gebhart/patrepeval huggingface dataset:
The Realization of a Pulsatile Implantable Impeller Pump with Low Hemolysis (1989)

A pulsatile implantable impeller pump with low hemolysis was developed without markedly increasing the complexity of the system compared with the nonpulsatile pump. The key to the question is to design a three-dimensional impeller with twisted vanes, compacted by an axial helical spiral and a radial logarithmic spiral so as to reduce the turbulent shear in the pump as the impeller changes its rotations per minute periodically to generate a physiologic pulsatile flow. Both mathematic computation of velocity distribution in the impeller and geometric illustration of the velocity triangle at the top of the vane have demonstrated that the peripheral velocity variation of blood cells in a twisted impeller will be less than that in an untwisted impeller. Thus, the main mechanical factor of hemolysis in the impeller pump, namely, the turbulent shear, should be reduced because it is proportional to the product of velocity variations measured in two perpendicular directions. In the in vitro experiments, the pump delivered 4 L/min mean flow at 100 mm Hg mean pressure (pulsed between 80-120 mm Hg) for more than 3 h in a circulatory model containing 700 ml of fresh citrated porcine blood. Every half hour, the free hemoglobin level in the plasma was tested, and the resulting index of hemolysis was about 0.020, slightly more than that of a nonpulsatile impeller pump developed in Shanghai. To compare hemolysis, the index of hemolysis of this pump is about 1/6 of that of the self-made diaphragm pump and 1/13 of that of the Polystan Pulsatile Pump.(ABSTRACT TRUNCATED AT 250 WORDS)
Endotoxin-tolerant Mice Have Mutations in Toll-like Receptor 4 (Tlr4) (1999)

Bacterial lipopolysaccharide (LPS) provokes a vigorous, generalized proinflammatory state in the infected host. Genetic regulation of this response has been localized to the Lps locus on mouse chromosome 4, through study of the C3H/HeJ and C57BL/10ScCr inbred strains. Both C3H/HeJ and C57BL/10ScCr mice are homozygous for a mutant Lps allele (Lpsd/d) that confers hyporesponsiveness to LPS challenge, and therefore exhibit natural tolerance to its lethal effects. Genetic and physical mapping of 1,345 backcross progeny segregating this mutant phenotype confined Lps to a 0.9-cM interval spanning 1.7 Mb. Three transcription units were identified within the candidate interval, including Toll-like receptor 4 (Tlr4), part of a protein family with members that have been implicated in LPS-induced cell signaling. C3H/HeJ mice have a point mutation within the coding region of the Tlr4 gene, resulting in a nonconservative substitution of a highly conserved proline by histidine at codon 712, whereas C57BL/ 10ScCr mice exhibit a deletion of Tlr4. Identification of distinct mutations involving the same gene at the Lps locus in two different hyporesponsive inbred mouse strains strongly supports the hypothesis that altered Tlr4 function is responsible for endotoxin tolerance.
Identification by electrospray ionization mass spectrometry of the sites of tyrosine phosphorylation induced in activated Jurkat T cells on the protein tyrosine kinase ZAP-70. (1994)

We have developed a rapid and sensitive two capillary-column chromatography and mass spectrometry-based method for the determination of protein phosphorylation sites following recovery of individual phosphopeptides from two-dimensional phosphopeptide maps. With a standard phosphopeptide, we demonstrate detection sensitivity of at least 250 fmol for this system. We applied this technique to the analysis of in vitro sites of tyrosine phosphorylation induced on the T cell-specific protein tyrosine kinase ZAP-70 in the absence and presence of p56lck. We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56lck. By comparative two-dimensional phosphopeptide mapping, we show that ZAP-70 isolated from Jurkat T cells also autophosphorylates at Tyr-292 and Tyr-126. Similar analysis of 32P-labeled Jurkat cells stimulated with anti-T cell receptor antibodies reveals Tyr-492 and Tyr-493 as the principal sites of T cell antigen receptor-induced tyrosine phosphorylation, with additional phosphorylation at the Tyr-292, but not the Tyr-126 autophosphorylation site. The high degree of sensitivity achieved with this technology should greatly facilitate the direct biochemical determination of inducible protein phosphorylation events, an experimental strategy that until now has been both time consuming and difficult.
Chiral linker-bridged bis-N-heterocyclic carbenes: design, synthesis, palladium complexes, and catalytic properties (2016)

A series of chiral bis(benzimidazolium) salts 10-19 with (1R,2R)-cyclohexene, (1R,2R)-diphenylethylene and (aR)-binaphthylene linkers have been designed and synthesized in 30-94% yield. Ten chiral bis(NHC) palladium complexes 20-28 have been synthesized and characterized by NMR, HRMS, elemental analysis and further confirmed by X-ray single crystal analysis. These bis(NHC)-Pd complexes showed obviously different catalytic properties in the asymmetric Suzuki-Miyaura coupling reactions. The (1R,2R)-cyclohexene-bridged bis(NHC)-Pd complex, (R,R)-23, achieved the highest yield of 90%, while complex (aR)-28, with a binaphthylene linker, showed the best enantioselectivity of 60 ee%. The structural analysis of these complexes suggested that such difference of catalytic performance has a close relationship with their coordination surroundings around metal centres.
Cytokine Production and Surface Marker Expression in Acute and Stable Multiple Sclerosis: Altered IL-12 Production and Augmented Signaling Lymphocytic Activation Molecule (SLAM)-Expressing Lymphocytes in Acute Multiple Sclerosis (1998)

Abstract Ag-stimulated IL-2 production and mitogen-stimulated type 1 and type 2 cytokine production by PBMC, as well as expression of Th1- and Th2-associated phenotypical markers, of B7-1, B7-2, and CD95 (Fas) on the surface of immune cells, and the serum concentration of soluble Apo-1/Fas were evaluated in multiple sclerosis (MS) patients with either acute (AMS) or stable (SMS) disease and in healthy controls (HC). Results showed that 1) Ag-stimulated IL-2 production is reduced in MS patients compared with that in HC; 2) mitogen-stimulated type 1 cytokine production is increased, and IL-10 production is reduced in MS patients compared with those in HC, and in AMS patients compared with those in SMS; 3) whereas production of the metabolically active p70 heterodimers is comparable in SMS, AMS, and HC, production of the p70 heterodimer and the p40 chains (total IL-12) is increased in SMS compared with that in AMS and HC; 4) CD4+, CD4+SLAM+, and CD4+CD7+ lymphocytes (preferentially type 1 cytokine-producing lymphocytes) are increased in MS compared with levels in HC; 5) B7-2- as well as Fas+-expressing monocytes are augmented in MS compared with those in HC, and serum soluble Apo-1/Fas is augmented in AMS compared with SMS and HC. These results confirm that a complex imbalance in both cytokine production and the Fas system is present in MS and indicate that different cytokine profiles may be observed in patients with acute or stable disease. The data also suggest that peculiar phenotypic populations are over-represented in MS patients, and for the first time show that SLAM expression is correlated with dysregulation of type 1 and type 2 cytokine production in human pathology.
Adaptive deadlock- and livelock-free routing with all minimal paths in torus networks (1994)

This paper consists of two parts. In the first part, two new algorithms for deadlock- and livelock-free wormhole routing in the torus network are presented. The first algorithm, called Channels, is for the n-dimensional torus network. This technique is fully-adaptive minimal, that is, all paths with a minimal number of hops from source to destination are available for routing, and needs only five virtual channels per bidirectional link, the lowest channel requirement known in the literature for fully-adaptive minimal worm-hole routing. In addition, this result also yields the lowest buffer requirement known in the literature for packet-switched fully-adaptive minimal routing. The second algorithm, called 4-Classes, is for the bidimensional torus network. This technique is fully-adaptive minimal and requires only eight virtual channels per bidirectional link. Also, it allows for a highly parallel implementation of its associated routing node. In the second part of this paper, four worm-hole routing techniques for the two-dimensional torus are experimentally evaluated using a dynamic message injection model and different traffic patterns and message lengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
GOING GLOBAL: CHOICES AND CHALLENGES (1986)

I would like to share with you what some of the experiences in globalizing have been at Black &amp; Decker, what some of the choices have been, and what future challenges are seen.
An Anatomy of Trading Strategies (1998)

In this article we use a single unifying framework to analyze the sources of profits to a wide spectrum of return-based trading strategies implemented in the literature. We show that less than 50% of the 120 strategies implemented in the article yield statistically significant profits and, unconditionally, momentum and contrarian strategies are equally likely to be successful. However, when we condition on the return horizon (short, medium, or long) of the strategy, or the time period during which it is implemented, two patterns emerge. A momentum strategy is usually profitable at the medium (3- to 12-months) horizon, while a contrarian strategy nets statistically significant profits at long horizons, but only during the 1926–1947 subperiod. More importantly, our results show that the cross-sectional variation in the mean returns of individual securities included in these strategies play an important role in their profitability. The cross-sectional variation can potentially account for the profitability of momentum strategies and it is also responsible for attenuating the profits from price reversals to long-horizon contrarian strategies.
Overexpression of Heat Shock Protein 27 Reduces Cortical Damage after Cerebral Ischemia (2009)

Heat shock protein 27 (HSP27) has a major role in mediating survival responses to a range of central nervous system insults, functioning as a protein chaperone, an antioxidant, and through inhibition of cell death pathways. We have used transgenic mice overexpressing HSP27 (HSP27tg) to examine the role of HSP27 in cerebral ischemia, using model of permanent middle cerebral artery occlusion (MCAO). Infarct size was evaluated using multislice T(2)-weighted anatomical magnetic resonance imaging (MRI) after 24 h. A significant reduction of 30% in infarct size was detected in HSP27tg animals compared with wild-type (WT) littermates. To gain some insight into the mechanisms contributing to cell death and its attenuation by HSP27, we monitored the effect of induction of c-jun and ATF3 on tissue survival in MCAO and their effects on the expression of endogenous mouse HSP25 and HSP70. It is important that, the c-jun induction seen at 4 h tended to be localized to regions that were salvageable in HSP27tg mice but became infarcted in WT animals. Our results provide support for the powerful neuroprotective effects of HSP27 in cerebral ischemia.
MicroRNA-375 and MicroRNA-221: Potential Noncoding RNAs Associated with Antiproliferative Activity of Benzyl Isothiocyanate in Pancreatic Cancer (2011)

The deregulated presence or absence of microRNAs (miRNAs) might play an important role in molecular pathways leading to neoplastic transformation. At present, it is also thought that the approaches to interfere miRNA functions should be helpful for developing novel therapeutic opportunities for human cancer. In this study, we provide evidence that the anticancer agent benzyl isothiocyanate (BITC) has the ability to modulate the level of miRNAs such as miR-221 and miR-375, known to be abnormally expressed in pancreatic cancer patients. Interestingly, ectopic expression of miR-375 or the enforced silencing of miR-221 in cultured pancreatic cancer cells attenuates cell viability and sensitizes antiproliferative action of BITC. We also show that the expression of putative tumor suppressor miR-375 is more abundant in nonpathological mice pancreata than those with Kras(G12D)-driven pancreatic intraepithelial neoplasia (PanIN). To the contrary, the expression of oncogenic miR-221 is significantly elevated in the mouse pancreas with PanIN lesions. Although miR-375 has been shown to be aberrantly expressed in pancreatic cancer patients, there has not been a comprehensive study to investigate the molecular pathways targeted by this miRNA in pancreatic cancer cells. Further analysis by gene expression microarray revealed that IGFBP5 and CAV-1, potential biomarkers of pancreatic cancer, were significantly downregulated in cells transfected with miR-375. Correlatively, elevated expression of IGFBP5 and CAV-1 was evident in the mouse pancreas with preneoplastic lesions in which the expression of miR-375 wanes. Taken together, our findings suggest that anticancer agent BITC might target the expression of miR-221 and miR-375 to switch hyperproliferative pancreatic cancer cells to a hypoproliferative state.
A method for estimating the probability of adverse drug reactions (1981)

The estimation of the probability that a drug caused an adverse clinical event is usually based on clinical judgment. Lack of a method for establishing causality generates large between-raters and within-raters variability in assessment. Using the conventional categories and definitions of definite, probable, possible, and doubtful adverse drug reactions (ADRs), the between-raters agreement of two physicians and four pharmacists who independently assessed 63 randomly selected alleged ADRs was 38% to 63%, kappa (k, a chance-corrected index of agreement) varied from 0.21 to 0.40, and the intraclass correlation coefficient of reliability (R[est]) was 0.49. Six (testing) and 22 wk (retesting) later the same observers independently reanalyzed the 63 cases by assigning a weighted score (ADR probability scale) to each of the components that must be considered in establishing causal associations between drug(s) and adverse events (e.g., temporal sequence). The cases were randomized to minimize the influence of learning. The event was assigned a probability category from the total score. The between-raters reliability (range: percent agreement = 83% to 92%; κ = 0.69 to 0.86; r = 0.91 to 0.95; R(est) = 0.92) and within-raters reliability (range: percent agreement = 80% to 97%; κ = 0.64 to 0.95; r = 0.91 to 0.98) improved (p < 0.001). The between-raters reliability was maintained on retesting (range: r = 0.84 to 0.94; R(est) = 0.87). The between-raters reliability of three attending physicians who independently assessed 28 other prospectively collected cases of alleged ADRs was very high (range: r = 0.76 to 0.87; R(est) = 0.80). It was also shown that the ADR probability scale has consensual, content, and concurrent validity. This systematic method offers a sensitive way to monitor ADRs and may be applicable to postmarketing drug surveillance. Clinical Pharmacology and Therapeutics (1981) 30, 239–245; doi:10.1038/clpt.1981.154
Mast Cells in Tumor Microenvironment Promotes the In Vivo Growth of Pancreatic Ductal Adenocarcinoma (2011)

Mast cells play an important role in PDAC growth and development in mouse models and are indicative of poor prognosis in humans, which makes them a potential novel therapeutic target.
4D embryonic cardiography using gated optical coherence tomography (2006)

Simultaneous imaging of very early embryonic heart structure and function has technical limitations of spatial and temporal resolution. We have developed a gated technique using optical coherence tomography (OCT) that can rapidly image beating embryonic hearts in four-dimensions (4D), at high spatial resolution (10-15 mum), and with a depth penetration of 1.5 - 2.0 mm that is suitable for the study of early embryonic hearts. We acquired data from paced, excised, embryonic chicken and mouse hearts using gated sampling and employed image processing techniques to visualize the hearts in 4D and measure physiologic parameters such as cardiac volume, ejection fraction, and wall thickness. This technique is being developed to longitudinally investigate the physiology of intact embryonic hearts and events that lead to congenital heart defects.
Physical and enzymic properties of a class II alcohol dehydrogenase isozyme of human liver: .pi.-ADH (1984)

Homogeneous class II alcohol dehydrogenase (pi-ADH) has been isolated from human liver homogenates by chromatography on DE-52 cellulose, 4-[3-[N-(6-amino-caproyl)amino]propyl]pyrazole-Sepharose, SP-Sephadex C-50, and agarose-hexane-AMP, yielding an enzyme that has a significantly higher specific activity and is markedly more stable than that isolated by an earlier procedure. pi-ADH is composed of two identical 40 000-dalton subunits, contains 4 mol of zinc/dimer, and is readily inhibited by metal-chelating agents. The purified enzyme binds two molecules of coenzyme per dimer, exhibits an absorption maximum at 280 nm, epsilon 280 = 57 000, and exhibits an isoelectric point of 8.6. The class II isozyme catalyzes the oxidation of a variety of alcohols with Km values ranging from 7 microM to 560 mM and with kcat values from 32 min-1 to 600 min-1 and demonstrates a preference for hydrophobic substrates. The kcat/Km ratio for ethanol oxidation exhibits a pH maximum at 10.4.
A Wearable Acceleration Sensor System for Gait Recognition (2007)

This paper addresses the problem of human recognition based on their gait acceleration signal characteristics produced by walking. A portable microprocessor-based data collection device was designed to measure the three-dimensional gait acceleration signals during human walking. The system consists of a tri-axial accelerometer, a MCU, 32 M bytes of RAM, and a data transfer module for data transfer. The device was fixed to the user's waist and three-dimensional acceleration signals were recorded at a sampling rate of 250 Hz. After completing the recording, data stored in the RAM were transferred to a personal computer for wavelet denoising, gait cycles dividing, and gait pattern extracting. Through the analysis in time domain and frequency domain, and using dynamic time warping to deal with the problems result from naturally occurring changes in walking speed, 1-nearest neighbor is used for individual identification. Experiments were performed on 21 subjects walking on their normal speed. The methods of gait analysis in time domain and frequency domain are applying, the equal error rate of 5.6% and 21.1% are achieved respectively. Our preliminary results indicate that it is possible to recognize users based on their gait acceleration.
&#947;-Secretase as a Target for Alzheimers Disease (2002)

The amyloid-beta peptide (Abeta) is the major protein component of the characteristic cerebral plaques of Alzheimer s disease (AD), and a large body of evidence supports a pathogenic role for this peptide. Thus, the proteases beta- and gamma-secretase that are responsible for carving Abeta out of its precursor protein are considered prime targets for therapeutic design. beta-Secretase is a membrane-anchored aspartyl protease of the pepsin family, while gamma-secretase is much more complex. gamma-Secretase requires presenilin, a multipass membrane protein that is the site of dozens of missense mutations that alter Abeta formation and cause hereditary AD. Two conserved aspartates in presenilin are required for gamma-secretase activity, and aspartyl protease transition-state analogue inhibitors of gamma-secretase bind directly to presenilins, strong evidence that presenilin is the catalytic component of a novel membrane aspartyl protease. gamma-Secretase appears to be a multi-component complex of integral membrane proteins, and so far presenilin and a single-pass membrane protein called nicastrin have been identified as members of this complex. A closely similar or identical protease activity is essential for a signaling pathway critical for embryogenesis and hematopoiesis, raising concerns about gamma-secretase as a target. The development of potent and selective inhibitors with good pharmacokinetic properties may soon address these concerns.
Sildenafil Induces Delayed Preconditioning Through Inducible Nitric Oxide Synthase–Dependent Pathway in Mouse Heart (2003)

Sildenafil citrate (Viagra) is the most widely used drug for treating erectile dysfunction in men. We recently demonstrated that it induces potent protective effects against ischemia-reperfusion (I-R) injury in rabbit hearts through the opening of mitochondrial ATP-dependent K+ channels. In the present study, we investigated the role of the NO-dependent signaling pathway in delayed cardioprotection by sildenafil. Adult male ICR mice were treated with saline or sildenafil (0.7 mg/kg IP) 24 hours before global I-R in the Langendorff mode. Infarct size was reduced from 27.6+/-3.3% in saline-treated control mice to 6.9+/-1.2% in sildenafil-treated mice (mean+/-SEM, P<0.05) without compromising cardiac function. Reverse transcription-polymerase chain reaction revealed a transient increase in endothelial and inducible NO synthase (eNOS and iNOS, respectively) mRNA in sildenafil-treated mice, peaking at 45 minutes (eNOS) and 2 hours (iNOS) after sildenafil injection. The magnitude of mRNA increase was more pronounced for iNOS than for eNOS. In addition, a significant increase in both iNOS and eNOS protein was detected 24 hours after sildenafil treatment. A selective inhibitor of iNOS, 1400W (10 mg/kg IP given 30 minutes before I-R), abolished sildenafil-induced protection (23.7+/-2.8%, P<0.05 versus sildenafil). These data suggest that the induction of NO synthase isoforms is an essential component of the signaling mechanism for sildenafil-induced delayed preconditioning. However, iNOS appears to be the primary isoform that mediates the robust cardioprotection.
CpG motifs present in bacteria DNA rapidly induce lymphocytes to secrete interleukin 6, interleukin 12, and interferon gamma. (1996)

Bacterial infection stimulates the host to mount a rapid inflammatory response. A 6-base DNA motif consisting of an unmethylated CpG dinucleotide flanked by two 5' purines and two 3' pyrimidines was shown to contribute to this response by inducing polygonal B-cell activation. This stimulatory motif is 20 times more common in the DNA of bacteria than higher vertebrates. The current work shows that the same motif induces the rapid and coordinated secretion of interleukin (IL) 6, IL-12, and interferon gamma (but not IL-2, IL-3, IL-4, IL-5, or IL-10) in vivo and in vitro. Stimulatory CpG DNA motifs induced B, T, and natural killer cells to secrete cytokine more effectively than did lipopolysaccharide. Thus, immune recognition of bacterial DNA may contribute to the cytokine, as well as the antibody production characteristic of an innate inflammatory response.