gebhart/patrepeval huggingface dataset:
Intermediate-density lipoprotein as an independent risk factor for aortic atherosclerosis in hemodialysis patients. (1998)

Patients with chronic renal failure often show accumulation of intermediate-density lipoprotein (IDL). Because recent studies have emphasized the atherogenicity of IDL in the general population, we evaluated the relationship between this lipoprotein and aortic atherosclerosis in uremic patients treated with hemodialysis. Aortic pulse wave velocity (PWV) was measured as a noninvasive index of sclerotic change of aorta in 205 hemodialysis patients and 184 age- and gender-matched healthy subjects. Fasting plasma lipoproteins were fractionated by ultracentrifugation into very low-density lipoprotein (VLDL), IDL, LDL, and HDL. Plasma lipoprotein (a) (Lp(a)) was measured by a latex immunoturbidimetric assay. Aortic PWV was significantly higher in the hemodialysis patients than in the control subjects. The hemodialysis group showed a significant increase in VLDL and IDL cholesterol, whereas their LDL and HDL cholesterol were lower than the control levels. Lp(a) levels did not differ between the two groups. In the hemodialysis population, VLDL, IDL, and LDL cholesterol correlated positively with aortic PWV adjusted for age, gender, smoking, and BP, whereas Lp(a) did not. Multiple regression analyses indicated that plasma triglycerides, independent of HDL cholesterol, had a significant association with aortic PWV in the hemodialysis patients but not in the control subjects. Further analyses revealed that aortic PWV in the hemodialysis patients had a significant and independent association with IDL cholesterol, whereas aortic PWV in the control subjects had significant and independent associations with HDL cholesterol and Lp(a). These results demonstrate that IDL is the lipoprotein fraction most closely associated with aortic PWV in the hemodialysis patients.
Platinum(II)-Oligonucleotide Coordination Based Aptasensor for Simple and Selective Detection of Platinum Compounds (2015)

Wide use of platinum-based chemotherapeutic regimens for the treatment for carcinoma calls for a simple and selective detection of platinum compound in biological samples. On the basis of the platinum(II)-base pair coordination, a novel type of aptameric platform for platinum detection has been introduced. This chemiluminescence (CL) aptasensor consists of a designed streptavidin (SA) aptamer sequence in which several base pairs were replaced by G-G mismatches. Only in the presence of platinum, coordination occurs between the platinum and G-G base pairs as opposed to the hydrogen-bonded G-C base pairs, which leads to SA aptamer sequence activation, resulting in their binding to SA coated magnetic beads. These Pt-DNA coordination events were monitored by a simple and direct luminol-peroxide CL reaction through horseradish peroxidase (HRP) catalysis with a strong chemiluminescence emission. The validated ranges of quantification were 0.12-240 μM with a limit of detection of 60 nM and selectivity over other metal ions. This assay was also successfully used in urine sample determination. It will be a promising candidate for the detection of platinum in biomedical and environmental samples.
Characterization and kinetic analysis of the intracellular domain of human protein tyrosine phosphatase β (HPTP β) using synthetic phosphopeptides (1994)

The intracellular domain of human protein tyrosine phosphatase beta (HPTP beta) (44 kDa) was expressed in bacteria, purified using epitope 'tagging' immunoaffinity chromatography, and characterized with respect to kinetic profile, substrate specificity and potential modulators of enzyme activity. A chromogenic assay based on the Malachite Green method was employed for the detection of inorganic phosphate (Pi) released from phosphopeptides by HPTP beta. This assay, modified so as to improve its sensitivity, was adapted to a 96-well microtitre plate format, and provided linear detection between 50 and 1000 pmol of Pi. The cytoplasmic domain of HPTP beta was strongly inhibited by vanadate, molybdate, heparin, poly(Glu, Tyr) (4:1) and zinc ions. In order to explore the substrate preferences of this PTPase, we generated 13-residue synthetic phosphotyrosine-containing peptides that corresponded to sites of physiological tyrosine phosphorylation. HPTP beta demonstrated kcat. values between 76 and 258 s-1 using four different phosphopeptides. The substrate preference of HPTP beta was in the order srcTyr-527 > PDGF-RTyr-740 > ERK1Tyr-204 >> CSF-1RTyr-708 with Km values ranging from 140 microM to greater than 10 mM. The variations in affinity were probably due to differences among the four phosphopeptides compared, particularly with respect to the character of the charged amino acids flanking the phosphotyrosine residue.
Distinct roles for LFA-1 affinity regulation during T-cell adhesion, diapedesis, and interstitial migration in lymph nodes (2009)

During the course of homing to lymph nodes (LNs), T cells undergo a multistep adhesion cascade that culminates in a lymphocyte function-associated antigen 1 (LFA-1)-dependent firm adhesion to the luminal surface of high endothelial venules (HEVs). The importance of LFA-1 affinity regulation in supporting T-cell arrest on HEVs has been well established, however, its importance in the postadhesion phase, which involves intraluminal crawling and diapedesis to the extravascular space, remains elusive. Here we have shown that LFA-1 affinity needs to be appropriately regulated to support these essential steps in the homing cascade. Genetically engineered T cells that were unable to properly down-regulate LFA-1 affinity underwent enhanced, chemokine-independent arrest in HEVs but showed perturbed intravascular crawling to transmigration sites and compromised diapedesis across HEVs. By contrast, the extravascular migration of T cells was insensitive to the affinity-enhancing LFA-1 mutation. These results highlight the requirement for balanced LFA-1 affinity regulation in intravascular and transvascular, but not extravascular, T-cell migration in LNs.
Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European community (1993)

Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.
Modulation of the c-Met/hepatocyte growth factor pathway in small cell lung cancer. (2002)

The c-Met receptor tyrosine kinase and its ligand HGF (hepatocyte growth factor) have been shown to be involved in angiogenesis, cellular motility, growth, invasion, and differentiation. The role of c-Met/HGF axis in small cell lung cancer (SCLC) has not been reported previously. We have determined the expression of p170(c-Met) precursor and p140(c-Met) beta-chain in seven SCLC cell lines by immunoblotting. We used the SCLC cell line H69, which expressed an abundant amount of c-Met to study the function and downstream effects of c-Met activation. Stimulation of H69 cells with HGF (40 ng/ml, 6-h stimulation) significantly altered cell motility of the SCLC cells with increased formation of filopodia and membrane ruffling, characterized as membrane blebbing, as well as increased migration of the cellular clusters were seen. We have further studied the signal transduction pathways of HGF/c-Met in the H69 cell line. The stimulation of H69 with HGF (40 ng/ml, >24 h, maximal at 1 h) increased the amount of reactive oxygen species formed by 34%. HGF stimulation (40 ng/ml, 7.5-min stimulation) of H69 cells showed increased tyrosine phosphorylated bands identified at M(r) 68,000, 120,000-140,000, and 200,000. Some of these tyrosine-phosphorylated bands were identified as the focal adhesion proteins paxillin, FAK, PYK2, and the c-Met receptor itself. Phospho-specific antibodies show that tyrosines at amino acid (a.a.) 31 of paxillin, and autophosphorylation sites at a.a. 397 of p125FAK, and a.a. 402 of PYK2 are phosphorylated in response to HGF/c-Met signaling. We also demonstrate that the Hsp90 inhibitor geldanamycin, which also affects c-Met, reduced the growth and viability of four of four SCLC cell lines by 25% to 85%, over a 72-h time period. Geldanamycin caused apoptosis of SCLC cells, as well as led to increased levels of Hsp70 but not Hsp90. These results demonstrate that c-Met/HGF pathway is functional in SCLC, and it would be useful to target this pathway toward novel therapy.
IL-7/Anti-IL-7 mAb Complexes Restore T Cell Development and Induce Homeostatic T Cell Expansion without Lymphopenia (2008)

IL-7, a member of the common gamma-chain family of cytokines, is essential for B and T lymphocyte development and homeostasis of mature T cell subsets. Thus, naive and memory T cells are both dependent on IL-7 for survival and homeostatic proliferation under lymphopenic conditions. In line with prior findings with IL-2, we show in this study that the biological activity of IL-7 in vivo is greatly increased by association with anti-IL-7 mAb. Under in vivo conditions, IL-7/mAb complexes displayed 50- to 100-fold higher activity than free IL-7 and induced massive expansion of pre-B cells. IL-7/mAb complexes also increased thymopoiesis in normal mice and restored thymopoeisis in IL-7-deficient mice. For mature T cells, IL-7/mAb complexes induced marked homeostatic proliferation of both naive and memory CD4(+) and CD8(+) cell subsets even under normal T cell-replete conditions. Finally, IL-7/mAb complexes were able to enhance the magnitude of the primary response of Ag-specific naive CD8(+) cells. The strong stimulatory activity of IL-7/mAb complexes could be useful for treatment of immunodeficiency and cancer.
Expression of the Activating Transcription Factor 3 Prevents c-Jun N-Terminal Kinase-Induced Neuronal Death by Promoting Heat Shock Protein 27 Expression and Akt Activation (2003)

Activating transcription factor 3 (ATF3) is induced and functions both as a cellular response to stress and to stimulate proliferation in multiple tissues. However, in the nervous system ATF3 is expressed only in injured neurons. Here we reveal a function of ATF3 in neurons under death stress. Overexpression of ATF3 by adenovirus inhibits the mitogen-activated kinase kinase kinase 1 (MEKK1)-c-Jun N-Terminal Kinase (JNK)-induced apoptosis and induces neurite elongation via Akt activation in PC12 cells and superior nerve ganglion neurons. A DNA microarray study reveals that ATF3 expression and JNK activation induce expression of the heat shock protein 27 (Hsp27). Immunoprecipitation analysis and promoter assay for Hsp27 expression suggest that both ATF3 and c-Jun are necessary for transcriptional activation of Hsp27. Hsp27 expression significantly inhibits JNK-induced apoptosis as well as Akt activation in PC12 cells and superior cervical ganglion neurons. We conclude that the combination of ATF3 and c-Jun induces the anti-apoptotic factor Hsp27, which directly or indirectly activates Akt, and thereby possibly inhibits apoptosis and induces nerve elongation. Our results suggest that ATF3- and c-Jun-induced Hsp27 expression is a novel survival response in neurons under death stress such as nerve injury.
Arterial Angiotensin II and Venous Immunoreactive Material before and during Angiotensin Infusion in Man (1972)

1. Angiotensin II together with any immunoreactive fragments of angiotensin were measured in arterial and venous plasma before and during infusion of angiotensin II amide in five normotensive subjects, both in sodium-replete and sodium-depleted states. Because the antibody used in the radioimmunoassay cross-reacted with larger angiotensin breakdown products and because these fragments are present in higher concentrations in venous than arterial plasma, samples of both were assayed. Measurements on venous plasma are referred to as immunoreactive material (IM). 2. Arterial plasma angiotensin II concentration (PAC) and venous IM were compared in two additional subjects during infusion of angiotensin II amide and of synthetic human angiotensin II. 3. Arterial PAC and venous IM increased in linear relation to the dose of angiotensin infused, similar results being obtained with angiotensin II amide and synthetic human angiotensin II. 4. Before infusion, venous IM and arterial PAC were comparable (A:V ratio = 0·99 ± 0·16, n = 29). During infusion venous IM was consistently lower than arterial PAC; with angiotensin II amide the A:V ratio was 1·72 ± 0·49 (n = 35), and with synthetic human angiotensin it was 1·63 ± 0·2 (n = 6). 5. Results of an in vitro study suggest that the formation of new angiotensin in the vein is not sufficient to explain the lower A:V ratio of PAC before infusion. 6. It is proposed that arterial PAC rather than venous IM should be measured when the relationship between blood levels and biological effects of the peptide are the object of the study, particularly during angiotensin infusion or when rapid changes in circulating angiotensin occur.
Effects of Xylooligosaccharides in Type 2 Diabetes Mellitus (2008)

The purpose of this study was to evaluate the effect of xylooligosaccharide (XOS) on the blood sugar, lipids and oxidative status in type 2 diabetes mellitus (DM). A total of 26 outpatient subjects of Taichung Veterans General Hospital, Taiwan, with HbA1c levels between 7.0 and 10.0% and triglyceride <400 mg/dL were enrolled in the present study. Subjects were supplemented with 4 g/d XOS (n=12) or a placebo (n=14) for 8 wk in a randomized double-blind clinical design. The results showed that the anthropometric values and nutrient intakes did not change during the experimental period. XOS supplementation not only reduced the glucose, HbA1c and fructosamine concentrations, but also decreased the levels of total cholesterol, low density lipoprotein (LDL) cholesterol, oxidized low density lipoprotein (ox-LDL) and apolipoprotein B. The activity of catalase of the erythrocyte sample decreased in the XOS group, but not the activities of superoxide dismutase and glutathione peroxidase. In conclusion, the dietary supplementation with XOS for 8 wk was effective in improving the blood sugar and lipids in type 2 diabetes, indicating that XOS-containing diets might be beneficial to DM subjects.
Identification of candidate biomarkers for the early detection of nasopharyngeal carcinoma by quantitative proteomic analysis (2014)

NPC is a lethal malignancy that is most prevalent in Southeast Asia, and early detection and treatment are essential for the survival and good prognosis of NPC patients. In the present work, we identified 26 differentially expressed proteins in NNET, AH and different stages of NPC tissues by using 2D-DIGE combined with MALDI-TOF/TOF analysis. Of these proteins, the down-regulation of ENO1 and over-expression of CYPA were confirmed with a high-throughput tissue microarray that included various stages of NPC tissues via an IHC assay, and the results indicated that the combination of ENO1 and CYPA can serve as a potential molecular marker for the early detection of NPC.
Functional Characterization of the Hansenula polymorpha HOC1, OCH1, and OCR1 Genes as Members of the Yeast OCH1 Mannosyltransferase Family Involved in Protein Glycosylation (2006)

The alpha-1,6-mannosyltransferase encoded by Saccharomyces cerevisiae OCH1 (ScOCH1) is responsible for the outer chain initiation of N-linked oligosaccharides. To identify the genes involved in the first step of outer chain biosynthesis in the methylotrophic yeast Hansenula polymorpha, we undertook the functional analysis of three H. polymorpha genes, HpHOC1, HpOCH1, and HpOCR1, that belong to the OCH1 family containing seven members with significant sequence identities to ScOCH1. The deletions of these H. polymorpha genes individually resulted in several phenotypes suggestive of cell wall defects. Whereas the deletion of HpHOC1 (Hphoc1Delta) did not generate any detectable changes in N-glycosylation, the null mutant strains of HpOCH1 (Hpoch1Delta) and HpOCR1 (Hpocr1Delta) displayed a remarkable reduction in hypermannosylation. Although the apparent phenotypes of Hpocr1Delta were most similar to those of S. cerevisiae och1 mutants, the detailed structural analysis of N-glycans revealed that the major defect of Hpocr1Delta is not in the initiation step but rather in the subsequent step of outer chain elongation by alpha-1,2-mannose addition. Most interestingly, Hpocr1Delta showed a severe defect in the O-linked glycosylation of extracellular chitinase, representing HpOCR1 as a novel member of the OCH1 family implicated in both N- and O-linked glycosylation. In contrast, addition of the first alpha-1,6-mannose residue onto the core oligosaccharide Man8GlcNAc2 was completely blocked in Hpoch1Delta despite the comparable growth of its wild type under normal growth conditions. The complementation of the S. cerevisiae och1 null mutation by the expression of HpOCH1 and the lack of in vitro alpha-1,6-mannosyltransferase activity in Hpoch1Delta provided supportive evidence that HpOCH1 is the functional orthologue of ScOCH1. The engineered Hpoch1Delta strain with the targeted expression of Aspergillus saitoi alpha-1,2-mannosidase in the endoplasmic reticulum was shown to produce human-compatible high mannose-type Man5GlcNAc2 oligosaccharide as a major N-glycan.
A Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity (2002)

A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense. These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species.
Transforming HR in partnership with the business at QBE Insurance (2009)

Purpose – The purpose of this paper is to describe the transformation of HR at QBE Insurance, which the company's group general manager, HR has led since joining the organization in 2003. The paper seeks to focus specifically on how the group HR team has engaged both the business and divisional HR teams across an international operation to enable this transformation.
Evaluation of link-level performance improvements by using smart antennas for the TD-CDMA based UTRA TDD mobile radio system (2002)

For third generation mobile radio systems like the TD-CDMA based UTRA TDD mode the use of smart antenna technology promises a substantial performance improvement on the up- and the downlink. The third generation mobile radio system UTRA with the TDD mode, which utilizes a combined CDMA and TDMA multiple access scheme, has been specified in the Third Generation Partnership Project (3GPP). The use of smart antennas at the base station reduces interference in two ways: on the uplink the intercell interference can be suppressed. The estimated spatial information about the users and interferers can then be used for beamforming on the downlink, which significantly reduces the interference also in this direction. Especially for terminals with a RAKE-receiver-structure a major performance improvement can be observed because of the intracell interference reduction. These performance improvements are expressed in concrete results derived from link-level simulations using the described technology and simulation environment.
Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans. (2001)

The beta-blockers comprise a group of drugs that are mostly used to treat cardiovascular disorders such as hypertension, cardiac arrhythmia, or ischemic heart disease. Each of these drugs possesses at least one chiral center, and an inherent high degree of enantioselectivity in binding to the beta-adrenergic receptor. For beta-blockers with a single chiral center, the (-) enantiomer possesses much greater affinity for binding to the beta-adrenergic receptors than antipode. The enantiomers of some of these drugs possess other effects, such as antagonism at alpha-adrenergic receptors or Class III antiarrhythmic activity. However, these effects generally display a lower level of stereoselectivity than the beta-blocking activity. Except for timolol, all of these drugs used systemically are administered clinically as the racemate. As a class, the beta blockers are quite diverse from a pharmacokinetic perspective, as they display a high range of values in plasma protein binding, percent of drug eliminated by metabolism or unchanged in the urine, and in hepatic extraction ratio. With respect to plasma concentrations attained after oral or intravenous dosing, in most cases the enantiomers of the beta-blockers show only a modest degree of stereoselectivity. However, the relative magnitude of the concentrations of the enantiomers in plasma is not constant in all situations and varies from drug to drug. Further, various factors related to the drug (e.g., dosing rate or enantiomer-enantiomer interaction) or the patient (e.g., racial background, cardiovascular function, or the patient metabolic phenotype) may affect the stereospecific pharmacokinetics and pharmacodynamics of beta-blockers. An understanding of the stereospecific pharmacokinetics and pharmacodynamics of beta-blockers may help clinicians to interpret and predict differences among patients in pharmacologic responses to these drugs.
Percutaneous repair of abdominal aortic aneurysms using the AneuRx stent graft and the percutaneous vascular surgery device (2002)

Endovascular exclusion of abdominal aortic aneurysms (AAAs) was developed in an effort to treat patients who were at high risk for complications following standard surgical repair. Stent grafts used for endovascular repair of AAAs require the use of large-bore sheaths and surgical exposure of the common femoral arteries (CFAs). To decrease the invasiveness of AAA repair, we attempted to perform the procedure percutaneously utilizing the Prostar XL Percutaneous Vascular Surgery Device and the preclose technique. Thirty patients underwent an attempted percutaneous AAA repair. These patients were followed prospectively to assess the success of the procedure. Twenty-eight patients (93%) had successful percutaneous repair of both CFA access sites. One patient had inadequate hemostasis of the 22 Fr CFA entry site and one patient had inadequate hemostasis of the 16 Fr CFA entry site. Both of these CFA sites underwent open surgical repair. The rate of successful repair of the 22 Fr CFA access site was 29 of 30 (96%); for the 16 Fr CFA access site, 29 of 30 (96%). No in-hospital groin complications were seen. The procedure time was 105 +/- 21 min. The estimated blood loss was 90.6 +/- 50 cc. The hemoglobin loss was 1.54 +/- 0.89 mg/dL and the hematocrit loss was 5.04% +/- 2.8%. Complete percutaneous endoluminal AAA repair is feasible using the preclose technique. CFAs with sheaths up to 22 Fr can be safely and successfully accessed and repaired percutaneously using this technique. This method provides secure hemostasis and reduces the invasiveness of procedures requiring large-bore sheaths.