gebhart/patrepeval huggingface dataset:
TNFSF10 (TRAIL), a p53 target gene that mediates p53-dependent cell death (2008)

We have identified TNFSF10 (TRAIL) as a p53-transcriptional target gene. There are two p53 DNA-binding sites in the human TNFSF10 promoter region, at 346 and 625 bp upstream of the transcription start site. A human p53-expressing adenovirus (Ad-p53) induced TRAIL mRNA and protein expression in HCT116 p53-/- human colon cancer cells. A human TRAIL-promoter reporter assay showed increased luciferase activity with the promoter vector that contains two p53 DNA-binding motifs,following Ad-p53 infection, compared to the control adenovirus infection. Using HCT116 cells, gene silencing of TNFSF10 by siRNA suppressed caspase 3 and 7 activity, even after treatment with the DNA-damaging chemotherapeutic agent adriamycin. TRAIL protein expression was elevated in adriamycin-treated breast cancer cells. In vivo, TRAIL expression was induced in mouse natural killer cells at 24 hours after systemic treatment with 5-Fluorouracil. p53-dependent TRAIL induction in natural killer cells after chemotherapy exposure provides a link between the tumor suppressor p53 and the host immune response during cancer therapy as well as a paracrine-mediated cell-extrinsic death response. Our findings provide new mechanistic insights into the signaling of p53-dependent cell death and tumor suppression, including the involvement of the host immune system and natural killer cells in vivo in the anti-tumor efficacy of chemotherapy.
MONOCONE--A MOBILE GRAVITY PLATFORM FOR THE ARCTIC OFFSHORE (1977)

This paper discusses a mobile, gravity platform for year-round petroleum operations in the Canadian Beaufort Sea. The Monocone is a coined name derived from Monopod which alludes to the platform's single structural column rising from the centre of a circular base, and Cone which refers to a movable conical collar selectively positioned on this column. The conical collar causes the ice to fail in flexure and at minimum loads by maintaining a constant water line diameter in different water depths. Ice and wave forces constitute the main loading conditions and these were developed theoretically and experimentally, the latter in ice model basins and in a wave tank. The environmental conditions and structural and foundation design of this prestressed concrete and steel structure are discussed, as well as model tank tests on seakeeping, towing, and lowering and raising procedures. The conical collar, if sufficiently large would allow controlled, near-vertical setdown of the platform to bottom in any water depth. In this paper, a Monocone platform for a maximum design water depth of 41.0 m is discussed.
Discretización temporal de la tormenta sintética de Chicago (1988)

espanolEl Metodo de Transformacion Precipitacion-Escorrentia es uno de los metodos utilizados fre- cuentemente para el calculo de hidrogramas de proyecto en areas urbanas. Su funcion de entra- da es un hietograma sintetico maximizado denominado tormenta de diseno. Aunque la distribucion temporal de la tormenta de diseno es a menudo expresada como una funcion continua, para su aplicacion en modelos de escurrimiento debe ser discretizada en intervalos de tiempo, general- mente coincidentes con el paso de tiempo computacional. A medida que dicho intervalo de tiempo es mayor, mayor es la atenuacion de la intensidad pico instantanea, principalmente en funciones de maximos agudos como la Tormenta de Chicago, lo cual modifica los resultados de la modelacion, principalmente en cuencas pequenas y cuando se aplican modelos no lineales. Cuanto mayor es el intervalo de tiempo usado para definir el Hietograma de Chicago, mayor es la atenuacion o amortiguamiento del caudal pico calculado. Se evalua la influencia de la dis- cretizacion temporal de la Tormenta de Chicago en los resultados de la simulacion de una cuen- ca urbana piloto de la ciudad de Santa Fe, Argentina, obtenidos por aplicacion del modelo SWMM (Storm Water Management Model) EnglishOne of the methods frequently used for the project hydrographs calculation in urban areas is the precip- itation runoff transformation method. Its input function is a synthetic maximized hyetograph that it is called storm. Although the temporal distribution of the design storm is often expressed as a continue func- tion, its application in runoff models needs to be discretized in time intervals that generally coincide with the computational time step. The greater the interval of time, the greater the instantaneus peak intensity attenu- ation, mainly in sharp maxima as the Chicago storm, that modifies the simulation results, specially in small basins and when no lineal models are applied. The greater the time interval used to define Chicago hyeto- graph, the greater the attenuation of the calculated peak flow.The results of the experimental basin simula- tion on Santa Fe city (Argentina) are obtained by the application of SWMM model (Storm Water Management Model). The temporal dicretization influence of the Chicago Storm on these results is evaluated here.
Electrochemical reactions. Part 20. Intramolecular cyclisation during the reduction of 2-chloro-NN-diphenylbenzamides (1977)

The aryl radical formed by reductive cleavage of the carbon–chlorine bond in 2-chloro-NN-diphenylbenzamide undergoes exclusive capture by the neighbouring N-phenyl group to yield N-phenylphenanthridone and biphenyl-2-carboxanilide. 2-Chloro-NN-di-4-tolylbenzamide undergoes a similar reaction.
The effect of filters on aseptic pipetting lifetime of mechanical and electronic pipettors and carryover during pipetting (1999)

The aseptic pipetting lifetime of air displacement pipettors during serial pipetting was investigated. When a Micrococcus luteusT culture was pipetted using no filter, less than 100 pipettings were required to contaminate the interiors of both mechanical and electronic pipettors with more than 103 cfu (n = 1890 pipettings). When a filter was placed in the pipettor tip cone, the sterility of the pipettor barrel was maintained for more than 500 pipettings (n = 2620) or 50–250 pipettings (n = 2520), depending on the filter type used. When a radioactive liquid or plasmid DNA was pipetted using no filter, contamination of the pipettor barrel occurred within less than 100 pipettings. A filter placed in the pipettor tip cone protected the interior of the pipettors against radioactive contamination for more than 250 pipettings and against DNA contamination for more than 500 pipettings. A pipettor barrel contaminated with M. luteusT caused carryover in 13% of the pipetting series. When a SCF filter was placed in the tip cone, no carryover was observed within 2620 pipettings. A tip cone filter replaced at intervals of 50–250 (polyethylene filter) or 500 (SCF filter) pipettings will protect the pipettor barrel from contamination and the samples from carryover.
Quantum Optimization of Fully Connected Spin Glasses (2015)

Quantum computing promises to be more efficient and significantly faster than today's classical computing. Researchers compare the performance of a quantum annealer with that of classical algorithms for the first time on hard spin-glass problems.
Caveolin-1 Potentiates Estrogen Receptor α (ERα) Signaling (1999)

Estrogen receptor alpha (ERalpha) is a soluble protein that mediates the effects of the gonadal estrogens such as 17beta-estradiol. Upon ligand binding, a cytoplasmic pool of ERalpha translocates to the nucleus, where it acts as a transcription factor, driving the expression of genes that contain estrogen-response elements. The activity of ERalpha is regulated by a number of proteins, including cytosolic chaperones and nuclear cofactors. Here, we show that caveolin-1 potentiates ERalpha-mediated signal transduction. Coexpression of caveolin-1 and ERalpha resulted in ligand-independent translocation of ERalpha to the nucleus as shown by both cell fractionation and immunofluorescence microscopic studies. Similarly, caveolin-1 augmented both ligand-independent and ligand-dependent ERalpha signaling as measured using a estrogen-response element-based luciferase reporter assay. Caveolin-1-mediated activation of ERalpha was sensitive to a well known ER antagonist, 4-hydroxytamoxifen. However, much higher concentrations of tamoxifen were required to mediate inhibition in the presence of caveolin-1. Interestingly, caveolin-1 expression also synergized with a constitutively active, ligand-independent ERalpha mutant, dramatically illustrating the potent stimulatory effect of caveolin-1 in this receptor system. Taken together, our results identify caveolin-1 as a new positive regulator of ERalpha signal transduction.
Beyond Fat--tree: Unidirectional Load--Balanced Multistage Interconnection Network (2008)

The fat-tree is one of the most widely-used topologies by interconnection network manufacturers. Recently, it has been demonstrated that a deterministic routing algorithm that optimally balances the network traffic can not only achieve almost the same performance than an adaptive routing algorithm but also outperforms it. On the other hand, fat-trees require a high number of switches with a non-negligible wiring complexity. In this paper, we propose replacing the fat--tree by a unidirectional multistage interconnection network (UMIN) that uses a traffic balancing deterministic routing algorithm. As a consequence, switch hardware is almost reduced to the half, decreasing, in this way, the power consumption, the arbitration complexity, the switch size itself, and the network cost. Preliminary evaluation results show that the UMIN with the load balancing scheme obtains lower latency than fat--tree for low and medium traffic loads. Furthermore, in networks with a high number of stages or with high radix switches, it obtains the same, or even higher, throughput than fat-tree.
A methodology for reflector classification analysis in complex geometric welded structures (1984)

Methodologie pour la classification et l'analyse des reflecteurs dans des structures soudees a geometrie complexe
Single nucleotide polymorphisms and the future of genetic epidemiology (2000)

In this review, we consider the motivation behind contemporary single nucleotide polymorphism (SNP) initiatives. Many of these initiatives are projected to involve large, population-based surveys. We therefore emphasize the utility of SNPs for genetic epidemiology studies. We start by offering an overview of genetic polymorphism and discuss the historical use of polymorphism in the identification of disease-predisposing genes via meiotic mapping. We next consider some of the unique aspects of SNPs, and their relative advantages and disadvantages in human population-based analyses. In this context, we describe and critique the following six different areas of application for SNP technologies: Gene discovery and mapping. Association-based candidate polymorphism testing. Diagnostics and risk profiling. Prediction of response to environmental stimuli, xenobiotics and diet. Homogeneity testing and epidemiological study design. Physiologic genomics. We focus on key issues within each of these areas in an effort to point out potential problems that might plague the use of SNPs (or other forms of polymorphism) within them. However, we make no claim that our list of considerations are exhaustive. Rather, we believe that they may provide a starting point for further dialog about the ultimate utility of SNP technologies. In addition, although our emphasis is placed on applications of SNPs to the understanding of human phenotypes, we acknowledge that SNP maps and technologies applied to other species (e.g. the mouse genome, pathogen genomes, plant genomes, etc.) are also of tremendous interest.
Electronic Principles: Physics, Models, and Circuits (1971)

This book begins with the physical principles involved in the operation of semiconductor components, proceeds through the physical electronics, modeling, and circuit characteristics of these components, and engages the questions and problems that arise in the computer-aided design of complex multicomponent functional assemblies of the type found in modern integrated-circuit packages.
Serum S100 – A Marker for Disease Monitoring in Metastatic Melanoma (1997)

The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.
Substrate Specificity of a Mutant Alanyl-Transfer Ribonucleic Acid Synthetase of <i>Escherichia coli</i> (1971)

The correlation between the in vivo functioning and the in vitro behavior of the thermolabile alanyl-transfer ribonucleic acid (tRNA) synthetase (ARS) of Escherichia coli strain BM113 is presented. As a measure for the ARS activity inside the cell, the amount of acylated tRNA(ala) in vivo was determined. The rapid drop of the per cent tRNA(ala) charged which was observed upon shifting a culture of BM113 to the nonpermissive temperature indicates that in vivo acylation of tRNA(ala) might be the growth-limiting step at high temperature. Since neither growth nor the in vivo charging level of tRNA(ala) was affected by the addition of high l-alanine concentrations to the medium, one may infer that impaired functioning of the mutant enzyme at 40 C seems not to be due to reduced affinity of the enzyme for the amino acid. Separation of bulk tRNA of E. coli and of yeast on benzoylated diethylaminoethyl cellulose and charging of the fractions of the column by wild-type and mutant ARS reveal that only those tRNA species aminoacylated by the wild-type enzyme are also charged by the mutant ARS. Determination of the K(m) values of wild-type and mutant ARS for the three isoaccepting tRNA(ala) species of E. coli shows a ca. 10-fold increase of the apparent K(m) values of the mutant enzyme for all three species. Thus, the mutation proportionally reduces the apparent affinity for tRNA(ala) without causing any detectable recognition errors. Investigation of heat inactivation kinetics of wild-type and mutant ARS without and in the presence of substrates provides further evidence that only the transfer site of the ARS is altered by the mutation. Moreover, whereas both enzymes possess the same pH optimum of the relative maximal velocity, their pH dependence of the K(m) values for tRNA is different. The K(m) of the wild-type enzyme decreases at pH values below 7.0 and that of the mutant enzyme shows the inverse tendency; this again indicates an alteration of the tRNA binding site.
Purification and characterization of Clostridium difficile toxin (1979)

Recent evidence indicates that toxigenic Clostridium difficile strains are a major cause of antimicrobial-associated ileocecitis in laboratory animals and pseudomembranous colitis in humans. C. difficile ATCC 9689 was cultivated in a synthetic medium to which 3% ultrafiltrated proteose peptone was added. Purification of the toxin from broth filtrate was accomplished through ultrafiltration (100,000 nominal-molecular-weight-limit membrane), precipitation with 75% (NH4)2SO4, and chromatographic separation using Bio-Gel A 5m followed by ion-exchange chromatography on a diethylaminoethyl-Sephadex A-25 column. The purified toxin displayed only one band on polyacrylamide gel electrophoresis, and approximately 170 pg was cytopathic for human amnion cells. The isolated toxin was neutralized by Clostridium sordelli antitoxin, heat labile (56 degrees C for 30 min), and inactivated at pH 4 and 9; it had an isoelectric point of 5.0, increased vascular permeability in rabbits, and caused ileocecitis in hamsters when injected intracecally. Treatment of the toxin with trypsin, chymotrypsin, pronase, amylase, or ethylmercurithiosalicylate caused inactivation, whereas lipase had no effect. By gel filtration, its molecular weight was estimated as 530,000. Upon reduction and denaturation, the toxin dissociated into 185,000- and 50,000-molecular-weight components, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Extensive dissociation yielded only the 50,000-molecular-weight component. The toxin appears to be protoplasmic and is released into the surrounding environment upon autolysis of the cells. Attempts to correlate specific enzymatic activity with the toxin have been unsuccessful. These studies will help delineate the role of C. difficile toxin in antimicrobial-associated colitis and diarrhea.
Detection of slow port scans in flow-based network traffic (2018)

Frequently, port scans are early indicators of more serious attacks. Unfortunately, the detection of slow port scans in company networks is challenging due to the massive amount of network data. This paper proposes an innovative approach for preprocessing flow-based data which is specifically tailored to the detection of slow port scans. The preprocessing chain generates new objects based on flow-based data aggregated over time windows while taking domain knowledge as well as additional knowledge about the network structure into account. The computed objects are used as input for the further analysis. Based on these objects, we propose two different approaches for detection of slow port scans. One approach is unsupervised and uses sequential hypothesis testing whereas the other approach is supervised and uses classification algorithms. We compare both approaches with existing port scan detection algorithms on the flow-based CIDDS-001 data set. Experiments indicate that the proposed approaches achieve better detection rates and exhibit less false alarms than similar algorithms.
Identification of <i>Mycobacterium ulcerans</i> in the Environment from Regions in Southeast Australia in Which It Is Endemic with Sequence Capture-PCR (2000)

We recently described the use of PCR to identify the environmental source of Mycobacterium ulcerans during an outbreak of ulcerative disease that occurred in a localized region of southeast Australia. The PCR used was based on amplification of the M. ulcerans-specific insertion sequence, IS2404. In this study we developed a new test that is a substantial improvement over the original PCR method in terms of sensitivity, reliability, and ease of use. In the new method magnetic bead sequence capture-PCR is used to detect two M. ulcerans sequences (IS2404 and IS2606) and total mycobacterial 16S ribosomal DNA. We used sequence capture-PCR to test water and plant material collected over a 12-month period during 1998 and 1999 from sites near the centers of two distinct foci of M. ulcerans infections. A golf course irrigation system in one area and a small shallow lake in another area repeatedly were PCR positive for M. ulcerans. Nearby sites and sites unrelated to the endemic areas were negative. Based on the PCR data, a most-probable-number method was used to estimate the concentration of M. ulcerans cells in positive samples from both regions. This procedure resulted in average concentrations of 0.5 cell per 100 ml of water and 40 cells per 100 g of detritus. Loss of the PCR signal coincided with a decrease in ulcerative disease in each area. These results provide further evidence that M. ulcerans may be transmitted from a point environmental source and demonstrate the utility of magnetic bead sequence capture-PCR for identification of nonculturable microbial pathogens in the environment.
Molecular genetics of inherited susceptibility to intracellular parasites. (1991)

In the mouse, innate susceptibility to infection with mycobacteria is controlled by the Bcg host resistance locus. Phenotypically, the locus displays two alleles, a dominant resistance and a recessive susceptibility allele. The cell type expressing the resistance locus is the mature tissue macrophage. We have immortalized macrophages from Bcgr and Bcgs mice and found that macrophage cell lines of Bcgr origin, in comparison to those derived from Bcgs mice have an increased microbicidal activity and show increased expression of a number of molecules known to be associated with macrophage activation. This is in agreement with our earlier finding that Bcgr macrophages are at an advanced stage of macrophage priming for activation. The Bcg gene is located on the proximal region of mouse Chromosome 1. We have obtained a detailed genetic map in the vicinity of Bcg and identified three markers within 1 cM of the resistance locus. These three markers have been used for the generation of a physical map of this area of mouse Chromosome 1 and can be used as anchor points for the cloning of the Bcg host resistance gene. The chromosomal segment in the proximity of the Bcg locus in the mouse is precisely conserved on the telomeric region of the long arm of human Chromosome 2. Investigations of linkage of genetic markers present on human Chromosome 2q with susceptibility to tuberculosis have so far generated a LOD score of + 2.4. Linkage of Chromosome 2q markers with susceptibility to mycobacterial disease supports the existence of susceptibility genes in humans and suggests a human homologue of the mouse Bcg gene as a prime candidate for a human innate susceptibility locus.
Thrombogenicity of radiofrequency ablation procedures: what factors influence thrombin generation? (2001)

Radiofrequency ablation procedures confer an increased risk of thrombosis. Catheterization and diagnostic study contribute largely to the thrombogenic stimulus. Thrombogenicity is increased in prolonged, complex procedures and is decreased in patients who have been administered heparin during the procedure.
Alcohol-Binding Sites in Distinct Brain Proteins: The Quest for Atomic Level Resolution (2011)

Defining the sites of action of ethanol on brain proteins is a major prerequisite to understanding the molecular pharmacology of this drug. The main barrier to reaching an atomic-level understanding of alcohol action is the low potency of alcohols, ethanol in particular, which is a reflection of transient, low-affinity interactions with their targets. These mechanisms are difficult or impossible to study with traditional techniques such as radioligand binding or spectroscopy. However, there has been considerable recent progress in combining X-ray crystallography, structural modeling, and site-directed mutagenesis to define the sites and mechanisms of action of ethanol and related alcohols on key brain proteins. We review such insights for several diverse classes of proteins including inwardly rectifying potassium, transient receptor potential, and neurotransmitter-gated ion channels, as well as protein kinase C epsilon. Some common themes are beginning to emerge from these proteins, including hydrogen bonding of the hydroxyl group and van der Waals interactions of the methylene groups of ethanol with specific amino acid residues. The resulting binding energy is proposed to facilitate or stabilize low-energy state transitions in the bound proteins, allowing ethanol to act as a "molecular lubricant" for protein function. We discuss evidence for characteristic, discrete alcohol-binding sites on protein targets, as well as evidence that binding to some proteins is better characterized by an interaction region that can accommodate multiple molecules of ethanol.
Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis (2008)

CIN is associated with a worse prognosis in CRC, and should be evaluated as a prognostic marker, together with MSI status, in all clinical trials, particularly those involving adjuvant therapies.