gebhart/patrepeval huggingface dataset:
Is atherosclerosis an autoimmune disease? (2014)

Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.
Recurrent involvement of the REL and BCL11Aloci in classical Hodgkin lymphoma (2002)

Comparative genomic hybridization studies have shown gains in chromosome region 2p as the most common imbalance in classical Hodgkin lymphoma (cHL). The minimal region of gain contained 2 candidate oncogenes, REL and BCL11A. This study examined the involvement of REL and BCL11A loci in 44 primary cases of cHL by combined immunophenotyping and interphase cytogenetics (FICTION). A median 2p13 copy number above the tetraploid range was detected in 24 (55%) cases. Adjustment for centromere 2 copy number indicated gains of 2p13 in 11 of 31 cHLs (35%) with 8 (26%) high-level amplifications. One cHL displayed selective amplification of the REL locus not affecting BCL11A; another case studied by FICTION and a cHL with cytogenetic 2p change investigated by fluorescence in situ hybridization showed signal patterns suggesting breakpoints in the region spanned by the REL probe. These data indicate that REL rather than BCL11A may be the target of the 2p13 alterations in cHL.
Increased cytotoxic activity of Pseudomonas exotoxin and two chimeric toxins ending in KDEL. (1991)

Pseudomonas exotoxin (PE) is a 66,000 molecular weight protein secreted by Pseudomonas aeruginosa. PE is made up of three domains, and PE40 is a form of PE which lacks domain Ia (amino acids 1-252) and has very low cytotoxicity because it cannot bind to target cells. The sequence Arg-Glu-Asp-Leu-Lys (REDLK) at the carboxyl terminus of Pseudomonas exotoxin has been shown to be important for its cytotoxic activity (Chaudhary, V. K., Jinno, Y., FitzGerald, D. J., and Pastan, I. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 308-312). In this study, we tested the effect of altering the carboxyl sequence of PE from REDLK to the characteristic endoplasmic reticulum retention sequence, KDEL, or to KDEL repeated three times (KDEL)3. We also made similar changes at the carboxyl terminus of two chimeric toxins in which domain I of PE (amino acids 1-252) was either replaced with transforming growth factor alpha (TGF alpha) to make TGF alpha-PE40 or with a single chain antibody (anti-Tac) reacting with the human interleukin 2 receptor to make anti-Tac(Fv)-PE40. Statistical analyses of our results demonstrate that PE and its derivatives ending in KDEL or (KDEL)3 are significantly more active than PE or derivatives ending in REDLK. We have also found that brefeldin A, which is known to perturb the endoplasmic reticulum, inhibits the cytotoxic action of PE. Our results suggest that the altered carboxyl terminus may enable the toxin to interact more efficiently with a cellular component involved in translocation of the toxin to the cytosol.
Achieving large spectral efficiencies from MU-MIMO with tens of antennas: Location-adaptive TDD MU-MIMO design and user scheduling (2010)

We consider schemes for joint scheduling training and downlink MU-MIMO in multi-cell deployments that can yield high cell and cell-edge throughputs with tens of antennas per base-station and single antenna terminals. TDD schemes are considered as they are able to support MU-MIMO over large antenna arrays despite the inherent training dimensionality bottleneck. The proposed schemes operate by dividing users into bins based on their relative location (pathloss) to different stations. MU-MIMO is then performed by splitting transmission resources among such bins, and optimizing the MU-MIMO design on a per-bin basis. We demonstrate the viability of these schemes in the context of a one-dimensional uniform cellular topology and show that high cell and cell-edge rates can be expected, provided the palette of per-bin signaling options is sufficiently large.
Rapid Activation of Neutral Sphingomyelinase by Hypoxia-Reoxygenation of Cardiac Myocytes (2000)

Elevated levels of oxygen free radicals have been implicated in the pathways of reperfusion injury to myocardial tissue. The targets for free radicals may include specific as well as random intracellular components, and part of the cellular response is the induction of extracellularly activated and stress-activated kinases. The intermediate signals that initiate these stress responses are not known. Here we show that one of the earliest responses of cardiac myocytes to hypoxia and reoxygenation is the activation of neutral sphingomyelinase and accumulation of ceramide. Ceramide increased abruptly after reoxygenation, peaking at 10 minutes with 225+/-40% of the control level. Neutral sphingomyelinase activity was induced with similar kinetics, and both activities remained elevated for several hours. c-Jun N-terminal kinase (JNK) was also activated within the same time frame. Treatment of cardiac myocytes with extracellular ceramides also activated JNK. Pretreating cells with antioxidants quenched sphingomyelinase activation, ceramide accumulation, and JNK activation. Ceramide did not accumulate in reoxygenated nonmuscle fibroblasts, and JNK was not activated by reoxygenation in these cells. The results identify neutral sphingomyelinase activation as one of the earliest responses of cardiac myocytes to the redox stress imposed by hypoxia-reoxygenation. The results are consistent with a pathway of ceramide-mediated activation of JNK.
Advances in kernel methods: support vector learning (1999)

Introduction to support vector learning roadmap. Part 1 Theory: three remarks on the support vector method of function estimation, Vladimir Vapnik generalization performance of support vector machines and other pattern classifiers, Peter Bartlett and John Shawe-Taylor Bayesian voting schemes and large margin classifiers, Nello Cristianini and John Shawe-Taylor support vector machines, reproducing kernel Hilbert spaces, and randomized GACV, Grace Wahba geometry and invariance in kernel based methods, Christopher J.C. Burges on the annealed VC entropy for margin classifiers - a statistical mechanics study, Manfred Opper entropy numbers, operators and support vector kernels, Robert C. Williamson et al. Part 2 Implementations: solving the quadratic programming problem arising in support vector classification, Linda Kaufman making large-scale support vector machine learning practical, Thorsten Joachims fast training of support vector machines using sequential minimal optimization, John C. Platt. Part 3 Applications: support vector machines for dynamic reconstruction of a chaotic system, Davide Mattera and Simon Haykin using support vector machines for time series prediction, Klaus-Robert Muller et al pairwise classification and support vector machines, Ulrich Kressel. Part 4 Extensions of the algorithm: reducing the run-time complexity in support vector machines, Edgar E. Osuna and Federico Girosi support vector regression with ANOVA decomposition kernels, Mark O. Stitson et al support vector density estimation, Jason Weston et al combining support vector and mathematical programming methods for classification, Bernhard Scholkopf et al.
Preparation, Characterization, and Surface Modification of Silver Particles (1998)

Colloidal silver has been formed either by irradiation with 253.7 nm light or by chemical reduction of AgClO4 in the presence of protective agents such as poly(vinylpyrrolidone), carboxy methyl cellulose, and gelatin. The particles were characterized by their absorption maximum and transmission electron micrographs. Peptization effect was observed in the presence of photosensitive benzophenone. Surface modification studies of silver particles in the presence of various complexing agents, viz., N-(hydoxyethyl)ethylenediaminetriacetic acid, iminodiacetic acid, nitrilotriacetic acid, 2-mercaptobenzimidazole, benzotriazole, 5-aminotetrazole, imidazole, and sanazole were carried out and it was shown that the reactivity of silver particles increases in their presence. However, in the presence of stabilizers, due to competitve reactions, partial recovery of the surface plasmon absorption band was observed. The Fermi potential of surface modified silver particles seems to lie in the range of −0.40 ± 0.05 V.
Near‐UV laser treatment of extrinsic dental enamel stains (2012)

Laser ablation of extrinsic enamel stains at 400 nm is observed to be most efficient above 3 J/cm(2) with minimal damage to the underlying enamel. Unsound underlying enamel is also observed to be selectively removed after irradiation.
Histamine is released in the wheal but not the flare following challenge of human skin in vivo: a microdialysis study (1997)

The mediator mechanisms of the cutaneous wheal and flare response, which underlies allergic skin and urticarial conditions, are controversial. The wheal results primarily from a direct effect of histamine on the local vascular bed but to what extent does histamine diffuse within the wheal? The flare is neurogenic, in origin, being disseminated within the dermis by axon reflexes, but do the neuropeptides released from the nerve endings cause the vasodilatation directly or do they induce the further release of histamine which then transduces the flare?We have addressed these questions by inserting 216 microns diameter microdialysis fibres into the dermis within the different areas of the wheal and flare to monitor changes in histamine levels provoked by intradermal injections of histamine, allergen, codeine and substance P. Twenty-one subjects participated in the investigations.The histamine concentration in unprovoked skin was 10.5 +/- 0.6 nM. As the dialysis efficacy was approximately 50%, this equates to tissue concentrations of 20 nM. All provicants released large amounts of histamine at the injection site, maximum histamine levels being 337-1293 nM. Diffusion of histamine within the wheal was poor, levels at 2.3 mm and 3.7 mm from the site of injection being 4-22% and 0.2-3.7% respectively of those 1 mm from the injection site. No increased histamine levels were detected in the flare with any provicant. Atraumatic delivery to the skin of histamine in infusion concentrations of 30-10,000 nM caused concentration-related effects, at least 100 nM being necessary to induce a significant increase in skin blood flow, a threshold of 300-1000 being required to stimulate a visible flare and a measurable erythema, and 3000-10,000 nM being the minimum for induction of a wheal. Thus the skin blood vessels and nerves are responsive to histamine, but at relatively high concentrations.These data support the theory that the flare reaction to focal histamine injection or release is a neurogenic reflex not involving histamine release at its effector end.
A new route to hydrophobic amino acids using copper-promoted reactions of serine-derived organozinc reagents (2000)

Copper-catalysed reaction of the serine-derived zinc reagent 1 with allylic electrophiles gives products arising formally from both SN2 and SN2′ pathways. These constitutional isomers can be separated, either directly, or in the case of (2S)-2-tert-butoxycarbonylamino-6-methylhept-5-enoic acid methyl ester (11) and (2S)-2-tert-butoxycarbonylamino-4,4-dimethylhex-5-enoic acid methyl ester (12) by selective epoxidation of 11. Hydrogenation of the double bond, followed by protecting group manipulation, allows the synthesis of the Fmoc-protected amino acids 3–7 ready for automated peptide synthesis.
Tobacco Mesophyll Protoplasts Synthesize 1,3-β-Glucanase, Chitinases, and “Osmotins” during in Vitro Culture (1990)

Tobacco (Nicotiana tabacum) mesophyll protoplasts synthesize six basic proteins (a, a′, a(1), b, b′, and c) which are undetectable in the leaf and whose synthesis is reduced by auxin (Y Meyer, L Aspart, Y Chartier [1984] Plant Physiol 75: 1027-1033). Polypeptides a, a′, and a(1) were shown to have similar mobilities on two-dimensional electrophoresis as one 1,3-β-glucanase and two chitinases from tobacco mosaic virus-infected leaves. In immunoblotting experiments, polypeptide a was recognized by specific antibodies raised against the 1,3-β-glucanase and a′ and a(1) reacted with anti-chitinase antibodies. Similarly, b and b′ comigrated with osmotin and its neutral counterpart, two proteins characteristic of salt-adapted tobacco cells, and reacted with anti-osmotin antibodies. In addition it has been shown that 1,3-β-glucanase and chitinase activities increased at the same time as a, a′, and a(1) accumulated in cultivated protoplasts. Finally, polypeptide c was also detected in tobacco mosaic virus-infected leaves but could not be identified as any of the pathogenesis-related proteins characterized so far in tobacco. Thus, cultivated tobacco protoplasts synthesize and accumulate typical stress proteins.
Role of calpain in spinal cord injury: effects of calpain and free radical inhibitors. (1998)

The demonstration of increased calpain activity, immunostaining, and expression at the gene (mRNA) and protein levels concomitant with ultrastructural degeneration and loss of axon and myelin proteins in lesioned cord have implicated a pivotal role for calpain in tissue destruction in spinal cord injury (SCI). Calpain, stimulated by free radicals, also mediates apoptotic cell death. These findings suggested that the use of calpain and lipid peroxidation drugs as therapeutic agents would protect cells and maintain the axon-myelin structural unit by preventing protein degradation. In order to examine this hypothesis, we treated SCI animals with calpain inhibitors (calpeptin) and/or methlprednisolone (MP), and antiinflammatory and free-radical inhibitor. SCI (40 g/cm) was induced by weight-drop, and 1 mg calpeptin or 165 mg MP/kg were given intravenously (i.v.) for 24 hours. Untreated injured animals receiving vehicle served as controls. Lesion 68-kDa and 200-kDa neurofilament proteins (NFPs) were analyzed by sodium dodecylsulfate polyarcylamide gel electrophoresis (SDS-PAGE) and chemiluminescence, and the extent of protein loss was quantitated. Loss of protein in the lesion of untreated cord amounted to 47% compared to sham control, while that for calpeptin- or MP-treated rats was 25-30%. Combination treatment with calpeptin and MP was slightly more effective in preventing NFP degradation, compared to either when used alone. Apopotic cell death in SCI as characterized by internucleosomal DNA fragmentation was also reduced following treatment with the inhibitors. The inhibition of cytoskeletal protein degradation suggests that calpain and free-radical inhibitors may rescue cells and preserve and maintain membrane structure by preventing protein breakdown, preserving motor function, and being neuroprotective.
Transformation of Bacteria by Electroporation (2003)

The use of an electrical field to permeabilize cells reversibly (electroporation) has become a valuable technique for transference of DNA into both eukaryotic and prokaryotic cells. Many species of bacteria have been successfully electroporated () and many strains of E. coli are routinely electrotransformed to efficiencies of 109 and 1010 transformants/µg DNA. Frequencies of transformation can be as high as 80% of the surviving cells and DNA capacities of nearly 10 µg of transforming DNA/mL are possible ().
Transcription-Mediated Binding of Peptide Nucleic Acid (PNA) to Double-Stranded DNA: Sequence-Specific Suicide Transcription (1996)

Peptide nucleic acid (PNA) forms sequence-specific (PNA)2/DNA triplexes with one strand of double-stranded DNA by strand invasion. When formed with the template strand of DNA such a (PNA)2/DNA triplex can arrest transcription elongation in vitro and can thus act as an anti-gene agent. One of the major obstacles to applying PNA as an anti-gene agent in vivo is that PNA strand invasion occurs at a very slow rate under moderate salt conditions. In the present study we show that transcription can increase the rate of sequence-specific PNA binding dramatically. Such transcription-mediated PNA binding occurs three times as efficiently when the PNA target is situated on the non- template strand as compared with the template strand. Since transcription can mediate template strand-associated (PNA)2/DNA complexes which arrest further elongation, the action of RNA polymerase results in repression of its own activity, i.e. suicide transcription. These findings are highly relevant for the possible future use of PNA as an anti-gene agent.
Metal binding affinity and structural properties of an isolated EF-loop in a scaffold protein (2001)

To establish an approach to obtain the site-specific calcium binding affinity of EF-hand proteins, we have successfully designed a series of model proteins, each containing the EF-hand calcium-binding loop 3 of calmodulin, but with increasing numbers of Gly residues linking the loop to domain 1 of CD2. Structural analyses, using different spectroscopic methods, have shown that the host protein is able to retain its native structure after insertion of the 12-residue calcium-binding loop and retains a native thermal stability and thermal unfolding behavior. In addition, calcium binding to the engineered CD2 variants does not result in a significant change from native CD2 conformation. The CD2 variant with two Gly linkers has been shown to have the strongest metal binding affinity to Ca(II) and La(III). These experimental results are consistent with our molecular modeling studies, which suggest that this protein with the engineered EF-loop has a calmodulin-like calcium binding geometry and backbone conformation. The addition of two Gly linkers increases the flexibility of the inserted EF-loop 3 from calmodulin, which is essential for the proper binding of metal ions.
OX40 Costimulatory Signals Potentiate the Memory Commitment of Effector CD8+ T Cells (2008)

A T cell costimulatory molecule, OX40, contributes to T cell expansion, survival, and cytokine production. Although several roles for OX40 in CD8(+) T cell responses to tumors and viral infection have been shown, the precise function of these signals in the generation of memory CD8(+) T cells remains to be elucidated. To address this, we examined the generation and maintenance of memory CD8(+) T cells during infection with Listeria monocytogenes in the presence and absence of OX40 signaling. We used the expression of killer cell lectin-like receptor G1 (KLRG1), a recently reported marker, to distinguish between short-lived effector and memory precursor effector T cells (MPECs). Although OX40 was dispensable for the generation of effector T cells in general, the lack of OX40 signals significantly reduced the number and proportion of KLRG1(low) MPECs, and, subsequently, markedly impaired the generation of memory CD8(+) T cells. Moreover, memory T cells that were generated in the absence of OX40 signals in a host animal did not show self-renewal in a second host, suggesting that OX40 is important for the maintenance of memory T cells. Additional experiments making use of an inhibitory mAb against the OX40 ligand demonstrated that OX40 signals are essential during priming, not only for the survival of KLRG1(low) MPECs, but also for their self-renewing ability, both of which contribute to the homeostasis of memory CD8(+) T cells.
Internal cardiac defibrillation in man: pronounced improvement with sequential pulse delivery to two different lead orientations. (1986)

Wider applicability of an implantable automatic defibrillator depends on achieving internal cardiac defibrillation consistently with the lowest possible energy. In animal studies, we have found that the cardiac defibrillation threshold could be reduced when sequential shocks separated in time and spacially arranged were delivered to the heart. We compared internal cardiac defibrillation using a single pulse shock delivered through an intravascular catheter with this new method for internal cardiac defibrillation in patients undergoing cardiac surgery for the correction of arrhythmias. For the single pulse shock and the first pulse of the sequential pulse shock, current was passed through an intravascular catheter with the catheter cathode at the apex of the right ventricle and the anode at the superior vena cava-atrial junction region. The second pulse of the sequential pulse countershock was delivered between the catheter cathode in the right ventricular apex and an oval plaque electrode secured on the laterobasal left ventricular epicardium as anode. With the single pulse alone for shock delivery, 12 patients could be defibrillated with an average of 20.1 +/- 16.8 J, with a corresponding leading-edge peak voltage and current of 836 +/- 319 V and 9.4 +/- 4.5 A, respectively. However, two of the patients could not be defibrillated with energies below 50 J. With the sequential pulse shock delivery, a significant reduction in all values were recorded. Mean total energy for defibrillation averaged 7.7 +/- 6.0 J. Leading-edge peak voltage and current from the catheter averaged 430 +/- 148 V and 5.0 +/- 2.8 A, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence for an Important Role of WRKY DNA Binding Proteins in the Regulation of NPR1 Gene Expression (2001)

The Arabidopsis NPR1 gene is a positive regulator of inducible plant disease resistance. Expression of NPR1 is induced by pathogen infection or treatment with defense-inducing compounds such as salicylic acid (SA). Transgenic plants overexpressing NPR1 exhibit enhanced resistance to a broad spectrum of microbial pathogens, whereas plants underexpressing the gene are more susceptible to pathogen infection. These results suggest that regulation of NPR1 gene expression is important for the activation of plant defense responses. In the present study, we report the identification of W-box sequences in the promoter region of the NPR1 gene that are recognized specifically by SA-induced WRKY DNA binding proteins from Arabidopsis. Mutations in these W-box sequences abolished their recognition by WRKY DNA binding proteins, rendered the promoter unable to activate a downstream reporter gene, and compromised the ability of NPR1 to complement npr1 mutants for SA-induced defense gene expression and disease resistance. These results provide strong evidence that certain WRKY genes act upstream of NPR1 and positively regulate its expression during the activation of plant defense responses. Consistent with this model, we found that SA-induced expression of a number of WRKY genes was independent of NPR1.