gebhart/patrepeval huggingface dataset:
Getting more from digital SNP data (2006)

The digital SNP method has been proposed for identifying loss of heterozygosity (LOH) in tumour tissue and correlating it with patients' clinical characteristics. The method evaluates a tumour's allelic count at a single nucleotide polymorphism (SNP) for which the patient's normal tissue is heterozygous. The count is used to classify the tumour as positive or negative for LOH, using the sequential probability ratio test (SPRT). However, the SPRT was not developed for analysing digital SNP experiments. When applied to digital SNP data, the SPRT has several anomalies that can result in both loss of data and tumour misclassification. The anomalies are caused by discrepancies between the design of digital SNP experiments and the setting for which SPRT was developed. We propose an alternative classification scheme based on the false discovery rate, and show that it outperforms the SPRT when applied to Digital SNP data.
Human α-l-iduronidase. Catalytic properties and an integrated role in the lysosomal degradation of heparan sulphate (1992)

The kinetic parameters (Km and kcat) of human liver alpha-L-iduronidase were determined with a variety of heparin-derived disaccharide and tetrasaccharide substrates. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrates heparin and heparan sulphate were maintained, were hydrolysed with catalytic efficiencies up to 255 times that observed for the simplest disaccharide substrate to be hydrolysed. The major aglycone structure that influenced both substrate binding and enzyme activity was the presence of a C-6 sulphate ester on the residue adjacent to the iduronic acid residue being hydrolysed. Sulphate ions and a number of substrate and product analogues were potent inhibitors of enzyme activity. Human liver alpha-L-iduronidase activity towards 4-methylumbelliferyl alpha-L-iduronide at pH 4.8 had two Km values of 37 microM and 1.92 mM with corresponding kcat. values of 299 and 650 mol of product formed/min per mol of enzyme respectively, which may explain the wide range of Km values previously reported for alpha-L-iduronidase activity toward its substrate. Skin fibroblast alpha-L-iduronidase activity towards the heparin-derived oligosaccharides was influenced by the same substrate aglycone structural features as was observed for the human liver enzyme. A comparison was made of the effect of substrate aglycone structure upon catalytic activities of the enzymes which act to degrade the highly sulphated regions of heparan sulphate. A model was proposed whereby the substrate is directed from alpha-L-iduronidase to subsequent enzyme activities to ensure the efficient degradation of heparan sulphate.
Analysis of the Human Oral Microbiome of Smokers and Non-Smokers Using PCR-RFLP and Ribotyping (2014)

Recent advances in the field of microbial and medical ecology emphasize the critical role played by oral bacteria in the delicate dynamic equilibrium of human health and disease, creating the need to define the bacterial communities associated with healthy and non-healthy conditions and to capture shifts in community structure germane to diagnosis. Employing PCR-RFLP of the 16S rDNA gene from metagenomes and plate-wash (cultured) bacteria of oral wash from 10 volunteers, this study evaluated the stability of oral bacteria in healthy subjects and documented community shifts in smokers. Sequence analysis of selected 16S gene amplicons cloned with the Gene Hunter PCR-Trap vector and pCR 4-TOPO cloning kits was conducted to determine the bacteria identity and diversity indices of the two groups. Ribopatterns generated by the restriction enzymes HaeIII and Sau3AI were significantly (p AluI using the GelCompare II software cluster analysis. A stable core of bacteria DNA fingerprint was detected in all healthy subjects, and remained unchanged over the study period of 3 months. Signature bands (1500 bp with HaeIII) in smokers and in non-smokers (800 bp and 700 bp with Sau3A1) were evidently suggesting the presence of potential biomarkers of healthy and non-healthy states. There was no significant difference in the DNA fingerprints of cultured and metagenomic extracts. The genera Xanthomonas, Streptococcus and phylum Candidatus occurred in large numbers in both groups, however, a major shift in composition with the dominance of gram-negative bacteria in smokers compared to healthy subjects was quite remarkable. Taxonomic diversity in smokers was quite high, including members of the genera Rothia, Synechococcus, Neisseria, Thiomargarita and Pyrobaculum. These data highlight the presence of a stable core microbiome amidst a wide diversity, identify a distinct smokers’ cluster and open the way for the search for potential biomarkers for specific diseases.
Antibody-mediated recovery from subcutaneous herpes simplex virus type 2 infection (1978)

Young adult mice infected with 3 X 10(6) plaque-forming units of herpes simplex virus type 2 (HSV-2) died within 9 to 12 days after spread of the virus from the sites of infection to the spinal cord and brain. Administration of HSV-2-neutralizing antisera prepared in syngenic mice or in rabbits inhibited spread of the virus from the footpad of infected animals and prevented death. A single intraperitoneal inoculum of antiserum (virus-neutralizing titer of 1:128) was effective in protecting mice when the antiserum was given at 8 to 48 h, but not at 72 h, after virus inoculation. Immune sera absorbed with HSV-2-infected cells no longer protected mice from subcutaneous infection, whereas absorption with noninfected cells had no effect. Thus, HSV-2-specific antibodies appeared to be responsible for the protection observed. If the mice were given a sublethal dose of irradiation (390 rads) at 24 h before antibody transfer, protection was no longer obtained. This suggested that the mechanism of protection probably was not solely due to in vivo neutralization of virus, but required the participation of a radiosensitive component which has not yet been defined.
Unexpected N-acetylation of capreomycin by mycobacterial Eis enzymes (2012)

Eis is a unique acetyltransferase capable of inactivating the anti-TB drug capreomycin, AGs and other lysine-containing compounds.
Comparison of Piroxicam, Meclofenamate, Ibuprofen, Aspirin, and Prostacyclin Efficacy in a Chronic Model of Cerebral Vasospasm (1983)

Previous studies have suggested that certain prostanoids are mediators of the pathological features of subarachnoid hemorrhage (SAH) and that a reduced synthesis of prostacyclin in the vessel wall might also contribute to the cerebral vasospasm associated with this malady. The present study was performed, therefore, to ascertain whether known inhibitors of prostanoid synthesis would negate the changes that accompany the intracisternal administration of 4 ml of autogenous arterial blood to dogs and whether prostacyclin would lyse the vasospasm that is present 24 hours after this intrathecal blood. Nonsteroidal anti-inflammatory drugs (NSAIDs) were given intravenously to anesthetized dogs 30 minutes before and again 3 hours after the intracisternal injection of blood. The induced cerebral vasospasm was studied arteriographically for 1 hour after the intrathecal blood and again on the following day. Behavioral recovery of the animals was also evaluated on the day after the simulated hemorrhage. The results show that, as a group, NSAIDs significantly (P less than 0.001) reduced the occurrence of vasospasm and behavioral change associated with intrathecal blood. However, piroxicam was more efficacious than meclofenamate, ibuprofen, or aspirin in preventing both the vascular and the behavioral changes observed. This efficacy may be due to the long half-life of piroxicam and to known and unknown pharmacological differences among these compounds. On the other hand, prostacyclin infused via the vertebral artery failed to affect the vasospasm present 24 hours after intrathecal blood. The findings suggest that a suitable NSAID could provide clinical protection from the deleterious consequences of SAH.
The Head-Disk Interface Roadmap to an Areal Density of Tbit/in2 (2013)

This paper reviews the state of the head-disk interface (HDI) technology, and more particularly the head-medium spacing (HMS), for today’s and future hard-disk drives. Current storage areal density on a disk surface is fast approaching the one terabit per square inch mark, although the compound annual growth rate has reduced considerably from ~100%/annum in the late 1990s to 20–30% today. This rate is now lower than the historical, Moore’s law equivalent of ~40%/annum. A necessary enabler to a high areal density is the HMS, or the distance from the bottom of the read sensor on the flying head to the top of the magnetic medium on the rotating disk. This paper describes the various components of the HMS and various scenarios and challenges on how to achieve a goal of 4.0–4.5 nm for the 4 Tbit/in 2 density point. Special considerations will also be given to the implication of disruptive technologies such as sealing the drive in an inert atmosphere and novel recording schemes such as bit patterned media and heat assisted magnetic recording.
Dual Substitution and Spark Plasma Sintering to Improve Ionic Conductivity of Garnet Li7La3Zr2O12 (2019)

Garnet Li<sub>7</sub>La<sub>3</sub>Zr<sub>2</sub>O<sub>12</sub> is one of the most promising solid electrolytes used for solid-state lithium batteries. However, low ionic conductivity impedes its application. Herein, we report Ta-doping garnets with compositions of Li<sub>7-x</sub>La<sub>3</sub>Zr<sub>2-x</sub>Ta<sub>x</sub>O<sub>12</sub> (0.1 ≤ x ≤ 0.75) obtained by solid-state reaction and free sintering, which was facilitated by graphene oxide (GO). Furthermore, to optimize Li<sub>6.6</sub>La<sub>3</sub>Zr<sub>1.6</sub>Ta<sub>0.4</sub>O<sub>12</sub>, Mg<sup>2+</sup> was select as a second dopant. The dual substitution of Ta<sup>5+</sup> for Zr<sup>4+</sup> and Mg<sup>2+</sup> for Li<sup>+</sup> with a composition of Li<sub>6.5</sub>Mg<sub>0.05</sub>La<sub>3</sub>Zr<sub>1.6</sub>Ta<sub>0.4</sub>O<sub>12</sub> showed an enhanced total ionic conductivity of 6.1 × 10<sup>-4</sup> S cm<sup>-1</sup> at room temperature. Additionally, spark plasma sintering (SPS) was applied to further densify the garnets and enhance their ionic conductivities. Both SPS specimens present higher conductivities than those produced by the conventional free sintering. At room temperature, the highest ionic conductivity of Li<sub>6.5</sub>Mg<sub>0.05</sub>La<sub>3</sub>Zr<sub>1.6</sub>Ta<sub>0.4</sub>O<sub>12</sub> sintered at 1000 °C is 8.8 × 10<sup>-4</sup> S cm<sup>-1</sup>, and that of Li<sub>6.6</sub>La<sub>3</sub>Zr<sub>1.6</sub>Ta<sub>0.4</sub>O<sub>12</sub> sintered at 1050 °C is 1.18 × 10<sup>-3</sup> S cm<sup>-1</sup>.
Mechanism Regulating Reactive Oxygen Species in Tumor-Induced Myeloid-Derived Suppressor Cells (2009)

Myeloid-derived suppressor cells (MDSC) are a major component of the immune suppressive network described in cancer and many other pathological conditions. Recent studies have demonstrated that one of the major mechanisms of MDSC-induced immune suppression is mediated by reactive oxygen species (ROS). However, the mechanism of this phenomenon remained unknown. In this study, we observed a substantial up-regulation of ROS by MDSC in all of seven different tumor models and in patients with head and neck cancer. The increased ROS production by MDSC is mediated by up-regulated activity of NADPH oxidase (NOX2). MDSC from tumor-bearing mice had significantly higher expression of NOX2 subunits, primarily p47(phox) and gp91(phox), compared with immature myeloid cells from tumor-free mice. Expression of NOX2 subunits in MDSC was controlled by the STAT3 transcription factor. In the absence of NOX2 activity, MDSC lost the ability to suppress T cell responses and quickly differentiated into mature macrophages and dendritic cells. These findings expand our fundamental understanding of the biology of MDSC and may also open new opportunities for therapeutic regulation of these cells in cancer.
Pierre Marie: Gifted Intellect, Poor Timing and Unchecked Emotionality (2003)

Pierre Marie was a prominent member of the French neurological world of the early twentieth century. Having been trained by the celebrated physician, J-M Charcot, Marie remained influenced by his teacher throughout his career. Because of this influence, his career can be logically divided into three phases: first, the early years under the direct mentorship of Charcot (1878-1893); secondly, the aftermath of Charcot's death when Marie left his teacher's institution, the Salpêtrière hospital and established himself at the Bicêtre hospital in southern Paris (1893-1918); and finally, Marie's return to the Salpêtrière to assume the original Charcot chaired professorship, albeit as an aged man (1918-1925). This essay examines Marie's career with an emphasis on documentation of the combined attributes of a gifted intellect as well as a heated emotionality. In the context of his time, these elements prompted Marie to enter into controversies and medico-political battles that advanced neurological knowledge, but likely disadvantaged him in his career successes.
Arrhythmias and heart rate variability during and after therapeutic hypothermia for cardiac arrest* (2009)

The use of therapeutic HT of 33 degrees C for 24 hours after CA was not associated with an increase in clinically significant arrhythmias. Preserved 24 to 48-hour HRV may be a predictor of favorable outcome in patients with CA treated with HT.
Regulation of the Amount of Starch in Plant Tissues by ADP Glucose Pyrophosphorylase (1992)

Starch, a major storage metabolite in plants, positively affects the agricultural yield of a number of crops. Its biosynthetic reactions use adenosine diphosphate glucose (ADPGlc) as a substrate; ADPGlc pyrophosphorylase, the enzyme involved in ADPGlc formation, is regulated by allosteric effectors. Evidence that this plastidial enzyme catalyzes a rate-limiting reaction in starch biosynthesis was derived by expression in plants of a gene that encodes a regulatory variant of this enzyme. Allosteric regulation was demonstrated to be the major physiological mechanism that controls starch biosynthesis. Thus, plant and bacterial systems for starch and glycogen biosynthesis are similar and distinct from yeast and mammalian systems, wherein glycogen synthase has been demonstrated to be the rate-limiting regulatory step.
Diffraction by band-limited fractal screens (1987)

The concept of band-limited fractals is introduced and used to describe the diffraction of electromagnetic and optical waves by irregular structures. This concept is demonstrated through the example of plane-wave diffraction by a fractal phase screen of finite extent. The effect of the fractal phase screen is noted on the evolution of an incident wave with the fractal dimension and other descriptors used as parameters. Of particular interest is the result that, for random fractal phase screens, the diffraction pattern from a single realization of the model phase screen can be identical to the pattern averaged over an ensemble of screens. In these cases an orderly pattern emerges from a chaotic one. This problem of fractal diffraction is of intrinsic interest because of the variety of problems found to be described by fractal, as opposed to Euclidean, geometry. The results have potential applications to the propagation of waves through random media, the reflection of waves from rough surfaces, and the characterization of these processes through remote means.
Highly efficient 1.3 µm Raman fibre amplifier (1998)

Using a newly developed phosphosilicate fibre-based Raman laser as a pump source, and a low-loss high Δn fibre, the authors have obtained a Raman gain of 40 dB at the 1.24 µm pump power of &lt; 700 mW.
Reduced Thrombin Formation and Altered Fibrin Clot Properties Induced by Polyunsaturated Omega-3 Fatty Acids on Top of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention (OMEGA-PCI Clot) (2011)

Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans.
“奥”林争霸，“金”落谁家——伦敦奥运夺金热门预测 (2012)

伦敦奥运会眨眼将至、各国运动员蓄势待发，势要全力以赴、一展风采。在奥林匹克的各项争霸赛中，自有巨星光芒万丈，更有新星冉冉升起。或许每个人心中部有自己看好的“奥”林英雄，他们能否问鼎“奥”林，捧得金牌归？
Evaluation of Sclerotinia Stem Rot Resistance in Oilseed Brassica napus Using a Petiole Inoculation Technique Under Greenhouse Conditions (2004)

A petiole inoculation technique was adapted for evaluating resistance of oilseed Brassica napus seedlings to Sclerotinia sclerotiorum. In the first of four experiments, four isolates of S. sclerotiorum were tested, two originating from soybean and two from B. napus. In all, 10 to 47 B. napus accessions were inoculated in the seedling stage and responses to isolates were evaluated using days to wilt (DW) and a lesion phenotype index (LP). There were no significant differences in virulence among the four isolates for DW and only slight differences for LP. However, significant differences (P < 0.0001) were observed among the B. napus accessions for DW and LP in this experiment and in subsequent experiments using one isolate. The responses of accessions were consistent among experiments and among evaluation criteria. Higher levels of resistance were found among winter-type than spring-type accessions, and among rapeseed-quality compared with canola-quality accessions. The most resistant accessions identified also were the most resistant when inoculated at the flowering stage. Terminal stems were inoculated immediately below the lowest flower and stem lesion length (SLL) was used to characterize the interaction phenotype of each accession. The petiole inoculation technique can be used successfully to differentiate oilseed B. napus germ plasm for response to S. sclerotiorum. This inoculation technique and the sources of resistance identified in this study may be used to determine inheritance resistance to S. sclerotiorum and for improving oilseed B. napus cultivars for resistance to this important pathogen.
HDL Cholesterol Efflux Capacity and Incident Cardiovascular Events (2014)

Cholesterol efflux capacity, a new biomarker that characterizes a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events in a population-based cohort. (Funded by the Donald W. Reynolds Foundation and others.).
Band alignment of the hybrid halide perovskites CH 3 NH 3 PbCl 3 ,C H 3 NH 3 PbBr 3 and CH 3 NH 3 PbI 3 (2015)

Organic–inorganic halide perovskites efficiently convert sunlight to electricity in solar cells. The choice of halide (Cl, Br or I) can be used to chemically tune the spectral response of the materials and the positions of the valence and conduction bands (i.e. the ionisation potential and electron affinity). Here the band offsets of the methylammonium lead halides are reported, including relativistic corrections and using the Pb 1s core level as a reference state. The binding energy of the valence band decreases monotonically down the series, primarily due to the change from 3p to 4p to 5p valence orbitals of the halide. Type I band alignments are predicted, which implies that Br and Cl secondary phases in CH3NH3PbI3 thin-films would act as barriers to charge transport in photovoltaic devices.
Sequence context of antisense RelA/NF-kB phosphorothioates determines specificity (1995)

The use of antisense oligomers to achieve inhibition of gene expression is complicated by frequent non-specific effects, and even the control oligomers often exhibit sequence-specific effects. We have recently shown that in diverse tumor-derived cell lines, a 24mer phosphorothioate oligomer antisense to the relA subunit of NF-kappa B transcription factor causes a block of cellular adhesion, inhibition of nuclear NF-kappa B and Sp1 DNA-binding activity and inhibition of tumor cell growth in vitro and in vivo. In this study we use the same model to attempt to define the limits of antisense specificity. We demonstrate that single base pair substitution can virtually abolish the antisense activity. The relative position of mismatches within the antisense sequence is critical to the loss of activity. Our results further indicate that antisense specificity is determined not only by the content of the sequence but also by its occurrence with reference to the surrounding sequences.
Quantitation of thymidylate synthase, dihydrofolate reductase, and DT-diaphorase gene expression in human tumors using the polymerase chain reaction. (1992)

A polymerase chain reaction (PCR)-based method was used to quantitate the expression levels of low abundance genes relevant to cancer drug activity. RNA from tumor samples as small as 20 mg was isolated and converted to cDNA using random hexamers. The 5' primers for the PCR contained a T7 polymerase promoter sequence, allowing the PCR-amplified DNA to be transcribed to RNA fragments. In each sample, the linear ranges of amplification of each cDNA of interest were established. Relative gene expressions were calculated by extrapolating the amounts of PCR products generated within the linear amplification regions of each gene to equal volumes of the cDNA solution. The method was accurate to less than a 2-fold difference in expression levels. Using beta 2-microglobulin and beta-actin gene expressions as internal reference standards and cDNA from HT-29 cells as an external linearity standard, we measured the relative expressions of thymidylate synthase, dihydrofolate reductase, and DT-diaphorase in a number of clinical tumor samples. The expressions of these genes varied from 50- to 100-fold among different tumors, although most of the values were grouped within about a 10-fold range. The amount of thymidylate synthase gene expression in tumor tissues was directly proportional to the content of thymidylate synthase protein. Those tumors with the lowest thymidylate synthase expression had the best response to both the 5-fluorouracil-leucovorin and 5-fluorouracil-cisplatin combinations.
Influence of Temperature on Low-Power Upconversion in Rubbery Polymer Blends (2009)

The upconverting properties of a dye cocktail composed of palladium(II) octaethylporphyrin (PdOEP, triplet sensitizer) and 9,10-diphenylanthracene (DPA, triplet acceptor/annihilator) were investigated as a function of temperature in several low glass transition temperature (T(g)) polymer hosts including an ethyleneoxide-epichlorohydrin copolymer (EO-EPI) and the polyurethanes Texin 270, Texin 285, and Tecoflex EG-80A. Selective excitation of PdOEP at 544 nm in the presence of DPA in these materials resulted in anti-Stokes blue emission from DPA, a consequence of sensitized triplet-triplet annihilation (TTA) photochemistry, confirmed by the quadratic dependence of the upconverted fluorescence intensity with respect to incident light power. The upconversion process was completely suppressed by cooling a PdOEP/DPA blend film to below the T(g) of the respective polymer. However, the blue emission was clearly visible by the naked eye upon heating these films to room temperature (290 K). Subsequently, the upconverted emission intensity increased with increasing temperature and was found to be completely reversible upon several heating and cooling cycles provided the temperature remained below 400 K. Heating samples above this temperature resulted in unrecoverable failure of the material to produce upconverted photons. The phosphorescence intensity decay of PdOEP in the polymer host, Tecoflex EG-80A, adequately fits to a sum of two exponential functions as well as the Kohlrausch-Williams-Watts (KWW) stretched exponential model. Increasing the temperature of the film increases the complexity and heterogeneity of the system as evidenced by the lower beta values obtained from the KWW model as the temperature increases.