gebhart/patrepeval huggingface dataset:
Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation (2009)

Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level. Antiangiogenic but not antiinflammatory metabolites/analogues of thalidomide induce chick limb defects. Both in vitro and in vivo, outgrowth and remodeling of more mature blood vessels is blocked temporarily, whereas newly formed, rapidly developing, angiogenic vessels are lost. Such vessel loss occurs upstream of changes in limb morphogenesis and gene expression and, depending on the timing of drug application, results in either embryonic death or developmental defects. These results explain both the timing and relative tissue specificity of thalidomide embryopathy and have significant implications for its use as a therapeutic agent.
CD25+CD4+regulatory T cells suppress CD4+T cell‐mediated pulmonary hyperinflammation driven byPneumocystis cariniiin immunodeficient mice (2002)

The CD4(+) T cell-mediated inflammatory response to Pneumocystis carinii (PC) critically contributes to the clinical severity of PC pneumonia. It has been suggested that lymphopenic conditions predispose individuals to this immunopathology, although the mechanisms remain poorly understood. Another set of evidence indicates that a subpopulation of CD4(+) T cells constitutively expressing the CD25 molecule prevent lymphopenia-induced autoimmunity and inflammatory bowel disease. We tested the ability of this CD25(+)CD4(+) population to regulate CD4(+) T cell-mediated inflammatory response to PC. Adoptive transfer of CD25(-)CD4(+) cells into PC-infected recombination-activating gene-2-deficient mice led to lethal pneumonia within 13 days post-transfer. PC infection appeared to trigger CD25(-)CD4(+) cells, since recipients with reduced PC load survived up to 5 weeks after transfer. In contrast, transfer of CD25(+)CD4(+) cells did not induce lethal pneumonia and prevented the development of the disease induced by CD25(-)CD4(+) cells. Furthermore, CD25(-)CD4(+) cells reduced the PC load in the lung, while CD25(+)CD4(+) cells suppressed this immune response. Our results indicate an essential role for CD25(+)CD4(+) T cells in the control of PC-driven immunopathology, and suggest that in immunocompromised hosts PC pneumonia may result from a deficiency in regulatory T cells.
Automotive Serial Controller Area Network (1986)

&lt;div class="htmlview paragraph"&gt;A high speed serial communication link has been developed for interconnecting electronic control units within automobiles. The incorporation of object oriented communication in conjunction with acceptance filtering introduces a new level of message handling efficiency and flexibility. Powerful error handling techniques guarantee safe operation in noisy automotive environments.&lt;/div&gt;
Variable increases of IgG and IgM antibodies in milk of IgA deficient women (1997)

Serum, milk and saliva from seven IgA deficient mothers were studied for the presence of IgA, IgG and IgM antibodies to Escherichia coli and poliovirus antigens. Different variable patterns were obtained. One mother had very much increased IgM and IgG antibodies in milk and saliva against both antigens; the milk IgG antibodies were 11-14 times higher than the reference milk pool. Another mother showed also striking increases of both IgM and IgG antibodies in milk, as well as in saliva where the increases were much higher for the poliovirus than the E. coli antibodies. Yet another mother showed a certain increase of IgM but not of IgG antibodies in the milk. The uneven appearance of IgG and IgM antibodies in serum and secretions suggests local production. So do the differences of antibody avidities, the variations in IgG subclass distribution of antibodies and different patterns after isoelectric focusing (IEF)/immunoblotting analysis of antibody spectrotypes in secretions and serum. The study illustrates the variable patterns of compensatory increases of IgG and IgM antibodies which may occur in IgA deficiency. It also shows that the milk from IgA deficient mothers can still be rich in antibodies, in spite of the lack of secretory IgA.
The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study (2007)

FNA is a safe intervention in patients undergoing EUS in a high-volume academic center, with a low postprocedural complication rate.
Motor Cortical Representation of Speed and Direction During Reaching (1999)

The motor cortical substrate associated with reaching was studied as monkeys moved their hands from a central position to one of eight targets spaced around a circle. Single-cell activity patterns were recorded in the proximal arm area of motor cortex during the task. In addition to the well-studied average directional selectivity ("preferred direction") of single-cell activity, we also found the time-varying speed of movement to be represented in the cortical activity. A single equation relating motor cortical discharge rate to these two parameters was developed. This equation, which has both independent (speed only) and interactive (speed and direction) components, described a large portion of the time-varying motor cortical activity during the task. Electromyographic activity from a number of upper arm muscles was recorded during this task. Muscle activity was also found to be directionally tuned; however, the distributions of preferred directions were found to be significantly different from cortical activity. In addition, the effect of speed on cortical and muscle activity was also found to be significantly different.
ChemInform Abstract: (.+‐.)‐(N‐Alkylamino)benzazepine Analogues: Novel Dopamine D1 Receptor Antagonists. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Immunogenicity and reactogenicity of a highly purified vaccine against tick‐borne encephalitis (1980)

Immunogenicity and reactogenicity of a vaccine containing inactivated tick-borne encephalitis virus prepared by continuous flow zonal ultracentrifugation were compared with those of a previously used, less purified vaccine. Antibody response as measured by hemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) was 93% after two vaccinations and 100% after a third dose. The zonally purified vaccine impressively reduced the incidence of side reactions. Pyrexia (greater than 37.3 degrees C) was recorded in only 4--10% of the vaccinees almost exclusively after first vaccinations compared to 17--68% with the old type of vaccine. When these results are evaluated according to criteria commonly used in the United States (ie, pyrexia greater than 100 degrees F = 37.8 degrees C), almost no fewer would be recorded. The frequency of systemic side reactions was even lower (statistically significant) after second and third vaccination. This highly purified vaccine therefore represents an effective and well-tolerated means for the immunoprophylaxis of TBE.
Design and Synthesis of Tricyclic Compounds with Enone Functionalities in Rings A and C:  A Novel Class of Highly Active Inhibitors of Nitric Oxide Production in Mouse Macrophages (2002)

Novel tricyclic compounds with enone functionalities in rings A and C, which were designed on the basis of the structure of a synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid, have been synthesized. Among them, 10 shows high inhibitory activity (IC(50) = 1 nM level) against production of nitric oxide induced by interferon-gamma in mouse macrophages and is orally active at 15 mg/kg (once) in a preliminary in vivo study using mouse peritoneal inflammation induced by thioglycollate and interferon-gamma.
Nanomechanical detection of cholera toxin using microcantilevers functionalized with ganglioside nanodiscs (2010)

The label-free detection of cholera toxin is demonstrated using microcantilevers functionalized with ganglioside nanodiscs. The cholera toxin molecules bind specifically to the active membrane protein encased in nanodiscs, nanoscale lipid bilayers surrounded by an amphipathic protein belt, immobilized on the cantilever surface. The specific molecular binding results in cantilever deflection via the formation of a surface stress-induced bending moment. The nanomechanical cantilever response is quantitatively monitored by optical interference. The consistent and reproducible nanomechanical detection of cholera toxin in nanomolar range concentrations is demonstrated. The results validated with such a model system suggest that the combination of a microcantilever platform with receptor nanodiscs is a promising approach for monitoring invasive pathogens and other types of biomolecular detection relevant to drug discovery.
Common-reflection-surface-based workflow for diffraction imaging (2011)

ABSTRACT Imaging of diffractions is a challenge in seismic processing. Standard seismic processing is tuned to enhance reflections. Separation of diffracted from reflected events is frequently used to achieve an optimized image of diffractions. We present a method to effectively separate and image diffracted events in the time domain. The method is based on the common-reflection-surface-based diffraction stacking and the application of a diffraction-filter. The diffraction-filter uses kinematic wavefield attributes determined by the common-reflection-surface approach. After the separation of seismic events, poststack time-migration velocity analysis is applied to obtain migration velocities. The velocity analysis uses a semblance based method of diffraction traveltimes. The procedure is incorporated into the conventional common-reflection-surface workflow. We apply the procedure to 2D synthetic data. The application of the method to simple and complex synthetic data shows promising results.
Activation of Yeast Polymerase II Transcription by Herpesvirus VP16 and GAL4 Derivatives In Vitro (1989)

Fusion proteins known to activate transcription in vivo were tested for the ability to stimulate transcription in vitro in a recently developed Saccharomyces cerevisiae RNA polymerase II transcription system. One fusion protein, whose activation domain was derived from the herpesvirus transcriptional activator VP16, gave more than 100-fold stimulation in the in vitro system. The order of effects of the various proteins was the same for transcription in vitro and in vivo, suggesting that the natural mechanism of activation is preserved in vitro.
Balancing transcriptional interference and initiation on the GAL7 promoter of Saccharomyces cerevisiae (2000)

Transcriptional termination of the GAL10 gene in Saccharomyces cerevisiae depends on the efficiency of polyadenylation. Either cis mutations in the poly(A) signal or trans mutations of mRNA 3' end cleavage factors result in GAL10 read-through transcripts into the adjacent GAL7 gene and inactivation (occlusion) of the GAL7 promoter. Herein, we present a molecular explanation of this transcriptional interference phenomenon. In vivo footprinting data reveal that GAL7 promoter occlusion is associated with the displacement of Gal4p transcription factors from the promoter. Interestingly, overexpression of Gal4p restores promoter occupancy, activates GAL7 expression, and rescues growth on the otherwise toxic galactose substrate. Our data therefore demonstrate a precise balance between transcriptional interference and initiation.
Establishment and characterization of a human gastric scirrhous carcinoma cell line in serum‐free chemically defined medium (1993)

We have established a human gastric scirrhous carcinoma cell line (designated as HSC-43) in a serum-free chemically defined medium (CDM) without any polypeptide growth factor, from a primary tumor of a 56-year-old male patient. HSC-43 cells grew in vitro in adherence with a population doubling time of 55 hr, and had the cytological properties of mucinous epithelial tumor cells. Cytogenetic analysis of the cells revealed pseudotetraploidy, with structural abnormalities of deletion at chromosome Iq25 and with 3 marker chromosomes. Some cells had retained features of signet-ring cells and caused fibroblastic proliferation when transplanted into athymic nude mice. The possible involvement of transforming growth factor-alpha (TGF-alpha), and its receptor, the epidermal-growth-factor receptor (EGFR), on the growth of HSC-43 cells was studied. Synthesis and secretion of TGF-alpha by HSC-43 cells were confirmed by biological assay and enzyme-linked immunosorbent assay. Radioreceptor analysis showed the presence of receptors for EGF in HSC-43 cells. Proliferation of HSC-43 cells was inhibited by antibodies against TGF-alpha and/or the EGFR. However, neither TGF-alpha nor epidermal growth factor (EGF) was effective in stimulating the cell growth of HSC-43 cells, irrespective of the cell density when supplemented exogenously. Our data suggest that TGF-alpha and EGFR play a role in the autocrine growth of HSC-43 cells. This may be another example of growth regulation of gastric carcinoma.
Thermal-noise-limited crystalline whispering-gallery-mode resonator for laser stabilization (2011)

We have stabilized an external cavity diode laser to a whispering gallery mode resonator formed by a protrusion of a single-crystal magnesium fluoride cylinder. The cylinder's compact dimensions ($\ensuremath{\lesssim}1 {\mathrm{cm}}^{3}$) reduce the sensitivity to vibrations and simplify the stabilization of its temperature in a compact setup. In a comparison to an ultrastable laser used for precision metrology we determine a minimum Allan deviation of $20 \mathrm{Hz}$ at an optical wavelength of 972 nm, corresponding to a relative Allan deviation of $6\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}14}$, at an integration time of $100 \mathrm{ms}$. This level of instability is compatible with the limits imposed by fundamental fluctuations of the material's refractive index at room temperature.
Synaptic structural abnormalities in the Ts65Dn mouse model of down syndrome (2004)

The Ts65Dn mouse is a genetic model for Down syndrome. Although this mouse shows abnormalities in cognitive function that implicate hippocampus as well as marked deficits in hippocampal long-term potentiation, the structure of the hippocampus has been little studied. We characterized synaptic structure in Ts65Dn and control (2N) mice, studying the hippocampus (fascia dentata, CA1) as well as the motor and somatosensory cortex, entorhinal cortex, and medial septum. Confocal microscopy was used to examine immunostained presynaptic boutons and to detail the structure of dendrites after Lucifer yellow microinjection. Both presynaptic and postsynaptic elements were significantly enlarged in Ts65Dn in all regions examined. The changes were detected at the youngest age examined (postnatal day 21) and in adults. In studies detailing the changes in fascia dentata and motor cortex, the enlargement of spines affected the entire population, resulting in the presence of spines whose volume was greatly increased. Electron microscopy confirmed that boutons and spines were enlarged and demonstrated abnormalities in the internal membranes of both. In addition, spine density was decreased on the dendrites of dentate granule cells, and there was reorganization of inhibitory inputs, with a relative decrease in inputs to dendrite shafts and an increase in inputs to the necks of spines. Taken together, the findings document widespread abnormalities of synaptic structure that recapitulate important features seen in Down syndrome. They establish the Ts65Dn mouse as a model for abnormal synapse structure and function in Down syndrome and point to the importance of studies to elucidate the mechanisms responsible for synapse enlargement.
Utilization of Gaussian functions for the rapid evaluation of molecular similarity (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUtilization of Gaussian functions for the rapid evaluation of molecular similarityA. C. Good, E. E. Hodgkin, and W. G. RichardsCite this: J. Chem. Inf. Comput. Sci. 1992, 32, 3, 188–191Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/ci00007a002https://doi.org/10.1021/ci00007a002research-articleACS PublicationsRequest reuse permissionsArticle Views395Altmetric-Citations149LEARN 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 options Get e-Alerts
Automated High-Throughput Identification and Characterization of Clinically Important Bacteria and Fungi using Rapid Evaporative Ionization Mass Spectrometry (2016)

Rapid evaporative ionization mass spectrometry (REIMS) has been shown to quickly and accurately speciate microorganisms based upon their species-specific lipid profile. Previous work by members of this group showed that the use of a hand-held bipolar probe allowed REIMS to analyze microbial cultures directly from culture plates without any prior preparation. However, this method of analysis would likely be unsuitable for a high-throughput clinical microbiology laboratory. Here, we report the creation of a customized platform that enables automated, high-throughput REIMS analysis that requires minimal user input and operation and is suitable for use in clinical microbiology laboratories. The ability of this high-throughput platform to speciate clinically important microorganisms was tested through the analysis of 375 different clinical isolates collected from distinct patient samples from 25 microbial species. After optimization of our data analysis approach, we achieved substantially similar results between the two REIMS approaches. For hand-held bipolar probe REIMS, a speciation accuracy of 96.3% was achieved, whereas for high-throughput REIMS, an accuracy of 93.9% was achieved. Thus, high-throughput REIMS offers an alternative mass spectrometry based method for the rapid and accurate identification of clinically important microorganisms in clinical laboratories without any preanalysis preparative steps.
Preparation of medium-ring cycloalkynes from 1-bromo-trans-cycloalkene derivatives (1976)

2-Bromo-3-methoxy-trans-cycloalkenes react very rapidly with potassium t-butoxide in anhydrous dimethyl sulphoxide solution at room temperature to give the corresponding 3-methoxycycloalkynes, usually in high yields. The preparation of 3-methoxycyclo-octyne (7a), 3-methoxycyclononyne (12a), 7-methoxycyclonon-1-en-5-yne(18), and 3-methoxycyclodecyne (20) is described. 3-Methoxycyclononyne (12a) readily isomerizes in the reaction medium to give the allene (13).2-Bromo-3-hydroxy-trans-cycloalkenes may similarly be converted into the corresponding 3-hydroxycycloalkynes, but protection of their hydroxy-groups by tetrahydropyranylation may be necessary before treatment with base. The preparation of cyclo-oct-2-ynol (7b) and cyclonon-2-ynol (12b) is described. The preparation, in modest yields, of the cyclodeca-1,6-diyne derivatives (23a and b) from the corresponding 2,7-dibromo-trans,trans-cyclodeca-1,6-dienes (22a and b) is reported. The preparation of 1-bromo-trans-cyclononene (28) and 1-bromo-trans,cis-cyclonona-1,5-diene (30c) and the conversion of the latter into cyclonon-1-en-5-yne (31) is described. The preparation of cyclononyne (2) from cyclonon-2-ynol (12b) is also described.
Docosahexaenoic acid shows no triglyceride-lowering effects but increases the peroxisomal fatty acid oxidation in liver of rats. (1993)

The effect of docosahexaenoic acid (DHA) on mitochondrial and peroxisomal fatty acid oxidation and on key enzymes in triglyceride metabolism was investigated in the liver of rats fed a standard diet, a cholesterol diet, and a pelleted chow diet. Unexpectedly, in all three rat models repeated administration of highly purified DHA (92% pure) at different doses and times, at a dose of 1000 mg/day per kg body weight, resulted in no significant decrease of hepatic and plasma concentration of triglycerides. The serum concentrations of cholesterol and phospholipids showed an increase in a time-dependent manner in rats fed the pelleted chow diet. The hepatic concentration of cholesterol was increased in rats fed the cholesterol diet and pelleted chow diet after administration of DHA compared to palmitic acid. In all rat models, treatment with DHA tended to increase the peroxisomal beta-oxidation. This was accompanied with a significant increase (1.5-fold) of fatty acyl-CoA oxidase activity. The mitochondrial fatty acid oxidation system and carnitine palmitoyl-transferase activity, however, were almost unchanged. Moreover, palmitoyl-CoA synthetase activity was increased, whereas the palmitoyl-CoA hydrolase activity was decreased. Neither microsomal phosphatidate phosphohydrolase activity nor cytosolic phosphatidate phosphohydrolase activity was affected by DHA feeding in the three rat models. Acyl-CoA:1,2-diacylglycerol acyltransferase activity was also unaffected. In contrast to docosahexanoic acid feeding, eicosapentaenoic acid (EPA) administration possessed a hypotriglyceridemic effect and resulted in an increase of mitochondrial and peroxisomal oxidation of fatty acids. Carnitine palmitoyltransferase activity was also stimulated. Phosphatidate phosphohydrolase activity was unaffected whereas diacylglycerol acyltransferase activity was increased by EPA treatment compared with palmitic acid feeding. The results indicate that docosahexaenoic acid, in contrast to eicosapentaenoic acid, does not inhibit the synthesis and secretion of triglycerides in the liver. In addition, the results emphasize the importance that stimulation of peroxisomal beta-oxidation by these n-3 fatty acids is not sufficient to decrease the serum levels of triglycerides. In addition, increased mitochondrial beta-oxidation of fatty acids and thereby decreased availability of nonesterified fatty acids may be a mechanism by which EPA inhibits triglyceride, and subsequently very low density lipoprotein-triglyceride, production. Whether DHA and EPA possess different metabolic properties should be considered.
Salt Selection (2006)

This chapter contains sections titled: Introduction Salt Formation and Polymorphism Target Properties of Active Substances for Drug Products Injectables Solid Dosage Forms Dosage Forms for Other Routes of Application Inhalation Topical Products and the Transdermal Route Basics of Salt Formation Ionization Constant Ionization and pH Solubility Approaches to Salt Screening Initial Data Selection of Salt Formers Automated Salt Screening Selection Procedures and Strategies Points to be Considered Final Decision Salt Form and Life Cycle Management of Drug Products Case Reports Overview of Salt Forms Selected Salt Selection Process Case 1: NVP-BS001 Case 2: NVP-BS002 Discussion and Decision Case 3: NVP-BS003 References