gebhart/patrepeval huggingface dataset:
PCR amplification of DNA microdissected from a single polytene chromosome band: a comparison with conventional microcloning (1989)

A novel alternative to microcloning for the production of region specific chromosomal DNA is described. In this method, 'microamplification', single bands are dissected from polytene chromosomes and digested with Sau3A. Oligonucleotide adaptors are ligated to these fragments to provide convenient priming sites for polymerase chain reaction amplification. In this way, as much as 1 microgram of DNA can be amplified from a single band. Probes made from PCR amplified DNA from two such dissections have been used to probe cloned DNA form a 100 kb chromosome walk. Whereas conventional microcloning has generated cloned EcoRI fragments corresponding to 3-4 kb of the walk, the PCR probes cover greater than 90% of this chromosomal region. Thus microamplification is significantly more effective than microcloning in providing probes for establishing chromosomal walks.
Protection against developmental retardation in apolipoprotein E-deficient mice by a fatty neuropeptide: Implications for early treatment of Alzheimer's disease (1997)

Stearyl-Nle17-VIP (SNV) is a novel agonist of vasoactive intestinal peptide (VIP) exhibiting a 100-fold greater potency than the parent molecule and specificity for a receptor associated with neuronal survival. Here, mice deficient in apolipoprotein E (ApoE), a molecule associated with the etiology of Alzheimer's disease, served as a model to investigate the developmental and protective effects of SNV. In comparison to control animals, the deficient mice exhibited (a) reduced amounts of VIP messenger RNA; (b) decreased cholinergic activity (c) significant retardation in the acquisition of developmental milestones: forelimb placing behavior and cliff avoidance behavior; and (d) learning and memory impairments. Daily injections of SNV to ApoE-deficient newborn pups resulted in increased cholinergic activity and marked improvements in the time of acquisition of behavioral milestones, with peptide-treated animals developing as fast as control animals and exhibiting improved cognitive functions after cessation of peptide treatment. Specificity was demonstrated in that treatment with a related peptide (PACAP), pituitary adenylate cyclase-activating peptide, produced only limited amelioration. As certain genotypes of ApoE increase the probability of Alzheimer's disease, early counseling and preventive treatments may now offer an important route for therapeutics design.
Involvement of Rho GTPases in the Transcriptional Inhibition of Preproendothelin-1 Gene Expression by Simvastatin in Vascular Endothelial Cells (2000)

Endothelial dysfunction is characterized by an impaired vasodilatory response to endothelial agonists as well as by alterations in adhesion and coagulation processes. 3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have been shown to be useful in the reversal of endothelial dysfunction, an effect that may be independent of the reduction in cholesterol levels. Both the L-arginine-nitric oxide-cGMP and endothelin pathways are involved in the regulation of vascular tone. Here, we show that the basal transcription rate of the preproendothelin-1 gene was decreased by simvastatin (10 micromol/L) in bovine aortic endothelial cells. Transfection studies with the preproendothelin-1 gene promoter showed that mevalonate (100 micromol/L) was able to prevent the inhibitory effect mediated by simvastatin. Protein geranylgeranylation, but not farnesylation, proved to be crucial for a correct expression of the preproendothelin-1 gene. The C3 exotoxin from Clostridium botulinum that selectively inactivates Rho GTPases, the processing of which involves geranylgeranylation, reproduced the inhibitory effect of simvastatin on the expression of preproendothelin-1. Overexpression of dominant-negative mutants of RhoA and RhoB led to a significant reduction in the preproendothelin-1 promoter activity, whereas the expression of wild-type and constitutively active forms of these proteins resulted in an increase, in support that Rho proteins are required for the basal expression of the preproendothelin-1 gene. Finally, we show that the Rho-dependent activation of the preproendothelin-1 gene transcription was inhibited by simvastatin. Thus, the control of vascular tone and proliferative response mediated by endothelin-1 is regulated at multiple levels, among which the Rho proteins play an essential role.
Activation of NF-?B protects hippocampal neurons against oxidative stress-induced apoptosis: Evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration (1997)

The transcription factor NF-kappaB is expressed in neurons wherein it is activated in response to a variety of stress- and injury-related stimuli including exposure to cytokines such as tumor necrosis factor-alpha (TNFalpha), and excitotoxic and oxidative insults. NF-kappaB may play a role in the anti-death actions of TNFalpha in cultured hippocampal neurons exposed to metabolic and oxidative insults. We now report that pretreatment of hippocampal cell cultures with agents that activate NF-kappaB (TNFalpha and C2-ceramide) confers resistance of neurons to apoptosis induced by the oxidative insults FeSO4 and amyloid beta-peptide (Abeta25-35). The neuroprotective actions of TNFalpha and ceramide were abolished in cultures cotreated with kappaB decoy DNA demonstrating a requirement for NF-kappaB activation for prevention of cell death. Levels of manganese superoxide dismutase (Mn-SOD) in neurons were increased following exposure of cultures to TNFalpha and ceramide in control cultures, but not in cultures cotreated with kappaB decoy DNA. FeSO4 and Abeta25-35 induced accumulation of mitochondrial peroxynitrite, and membrane lipid peroxidation, in neurons. Peroxynitrite accumulation and lipid peroxidation were largely prevented in neurons pretreated with TNFalpha and ceramide prior to exposure to FeSO4 and Abeta25-35, an effect blocked by kappaB decoy DNA. Immunoreactivity of neurons with an anti-nitrotyrosine antibody was increased following exposure to FeSO4 and Abeta25-35; TNFalpha and C2-ceramide suppressed protein tyrosine nitration, and kappaB decoy DNA blocked the effects of TNFalpha and C2-ceramide. Finally, the peroxynitrite scavenger uric acid protected neurons against apoptosis induced by FeSO4 and Abeta, and suppressed peroxynitrite accumulation. We conclude that, by inducing production of Mn-SOD and suppressing peroxynitrite formation and membrane lipid peroxidation, NF-kappaB plays an anti-apoptotic role in neurodegenerative conditions that involve oxidative stress. The data further suggest important roles for peroxynitrite and NF-kappaB in the pathogenesis of neuronal degeneration in Alzheimer's disease.
Piezoelectric ceramics and ultrasonic transducers (1989)

The author reviews the basic characteristics and progress in transducer properties of the different types of piezoelectric ceramics. The application of these materials in practical ultrasonic transducers is also reported.
Antineoplastic agent. 174. Isolation and structure of the cytostatic depsipeptide dolastatin 13 from the sea hare Dolabella auricularia (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntineoplastic agent. 174. Isolation and structure of the cytostatic depsipeptide dolastatin 13 from the sea hare Dolabella auriculariaGeorge R. Pettit, Yoshiaki Kamano, Cherry L. Herald, Claude Dufresne, Ronald L. Cerny, Delbert L. Herald, Jean M. Schmidt, and Haruhisa KizuCite this: J. Am. Chem. Soc. 1989, 111, 13, 5015–5017Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/ja00195a084https://doi.org/10.1021/ja00195a084research-articleACS PublicationsRequest reuse permissionsArticle Views341Altmetric-Citations76LEARN 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-Alertsclose Get e-Alerts
Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans (1989)

To examine the importance of first-phase insulin secretion on total body glucose homeostasis, six normal subjects (age, 24 +/- 1 yr; ideal body wt, 100 +/- 1%) received three hyperglycemic (+75 mg/100 ml) clamp studies in combination with [3-3H]glucose: study I, 150 min hyperglycemic clamp; study II, hyperglycemic clamp plus somatostatin (6 micrograms/min) plus basal glucagon replacement (0.4 ng.kg-1.min-1) plus an insulin infusion designed to mimic only the second phase of insulin secretion; and study III, hyperglycemic clamp plus somatostatin plus basal glucagon plus an insulin infusion designed to mimic both the first and second phase of insulin secretion. Basal plasma C-peptide concentrations averaged 0.21 +/- 0.01 pmol/ml in the three study protocols. In study I the plasma C-peptide response demonstrated an early burst within the first 10 min followed by a gradually increasing phase of C-peptide secretion that lasted until the end of the study. In studies II and III plasma C-peptide declined within the first 10 min after somatostatin was started and averaged 0.06 +/- 0.01 and 0.05 +/- 0.01 pmol/min, respectively. Basal hepatic glucose production (2.3 +/- 0.2 mg.kg-1.min-1) was suppressed by 90% at 20 min and remained suppressed thereafter in studies I and III. In contrast, in study II hepatic glucose production was inhibited by only 50% (1.1 +/- 0.2 mg.kg-1.min-1) at 60 min (P less than 0.01 vs. studies I and III) and remained incompletely suppressed even after 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Simulation-Assignment-Based Travel Time Prediction Model for Traffic Corridors (2012)

Travel time prediction in Advanced Traveler Information Systems is an important issue, because travel time is a major factor in motorists' decisions to avoid congestion and incidents. A simulation-assignment-based travel time prediction model for traffic corridors is constructed in this paper. Based on the concept of simulation-assignment models, two algorithms-the flowand the vehicle-based models-are proposed for travel time prediction. One of the critical issues in simulation-assignment models is how reliable time-dependent origin-destination (O-D) trip tables are generated. A dynamic O-D estimation and prediction procedure is developed to generate time-dependent O-D demand data for simulating vehicle movements using DynaTAIWAN: a simulation-assignment model. The empirical travel time data that were collected from electronic toll stations are used to validate the travel times that were predicted by the proposed models. The mean absolute percentage errors (RMSPEs) and root-mean-square percentage errors are less than 20% and 26% for the vehicle-based model and less than 10% and 12% for the flow-based model, respectively. The results show that the proposed algorithms predict reasonable travel times for traffic corridors.
2,3-Butanediol Production by Acetogenic Bacteria, an Alternative Route to Chemical Synthesis, Using Industrial Waste Gas (2011)

2,3-Butanediol (23BD) is a high-value chemical usually produced petrochemically but which can also be synthesized by some bacteria. To date, the best microbial 23BD production rates have been observed using pathogenic bacteria in fermentation systems that depend on sugars as the carbon and energy sources for product synthesis. Here we present evidence of 23BD production by three nonpathogenic acetogenic Clostridium species-Clostridium autoethanogenum, C. ljungdahlii, and C. ragsdalei-using carbon monoxide-containing industrial waste gases or syngas as the sole source of carbon and energy. Through an analysis of the C. ljungdahlii genome, the complete pathway from carbon monoxide to 23BD has been proposed. Homologues of the genes involved in this pathway were also confirmed for the other two species investigated. A gene expression study demonstrates a correlation between mRNA accumulation from 23BD biosynthetic genes and the onset of 23BD production, while a broader expression study of Wood-Ljungdahl pathway genes provides a transcription-level view of one of the oldest existing biochemical pathways.
The thermodynamic advantage of DNA oligonucleotide 'stacking hybridization' reactions: energetics of a DNA nick (1997)

'Stacking hybridization reactions' wherein two or more short DNA oligomers hybridize in a contiguous tandem orientation onto a longer complementary DNA single strand have been employed to enhance a variety of analytical oligonucleotide hybridization schemes. If the short oligomers anneal in perfect head-to-tail register the resulting duplex contains a nick at every boundary between hybridized oligomers. Alternatively, if the short oligomers do not hybridize precisely in register, i.e. single strand regions on the longer strand are left unbound, gaps are formed between regions where short oligomers bind. The resulting gapped DNA duplexes are considerably less stable than their nicked duplex analogs. Formation of base pair stacking interactions between neighboring oligomers at the nicks that do not occur in gapped duplexes has been proposed as the source of the observed added stability. However, quantitative evidence supporting this hypothesis for DNA has not been reported. Until now, a direct comparison of the thermodynamics of DNA nicks versus DNA gaps has not been performed. In this communication we report such a comparison. Analysis of optical melting experiments in a well defined molecular context enabled quantitative evaluations of the relative thermodynamic difference between nicked and gapped DNA duplexes. Results of the analysis reveal that a nick may be energetically favored over a gap by at least 1.4 kcal/mol and perhaps as much as 2.4 kcal/mol. The presence of a 5'phosphate at a nick or gap fails to significantly affect their stabilities.
5-hydroxytryptamine stimulates glucose transport in cardiomyocytes via a monoamine oxidase-dependent reaction (1995)

This study deals with the effect of 5-hydroxytryptamine (5-HT; serotonin) on glucose transport in isolated rat cardiac myocytes. In these cells, 5-HT (10-300 microns), as well as tryptamine, 5-methoxytryptamine and dopamine, elicited a 3-5 fold increase in glucose transport, as compared with control. This effect was maximal after 90 min, and was concomitant with a 1.8- and 1.5-fold increase in the amounts of glucose transporters GLUT1 and GLUT4 at the cell surface of the cardiomyocytes, as determined by using the photoaffinity label 3H-2-N-[4-(1-azi-2,2,2-trifluoroethyl)benzoyl]-1,3-bis-(D-manno s-4-yl) propyl-2-amine (3H-ATB-BMPA). In contrast, 3-3000 microM of the selective 5-HT receptor agonists 5-carboxyamido-tryptamine, alpha-methyl-serotonin, 2-methyl-serotonin or renzapride failed to stimulate glucose transport. The effect of 5-HT was not affected by (i) the 5-HT receptor antagonists methysergide (1 microM), ketanserin (1 microM), cyproheptadine (1 microM), MDL 72222 (1 microM) or ICS 205-930 (3 microM), nor by (ii) the adrenergic receptor antagonists prazosin (1 microM), yohimbine (1 microM) or propranolol (5 microM), nor by (iii) the dopaminergic antagonists SCH 23390 (1 microM) or haloperidol (1 microM). The monoamine oxidase inhibitors clorgyline (1 microM) and tranylcypromine (1 microM) completely suppressed the effect of 5-HT, whereas the control and insulin-stimulated rates of glucose transport were unaffected. Addition of catalase or glutathione diminished the 5-HT-dependent stimulation of glucose transport by 50%; these two factors are known to favour the degradation of H2O2 (which can be formed during the deamination of amines by monoamine oxidases). Glutathione also depressed the stimulatory action of exogenously added H2O2 (20 microM) by 30%. Furthermore, in cells treated with 5_HT, a time-dependent accumulation of 5-hydroxy-1H-indol-3-ylacetic acid (a product of 5-HT metabolism via monoamine oxidases) was observed, which paralleled the changes in glucose transport. In conclusion, the stimulation of glucose transport by 5-HT in cardiomyocytes is not mediated by a 5-HT1, 5-HT2, 5-HT3 or 5-HT4 receptor, nor by an adrenergic or dopaminergic receptor, but is likely to occur through the degradation of by a monoamine oxidase and concomitant formation of H2O2.
Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal (2013)

The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics.
Neural apoptosis (1995)

Apoptosis is a mode of cell death in which the cell plays an active role in its own demise. The study of neural apoptosis, the identification of genes controlling apoptosis, and the examination of the mechanisms by which these genes achieve their effects have assumed increasing importance over the past few years. This is because (1) neural apoptosis occurs not only in development, but also in pathophysiological states such as stroke, glutamate toxicity, and beta-amyloid peptide toxicity; (2) genes that control apoptotic cell death, such as bcl-2, p35, p53, and p75NTR, also modulate necrotic neural death in some cases; (3) the emerging mechanisms by which these genes control apoptosis may be relevant for understanding neurodegenerative processes, and for the design of therapeutic agents; and (4) the findings that the cell plays an active role in its own demise, and that specific gene products are involved, suggest that therapeutic intervention may be feasible.
Methylation patterns in cell‐free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients (2010)

Abnormal DNA methylation is a feature of most types of cancer, which is reflected in cell-free circulating DNA in plasma. It is, however, unknown whether surgical removal of the tumor and subsequent therapy induces changes in plasma DNA methylation, which can be used to monitor treatment. In this pilot study, methylation in cell-free plasma DNA of 20 breast cancer patients was determined by the previously developed MethDet-56 technique. Samples at three time points were analyzed-before surgery (baseline), after surgery (to evaluate the effects of resection) and after surgery on tamoxifen therapy (to determine the effects of treatment). Methylation patterns of healthy controls were used as a reference for all comparisons. Seven promoters were differentially methylated (p < 0.05) in at least one comparison; three changed after surgery; another one changed after beginning of tamoxifen treatment; and four were differentially methylated in baseline versus combined treatment samples. Increased methylation of PR PROX, MDGI, PAX 5 and RARβ2 at baseline (presurgery) diminished toward the healthy controls with the lowest methylation in the combined treatment group. Surgery alone decreased methylation in PAX 5 and RARβ2, whereas tamoxifen treatment changed methylation only in the B promoter of ESR1. Methylation patterns in cell-free plasma DNA change after surgery and tamoxifen treatment, most significantly-after combined treatment. The baseline (presurgery) patterns become similar to those of healthy controls, suggesting that methylation patterns in cell-free plasma DNA may be used to monitor treatment.
Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood (1985)

To confirm the pathogenesis and the genetic background of neonatal- onset purpura fulminans, two unrelated infants with this rare thrombotic syndrome and 47 of their asymptomatic relatives were studied. In both families, 27 subjects with hereditary partial deficiency of protein C, including both parents of each patient, were identified. The patient in whom it was possible to evaluate protein C directly showed no detectable levels of this plasma component. These findings confirm the linkage of neonatal purpura fulminans to a genetic trait with established mendelian transmission and strongly suggest that the syndrome is an expression of homozygosity for protein C deficiency. The dramatic clinical picture and the type of pathologic change that develops as a result of the lack of circulating protein C emphasize the vital role of this protein in protection from thrombin generation, mainly within the microvascular system. However, our data do not contribute to the evidence that partial familial protein C deficiency is associated with a major risk of venous thromboembolism.
A robust sequential approach for the detection of defective pixels in an image sensor (1999)

Large image sensors usually contain same defects. Defects are pixels with abnormal photo-responsibility. As a result they often generate outputs different from their adjacent pixel outputs and seriously degrade the visual quality of the captured images. However, it is not economically feasible to produce sensors with no defects for rendering images. A limited number of defects are usually allowed in an image sensor as long as the defective outputs can be corrected with post signal processing techniques. In this paper we present a robust sequential approach for detecting sensor defects from a sequence of images captured by the sensor. With this approach no extra non-volatile memory is required in the sensor device to store the locations of sensor defects. In addition, the detection and correction of image defective outputs can be performed efficiently in a computer host. Experimental results of this approach are reported in the paper.