gebhart/patrepeval huggingface dataset:
Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins (1994)

Attack by reactive oxygen intermediates, common to many kinds of cell/tissue injury, has been implicated in the development of diabetic and other vascular diseases. Such oxygen-free radicals can be generated by advanced glycation end products (AGEs), which are nonenzymatically glycated and oxidized proteins. Since cellular interactions of AGEs are mediated by specific cellular binding proteins, receptor for AGE (RAGE) and the lactoferrin-like polypeptide (LF-L), we tested the hypothesis that AGE ligands tethered to the complex of RAGE and LF-L could induce oxidant stress. AGE albumin or AGEs immunoisolated from diabetic plasma resulted in induction of endothelial cell (EC) oxidant stress, including the generation of thiobarbituric acid reactive substances (TBARS) and resulted in the activation of NF-kappa B, each of which was blocked by antibodies to AGE receptor polypeptides and by antioxidants. Infusion of AGE albumin into normal animals led to the appearance of malondialdehyde determinants in the vessel wall and increased TBARS in the tissues, activation of NF-kappa B, and induction of heme oxygenase mRNA. AGE-induced oxidant stress was inhibited by pretreatment of animals with either antibodies to the AGE receptor/binding proteins or antioxidants. These data indicate that interaction of AGEs with cellular targets, such as ECs, leads to oxidant stress resulting in changes in gene expression and other cellular properties, potentially contributing to the development of vascular lesions. Further studies will be required to dissect whether oxidant stress occurs on the cell surface or at an intracellular locus.
Macrophage-mediated cytotoxicity: role of a soluble macrophage cytotoxic factor similar to lymphotoxin and tumor necrosis factor. (1983)

Guinea pig peritoneal macrophages, when activated for cytotoxicity by the calcium ionophore A23187 or lipopolysaccharide, produce a cytotoxic factor [macrophage cytotoxic factor (M phi-CF)] that is not blocked by catalase or protease inhibitors. Fractionation of culture supernates containing M phi-CF by gel filtration revealed one peak of cytotoxic activity of Mr approximately 45,000, the same as guinea pig lymphotoxin (LT). Antiserum prepared against purified guinea pig LT completely neutralized the cytotoxic activity of M phi-CF. In addition, the cytotoxic factor in guinea pig tumor necrosis serum was found to have a Mr of 45,000 and was neutralized by anti-LT. Thus, M phi-CF is physicochemically and immunochemically similar to LT and tumor necrosis factor, if not identical. To investigate the role of M phi-CF in macrophage-mediated cytotoxicity, anti-LT was added to A23187- or lipopolysaccharide-activated macrophages before addition of L-929 target cells. In 10 of 16 experiments, the inhibition of macrophage-mediated cytotoxicity was 100%. In the others, cytotoxicity was blocked partially, the lowest inhibition being 49%. The effectiveness of inhibition appeared to be inversely related to the intensity of macrophage activation. These results indicate that M phi-CF plays a significant role in macrophage-mediated cytotoxicity but involvement of another mechanism cannot be excluded.
Development of Nitrile-Based Peptidic Inhibitors of Cysteine Cathepsins (2010)

It is now becoming clear that several papain-like cysteine cathepsins are involved in the pathophysiology of diseases such as osteoporosis, autoimmune disorders, and cancer. Therefore, the development of potent and selective cathepsin inhibitors is an attractive subject for medicinal chemists. New advances have been made for nitrile-based inhibitors, leading to the identification of the cathepsin K inhibitor odanacatib and other candidates with potential for therapeutic use. This review summarizes the development of peptidic and peptidomimetic compounds with an electrophilic nitrile 'warhead' as inhibitors of the cysteine cathepsins B, S, L, C, and K. Peptide nitriles have been shown to reversibly react with the active site cysteine under formation of a covalent thioimidate adduct. The structural optimization with respect to the positions P3, P2, P1, P1', and P2' resulted in the identification of potent and selective inhibitors of the corresponding cathepsins. The underlying structure-activity relationships are discussed herein.
Clipping Prevention Scheme for MPEG Surround (2008)

ABSTRACTMPEG Surround has a potential clipping problem since its encoding is based on downmixing a multichannel signal. We propose a clipping prevention scheme for MPEG Surround, which is composed of modification and recovery processes of a downmix signal with recovery information conveyed in arbitrary downmix gains of an MPEG Surround bitstream. Experiments show that the proposed scheme effectively prevents sound quality degradation caused by clipping problems with negligible additional bit rates.
Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2. (1988)

CD28 is an Ag of 44-kDa Mr that is expressed on the membrane of the majority of human T cells and that is recognized by mAb 9.3. The functional effects of mAb 9.3 on peripheral blood T cells were studied. mAb 9.3 was not mitogenic, unless it was combined with PMA. When CD28 was cross-linked after binding of mAb 9.3 to the T cell by immobilized or soluble anti-mouse IgG, T cells proliferated in response to rIL-2, provided that monocytes were also present. The additional signal required for IL-2 responsiveness after cross-linking of CD28 could also be delivered in cultures of purified T cells by a cellfree monocyte culture supernatant. Expression of IL-2R on about 10% of the T cells was demonstrated by staining with an anti-IL-2R mAb, and was found to be largely restricted to CD4+ cells. The active compound responsible for the helper signal in the monocyte culture supernatant was identified as IL-6 because purified IL-6 (but not IL-1 beta) had similar activity and because an antiserum to IL-6 (but not an antiserum to IL-1 beta) neutralized the activity of the monocyte supernatant and blocked T cell proliferation. An anti-IL-2R antibody also completely inhibited T cell proliferation induced by the combination of mAb 9.3, IL-2, and IL-6. Our results provide evidence that cross-linking of CD28 induces functional IL-2R and that this activity is dependent on a helper signal provided by monocytes, more specifically IL-6. Moreover, our results indicate that IL-6 (previously called B cell stimulatory factor-2) is active on T cells. If a natural ligand for CD28 can be identified, the mechanism of induction of IL-2 responsiveness described here might explain how T cells become nonspecifically involved in an ongoing cellular immune reaction.
DESFAVORABLE PARA MÉXICO, EL PLAN PUEBLA-PANAMÁ (2002)

POR LAS CONDICIONES SOCIALES DE MEXICO, EL PLAN PUEBLA-PANAM  (PPP) ES DESFAVORABLE PARA EL PAIS, PUES FOMENTARIA LA CONCENTRACION DE LA RIQUEZA, ASEGURO ERSULA OSWALD SPRING, DEL CENTRO REGIONAL DE INVESTIGACIONES MULTIDISCIPLINARIAS. ADEMAS, AGREGO, MEXICO ENFRENTA BARRERAS COMERCIALES, COMPETENCIA DESLEAL, SUBSIDIOS, ATRASO TECNOLOGICO, MEDIDAS PROTECCIONISTAS, CONTUBERNIOS ENTRE GOBIERNO Y GRANDES EMPRESAS, Y MEDIDAS DISCRIMINATORIAS. DURANTE SU PARTICIPACION EN EL SEMINARIO DE DESARROLLO MESOAMERICANO, EFECTUADO EN EL INSTITUTO DE INVESTIGACIONES ECONOMICAS (IIEC), OSWALD SPRING MENCIONO QUE EL PAIS ENFRENTA DIVERSOS NUDOS CONFLICTUALES QUE PODRIAN REPRODUCIRSE CON EL PPP: POBREZA, INEQUIDAD, MISERIA, VIOLENCIA, DISCRIMINACION Y PERDIDA DE LA BIODIVERSIDAD. EN SU OPINION, DICHO PLAN ES UN PROYECTO GEOESTRATEGICO QUE, POR UN LADO, REPRESENTA LA OPCION DEL MANEJO DE CANAL DE PANAM  Y, POR OTRO, EL USO DE RECURSOS B SICOS COMO EL PETROLEO Y LA BIODIVERSIDAD, LOS CUALES SIEMPRE HAN ABUNDADO EN EL ISTMO DE TEHUANTEPEC. MICHELLE CHAUVET, DE LA UAM, UNIDAD AZCAPOTZALCO, TAMBIEN PARTICIPO EN EL SEMINARIO. AFIRMO QUE LOS PAISES DE LATINOAMERICA CUENTAN CON UNA GRAN BIODIVERSIDAD; SIN EMBARGO, LA EVALUACION DE LOS IMPACTOS -POR EL USO DE LOS TRANSGENICOS- SE HA HECHO PARA LUGARES CON PR CTICAS AGRICOLAS DIFERENTES A LAS DE LA REGION, POR LO QUE DEBEN HACERSE EVALUACIONES APEGADAS A LA REALIDAD. PARA TRANSFORMAR LA AMENAZA EN OPORTUNIDAD -EN TORNO A LAS INNOVACIONES TECNOLOGICAS-, LA SOCIEDAD, CON INSTITUCIONES DEMOCR TICAS SOLIDAS, TENDR  MEJORES Y MAYORES POSIBILIDADES DE INFLUIR A SU VEZ EN UN CONTROL MAS DEMOCR TICO DE LA TECNOLOGIA, COMENTO.
Genotyping and Expression Analysis of IDO2 in Human Pancreatic Cancer: A Novel, Active Target (2009)

This is the first study to report IDO2 expression in PDA and related cancers indicating that IDO2 genetic polymorphisms do not negate interferon-gamma-inducible protein expression. Taken together, our data strongly suggest that the clinical lead compound d-1-methyl-tryptophan might be useful in treatment of PDA.
Multimedia systems: an overview (1994)

Advances in distributed multimedia systems have begun to significantly affect the development of on-demand multimedia services. Researchers are working within established computer areas to transform existing technologies and develop new ones. Multimedia is shown as the merging of computing, communications, and broadcasting.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
C. elegans Model Identifies Genetic Modifiers of α-Synuclein Inclusion Formation During Aging (2008)

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders.
Efficient nonlinear channel identification using cyclostationary signal analysis (1993)

A new set of efficient blind nonlinear channel identification methods is presented that exploits the cyclostationary nature of signals in many applications. The methods are of the batch type, use only the cyclic autocorrelation or cyclic cepstrum of the received signal, and can be used for real or complex (causal or noncausal) finite-memory quadratic Volterra models. In most cases, the solutions are direct and no equations need to be solved. Identification of various nonlinear models is discussed with the fractionally spaced impulse data train input. A simple method is considered for estimating the memory in a quadratic Volterra model. It is shown that the proposed methods can identify the nonminimum phase linear subsystems of the nonlinear channel model. Computer simulation results support the theory.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Soil carbon stock and its changes in northern China's grasslands from 1980s to 2000s (2010)

Climate warming is likely to accelerate the decomposition of soil organic carbon (SOC) which may lead to an increase of carbon release from soils, and thus provide a positive feedback to climate change. However, SOC dynamics in grassland ecosystems over the past two decades remains controversial. In this study, we estimated the magnitude of SOC stock in northern China's grasslands using 981 soil profiles surveyed from 327 sites across the northern part of the country during 2001-2005. We also examined the changes of SOC stock by comparing current measurements with historical records of 275 soil profiles derived from China's National Soil Inventory during the 1980s. Our results showed that, SOC stock in the upper 30 cm in northern China's grasslands was estimated to be 10.5 Pg C (1 Pg=1015 g), with an average density (carbon stock per area) of 5.3 kg C m-2. SOC density (SOCD) did not show significant association with mean annual temperature, but was positively correlated with mean annual precipitation. SOCD increased with soil moisture and reached a plateau when soil moisture was above 30%. Site-level comparison indicated that grassland SOC stock did not change significantly over the past two decades, with a change of 0.08 kg C m-2, ranging from -0.30 to 0.46 kg C m-2 at 95% confidence interval. Transect-scale comparison confirmed that grassland SOC stock remained relatively constant from 1980s to 2000s, suggesting that soils in northern China's grasslands have been carbon neutral over the last 20 years.
Lossy source coding with Gaussian or erased side-information (2009)

In this paper we find properties that are shared between two seemingly unrelated lossy source coding setups with side-information. The first setup is when the source and side-information are jointly Gaussian and the distortion measure is quadratic. The second setup is when the side-information is an erased version of the source. We begin with the observation that in both these cases the Wyner-Ziv and conditional rate-distortion functions are equal. We further find that there is a continuum of optimal strategies for the conditional rate distortion problem in both these setups. Next, we consider the case when there are two decoders with access to different side-information sources. For the case when the encoder has access to the side-information we establish bounds on the rate-distortion function and a sufficient condition for tightness. Under this condition, we find a characterization of the rate-distortion function for physically degraded side-information. This characterization holds for both the Gaussian and erasure setups.
Communications Applications of Microelectromechanical Systems (1998)

An overview of recent progress in the research and development of microelectromechanical devices for use in wireless communication sub-systems is presented. Among the specific devices described are tunable micromachined capacitors, integrated high-Q inductors, low loss micromechanical switches, and micro-scale vibrating mechanical resonators with Q’s in the tens of thousands. Specific applications are reviewed for each of these components with emphasis on methods for miniaturization and performance enhancement of existing and future wireless transceivers.
Efficient Phase Transfer of Luminescent Thiol-Capped Nanocrystals:  From Water to Nonpolar Organic Solvents (2002)

Highly luminescent thiol-capped CdTe and HgTe nanocrystals synthesized in aqueous solutions were subject to a partial exchange of capping ligands with 1-dodecanethiol and transferred into different nonpolar organic solvents. It was found that acetone plays an important role in an efficient phase transfer of the nanocrystals. Both CdTe and HgTe nanocrystals retain their luminescence properties after being transferred to organic solvents, thus providing a new source of easily processable luminescent materials for possible applications in photovoltaics and optoelectronics.
Unnatural Amino Acid Mutagenesis of Green Fluorescent Protein (2002)

Unnatural amino acid mutagenesis has been used to selectively substitute tyrosine 66 of green fluorescent protein (GFP) with five novel amino acids: p-amino-L-phenylalanine, p-methoxy-L-phenylalanine, p-iodo-L-phenylalanine, p-bromo-L-phenylalanine, and L-3-(2-naphthyl)alanine. The absorbance and emission maxima of the resulting mutant GFPs span the range from 375 to 435 nm and 428 to 498 nm, respectively. The spectral properties of the mutant GFPs, including the absorbance and fluorescence maxima and quantum yields, correlate with the structural and electronic properties of the substituents on the amino acids.
Population pharmacokinetics of TC‐5214, a nicotinic channel modulator, in phase I and II clinical studies (2014)

TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder. A comprehensive population pharmacokinetic (POP PK) model of TC-5214 was developed using nonlinear mixed-effects modeling of pooled plasma concentration data from 6 early phase I studies in 179 healthy participants or patients with non-MDD and 1 phase II study in 68 MDD patients. Concentration-time profiles of TC-5214 after either single or multiple oral doses of TC-5214 was described by a one-compartment model with first-order absorption with lag time and first-order elimination. Covariate analysis revealed that creatinine clearance was a significant covariate on clearance and that body weight significantly influenced the central volume of distribution. The final model (with identified covariates) was used to simulate steady-state exposure for patients with impaired renal function. Results from forest plots reveal that patients with moderate to severe renal impairment or end stage renal disease are associated with significantly higher Cssmax and AUC compared to patients with normal renal function. The proposed final POP PK model could be employed in defining a TC-5214 dosage regimen in patients with impaired renal function.
The surprising Archaea: discovering another domain of life (2001)

Foreword 1. Meeting some Archaea 2. Their Discovery 3. Finding them in nature (and bringing them home) 4. Archaeal portraits 5. Where they live (and how they manage) 6. From a historical perspective 7. Making a living (obtaining energy) 8. Archaea as ancestors 9. Looking forward Additional reading
Effect of amino acid substitutions on calmodulin binding and cytolytic properties of the LLP-1 peptide segment of human immunodeficiency virus type 1 transmembrane protein (1995)

Previous studies have identified two highly basic amphipathic helical regions in the human immunodeficiency virus type 1 transmembrane protein that, in vitro, display both cytolytic and calmodulin-binding and -inhibitory properties that could contribute to cellular dysfunctions and cytopathogenesis during a persistent viral infection. In the current study, the structural specificity of the cytolytic and calmodulin-binding activities of the human immunodeficiency virus type 1 lentivirus lytic peptide (LLP-1) are examined with synthetic peptide homologs and analogs. The results of these studies demonstrate that even minor changes in LLP-1 amino acid content can markedly affect these properties, suggesting that sequence variation in these highly conserved LLP sequences may correlate with alterations in viral cytopathic properties.
Swainsonine Stimulation of the Proliferation and Colony Forming Activity of Murine Bone Marrow (1991)

Swainsonine, an indolizidine alkaloid, was recently reported to exhibit both antineoplastic and immunomodulatory activities (Humphries, M.J.; Olden, K. Asparagine-linked oligosaccharides and tumor metastasis. Pharmacol. Ther. 44:85-105; 1989). In this study, we show that systemically administered swainsonine promoted the proliferation of murine bone marrow (BM) cells. Animals that received swainsonine intravenously exhibited a significant increase (approximately 5-10 fold) in BM cellularity, engraftment efficiency, and colony forming unit activity using in vitro or in vivo assays. BM cells derived from swainsonine-treated animals or treated with swainsonine in vitro also exhibited a 4-5 fold increase in [3H]-thymidine incorporation, suggesting that a larger fraction of the cells was in the S-phase of the cell cycle. This provides the first evidence that swainsonine, which stimulates the production of cytokines by cells of the immune system, promoted the proliferation of BM progenitor cells. These results suggest that swainsonine could prove valuable in patients undergoing intensive chemoradiotherapy or autologous BM transplantation by decreasing or possibly eliminating leukopenia or myelosuppression often associated with these procedures; it may also be a useful probe to investigate the mechanism of normal hematopoieses.
Methods for Detecting Binding Proteins: An Introduction (2003)

The identification of proteins that bind protein kinase C (PKC) is essential to understanding the contributions of PKCs to signaling pathways. A number of the methods are uniquely applicable to this family of serine/threonine kinases. The PKC family contains at least 10 closely related members with overlapping substrate specificities (1,2). Therefore, isozyme-specific phosphorylation of substrates must be caused in part by isozyme-specific subcellular localization, isozyme-specific proximity to substrates, and/or to regulation of activity in an isozyme-specific manner (3). There is some selectivity in the regulation of catalytic activity of PKC classes rather than individual isozymes. The classic (cPKC) enzymes α, βI, βII, and γPKC are activated by phosphatidylserine (PS), diacylglycerol (DG), and calcium, the novel (nPKC) enzymes δ, ε, θ, and ηPKC require PS and DG only, and the atypical (aPKC) enzymes ζ, and λ/ιPKC are activated by PS and possibly phosphatidylinositol-3,4,5-trishosphate, and ceramide (1,4,5).
A riboflavin auxotroph of Actinobacillus pleuropneumoniae is attenuated in swine (1996)

Actinobacillus pleuropneumoniae is the etiological agent of a highly contagious and often fatal pleuropneumonia in swine. A riboflavin-requiring mutant of A. pleuropneumoniae serotype 1, designated AP233, was constructed by deleting a portion of the riboflavin biosynthetic operon (ribGBAH) and replacing it with a gene cassette encoding kanamycin resistance. The genes affected included both the alpha- and beta-subunits of riboflavin synthase as well as a bifunctional enzyme containing GTP cyclohydrase and 3,4-dihydroxy-2-butanone-4-phosphate synthase activities. AP233 was unable to grow in the absence of exogenous riboflavin but otherwise was phenotypically identical to the parent wild-type strain. Experimental infection studies with pigs demonstrated that the riboflavin-requiring mutant was unable to cause disease, on the basis of mortality, lung pathology, and clinical signs, at dosages as high as 500 times the normal 50% lethal dose for the wild-type parent. This is the first demonstration of the attenuation of A. pleuropneumoniae by introduction of a defined mutation in a metabolic gene and the first demonstration that mutations in the genes required for riboflavin biosynthesis can lead to attenuation in a bacterial pathogen.