gebhart/patrepeval huggingface dataset:
A Human Pharmacological Study Comparing Conventional Heparin and a Low Molecular Weight Heparin Fragment (1985)

The pharmacokinetics of a heparin fragment of low molecular weight (LMWH) of 4000-5000 D and unfractioned standard heparin (UFH) have been studied after i.v. injections of different doses and infusions in 8 humans. The heparin activity was significantly higher and the effect on APTT lower after LMWH fragment as compared to UFH in the same doses. The half-life of heparin activity was about 1 hr for UFH and about 2 hr for LMWH. LMWH was found to be eliminated according to first order kinetics and there were no signs of dose dependency.
Immunity to Calicivirus Infection (2000)

The evolution of our understanding of immunity to calicivirus infection, using Norwalk virus as the prototype, is discussed in three stages: (1) "ancient times (1972-1978), when human volunteer studies prevailed, (2) the "middle ages (1978-1990), which were characterized by the development and implementation of solid-phase immunoassays based on native viral antigens, and (3) "modern times (1990 to present), which began with the cloning of the genome of the noncultivatable 8FIIa strain of Norwalk virus and resulted in a readily available source of recombinant virus-like particles that have revolutionized the study of caliciviruses. Throughout these stages, it has been shown repeatedly that short-term immunity develops to homologous virus. However, the search for determinants of long-term immunity continues. These studies will likely be facilitated by the newest reagents-the noninfectious recombinant virus-like particles-used in the setting of human volunteer studies and large epidemiologic studies.
Regulation of the epidermal growth factor receptor by growth-modulating agents: effects of staurosporine, a protein kinase inhibitor. (1990)

Staurosporine is a potent microbial inhibitor of a number of protein kinases, including protein kinase C, cyclic AMP-dependent kinase, and the tyrosine kinase pp60src. We have used staurosporine to investigate the role of phosphorylation in the regulation of the epidermal growth factor (EGF) receptor in both human epidermal carcinoma A431 cells and mouse Swiss 3T3 fibroblasts. We report here that staurosporine treatment causes enhancement in high affinity EGF binding and a decrease in the phosphorylation state of the unstimulated receptor at a number of residues, including threonine 669. Staurosporine also antagonizes the inhibition of high affinity EGF binding and the increase in phosphorylation state of the unstimulated EGF receptor by phorbol esters and the calcium ionophore A23187. Staurosporine is an effective inhibitor of the EGF-stimulated receptor tyrosine kinase in vitro and thus does not enhance EGF stimulation of EGF receptor autophosphorylation in vivo. These results suggest that phosphorylation plays a major role in the regulation of the high affinity binding state of the EGF receptor in both unstimulated and mitogenically activated cells.
Platelets and artificial surfaces: the effects of drugs (1981)

Contact of blood with a foreign surface activates platelets and leads to their consumption. This property is shared by most non-biological materials, including air, but can be reduced by an optimal balance of hydrophobicity and hydrophilicity, minimal capacity for hydrogen bonding, avoidance of crystallinity, maintenance of polymer backbone mobility, and other manipulations of the chemistry of the polymer. None the less, no totally non-thrombogenic artificial surface has been developed. Attention has therefore turned to suppression of platelet-surface interaction by drugs that alter platelet function. Agents that block cyclo-oxygenase inhibit surface-induced secretion and aggregation but have no effect on platelet adhesion. Drugs that increase platelet cyclic AMP levels have a dose-related effect, which at high concentrations can eliminate adhesion to surfaces. The most successful agent, prostacyclin, has achieved total protection of platelets during cardiopulmonary bypass, with preservation of normal platelet number and function. Associated vasodilatation is a notable side effect, and hypotension may prove to be a significant problem in clinical practice. The development of more selective analogues with minimal vasodepressor activity is to be encouraged.
Safe long-term repeated disruption of the blood-brain barrier using an implantable ultrasound device: a multiparametric study in a primate model (2016)

OBJECTIVE The main limitation to the efficacy of chemotherapy for brain tumors is the restricted access to the brain because of the limited permeability of the blood-brain barrier (BBB). Previous animal studies have shown that the application of pulsed ultrasound (US), in combination with the intravenous injection of microbubbles, can temporarily disrupt the BBB to deliver drugs that normally cannot reach brain tissue. Although many previous studies have been performed with external focused US transducers, the device described in the current work emits US energy using an unfocused transducer implanted in the skull thickness. This method avoids distortion of the US energy by the skull bone and allows for simple, repetitive, and broad disruption of the BBB without the need for MRI monitoring. The purpose of the present study was to determine if the BBB can be safely and repeatedly disrupted using such an implantable unfocused US device in a primate model. METHODS An 11.5-mm-diameter, 1-MHz, planar US device was implanted via a bur hole into the skull of 3 primates (2 Papio anubis [olive] baboons and 1 Macaca fascicularis [macaque]) for 4 months. Pulsed US sonications were applied together with the simultaneous intravenous injection of sulfur hexafluoride microbubbles (SonoVue) every 2 weeks to temporarily disrupt the BBB. In each primate, a total of 7 sonications were performed with a 23.2-msec burst length (25,000 cycles) and a 1-Hz pulse repetition frequency at acoustic pressure levels of 0.6-0.8 MPa. Potential toxicity induced by repeated BBB opening was analyzed using MRI, PET, electroencephalography (EEG), somatosensory evoked potential (SSEP) monitoring, behavioral scales, and histopathological analysis. RESULTS The T1-weighted contrast-enhanced MR images acquired after each sonication exhibited a zone of hypersignal underneath the transducer that persisted for more than 4 hours, indicating a broad region of BBB opening in the acoustic field of the implant. Positron emission tomography images with fluorine-18-labeled fluorodeoxyglucose (FDG) did not indicate any changes in the cerebral metabolism of glucose. Neither epileptic signs nor pathological central nerve conduction was observed on EEG and SSEP recordings, respectively. Behavior in all animals remained normal. Histological analysis showed no hemorrhagic processes, no petechia, and extravasation of only a few erythrocytes. CONCLUSIONS The studies performed confirm that an implantable, 1-MHz US device can be used to repeatedly open the BBB broadly in a large-animal model without inducing any acute, subacute, or chronic lesions.
Protein and Chemical Microarrays—Powerful Tools for Proteomics (2003)

In the last few years, protein and chemical microarrays have emerged as two important tools in the field of proteomics. Specific proteins, antibodies, small molecule compounds, peptides, and carbohydrates can now be immobilized on solid surfaces to form high-density microarrays. Depending on their chemical nature, immobilization of these molecules on solid support is accomplished by in situ synthesis, nonspecific adsorption, specific binding, nonspecific chemical ligation, or chemoselective ligation. These arrays of molecules can then be probed with complex analytes such as serum, total cell extracts, and whole blood. Interactions between the analytes and the immobilized array of molecules are evaluated with a number of different detection systems. In this paper, various components, methods, and applications of the protein and chemical microarray systems are reviewed.
Tumor Necrosis Factor Induces Phosphorylation and Translocation of BAD through a Phosphatidylinositide-3-OH Kinase-dependent Pathway (1999)

Tumor necrosis factor (TNF) induced the phosphorylation of BAD at serine 136 in HeLa cells under conditions that are not cytotoxic. BAD phosphorylation by TNF was dependent on phosphatidylinositide-3-OH kinase (PI3K) and was accompanied by the translocation of BAD from the mitochondria to the cytosol. Blocking the phosphorylation of BAD and its translocation to the cytosol with the PI3K inhibitor wortmannin activated caspase-3 and markedly potentiated the cytotoxicity of TNF. Transient transfection with a PI3K dominant negative mutant or a dominant negative mutant of the serine-threonine kinase Akt, the downstream target of PI3K and the enzyme that phosphorylates BAD, similarly potentiated the cytotoxicity of TNF. By contrast, transfection with a constitutively active Akt mutant protected against the cytotoxicity of TNF in the presence of wortmannin. Phosphorylation of BAD prevents its interaction with the antiapoptotic protein Bcl-XL. Transfection with a Bcl-XL expression vector protected against the cytotoxicity of TNF in the presence of wortmannin. The mechanism by which the inhibition of the phosphorylation of BAD is likely linked to the induction of lethal mitochondrial damage in TNF-intoxicated cells is discussed.
Vasopressin as an alternative to norepinephrine in the treatment of milrinone-induced hypotension (2000)

Vasopressin at very low doses appears to be an effective vasopressor for milrinone-induced hypotension.
[Identification of mutations in the human EXT1 and EXT2 genes]. (1999)

EXT is a genetically heterogeneous bone disorder caused by the mutation of EXT tumor suppressor gene. These results could be directly applied in the genetic counseling and prenatal genetic diagnosis of EXT.
Tightly centromere-linked gene (SPO15) essential for meiosis in the yeast Saccharomyces cerevisiae. (1986)

We used DNA fragments from the centromere regions of yeast (Saccharomyces cerevisiae) chromosomes III and XI to examine the transcriptional activity within this chromosomal domain. DNA transcripts were found 200 to 300 base pairs from the 250-base-pair centromere core and lie within an ordered chromatin array. No transcripts were detected from the functional centromere region. We examined the cellular function of one of these tightly centromere-linked transcripts. (CEN11)L, by disrupting the coding sequences in vivo and analyzing the phenotype of the mutant yeast cell. Diploids heterozygous for the (CEN11)L disruption sporulated at wild-type levels, and the absence of the (CEN11)L gene product had no effect on the viability or mitotic growth of haploid cells. Diploids homozygous for the (CEN11)L disruption were unable to sporulate when induced by the appropriate nutritional cues. The mutant cells were competent for intragenic recombination and appeared to be blocked at the mononucleate stage. The temporal ordering of (CEN11)L function with respect to the sporulation mutant spo13 suggests that the (CEN11)L gene product may be required at both the first and second meiotic cell divisions. This new sporulation gene has been termed SPO15.
Chromosomal gene organization of the human granulocyte colony-stimulating factor receptor (1992)

The human chromosomal gene for the granulocyte CSF (G-CSF) receptor was molecularly cloned from a human gene library. The gene is about 16.5 kb long, and present in a single copy per haploid human genome. The human G-CSF receptor gene consists of 17 exons, and the sequences of exons are completely identical to those of cDNAs isolated from human U-937 myeloid leukemia or placenta cDNA libraries. The G-CSF receptor can be subdivided into several regions: an Ig-like domain, a cytokine receptor homologous domain, three fibronectin type III domains, a transmembrane domain, and a cytoplasmic region. Exons 3-17 code for the G-CSF receptor protein, and each subdomain of the receptor is encoded by a set of exons. Primer extension analysis of the G-CSF receptor mRNA identified major and minor transcription start sites. There is no canonical "TATA" box upstream of the CAP site. About 110 nucleotides upstream of the transcription initiation site of the gene, there is an element of 18 nucleotides that is homologous to the sequences found in the promoter of human myeloperoxidase and neutrophil elastase genes.
Excitation strategies for optical lattice microscopy (2005)

Recently, new classes of optical lattices were identified, permitting the creation of arbitrarily large two- and three-dimensional arrays of tightly confined excitation maxima of controllable periodicity and polarization from the superposition of a finite set of plane waves. Here, experimental methods for the generation of such lattices are considered theoretically in light of their potential applications, including high resolution dynamic live cell imaging, photonic crystal fabrication, and quantum simulation and quantum computation using ultracold atoms.
Expansion of CCR5+ CD4+ T-lymphocytes in the course of active pulmonary tuberculosis (2004)

Nonsyncytium inducing, macrophage tropic HIV strains predominate in the course of active tuberculosis (TB). The present study assesses the expression of CCR5 in CD4+ T-lymphocytes from blood and bronchoalveolar lavage (BAL) of TB patients, non-TB lung disease controls and healthy controls. Memory (CD45RO+), recently activated (CD69+), proliferating (Ki67+) CCR5+ or CCR3+ CD4+ T-lymphocytes were determined by multiparametric flow cytometry analysis. Results show that BAL CD4+ T-lymphocytes expressing CCR5 or CCR3 were significantly increased when compared to peripheral blood both in patients and in healthy controls. However, the data show that the proportions of peripheral blood CCR5+ CD4+ and CCR3+ CD4+ T-lymphocytes and BAL CCR5+ CD4+ T-lymphocytes, but not BAL CCR3+ CD4+ T-lymphocytes, were significantly increased in TB patients. Furthermore, the observation that BAL CCR5+ CD4+ T-lymphocytes from TB patients expressed early activation markers, were not proliferating and showed down-regulation of CCR5 expression suggests recruitment and trapping at the site of disease. Altogether, these results suggest that the lower respiratory tract mucosa may provide cellular targets accessible for efficient transmission of macrophage tropic HIV-1 variants and that tuberculosis may enhance this phenomenon.
Cellular Camouflage: Fooling the Immune System with Polymers (1998)

Immunological recognition of foreign cells is a primary concern in both transfusion and transplantation medicine. Our unique approach to this problem is to globally camouflage the surface of the foreign cell using nonimmunogenic, long chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of red blood cells effectively attenuates both antibody binding to surface epitopes and decreases the inherent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and exhibit normal in vivo survival in animal models. Pegylation of white blood cells (particularly antigen presenting cells and T lymphocytes) surprisingly prevents recognition of foreign class II molecules and prevents T cell proliferation in response to foreign MHC molecules. Potential applications for the covalent binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells include, but are not limited to: 1) derivatized RBC to diminish transfusion reactions arising from sensitization to minor blood group antigens (allosensitization) in the chronically transfused (e.g., sickle and thalassemia patients); 2) use of mPEG modification of "passenger" lymphocytes to prevent immune recognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to prevent/diminish acute tissue rejection. In contrast to highly specific blocking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the generation of globally camouflaged (i.e., stealth) cells may more effectively prevent the often complex and redundant events leading to immune recognition of foreign cells.
Structures and configurations of ciguatoxin from the moray eel Gymnothorax javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicus (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructures and configurations of ciguatoxin from the moray eel Gymnothorax javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicusMichio Murata, Anne M. Legrand, Yoshihiko Ishibashi, Masakazu Fukui, and Takeshi YasumotoCite this: J. Am. Chem. Soc. 1990, 112, 11, 4380–4386Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://pubs.acs.org/doi/10.1021/ja00167a040https://doi.org/10.1021/ja00167a040research-articleACS PublicationsRequest reuse permissionsArticle Views1327Altmetric-Citations414LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Magnetic Sensors for Protease Assays (2003)

Superparamagnetic nanosensors conjugated to avidin (CLIO-A) can be used to measure sensitively and quantitively the proteolytic cleavage of bi-biotinylated peptide substrates (rods in the scheme) by changes in magnetic resonance properties. This approach may be generalized to determine the activity of a wide range of hydrolytic enzymes.
Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes (1992)

Previous analyses of the uteroglobin gene promoter revealed a GT1 box which is also found in the SV40 enhancer. The GT1 element in the context of the uteroglobin promoter is active in Ishikawa cells, a human endometrial cell line, but not in HeLa cells. Here we report the cloning by recognition site screening of two factors (SPR-1 and SPR-2) which bind to this GT1 motif. SPR-1 and SPR-2 are homologues of the transcription factor Sp1. All three proteins are closely related members of a gene family encoding proteins with very similar structural features. Like Sp1, SPR-1 and SPR-2 contain glutamine and serine/threonine rich amino acid stretches. Most significantly, the DNA binding domains of all three proteins are highly conserved and they recognize GT as well as GC boxes identically. SPR-2 mRNA is expressed ubiquitously, whereas SPR-1 transcripts are abundant in the brain but barely detectable in other organs. The possible function of these factors for the activity of the uteroglobin promoter is discussed.
ChemInform Abstract: CYANOBOROHYDRIDE. UTILITY AND APPLICATIONS IN ORGANIC SYNTHESIS. A REVIEW (1980)

Abstract Review: Dieser Übersichtsartikel beschreibt die Anwendung von Na(BH 3 CN) zur Reduktion polarer Doppelbindungen, z.B. von Aldehyden, Ketonen, Hydrazonen etc., und zur Substitution geeigneter Austrittsgruppen durch Hydrid.
Isolation and characterization of a NADP-dependent glutamate dehydrogenase gene from the primitive eucaryote Giardia lamblia. (1992)

Giardia lamblia is believed to be the earliest branching derivative from the eucaryotic lineage. Genomic and cDNA clones encoding the giardia NADP-dependent glutamate dehydrogenase have been isolated and characterized. Southern hydridization using genomic DNA indicates that the gene encoding this activity is unique and single copy. Primer extension, S1 nuclease protection, and genomic and cDNA sequence analysis demonstrate that gene transcripts are initiated within a conserved AT-rich sequence element immediately preceding the ATG translation initiation codon and the short 5' untranslated region is not extended by transsplicing. The open reading frame is 1350 nucleotides in length and encodes a protein of 449 amino acids. The reading frame is not interrupted by introns and the primary transcript is probably not subjected to RNA editing. In the strictly anaerobic metabolism of giardia, NADP-dependent glutamate dehydrogenase activity participates along with alanine aminotransferase, in the cyclic dissipation of reducing equivalents (NADPH) through the conversion of pyruvate to alanine. The deduced amino acid sequence of the giardia protein exhibits substantial homology to numerous fungal and eubacterial NADP-dependent glutamate dehydrogenases. Comparisons of alignment gap positions and amino acid identities indicate that the giardia sequence is at least as similar or more similar to the eubacterial sequence than it is to the fungal sequence. This supports the hypothesis that giardia diverged very early from the eucaryotic lineage.
Immunological Memory and Protective Immunity: Understanding Their Relation (1996)

The immune system can remember, sometimes for a lifetime, the identity of a pathogen. Understanding how this is accomplished has fascinated immunologists and microbiologists for many years, but there is still considerable debate regarding the mechanisms by which long-term immunity is maintained. Some of the controversy stems from a failure to distinguish between effector and memory cells and to define their roles in conferring protection against disease. Here the current understanding of the cellular basis of immune memory is reviewed and the relative contributions made to protective immunity by memory and effector T and B cells are examined.
The Effects of Water Mist on the Compartment Fire (2004)

The present study investigates the fire suppression characteristics using a water mist fire suppression system. Numerical simulations of fire suppression with water mist are performed with considering the interaction of fire plume and water spray. The predicted temperature fields of smoke layer are compared with those of measured data. Numerical results agree with the experimental results within 10℃ in the case without water mist. In the case of fire suppression with water mist, numerical results do not predict well for temperature field in the gradual cooling region after water mist injection. But the predicted results of initial fire suppression are in good agreement with those of measured data. The reason for the discrepancy between predicted and measured data is due to the poor combustion modeling during the injection of water mist. More elaborate models for numerical simulation are required for better predictions of the fire suppression characteristics using water mist.
Ion channels and disease : channelopathies (2000)

Preface. Introduction. From Gene to Protein. How Channels Work. Methods for Studying Ion Channels. Voltage-Gated Na+ Channels. Voltage-Gated K+ Channels. Ca-Activated K+ Channels. Inward Rectifier K+ Channels. Voltage-Gated Ca2+ Channels. Voltage-Gated Cl- Channels. Cyclic Nucleotide-Gated Channels. CFTR. Epithelia Na+ Channels. Ligand-Gated Ca2+ Channels. ACh Receptor Channels. Glutamate Receptor Channels. Glycine Receptors. GABA Receptors. Water Channels. Gap Junction Channels. Antibodies to Ion Channels. Ion Channels in Viruses. Ion Channels as Lethal Agents. A Miscellany of Ion Channels. The Last Word. References. Subject Index.