gebhart/patrepeval huggingface dataset:
Phasic mechanoreceptor stimuli can induce phasic activation of upper airway muscles in humans (2001)

1. Upper airway dilator muscles are phasically activated throughout breathing by respiratory pattern generator neurons. Studies have shown that non-physiological upper airway mechanoreceptive stimuli (e.g. rapidly imposed pulses of negative pressure) also activate these muscles. Such reflexes may become activated during conditions that alter airway resistance in order to stabilise airway patency. 2. To determine the contribution of ongoing mechanoreceptive reflexes to phasic activity of airway dilators, we assessed genioglossal electromyogram (GG EMG: rectified with moving time average of 100 ms) during slow (physiological) oscillations in negative pressure generated spontaneously and passively (negative pressure ventilator). 3. Nineteen healthy adults were studied while awake, during passive mechanical ventilation across normal physiological ranges of breathing rates (13-19 breaths min-1) and volumes (0.5-1.0 l) and during spontaneous breathing across the physiological range of end-tidal carbon dioxide (PET,CO2; 32-45 mmHg). 4. Within-breath phasic changes in airway mechanoreceptor stimuli (negative pressure or flow) were highly correlated with within-breath phasic genioglossal activation, probably representing a robust mechanoreceptive reflex. These reflex relationships were largely unchanged by alterations in central drive to respiratory pump muscles or the rate of mechanical ventilation within the ranges studied. A multivariate model revealed that tonic GG EMG, PET,CO2 and breath duration provided no significant independent information in the prediction of inspiratory peak GG EMG beyond that provided by epiglottic pressure, which alone explained 93 % of the variation in peak GG EMG across all conditions. The overall relationship was: Peak GG EMG = 79.7 - (11.3 X Peak epiglottic pressure), where GG EMG is measured as percentage of baseline, and epiglottic pressure is in cmH2O. 5. These data provide strong evidence that upper airway dilator muscles can be activated throughout inspiration via ongoing mechanoreceptor reflexes. Such a feedback mechanism is likely to be active on a within-breath basis to protect upper airway patency in awake humans. This mechanism could mediate the increased genioglossal activity observed in patients with obstructive sleep apnoea (i.e. reflex compensation for an anatomically smaller airway).
Immunological and structural homology between human T-cell leukemia virus type I envelope glycoprotein and a region of human interleukin-2 implicated in binding the beta receptor (1988)

The N-terminal segment of human interleukin-2 (hIL-2) appears to mediate binding of the beta hIL-2 receptor (R. Robb, C. Rusk, J. Yodoi, and W. Greene, Proc. Natl. Acad. Sci. USA 84:2002-2006, 1987). An affinity-purified antibody prepared against this peptide segment (p81) is shown here to cross-react with a homologous region of the human T-cell leukemia virus type I (HTLV-I) envelope glycoprotein, raising the interesting possibility that the envelope glycoprotein of HTLV-I can interact with the beta hIL-2 receptor.
Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. (1993)

Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist. By examining the fit of the linkage data to different penetrance functions, the cumulative risk associated with the 17q gene was estimated to be 59% by age 50 years and 82% by age 70 years. The corresponding estimates for the breast-ovary families were 67% and 76%, and those for the families without ovarian cancer were 49% and 90%; these penetrance functions did not differ significantly from one another.
WNT Signaling Pathway and Stem Cell Signaling Network (2007)

WNT signals are transduced to the canonical pathway for cell fate determination, and to the noncanonical pathway for control of cell movement and tissue polarity. Canonical WNT signals are transduced through Frizzled family receptors and LRP5/LRP6 coreceptor to the beta-catenin signaling cascade. Microtubule affinity-regulating kinase (PAR-1) family kinases, casein kinase I epsilon (CKI epsilon), and FRAT are positive regulators of the canonical WNT pathway, whereas APC, AXIN1, AXIN2, CKI alpha, NKD1, NKD2, beta TRCP1, beta TRCP2, ANKRD6, Nemo-like kinase (NLK), and peroxisome proliferator-activated receptor gamma (PPAR gamma) are negative regulators. Nuclear complex, consisting of T-cell factor/lymphoid enhancer factor, beta-catenin, BCL9/BCL9L, and PYGO, activates transcription of canonical WNT target genes such as FGF20, DKK1, WISP1, MYC, CCND1, and Glucagon (GCG). Noncanonical WNT signals are transduced through Frizzled family receptors and ROR2/RYK coreceptors to the Dishevelled-dependent (Rho family GTPases and c-jun NH(2)-terminal kinase) or the Ca(2+)-dependent (NLK and nuclear factor of activated T cells) signaling cascades. WNT signals are context-dependently transduced to both pathways based on the expression profile of WNT, SFRP, WIF, DKK, Frizzled receptors, coreceptors, and the activity of intracellular WNT signaling regulators. Epigenetic silencing and loss-of-function mutation of negative regulators of the canonical WNT pathway occur in a variety of human cancer. WNT, fibroblast growth factor (FGF), Notch, Hedgehog, and transforming growth factor beta/bone morphogenetic protein signaling network are implicated in the maintenance of tissue homeostasis by regulating self-renewal of normal stem cells as well as proliferation or differentiation of progenitor (transit-amplifying) cells. Breakage of the stem cell signaling network leads to carcinogenesis. Nonsteroidal anti-inflammatory drugs and PPAR gamma agonists with the potential to inhibit the canonical WNT signaling pathway are candidate agents for chemoprevention. ZTM000990 and PKF118-310 are lead compounds targeted to the canonical WNT signaling cascade. Anti-WNT1 and anti-WNT2 monoclonal antibodies show in vitro effects in cancer treatment. After the optimization, derivatives of small-molecule compound and human monoclonal antibody targeted to the WNT signaling pathway could be used in cancer medicine.
16 (2012)

Introduction: Sepsis in the ageing population carries a high morbidity and mortality, thus requires better pre-clinical models for improved therapies. Insect-based methods have been used in understanding innate immunity as well as ageing; however Drosophila has not been used to study ageing and sepsis. Sepsis causes impaired mitochondrial activity similar to ageing, but in an accelerated time period. In Drosophila, ageing has been demonstrated to produce a decline in geotaxis; an objective metric of mobility, however it is unknown if sepsis also does. Furthermore, it is unknown how ageing affects the response to sepsis in Drosophila. Hypothesis: We hypothesized that sepsis mimics an accelerated process of aging as assessed by geotaxis, and mitochondrial activity, with this hypothesis we also tested the fidelity and candidacy of this model to mimic human disease. Methods: We used 360 male Drosophila melanogaster flies, half were 3-5 days old and the other half 18-20 days old. We divided each age strata in 3 groups a) infected, b) sham needle pricked, c) control. Group A was infected by thoracic needle pricking with a bacterial solution containing 5 x10^7/ml of S. aureus. We measured geotaxis and cytochrome c oxidase activity (COX). Geotaxis was measured before and 18 hours after intervention with automated digital images. Mitochondrial COX was measured by colorimetric assay. All data was analyzed with parametric tests. Results: At baseline geotaxis in mature flies was 28.1% lower than in young flies (p<0.001). Infection also caused a decline in geotaxis in both age groups of 26.8% (p=0.001) in mature and 31.5% (p<0.001) in young flies from baseline. There was no difference in COX between age groups after infection (p=0.37). Compared to control group, infected young and mature flies had declining trends in COX but only significant in the young (20.64%, p=0.006; 7.65%, p=0.09, respectively). Conclusions: Sepsis profoundly affects cellular and systemic end points as shown by a decline in cytochrome C oxidase activity and geotaxis in young flies. In the mature flies, we found a significant impairment of motor function but not of mitochondrial activity as was expected, suggesting age-specific differences in response to injury.
Pharmacologic reversal of drug resistance in ovarian cancer. (1985)

Drug resistance is a major problem in the treatment of ovarian cancer. We have developed human ovarian cancer cell lines with varying degrees of resistance and sensitivity to cisplatin, melphalan, and doxorubicin. The steep dose-response relationships in other lines support the rationale for high-dose therapy either by intraperitoneal or systemic administration of drugs. The demonstration that some of the resistant cell lines have a decreased accumulation of doxorubicin and that resistance in these lines can be reversed by a calcium channel blocker has led to a clinical trial of verapamil plus doxorubicin in refractory ovarian cancer patients. It has also been demonstrated that resistance to cisplatin and melphalan is associated with increased levels of glutathione. Pharmacologic depletion of glutathione with buthionine sulfoximine, an inhibitor of glutathione synthesis, increases the cytotoxicity of melphalan and cisplatin in drug sensitive and resistant cell lines.
THE PREPARATION OF GARAMINE, A NOVEL PSEUDODISACCHARIDE FROM SISOMICIN (1973)

All compounds gave satisfactory microanalytical, and spectral data. ** Identical in all respects with authentic samples.
Extracting and composing robust features with denoising autoencoders (2008)

Previous work has shown that the difficulties in learning deep generative or discriminative models can be overcome by an initial unsupervised learning step that maps inputs to useful intermediate representations. We introduce and motivate a new training principle for unsupervised learning of a representation based on the idea of making the learned representations robust to partial corruption of the input pattern. This approach can be used to train autoencoders, and these denoising autoencoders can be stacked to initialize deep architectures. The algorithm can be motivated from a manifold learning and information theoretic perspective or from a generative model perspective. Comparative experiments clearly show the surprising advantage of corrupting the input of autoencoders on a pattern classification benchmark suite.
VI.—On the artificial production of coumarin and formation of its homologues (1868)

The first page of this article is displayed as the abstract.
Control of TRAIL-Induced Apoptosis by a Family of Signaling and Decoy Receptors (1997)

TRAIL (also called Apo2L) belongs to the tumor necrosis factor family, activates rapid apoptosis in tumor cells, and binds to the death-signaling receptor DR4. Two additional TRAIL receptors were identified. The receptor designated death receptor 5 (DR5) contained a cytoplasmic death domain and induced apoptosis much like DR4. The receptor designated decoy receptor 1 (DcR1) displayed properties of a glycophospholipid-anchored cell surface protein. DcR1 acted as a decoy receptor that inhibited TRAIL signaling. Thus, a cell surface mechanism exists for the regulation of cellular responsiveness to pro-apoptotic stimuli.
Performances of Mass-Sensitive Devices for Gas Sensing:  Thickness Shear Mode and Surface Acoustic Wave Transducers (1996)

In this work we investigated different thickness shear mode resonators (TSMRs) with fundamental frequencies of 10 and 30 MHz and surface acoustic wave devices with fundamental frequencies of 80 and 433 MHz. Four aspects were of primary interest in this comparison: noise levels and signal-to-noise ratios (S/N), influence of the polymer film thickness, influence of temperature on the transducer signal before and after coating, and minimum threshold values for monitoring different volatile organic compounds in the environment. We limited our investigations to a temperature range between 298 and 308 K, with 303 K the routine measuring temperature. Analyte concentrations (n-octane, tetrachloroethene) were chosen from the minimum detection limit up to 5000 μg/L. The temperature was found to strongly affect the performance of all the devices. The sorption of the analyte vapors into the polymeric films was demonstrated to be transducer-independent (identical partition coefficients for all the devices). The 30 MHz TSMRs showed very satisfying results in terms of S/N and limits of detection.
Determinants of Leukocyte Margination in Rectangular Microchannels (2009)

Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology.
[Relationship between DEK oncogene expression and oral squamous cell carcinoma]. (2014)

DEK may play an important role in the occurrence and metastasis of OSCC.
Complete regression of a previously untreated melanoma brain metastasis with ipilimumab (2010)

Anecdotal cases of partial or complete responses have been reported after ipilimumab therapy for stage IV melanoma with brain metastasis treated earlier by surgery or radiosurgery. We report the first case of ipilimumab monotherapy resulting in durable complete remission of untreated, progressive brain metastases in a patient with stage IV melanoma. This case and earlier reports provide support for the further evaluation of ipilimumab in melanoma patients with brain metastasis.
Stabilization of α‐chymotrypsin by ionic liquids in transesterification reactions (2001)

Five different ionic liquids, based on dialkylimidazolium and quaternary ammonium cations associated with perfluorinated and bis (trifluoromethyl) sulfonyl amide anions, were used as reaction media to synthesize N-acetyl-L-tyrosine propyl ester by transesterification with alpha-chymotrypsin at 2% (v/v) water content at 50 degrees C. The synthetic activity was reduced by the increase in alkyl chains length of cations and by increases in anion size, which was related to the decrease in polarity. Incubation of the enzyme (with and without substrate) in ionic liquids exhibited first-order deactivation kinetics at 50 degrees C, allowing determination of deactivation rate constants and half-life times (1-3 h). Ionic liquids showed a clear relative stabilization effect on the enzyme, which was improved by increased chain length of the alkyl substituents on the imidazolium ring cations and the anion size. This effect was 10-times enhanced by the presence of substrate. For example, 1-butyl-3-methylimidazolium hexafluorophosphate increased the alpha-chymotrypsin half-life by 200 times in the presence of substrate with respect to the 1-propanol medium. These results show that ionic liquids are excellent enzyme-stabilizing agents and reaction media for clean biocatalysis in non-conventional conditions.
Interaction and co-encapsidation of human immunodeficiency virus type 1 Gag and Vif recombinant proteins. (1998)

Human immunodeficiency virus type 1 (HIV-1) wild-type (WT) virion infectivity factor (Vif) protein (Vifwt) and full-length Gag precursor (Pr55Gag) were found to be co-encapsidated into extracellular, membrane-enveloped virus-like particles released by budding from Sf9 cells co-expressing the two recombinant proteins in trans, with an average copy number of 3.5+/-0.6 Vifwt per 100 Pr55Gag molecules. No preferential localization at the plasma membrane was observed for recombinant Vif in the absence of Gag expression, and a significant proportion of Vif accumulated within the nucleus. Two conserved motifs, W89RKRRY94 and P156KKIKP161, seemed to act as nuclear addressing signals. The Pr55Gag and Vifwt interacting domains were analysed by biopanning of a phage-displayed hexapeptide library. The Vif-binding domain, which spanned residues H421-T470 in Pr55Gag, corresponded to the C-terminal region of nucleocapsid (NC), including the second zinc finger, the intermediate spacer peptide sp2 and the N-terminal half of the p6 domain. Deletions in these Gag domains significantly decreased the Vif encapsidation efficiency, and complete deletion of NC abolished Vif encapsidation. In Vif, four discrete Gag-binding sites were identified, within residues T68-L81 (site I) and W89-P100 (site II) in the central domain, and within residues P162-R173 (III) and P177-M189 (IV) at the C terminus. Substitutions in site I and deletion of site IV were detrimental to Vif encapsidation, whereas substitution of basic residues for alanine in sites III and IV had a positive effect. The data suggest a direct intracellular Gag-Vif interaction and the occurrence of a Pr55Gag-mediated membrane-targeting pathway for Vif in Sf9 cells.
Plug-Flow Reactor for Continuous Hydrolysis of Glucans and Xylans from Pretreated Corn Fiber (2005)

Pressure cooking of corn fiber in liquid water at 160 °C and a pH maintained at 4−7 produces an aqueous stream of dissolved glucans, xylans, proteins, phenolics, and minerals. We report hydrolysis of these oligosaccharides to glucose and xylose in a fixed-bed reactor packed with a macroreticular strong cation exchanger. The aqueous stream is first contacted with the cation exchanger at room temperature where proteins, phenolics, minerals, and other catalyst fouling components are removed. The material is then passed over a packed-bed of the same catalyst at 130 °C to give 88% hydrolysis for a space time of 105 min. Comparison of cation exchanger in a plug-flow versus a batch reactor for hydrolysis of oligosaccharides as well as for hydrolysis of the disaccharide cellobiose shows that yields at 110−160 °C are greatest for a plug-flow reactor. Maximum glucose yield increases as hydrolysis temperature increases and reaches 90% at 160 °C, which was the highest temperature tested in this study. A model of reactor performance based on first-order kinetics with diffusion resistance fit the data for cellobiose with an observed hydrolysis yield of 90% at a residence time of 3.5 min at 160 °C. A preliminary economic analysis shows 1 lb of catalyst that generates 1000 lb of glucose will give incremental costs of between $0.01 and $0.18/gal of ethanol, depending on catalyst cost. Further improvements in catalyst life and selectivity could result in an alternative or complimentary approach to enzyme hydrolysis for biomass pretreatment processes that generate water-soluble glucans and xylans from corn fiber and other cellulosic residues. Ultimately a sequential, continuous pretreatment and hydrolysis system is envisioned that has the added benefit of minimizing reactor volumes in large-scale cellulose to ethanol plants.
The inverted repeat as a recognizable structural feature in supercoiled DNA molecules. (1980)

The single-strand-specific endonuclease S1 from Aspergillus oryzae introduces highly selective cleavages into supercoiled covalently closed circular DNA molecules, but not into their previously linearized counterparts. The cleavage sites are inverted repeats of unit length between 9 and 13 base pairs, separated by a nonrepetitious 2-6 base pairs. Such regions may adopt hairpin or similar structures stabilized by the negative superhelix density and may constitute recognition sites for cellular proteins.
New Voltage Source Converter Topology for HVDC Grid Connection of Offshore Wind Farms (2004)

Abstract- Large offshore wind farms are recently emerging as promising alternative power sources. Long distances between offshore generation and onshore distribution grid demand new solutions for their connection to the AC network. HVDC systems based on voltage source converters (VSC) are a promising alternative to conventional AC transmission above a certain cable length. This paper presents a new VSC transmission topology for HVDC grid connection of offshore wind farms.
Thein vitroandin vivoeffects of clofazimine on the motility of neutrophils and transformation of lymphocytes from normal individuals (1982)

The effects of clofazimine on neutrophil motility to endotoxin activated serum and mitogen-in duced lymphocyte transformation of leucocytes from normal individuals in vitro, and after ingestion of clofaz imine by normal adult volunteers have been assesse d. Clofazimine caused a progressive dose-dependent in hibition of neutrophil motility and of lymphocyte transformation in vitro. Ingestion of the drug by normal volunteers was accompanied by decreased neutrophil motility and lympho cyte transformation to mitogens. These fin dings suggest that the anti inflammatory properties of clofazimine are related to inhibition of these cellular immune functions.