gebhart/patrepeval huggingface dataset:
Nonisotropic Enzyme-Inhibitor Interactions: A Novel Nonoxidative Mechanism for Quantum Proteolysis by Human Neutrophils (1995)

Traditional theories of enzyme kinetics do not model the influences of rapidly changing and nonisotropic enzyme concentrations in real-world systems. We have modeled local enzyme concentrations in space and time following quantal release of human leukocyte elastase (HLE) from cytoplasmic granules of polymorphonuclear neutrophils (PMN). Calculations from first principles indicate that approximately 67,000 molecules of HLE are stored in each azurophil granule at a mean concentration of 5.33 mM, which exceeds pericellular inhibitor concentrations in vivo by nearly 3 orders of magnitude. Diffusion analysis predicts obligate catalytic activity (excess of local enzyme over inhibitor concentration) that extends to 1.33 microns from the site of granule extrusion (7.8-fold larger than the mean radius of the granule), with a duration of 12.4 ms, when the pericellular concentration of alpha 1-antitrypsin equals that of normal plasma. In contrast, when PMN are bathed in alpha 1-antitrypsin concentrations found in plasma from individuals with alpha 1-antitrypsin deficiency, the radius and duration of obligate catalytic activity are increased 2.5-fold and 6.2-fold, respectively. These simulations agree remarkably well with our recent direct observations and provide a novel, nonoxidative mechanism by which quantum bursts of extracellular proteolytic activity occur despite proteinase inhibitors in the bathing medium. Titration of local enzyme-inhibitor concentration is the dominant determinant of the size and duration of such events. This construct provides new insights into the pathogenesis of tissue injury in alpha 1-antitrypsin deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Nationalisme occidental et nationalisme oriental [2001] (2013)

Par bonheur, on n’entend plus beaucoup parler des « valeurs asiatiques ». L’idee qu’il existe une forme de nationalisme specifique a cette region du monde a cependant la vie dure. Son origine premiere remonte a plus d’un siecle, a l’epoque ou un imperialisme europeen raciste affirmait, pour reprendre le poeme de Kipling : « l’Orient est l’Orient, l’Occident est l’Occident, et jamais ils ne parviendront a se comprendre. » Au debut du xxe siecle, dans differentes parties d’Asie, un certain nombre de nationalismes ont repris a leur compte cette idee d’une dichotomie raciale irreductible, afin de mobiliser la resistance populaire contre une domination jugee des lors completement etrangere. Cette dichotomie est-elle vraiment justifiable, que ce soit theoriquement ou empiriquement ?
Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient (1998)

We have examined doxorubicin's (DOX) physical state in solution and inside EPC/cholesterol liposomes that were loaded via a transmembrane pH gradient. Using cryogenic electron microscopy (cryo-EM) we noted that DOX loaded to 200-300 mM internal concentrations in citrate containing liposomes formed linear, curved, and circular bundles of fibers with no significant interaction/perturbation of the vesicle membrane. The individual DOX fibers are putatively comprised of stacked DOX molecules. From end-on views of bundles of fibers it appeared that they are aligned longitudinally in a hexagonal array with a separation between fibers of approx. 3-3.5 nm. Two distinct small angle X-ray diffraction patterns (oblique and simple hexagonal) were observed for DOX-citrate fiber aggregates that had been concentrated from solution at either pH 4 or 5. The doxorubicin fibers were also present in citrate liposomes loaded with only one-tenth the amount of doxorubicin used above (approx. 20 mM internal DOX concentration) indicating that the threshold concentration at which these structures form is relatively low. In fact, from cryo-EM and circular dichroism spectra, we estimate that the DOX-citrate fiber bundles can account for the vast majority (>99%) of DOX loaded via a pH gradient into citrate buffered liposomes. DOX loaded into liposomes containing lactobionic acid (LBA), a monoanionic buffer to control the internal pH, remained disaggregated at internal DOX concentrations of approx. 20 mM but formed uncondensed fibers (no bundles) when the internal DOX concentration was approx. 200 mM. This finding suggests that in the citrate containing liposomes the citrate multianion electrostatically bridged adjacent fibers to form the observed bundles. 13C-NMR measurements of [1,5-13C]citrate inside liposomes suggested that citrate 'bound' to the DOX complex and 'free' citrate rapidly exchange indicating that the citrate-DOX interaction is quite dynamic. DOX release into buffer was relatively slow (<4% at 1 h) from liposomes containing DOX fibers (in citrate loaded to a low or high DOX concentration or in LBA liposomes loaded to a high internal DOX concentration). LBA containing liposomes loaded with disaggregated DOX, where the internal DOX concentration was only approx. 20 mM, experienced an osmotic stress induced vesicle rupture with as much as 18% DOX leakage in less than 10 min. The possible implications for this in vivo are discussed.
Hierarchical geographical modeling of user locations from social media posts (2013)

With the availability of cheap location sensors, geotagging of messages in online social networks is proliferating. For instance, Twitter, Facebook, Foursquare, and Google+ provide these services both explicitly by letting users choose their location or implicitly via a sensor. This paper presents an integrated generative model of location and message content. That is, we provide a model for combining distributions over locations, topics, and over user characteristics, both in terms of location and in terms of their content preferences. Unlike previous work which modeled data in a flat pre-defined representation, our model automatically infers both the hierarchical structure over content and over the size and position of geographical locations. This affords significantly higher accuracy --- location uncertainty is reduced by 40% relative to the best previous results [21] achieved on location estimation from Tweets.
Analysis of Cytotoxic T Lymphocyte Responses to SIV Proteins in SIV-Infected Macaques Using Antigen-Specific Stimulation with Recombinant Vaccinia and Fowl Poxviruses (1994)

Methods to analyze CD8+ CTL responses to simian immunodeficiency virus (SIV)-encoded proteins are essential to understand lentivirus immunopathogenesis and protective immune responses. Recombinant infectious shuttle vectors are useful for analyzing CTL responses to many viruses, including HIV. Therefore, CTL responses in SIV-infected Macaca fascicularis to SIV env and SIV gag/pol were evaluated using specific antigen stimulation with recombinant vaccinia (rVV) and fowl poxviruses (rFPV) containing SIV genes. Peripheral blood mononuclear cells from SIV-infected animals were stimulated with autologous cells infected with rVV expressing SIV env/gag/pol, and CTLs specific for SIV env and for SIV gag/pol were detected by testing for lytic activity in target cells expressing these genes separately. Lymphocyte subset purifications from the effector population demonstrated that the CTL response was mediated by CD8+ cells, and the use of brefeldin A to selectively block antigen presentation in association with MHC class I products affirmed this cytolytic activity was class I restricted. The use of rVV to analyze responses to SIV genes is potentially problematic in hosts immunized to vaccinia. Fowl poxvirus is an alternative virus that has many of the molecular advantages of vaccinia virus but is genomically distinct. Therefore, the ability of rFPV to expand and detect SIV-specific CTLs was evaluated. Although there was no cytopathic effect following infection with rFPV, macaque cells infected with this vector did express rFPV gene products, and could be used as stimulator and target cells to detect SIV-specific CD8+ CTLs. The results suggest that these recombinant viral vectors can be used to specifically stimulate CD8+, MHC class I-restricted CTLs reactive to SIV proteins, and should facilitate evaluating CTL responses in both SIV-infected animals and animals vaccinated against SIV.
Bradykinin B1 and B2 receptors, tumour necrosis factor α and inflammatory hyperalgesia (1999)

The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+ a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude.
Regulation of adult cardiocyte growth: effects of active and passive mechanical loading (1997)

Fluctuations in hemodynamic load have been documented to modulate contractile protein turnover and myofibrillar structure in the heart; however, the relative importance of active and passive loading in regulating adult cardiocyte growth remains unresolved. To address this issue at the cellular level, adult feline cardiocytes were cultured either on Silastic membranes or plastic surfaces. Cardiocyte-laden membranes were stretched 10% of their rest length to enhance passive loading, whereas heart cells cultured on plastic or Silastic were field stimulated at 1 Hz to mimic active loading. Turnover of contractile proteins and structural integrity of the contractile-cytoskeletal apparatus were monitored for periods ranging from 4 to 72 h. Active and passive loading elevated contractile protein synthesis nearly equally (approximately 50%) and promoted the attachment of remodeled myofibrils to vinculin-positive focal contacts and/or costameres during the first 24 h of loading. Thereafter, rates of contractile protein synthesis returned to control values in passively stretched heart cells but remained elevated in field-stimulated cultures. The fractional rate of growth was increased significantly (approximately 8%/day) in electrically paced cells, whereas in passively stretched cardiocytes the growth rate rose only modestly (approximately 2%/day). Changes in the rate of myocyte growth appeared more closely correlated with the development of focal contacts and myofibril remodeling than with changes in myofibrillar protein turnover per se. 2,3-Butanedione monoxime, nifedipine, and, to a lesser extent, ryanodine blocked field-stimulated contractile protein synthesis and myofibrillar remodeling but had no impact on protein turnover or myofibril reassembly in passively loaded cardiocytes. The results of these experiments imply that both active and passive loading stimulate contractile protein turnover and myofibril remodeling, but the generation of active tension accelerates cardiocyte growth to a greater extent than passive loading. Furthermore, pharmacological interventions suggest that unique pathways may mediate these cellular events in actively and passively loaded adult cardiocytes.
Prolonged Incubation in PUGNAc Results in Increased Protein O-Linked Glycosylation and Insulin Resistance in Rat Skeletal Muscle (2004)

Increased flux through the hexosamine biosynthetic pathway and increased O-linked glycosylation (N-acetylglucosamine [O-GlcNAc]) of proteins have been implicated in insulin resistance. Previous research in 3T3-L1 adipocytes indicated that insulin-stimulated glucose uptake and phosphorylation of Akt were reduced after incubation with O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc; 100 micromol/l), an inhibitor of the O-GlcNAcase that catalyzes removal of O-GlcNAc from proteins. Therefore, in this study, we tested the effects of PUGNAc on skeletal muscle. Incubation of rat epitrochlearis muscles for 19 h with 100 micromol/l PUGNAc resulted in a marked increase in O-GlcNAcylation of multiple proteins. Incubation with PUGNAc reduced glucose transport with a physiologic insulin concentration without affecting glucose transport without insulin or with supraphysiologic insulin. PUGNAc did not significantly alter insulin-stimulated phosphorylation of Akt (serine and threonine) or its substrates glycogen synthase kinase (GSK)3 alpha and GSK3 beta. Insulin stimulated a dose-dependent (12.0 > 0.6 > 0 nmol/l) increase in the phosphorylation of a 160-kDa protein detected using an antibody against an Akt substrate phosphomotif. PUGNAc treatment did not alter phosphorylation of this protein. These results indicate that PUGNAc is an effective inhibitor of O-GlcNAcase in skeletal muscle and suggest that O-GlcNAc modification of proteins can induce insulin resistance in skeletal muscle independent of attenuated phosphorylation of Akt, GSK 3 alpha, GSK3 beta, and a 160-kDa protein with an Akt phosphomotif.
Surface Modification with Cross-Linked Random Copolymers:  Minimum Effective Thickness (2007)

Ultrathin films of benzocyclobutene (BCB)-functionalized random copolymer with styrene and methyl methacrylate, P(S-r-BCB-r-MMA), with thicknesses ranging from 0 to 10.5 nm, were thermally cross-linked on Si substrates. The penetration of deuterated PMMA (dPMMA) into the P(S-r-BCB-r-MMA) films and the microdomain orientation of PS-b-PMMA diblock copolymers on P(S-r-BCB-r-MMA) coated substrates were investigated by neutron reflectivity (NR) and scanning force microscopy (SFM), respectively. NR measurements on bilayers of dPMMA on cross-linked P(S-r-BCB-r-MMA) showed that the neutron scattering length density (SLD) at the substrate was equal to that of P(S-r-BCB-r-MMA) if the P(S-r-BCB-r-MMA) film was thicker than ∼5.5 nm. With decreasing thickness of the P(S-r-BCB-r-MMA) film, the SLD at the substrate increased, characteristic of an increasing penetration of the dPMMA. When thin films of PS-b-PMMA diblock copolymer having cylindrical microdomains are placed on surfaces modified with cross-linked films of P(S-r-BCB-r-MMA) thinner than ∼5.5 nm, the cylindrical microdomains orient parallel to the surface, whereas for thicker films, the microdomains orient normal to the surface. Both of these results indicate that interfacial interactions are screened when the P(S-r-BCB-r-MMA) film is thicker than ∼5.5 nm.
Distinct patterns of chemokine expression are associated with leukocyte recruitment in alcoholic hepatitis and alcoholic cirrhosis (1998)

Alcoholic liver disease is associated with three histologically distinct processes: steatosis (parenchymal fat accumulation), alcoholic hepatitis (characterized by parenchymal infiltration by neutrophil polymorphs), and alcoholic cirrhosis (in which chronic inflammation and fibrosis dominate). Chemokines are cytokines that promote subset-specific leukoycte recruitment to tissues and could therefore play a crucial role in determining which leukocyte subsets are recruited to the liver in alcoholic liver disease. This paper reports that chemokine expression is increased in the liver of patients with alcoholic liver disease and, moreover, that distinct patterns of chemokine expression are associated with the different inflammatory responses to alcohol. Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and MIP-1 beta were all detected in the parenchyma at sites of inflammation in alcoholic hepatitis, whereas in alcoholic cirrhosis, chemokines were restricted to inflammatory cells and endothelium in the fibrous septa and portal tracts. In alcoholic hepatitis, chemokine transcription was localized to sinusoidal cells, leukocytes, and fibroblasts in areas of parenchymal inflammation, but hepatocytes, despite staining strongly for chemokine protein, were negative. In alcoholic cirrhosis, chemokine mRNA was detected in portal tract endothelium, leukocytes, and fibroblasts. Thus, alcoholic hepatitis and alcoholic cirrhosis are associated with distinct patterns of chemokine expression that are likely to be important factors in determining whether a patient develops acute parenchymal inflammation and alcoholic hepatitis, or chronic septal inflammation and alcoholic cirrhosis.
A New Technique to Assist Epidural Needle Placement (2010)

This is the first study to introduce a new optical method to localize epidural space in a porcine model. Epidural space could be identified by the changes in the reflective pattern of light emitted at 650 nm, which were specific for the ligamentum flavum and dural tissue. Real-time optical information successfully guided a modified Tuohy needle into the epidural space.
Pyrimidine nucleoside monophosphate kinase isolated from pig brain homogenate catalyzes disproportionation of phosphate between two CDP molecules. (1992)

An enzyme fraction that catalyzes CTP formation from CDP was purified from pig brain homogenate to a single band on SDS-PAGE. The preparation had a molecular weight of about 36,000 and showed a high activity of phosphorylating CMP and UMP by ATP and turned out to be one of pyrimidine nucleoside monophosphate kinases. It also catalyzes UTP formation from UDP, although rather weakly. These characteristics show that the enzyme species from pig brain homogenate has a rather broad specificity toward phosphate donor in phosphorylating nucleoside monophosphate.
Role of intrathymic clonal deletion and peripheral anergy in transplantation tolerance induced by bone marrow transplantation in mice conditioned with a nonmyeloablative regimen. (1994)

We have investigated the mechanism of tolerance induced by allogeneic bone marrow transplantation (BMT) in mice conditioned with a nonmyeloablative regimen. Permanent mixed chimerism and skin allograft tolerance were achieved when recipient B10 (H-2b) mice were pre-treated with anti-CD4 and anti-CD8 mAbs, thymic irradiation, and 3 Gy whole body irradiation, followed by injection of B10.A (H-2a) bone marrow cells. V beta 11+ T cells are normally deleted in I-E+ B10.A mice, but not in I-E- B10 mice. In spleens of mixed B10.A-->B10 chimeras, V beta 11+ B10 T cells were reduced but detectable in the first 6 wk after BMT, and later became undetectable. Splenic V beta 11+ T cells were unresponsive to receptor cross-linking with V beta 11-specific mAb, demonstrating anergy. B10 V beta 11+ T cells were also detected in spleens of mice that were thymectomized before BMT. In PBL of chimeras, V beta 11+ T cells were undetectable for at least 1.5 yr. Thymocyte chimerism and extensive clonal deletion of mature V beta 11+ B10 thymocytes were observed as early as 10 days post-BMT and at all subsequent time points in thymi of mixed chimeras. Rare I-E+ donor cells were detected in day 10 thymi, and these increased progressively in frequency at later times. In chimeras prepared in the reciprocal strain combination, B10-->B10.A, B10 donor V beta 11+ T cells were undetectable in PBL. Together, our results implicate both central clonal deletion and peripheral clonal anergy in tolerance induced with our regimen. A very low number of intrathymic donor cells or low density of Ag expression is sufficient to mediate extensive clonal deletion of thymocytes that recognize donor Ags.
Associations of sleep disturbance with ADHD: implications for treatment (2014)

Attention-deficit/hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep. The relationships of ADHD with sleep problems, psychiatric comorbidities and medications are complex and multidirectional. Evidence from published studies comparing sleep in individuals with ADHD with typically developing controls is most concordant for associations of ADHD with: hypopnea/apnea and peripheral limb movements in sleep or nocturnal motricity in polysomnographic studies; increased sleep onset latency and shorter sleep time in actigraphic studies; and bedtime resistance, difficulty with morning awakenings, sleep onset difficulties, sleep-disordered breathing, night awakenings and daytime sleepiness in subjective studies. ADHD is also frequently coincident with sleep disorders (obstructive sleep apnea, peripheral limb movement disorder, restless legs syndrome and circadian-rhythm sleep disorders). Psychostimulant medications are associated with disrupted or disturbed sleep, but also 'paradoxically' calm some patients with ADHD for sleep by alleviating their symptoms. Long-acting formulations may have insufficient duration of action, leading to symptom rebound at bedtime. Current guidelines recommend assessment of sleep disturbance during evaluation of ADHD, and before initiation of pharmacotherapy, with healthy sleep practices the first-line option for addressing sleep problems. This review aims to provide a comprehensive overview of the relationships between ADHD and sleep, and presents a conceptual model of the modes of interaction: ADHD may cause sleep problems as an intrinsic feature of the disorder; sleep problems may cause or mimic ADHD; ADHD and sleep problems may interact, with reciprocal causation and possible involvement of comorbidity; and ADHD and sleep problems may share a common underlying neurological etiology.
The Shadow Meets the Mask: Pyramid‐Based Shadow Removal (2008)

Abstract In this paper we propose a novel method for detecting and removing shadows from a single image thereby obtaining a high‐quality shadow‐free image. With minimal user assistance, we first identify shadowed and lit areas on the same surface in the scene using an illumination‐invariant distance measure. These areas are used to estimate the parameters of an affine shadow formation model. A novel pyramid‐based restoration process is then applied to produce a shadow‐free image, while avoiding loss of texture contrast and introduction of noise. Unlike previous approaches, we account for varying shadow intensity inside the shadowed region by processing it from the interior towards the boundaries. Finally, to ensure a seamless transition between the original and the recovered regions we apply image inpainting along a thin border. We demonstrate that our approach produces results that are in most cases superior in quality to those of previous shadow removal methods. We also show that it is possible to easily composite the extracted shadow onto a new background or modify its size and direction in the original image.
Synthesis of Conformationally Constrained Spirohydantoins with a Dibenzo[a,d]heptadiene Ring (2000)

Conformationally constrained dibenzo[a,d]cycloheptadiene-based spirohydantoins were prepared from dibenzosuberone via the transformation of the α-hydroxy ester to the azido ester, followed by its reduction to the amino ester, and cyclization of the carbomethoxy N,N′-asymmetric ureas, derived from the amino ester with triphosgene and a variety of amines. A novel ring expansion reaction was also observed in the process.