gebhart/patrepeval huggingface dataset:
Vagus Nerve Stimulation for Treatment of Partial Seizures: 2. Safety, Side Effects, and Tolerability (1994)

Vagus nerve stimulation (VNS) significantly reduces the frequency of partial seizures in refractory epilepsy patients. We examined the serious adverse events, side effects, and tolerability as they relate to the surgical implant procedure and the stimulating device. We also reviewed potential drug interactions, device output complications, and impact of the therapy on overall health status. We analyzed the first 67 patients to exist the acute phase of the EO3 VNS trial comparing high (therapeutic) VNS to low (less or noneffective) VNS. Data were collected from case report forms used at each of the four visits during the 12-week baseline and at each of the four visits during the 14-week randomized phase of the trial. No significant complications were reported as a result of the implant procedure. Serious adverse events included 1 patient who experienced direct current to the vagus nerve owing to generator malfunction resulting in left vocal cord paralysis and withdrawal of the patient from the study. No clinically significant effects on vital signs, cardiac function, or gastric function were detected. Side effects associated with VNS in the high group were hoarseness (35.5%), coughing (13.9%), and throat pain (12.9%). In the low group, only hoarseness (13.9%) and throat pain (13.9%) were associated with VNS. These effects generally wrre not considered clinically significant and occurred primarily during the stimulation pulses. No patients discontinued VNS therapy during the acute phase because of side effects associated with normal stimulation. Except for the one instance of a short circuit in the system resulting in a direct current, stimulating system complications were minor, limited to programming, unscheduled stimulation, and high lead impedance. Patients, investigators, and patient companions rated patients receiving high stimulation as more "improved" than those receiving low stimulation in regards to overall health status. Antiepileptic drug (AED) plasma concentrations were not affected by VNS. The implant procedure, stimulating system, and therapy proved safe and tolerable during the study. The high percentage (67 of 68) of patients completing the study reflects patient acceptance and tolerability of this mode of therapy.
Micromachine‐Enabled Capture and Isolation of Cancer Cells in Complex Media (2011)

Microrockets detect cancer: A micromachine is used for the in vitro isolation of pancreatic cancer cells in complex media. The strategy is based on the selective binding and transport ability of antibody-functionalized microengine rockets: these microrockets selectively recognize the surface antigens overexpressed by pancreatic cancer cells, and capture and transport the cancer cells over a preselected path (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Effects of Autocrine Human Growth Hormone (hGH) on Human Mammary Carcinoma Cell Behavior Are Mediated via the hGH Receptor (2001)

The human GH (hGH) antagonist B2036 combines a single amino acid substitution impairing receptor binding site 2 (G120K) with eight additional amino acid substitutions that improve binding site 1 affinity. B2036 does not bind, activate, or antagonize the human PRL receptor and therefore is suitable to determine cellular effects mediated specifically through the hGH receptor. We have used this hGH receptor specific antagonist in MCF-7 cells stably transfected with either the hGH gene (MCF-hGH) or a translation deficient hGH gene (MCF-MUT) to determine whether the effects of autocrine hGH on mammary carcinoma cell behavior are mediated via the hGH receptor. Enhanced JAK2 tyrosine phosphorylation observed in MCF-hGH cells compared with MCF-MUT cells is abrogated by B2036 as is the autocrine hGH stimulated increase in total cell number and DNA synthesis. Interestingly, autocrine hGH functions as a potent inhibitor of apoptosis induced by serum withdrawal compared with exogenously added hGH, and the protection against apoptosis afforded by autocrine hGH is abrogated by B2036. B2036 also inhibited autocrine hGH stimulated transcriptional activation mediated by either STAT5, CHOP (p38 MAP kinase specific) or Elk-1 (p44/42 MAP kinase specific). Finally, B2036 inhibited the autocrine hGH-dependent enhancement of the rate of mammary carcinoma cell spreading on a collagen matrix. Thus, the effects of autocrine hGH on human mammary carcinoma cell behavior are mediated via the hGH receptor.
ASM on Recombinant DNA (1977)

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Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East. (1997)

Hepatitis C virus (HCV) type 4 is the predominant genotype found throughout the Middle East and parts of Africa, often in association with high population prevalence as in Egypt. To investigate more fully its evolutionary relationship with other genotypes of HCV, and to study its overall genome organization, we have determined the entire sequence encompassing the coding region of the genotype 4a isolate ED43, obtained from an HCV-infected individual from Egypt. The sequence of ED43 contained a single open reading frame encoding a polyprotein of 3008 amino acids (aa), smaller than that reported for other HCV genotypes which vary from 3010 aa to 3037 aa. The nucleotide and amino acid sequences were compared with the full-length sequences already reported for genotypes 1a, 1b, 1c, 2a, 2b, 2c, 3a, 3b and those of isolates JKO49 and JKO46 described as types 10a and 11a. The differences in length of the polyprotein originated in variable regions in the E2 and NS5A genes. The complete sequence of ED43 confirmed the classification of type 4 as a separate major genotype.
Re-examination of the Cycloaddition of Cycloheptatriene with Maleic Anhydride (1971)

Abstract Cycloaddition of cycloheptatriene to maleic anhydride was re-examined and found to produce, in addition to the reported main product anti-tricyclo[3.2.2.02,4]non-6-endo-8,endo-9-dicarboxylic anhydride (1), the exo, exo isomer of this compound (4) and bicyclo[3.2.2]nona-2,6-diene-endo-8,endo-9-dicarboxylic anhydride (5). Evidence for these structures involving the orientation of the cyclopropane ring in 1 and 4 and the configuration of the carboxylic anhydride was provided by PMR spectroscopy using the intramolecular nuclear Overhauser effect and paramagnetic induced shift due to tris(dipivalomethanato)europium(III). The structure assignment by Alder and Jacobs for 1 was found to be correct, but not the one by Schenk et al The difference in free energies of activation leading to 1 and 4 was determined.
Antibody-Induced Mitogenicity Mediated by a Chimeric CD2– c- fms Receptor (1990)

A chimeric receptor composed of the extracellular domain of the human T-cell antigen CD2 (T11) joined to the membrane-spanning segment and the intracellular tyrosine kinase domain of the human colony-stimulating factor 1 receptor (CSF-1R) was expressed in murine NIH 3T3 fibroblasts. Stimulation of these cells with monoclonal antibodies to CD2 induced phosphorylation of the chimeric glycoprotein on tyrosine, receptor downmodulation, and mitogenesis. In contrast, neither human CSF-1R nor the chimeric receptor was able to function in interleukin-2-dependent murine T cells. In fibroblasts, then, CSF-1 per se is not required for activation of the receptor kinase or for a biological response, whereas in T cells, CSF-1R may be unable to engage the downstream signal transduction machinery.
The HTML sourcebook : a complete guide to HTML 3.0 (1996)

Introduction to the HyperText Markup Language HTML and Document Design The Design of HTML Document Collections HTML in Detail The Next Generation HTML 3, Stylesheets, and Applets Uniform Resource Locators (URLs) The HTTP Protocol Communication with the Common Gateway Interface CGI Programs and Tools HTML and Web Utilities and Tools Web Developer Resources Real-World Examples Appendices Glossary Index.
Highly Active, Stable, and Selective Well-Defined Silica Supported Mo Imido Olefin Metathesis Catalysts (2007)

Grafting 2 [Mo(⋮NAr)(CHCMe2R1)(NR2)2] on SiO2-(700) gives selectively [(⋮SiO)Mo(⋮NAr)(CHCMe2R1)(NR2)] (1), according to mass balance analysis, IR, and NMR spectroscopies. The replacement of one amido group by a siloxy group from the surface of silica dramatically increased the reactivity of the Mo complex in olefin metathesis, and the remaining amido ligand brings stability and selectivity to the system as evidenced by the absence of formation of 1-butene in the metathesis of propene and the high turnovers obtained for the metathesis of ethyl oleate.
[Phosphatidylcholine induces an increase in the production of interleukin-6 and improves survival of rats with neonatal sepsis caused by Klebsiella pneumoniae]. (1996)

Infections by gram-negative bacteria are one of the major causes of death in newborns. Bacterial clearance is deficient in septic neonates, which seems to increase their susceptibility to infections. In this study, we observed a significant improvement in clearance of Klebsiella pneumoniae in newborn wistar rats inoculated by intraperitoneal via with 800 mg k soybean phosphatidylcholine (PC), compared to the control group injected with PBS (p 0.05). The overall survival rate was improved (p 0.05) and the white blood cell counts showed a greater leukocytosis and neutrophilia during the peak of bacteremia in the PC treated animals. Circulating levels of interleukin-6 were greater in the PC group, which developed an intense splenic hematopoiesis of the granulocyte (p 0.05) and megakariocyte series (p 0.01). No significant changes were observed in bone marrow granulocyte deposits in both study groups. The improvement in survival rate, the changes in leukocyte counts and the splenic hematopoiesis may be associated with the increased production of IL-6. These results suggest that IL-6 plays a role in the protection mechanism induced by PC in this experimental model of newborn septicemia. PC seems to be an immunomodulator of the acute response to gram-negative bacterial infection.
Improved focused ion beam fabrication of near-field apertures using a silicon nitride membrane (2008)

We report an improved fabrication method for C-shaped near-field apertures resonant in the near-IR regime. The apertures are created in a metal layer on a silicon nitride membrane using a focused ion beam and a through membrane milling technique that avoids two problems with fabricating very small apertures: gallium contamination and edge rounding. Finite-difference time-domain simulations predict a 63x more intense near field with a 2.2x smaller spot versus conventionally milled apertures. We verify the position of the simulated resonance peaks with experimental far-field transmission measurements where we also find an increase of 8.8x in intensity. Our method has applications to many other plasmonic devices including bow-tie and fractal apertures, periodic arrays, and gratings.
Activation Force and Travel effects on Overexertion in Repetitive Key Tapping (1997)

Key switch design parameters, including make force, make travel, and over travel, were investigated for minimizing operator-exerted force while maximizing key-tapping speed. A mechanical apparatus was designed, constructed, and used for independently controlling key switch parameters and for directly measuring finger exertions during repetitive key tapping using strain gauge load cells. The task for the 25 participants involved using the index finger of the dominant hand to repeatedly depress a single key as rapidly as possible. Participants received visual and auditory feedback upon a successful keystroke. Peak force exerted decreased 24% and key-tapping rate increased 2% when over travel was distended from 0.0 to 3.0 mm. Although peak force exerted was not significantly affected by make point travel, key-tapping rate increased 2% when make point travel was reduced from 4.0 to 1.0 mm. These results indicate that key switch mechanisms that provide adequate over travel might enable operators to exert less force during repetitive key tapping without inhibiting performance.
Synthesis of dl-.ALPHA.-tocopherol and dl-.ALPHA.-tocotrienol. (1983)

α-Tocopherol (1) and α-tocotrienol (2) were synthesized in racemic form by a method in which their side chains were constructed by the coupling reaction of a key intermediate, 6-methoxymethoxy-2, 5, 7, 8-tetramethyl-2-(5-mercaptothiazolinyl-4-methyl-3-penten-1-yl) chroman (7), with geranyl bromide. Desulfurization of the reaction product and then hydrolysis afforded α-tocotrienol, which, upon reduction, gave the desired α-tocopherol in good yield. This method, using a mercaptothiazolinyl derivative, is more convenient than previous approaches which use the Wittig or Grignard reaction for the synthesis of the side chain.
Adsorption of proteins from plasma to a series of hydrophilic‐hydrophobic copolymers. II. Compositional analysis with the prelabeled protein technique (1981)

Plasma protein adsorption is an important initial event in the response of tissue to foreign materials. Little is known about the way in which the chemical properties of materials influence the nature of the adsorbed layer and thus the later cellular responses. In this study, the amounts of fibrinogen, immunoglobulin G, albumin, and hemoglobin adsorbed from plasma to a series of HEMA-EMA random copolymers varying in hydrophilicity was measured. The adsorption of each protein varied in a characteristic way with copolymer composition probably reflecting a different affinity of the proteins for the various copolymers. A complex variation in the composition of the adsorbed protein layer on polymers varying in hydrophilicity was thus evident. Surface enrichment of the proteins, calculated as the ratio of the surface and bulk fraction of each protein, also varied with copolymer composition, and indicated substantial differences in the composition of the surface and bulk phases. Surface area variations among the copolymers, preferential adsorption of 125I proteins, and the possibility of structural degradation of 1,25I proteins in plasma were investigated but did not appear to influence the adsorption results. The ability of polymers to fractionate plasma proteins and concentrate them at their surface is concluded to be a key factor in the complex processes which determine the compatibility of polymers in vivo.
Cryptic Properties of a Cluster of Dominant Flavivirus Cross-Reactive Antigenic Sites (2006)

A number of flaviviruses are important human pathogens, including yellow fever, dengue, West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Infection with or immunization against any of these viruses induces a subset of antibodies that are broadly flavivirus cross-reactive but do not exhibit significant cross-neutralization. Nevertheless, these antibodies can efficiently bind to the major envelope protein (E), which is the main target of neutralizing and protective antibodies because of its receptor-binding and membrane fusion functions. The structural basis for this phenomenon is still unclear. In our studies with TBE virus, we have provided evidence that such cross-reactive antibodies are specific for a cluster of epitopes that are partially occluded in the cage-like assembly of E proteins at the surfaces of infectious virions and involve-but are not restricted to-amino acids of the highly conserved internal fusion peptide loop. Virus disintegration leads to increased accessibility of these epitopes, allowing the cross-reactive antibodies to bind with strongly increased avidity. The cryptic properties of these sites in the context of infectious virions can thus provide an explanation for the observed lack of efficient neutralizing activity of broadly cross-reactive antibodies, despite their specificity for a functionally important structural element in the E protein.
Stress testing in valve disease (2007)

tress testing is a cornerstone in the evaluation of patients with coronary artery disease and its results are always integrated into any clinical decisions. In contrast, valvular heart disease is usually considered static and its management relies upon resting evaluation only. However, most valve diseases have a dynamic component. Changes in loading conditions and contractility during a patient's life may lead to alterations in the severity of lesions, good or poor ventricular contractile reserve, altered volume-dependent compliance of heart chambers, and ventricular arterial coupling. Thus, there may be a need for stress testing and imaging in this setting. Exercise testing in particular can induce symptoms, reveal the dynamics of the valve and the ventricle, and evaluate the changes in forward output, retrograde flow and pulmonary pressures. The current primary role of stress testing in valve disease is to provide an objective assessment of functional disability which is of the utmost importance in patients who often adapt and reduce their physical activity, thus masking their symptoms. The Euro Heart Survey on valvular disease recently showed that stress testing is underused in Europe, or used for inappropriate purposes. he following questions will be addressed for each of the left valvular heart diseases: c Who needs stress testing? c How to test: which stress modality should be used? c Which parameters should be measured and followed-in other words, should the valve, the ventricle, or both, be tested? c How can the results help in the patient's management?
P3‐315: Ttp488 path to registration: Leveraging enrichment strategies (2015)

TTP488, an antagonist at the Receptor for Advanced Glycation End products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). A previous report describes decreased decline in ADAS-cog (delta=3.1, p=0.008 at 18 months, ANCOVA with multiple imputation), relative to placebo. Although, the Phase 2 clinical trial demonstrated efficacy in mild-to-moderate AD, leveraging enrichment strategies, the phase 3 clinical trial will include patients with mild AD only. The objectives of the clinical trial design were to minimize variance and optimize standardization, while fulfilling the registration requirements to demonstrate the efficacy of TTP488 on cognitive [(ADAS-cog)] and global function [(CDR-sb)] measures in patients with mild AD. Clinical trial Design:This is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating the efficacy and safety of 18 months of treatment with TTP488 relative to placebo conducted in approximately 800 mild (MMSE 21-26) AD patients who are on stable background SoC (acetylcholinesterase inhibitors and/or memantine). The clinical trial design includes two separate studies conducted under a single protocol, Clinical trial A and Clinical trial B, which are randomized separately and each of which has 90% power to detect expected differences on both co-primary endpoints. Patients will be randomly assigned to TTP488 (5 mg/day) or placebo in a 1:1 randomization (approximately 200/treatment/clinical trial). The co-primary endpoints will be change from Baseline in the ADAS-cog at Month 18 and change from Baseline in the CDR-sb at Month 18. The key secondary endpoint will be change from Baseline in brain volumetrics (e.g., whole brain volume, ventricular volume, hippocampal volume) at Month 18; other secondary endpoints will include measurements of cognitive and global function. For analysis of co-primary endpoints, data will be analyzed separately; for secondary endpoints including imaging, safety, and exploratory endpoints, data will be pooled across the studies. This is the first phase 3 clinical trial investigating a soluble RAGE inhibitor in the treatment of AD. Two studies under a single protocol ensure consistency and reduce variability. The design was granted agreement under the Special Protocol Assessment by FDA.
Retinoic Acid and the Development of the Endoderm (2015)

Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of the embryo proper.
Oncogenic KIT-containing exosomes increase gastrointestinal stromal tumor cell invasion (2013)

During tumor development, constant interplay occurs between tumor cells and surrounding stromal cells. We report evidence that gastrointestinal stromal tumor (GIST) cells invade the interstitial stroma through the release of the oncogenic protein tyrosine kinase (KIT)-containing exosomes, which triggers the phenotypic conversion of progenitor smooth muscle cells to tumor-promoting cells. These recipient cells display morphologic changes and acquire tumor-associated phenotypes, including enhanced adhesion to extracellular matrix proteins, activation of intracellular pathways downstream of KIT, expression of Interstitial Cell of Cajal-like markers, and release of various matrix metalloproteinases (MMPs), particularly MMP1. This report shows stimulation of MMP1 production by stromal cells via uptake of tumor-derived exosomes, which leads to tumor cell invasion. Exosomes derived from GIST patients but not healthy donors show enhanced MMP1 secretion by smooth muscle cells and tumor cell invasion, whereas selective blocking of exosome-mediated MMP1 secretion decreases tumor invasiveness. Our study indicates that exosome release and subsequent MMP1 induction creates a positive feedback mechanism established between tumor and stromal cells that drives GIST development and offers unique insights for potential therapeutic strategies to block GIST progression and metastatic spread.
Pfinder: real-time tracking of the human body (1997)

Pfinder is a real-time system for tracking people and interpreting their behavior. It runs at 10 Hz on a standard SGI Indy computer, and has performed reliably on thousands of people in many different physical locations. The system uses a multiclass statistical model of color and shape to obtain a 2D representation of head and hands in a wide range of viewing conditions. Pfinder has been successfully used in a wide range of applications including wireless interfaces, video databases, and low-bandwidth coding.