gebhart/patrepeval huggingface dataset:
Capillary electrophoresis coupled to mass spectrometer for automated and robust polypeptide determination in body fluids for clinical use (2004)

We describe the application of capillary electrophoresis (CE) coupled on-line to an electrospray ionization-time of flight-mass spectrometer (ESI-TOF-MS) to the analysis of human urine and serum for the identification of biomarkers for clinical diagnostics. CE-MS led to display > 1000 polypeptides present in complex biological samples within 45-60 min in a single analysis run. To extract the information of the CE-MS spectra in a timely fashion, a software was designed to automatically deconvolute and normalize the spectra. Both urine and serum contain several hundred polypeptides in samples from healthy individuals. Hence, it is possible to establish typical "normal urine" or "normal serum" polypeptide patterns. Samples from patients with different diseases display polypeptide patterns that differ significantly from those obtained from healthy individuals. Examining series of patients with the same disease allowed the establishment of polypeptide patterns typical for specific diseases. This permits the search for marker peptides specific for diseases. The data indicate that a single polypeptide present in all patients with the same disease, but absent in all healthy control individuals does not exist. The combination of several polypeptides found in either urine or serum or both are forming a specific pattern, which is indicative not only for the particular disease, but also for the stage of disease. CE-MS detects many polypeptides in single samples and the application of the software to the search of identical polypeptides excreted in urine allows the unbiased diagnosis based on a pattern and does not rely on single disease markers.
Bile salt hydroxylation as a mechanism for detoxification in SPGP knockout mice (2009)

In humans, mutations in the Sister of P-glycoprotein (spgp) gene involved in bile salt transport lead to progressive familial intrahepatic cholestasis type 2 (PFIC2). Generation of the spgp[sup -/-] mice demonstrated that the mice are not affected as severely as humans. Analysis of the biliary bile salt pool of the spgp[sup -/-] mice indicated the presence of tetrahydroxylated bile salts. However, the transport rate of the hydrophilic bile salts was unaffected. Examination of tetrahydroxylated bile salts as a possible detoxification mechanism requires identification and characterization of the enzyme involved. Development of an HPLC bile salt separation method generated bile salt profiles of spgp[sup -/-] and wild-type mice fed a normal or 0.5% cholic acid (CA) enriched diet. Analysis of the profiles suggested the 2-day change in diet had little effect on the already elevated levels of tetrahydroxylated bile salt levels in the spgp[sup -/-] mice. However, wild-type mice produced increased levels of the tetrahydroxylated bile salt when fed the 0.5% CA diet. Three tetrahydroxylated bile salt species were present in the HPLC profiles. Expression analysis of the CYP3A family, the three major enzymes in bile salt synthesis, and five of the main nuclear receptors involved in the regulation of cholesterol and bile salt metabolism was performed using Northern Blot analysis and real-time PCR. When tetrahydroxylated bile salt levels were compared to the mRNA expression levels, there was little correlation to the candidate genes tested. Furthermore, the reduction in CYP7A1 and CYP8B1 expression levels under the 0.5% CA supplemented diet indicated substrates from these pathways are not involved in the synthesis of the tetrahydroxylated bile salts. Consequently, it is believed that bile salt tetrahydroxylation is either regulated at the protein level or is due to expression of a gene not tested.
The β2-Adrenergic Receptor Delivers an Antiapoptotic Signal to Cardiac Myocytes Through Gi-Dependent Coupling to Phosphatidylinositol 3′-Kinase (2000)

Recent studies have shown that chronic beta-adrenergic receptor (beta-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective beta(1)- and beta(2)-AR subtype stimulation on apoptosis induced by hypoxia or H(2)O(2) in rat neonatal cardiac myocytes. Although neither beta(1)- nor beta(2)-AR stimulation had any significant effect on the basal level of apoptosis, selective beta(2)-AR stimulation protected myocytes from apoptosis. beta(2)-AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3'-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. beta(1)-AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked beta(2)-AR-mediated protection from apoptosis as well as the beta(2)-AR-stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked beta(2)-AR-mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on beta(2)-AR-mediated protection. These findings demonstrate that beta(2)-ARs activate a PI-3K-dependent, pertussis toxin-sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.
Genetic and epigenetic inactivation of TNFRSF10C in human prostate cancer (2008)

We found a notably high frequency of promoter CGI methylation and deletion of TNFRSF10C in PCa tissues. Our results indicated that inactivation of TNFRSF10C by chromosomal deletion and promoter methylation may play an important role in PCa development.
Atrial Fibrillation Ablation with Esophageal Cooling with a Cooled Water‐Irrigated Intraesophageal Balloon: A Pilot Study (2006)

Introduction: A left atrioesophageal fistula is an uncommon but devastating complication that may occur during atrial fibrillation (AF) ablation, and may be due to thermal injury occurring during the radiofrequency (RF) ablation. We examined the feasibility of an esophageal cooling (ECO) method using a cooled water‐irrigated intraesophageal balloon (IB). Methods and Results: Eight patients with drug‐refractory AF underwent RF catheter ablation to encircle the ipsilateral pulmonary veins. During the RF ablation at the posterior left atrium, the esophageal lumen was cooled using a 9‐Fr. IB catheter with a balloon length of 40 mm and diameter of 10 mm, in which cooled water, with a water temperature of 4.5 ± 3.1 °C, was irrigated while the luminal esophageal temperature (LET) was measured with an intraesophageal probe placed at a site close to the tip of the ablation catheter. In the control, the LET increased from 36.4 ± 0.8 °C to 40.5 ± 1.7 °C within 26.1 ± 8.2 seconds during 3.9 ± 1.2 RF energy applications, whereas with the ECO the LET decreased to 30.2 ± 2.9 °C at baseline (P&lt;0.01 vs control), and increased only to 33.5 ± 2.9 °C (P&lt;0.01 vs control) at most, within 30 seconds during 3.9 ± 1.2 RF energy applications. All pulmonary veins were successfully isolated in all patients without any complications. During a follow‐up period of 3.1 ± 1.2 months, no esophageal injuries were observed and all but one patient have been free from any symptoms. Conclusions: Use of an IB successfully lowers LET. This might have the potential of preventing esophageal injury, although further study is required.
Immune Responses, Virus Infections and Disease (1990)

Abstract Viral diseases of higher vertebrates result from unique interactions between the virus and the immune system. Until very recently it has not been possible to describe these interactions fully for any virus, nor to understand them in mechanistic terms. This study begins with a background introduction for non-immunologists and continues to explore eight virus systems of importance in human disease. The contributors explain current understanding of the immune responses generated in each infection and signpost areas of incomplete or tentative knowledge. Possible mechanisms by which immune responses are expressed or suppressed are discussed, particularly in regard to the modulation of MHC antigens.
The Calcium-binding Sites of Heparinase I fromFlavobacterium heparinum Are Essential for Enzymatic Activity (1999)

In the accompanying paper (Shriver, Z., Liu, D., Hu, Y., and Sasisekharan, R. (1999) J. Biol. Chem. 274, 4082-4088), we have shown that calcium binds specifically to heparinase I and have identified two major calcium-binding sites (CB-1 and CB-2) that partly conform to the EF-hand calcium-binding motif. In this study, through systematic site-directed mutagenesis, we have confirmed the accompanying biochemical studies and have shown that both CB-1 and CB-2 are involved in calcium binding and enzymatic activity. More specifically, we identified critical residues (viz. Asp210, Asp212, Gly213, and Thr216 in CB-1 and Asn375, Tyr379, and Glu381 in CB-2) that are important for calcium binding and heparinase I enzymatic activity. Mutations in CB-1 resulted in a lower kcat, but did not change the product profile of heparinase I action on heparin; conversely, mutations in CB-2 not only altered the kcat for heparinase I, but also resulted in incomplete degradation, leading to longer saccharides. Fluorescence competition experiments along with heparin affinity chromatography suggested that mutations in CB-1 alter heparinase I activity primarily through decreasing the enzyme's affinity for its calcium cofactor without altering heparin binding to heparinase I. Compared with CB-1 mutations, mutations in CB-2 affected calcium binding to a lesser extent, but they had a more pronounced effect on heparinase I activity, suggesting a different role for CB-2 in the enzymatic action of heparinase I. These results, taken together with our accompanying study, led us to propose a model for calcium binding to heparinase I that includes both CB-1 and CB-2 providing critical interactions, albeit via a different mechanism. Through binding to CB-1 and/or CB-2, we propose that calcium may play a role in the catalytic mechanism and/or in the exolytic processive mechanism of heparin-like glycosaminoglycan depolymerization by heparinase I.
Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors (2014)

Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered.
Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma (2001)

Faecal calprotectin is a simple and sensitive non-invasive marker of colorectal cancer and adenomatous polyps. It is more sensitive than faecal occult blood tests for detection of colorectal neoplasia at the cost of a somewhat lower specificity.
Research on data mining models for the internet of things (2010)

In this paper, we propose four data mining models for the Internet of Things, which are multi-layer data mining model, distributed data mining model, Grid based data mining model and data mining model from multi-technology integration perspective. Among them, multi-layer model includes four layers: (1) data collection layer, (2) data management layer, (3) event processing layer, and (4) data mining service layer. Distributed data mining model can solve problems from depositing data at different sites. Grid based data mining model allows Grid framework to realize the functions of data mining. Data mining model from multi-technology integration perspective describes the corresponding framework for the future Internet. Several key issues in data mining of IoT are also discussed.
Adenosine A3receptor stimulation induces protection of skeletal muscle from eccentric exercise-mediated injury (2010)

Effective therapy to reduce skeletal muscle injury associated with severe or eccentric exercise is needed. The purpose of this study was to determine whether adenosine receptor stimulation can mediate protection from eccentric exercise-induced muscle injury. Downhill treadmill exercise (-15 degrees ) was used to induce eccentric exercise-mediated skeletal muscle injury. Experiments were conducted in both normal wild-type (WT) mice and also in beta-sarcoglycan knockout dystrophic mice, animals that show an exaggerated muscle damage with the stress of exercise. In the vehicle-treated WT animals, eccentric exercise increased serum creatine kinase (CK) greater than 3-fold to 358.9 +/- 62.7 U/l (SE). This increase was totally abolished by stimulation of the A(3) receptor. In the dystrophic beta-sarcoglycan-null mice, eccentric exercise caused CK levels to reach 55,124 +/- 5,558 U/l. A(3) receptor stimulation in these animals reduced the CK response by nearly 50%. In the dystrophic mice at rest, 10% of the fibers were found to be damaged, as indicated by Evans blue dye staining. While this percentage was doubled after exercise, A(3) receptor stimulation eliminated this increase. Neither the A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine (0.05 mg/kg) nor the A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (0.07 mg/kg) protected skeletal muscle from eccentric exercise injury in WT or dystrophic mice. The protective effect of adenosine A(3) receptor stimulation was absent in mice, in which genes for phospholipase C beta2/beta3 (PLCbeta2/beta3) and beta-sarcoglycan were deleted. The present study elucidates a new protective role of the A(3) receptor and PLCbeta2/beta3 and points to a potentially effective therapeutic strategy for eccentric exercise-induced skeletal muscle injury.
5-(Tetradecyloxy)-2-furancarboxylic acid and related hypolipidemic fatty acid-like alkyloxyarylcarboxylic acids (1977)

5-(Tetradecyloxy)-2-furancarboxylic acid (91, RMI 14514) was found to lower blood lipids and to inhibit fatty acid synthesis with minimal effects on liver weight and liver fat content. This fatty acid-like compound represents a new class of hypolipidemic agent; it is effective in rats and monkeys. The compound resulted from discovery of hypolipidemic activity in certain beta-keto esters, postulation and confirmation of the corresponding benzoic acids as active metabolites, and systematic exploration of the structure--activity relationships.
Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement (1983)

Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.
A microRNA expression signature of human solid tumors defines cancer gene targets (2006)

Small noncoding microRNAs (miRNAs) can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. From a large-scale miRnome analysis on 540 samples including lung, breast, stomach, prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA signature composed by a large portion of overexpressed miRNAs. Among these miRNAs are some with well characterized cancer association, such as miR-17-5p, miR-20a, miR-21, miR-92, miR-106a, and miR-155. The predicted targets for the differentially expressed miRNAs are significantly enriched for protein-coding tumor suppressors and oncogenes (P < 0.0001). A number of the predicted targets, including the tumor suppressors RB1 (Retinoblastoma 1) and TGFBR2 (transforming growth factor, beta receptor II) genes were confirmed experimentally. Our results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.
Regulation of Murine Airway Eosinophilia and Th2 Cells by Antigen-Conjugated CpG Oligodeoxynucleotides as a Novel Antigen-Specific Immunomodulator (2000)

The characteristic features of bronchial asthma reflect the orchestrated activity of Th2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype. We have previously reported that intratracheal coadministration of CpG and allergen inhibited airway eosinophilia and hyperresponsiveness in a synergistic manner. To substantiate the synergism between CpG and Ag, we introduced a covalently linked conjugate between CpG and Ag and examined the efficacy on airway eosinophilia and Th2 cytokine production. We found that the conjugated form of CpG plus Ag was 100-fold more efficient in regulating airway eosinophilia than the unconjugated mixture. The inhibitory effects lasted for at least 2 mo. The inhibition of airway eosinophilia by the conjugate was Ag specific and associated with an improvement of the airway hyperresponsiveness and the unresponsiveness of the Ag-specific Th2 cells in the regional lymph nodes. The CpG-Ag conjugate was 100-fold more effective than the unconjugated mixture for inducing in vitro Th1 differentiation in an IL-12-dependent manner. Our data show that CpG conjugated to Ag can work as a novel Ag-specific immunomodulator and imply that inhalation of allergen-CpG conjugate could be a desensitization therapy for patients with bronchial asthma.
Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review (2006)

Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.
Cutting Edge: Monarch-1 Suppresses Non-Canonical NF-κB Activation and p52-Dependent Chemokine Expression in Monocytes (2007)

CATERPILLER (NOD, NBD-LRR) proteins are rapidly emerging as important mediators of innate and adaptive immunity. Among these, Monarch-1 operates as a novel attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. However, the molecular mechanisms by which Monarch-1 performs this important function are not well understood. In this report, we show that Monarch-1 inhibits CD40-mediated activation of NF-kappaB via the non-canonical pathway in human monocytes. This inhibition stems from the ability of Monarch-1 to associate with and induce proteasome-mediated degradation of NF-kappaB inducing kinase. Congruently, silencing Monarch-1 with shRNA enhances the expression of p52-dependent chemokines.
Computer-aided coordination of power system protection (2004)

In electrical power networks, faults can occur for various reasons. The task of the protection devices in electrical power systems (EPS) is to detect these faults and to eliminate the faulty parts of an EPS. In order to minimize the fault's consequences, different protection devices have to be coordinated. In this article, a computer-aided approach is described that should help project-planning engineers with this task and reduce the very time-consuming procedure of protection-strategy development and documentation preparation to a minimum. The main goal of the proposed concept is to make the tool as user-friendly as possible. The user communicates with a program system and device databases via a graphical user interface (GUI), which enables the visualization of a network. The clear graphical representation of the problem reduces the possibility of human errors. In this paper, the concept of the tool for overcurrent, overload and distance-protection coordination, its main features, and a typical example are presented.
ShuttleDB: Database-Aware Elasticity in the Cloud (2014)

Motivated by the growing popularity of database-as-a-service clouds, this paper presents ShuttleDB, a holis-tic approach enabling flexible, automated elasticity of database tenants in the cloud. We first propose a database-aware live migration and replication method designed to work with off-the-shelf databases without any database engine modifications. We then combine these database-aware techniques with VM-level mech-anisms to implement a flexible elasticity approach that can achieve efficient scale up, scale out, or scale back for diverse tenants with fluctuating workloads. Our experi-mental evaluation of the ShuttleDB prototype shows that by applying migration and replication techniques at the tenant level, automated elasticity can be achieved both intra- and inter-datacenter in a database agnostic way. We further show that ShuttleDB can reduce the time and data transfer needed for elasticity by 80 % or more com-pared to tenant-oblivious approaches. 1
Functional properties of four splice variants of a human pancreatic tandem-pore K+ channel, TALK-1 (2003)

TALK-1a, originally isolated from human pancreas, is a member of the tandem-pore K+ channel family. We identified and characterized three novel splice variants of TALK-1 from human pancreas. The cDNAs of TALK-1b, TALK-1c, and TALK-1d encode putative proteins of 294, 322, and 262 amino acids, respectively. TALK-1a and TALK-1b possessed all four transmembrane segments, whereas TALK-1c and TALK-1d lacked the fourth transmembrane domain because of deletion of exon 5. Northern blot analysis showed that among the 15 tissues examined, TALK-1 was expressed mainly in the pancreas. TALK-1a and TALK-1b, but not TALK-1c and TALK-1d, could be functionally expressed in COS-7 cells. Like TALK-1a, TALK-1b was a K+-selective channel that was active at rest. Single-channel openings of TALK-1a and TALK-1b were extremely brief such that the mean open time was <0.2 ms. In symmetrical 150 mM KCl, the apparent single-channel conductances of TALK-1a and TALK-1b were 23 +/- 3 and 21 +/- 2 pS at -60 mV and 11 +/- 2 and 10 +/- 2 pS at +60 mV, respectively. TALK-1b whole cell current was inhibited 31% by 1 mM Ba2+ and 71% by 1 mM quinidine but was not affected by 1 mM tetraethylammonium, 1 mM Cs+, and 100 microM 4-aminopyridine. Similar to TALK-1a, TALK-1b was sensitive to changes in external pH. Acid conditions inhibited and alkaline conditions activated TALK-1a and TALK-1b, with a K1/2 at pH 7.16 and 7.21, respectively. These results indicate that at least two functional TALK-1 variants are present and may serve as background K+ currents in certain cells of the human pancreas.