gebhart/patrepeval huggingface dataset:
Spreading Depression: From Serendipity to Targeted Therapy in Migraine Prophylaxis (2009)

Despite the relatively well-characterized headache mechanisms in migraine, upstream events triggering individual attacks are poorly understood. This lack of mechanistic insight has hampered a rational approach to prophylactic drug discovery. Unlike targeted abortive and analgesic interventions, mainstream migraine prophylaxis has been largely based on serendipitous observations (e.g. propranolol) and presumed class effects (e.g. anticonvulsants). Recent studies suggest that spreading depression is the final common pathophysiological target for several established or investigational migraine prophylactic drugs. Building on these observations, spreading depression can now be explored for its predictive utility as a preclinical drug screening paradigm in migraine prophylaxis.
Development of a microfabricated scanning endoscope using SU-8-based optical waveguide (2003)

Flexible medical endoscopes currently used in medicine have many problems and a fundamental tradeoffs. Either resolution or field of view is sacrificed when the scope diameter is less than 3mm, since the minimum pixel size is usually at least 4 microns in a pixel-array such as a camera or fiber bundle. Previous work has shown the design of a micromachined cantilever beam able to realize a 100&mu;m wide, one dimension scanning pattern. First mode resonances of the cantilever scanner are found between 16-52 kHz with response amplitudes ranging from 62.5 to 420 &mu;m. Since cantilever waveguides with resonant frequencies above 20 kHz are potentially suitable for video rate scanning, these devices may be used for image acquisition and display. Described in this work is an alternative method of design for a micro-optical scanning endoscope. The endoscope consists of an optical waveguide microfabricated using SU-8 photoresist. SU-8 is a high contrast, negative tone, chemically amplified, epoxy based photoresist chosen for its high aspect ratio (~15:1) for imaging near vertical sidewalls. With the use of SU-8, we were able to fabricate a much larger waveguide (~85 &mu;m) as compared to the previous silicon oxide method (~3 &mu;m) An overall larger device makes coupling a fiber into the waveguide much easier and increases the amount of light coupled into the cantilever beams. The neagactively toned epoxy resin based SU-8 also increases the device durability and simplifies the fabrication process.
Thiazoline Ring Formation from 2- Methylcysteines and 2-Halomethylalanines (2002)

A systematic survey of conditions and substrates for the formation of 2,4,4-trisubstituted thiazoline rings is presented.The substitution patterns of these thiazolines is particularly relevant for the synthesis of the tantazole, mirabazole, and thiangazole classes of natural products, which contain a linear array of these heterocycles.Methods for the formation of these thiazolines from 2-methyl cysteines and 2-halomethylalanines are discussed.
Spatial Registration of Multispectral and Multitemporal Digital Imagery Using Fast Fourier Transform Techniques (1970)

A system for spatial registration of digitized multispectral and multitemporal imagery is described. Multispectral imagery can be obtained from sources such as multilens cameras, multichannel optical-mechanical line scanners, or multiple vidicon systems which employ filters or other spectral separation techniques to sense selected portions of the spectrum. Spatial registration is required so that multidimensional analysis can be performed on contextually similar image elements from different wavelength bands and at different times. The general registration problem is discussed first; then the fast Fourier transform (FFT) technique for cross correlation of misregistered imagery to determine spatial distances is discussed in detail. A method of achieving translational, rotational, and scaling corrections between images is described. Results of correlation analysis of multispectral scanner imagery and digitized satellite photography is presented. Use of the system for registration of multispectral airborne line-scanner imagery and space photography is described. Application of the techniques to preprocessing of earth resources satellite imagery from systems such as the earth-resources technology satellite (ERTS) scanner and vidicon system is discussed in conclusion.
Analogues of a Locked Nucleic Acid with Three-Carbon 2‘,4‘-Linkages:  Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure (2006)

Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2',4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (DeltaT(m) approximately 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (DeltaT(m) approximately 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.
TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+T cell epitopes (2015)

Despite the availability of major histocompatibility complex (MHC)-binding peptide prediction algorithms, the development of T-cell vaccines against pathogen and tumor antigens remains challenged by inefficient identification of immunogenic epitopes. CD8(+) T cells must distinguish immunogenic epitopes from nonimmunogenic self peptides to respond effectively against an antigen without endangering the viability of the host. Because this discrimination is fundamental to our understanding of immune recognition and critical for rational vaccine design, we interrogated the biochemical properties of 9,888 MHC class I peptides. We identified a strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes of MHC allomorphs, which permitted us to develop and train a hydrophobicity-based artificial neural network (ANN-Hydro) to predict immunogenic epitopes. The immunogenicity model was validated in a blinded in vivo overlapping epitope discovery study of 364 peptides from three HIV-1 Gag protein variants. Applying the ANN-Hydro model on existing peptide-MHC algorithms consistently reduced the number of candidate peptides across multiple antigens and may provide a correlate with immunodominance. Hydrophobicity of TCR contact residues is a hallmark of immunogenic epitopes and marks a step toward eliminating the need for empirical epitope testing for vaccine development.
Genetic diversity of Propionibacterium acnes strains isolated from human skin in Japan and comparison with their distribution in Europe (2012)

Propionibacterium acnes, a commensal of human skin, is also an opportunistic pathogen of common acne and certain infectious diseases. However, it is still not obvious which strain is pathogenic for a certain infectious disease, and investigations to characterize pathogenic strains using molecular typing methods such as MLST using several housekeeping genes have been undertaken. However, to date, such analysis has focused mainly on strains isolated from Europeans, and it is unclear whether the clonal distribution in other parts of the world is similar. Here, we analysed 50 strains of P. acnes from healthy humans and patients with atopic dermatitis (AD) in Japan and utilized MLST of seven housekeeping genes to study their clonal patterns. The MLST successfully typed the strains into five types, IA, IB1, IB2, II and III. Strains that belonged to types IA, IB and II were common on the human skin of both populations (Europe and Japan), but this study demonstrated what we believe to be the first association of type III strains with human skin, existing on the skin of both the AD and non-AD population. These results indicate the global existence of type III strains on human skin.
Dominant Cytotoxic T Lymphocyte Response to the Immediate‐EarlyTrans‐ Activator Protein, BZLF1, in Persistent Type A or B Epstein‐Barr Virus Infection (1997)

Five healthy human leukocyte antigen-B8 (HLA-B8)-positive virus carriers were studied to investigate the CD8+ cytotoxic T lymphocyte (CTL) response to an HLA-B8-restricted peptide, RAKFKQLLQ, located in the Epstein-Barr virus (EBV) immediate-early trans-activator protein, BZLF1. Of the 5 virus carriers, 4 were infected with type A and 1 with type B EBV. Using limiting-dilution analysis of peripheral blood mononuclear cells, a high RAKFKQLLQ-specific CTL precursor frequency was demonstrated after specific peptide or autologous lymphoblastoid cell line stimulation in both type A and type B EBV carriers. The RAKFKQLLQ-specific CTL precursor frequencies in all 5 persons were at least as dominant as those observed with two other EBV-associated, HLA-B8-restricted latent epitopes, FLRGRAYGL and QAKWRLQTL. These findings show that healthy virus carriers maintain a high frequency of BZLF1-specific memory T cells, potentially to control virus spread from lytically infected cells.
Enhanced high density oligonucleotide array-based sequence analysis using modified nucleoside triphosphates (1998)

Pairs of high density oligonucleotide arrays (DNA chips) consisting of >96 000 oligonucleotides were designed to screen the entire 5.53 kb coding region of the hereditary breast and ovarian cancer BRCA1 gene for all possible sequence changes in the homozygous and heterozygous states. Single-stranded RNA targets were generated by PCR amplification of individual BRCA1 exons using primers containing T3 and T7RNA polymerase promoter tails followed by in vitro transcription and partial fragmentation reactions. Fluorescent hybridization signals from targets containing the four natural bases to >5592 different fully complementary 25mer oligonucleotide probes on the chip varied over two orders of magnitude. To examine the thermodynamic contribution of rU.dA and rA.dT target.probe base pairs to this variability, modified uridine [5-methyluridine and 5-(1-propynyl)-uridine)] and modified adenosine (2,6-diaminopurine riboside) 5'-triphosphates were incorporated into BRCA1 targets. Hybridization specificity was assessed based upon hybridization signals from >33 200 probes containing centrally localized single base pair mismatches relative to target sequence. Targets containing 5-methyluridine displayed promising localized enhancements in hybridization signal, especially in pyrimidine-rich target tracts, while maintaining single nucleotide mismatch hybridization specificities comparable with those of unmodified targets.
A Maximized Sequential Probability Ratio Test for Drug and Vaccine Safety Surveillance (2011)

Because of rare but serious adverse events, pharmaceutical drugs and vaccines are sometimes withdrawn from the market, either by a government agency such as the Food and Drug Administration (FDA) in the United States or by the manufacturing pharmaceutical company. In other cases, a drug may be generally safe but increase the risk for serious adverse events for certain subpopulations such as pregnant women or people with heart problems. Due to limited sample size and selected study populations, rare adverse events are often impossible to detect during phase 3 trials conducted before the drug is approved for general use. It is then important to conduct post-approval drug safety surveillance, using, for example, health insurance claims data. In such surveillance, the goal should be to detect serious adverse events as early as possible without too many false alarms, and it is then natural to use a continuous or near-continuous sequential test procedure that reevaluates the data on a daily or weekly basis.
Absorption of beta‐adrenoceptor antagonists to Amberlite resin. (1983)

The adsorption of beta-adrenoceptor blockers and the partial beta-adrenoceptor agonist prenalterol was studied in an in vitro haemoperfusion (HP) model. Metoprolol, alprenolol, propranolol and prenalterol adsorb well from the blood to the resin with extraction ratios nearing 1.0. Extraction ratio for practolol was 0.68 and for atenolol 0.49. Protein binding has little effect on the degree of adsorption, which is more dependent on water solubility.
Nutrition management in acute renal failure. (1993)

A case report is presented in which a man developed acute renal failure after a surgical misadventure. The initial management, postoperative course with the manifestation of acute tubular necrosis with oliguria and its physiological sequelae, nutrition management in the context of the overall treatment, hospital course, and patient's disease are discussed in detail. The rationale for giving nutrition support, the general considerations for providing nutrients, and the specific nutrition considerations as they pertain to the patient under discussion are outlined to provide a comprehensive guide and overview of the nutrition management of a patient with acute renal failure.
Specific Binding of Glucose-derivatized Polymers to the Asialoglycoprotein Receptor of Mouse Primary Hepatocytes (2001)

In this study, we designed a novel amphiphilic poly-(p-N-vinylbenzyl-D-glucuronamide) (PV6Gna) modified at the 6-OH position of glucose for hepatocyte recognition to address the mechanism of the interaction between mouse primary hepatocytes and the PV6Gna. PV6Gna bound to lectins specific for glucose but not galactose as did other glucose-derivatized polymers. However, hepatocyte adhesion onto the PV6Gna surface was inhibited in the presence of galactose and its analogues but not in the presence of glucose and its analogues. We also showed that hepatocyte adhesion to the PV6Gna surface was inhibited dose dependently by asialofetuin (ASF). Interactions between soluble PV6Gna and hepatocytes were inhibited by GalNAc, ASF, and EGTA in flow cytometry analysis using fluorescein isothiocyanate-conjugated PV6Gna. Hepatocyte adhesion to the PV6Gna surface was inhibited more effectively by GalNAc than by methyl beta-D-galactose. In flow cytometry analysis and cell adhesion assay, ASF competed for the inhibition of interaction between PV6Gna and hepatocytes 0.5-4 x 10(5)-fold more effectively than did GalNAc. These results demonstrate involvement of asialoglycoprotein receptors (ASGPRs) in the interaction between PV6Gna and hepatocytes. Furthermore, to clarify the mechanism of the interaction between glycopolymers modified at the 6-OH position of glucose and the hepatocyte, we prepared a gel particle containing 6-O-methacryloyl-d-glucose (PMglc) synthesized by an enzymatic method. ASGPRs could be detected using Western blot analysis following precipitation with PMglc in hepatocyte cell lysate. The precipitation of ASGPRs was inhibited in the presence of galactose, ASF, PV6Gna, and EGTA. The precipitation was inhibited more effectively by GalNAc than by methyl beta-d-galactose. ASGPRs were rarely precipitated by PMglc in the cell lysate that had been treated with ASF-conjugated Sepharose. Taken together, we suggest that mouse primary hepatocytes adhere to the PV6Gna surface mediated by ASGPRs, which specifically interacted with the glycopolymers modified at the C-6 position of glucose.
Recognition Memory for Faces by Retardates and Normals (1972)

Sequences of 10 faces and also sequences of 10 half faces were shown to adolescent familial retardates and normal Ss of equal MA. Recognition memory was tested by asking S to discriminate the 10 stimuli that had been seen from 10 distractors. The retardates' performance was equal to that of the normals when whole faces were to be remembered but the normals were superior when half faces were employed. The results suggest that the symmetry of the human face may provide redundancy which aids the retardates' performance.
Hardware Support for Cost-Effective System-Level Protection in Multi-core SoCs (2015)

The increasing adoption of multi-core Systems-on-Chip (SoC) in critical systems has turned security into an important design requirement. In addition to making a SoC tamper-resistant by embedding cryptographic solutions, in order to make a system robust, we need to control the level of access to the critical functions and capabilities. We propose a hardware protection architecture to enhance a traditional SoC platform in terms of protection. These hardware enhancements focus on isolating physical memory compartments by applying access rules, thus we allow dynamic security policies to be enforced at the hardware for protection against untrustworthy hardware or software components. We present and analyze an implementation of a prototype that allows sixteen concurrently active protection domains at a system cost of less that three percent and negligible operational overhead.
Effects of Recombinant Human Thrombopoietin Alone and in Combination with Erythropoietin and Early‐Acting Cytokines on Human Mobilized Purified CD34 + Progenitor Cells Cultured in Serum‐Depleted Medium (1997)

The effects of recombinant thrombopoietin (TPO) alone and in combination with erythropoietin (EPO) and early-acting cytokines such as interleukin 3 (IL-3), stem cell factor (SCF) and GM-CSF on highly purified mobilized human CD34+ progenitor cells were studied in a serum-depleted culture system. Eight leukapheresis samples were cultured for seven days and analyzed; aliquots were replated and re-evaluated on day 12. Three-color flow cytometry was used together with morphologic analysis to determine proliferation and megakaryocytic or erythroid maturation. TPO alone was sufficient for cell survival and proliferation in serum-depleted medium. In the absence of other growth factors, almost all CD34+ cells differentiated along the megakaryocytic pathway within 12 days. Concomitantly, the progenitor cells gradually acquired the morphologic features of mature megakaryocytes. After exposure to TPO for one week, 50% of the cells still expressed CD34; by day 12 the remaining CD34+ cells (11%) were all coexpressing CD41. TPO alone did not support proliferation of glycophorin-A-positive cells. The addition of TPO to early-acting cytokines (EPO, GM-CSF, SCF and/or IL-3) not only increased the overall megakaryocyte expansion, but also generated a different maturation pattern of the CD41+ megakaryocyte progenitors. It further doubled the number of erythroid cells and c-kit+ cells in the second week of culture. Interestingly, the overall number of CD34+ cells was increased about fivefold when TPO was added to the early-acting cytokines, with a marked expansion of the CD34+/CD41+ and CD34+/CD117+ subpopulations. TPO can augment the pool of committed progenitors, thereby increasing the number of its own target cells and the number of EPO-responsive cells. These properties make TPO an interesting cytokine for the ex vivo expansion of human progenitor cells.
Morphological and Biochemical Analyses of Amyloid Plaque Core Proteins Purified from Alzheimer Disease Brain Tissue (1993)

Amyloid plaque cores were purified from Alzheimer disease brain tissue. Plaque core proteins were solubilized in formic acid which upon dialysis against guanidinium hydrochloride (GuHCl) partitioned into soluble (approximately 15%) and insoluble (approximately 85%) components. The GuHCl-soluble fraction contained beta-amyloid1-40, whereas the GuHCl-insoluble fraction was fractionated into six components by size exclusion HPLC: S1 (> 200 kDa), S2 (200 kDa), S3 (45 kDa), S4 (15 kDa), S5 (10 kDa), and S6 (5 kDa). Removal of the GuHCl reconstituted 10-nm filaments composed of two intertwined 5-nm strands. Fractions S5 and S6 also yielded filamentous structures when treated similarly, whereas fractions S1-S4 yielded amorphous aggregates. Chemical analysis identified S4-S6 as multimeric and monomeric beta-amyloid. Immunochemical analyses revealed alpha 1-antichymotrypsin and non-beta-amyloid segments of the beta-amyloid precursor protein within fractions S1 and S2. Several saccharide components were identified within plaque core protein preparations by fluorescence and electron microscopy, as seen with fluorescein isothiocyanate- and colloidal gold-conjugated lectins. We have shown previously that this plaque core protein complex is more toxic to neuronal cultures than beta-amyloid. The non-beta-amyloid components likely mediate this additional toxicity, imposing a significant influence on the pathophysiology of Alzheimer disease.
Protective Role of Beta Interferon in Host Defense against Influenza A Virus (2006)

Type I interferon (IFN), which includes the IFN-alpha and -beta subtypes, plays an essential role in host defense against influenza A virus. However, the relative contribution of IFN-beta remains unresolved. In mice, type I IFN is effective against influenza viruses only if the IFN-induced resistance factor Mx1 is present, though most inbred mouse strains, including the recently developed IFN-beta-deficient mice, bear only defective Mx1 alleles. We therefore generated IFN-beta-deficient mice carrying functional Mx1 alleles (designated Mx-BKO) and compared them to either wild-type mice bearing functional copies of both IFN-beta and Mx1 (designated Mx-wt) or mice carrying functional Mx1 alleles but lacking functional type I IFN receptors (designated Mx-IFNAR). Influenza A virus strain SC35M (H7N7) grew to high titers and readily formed plaques in monolayers of Mx-BKO and Mx-IFNAR embryo fibroblasts which showed no spontaneous expression of Mx1. In contrast, Mx-wt embryo fibroblasts were found to constitutively express Mx1, most likely explaining why SC35M did not grow to high titers and formed no visible plaques in such cells. In vivo challenge experiments in which SC35M was applied via the intranasal route showed that the 50% lethal dose was about 20-fold lower in Mx-BKO mice than in Mx-wt mice and that virus titers in the lungs were increased in Mx-BKO mice. The resistance of Mx-BKO mice to influenza A virus strain PR/8/34 (H1N1) was also substantially reduced, demonstrating that IFN-beta plays an important role in the defense against influenza A virus that cannot be compensated for by IFN-alpha.
A Unifying Nitrososynthase Involved in Nitrosugar Biosynthesis (2008)

Herein we describe the cloning, functional expression and initial characterization of ORF36 from Micromonospora carbonacae var. africana and rubN8 from Streptomyces achromogenes var. rubradiris. The purified enzymes play the same role, the double-oxidation of TDP-evernosamine to TDP-evernitrosose in the everninomycin and rubradirin pathways, respectively.
Nucleotide sequence of region preceding trp mRNA initiation site and its role in promoter and operator function. (1976)

The nucleotide sequence of the region preceding the transcription initiation site of the tryptophan operon of Escherichia coli was determined. Essentially all of the trp operator precedes the transcribed portion of the operon. The deduced sequence contains the recognition site of endonuclease Hpa I. This site is protected from Hpa I cleavage by RNA polymerase and by trp repressor. Regions of 2-fold symmetry are present in the DNA sequence.
Studies on the Syntheses of Heterocyclic Compounds. CLIX. The Reaction of 2-Nitro-1-indanone Oxime with Formalin and Hydrochloric Acid (1966)

Attempted deoximation of 2-nitro-1-indanone oxime (I) with formalin and hydrochloric acid in acetone gave unexpected compounds, namely, 2-hydroxymethyl-2-nitro-1-indanone oxime (IV), 2-hydroxymethyl-2-nitro-1-indanone (V), and 2-nitro-1-indanone (VI).