-Producing Cells Is Induced by Injury in Adult Pancreatic Islets (1997)

The ability of the adult pancreas to generate new insulin (β) cells has been controversial because of difficulties in unequivocally identifying the precursor population. We recently determined that β cells were generated during development from precursors that expressed the homeodomain-containing transcription factor pancreas duodenum homeobox gene-1 (PDX-1). To investigate whether PDX-1+ stem cells are present in adult pancreas, we examined two animal models of diabetes. One model was produced by injecting adult mice with streptozotocin (SZ), a toxin that produces hyperglycemia due to rapid and massive β cell death. After SZ-mediated elimination of existing IN+/PDX-1+ cells, a population of somatostatin (SOM)+/PDX-1+ cells, a cell type thought to represent an embryonic islet precursor cell, appeared in islets. The appearance of SOM+/PDX-1+ cells was followed in time by the differentiation to SOM+/IN+/PDX-1+cells. SOM+/PDX-1+ cells also appeared in islets of nonobese diabetic mice, a strain of mice in which β cell destruction is immune-mediated. Our findings establish the existence of PDX-1+ β cell precursors in the adult pancreas and indicate that their differentiation is induced by islet injury .
Comparison of Three Different Fat Graft Preparation Methods (2013)

Washing with filtration within a closed system produces a fat graft with higher tissue viability and lower presence of contaminants compared with grafts prepared by alternate methods.
SuperWeb: research issues in Java-based global computing (1997)

The Internet, in particular the World Wide Web, continues to expand at an amazing pace. We propose a new infrastructure, SuperWeb, to harness global resources, such as CPU cycles or disk storage, and make them available to every user on the Internet. SuperWeb has the potential for solving parallel supercomputing applications involving thousands of co-operating components on the Internet. However, we anticipate that initial implementations will be used inside large organizations with large heterogeneous intranets. Our approach is based on recent advances in Internet connectivity and the implementation of safe distributed computing realized by languages such as Java. Our SuperWeb prototype consists of brokers, clients and hosts. Hosts register a fraction of their computing resources (CPU time, memory, bandwidth, disk space) with resource brokers. Clients submit tasks that need to be executed. The broker maps client computations onto the registered hosts. We examine an economic model for trading computing resources, and discuss several technical challenges associated with such a global computing environment. © 1997 John Wiley & Sons, Ltd.
Development and application of a sensitive radioimmunoassay for human granulocyte-macrophage colony-stimulating factor able to measure normal concentrations in blood. (1993)

A radioimmunoassay (RIA) for human granulocyte-macrophage colony-stimulating factor (GM-CSf) was developed based on antibodies from rabbits immunized with glycosylated recombinant human (rh) GM-CSF. The antibodies are specific for human GM-CSF and do not crossreact with other human hematopoietic growth factors or mouse GM-CSF. The antibodies also react with nonglycosylated rhGM-CSF, so E. coli-derived rhGM-CSF can be assayed as well. The RIA has a measuring range of about 10 to 200 pg/mL. Normal blood was found to contain 13 to 24 pg/mL (95% limits) with a mean of 18.5 pg/mL (n = 34). Monoclonal antibodies against GM-CSF could remove GM-CSF from normal human serum, thus ensuring that the GM-CSF measured in serum is real and does not represent nonspecific reactivity with our polyclonal rabbit antibodies. While previously published methods have been unable to measure GM-CSF in human serum under normal conditions, our more sensitive RIA does confirm the presence of small amounts of GM-CSF in serum or plasma and can therefore be used to detect fluctuations of GM-CSF in health and in disease.
Type I collagen in solution. Structure and properties of fibril fragments. (1980)

We have measured the diffusion coefficient and weight average molecular weight of type I collagen fibril fragments obtained by acid extraction of rat tail tendons and neutral extraction of lathyritic chick skin, using laser light scatttering techniques. The molecular weight and translational diffusion coefficient were found to be 8.05 +/- 0.40 x 10(5) and 0.450 +/- 0.04 x 10 (-7) cm2/s, respectively, for preparations which contain aggregates in 0.01 M HCl, and 2.82 +/- 0.20 x 10 (5) and 0.780 +/- 0.04 x 10 (-7) cm(2)/s for collagen single molecules. Using these data, as well as the theoretical diffusion coefficient for a single collagen molecule, models for various staggering modes and aggregate mixtures were developed in an attempt to understand the structure of the fibril components present in solution. It was found that several models with 1 to 4 D (D = 67 nm) staggers fit the experimental data for the aggregated preparations. Analysis of the end-to-end distance of negatively stained segment long spacing crystallites prepared from solutions containing fibril fragments and the banding pattern of positively stained segment long spacing crystallites suggest that collagen solutions contain linear aggregates with 4 D and possibly 4.4 D staggers in agreement with light scattering data. Thermal denaturation studies demonstrate that the apparent melting point of cross-linked linear aggregates, 33.5 +/- 0.5 degrees C, is identical with that of single molecules at pH 2.0. We conclude that a linear filament with predominant 4 D stagger is a basic unit of type I collagen fibrillar structure.
Pharmacology of Local Anesthetic Agents (1981)

Local anesthetic agents may be classified according to their intrinsic anesthetic potency and duration of activity. Procaine and chloroprocaine are relatively weak, short-acting drugs. Lidocaine, mepivacaine, and prilocaine represent agents of intermediate potency and duration of action. Tetracaine, bupivacaine, and etidocaine are highly potent, long-acting agents. The toxicity of local anesthetic drugs is usually due to inadvertent rapid intravascular injection or extravascular administration of an excessive amount. Intravascular toxicity is correlated with intrinsic anesthetic potency, whereas toxicity following extravascular injections is a function of physiological disposition characteristics of the various agents, such as rate of vascular absorption, rate of tissue redistribution, and rate of metabolism. The central nervous system is most susceptible to the toxic effects of local anesthetic agents. Signs and symptoms of CNS excitation followed by depression are the most common manifestations of local anesthetic toxicity. Cardiovascular depression may also occur following administration of excessive doses of local anesthetic agents or following high spinal or epidural anesthesia.
Purification and Characterization of 1-O-Acylceramide Synthase, a Novel Phospholipase A2 with Transacylase Activity (1998)

A novel pathway for ceramide metabolism, 1-O-acylceramide formation, was previously reported (Abe, A., Shayman, J. A., and Radin, N. S. (1996) J. Biol. Chem. 271, 14383-14389). In this pathway a fatty acid in the sn-2 position of phosphatidylethanolamine or phosphatidylcholine is transferred to the 1-hydroxyl position of ceramide. An enzyme that catalyzes the esterification of N-acetylsphingosine was purified from the postmitochondrial supernatant of calf brain through consecutive steps, including ammonium sulfate fractionation, DEAE-Sephacel, phenyl-Sepharose, S-Sepharose, Sephadex G-75, concanavalin A-agarose, and heparin-Sepharose chromatography. The molecular mass of the enzyme was determined to be 40 kDa by gel filtration on Sephadex G-75. The enzyme bound to concanavalin A-agarose column was eluted with the buffer containing 500 mM alpha-methyl-D-mannopyranoside. Further purification by heparin-Sepharose chromatography resulted in separation of two peaks of enzyme activity. Coincidence between the transacylase activity and a stained protein of a molecular mass of 40 kDa was observed, as determined by SDS-polyacrylamide gel electrophoresis and recovery after separation over an acidic native gel. The second peak of activity from the heparin-Sepharose chromatography represented a purification of 193,000-fold. These results are consistent with the enzyme being a glycoprotein of a molecular mass of about 40 kDa with a single polypeptide chain. The purified enzyme had a pH optimum at pH 4.5. The divalent cations Ca2+ and Mg2+ enhanced but were not essential for the transacylase activity. Neither activation nor inactivation of the enzyme activity was observed in the presence of 2 mM ATP or 2 mM dithiothreitol. Preincubation of the enzyme with 1 mM N-ethylmaleimide, 1 mM phenylmethylsulfonyl fluoride, or 3.1 microM bromoenol lactone, a potent inhibitor of cytosolic Ca2+-independent phospholipase A2, had no significant effect on the enzyme activity. The enzyme activity was completely abolished in the presence of greater than 773 microM Triton X-100. Partial inhibition of the enzyme activity was observed in the presence of 10-100 microg/ml heparin. In the absence of N-acetylsphingosine, the enzyme acted as a phospholipase A2. These results strongly suggest that 1-O-acylceramide synthase is both a transacylase and a novel phospholipase A2.
Domain structure of the carboxyl-terminal half of human plasma fibronectin. (1983)

The organization of domains in the COOH-terminal half of human plasma fibronectin was analyzed after controlled tryptic hydrolysis.In physiological salt so- lutions, fragments from this region interact with fibrin, heparin, and the cell surface, but not with actin, Stuphylococcus aureus, or native DNA.Each of the four major tryptic fragments (designated 7,9,13, and 22) was purified by sequential affinity-and DEAE-column chromatography.The relationships between these fragments were examined by affinity chromatography, sequential tryptic cleavage, and two-dimensional peptide mapping; in addition, cell-spreading activity and content of carbohydrate and free sulfhydryl groups were also determined for each fragment.The apparent relative order of binding sites is cellbinding domain (fragment 13, M, = 75,000); heparinbinding domain (subfragment 20c of fragment 9, M, = 38,000); fibrin-binding domain (fragment 22, Mr = 34,000) for the A chain, and cell-binding domain (fragment 13); heparin-binding domain (NH2-terminal part of subfragment 15 of fragment 7, M, = 58,000), and fibrin-binding domain (COOH-terminal part of subfragment 15) for the B chain.Carbohydrates and a free sulfhydryl group are present in the cell-binding region, and a second free sulihydryl or labile disulfide appears to be present on both chains in the fibrin-binding region.An apparent region of difference between the chains is present between COOH-terminal heparin-and fibrin-binding domains.These studies provide a map of the domains in the COOH-terminal half of fibronectin, and they indicate relatively limited structural and functional differences between the A and B chains of fibronectin.This map and the establishment of purification protocols for fragments spanning this entire region should also be useful in future analyses of fibronectin primary structure.The adhesive glycoprotein fibronectin appears to function in a wide variety of cellular functions, including cell-to-substratum adhesion, cell-to-cell adhesion, ceU migration, cell growth, embryonic differentiation, regulation of cell morphology and alignment, wound healing, and reticuloendothelial clearance of colloidal debris (1-8).These biological activities
Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. (1994)

The N-terminal domain of the c-Myc protein has been reported to be critical for both the transactivation and biological functions of the c-Myc proteins. Through detailed phosphopeptide mapping analyses, we demonstrate that there is a cluster of four regulated and complex phosphorylation events on the N-terminal domain of Myc proteins, including Thr-58, Ser-62, and Ser-71. An apparent enhancement of Ser-62 phosphorylation occurs on v-Myc proteins having a mutation at Thr-58 which has previously been correlated with increased transforming ability. In contrast, phosphorylation of Thr-58 in cells is dependent on a prior phosphorylation of Ser-62. Hierarchical phosphorylation of c-Myc is also observed in vitro with a specific glycogen synthase kinase 3 alpha, unlike the promiscuous phosphorylation observed with other glycogen synthase kinase 3 alpha and 3 beta preparations. Although both p42 mitogen-activated protein kinase and cdc2 kinase specifically phosphorylate Ser-62 in vitro and cellular phosphorylation of Thr-58/Ser-62 is stimulated by mitogens, other in vivo experiments do not support a role for these kinases in the phosphorylation of Myc proteins. Unexpectedly, both the Thr-58 and Ser-62 phosphorylation events, but not other N-terminal phosphorylation events, can occur in the cytoplasm, suggesting that translocation of the c-Myc proteins to the nucleus is not required for phosphorylation at these sites. In addition, there appears to be an unusual block to the phosphorylation of Ser-62 during mitosis. Finally, although the enhanced transforming properties of Myc proteins correlates with the loss of phosphorylation at Thr-58 and an enhancement of Ser-62 phosphorylation, these phosphorylation events do not alter the ability of c-Myc to transactivate through the CACGTG Myc/Max binding site.
假想中国“入世”第一天 (2001)

中国加入世贸组织，毫无疑问将成为世界经济舞台在21世纪第一个亮点。世界对此的关注程度也达到了一个很高的热度。《纽约时报》资深记者克雷格·S·史密斯从一个独特的视角为我们表露了在西方人眼中“入世”给中国带来的变化。希望在不远的一天我们能验证它的真实。
Prophylactic and therapeutic efficacies of a selective inhibitor of the immunoproteasome for Hashimoto's thyroiditis, but not for Graves' hyperthyroidism, in mice (2012)

Major histocompatibility complex (MHC) class I-restricted T cell epitopes are generated mainly by the immunoproteasome in antigen-presenting cells. Therefore, inhibition of activity of this proteolytic complex molecule is thought to be a potential treatment for cell-mediated autoimmune diseases. We therefore studied the efficacy of an immunoproteasome inhibitor, ONX 0914 (formerly PR-957), for the treatment of autoimmune thyroid diseases, including cell-mediated Hashimoto's thyroiditis and autoantibody-mediated Graves' hyperthyroidism using mouse models. Our data show that ONX 0914 was effective prophylactically and therapeutically at suppressing the degree of intrathyroidal lymphocyte infiltration and, to a lesser degree, the titres of anti-thyroglobulin autoantibodies in non-obese diabetic (NOD)-H2(h4) mice, an iodine-induced autoimmune thyroiditis model. It also inhibited differentiation of T cells to T helper type 1 (Th1) and Th17 cells, effector T cell subsets critical for development of thyroiditis in this mouse strain. In contrast, its effect on the Graves' model was negligible. Although ONX 0914 exerts its immune-suppressive effect through not only suppression of immune proteasome but also other mechanism(s), such as inhibition of T cell differentiation, the present results suggest that the immunoproteasome is a novel drug target in treatment of Hashimoto's thyroiditis in particular and cell-mediated autoimmune diseases in general.
Radiofrequency sacroiliac joint denervation for sacroiliac syndrome (2001)

This study suggests that RF denervation of the SI joint can significantly reduce pain in selected patients with sacroiliac syndrome for a protracted time period. Moreover, certain abnormal physical findings (i.e., SI joint pain provocation tests) revert to normal for the duration of the analgesia.
Type-I Diabetes: A Chronic Autoimmune Disease of Human, Mouse, and Rat (1990)

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
Millimeter-wave generation and characterization of a GaAs FET by optical mixing (1990)

Coherent mixing of optical radiation from a tunable continuous-wave dye laser and a stabilized He-Ne laser was used to generate millimeter-wave signals in GaAs FETs attached to printed-circuit millimeter-wave antennas. The generated signal was further down-converted to a 2-GHz IF by an antenna-coupled millimeter-wave local oscillator at 62 GHz. Detailed characterizations of power and S/N under different bias conditions have been performed. This technique is expected to allow signal generation and frequency-response evaluation of millimeter-wave devices at frequencies as high as 100 GHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cytoplasmic intron retention, function, splicing, and the sentinel RNA hypothesis (2013)

Cytoplasmic splicing represents a newly emerging level of transcriptional regulation adding to the molecular diversity of mammalian cells. As examples of this noncanonical form of transcript processing are discovered, the evidence of its importance to normal cellular function grows. Work from a number of groups using a variety of cell types is steadily identifying a large number of transcripts (and soon to be even larger as genome-wide analyses of retained introns across a number of cellular phenotypes are currently underway) that undergo some level of regulated endogenous extranuclear splicing as part of their normal biosynthetic pathway. Here, we review the existing data covering cytoplasmic retained intron sequences and suggest that such sequences may be a component of 'sentinel RNA' that serves to generate transcript variants within the cytoplasm as well as a source for RNA-based secondary messages.
Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1) (2017)

Entrectinib, a potent oral inhibitor of the tyrosine kinases TRKA/B/C, ROS1, and ALK, was evaluated in two phase I studies in patients with advanced or metastatic solid tumors, including patients with active central nervous system (CNS) disease. Here, we summarize the overall safety and report the antitumor activity of entrectinib in a cohort of patients with tumors harboring <i>NTRK1/2/3, ROS1</i>, or <i>ALK</i> gene fusions, naïve to prior TKI treatment targeting the specific gene, and who were treated at doses that achieved therapeutic exposures consistent with the recommended phase II dose. Entrectinib was well tolerated, with predominantly Grades 1/2 adverse events that were reversible with dose modification. Responses were observed in non-small cell lung cancer, colorectal cancer, mammary analogue secretory carcinoma, melanoma, and renal cell carcinoma, as early as 4 weeks after starting treatment and lasting as long as >2 years. Notably, a complete CNS response was achieved in a patient with <i>SQSTM1-NTRK1</i>-rearranged lung cancer.<b>Significance:</b> Gene fusions of <i>NTRK1/2/3, ROS1</i>, and <i>ALK</i> (encoding TRKA/B/C, ROS1, and ALK, respectively) lead to constitutive activation of oncogenic pathways. Entrectinib was shown to be well tolerated and active against those gene fusions in solid tumors, including in patients with primary or secondary CNS disease. <i>Cancer Discov; 7(4); 400-9. ©2017 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 339</i>.
Providing Residential Services for Children and Young People: A Multidisciplinary Perspective C. Street Aldershot: Ashgate Publishing, 1999. pp. 247. £39.95 (hb). (2001)

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Development of Methods for the Synthesis of Libraries of Substituted Maleimides and α,β-Unsaturated-γ-butyrolactams (2011)

Synthetic methods for the preparation of maleimide and α,β-unsaturated-γ-butyrolactam compound collections are described. These routes take advantage of Pd cross-coupling and conjugate addition/elimination reactions to permit the facile production of bisaryl-maleimides, anilinoaryl-maleimides, and bisanilino-maleimides while allowing control over the synthesis of symmetrical or nonsymmetrical derivatives. Similarly, the chemistry developed allows for the generation of bisaryl substituted α,β-unsaturated-γ-butyrolactams. The scope and limitations of the approaches are presented.
Replacement of Integration Host Factor Protein-induced DNA Bending by Flexible Regions of DNA (1999)

The Escherichia coli integration host factor (IHF) protein is required for site-specific recombination of bacteriophage lambda DNA. Previously, we had shown that alternative modules of static DNA curvature could partially replace IHF in recombination. Now we use regions of single-stranded DNA as a flexible tether to address whether the function of IHF in recombination is simply to reduce persistence length. Although we find that these modules clearly enhance recombination in the absence of IHF, they are not perfect replacements. In addition, evidence is presented that the efficacy of a flexibility swap is specific to a particular IHF site. This may indicate that additional functions beyond simple deformation of DNA are required of IHF. During the course of these experiments we discovered that these flexible sequences are still specific sites for IHF binding and function.
THE ISOLATION AND TRANSPLANTATION OF FOETAL MOUSE PROISLETS (1982)

A method is described for the isolation of "proislets' from mouse foetal pancreas. Histologically, isolated proislets are composed of undifferentiated tissue which does not stain with aldehyde fuchsin. Following isotransplantation, proislets develop into well differentiated islets with beta cell granulation. In addition, isografts consisting of proislets harvested from 8 foetal mouse pancreases have the functional capacity to reverse Streptozotocin-induced diabetes. Proislets appear to represent foetal precursor islet tissue.
The search for peripheral biomarkers for major depression: Benefiting from successes in the biology of smoking (2014)

The search for robust, clinically useful markers for major depression (MD) has been relatively unproductive. This is unfortunate because MD is one of the largest socio-economic challenges for much of the world and the development of reliable biomarkers for MD could aid in the prevention or treatment of this common syndrome. In this editorial, we compare the approaches taken in the search for biomarkers for MD to that of the more successful searches for biomarkers for tobacco use, and identify several substantive barriers. We suggest that many of the existing clinical repositories used in these biomarkers searches for MD may be of limited value. We conclude that in the future greater attention should be given to the clinical definitions, characterization of confounding environmental factors and age of subjects included in studies. © 2014 Wiley Periodicals, Inc.
Characterization of Block Copolymers by Liquid Adsorption Chromatography at Critical Conditions. 1. Diblock Copolymers (2000)

Liquid adsorption chromatography at critical conditions (LACCC) in normal and in reversed-phase modes provides independent information on the molar mass distributions of both blocks of poly(methyl methacrylate)-block-poly(tert-butyl methacrylate), even if no information about the precursor is available. In addition, the amount of unreacted precursor can be determined, even if its molar mass is comparable to that of the total block copolymer. The reversal of elution order by changing of stationary and mobile phases makes it possible to independently characterize each block in the SEC mode of the LACCC system. Thus, complete structural information is obtained even without using two-dimensional chromatographic techniques.