gebhart/patrepeval huggingface dataset:
Neuroinflammation: a potential therapeutic target (2005)

The increased appreciation of the importance of glial cell-propagated inflammation (termed 'neuroinflammation') in the progression of pathophysiology for diverse neurodegenerative diseases, has heightened interest in the rapid discovery of neuroinflammation-targeted therapeutics. Efforts include searches among existing drugs approved for other uses, as well as development of novel synthetic compounds that selectively downregulate neuroinflammatory responses. The use of existing drugs to target neuroinflammation has largely met with failure due to lack of efficacy or untoward side effects. However, the de novo development of new classes of therapeutics based on targeting selective aspects of glia activation pathways and glia-mediated pathophysiologies, versus targeting pathways of quantitative importance in non-CNS inflammatory responses, is yielding promising results in preclinical animal models. The authors briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to onset or progression of neurodegenerative diseases. The authors conclude with opinions based on recent experimental proofs of concept using preclinical animal models of pathophysiology. The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component.
Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells. (1993)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in growth and differentiation of myeloid cells. We previously reconstituted high-affinity human GM-CSF receptor (hGM-CSFR) in a pro-B cell line, BA/F3, by cotransfecting alpha- and beta-chain cDNA clones and showed that the reconstituted receptor could transduce growth-promoting signals. The high-affinity hGM-CSFR was also reconstituted in mouse NIH 3T3 cells, but its ability to transduce signals in fibroblasts remained undetermined. In the present study, we further characterized signal transduction by the reconstituted hGM-CSFR in both NIH 3T3 cells and BA/F3 cells. We found that the reconstituted hGM-CSFR transduces signals in NIH 3T3 fibroblasts and BA/F3 cells in response to hGM-CSF to activate transcription of the c-fos, c-jun, and c-myc proto-oncogenes. hGM-CSF also induces protein tyrosine phosphorylation and DNA synthesis in both cell types. These results indicated that hGM-CSFR is functional in fibroblasts, that signal transduction via hGM-CSFR in fibroblasts involves tyrosine kinase(s), and that association of hGM-CSFR with a factor(s) specific to hematopoietic cell lineage is not essential to transduce growth-promoting signals.
A retrofit 60 Hz current sensor for power monitoring at the circuit breaker panel (2010)

Improved signal conditioning electronics and new experimental results are presented for a sensor that measures current flow in a circuit breaker. A PIC microcontroller optimizes the phase reference for the synchronous detection system on startup eliminating the need for I/Q demodulation. Ultimately, the parts count of the signal conditioning electronics is halved compared to the previous work. Experimental results are presented demonstrating the sensor's response to 60 Hz signals with higher harmonic content and to step transients in 60 Hz signal amplitudes. The proposed current sensor does not require permanent modification of the breaker panel or the circuit breaker itself. The intent of this work is to develop a low-cost, non-intrusive, retrofit sensor for centralized power monitoring at the circuit breaker.
Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations. (1992)

Glucose toxicity of the pancreatic beta cell is considered to play a secondary role in the pathogenesis of type II diabetes mellitus. To gain insights into possible mechanisms of action of glucose toxicity, we designed studies to assess whether the loss of insulin secretion associated with serial passages of HIT-T15 cells might be caused by chronic exposure to high glucose levels since these cells are routinely cultured in media containing supramaximal stimulatory concentrations of glucose. We found that late passages of HIT cells serially cultured in media containing 11.1 mM glucose lost insulin responsivity and had greatly diminished levels of insulin content and insulin mRNA. In marked contrast, late passages of HIT cells cultured serially in media containing 0.8 mM glucose retained insulin mRNA, insulin content, and insulin responsivity to glucose in static incubations and during perifusion with glucose. No insulin gene mutation or alteration of levels of GLUT-2 were found in late passages of HIT cells cultured with media containing 11.1 mM glucose. These data uniquely indicate that loss of beta cell function in HIT cells passed serially under high glucose conditions is caused by loss of insulin mRNA, insulin content, and insulin secretion and is preventable by culturing HIT cells under low glucose conditions. This strongly suggests potential genetic mechanisms of action for glucose toxicity of beta cells.
Aminopeptidase Profiling Using a Time-Resolved, 96-Well Plate Filter Fluorimeter (1997)

A novel fluorimeter has been developed that combines the selectivity of time-resolved detection and the sample throughput of a 96-well plate reader. With improved background rejection via temporal resolution, a reduction in the limit of detection by a factor of 600 was attained over that of a commercially available 96-well plate fluorimeter. The excellent limit of detection was utilized to differentiate two closely related species of Pseudomonas, P. fluorescens and P. aureofaciens, at a bacterial concentration of 500,000 cells per well with only 15 min of incubation. High sample throughput was demonstrated by incubation of six bacteria samples and data collection in an amino acid 12-nutrient profile within 30 min.
The determination of enzyme inhibitor constants (1953)

Research Article| August 01 1953 The determination of enzyme inhibitor constants M. Dixon M. Dixon 1Biochemical Laboratory, University of Cambridge Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd © 1953 CAMBRIDGE UNIVERSITY PRESS1953 Biochem J (1953) 55 (1): 170–171. https://doi.org/10.1042/bj0550170 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation M. Dixon; The determination of enzyme inhibitor constants. Biochem J 1 August 1953; 55 (1): 170–171. doi: https://doi.org/10.1042/bj0550170 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1953 CAMBRIDGE UNIVERSITY PRESS1953 Article PDF first page preview Close Modal You do not currently have access to this content.
Short-chain fatty acid formation at fermentation of indigestible carbohydrates (2001)

Short chain fatty acids (SCFAs; acetic, propionic and butyric acid) are formed during bacterial fermentation of carbohydrates in the colon. The interest in SCFA production is related to an increasing body of knowledge of the physiological effects of these acids. SCFAs are important anions in the colonic lumen and serve locally as nutrients for the mucosa cells, stimulating mucosal proliferation and blood flow. Especially butyric acid has been emphasized. It is the main energy substrate for the colonocytes and has been suggested to play a role in the prevention and treatment of diseases of the colonic mucosa, such as distal ulcerative colitis and cancer. SCFA production decreases the luminal pH, and may thereby stimulate mineral absorption and reduce secondary bile acid formation in the colon. Colonic generation of SCFAs has also been related to systematic and metabolic effects, e.g. SCFAs may influence the motility along the gastrointestinal tract and propionic acid has been suggested to inhibit the cholesterol synthesis from acetic acid in the liver. The SCFA formed at fermentation is quantitatively and qualitatively influenced by the type and amount of carbohydrate substrate. Further, certain combinations of carbohydrates may have synergistic effects on the SCFA pattern and may also shift the site of fermentation. This opens possibilities to design foods with tailored features regarding SCFA release in the human colon with potential health implications. There is a potential that in the future it will be possible to control SCFA production in the colon regarding pattern and place for release. Keywords: Carbohydrates, dietary fibre, fermentation, SCFA, resistant starch
Large-scale multimodal semantic concept detection for consumer video (2007)

In this paper we present a systematic study of automatic classification of consumer videos into a large set of diverse semantic concept classes, which have been carefully selected based on user studies and extensively annotated over 1300+ videos from real users. Our goals are to assess the state of the art of multimedia analytics (including both audio and visual analysis) in consumer video classification and to discover new research opportunities. We investigated several statistical approaches built upon global/local visual features, audio features, and audio-visual combinations. Three multi-modal fusion frameworks (ensemble, context fusion, and joint boosting) are also evaluated. Experiment results show that visual and audio models perform best for different sets of concepts. Both provide significant contributions to multimodal fusion, via expansion of the classifier pool for context fusion and the feature bases for feature sharing. The fused multimodal models are shown to significantly reduce the detection errors (compared to single modality models), resulting in a promising accuracy of 83% over diverse concepts. To the best of our knowledge, this is the first work on systematic investigation of multimodal classification using a large-scale ontology and realistic video corpus.
The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes (1990)

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a lambda gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu160----His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a lambda max at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation (turnover number of 15 min-1) and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 kDa, the former of which appeared to correlate with human microsomal coumarin 7-hydroxylase activity. A more striking correlation was found between IIA mRNA and enzyme activity. The rat antibody was able to completely abolish coumarin 7-hydroxylase activity in 12 liver samples. In addition, kinetics of coumarin metabolism in two livers were monophasic over the substrate concentration tested. Km values obtained from human liver (2.3 microM) were similar to those obtained from lysates of hepatoma cells expressing IIA3 (3.6-7.1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental models of Parkinson's disease: insights from many models. (1999)

Toxin-induced and genetic experimental models have been invaluable in investigating idiopathic Parkinson's disease (PD). The neurotoxins--reserpine, 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and methamphetamine--have been used to develop parkinsonian models in a wide variety of species. Both 6-OHDA and MPTP can replicate the neurochemical, morphologic, and behavioral changes seen in human disease. The unilateral 6-OHDA rat model is an excellent model for testing and determining modes of action of new pharmacologic compounds. The nonhuman primate MPTP-induced parkinsonian model has behavioral features that best approximate idiopathic PD. These induced and genetic models have been used to study the pathophysiology of the degenerating nigrostriatal system and to evaluate novel therapeutic strategies. Important differences within these models provide insights into various aspects of the dopaminergic phenotype and its role as a target in disease. These models provide an avenue to evaluate many anti-parkinsonian compounds, such as levodopa, which was first evaluated in an animal model and is the gold standard of parkinsonian treatment today.
Studies on the Mechanism of Acetonitrile Toxicity I: Whole Body Autoradiographic Distribution and Macromolecular Interaction of 2–14C‐Acetonitrile in Mice* (1992)

Acetonitrile, a commonly used solvent is known to cause central nervous system dysfunctions. In order to gain an insight onto the mechanism of acetonitrile toxicity, we studied the kinetics of acetonitrile distribution in mice. Male ICR mice were given a tracer dose of 2-14C-acetonitrile intravenously (60 mu mol/kg or 684 mu Ci/kg, spec. act. 11.4 mCi/mmol). At various time intervals (5 min., 0.5, 1, 4, 8, 24 and 48 hr) after treatment, mice were anaesthetized and frozen by immersion in a dry ice/hexane mixture, or they were dissected for collection of organs and tissues. Frozen mice were processed for whole body autoradiography, which allows the detection of non-volatile metabolites of acetonitrile at their sites of accumulation. Covalent binding of acetonitrile metabolites in tissues was determined using trichloroacetic acid followed by ethanol/ether extraction techniques. Whole body autoradiography revealed heavy localization of acetonitrile metabolites in the gastrointestinal tissues and bile. At 5 min., the highest levels of radioactivity occurred in the liver and kidney; levels declined over time. At 24 and 48 hr, acetonitrile derived radioactivity were detected in the gastrointestine, thymus, liver and male reproductive organs. Covalent binding studies at 24 and 48 hr after treatment indicated that 40-50% of the total radioactivity present in the liver was bound to the macromolecular fractions of the tissues. The radioactivity contents of other organs were, in large part (40-50% of total), present in the lipid fraction of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
A Direct Determination of the Magnetic Moment of the Protons in Units of the Nuclear Magneton (1951)

A direct measurement of the proton magnetic moment in units of the nuclear magneton has been made, using the method of Alvarez and Bloch. The experiment consists of comparison of the nuclear magnetic resonance frequency of protons with the orbital frequency of protons revolving in the same homogeneous field. The resonance frequency of protons in water has been measured by the method of nuclear induction; the orbital frequency has been measured by a special device: a small decelerating cyclotron operated at an odd multiple of the fundamental cyclotron frequency.The device has been operated in a field of about 5300 gauss at all odd multiples from the first to the eleventh, with a corresponding range of the dee frequency between 8.1 and 89 Mc/sec. As expected, the sharpness of the cyclotron resonance was observed to greatly increase at the higher multiples; besides this advantage for obtaining high accuracy, the comparison of the results at different multiples also furnished an important check on the reliability of the measurements.An approximate theory for the shape of the cyclotron resonance curves has been developed, and its qualitative agreement with the observations has been established. The perturbing effects of extraneous electric and magnetic fields have been investigated, both theoretically and experimentally, and found to be negligible. With the smallest relative half-width of resonance about 1/10,000, which was observed at the higher multiples, and guided by the interpretation of the resonance shape, the magnetic moment of the proton has been found to be 2.7924\ifmmode\pm\else\textpm\fi{}0.0002 nuclear magnetons.
Treatment of Bacterial Infections of the Female Urinary Tract by Immunization of the Patients (1987)

In an open comparative study 400 patients with urinary tract infections were randomly allocated to two treatment groups. In 202 patients an immune stimulation against uropathogenic bacteria was produced with a new preparation, SolcoUrovac, and only in exceptional cases with pronounced symptomatology was antibiotic therapy given, while in the control group (n = 198) all patients were treated with nitrofurantoin or with another appropriate antibiotic, according to the antibiogram. In the subsequent 12-month observation period 28 infections occurred in 23 patients of the immune-stimulated group and 84 in 47 patients of the control group. This difference is statistically significant (p less than or equal to 0.001). The preventive effect of the SolcoUrovac therapy was particularly impressive in patients with recurrent urinary tract infections. Thirty-two patients from each group with similar case histories, as matched pairs, were evaluated separately. The relapse rate in the 12-month observation period amounted to 2 re-infections in the group treated with immunotherapy and to 29 in the control group. All side-effects were recorded. No adverse effects were observed in pregnant women or in their offspring.
Über einige Derivate des Triazolo‐pyrimidins (1951)

Abstract Ausgehend von den entsprechenden 2,6‐substituierten 4,5‐Diamino‐pyrimidinen wurden fünf mit Guanin isostere Derivate des Triazolo‐pyrimidins dargestellt.
Stretching-induced interconnect delamination in stretchable electronic circuits (2010)

Stretchable electronics offer increased design freedom of electronic products. Typically, small rigid semiconductor islands are interconnected with thin metal conductor lines on top of, or encapsulated in, a highly compliant substrate, such as a rubber material. A key requirement is large stretchability, i.e. the ability to withstand large deformations during usage without any loss of functionality. Stretching-induced delamination is one of the major failure modes that determines the amount of stretchability that can be achieved for a given interconnect design. During peel testing, performed to characterize the interface behaviour, the rubber is severely lifted at the delamination front while at the same time fibrillation of the rubber at the peel front is observed by ESEM analyses. The interface properties are established by combining the results of numerical simulations and peeling experiments at two distinct scales: the global force–displacement curves and local rubber lift geometries. The thus quantified parameters are used to predict the delamination behaviour of zigzag- and horseshoe-patterned interconnect structures. The accuracy of these finite element simulations is assessed by a comparison of the calculated evolution of the shape of the interconnect structures and the fibrillation areas during stretching with experimental results obtained by detailed in situ analyses.
Trk kinase inhibitors as new treatments for cancer and pain (2009)

Several series of Trk inhibitors with excellent in vitro potencies have been reported and a number of compounds have gone into the clinic. It should be noted that few of these inhibitors are Trk selective, demonstrating that targeting Trk kinases for treatment of pain and/or cancer offers a promising but also challenging approach.
Association of herpesviruses in the aqueous humor of patients with serpiginous choroiditis: a polymerase chain reaction-based study (2002)

VZV and HSV DNA were detected in a subset of patients with serpiginous choroiditis, suggesting that these viruses may function in the pathogenesis of this disease.
Recent applications of the CuI-catalysed Huisgen azide–alkyne 1,3-dipolar cycloaddition reaction in carbohydrate chemistry (2007)

This article surveys recent applications of Cu(I)-catalysed 1,3-dipolar cycloaddition of azides and alkynes in carbohydrate chemistry, highlighting developments in the preparation of simple glycoside and oligosaccharide mimetics, glyco-macrocycles, glycopeptides, glyco-clusters and carbohydrate arrays.
Synthesis of Optically Complex Core–Shell Colloidal Suspensions: Pathways to Multiplexed Biological Screening (2003)

Abstract The ability to generate enormous random libraries of DNA probes via split‐and‐mix synthesis on solid supports is an important biotechnological application of colloids that has not been fully utilized to date. To discriminate between colloid‐based DNA probes each colloidal particle must be ‘encoded’ so it is distinguishable from all other particles. To this end, we have used novel particle synthesis strategies to produce large numbers of optically encoded particles suitable for DNA library synthesis. Multi‐fluorescent particles with unique and reproducible optical signatures (i.e., fluorescence and light‐scattering attributes) suitable for high‐throughput flow cytometry have been produced. In the spectroscopic study presented here, we investigated the optical characteristics of multi‐fluorescent particles that were synthesized by coating silica ‘core’ particles with up to six different fluorescent dye shells alternated with non‐fluorescent silica ‘spacer’ shells. It was observed that the diameter of the particles increased by up to 20 % as a result of the addition of twelve concentric shells and that there was a significant reduction in fluorescence emission intensities from inner shells as an increasing number of shells were deposited.
Cloning and Characterization of Two Extracellular Heparin-degrading Endosulfatases in Mice and Humans (2002)

Here we report the cloning of a full-length cDNA encoding the human ortholog (HSulf-1) of the developmentally regulated putative sulfatases QSulf-1 (Dhoot, G. K., Gustafsson, M. K., Ai, X., Sun, W., Standiford, D. M., and Emerson, C. P., Jr. (2001) Science 293, 1663-1666) and RSulfFP1 (Ohto, T., Uchida, H., Yamazaki, H., Keino-Masu, K., Matsui, A., and Masu, M. (2002) Genes Cells 7, 173-185) as well as a cDNA encoding a closely related protein, designated HSulf-2. We have also obtained cDNAs for the mouse orthologs of both Sulfs. We demonstrate that the proteins encoded by both classes of cDNAs are endoproteolytically processed in the secretory pathway and are released into conditioned medium of transfected CHO cells. We demonstrate that the mammalian Sulfs exhibit arylsulfatase activity with a pH optimum in the neutral range; moreover, they can remove sulfate from the C-6 position of glucosamine within specific subregions of intact heparin. Taken together, our results establish that the mammalian Sulfs are extracellular endosulfatases with strong potential for modulating the interactions of heparan sulfate proteoglycans in the extracellular microenvironment.