gebhart/patrepeval huggingface dataset:
Interaction of the Transforming Growth Factor-β Type I Receptor with Farnesyl-protein Transferase-α (1995)

Transforming growth factor-beta 1 (TGF-beta 1) is the prototype of a large family of molecules that regulate a variety of biological processes. The type I (T beta R-I) and type II (T beta R-II) receptors for TGF-beta 1 are transmembrane serine/threonine kinases, forming a heteromeric signaling complex. Recent studies have shown that T beta R-II is a constitutively active kinase and phosphorylates T beta R-I upon ligand binding, suggesting that T beta R-I is the effector subunit of the receptor complex, which transduces signals to intracellular targets. This model has been further confirmed by the identification of constitutively active T beta R-I that mediates TGF-beta 1-specific cellular responses in the absence of ligand and T beta R-II. To investigate signaling by TGF-beta 1, we have sought to isolate proteins that interact with the cytoplasmic region of T beta R-I. One of the proteins identified was the alpha subunit of farnesyl-protein transferase (FT alpha) that modifies a series of peptides including Ras. T beta R-I specifically interacts with FT alpha in the yeast two-hybrid system. Glutathione S-transferase-T beta R-I fusion proteins bind FT alpha translated in vitro. T beta R-I also phosphorylates FT alpha. We further show that the constitutively active T beta R-I interacted with FT alpha very strongly whereas an inactive form of T beta R-I did not. These results suggest that FT alpha may be one of the substrates of the activated T beta R-I kinase.
Drug-Induced Epistaxis? (1990)

To assess the aetiological contribution made to spontaneous epistaxis in adults over the age of 50 years by various groups of drugs, a controlled study was designed. Fifty-three consecutive epistaxis patients were compared with 50 controls. Significant differences were found between the groups in their consumption of warfarin, dipyridamole and non-steroidal anti-inflammatory drugs. Hypertension was equally common in the two groups, but tended to be less well controlled in the epistaxis patients compared to the controls. It is thought that the link between the use of non-steroidal anti-inflammatory drugs and the occurrence of epistaxis may be due to alteration of platelet function.
The Effects of Nicotine in Dermal Plaster on Cognitive Functions in Patients with Alzheimers Disease (1996)

Eighteen patients with probable Alzheimer's disease (NINCDS/ADRDA criteria) participated in a placebo-controlled, double-blind study, with a crossover design. The patients had mild or moderate dementia (MMSE = 20.3 +/- 4.6, range 12-28). The trial consisted of two 4-week periods with a 2-week washout period in between. Nicotine was given in the form of dermal plasters. Most of the patients tolerated the highest doses of 21 mg nicotine/24 h, but some received 14 mg/24 h. The effect was monitored with tests of short-term memory, verbal fluency, attention and psychomotor speed. Nicotine was also determined in the blood. Short-term memory improved significantly after 4 weeks of treatment, both on nicotine and placebo (p < 0.05/p < 0.01). The results of our study thus do not indicate that nicotine applied in the form of dermal plasters is of any significance in the treatment of memory deficits in patient with Alzheimer's disease.
Early Trends for Invasive Pneumococcal Infections in Children After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine (2013)

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced for routine administration to infants and children in 2010 in the United States. We have monitored clinical and microbiologic features of invasive pneumococcal infections among children before and after PCV13 use. Methods: Infants and children cared for at 8 children hospitals in the United States with culture-proven invasive infections caused by S. pneumoniae were identified in an ongoing prospective surveillance study. Demographic and clinical data were recorded on a standard case report form. Serotype and antimicrobial susceptibilities of isolates were determined. Results: Since routine PCV13 immunization in 2010, invasive pneumococcal infections decreased 42% overall and 53% for children <24 months of age in 2011 compared with the average number of cases for 2007 to 2009. PCV13 serotype isolates decreased 57% during these same time periods; 19A, 7F and 3 decreased by 58%, 54% and 68%, respectively. The number of infections caused by serotypes 1 and 6C also decreased in 2011. The most common non-PCV13 serotypes encountered in 2010 and 2011 combined were 33F, 22F, 12, 15B, 15C, 23A and 11. Bacteremia, pneumonia and mastoiditis cases decreased more than meningitis cases. Conclusions: After the introduction of PCV13, invasive pneumococcal infections decreased among 8 children hospitals compared with the 3 years before PCV13 use. Slight increases in some non-PCV13 serotype isolates were noted in 2011. Continued surveillance is necessary to determine the effectiveness of PCV13 including herd protection as well as any emerging invasive serotypes.
Pharmacokinetic and pharmacodynamic study of a novel chimeric natriuretic peptide, CD-NP, in the normal dog (2007)

Background CD-NP is a novel Mayo-designed cGMP-activating chimeric natriuretic peptide (NP) that consists of the 22amino-acid (AA) residues of C-type natriuretic peptide (CNP) and the 15-AA C-terminus of Dendroaspis NP [1]. The rationale for its design was to transform CNP, a cardioprotective peptide with limited renal actions, into a chimeric peptide with both cardiovascular and renal effects. Previous studies from our laboratory have demonstrated that CD-NP was natriuretic, diuretic, cardiac-unloading, and renin-suppressing [1]. In this investigation, we studied the pharmacokinetics (PK) of CD-NP for the first time and further evaluated its pharmacodynamic profile in vivo.
A human protein containing multiple types of protease-inhibitory modules (2001)

By using sensitive homology-search and gene-finding programs, we have found that a genomic region from the tip of the short arm of human chromosome 16 (16p13.3) encodes a putative secreted protein consisting of a domain related to the whey acidic protein (WAP) domain, a domain homologous with follistatin modules of the Kazal-domain family (FS module), an immunoglobulin-related domain (Ig domain), two tandem domains related to Kunitz-type protease inhibitor modules (KU domains), and a domain belonging to the recently defined NTR-module family (NTR domain). The gene encoding these WAP, FS, Ig, KU, and NTR modules (hereafter referred to as the WFIKKN gene) is intron-depleted--its single 1,157-bp intron splits the WAP module. The validity of our gene prediction was confirmed by sequencing a WFIKKN cDNA cloned from a lung cDNA library. Studies on the tissue-expression pattern of the WFIKKN gene have shown that the gene is expressed primarily in pancreas, kidney, liver, placenta, and lung. As to the function of the WFIKKN protein, it is noteworthy that it contains FS, WAP, and KU modules, i.e., three different module types homologous with domains frequently involved in inhibition of serine proteases. The protein also contains an NTR module, a domain type implicated in inhibition of zinc metalloproteinases of the metzincin family. On the basis of its intriguing homologies, we suggest that the WFIKKN protein is a multivalent protease inhibitor that may control the action of multiple types of serine proteases as well as metalloproteinase(s).
New Approaches to Inhibiting Platelets and Coagulation (2015)

Ischemic heart disease and stroke are major causes of death and morbidity worldwide. Coronary and cerebrovascular events are a consequence of thrombus formation caused by atherosclerotic plaque rupture or embolism, both of which result from platelet activation and aggregation and thrombin-mediated fibrin generation via the coagulation cascade. Current and emerging antiplatelet and anticoagulant agents are evolving rapidly. The use of aspirin for primary prevention continues to be controversial, as are the doses appropriate for secondary prevention. Development of new oral and intravenous adenosine diphosphate P2Y12 inhibitors and novel antiplatelet agents continues to transform the landscape of antiplatelet therapy. Oral anticoagulation has advanced with the use of direct thrombin and factor Xa inhibitors that do not require therapeutic monitoring. In this review, we discuss the pharmacology and growing clinical evidence for traditional and new antiplatelet and anticoagulant therapies.
Monolithic process for co-integration of GaAs and silicon circuits (2003)

A monolithic process to co-integrate Si and GaAs circuits on a single chip is described. The co-integration has been realized through the epitaxial growth of a GaAs layer on a prefabricated Si wafer, resulting in a coplanar structure appropriate for IC processing. A composite ring oscillator consisting of Si CMOS and GaAs MESFET inverters connected in a ring was fabricated as a demonstration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Person Re-identification Using Spatial Covariance Regions of Human Body Parts (2010)

In many surveillance systems there is a requirement to determine whether a given person of interest has already been observed over a network of cameras. This is the person re-identification problem. The human appearance obtained in one camera is usually different from the ones obtained in another camera. In order to re-identify people the human signature should handle difference in illumination, pose and camera parameters. We propose a new appearance model based on spatial covariance regions extracted from human body parts. The new spatial pyramid scheme is applied to capture the correlation between human body parts in order to obtain a discriminative human signature. The human body parts are automatically detected using Histograms of Oriented Gradients (HOG). The method is evaluated using benchmark video sequences from i-LIDS Multiple-Camera Tracking Scenario data set. The re-identification performance is presented using the cumulative matching characteristic (CMC) curve. Finally, we show that the proposed approach outperforms state of the art methods.
Evaluation of a Point-of-Care Test, BVBlue, and Clinical and Laboratory Criteria for Diagnosis of Bacterial Vaginosis (2005)

Bacterial vaginosis (BV) remains the most common cause of abnormal vaginal discharge in women of reproductive age and is associated with increased susceptibility to human immunodeficiency virus and sexually transmitted infections and preterm delivery. Present diagnostic methods require access to microscopy and laboratory expertise; however, the majority of women, particularly those in populations with a high prevalence of BV, do not have access to clinical services with on-site microscopy capabilities. We evaluated a point-of-care test for the diagnosis of BV, the BVBlue test, with 288 women attending a sexual health service with symptoms of abnormal vaginal discharge and/or odor. The BVBlue test performed well compared with conventional diagnostic methods for the assessment of women with symptoms suggestive of BV at the bedside and significantly better than other simple tests, such as vaginal pH determination and the amine test, that do not require microscopy. The BVBlue test was sensitive (88%; 95% confidence interval [CI], 81 to 93%) and specific (95%; 95% CI, 91 to 98%) compared to the method of Nugent et al. (R. P. Nugent, M. A. Krohn, and S. L. Hillier, J. Clin. Microbiol. 29:297-301, 1991) and performed well compared with the method of Amsel et al. (R. Amsel, P. A. Totten, C. A. Spiegel, K. C. Chen, D. Eschenbach, and K. K. Holmes, Am. J. Med. 74:14-22, 1983), with a sensitivity of 88% (95% CI, 81 to 93%) and a specificity of 91% (95% CI, 85 to 94%). The BVBlue test is a simple, rapid, and objective test for the diagnosis of BV and has the potential to facilitate prompt diagnosis and appropriate treatment of BV in the absence of microscopy. The majority of women at the greatest risk for the sequelae of BV are not in settings where the conventional diagnostic methods are either practical or possible, and they would greatly benefit from access to rapid and reliable point-of-care tests to improve the diagnosis and management of BV.
Matrix metalloproteinase-9 expression in post-hypoxic human brain capillary endothelial cells: H2O2 as a trigger and NF-κB as a signal transducer (2003)

The haemorrhagic transformation in ischemic stroke involves disruption of the integrity of the microvascular beds, partially based on the action of matrix metalloproteinases (MMPs). The objective of the present study was to evaluate the contribution of microvascular endothelial cells from human brain (HBECs) to MMPs' expression and regulation under conditions relevant to brain ischemia. MMPs and their inhibitors were examined with zymography, Western-blotting, ELISA and MMP-activity assay in cultured HBECs. Four-hour hypoxia (pO(2)=60 mmHg) elevated the level of MMP-9 in the supernatant of the HBECs and this early response required collagen-matrix. Active oxygen species sustained the increased MMP-9 activity for at least 24 h. In the post-hypoxic period 20 micro mol/L H(2)O(2) caused a 6-fold increase in the specific activity of MMP-9 over the normoxic cells and a comparable effect was exerted by thrombin (50 nmol/L) and leukocyte elastase (10 nmol/L). The role of NF-kappaB, a redox-state sensitive transcription factor, was evaluated with immunofluorescence confocal microscopy and immunoblotting of nuclear and cytoplasmic extracts. The oxidative stress-dependent MMP-9 induction was accompanied by a significant increase in the NF-kappaB localized in the nuclei and these responses were blunted with a proteasome inhibitor (MG132). Consequently, according to our in vitro data HBECs are a source of MMP-9, which is under the control of triggers relevant to the ischemic/reperfused brain (reactive oxygen species, thrombus and inflammation related proteases) and this regulation is partially based on NF-kappaB activation. The reported regulation of endothelium-derived MMP-9 supports its potential involvement in the post-hypoxic disturbances of the cerebral microcirculation.
P-selectin glycoprotein ligand-1–deficient mice have impaired leukocyte tethering to E-selectin under flow (2002)

P-selectin glycoprotein ligand-1 (PSGL-1) mediates rolling of leukocytes on P-selectin under flow. The glycoproteins that enable leukocyte tethering to or rolling on E-selectin are not known. We used gene targeting to prepare PSGL-1-deficient (PSGL-1-/-) mice, which were healthy but had moderately elevated total blood leukocytes. Fluid-phase E-selectin bound to approximately 70% fewer sites on PSGL-1-/- than PSGL-1+/+ neutrophils. Compared with PSGL-1+/+ leukocytes, significantly fewer PSGL-1-/- leukocytes rolled on E-selectin in vitro, because their initial tethering to E-selectin was impaired. The residual cells that tethered rolled with the same shear resistance and velocities as PSGL-1+/+ leukocytes. Compared with PSGL-1+/+ mice, significantly fewer PSGL-1-/- leukocytes rolled on E-selectin in TNF-alpha-treated venules of cremaster muscle in which P-selectin function was blocked by an mAb. The residual PSGL-1-/- leukocytes that tethered rolled with slow velocities equivalent to those of PSGL-1+/+ leukocytes. These results reveal a novel function for PSGL-1 in tethering leukocytes to E-selectin under flow.
T Cell Protocols (2009)

With a wide variety of investigative approaches, T cell immunology is a vital and open field of study. In T Cell Protocols, Second Edition, an international panel of experts contribute fully updated classic protocols as well as newly established novel techniques for the study of T lymphocyte biology. Written in the highly successful Methods in Molecular Biology™ series format, the chapters in this volume provide brief introductions to the topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and Notes sections which collect expert tips on troubleshooting and avoiding known pitfalls. Up-to-date and easy to use, T Cell Protocols, Second Edition is an ideal guide for young investigators new to the complex field of immunology as well as a valuable, concise resource for experienced scientists searching for clear, efficacious descriptions of novel methods
Nanometer-Scale Fabrication by Simultaneous Nanoshaving and Molecular Self-Assembly (1997)

Nanostructures down to a few nanometers in size and composed of close-packed and well-ordered molecules have been fabricated by simultaneous nanoshaving using an atomic force microscopy (AFM) tip and alkanethiols' self-assembly on gold. Compared with other microfabrication methods, this procedure allows more precise control in terms of the size and geometry of the fabricated features. An edge resolution better than 2 nm can be routinely obtained. In addition, the fabricated nanostructures can be quickly changed, modified, and characterized in situ. These advantages should make this method very useful in the development of prototypical nanoelectronic devices and, perhaps more importantly, in the study of spatially confined chemical reactions.
Challenges and some new directions in channel coding (2015)

Three areas of ongoing research in channel coding are surveyed, and recent developments are presented in each area: spatially coupled Low-Density Parity-Check (LDPC) codes, non-binary LDPC codes, and polar coding.
PET-based human dosimetry of 18F-galacto-RGD, a new radiotracer for imaging alpha v beta3 expression. (2006)

(18)F-Galacto-RGD demonstrates high metabolic stability, a favorable biodistribution, and a low radiation dose. Consequently, this tracer can safely be used for noninvasive imaging of molecular processes involving the alpha v beta3 integrin and for the planning and monitoring of therapeutic approaches targeting alpha v beta3.
Intracellular pH and Tyrosine Phosphorylation but Not Calcium Determine Shear Stress–Induced Nitric Oxide Production in Native Endothelial Cells (1996)

Signalling pathways determining the shear stress-induced production of NO from endothelial cells in situ were investigated using a bioassay system in which shear stress was increased by inducing vasoconstriction in an endothelium-intact donor segment (rabbit iliac artery) while maintaining a constant luminal perfusion rate. Shear stress-induced NO production, as assessed by changes in the tone of a preconstricted endothelium-denuded detector ring, was biphasic and consisted of an initial transient (20- to 25-minute) Ca(2+)-dependent phase followed by a Ca(2+)-independent plateau phase, which was maintained as long as the donor segment remained constricted. Stretching the donor segments to their in vivo length abolished the initial phase without affecting the plateau phase of NO release. Inhibition of the Na(+)-H+ exchanger using HOE 694 elicited an intracellular acidification which attenuated shear stress-induced NO production. The specific protein kinase C inhibitor, Ro 31-8220, was without effect, whereas the unspecific inhibitors, staurosporine and calphostin C, abolished the shear stress-induced production of NO. Erbstatin A, a tyrosine kinase inhibitor, attenuated the shear stress-induced tyrosine phosphorylation of specific cellular proteins and abrogated the associated NO production. In summary, these data indicate that shear stress activates the NO synthase at basal levels of [Ca2+]i via a mechanotransduction cascade that involves tyrosine phosphorylation and can be modulated by changes in pHi. The apparent fundamental alteration of the endothelial NO synthase under shear stress that renders its maintained activation independent of an increase in [Ca2+]i is probably the consequence of a change in the enzyme microenvironment.
Effects of sub‐perception threshold spinal cord stimulation in neuropathic pain: A randomized controlled double‐blind crossover study (2011)

Sub-threshold stimulation under otherwise conventional stimulation parameters has a measurable but not clinically sufficient effect. Thus, the pain relieving effect elicited by SCS is not necessarily linked to the perceptibility of stimulation but may instead be attributed to the intensity of the electric field.
TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal (2013)

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
Electrochemical hydrogen termination of boron-doped diamond (2010)

Boron-doped diamond is a promising transducer material for numerous devices which are designed for contact with electrolytes. For optimized electron transfer the surface of diamond needs to be hydrogen terminated. Up to now H-termination of diamond is done by plasma chemical vapor deposition techniques. In this paper, we show that boron-doped diamond can be H-terminated electrochemically by applying negative voltages in acidic solutions. Electrochemical H-termination generates a clean surface with virtually no carbon–oxygen bonds (x-ray photoelectron spectroscopy), a reduced electron affinity (scanning electron microscopy), a highly hydrophobic surface (water contact angle), and a fast electron exchange with Fe(CN)6−3/−4 (cyclic voltammetry).