gebhart/patrepeval huggingface dataset:
Role of Leptin in the Regulation of Glucagon-Like Peptide-1 Secretion (2003)

Glucagon-like peptide-1 (GLP-1), released from intestinal endocrine L cells, is a potent insulinotropic hormone. GLP-1 secretion is diminished in obese patients. Because obesity is linked to abnormal leptin signaling, we hypothesized that leptin may modulate GLP-1 secretion. Leptin significantly stimulated GLP-1 secretion (by up to 250% of control) from fetal rat intestinal cells, a mouse L cell line (GLUTag), and a human L cell line (NCI-H716) in a dose-dependent manner (P < 0.05-0.001). The long form of the leptin receptor was shown to be expressed, and leptin induced the phosphorylation of STAT3 in the three cell types. The leptin receptor was also expressed by rodent and human intestinal L cells, and leptin (1 mg/kg i.p.) significantly stimulated GLP-1 secretion in rats and ob/ob mice. To determine the effect of leptin resistance on GLP-1 secretion, C57BL/6 mice were fed a high-fat (45%) or low-fat (10%) diet for 8 weeks. Mice on the high-fat diet became obese; developed glucose intolerance, hyperinsulinemia, and hyperleptinemia; and were leptin resistant. Mice on the high-fat diet also had twofold lower basal plasma GLP-1 and a diminished GLP-1 response to oral glucose, by 28.5 +/- 5.0% (P < 0.05). These results show for the first time that leptin stimulates GLP-1 secretion from rodent and human intestinal L cells, and they suggest that leptin resistance may account for the decreased levels of GLP-1 found in obese humans.
Activity of linezolid against Gram-positive cocci possessing genes conferring resistance to protein synthesis inhibitors (2000)

Linezolid belongs to a new class of antimicrobials, the oxazolidinones, that act by inhibiting protein synthesis. To detect cross-resistance with other inhibitors of protein synthesis (chloramphenicol, macrolides, lincosamides, streptogramins, aminoglycosides and tetracyclines), the in vitro activity of linezolid was determined against isolates harbouring known genes conferring resistance to these antimicrobials. Neither the presence of modifying enzymes (LinA, LinA', LinB, Vgb, Vat, SatA, ANT(4') (4")-I, AAC(6')-APH(2"), APHA-3 and Cat), nor the presence of an efflux mechanism (MsrA, MefE, MefA, MreA, Vga, TetK and TeL), nor the modification or protection of antimicrobial target (because of ribosomal methylases or TetM and TetO) affected linezolid activity as demonstrated by similar in vitro activity against resistant isolates and sensitive control isolates.
Compounding and stability evaluation of atorvastatin extemporaneous oral suspension using tablets or pure powder (2016)

AtC extemporaneous suspension was successfully prepared using tablets as a source of AtC or pure AtC powder. However, S<sub>t</sub>4 had a better dissolution profile than S<sub>p</sub>4. This study provides a solution for patients with swallowing difficulties or feeding tubes who are unable to take medicines in solid oral dosage forms. Community pharmacists can prepare the suspension using AtC tablets as the source of the active ingredient.
Adsorption and Covalent Coupling of ATP-Binding DNA Aptamers onto Cellulose (2006)

With the long-term goal of developing paper surfaces that will detect pathogens, we have investigated physical adsorption and covalent coupling as strategies for treating cellulose surfaces with a DNA aptamer that binds ATP. Physical adsorption was reversible and the isotherms fitted the Langmuir equation with an adsorption maximum of 0.105 mg/m2 at high ionic strength (300 mM NaCl, 25 mM Tris-HCl) and only 0.024 mg/m2 in lower ionic strength buffer (25 mM Tris-HCl). Covalent coupling of amine-terminated aptamer with oxidized cellulose film (Schiff base + reduction) gave 25% coupling efficiency while maintaining the aptamer activity which was illustrated by using a known fluorescent aptamer that is capable of ATP detection. Therefore, covalent coupling, without spacer molecules, is a promising approach for supporting biosensing aptamers on cellulose.
Breadth first search vectorization on the Intel Xeon Phi (2016)

Breadth First Search (BFS) is a building block for graph algorithms and has recently been used for large scale analysis of information in a variety of applications including social networks, graph databases and web searching. Due to its importance, a number of different parallel programming models and architectures have been exploited to optimize the BFS. However, due to the irregular memory access patterns and the unstructured nature of the large graphs, its efficient parallelization is a challenge. The Xeon Phi is a massively parallel architecture available as an off-the-shelf accelerator, which includes a powerful 512 bit vector unit with optimized scatter and gather functions. Given its potential benefits, work related to graph traversing on this architecture is an active area of research.
Mechanical deformation and failure of electrospun polyacrylonitrile nanofibers as a function of strain rate (2007)

The mechanical deformation of 12μm long electrospun polyacrylonitrile (PAN) nanofibers with diameters of 300–600nm was investigated. The nanofibers were subjected to cold drawing in atmospheric conditions and at strain rates between 10−2 and 10−4s−1. The ultimate strain of the PAN nanofibers was 60%–130% varying monotonically with the strain rate. On the contrary, the fiber tensile strength, ranging between 30 and 130MPa, varied nonmonotonically with the slowest drawing rate resulting in the largest ductilities and fiber strengths. At the two faster rates, the large fiber ductilities originated in the formation of a cascade of ripples (necks), while at the slowest strain rate, the nanofibers deformed homogeneously allowing for the largest engineering strengths and extension ratios.
The nuts and bolts of college writing (2002)

Unusual for a style handbook, Nuts and Bolts embeds writing advice in essays that identify rhetorical structures as tools for "shaping your ideas, questions and convictions to share with others." While it offers suggestions that will help writers fine-tune their sentences and paragraphs, it has a lot to say about the machinery of college writing on a grander scale--the switches, transformers, and fans which must function well before a unit can be bolted together.
Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis (2012)

The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells.
[DOT1: a distinct class of histone lysine methyltransferase]. (2007)

Lysine methylation is an important covalent modification of histone and has fundamental and divers roles in biological processes including regulation of chromatin structure dynamics and gene expression. Recently, a distinct class of histone lysine methyltransferase DOT1 was found to methylate histone H3 lysine79 (H3K79) residue, which is located on the accessible face of the core nucleosome. The DOT1 proteins do not contain a SET domain, a conserved sequence motif found in all previously characterized histone H3 lysine methyltransferases that act on the histone N-termianl tail. The characteristics of DOT1 proteins and H3K79 methylation suggest that they may have important and characteristic functions. Here, we summarize recent advances in specific structure of DOT1 protein, biological functions of DOT1 proteins and H3K79 methylation and trans-histone regulatory1 between histone H2B ubiquitination and H3K79 methylation.
The mechanism of threshold switching in amorphous alloys (1978)

This paper surveys the characteristics of threshold switching systems and examines the evidence for threshold switching as an electronic process. A semiquantitative model is proposed for the nature of the ON---state. The OFF---ON transition is also discussed in the light of recent experimentation, as are the principal aspects of the problem still in need of furthur clarification.
Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora (1993)

In vivo colonization by different Lactobacillus strains on human intestinal mucosa of healthy volunteers was studied together with the effect of Lactobacillus administration on different groups of indigenous bacteria. A total of 19 test strains were administered in fermented oatmeal soup containing 5 x 10(6) CFU of each strain per ml by using a dose of 100 ml of soup per day for 10 days. Biopsies were taken from both the upper jejunum and the rectum 1 day before administration was started and 1 and 11 days after administration was terminated. The administration significantly increased the Lactobacillus counts on the jejunum mucosa, and high levels remained 11 days after administration was terminated. The levels of streptococci increased by 10- to 100-fold in two persons, and the levels of sulfite-reducing clostridia in the jejunum decreased by 10- to 100-fold in three of the volunteers 1 day after administration was terminated. In recta, the anaerobic bacterium counts and the gram-negative anaerobic bacterium counts decreased significantly by the end of administration. Furthermore, a decrease in the number of members of the Enterobacteriaceae by 1,000-fold was observed on the rectal mucosa of two persons. Randomly picked Lactobacillus isolates were identified phenotypically by API 50CH tests and genotypically by the plasmid profiles of strains and by restriction endonuclease analysis of chromosomal DNAs.(ABSTRACT TRUNCATED AT 250 WORDS)
The B Cell Receptor Itself Can Activate Complement to Provide the Complement Receptor 1/2 Ligand Required to Enhance B Cell Immune Responses In Vivo (2003)

B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting "natural" IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.
Hepatocyte Growth Factor/Scatter Factor Binds with High Affinity to Dermatan Sulfate (1998)

We have demonstrated by affinity chromatography that hepatocyte growth factor/scatter factor (HGF/SF) binds strongly to dermatan sulfate (DS), with a similar ionic strength dependence to that previously seen with heparan sulfate (HS). Analysis of binding kinetics on a biosensor yields an equilibrium dissociation constant, KD, of 19.7 nM. This corresponds to a 10-100-fold weaker interaction than that with HS, primarily due to a faster dissociation rate of the complex. The smallest DS oligosaccharide with significant affinity for HGF/SF by affinity chromatography appears to be an octasaccharide. A sequence comprising unsulfated iduronate residues in combination with 4-O-sulfated N-acetylgalactosamine is sufficient for high affinity binding. The presence of 2-O-sulfation on the iduronate residues does not appear to be inhibitory. These observations concur with our previous suggestions, from analyses of HS binding (Lyon, M., Deakin, J. A., Mizuno, K., Nakamura, T., and Gallagher, J.T. (1994) J. Biol. Chem. 269, 11216-11223), that N-sulfation of hexosamines and 2-O-sulfation of iduronates are not absolute requirements for glycosaminoglycan binding to HGF/SF. This is the first described example of a high affinity interaction between a growth factor and DS, and is likely to have significant implications for the biological activity of this paracrine-acting factor.
On the role of the transmembrane anchor sequence of influenza hemagglutinin in target cell recognition by class I MHC-restricted, hemagglutinin-specific cytolytic T lymphocytes. (1987)

We have examined the requirement for the transmembrane hydrophobic anchor sequence of the influenza hemagglutinin (HA) in the formation of the antigenic moiety on the surface of target cells recognized by class I MHC-restricted murine CTL. For this analysis we have used a line of CV-1 monkey epithelial cells that express the transfected murine H-2Kd gene product as target cells and have used recombinant SV40-based late replacement vectors to achieve expression of genes encoding wild-type and mutant forms of HA. We have found that the majority of Kd-restricted HA-specific CTL clones recognize target cells that express a secreted HA molecule that lacks the transmembrane and cytoplasmic domains of the parent glycoprotein. Several Kd-restricted CTL clones that recognize subtype-specific and crossreactive epitopes on HA fail to recognize the anchor-negative, secreted HA or chimeric HA molecules containing the transmembrane and cytoplasmic domains of unrelated glycoproteins. These CTL clones appear to be directed to antigenic epitopes located within the transmembrane domain of HA, as defined by their capacity to recognize target cells sensitized with a synthetic 23-amino-acid peptide corresponding to sequences within this domain. The implications of these results for class I MHC-restricted CTL recognition are discussed.
Kinase-Independent Functions for Itk in TCR-Induced Regulation of Vav and the Actin Cytoskeleton (2005)

The Tec family kinase Itk is an important regulator of Ca(2+) mobilization and is required for in vivo responses to Th2-inducing agents. Recent data also implicate Itk in TCR-induced regulation of the actin cytoskeleton. We have evaluated the requirements for Itk function in TCR-induced actin polarization. Reduction of Itk expression via small interfering RNA treatment of the Jurkat human T lymphoma cell line or human peripheral blood T cells disrupted TCR-induced actin polarization, a defect that correlated with decreased recruitment of the Vav guanine nucleotide exchange factor to the site of Ag contact. Vav localization and actin polarization could be rescued by re-expression of either wild-type or kinase-inactive murine Itk but not by Itk containing mutations affecting the pleckstrin homology or Src homology 2 domains. Additionally, we find that Itk is constitutively associated with Vav. Loss of Itk expression did not alter gross patterns of Vav tyrosine phosphorylation but appeared to disrupt the interactions of Vav with SLP-76. Expression of membrane-targeted Vav, Vav-CAAX, can rescue the small interfering RNA to Itk-induced phenotype, implicating the alteration in Vav localization as directly contributing to the actin polarization defect. These data suggest a kinase-independent scaffolding function for Itk in the regulation of Vav localization and TCR-induced actin polarization.
Comparative sequence analysis of tmRNA (1999)

Minimal secondary structures of the bacterial and plastid tmRNAs were derived by comparative analyses of 50 aligned tmRNA sequences. The structures include 12 helices and four pseudoknots and are refinements of earlier versions, but include only those base pairs for which there is comparative evidence. Described are the conserved and variable features of the tmRNAs from a wide phylogenetic spectrum, the structural properties specific to the bacterial subgroups and preliminary 3-dimensional models from the pseudoknotted regions.
A 24-base-pair sequence 3' to the human erythropoietin gene contains a hypoxia-responsive transcriptional enhancer. (1993)

Erythropoietin (Epo) synthesis increases in response to hypoxia. The hepatoma cell line Hep 3B produces low basal levels of Epo mRNA which increase markedly with hypoxia. To define the sequences necessary for this response, we linked fragments of the human Epo gene to a luciferase vector, introduced these plasmids into Hep 3B cells and assayed for luciferase activity after growth in 1% or 21% oxygen. A 621-bp Epo promoter fragment resulted in a 2.4-fold increase in luciferase activity with hypoxia. We tested several Epo gene fragments upstream of this Epo promoter fragment and found that a 613-bp Bgl II-Pvu II 3' fragment had a 10-fold increase in activity with hypoxia regardless of orientation. This fragment had a similar level of activity when linked to a simian virus 40 promoter. Portions of this fragment retained activity, including a 38-bp Apa I-Taq I fragment that had a 17-fold increase in activity with hypoxia. Deletion of nt 4-13 or 19-28 from this 38-bp fragment resulted in a loss of activity. The 24-bp upstream portion of the 38-bp fragment showed an 8-fold increase in activity with hypoxia. However, deletion of nt 19-24 or mutagenesis of nt 21 or 22 in this 24-bp fragment resulted in loss of activity. Our studies indicate that the transcriptional response of the human Epo gene to hypoxia is mediated in part by promoter sequences and to a greater degree by an enhancer element located in a 24-bp portion of the 3' flanking sequence of the gene.
The Effects of MPL-Ligand, Interleukin-6 and Interleukin-11 on Megakaryocyte and Platelet Alpha-granule Proteins (1998)

Thrombopoietin (Mpl ligand), interleukin-6 (IL-6), and interleukin-11 (IL-11) differ in their effects on megakaryocyte maturation and development. In the present study, the impact of these thrombocytopoietic cytokines on biochemical and structural granule and membrane components was examined. Western blotting was performed on equivalent amounts of isolated megakaryocyte or platelet protein and the relative intensities of the enhanced chemiluminescent-visualized bands were quantitated by densitometry. Megakaryocyte growth and development factor (MGDF), a recombinant thrombopoietin-related molecule, significantly increased megakaryocyte fibronectin (72%), thrombospondin (55%), von Willebrand factor (28%) and p-selectin (CD62p) (37%) when compared to equivalent amounts of protein from saline-treated controls (p<0.01). Megakaryocyte fibrinogen was not increased. Ultrastructurally, there was a marked increase in ribosomes and rough endoplasmic reticulum even in mature-appearing megakaryocytes. Platelets from MGDF-treated mice showed small increases in fibronectin (8%), and CD62p (18%), but did not show increases in other measured alpha-granule proteins. Neither IL-6 nor IL-11 increased megakaryocyte or platelet alpha-granule proteins over levels observed in saline controls. IL-11 treated megakaryocytes, while also exhibiting an increase in ribosomes, were characterized by prominent cytoplasmic fragmentation. The study demonstrates the impact of Mpl ligand in increasing synthesized megakaryocyte alpha-granule proteins and of IL-11 in promoting megakaryocyte fragmentation.
Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function (2010)

Our study suggests a new role for MDSCs in HCC development by suppressing host immune responses, and these findings have important implications when designing immunotherapy protocols.
Macrophages and Dendritic Cells during the Early Stages of Antigen‐Induced Arthritis in Rats: Immunohistochemical Analysis of Cryostat Sections of the Whole Knee Joint (1989)

The appearance of different macrophage subpopulations, Ia-positive antigen-presenting dendritic cells and of T and B lymphocytes was studied in early phases of antigen-induced arthritis in rat knee joints. Cryostat sections of whole knee joints were analysed with immunohistochemical techniques using monoclonal antibodies against rat macrophages, Ia-antigen, and lymphocyte subpopulations. The results showed that in the early phases of the development of arthritis, the synovium was already infiltrated by many monocytes, young macrophages, granulocytes, perivascular Ia-positive non-lymphoid cells, some mature tissue macrophages, and only few T lymphocytes. In later phases not only monocytes, young macrophages and Ia-positive cells became more prominent but also the more mature ED2 positive macrophages and the ED3 positive macrophages that are normally confined to lymphoid organs became increasingly important. The T-cell population increased to some extent in later phases of arthritis induction, possibly induced by clustering with the Ia-positive cells.
Formative design evaluation of superbook (1989)

SuperBook is a hypertext browsing system designed to improve the usability of conventional documents. Successive versions of SuperBook were evaluated in a series of behavioral studies. Students searched for information in a statistics text. presented either in conventional printed form or in SuperBook form. The best version of SuperBook enabled students to answer search questions more quickly and accurately than they could with the conventional text. Students wrote higher quality “open-book” essays using SuperBook than they did with the conventional text, and their subjective ratings of the documentation strongly favored SuperBook. This work is a case study of formative design-evaluation. Behavioral evaluation of the first version of SuperBook showed how design factors and user strategies affected search and established baseline performance measures with printed text. The second version of SuperBook was implemented with the goal of improving search accuracy and speed. User strategies that had proved effective in the first study were made very easy and attractive to use. System response time for common operations was greatly improved. Behavioral evaluation of the new SuperBook demonstrated its superiority to printed text and suggested additional improvements that were incorporated into “MiteyBook,” a SuperBook implementation for PC-size screens. Search with MiteyBook proved to be approximately 25 percent faster and 25 percent more accurate than that obtained with a conventional printed book.