gebhart/patrepeval huggingface dataset:
Tau-Focused Immunotherapy for Alzheimers Disease and Related Tauopathies (2009)

Immunotherapies targeting the amyloid-beta (Abeta) peptide in Alzheimer's disease (AD) have consistently been effective in mouse studies and shown promise in clinical trials, although some setbacks have occurred. First, encephalitis was observed in a small subset of patients. More recent autopsy data from a few subjects suggests that clearance of Abeta plaques may not halt cognitive deterioration once impairments are evident, emphasizing the need for other more effective approaches at that stage of the disease. Another important target in AD is the neurofibrillary tangles and its precursors, composed primarily of hyperphosphorylated tau proteins, which correlate well with the degree of dementia. As Abeta and tau pathologies are likely synergistic, targeting both together may be more effective, and perhaps essential as early diagnosis prior to cognitive decline is currently unavailable. Also, Abeta immunotherapy results in a very limited indirect clearance of tau aggregates, showing the importance of developing a separate therapy that directly targets pathological tau. Our findings in two tangle mouse models indicate that active immunization targeting an AD phospho-tau epitope reduces aggregated tau in the brain and prevents/slows progression of the tangle-related behavioral phenotype, including cognitive impairment. These antibodies enter the brain and bind to pathological tau within neurons although the therapeutic effect may at least in part be due to clearance of extracellular tau that may have biological effects. We are currently clarifying the mechanism of these promising findings, determining its epitope specificity as well as assessing the feasibility of this approach for clinical trials.
Protecting Groups for the Synthesis of Ribonucleic Acids (2001)

Methods for the regioselective introduction of alkoxymethyl-groups into the 2'-O-position of 5'-O-dimethoxytritylated, nucleobase-protected ribonucleosides and for the N-alkyloxycarbonylation of adenine and guanine nucleosides were developed. These methods were used for the preparation of RNA-phosphoramidites carrying novel fluoride- and photolabile sugar and nucleobase protecting groups.
Realtime ray tracing of dynamic scenes on an FPGA chip (2004)

Realtime ray tracing has recently established itself as a possible alternative to the current rasterization approach for interactive 3D graphics. However, the performance of existing software implementations is still severely limited by today's CPUs, requiring many CPUs for achieving realtime performance.In this paper we present a prototype implementation of the full ray tracing pipeline on a single FPGA chip. Running at only 90 MHz it achieves realtime frame rates of 20 to 60 frames per second over a wide range of 3D scenes and includes support for texturing, multiple light sources, and multiple levels of reflection or transparency. A particular interesting feature of the design in the re-use of the transformation unit necessary for supporting dynamic scenes also for other tasks, including efficient ray-triangle intersection as well as shading computations. Despite the additional support for dynamic scenes this approach reduces the overall hardware cost by 68%.We evaluate the design and its implementation across a wide set of example scenes and demonstrate the benefits of dedicated realtime ray tracing hardware.
The Tyrosine Kinase Inhibitor CGP57148B Selectively Inhibits the Growth of BCR-ABL–Positive Cells (1997)

The Philadelphia chromosome found in virtually all cases of chronic myeloid leukemia (CML) and in about one third of the cases of adult acute lymphoblastic leukemia is formed by a reciprocal translocation between chromosomes 9 and 22 that results in the fusion of BCR and ABL genetic sequences. This BCR-ABL hybrid gene codes for a fusion protein with deregulated tyrosine kinase activity that can apparently cause malignant transformation. CGP57148B, a 2-phenylaminopyrimidine derivative, has been shown to selectively inhibit the tyrosine kinase of ABL and BCR-ABL. We report here that this compound selectively suppresses the growth of colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid derived from CML over a 2-logarithmic dose range with a maximal differential effect at 1.0 micromol/L. However, almost all CML colonies that grow in the presence of 1.0 micromol/L CGP57148B are BCR-ABL-positive, which may reflect the fact that residual normal clonogenic myeloid precursors are infrequent in most patients with CML. We also studied the effects of CGP57148B on hematopoietic cell lines. Proliferation was suppressed in most of the BCR-ABL-positive lines; all five BCR-ABL-negative lines were unaffected. We conclude that this new agent may have significant therapeutic applications.
Dysregulation of Met receptor tyrosine kinase activity in invasive tumors (2002)

The MET protooncogene was discovered because of the ability of oncogenic Met to mediate chemically induced transformation of a human osteogenic sarcoma cell line (1). The normal product of this gene, Met, is an unusual receptor tyrosine kinase that can be distinguished from most other such proteins on the basis of its biosynthesis and its structural features. This transmembrane protein is synthesized as a single-chain precursor, which undergoes intracellular proteolytic cleavage at a basic amino acid site, yielding a disulfide-linked heterodimer. Its C-terminal, intracellular region contains a multifunctional docking site that binds to various signaling molecules. These features define a Met receptor tyrosine kinase family consisting of three related proteins, Met, Ron, and c-Sea, the last of which may be the chicken ortholog of Ron.
Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia (2004)

GRM3, a metabotropic glutamate receptor-modulating synaptic glutamate, is a promising schizophrenia candidate gene. In a family-based association study, a common GRM3 haplotype was strongly associated with schizophrenia (P = 0.0001). Within this haplotype, the A allele of single-nucleotide polymorphism (SNP) 4 (hCV11245618) in intron 2 was slightly overtransmitted to probands (P = 0.02). We studied the effects of this SNP on neurobiological traits related to risk for schizophrenia and glutamate neurotransmission. The SNP4 A allele was associated with poorer performance on several cognitive tests of prefrontal and hippocampal function. The physiological basis of this effect was assessed with functional MRI, which showed relatively deleterious activation patterns in both cortical regions in control subjects homozygous for the SNP4 A allele. We next looked at SNP4's effects on two indirect measures of prefrontal glutamate neurotransmission. Prefrontal N-acetylaspartate, an in vivo MRI measure related to synaptic activity and closely correlated with tissue glutamate, was lower in SNP4 AA homozygotes. In postmortem human prefrontal cortex, AA homozygotes had lower mRNA levels of the glial glutamate transporter EAAT2, a protein regulated by GRM3 that critically modulates synaptic glutamate. Effects of SNP4 on prefrontal GRM3 mRNA and protein levels were marginal. Resequencing revealed no missense or splice-site SNPs, suggesting that the intronic SNP4 or related haplotypes may exert subtle regulatory effects on GRM3 transcription. These convergent data point to a specific molecular pathway by which GRM3 genotype alters glutamate neurotransmission, prefrontal and hippocampal physiology and cognition, and thereby increased risk for schizophrenia.
Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling (2006)

Activin type II receptors (ActRIIs) including ActRIIA and ActRIIB are serine/threonine kinase receptors that form complexes with type I receptors to transmit intracellular signaling of activins, nodal, myostatin and a subset of bone morphogenetic proteins. ActRIIs are unique among serine/threonine kinase receptors in that they associate with proteins having PSD-95, Discs large and ZO-1 (PDZ) domains. In our previous studies, we reported specific interactions of ActRIIs with two independent PDZ proteins named activin receptor-interacting proteins 1 and 2 (ARIP1 and ARIP2). Overexpression of both ARIP1 and ARIP2 reduce activin-induced transcription. Here, we report the isolation of two isoforms of ARIP2 named ARIP2b and 2c. ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. ARIP2 and its isoforms have one PDZ domain in the NH2-terminal region, and interact with ActRIIA. Although PDZ domains containing GLGF motifs of ARIP2b and 2c are identical to that of ARIP2, their COOH-terminal sequences differ from that of ARIP2. Interestingly, unlike ARIP2, overexpression of ARIP2b or 2c did not affect ActRIIA internalization. ARIP2b/2c inhibit inhibitory actions of ARIP2 on activin signaling. ARIP2 is widely distributed in mouse tissues. ARIP2b/2c is expressed in more restricted tissues such as heart, brain, kidneys and liver. Our results indicate that although both ARIP2 and ARIP2b/2c interact with activin receptors, they regulate ActRIIA function in a different manner.
Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions (2004)

N-terminal pyroglutamate (pGlu) formation from glutaminyl precursors is a posttranslational event in the processing of bioactive neuropeptides such as thyrotropin-releasing hormone and neurotensin during their maturation in the secretory pathway. The reaction is facilitated by glutaminyl cyclase (QC), an enzyme highly abundant in mammalian brain. Here, we describe for the first time that human and papaya QC also catalyze N-terminal glutamate cyclization. Surprisingly, the enzymatic Glu(1) conversion is favored at pH 6.0 while Gln(1) conversion occurs with an optimum at pH 8.0. This unexpected finding might be of importance for deciphering the events leading to deposition of highly toxic pyroglutamyl peptides in amyloidotic diseases.
Reproducibility of Nerve Fiber Thickness, Macular Thickness, and Optic Nerve Head Measurements Using StratusOCT (2004)

StratusOCT demonstrated reproducible measurements of NFL thickness, macular thickness, and optic nerve head parameters. The best reproducibility was found for dilated standard scanning for NFL and ONH parameters and for dilated high-density scanning for macular parameters.
Deep-sequencing of endothelial cells exposed to hypoxia reveals the complexity of known and novel microRNAs (2012)

In order to understand the role of microRNAs (miRNAs) in vascular physiopathology, we took advantage of deep-sequencing techniques to accurately and comprehensively profile the entire miRNA population expressed by endothelial cells exposed to hypoxia. SOLiD sequencing of small RNAs derived from human umbilical vein endothelial cells (HUVECs) exposed to 1% O₂ or normoxia for 24 h yielded more than 22 million reads per library. A customized bioinformatic pipeline identified more than 400 annotated microRNA/microRNA* species with a broad abundance range: miR-21 and miR-126 totaled almost 40% of all miRNAs. A complex repertoire of isomiRs was found, displaying also 5' variations, potentially affecting target recognition. High-stringency bioinformatic analysis identified microRNA candidates, whose predicted pre-miRNAs folded into a stable hairpin. Validation of a subset by qPCR identified 18 high-confidence novel miRNAs as detectable in independent HUVEC cultures and associated to the RISC complex. The expression of two novel miRNAs was significantly down-modulated by hypoxia, while miR-210 was significantly induced. Gene ontology analysis of their predicted targets revealed a significant association to hypoxia-inducible factor signaling, cardiovascular diseases, and cancer. Overexpression of the novel miRNAs in hypoxic endothelial cells affected cell growth and confirmed the biological relevance of their down-modulation. In conclusion, deep-sequencing accurately profiled known, variant, and novel microRNAs expressed by endothelial cells in normoxia and hypoxia.
Designing user-adapted interfaces (1997)

Article Free Access Share on Designing user-adapted interfaces: the unified design method for transformable interactions Authors: A. Savidis Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, Greece Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, GreeceView Profile , A. Paramythis Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, Greece Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, GreeceView Profile , D. Akoumianakis Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, Greece Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, GreeceView Profile , C. Stephanidis Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, Greece Institute of Computer Science, Foundation for Research and Technology-Hellas (FORTH), Science and Technology Park of Crete, P.O. Box 1385, GR 711 10, Heraklion, Crete, GreeceView Profile Authors Info & Claims DIS '97: Proceedings of the 2nd conference on Designing interactive systems: processes, practices, methods, and techniquesAugust 1997 Pages 323–334https://doi.org/10.1145/263552.263636Published:01 August 1997Publication History 7citation1,246DownloadsMetricsTotal Citations7Total Downloads1,246Last 12 Months25Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Optically pumped lasing of ZnO at room temperature (1997)

We report the observation of optically pumped lasing in ZnO at room temperature. Thin films of ZnO were grown by plasma-enhanced molecular beam epitaxy on (0001) sapphire substrates. Laser cavities formed by cleaving were found to lase at a threshold excitation intensity of 240 kW cm−2. We believe these results demonstrate the high quality of ZnO epilayers grown by molecular beam epitaxy while clearly demonstrating the viability of ZnO based light emitting devices.
Infliximab induces clinical, endoscopic and histological responses in refractory ulcerative colitis (2004)

infliximab may be an effective and safe therapy for some patients with ulcerative colitis refractory to other forms of therapy, although controlled studies are needed to assess its role in the general management of this disease.
Effects of feed intake on particle distribution, passage of digesta, and extent of digestion in the gastrointestinal tract of cattle (1991)

Four nonlactating Holstein dairy cows (means +/- SD BW = 692 +/- 49 kg) were used in a 4 x 4 Latin square design experiment to determine changes in distribution of particles within the ruminoreticulum (RR) and total digestive tract in cattle fed a forage-based diet at four intake levels. Relationships between chewing activities and rates of particle breakdown, passage, and digestion were also determined. Percentage of large particles increased linearly in the dorsal rumen (P = .001), ventral rumen (P = .004), reticulum (P = .007), duodenum (P = .007), and feces (P = .006) as DMI increased. Particles of sizes less than or equal to 2,000 microns, eligible to pass from the RR, constituted 60 to 92% of particle DM in the RR. Increased feed intake resulted in a longer (P = .003) eating but a shorter (P = .008) ruminating time per kilogram of DM intake, whereas total chewing time per kilogram of DMI was not affected (P = .12). Passage rate constants of NDF from the RR increased (P = .03) with intake. There was no change (P = .87) in the rate constant for particle breakdown in the dorsal rumen with increased intake. Neither fractional passage rate of NDF nor the rate constant for particle breakdown was related to time spent eating (P + .12; P = .34) or time spent ruminating (P = .11; P = .55). It was concluded that rate of passage of small particles from the RR was a determinant of passage from the RR and that changes in rates of passage and breakdown of particles could only be partially explained by changes in chewing activities.
Plantar Pressure Changes Using a Novel Negative Pressure Wound Therapy Technique (2004)

This study evaluated changes in pressure imparted to diabetic foot wounds using a novel negative pressure bridging technique coupled with a robust removable cast walker. Ten patients had plantar pressures assessed with and without a bridged negative pressure dressing on the foot. Off-loading was accomplished with a pressure-relief walker. Plantar pressures were recorded using two pressure-measurement systems. The location and value of peak focal pressure (taken from six midgait steps) were recorded at the site of ulceration. Paired analysis revealed a large difference (mean +/- SD, 74.6% +/- 6.0%) between baseline barefoot pressure and pressure within the pressure-relief walker (mean +/- SD, 939.1 +/- 195.1 versus 235.7 +/- 66.1 kPa). There was a mean +/- SD 9.9% +/- 5.6% higher pressure in the combination device compared with the pressure-relief walker alone (mean +/- SD, 258.0 +/- 69.7 versus 235.7 +/- 66.1 kPa). This difference was only 2% of the initial barefoot pressure imparted to the wound. A modified negative pressure dressing coupled with a robust removable cast walker may not impart undue additional stress to the plantar aspect of the foot and may allow patients to retain some degree of freedom (and a potentially reduced length of hospital stay) while still allowing for the beneficial effects of negative pressure wound therapy and sufficient off-loading.
Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes (2008)

A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)
A carbon dioxide insertion reaction into the Co-H bond of nitrogentris (triphenylphosphine)cobalt hydride (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA carbon dioxide insertion reaction into the Co-H bond of nitrogentris (triphenylphosphine)cobalt hydrideLyong Sun Pu, Akio Yamamoto, and Sakuji IkedaCite this: J. Am. Chem. Soc. 1968, 90, 14, 3896Publication Date (Print):July 1, 1968Publication History Published online1 May 2002Published inissue 1 July 1968https://pubs.acs.org/doi/10.1021/ja01016a072https://doi.org/10.1021/ja01016a072research-articleACS PublicationsRequest reuse permissionsArticle Views558Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Contact allergy: Predictive testing in man (1976)

Predictive tests are of value in forecasting the response of a population to a sensitizer; diagnostic testing is used to determine what substances may actually be producing dermatologic problems. Skin sensitization predictive and diagnostic data for the eleven most frequently encountered skin sensitizers in Western Europe, Canada and the United States are reviewed. These compounds include two drugs (benzocaine and neomycin), two cosmetic ingredients (p-phenylenediamine and balsam of Peru), four preservatives (formaldehyde, ethylenediamine, parabens and mercurials) and three ingredients of wearing apparel (nickel, chromium and thiram). Many of the data were collected by the North American Contact Dermatitis Group and the International Contact Dermatitis Research Group on tests with 1,200 and 4,825 dermatologic patients, respectively; the remainder were obtained by individual investigators with smaller groups of subjects. The data obtained by various investigators are discussed in relation to the factors which affect the extent and degree of sensitization which they can cause.
INVOLVEMENT OF INDOLE‐3‐ACETIC ACID PRODUCED BY THE GROWTH‐PROMOTING BACTERIUM AZOSPIRILLUM SPP. IN PROMOTING GROWTH OF CHLORELLA VULGARIS1 (2008)

Involvement of indole-3-acetic acid (IAA), produced by the microalgae-growth-promoting bacteria Azospirillum brasilens and A. lipoferum, in promoting growth of the microalga Chlorella vulgaris Beij. was studied. Four wildtype strains of Azospirillum and their IAA-deficient mutants were co-immobilized with C. vulgaris in alginate beads. Cultures were grown in synthetic growth medium supplemented with tryptophan. Growth promotion of microalgae and production of exogenous IAA by Azospirillum spp. were monitored. All wildtype Azospirillum spp. produced significant but varying amounts of IAA, while their mutant forms produced significantly less. The results demonstrated a significant growth promotion in Chlorella cultures when immobilized with the four wildtype strains of Azospirillum, while very low or no enhanced growth was induced by the four IAA-deficient mutants, compared to when C. vulgaris is immobilized alone. A complementation experiment, where an IAA-attenuated mutant (A. brasilense SpM7918) was supplemented with IAA produced by its parental wildtype strain (A. brasilense Sp6), restored growth promotion in the microalgae-mutant culture.
Developing a planning process for large conferences (1985)

Abstract Successful conference planning begins with a well‐organized plan.