gebhart/patrepeval huggingface dataset:
Salt-Inducible Kinase 1 (SIK1) Is Induced by Gastrin and Inhibits Migration of Gastric Adenocarcinoma Cells (2014)

Salt-inducible kinase 1 (SIK1/Snf1lk) belongs to the AMP-activated protein kinase (AMPK) family of kinases, all of which play major roles in regulating metabolism and cell growth. Recent studies have shown that reduced levels of SIK1 are associated with poor outcome in cancers, and that this involves an invasive cellular phenotype with increased metastatic potential. However, the molecular mechanism(s) regulated by SIK1 in cancer cells is not well explored. The peptide hormone gastrin regulates cellular processes involved in oncogenesis, including proliferation, apoptosis, migration and invasion. The aim of this study was to examine the role of SIK1 in gastrin responsive adenocarcinoma cell lines AR42J, AGS-GR and MKN45. We show that gastrin, known to signal through the Gq/G11-coupled CCK2 receptor, induces SIK1 expression in adenocarcinoma cells, and that transcriptional activation of SIK1 is negatively regulated by the Inducible cAMP early repressor (ICER). We demonstrate that gastrin-mediated signalling induces phosphorylation of Liver Kinase 1B (LKB1) Ser-428 and SIK1 Thr-182. Ectopic expression of SIK1 increases gastrin-induced phosphorylation of histone deacetylase 4 (HDAC4) and enhances gastrin-induced transcription of c-fos and CRE-, SRE-, AP1- and NF-κB-driven luciferase reporter plasmids. We also show that gastrin induces phosphorylation and nuclear export of HDACs. Next we find that siRNA mediated knockdown of SIK1 increases migration of the gastric adenocarcinoma cell line AGS-GR. Evidence provided here demonstrates that SIK1 is regulated by gastrin and influences gastrin elicited signalling in gastric adenocarcinoma cells. The results from the present study are relevant for the understanding of molecular mechanisms involved in gastric adenocarcinomas.
Cooperation Between VEGF and TNF-α Is Necessary for Exposure of Active Tissue Factor on the Surface of Human Endothelial Cells (1999)

This study was undertaken to characterize tissue factor (TF) induction, localization, and functional activity in cultured human umbilical vein endothelial cells (HUVECs) exposed to recombinant vascular endothelial growth factor (rVEGF) and recombinant tumor necrosis factor-alpha (rTNF-alpha). rVEGF (1 nmol/L) and rTNF-alpha (500 U/mL) synergistically increased TF mRNA, protein, and total activity, as measured in cell lysates. To examine surface TF expression, living cells were treated with antibody to TF and examined microscopically. Almost no staining was seen in control cells or cells treated with a single agent. In contrast, cells treated with both agonists showed intense membrane staining with surface patches, appearing as buds by confocal microscopy. To determine surface TF activity, studies were performed using a parallel-plate flow chamber, which allows detection of factor Xa generation on living cells. rVEGF and rTNF-alpha induced little surface TF activity (0.032+/-0.008 and 0.014+/-0.008 fmol/cm2, respectively). In combination, they significantly increased TF expression on the cell surface (0.429+/-0.094 fmol/cm2, P<0.05). These data indicate that the synergistic effect of rVEGF and rTNF-alpha is necessary to generate functional TF on the surface of endothelial cells. The requirement for multiple agonists to expose active TF may serve to protect endothelial cells from acting as a procoagulant surface, even under conditions of cell perturbation.
Autoimmune Haemolysis in Childhood and Adolescence (1984)

The clinico-pathological features of 42 children with autoimmune haemolysis are described. Over 65% of cases were seen before their 5th birthday. In this group males predominated by the ratio of 2.5:1, but in the older children both sexes were equally affected. The incidence decreased from 1 in 188 X 10(3) in young males to 1 in 1,780 X 10(3) in children over 10. Cases were classified serologically. Of particular note was the frequency of Donath-Landsteiner haemolysis which equalled that due to warm autoantibodies; together these groups made up 79% of the total cases. Most haemolytic episodes followed an acute infection. This was frequently mild and often involved the upper respiratory tract; in only 2 patients was haemolysis associated with underlying collagenosis. Typically there was a sudden onset of pallor and malaise; jaundice, splenomegaly and hepatomegaly were found in about half the subjects. Haemoglobinuria was characteristic of Donath-Landsteiner haemolysis. The illness was severe, with Hb levels falling below 6.0 g/dl in 28 patients. Prednisolone, blood transfusion and, where indicated, antibiotics were usually effective in treating the illness, with splenectomy reserved for cases where this treatment was unsatisfactory. In several individuals no treatment was required. Recovery was rapid, and complete recovery occurred in 83% of patients, usually within 6 months. Although 2 patients died, a generally optimistic prognosis can be given, particularly in the absence of an underlying chronic disorder.
In vitro Evaluation of the Pollen Extract Cernitin T‐60, in the Regulation of Prostate Cell Growth (1990)

Nine human-derived cancer and non-cancer continuous cell lines were employed to evaluate the relative in vitro activity of the pollen extract, Cernitin T-60. Responses of the cell lines to the drug were assessed by measuring growth and cell survival as determined by cell count. The results demonstrated that of the 9 continuous cell lines tested, only those derived from the human prostate were growth inhibited by the pollen extract, whereas the non-prostate derived cells exhibited variable degrees of resistance to the T-60. The selectivity of the drug for the prostate cell lines was even more pronounced in the hormone-independent models, suggesting that there might be a place for the pollen extract in the control of abnormal growth in hormone-insensitive cells.
Improved beam waist formula for ultrashort, tightly focused linearly, radially, and azimuthally polarized laser pulses in free space (2014)

We derive an asymptotically accurate formula for the beam waist of ultrashort, tightly focused fundamental linearly polarized, radially polarized, and azimuthally polarized modes in free space. We compute the exact beam waist via numerical cubature to ascertain the accuracy with which our formula approximates the exact beam waist over a broad range of parameters of practical interest. Based on this, we describe a method of choosing parameters in the model given the beam waist and pulse duration of a laser pulse.
Meta‐analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences (2007)

A meta-analysis, unlike a literature review, synthesizes previous studies into new results. Pooled data from 211 studies measured ligand binding affinities at human (Hs) or rat (Rn) cannabinoid receptors CB1 and CB2. Cochrane methods were modified for this non-clinical analysis. Meta-regression detected data heterogeneity arising from methodological factors: use of sectioned tissues, lack of PMSF and choice of radioligand. Native brain tissues exhibited greater affinity (lower nM) than transfected cells, but the trend fell short of significance, as did the trend between centrifugation and filtration methods. Correcting for heterogeneity, mean Ki values for delta 9-tetrahydrocannabinol differed significantly between HsCB1 and RnCB1 (25.1 and 42.6 nM, respectively) but not between HsCB1 and HsCB2 (25.1 and 35.2). Mean Kd values for HsCB1, RnCB1 and HsCB2 of CP55,940 (2.5, 0.98, 0.92) and WIN55,212-2 (16.7, 2.4, 3.7) differed between HsCB1 and RnCB1 and between HsCB1 and HsCB2. SR141716A differed between HsCB1 and RnCB1 (2.9 and 1.0 nM). Anandamide at HsCB1, RnCB1 and HsCB2 (239.2, 87.7, 439.5) fell short of statistical differences due to heterogeneity. We consider these Kd and Ki values to be the most valid estimates in the literature. Sensitivity analyses did not support the numerical validity of cannabidiol, cannabinol, 2-arachidonoyl glycerol and all ligands at RnCB2. Aggregate rank order analysis of CB(1) distribution in the brain (pooled from 119 autoradiographic, immunohistochemical and in situ hybridization studies) showed denser HsCB1 expression in cognitive regions (cerebral cortex) compared to RnCB1, which was relatively richer in movement-associated areas (cerebellum, caudate-putamen). Implications of interspecies differences are discussed.
The Influence of CCL3L1 Gene-Containing Segmental Duplications on HIV-1/AIDS Susceptibility (2005)

Segmental duplications in the human genome are selectively enriched for genes involved in immunity, although the phenotypic consequences for host defense are unknown. We show that there are significant interindividual and interpopulation differences in the copy number of a segmental duplication encompassing the gene encoding CCL3L1 (MIP-1alphaP), a potent human immunodeficiency virus-1 (HIV-1)-suppressive chemokine and ligand for the HIV coreceptor CCR5. Possession of a CCL3L1 copy number lower than the population average is associated with markedly enhanced HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This susceptibility is even greater in individuals who also possess disease-accelerating CCR5 genotypes. This relationship between CCL3L1 dose and altered HIV/AIDS susceptibility points to a central role for CCL3L1 in HIV/AIDS pathogenesis and indicates that differences in the dose of immune response genes may constitute a genetic basis for variable responses to infectious diseases.
Smooth muscle specific expression of calponin (1990)

Calponin is an actin-, calmodulin-, and tropomyosin-binding protein that has been isolated from smooth muscle tissue. Using a monoclonal antibody specific for avian calponin, we demonstrate a differentiation-linked increase in calponin expression in embryonic chick gizzard. Cultivation of gizzard smooth muscle cells in vitro resulted in a down-regulation of calponin expression after the first 48 h that was paralleled by a loss of synthesis of metavinculin and the high molecular weight isoform of caldesmon. In early cultures of smooth muscle cells calponin was localised in the actin-containing stress fibres but labelling was restricted to the central parts of the actin cytoskeleton. Calponin expression is suggested as a potentially useful index of smooth muscle differentiation.
Using Micromachining, Molecular Self-Assembly, and Wet Etching to Fabricate 0.1-1-.mu.m-scale structures of Gold and Silicon (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUsing Micromachining, Molecular Self-Assembly, and Wet Etching to Fabricate 0.1-1-.mu.m-scale structures of Gold and SiliconNicholas L. Abbott, Amit Kumar, and George M. WhitesidesCite this: Chem. Mater. 1994, 6, 5, 596–602Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/cm00041a007https://doi.org/10.1021/cm00041a007research-articleACS PublicationsRequest reuse permissionsArticle Views470Altmetric-Citations62LEARN 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
Dual Phosphorylation of Btk by Akt/Protein Kinase B Provides Docking for 14-3-3ζ, Regulates Shuttling, and Attenuates both Tonic and Induced Signaling in B Cells (2013)

Bruton's tyrosine kinase (Btk) is crucial for B-lymphocyte activation and development. Mutations in the Btk gene cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. Using tandem mass spectrometry, 14-3-3ζ was identified as a new binding partner and negative regulator of Btk in both B-cell lines and primary B lymphocytes. The activated serine/threonine kinase Akt/protein kinase B (PKB) phosphorylated Btk on two sites prior to 14-3-3ζ binding. The interaction sites were mapped to phosphoserine pS51 in the pleckstrin homology domain and phosphothreonine pT495 in the kinase domain. The double-alanine, S51A/T495A, replacement mutant failed to bind 14-3-3ζ, while phosphomimetic aspartate substitutions, S51D/T495D, caused enhanced interaction. The phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 abrogated S51/T495 phosphorylation and binding. A newly characterized 14-3-3 inhibitor, BV02, reduced binding, as did the Btk inhibitor PCI-32765 (ibrutinib). Interestingly, in the presence of BV02, phosphorylation of Btk, phospholipase Cγ2, and NF-κB increased strongly, suggesting that 14-3-3 also regulates B-cell receptor (BCR)-mediated tonic signaling. Furthermore, downregulation of 14-3-3ζ elevated nuclear translocation of Btk. The loss-of-function mutant S51A/T495A showed reduced tyrosine phosphorylation and ubiquitination. Conversely, the gain-of-function mutant S51D/T495D exhibited intense tyrosine phosphorylation, associated with Btk ubiquitination and degradation, likely contributing to the termination of BCR signaling. Collectively, this suggests that Btk could become an important new candidate for the general study of 14-3-3-mediated regulation.
Effects of Dichloroisoproterenol on Blood Sugar and Plasma Free Fatty Acids. (1962)

Summary3,4,Dichloroisopropylarterenol (DCI) elevates the FFA level in anesthetized dogs. However, in vitro it does not cause FFA release from adipose tissue. Isoproterenol induces elevations of plasma FFA and glucose which are reduced by DCI (4 mg kg). Glucagon hyperglycemia is also antagonized by DCI. DCI effects in vivo can be overridden by increasing the dose of isoproterenol or glucagon.
Carrying Label Information in BGP-4 (2001)

This document specifies the way in which the label mapping information for a particular route is piggybacked in the same Border Gateway Protocol (BGP) Update message that is used to distribute the route itself. When BGP is used to distribute a particular route, it can be also be used to distribute a Multiprotocol Label Switching (MPLS) label which is mapped to that route.
Long-Term Preservation of Ischemic Myocardium after Experimental Coronary Artery Occlusion (1978)

The results of experiments with indirect methods have suggested that various interventions reduce infarct size after coronary artery occlusion. To determine and quantify directly both the short- and long-term effects of several interventions on myocardial salvage without relying on indirect methods, the left coronary artery was occluded in 880 rats; they were then given either no treatment or one of the following interventions: (a) hyaluronidase, an enzyme that hydrolyzes interstitial glycoproteins, 1,500 National Formulary (NF) U/kg i.v. 5 min and 24 h after occlusion; (b) cobra venom factor, a protein that depletes the third component of complement, 20 U/kg i.v. 5 min after occlusion; (c) a glucocorticoid: hydrocortisone, 50 mg/kg i.v. 5 min after occlusion; or the five-fold more potent methylprednisolone (MP): (i) 50 mg/kg i.v. 5 min after occlusion or (ii) 50 mg/kg i.v. 5 min after occlusion followed by 50 mg/kg i.m. 3, 6, and 24 h after occlusion; or (d) reserpine, an agent that depletes the heart of catecholamines, 0.5 mg/kg i.m. once on each of the 3 days before occlusion. The animals were sacrificed either 2 days after occlusion, i.e., at the time of peak necrosis, or after 3 wk, i.e., after the infarct was completely healed. The amount of preserved myocardium was then assessed by two independent techniques: planimetric measurement of serial histologic sections and creatine kinase activity of the whole left ventricle. The amount of normal myocardium preserved at 21 days postocclusion was significantly increased, by 22.3+/-7.8% (P < 0.025) after the administration of hyaluronidase, by 25.3+/-5.8% (P < 0.005) after cobra venom factor, by 14.5+/-6.9% (P < 0.05) after hydrocortisone, by 20.8+/-8.2% (P < 0.025) after the single dose of MP, by 20.9+/-3.9% (P < 0.001) after the four doses of MP, and by 10.2+/-3.7% (P < 0.05) as a result of pretreatment with reserpine. The four doses of MP significantly thinned the infarct-by 25.6+/-2.9% (P < 0.001)-and although ventricular rupture did not occur, the intervention caused distension of the left ventricle as a result of stretching of the infarcted tissue during scar formation. Thus, myocardium acutely jeopardized by ischemia can be preserved on a long-term basis.
ASIC3, an Acid-Sensing Ion Channel, is Expressed in Metaboreceptive Sensory Neurons (2005)

Our data indicates that: 1) ASIC3 is expressed in a restricted population of nociceptors and probably in some non-nociceptors; 2) co-expression of ASIC3 and CGRP, and the absence of P2X3, are distinguishing properties of a class of sensory neurons, some of which innervate blood vessels. We suggest that these latter afferents may be muscle metaboreceptors, neurons that sense the metabolic state of muscle and can trigger pain when there is insufficient oxygen.
Surface Proteins of Gram-Positive Bacteria and Mechanisms of Their Targeting to the Cell Wall Envelope (1999)

The cell wall envelope of gram-positive bacteria is a macromolecular, exoskeletal organelle that is assembled and turned over at designated sites. The cell wall also functions as a surface organelle that allows gram-positive pathogens to interact with their environment, in particular the tissues of the infected host. All of these functions require that surface proteins and enzymes be properly targeted to the cell wall envelope. Two basic mechanisms, cell wall sorting and targeting, have been identified. Cell well sorting is the covalent attachment of surface proteins to the peptidoglycan via a C-terminal sorting signal that contains a consensus LPXTG sequence. More than 100 proteins that possess cell wall-sorting signals, including the M proteins of Streptococcus pyogenes, protein A of Staphylococcus aureus, and several internalins of Listeria monocytogenes, have been identified. Cell wall targeting involves the noncovalent attachment of proteins to the cell surface via specialized binding domains. Several of these wall-binding domains appear to interact with secondary wall polymers that are associated with the peptidoglycan, for example teichoic acids and polysaccharides. Proteins that are targeted to the cell surface include muralytic enzymes such as autolysins, lysostaphin, and phage lytic enzymes. Other examples for targeted proteins are the surface S-layer proteins of bacilli and clostridia, as well as virulence factors required for the pathogenesis of L. monocytogenes (internalin B) and Streptococcus pneumoniae (PspA) infections. In this review we describe the mechanisms for both sorting and targeting of proteins to the envelope of gram-positive bacteria and review the functions of known surface proteins.
A self-aligned airgap interconnect scheme (2009)

A new air-gap interconnect scheme with no additional patterning step successfully resolves the issue of unlanded via, and provides good interconnect reliability and improved packaging margin. We demonstrate that the insertion of airgaps in a very low-k dielectric (k=2.5) reduces the RC value of a 0.07 um/0.07 um comb structure by ~14%, which is equivalent to an effective dielectric constant about 2.2.
Analysis and design of a dual-band circularly polarized microstrip patch antenna (1995)

In the last decade a great effort has been made concerning research on frequency agility of microstrip patch antennas. In all these attempts an increase in length or height of the patch is generally expected and there is a tradeoff between wider bandwidth and good axial ratio. This paper presents the analysis and design of a novel dual-band circularly polarized microstrip patch antenna using a spur-line band-stop filter and a perturbation segment technique. This dual frequency operation can be obtained without increasing either the size or the thickness of the patch while other features are not degraded.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness (1997)

The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin (IL) 5 secreted from antigen-specific CD4+ T cells of the T helper cell (Th) 2 subset. However, while it is established that costimulation through CD28 is required for TCR-mediated activation and IL-2 production, the importance of this mechanism for the induction of a Th2 immune response is less clear. In the present study, we administered the fusion protein CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to determine whether CD28/CTLA-4 ligands are required for allergen-induced eosinophil accumulation and the production of Th2 cytokines. Administration of CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the production of IL-4, IL-5, and IL-10 by 70-80% and enhanced interferon-gamma production from CD3-T cell receptor-activated lung Thy1.2+ cells. Allergen exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation, although was less effective in inhibiting Th2 cytokine production. The anti-B7-2, but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness in vivo. In all of the parameters assessed, the combination of both the anti-B7-1 and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We propose that strategies aimed at inhibition of CD28 interactions with B7-2 molecules may represent a novel therapeutic target for the treatment of lung mucosal allergic inflammation.
Storage Hierarchy Optimization Procedure (1975)

The goal of storage hierarchies is to combine several storage technologies in such a way as to approach the performance of the fastest component technology and the cost of the least expensive one. This paper presents optimization techniques for a storage hierarchy subject to quantity-sensitive component costs. It is assumed that a finite (and probably small) set of technologies is available. Each technology is characterized by an access time and two cost parameters. We assume that statistical summaries of address sequences are available. We present solutions to four problems of increasing complexity: 1) minimization of access time for a fixed cost and preassigned page sizes; 2) optimization of a generalized price-performance function under preassigned page sizes; 3) minimization of access time for a fixed cost when page sizes are allowed to vary; 4) optimization of a generalized price-performance function when page sizes are allowed to vary.