gebhart/patrepeval huggingface dataset:
Response of a human T cell clone to a large panel of altered peptide ligands carrying single residue substitutions in an antigenic peptide: characterization and frequencies of TCR agonism and TCR antagonism with or without partial activation (1996)

A CD4+ human T cell clone YN5-32 recognized a streptococcal M12p54-68 peptide in the context of HLA-DR4 and produced a large amount of IFN-gamma. We investigated responses of YN5-32 to 156 independent analogue peptides carrying single residue substitutions at residues 57 (position 1 (p1)) to 65 (p9) of the peptide. Approximately 30% of analogues at either Leu57 (p1), Ala60 (p4), or Asn62 (p6) residues exhibited TCR agonism to stimulate various magnitudes of proliferative responses in the T cell clone, and analogues exhibiting TCR antagonism are rare in these three residues. In analogues at either Glu58 (p2), Gln59 (p3), Tyr61 (p5), or Glu63 (p7) residue, 30 to 50% exhibited TCR antagonism. About 10% of analogues at Glu58 (p2) or Tyr61 (p5) stimulated proliferative responses, while 30 to 50% of analogues at Gln59 (p3) or Glu63 (p7) did so. Some of these TCR antagonistic analogues carrying relatively conservative amino acid substitutions partially activated the T cells to induce large increases in size and expression levels of CD4, CD11a (LFA-1), CD28, CD49d (VLA-4), and CD95 (Fas), and small increases in CD25 and CD44 expressions on the cell surface. None of the partially activating antagonistic analogues induced IFN-gamma production or anergy in T cells. Analogues with replacements of acidic amino acids at either Leu64 (p8) or Ser65 (p9) residue had dominant negative effects on T cell proliferation. Thus, altered peptide ligands with single residue substitutions in the antigenic peptide frequently stimulated the human T cell clone, in at least three different ways to exhibit agonism, antagonism, and antagonism with partial activation. Frequencies of analogue peptides exhibiting these three different effects on the T cell clone differed depending on the residue of the peptide substituted. Altered T cell responses induced by analogue peptides of a T cell epitope provide a system to analyze activation signals mediated by TCR, and to manipulate T cell responses.
Vicious Cycles Within the Neuropathophysiologic Mechanisms of Alzheimers Disease (2006)

Rigorous scientific research has identified multiple interactive mechanisms that parallel and are likely causative of the development of Alzheimer's disease (AD). Causative mechanisms include genomics, the creation of amyloid beta (Abeta), factors inhibiting the Abeta removal process, the transformation of Abeta to its toxic forms (various forms of Abeta aggregation), and lastly the oxidative, inflammatory, and other effects of toxic Abeta. Fibrillar beta-amyloid peptide, a major component of senile plaques in AD brain, is known to induce microglial-mediated neurotoxicity under certain conditions, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins. Abeta-42 oligomers that are soluble and highly neurotoxic, referred to as Abeta-derived diffusible ligands (ADDLs), assemble under conditions that block fibril formation. These oligomers bind to dendrite surfaces in small clusters with ligand-like specificity and are capable of destroying hippocampal neurons at nanomolar concentrations. Evidence is presented that AD is triggered by these soluble, neurotoxic assemblies of Abeta rather than the late stage pathology landmarks of amyloid plaques and tangles. The premise is that AD symptoms stem from aberrant nerve cell signaling and synaptic failure rather than nerve cell death, which nevertheless follows and exacerbates the initial pathologies of AD. The defective clearance of amyloid leads to amyloid angiopathy that in turn perpetuates hypoperfusion that affects formation as well as absorption of CSF thereby altering clearance of amyloid and promoting vascular and parenchymal deposition[1]. Hypoperfusion, the defective clearance of amyloid, and resultant increase in amyloid deposition thus represent a vicious cycle. Chronic vascular hypoperfusion-induced mitochondrial failure results in oxidative damage, which drives caspase 3-mediated Abeta peptide secretion and enhances amyloidogenic APP processing. Intracellular Abeta accumulation in turn promotes a significant oxidative and inflammatory mechanism that generates a vicious cycle of Abeta generation and oxidation, each accelerating the other. Abeta activates astrocytes that add to the oxidative imbalance, upregulate the expression of APP via TGF-beta, and are capable of expressing BACE1. Each of these 3 actions accelerates the larger cycle of cholinergic neuron destruction. As oxidative stress induces lesions of cholinergic nuclei producing a reduction in cholinergic neurotransmission, a subsequent increase in cortical APP involving PKCepsilon leads to accelerated amyloidogenic APP metabolism. The linkage of cholinergic activation and APP metabolism completes an additional feedback loop wherein the damage wrought by Abeta accelerates further Abeta production. A comprehensive vision of the neuropathophysiologic mechanisms that result in AD reveals several vicious cycles within a larger vicious cycle, that is to say, a number of interactive systems that each, once set in motion, amplify their own processes, thus accelerating the development of AD.
Temperature Dependence of Molecular Orientation on the Surfaces of Semifluorinated Polymer Thin Films (1999)

Near-edge X-ray absorption fine structure is used to investigate the temperature dependence of molecular orientation of semifluorinated liquid crystalline (SF-LC) mesogens, which are attached to the modified isoprene backbone of (i) a poly(1,2-isoprene) homopolymer and (ii) a diblock copolymer consisting of polystyrene and poly(1,2-isoprene) blocks. Our experiments reveal the existence of two temperature regions in which the surface orientation of the SF-LC mesogens changes abruptly, but even 30 K above the highest such temperature region the surface orientation does not become isotropic. The lower temperature surface transition for both homopolymer and block copolymer occurs close to the temperature of the bulk homopolymer smectic-B to smectic-A transition and well above the bulk smectic-B to smectic-A transition in the block copolymer. It seems to be controlled exclusively by the ordering phenomena originating from the surface. In contrast, the change in the surface organization of the SF-LC mesogens at higher temperatures can be associated with the bulk LC transition from the smectic-A to the isotropic phase.
Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis' (2004)

Increased oxidative stress in diabetes mellitus may underlie the development of endothelial cell dysfunction by decreasing the availability of nitric oxide (NO) as well as by activating pro-inflammatory pathways. In the arterial wall, redox imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric oxide synthase (eNOS). This results in decreased production and increased consumption of NO, and generation of free radicals, such as superoxide and peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative phosphorylation, resulting in inhibition of electron transport and increased transfer of electrons to molecular oxygen to form superoxide and other oxidant radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes.
FPGA implementation of heterogeneous multicore platform with SIMD/MIMD custom accelerators (2012)

Heterogeneous multi-core architecture with CPUs and accelerators attract many attentions since they can achieve power-efficient computing in various areas from low-power embedded processing to high-performance computing. Since the optimal architecture is different from application to applications, it is important to explore suitable architectures for different applications. In this paper, we propose an FPGA-based heterogeneous multi-core platform with custom accelerators for power-efficient computing. Our platform allows to select the most suitable accelerator according to the requirements of an application. Moreover, we optimize the number of ALUs, memory and interconnection network of the selected accelerators to increase the performance and to reduce the power consumption. Experimental results with simple media processing applications times power-efficient compared to the GPU.
Metal Ion Binding to Human Hemopexin (2005)

Binding of divalent metal ions to human hemopexin (Hx) purified by a new protocol has been characterized by metal ion affinity chromatography and potentiometric titration in the presence and absence of bound protoheme IX. ApoHx was retained by variously charged metal affinity chelate resins in the following order: Ni(2+) > Cu(2+) > Co(2+) > Zn(2+) > Mn(2+). The Hx-heme complex exhibited similar behavior except the order of retention of the complex on Zn(2+)- and Co(2+)-charged columns was reversed. One-dimensional (1)H NMR of apoHx in the presence of Ni(2+) implicates at least two His residues and possibly an Asp, Glu, or Met residue in Ni(2+) binding. Potentiometric titrations establish that apoHx possesses more than two metal ion binding sites and that the capacity and/or affinity for metal ion binding is diminished when heme binds. For most metal ions that have been studied, potentiometric data did not fit to binding isotherms that assume one or two independent binding sites. For Mn(2+), however, these data were consistent with a high-affinity site [K(A) = (15 +/- 3) x 10(6) M(-)(1)] and a low-affinity site (K(A) <or= 2 x10(3) M(-)(1)). Binding of Cu(2+) and Zn(2+) to the Hx-heme complex produced significant changes in the Soret-CD spectrum of the Hx-heme complex that were reversed with addition of EDTA. Possibly, these metal ions bind near the heme binding site and perturb the electronic environment of the heme, or their binding induces exchange of one axial His ligand to the heme iron with another adjacent His residue. A possible role for Hx in the maintenance of metal ion homeostasis is discussed.
Characterization of a 64 channel PET detector using photodiodes for crystal identification (1997)

The authors present performance results for a prototype PET detector module consisting of 64 LSO scintillator crystals (3/spl times/3/spl times/20 mm) coupled on one end to a single photomultiplier tube and on the opposite end to a 64 pixel array of 3 mm square silicon photodiodes (typical pixel parameters are 5 pF capacitance, 300 pA dark current, and 73% quantum efficiency at 415 nm). The photomultiplier tube (PMT) provides an accurate timing pulse and energy threshold for all crystals in the module, the silicon photodiodes (PD) identify the crystal of interaction, the sum (PD+PMT) provides a total energy signal, and the PD/(PD+PMT) ratio determines the depth of interaction. With 32 of the channels instrumented, the detector module correctly identifies the crystal of interaction (where "correct" includes the adjacent 4 crystals) 79/spl plusmn/4% of the time with high detection efficiency. The timing resolution for a single LSO detector module is 750 ps fwhm, while its pulse height resolution at 511 keV is 24/spl plusmn/3% fwhm. The depth of interaction measurement resolution is 8/spl plusmn/1 mm fwhm.
Satellite tobacco ringspot virus RNA: A subset of the RNA sequence is sufficient for autolytic processing (1986)

The satellite RNA of tobacco ringspot virus depends upon tobacco ringspot virus for its replication and source of coat protein. The satellite RNA reduces virus accumulation and the severity of virus-induced symptoms. Repetitive sequence, dimeric, and higher forms of the satellite RNA are known to autolytically process to form biologically active monomeric RNA of 359 nucleotide residues [Prody, G. A., Bakos, J. T., Buzayan, J. M., Schneider, I. R. & Bruening, G. (1986) Science 231, 1577-1580], with a 5'-hydroxyl and a 2',3'-cyclic phosphodiester as the new terminal groups. We show here that transcripts of full-length and truncated DNA clones of the satellite RNA sequence also process in a nonenzymic reaction. One such transcript was an RNA that has about one-fourth of the satellite RNA sequence, representing the 3'-terminal and 5'-terminal portions of monomeric RNA joined in the junction that is cleaved in dimeric RNA. This RNA autolytically processed more efficiently than molecules with a larger proportion of the satellite RNA nucleotide sequence.
Superoleophobic Surfaces through Control of Sprayed-on Stochastic Topography (2012)

The liquid repellency and surface topography characteristics of coatings comprising a sprayed-on mixture of fluoroalkyl-functional precipitated silica and a fluoropolymer binder were examined using contact and sliding angle analysis, electron microscopy, and image analysis for determination of fractal dimensionality. The coatings proved to be an especially useful class of liquid repellent materials due to their combination of simple and scalable deposition process, low surface energy, and the roughness characteristics of the aggregates. These characteristics interact in a unique way to prevent the buildup of binder in interstitial regions, preserving re-entrant curvature across multiple length scales, thereby enabling a wide range of liquid repellency, including superoleophobicity. In addition, rather than accumulating in the interstices, the binder becomes widely distributed across the surface of the aggregates, enabling a mechanism in which a simple shortage or excess of binder controls the extent of coating roughness at very small length scales, thereby controlling the extent of liquid repellence.
Liquid-crystal microlens with a beam-steering function (1997)

A novel beam-steering device that makes use of a nematic liquid crystal (LC) is proposed and demonstrated. The beam-steering function is attained with a LC microlens with a divided hole-patterned electrode structure (DE-LC microlens). Optical properties of the DE-LC microlens are investigated and three-dimensional variable-focusing and beam-steering properties are verified experimentally for the first time, to our knowledge.
Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure (2004)

Diabetes is a chronic, progressively worsening disease associated with a variety of microvascular and macrovascular complications. Cardiovascular disease (CVD) is the main cause of death in these patients (1,2). During the past decade, numerous drugs have been introduced for the treatment of type 2 diabetes that, used in monotherapy or in combination therapy, are effective in lowering blood glucose to achieve glycemic goals and in reducing diabetes-related end-organ disease.

Two such drugs, rosiglitazone and pioglitazone, belong to the class called thiazolidinediones (TZDs) (3). Troglitazone, the first agent of this class to be approved, was effective in controlling glycemia but was removed from the market because of serious liver toxicity. Both rosiglitazone and pioglitazone are indicated either as monotherapy or in combination with a sulfonylurea, metformin, or insulin when diet, exercise, and a single agent do not result in adequate glycemic control (4) (package insert Avandia [rosiglitazone maleate; GlaxoSmithKline] and Actos (5) [pioglitazone hydrochloride; Takeda Pharmaceuticals]). In addition to lowering blood glucose, both drugs may benefit cardiovascular parameters, such as lipids, blood pressure, inflammatory biomarkers, endothelial function, and fibrinolytic status (6,7).

These beneficial effects of TZDs on glycemia and cardiovascular risk factors have made them attractive agents in patients with type 2 diabetes who are at high risk for CVD. There is a growing recognition, however, that edema can occur in patients treated with either drug. Because people with diabetes are at increased risk for CVD and many have preexisting heart disease, the edema that sometimes accompanies the use of a TZD can be cause for concern, as it may be a harbinger or sign of congestive heart failure (CHF). An analysis of Medicare beneficiaries hospitalized with the diagnosis of diabetes and CHF indicated that the number of these patients discharged on TZDs had increased from …
Genetic analysis of the human immunodeficiency virus type 1 integrase protein (1994)

Single-amino-acid changes in a highly conserved central region of the human immunodeficiency virus type 1 (HIV-1) integrase protein were analyzed for their effects on viral protein synthesis, virion morphogenesis, and viral replication. Alteration of two amino acids that are invariant among retroviral integrases, D116 and E152 of HIV-1, as well as a mutation of the highly conserved amino acid S147 blocked viral replication in two CD4+ human T-cell lines. Mutations of four other highly conserved amino acids in the region had no detectable effect on viral replication, whereas mutations at two positions, N117 and Y143, resulted in viruses with a delayed-replication phenotype. Defects in virion precursor polypeptide processing, virion morphology, or viral DNA synthesis were observed for all of the replication-defective mutants, indicating that changes in integrase can have pleiotropic effects on viral replication.
A set of plant expression vectors for transcriptional and translational fusions (1987)

Journal Article A set of plant expression vectors for transcriptional and translational fusions Get access Reinhard Töpfer, Reinhard Töpfer Max-Planck-Institut für Züchtungsforschung5000 Köln 30, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Volker Matzeit, Volker Matzeit Max-Planck-Institut für Züchtungsforschung5000 Köln 30, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Bruno Gronenborn, Bruno Gronenborn Max-Planck-Institut für Züchtungsforschung5000 Köln 30, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Jozef Schell, Jozef Schell Max-Planck-Institut für Züchtungsforschung5000 Köln 30, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Hans-Henning Steinbiss Hans-Henning Steinbiss Max-Planck-Institut für Züchtungsforschung5000 Köln 30, FRG Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 14, 24 July 1987, Page 5890, https://doi.org/10.1093/nar/15.14.5890 Published: 24 July 1987 Article history Accepted: 17 June 1987 Published: 24 July 1987
Can Egalitarianism Survive Internationalization (1997)

Can egalitarianism survive internationalization? Yes, but survival also requires that egalitarianism shed its social democratic form.Our argument for this laconic answer proceeds in five steps.We start by introducing the terms of our question (egalitarianism and internationalization), and explaining why we think internationalization need not defeat egalitarianism.Next, we sketch an account of the troubles faced by social democracy as a specific form of egalitarian politics, an account that suggests new conditions that a successor egalitarian politics needs to meet.Third and fourth, we sketch such an alternative -a new egalitarian strategy and project -first considering its governance strategy and political base and then its specifically egalitarian policy components.Fifth and finally, we return to internationalization, arguing that this new egalitarianism can meet the challenges it presents.Though we present our argument in abstract terms, the United States (the case we know best) provides an implicit point of reference throughout.This may invite objection, as the strength and relative independence of the U.S. may make it seem an easy case (our own view is that the great internal diversity of U.S. society, along with the relatively weak hold of egalitarianism on politics within it, make it at least as much a hard one), but the objection does not particularly concern us.Our principal purpose here is to argue against a very general line of argument that draws skeptical conclusions about the contemporary relevance of egalitarian ideals on the basis of alleged facts about internationalization, and to suggest a new sort of egalitarian politics robust in light of those (and other, in our view more relevant) facts.If our discussion of the new egalitarianism is plausible, then there is no compelling argument for skepticism.We might then proceed to considering whether our positive view is limited to the American case, but interna-
Polymer-Encapsulated Schwannoma Cells Expressing Human Nerve Growth Factor Promote the Survival of Cholinergic Neurons after a Fimbria-Fornix Transection (1995)

Many investigators have recently used genetically modified primary fibroblasts of fibroblast cell lines (e.g., 3T3, 208F, or BHK cells) to deliver recombinant nerve growth factor (NGF) into the CNS. In the current study, SCT-1 cells, a Schwannoma cell line derived from a transgenic mouse, were transfected with a human NGF (hNGF) cDNA. After selection, these cells were encased within a polymer capsule and implanted into the ventricles of fimbria-fornix lesioned rats. Encapsulated, non-transfected cells served as controls. Results demonstrated that the hNGF transgene is expressed for at least 3 weeks after implantation. Moreover, the cells did not overgrow the capsule. Recombinant hNGF was able to save &gt;70% of lesioned cholinergic neurons, as assessed by NGF-receptor (NGFr) and choline acetyltransferase (ChAT) immunohistochemistry, from cell death. The number of cholinergic neurons in animals that received control capsules (i.e., nontransfected SCT-1 cells) was similar to lesion only animals (i.e., ~27% and ~33% for NGFr- and ChAT-positive neurons, respectively. These results show that SCT-1 cells can be used to deliver biologically active hNGF into the lesioned rat brain.
Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry (2006)

Assessment of Alzheimer's disease (AD)-related neurofibrillary pathology requires a procedure that permits a sufficient differentiation between initial, intermediate, and late stages. The gradual deposition of a hyperphosphorylated tau protein within select neuronal types in specific nuclei or areas is central to the disease process. The staging of AD-related neurofibrillary pathology originally described in 1991 was performed on unconventionally thick sections (100 mum) using a modern silver technique and reflected the progress of the disease process based chiefly on the topographic expansion of the lesions. To better meet the demands of routine laboratories this procedure is revised here by adapting tissue selection and processing to the needs of paraffin-embedded sections (5-15 mum) and by introducing a robust immunoreaction (AT8) for hyperphosphorylated tau protein that can be processed on an automated basis. It is anticipated that this revised methodological protocol will enable a more uniform application of the staging procedure.