gebhart/patrepeval huggingface dataset:
Ligation of intestinal epithelial CD1d induces bioactive IL-10: Critical role of the cytoplasmic tail in autocrine signaling (1999)

The intestinal epithelium is anatomically positioned to serve as the critical interface between the lumen and the mucosal immune system. In addition to MHC class I and II antigens, intestinal epithelia constitutively express the nonclassical MHC molecule CD1d, a transmembrane molecule with a short cytoplasmic tail expressed as a beta(2)-microglobulin-associated 48-kDa glycoprotein and novel beta(2)-microglobulin-independent 37-kDa nonglycosylated protein on intestinal epithelia. At present, it is not known whether extracellular ligands can signal intestinal epithelial CD1d. To define signaling of CD1d cytoplasmic tail, retrovirus-mediated gene transfer was used to generate stable cell lines expressing wild-type CD1d or a chimeric molecule (extracellular CD1d and cytoplasmic CD1a), and surface CD1d was triggered by antibody crosslinking. Although wild-type CD1d was readily activated (tyrosine phosphorylation), no demonstrable signal was evident in cell lines expressing the chimeric molecule. Subsequent studies revealed that anti-CD1d crosslinking specifically induces epithelial IL-10 mRNA and protein and is blocked by the tyrosine kinase inhibitor genistein. Further studies addressing epithelial-derived IL-10 revealed that anti-CD1d crosslinking attenuates IFN-gamma signaling and that such attenuation is reversed by addition of functionally inhibitory IL-10 antibodies. These results define signaling through surface CD1d, and, importantly, they demonstrate that this pathway may serve to dampen epithelial proinflammatory signals.
Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities (2019)

Microglia are the resident macrophages of the central nervous system. They play key roles in brain development, and physiology during life and aging. Equipped with a variety of molecular sensors and through the various functions they can fulfill, they are critically involved in maintaining the brain's homeostasis. In Alzheimer disease (AD), microglia reaction was initially thought to be incidental and triggered by amyloid deposits and dystrophic neurites. However, recent genome-wide association studies have established that the majority of AD risk loci are found in or near genes that are highly and sometimes uniquely expressed in microglia. This leads to the concept of microglia being critically involved in the early steps of the disease and identified them as important potential therapeutic targets. Whether microglia reaction is beneficial, detrimental or both to AD progression is still unclear and the subject of intense debate. In this review, we are presenting a state-of-knowledge report intended to highlight the variety of microglial functions and pathways shown to be critically involved in AD progression. We first address both the acquisition of new functions and the alteration of their homeostatic roles by reactive microglia. Second, we propose a summary of new important parameters currently emerging in the field that need to be considered to identify relevant microglial targets. Finally, we discuss the many obstacles in designing efficient therapeutic strategies for AD and present innovative technologies that may foster our understanding of microglia roles in the pathology. Ultimately, this work aims to fly over various microglial functions to make a general and reliable report of the current knowledge regarding microglia's involvement in AD and of the new research opportunities in the field.
Statistical interpolation methods (2010)

Statistical methods of interpolation are all based on assuming that the process being reconstructed (for the purpose of this report, a temperature field in space or time or both) can be modeled as a random process. The best-known examples occur in spatial statistics, including the technique widely known as kriging, and in time series analysis. The process may depend on unknown parameters, which have to be estimated as part of the interpolation procedure. Once the process is specified, including any estimated parameters, optimal interpolators are calculated either by finding the best linear interpolator (the linear combination of known observations that minimizes the mean squared prediction error) or by computing a given function of the conditional probability distribution of the predicted quantity conditional observations. That function can be determined by appealing to statistical decision theory.
A Replication-Competent, Neuronal Spread-Defective, Live Attenuated Herpes Simplex Virus Type 1 Vaccine (2008)

Herpes simplex virus type 1 (HSV-1) produces oral lesions, encephalitis, keratitis, and severe infections in the immunocompromised host. HSV-1 is almost as common as HSV-2 in causing first episodes of genital herpes, a disease that is associated with an increased risk of human immunodeficiency virus acquisition and transmission. No approved vaccines are currently available to protect against HSV-1 or HSV-2 infection. We developed a novel HSV vaccine strategy that uses a replication-competent strain of HSV-1, NS-gEnull, which has a defect in anterograde and retrograde directional spread and cell-to-cell spread. Following scratch inoculation on the mouse flank, NS-gEnull replicated at the site of inoculation without causing disease. Importantly, the vaccine strain was not isolated from dorsal root ganglia (DRG). We used the flank model to challenge vaccinated mice and demonstrated that NS-gEnull was highly protective against wild-type HSV-1. The challenge virus replicated to low titers at the site of inoculation; therefore, the vaccine strain did not provide sterilizing immunity. Nevertheless, challenge by HSV-1 or HSV-2 resulted in less-severe disease at the inoculation site, and vaccinated mice were totally protected against zosteriform disease and death. After HSV-1 challenge, latent virus was recovered by DRG explant cocultures from <10% of vaccinated mice compared with 100% of mock-vaccinated mice. The vaccine provided protection against disease and death after intravaginal challenge and markedly lowered the titers of the challenge virus in the vagina. Therefore, the HSV-1 gEnull strain is an excellent candidate for further vaccine development.
Inhibition of Experimental Periodontitis by a Topical Boron-based Antimicrobial (2008)

AN0128 is a boron-containing compound with antibacterial and anti-inflammatory properties. To test its potential effectiveness in treating periodontal disease, we induced experimental periodontitis in the rat by placing ligatures and assessed the impact of AN0128 and positive and negative controls by micro-CT and histologic measurements. The formation of an inflammatory infiltrate was measured in hematoxylin-and-eosin-stained sections. Daily application of AN0128 (1%) compared with controls reduced bone loss by 38 to 44% (P < 0.05), while vehicle alone had no effect (P > 0.05). The reduction in bone loss with AN0128 was similar to that achieved with a NSAID, ketorolac, and Total toothpaste containing triclosan. AN0128 also reduced the level of gingival inflammation 42% compared with the ligature only (P < 0.05), whereas vehicle alone had no effect (P > 0.05). The results indicate that AN0128 significantly reduces the formation of an inflammatory infiltrate and reduces bone loss, measured histologically and by micro-CT.
A new definition of neuropathic pain (2011)

Jensen, Troels S.*,1; Baron, Ralf2; Haanpää, Maija3; Kalso, Eija4; Loeser, John D.5; Rice, Andrew S.C.6; Treede, Rolf-Detlef7 Author Information
Enzymes that process somatostatin precursors. A novel endoprotease that cleaves before the arginine-lysine doublet is involved in somatostatin-28 convertase activity of rat brain cortex. (1987)

The selective processing activity which generates both the NH2- and COOH-terminal fragments of the octacosapeptide somatostatin-28 (S-28) was investigated. Separation into two distinct proteolytic activities was achieved by ion-exchange chromatography. An endoprotease cleaving either the substrate Pro-Arg-Glu-Arg-Lys-Ala-Gly-Ala-Lys-Asn-Tyr-NH2, i.e. [Ala17,Tyr20]S-28-(10-20)-NH2 (peptide I), or the octacosapeptide somatostatin-28, on the NH2 side of the Arg-Lys doublet was separated from an aminopeptidase B-like activity. Whereas the endoprotease cleaves a single peptide bond, between Glu12 and Arg13 of S-28, the aminopeptidase B-like enzyme removes both Arg13 and Lys14 stepwise from the NH2 terminus of the corresponding COOH-terminal fragment. This endoprotease activity peaks around pH 8.5, whereas the optimal aminopeptidase B-like activity is in the pH range 6.2-8.5. Combination of both enzymes resulted in the recovery of the overall S-28 convertase activity with an optimal pH at 7. In addition, this endoprotease appears to be very sensitive to divalent cations since it is strongly inhibited by chelating agents. The use of selectively modified undecapeptides derived from the reference substrate peptide I by a single modification of the amino acids Glu12, Arg13, and Lys14 at the cleavage locus showed that both basic residues are critically important, whereas Glu12 is not. It is proposed that S-28 processing involves a divalent cation-sensitive endoprotease that is sensitive to thiol reagents, which cleaves before the Arg-Lys doublet, which is not trypsin-like, and whose action is coupled to an aminopeptidase B-like enzyme.
Protein kinase Cδ and c‐Abl kinase are required for transforming growth factor β induction of endothelial–mesenchymal transition in vitro (2011)

These results indicate that c-Abl and PKCδ are crucial for TGFβ-induced EndoMT and that imatinib mesylate and rottlerin or similar kinase inhibitor molecules may be effective therapeutic agents for SSc and other fibroproliferative vasculopathies in which EndoMT plays a pathogenetic role.
A multi-stage image charge detector made from printed circuit boards (2013)

We present the first reported instance of an image-charge detector for charged particles in which detection elements are patterned onto printed circuit boards. In contrast to conventional techniques involving separately machined and positioned segments of metal tubing, this technique is much simpler to assemble, align, and connect to electrical wiring, with no loss in sensitivity. The performance of single-stage and 5-stage charge detectors is demonstrated using electrospray-charged, micrometer-size polystyrene spheres. Both velocity and charge of each particle are measured. Multiple detection stages--which require no extra effort to pattern or setup compared with a single stage--result in an ensemble averaging effect, improving the detection limit over what can be achieved with a single-stage detector. A comparison is made between the printed circuit board detector and a conventional tubular charge detector and found to be statistically equivalent. These results demonstrate and illustrate that devices for detection, analysis, and/or manipulation of charged particles and ions can be made using printed circuit boards rather than using separately fabricated metal electrodes.
Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth (2015)

In this single-center case series involving young patients with relapsed or refractory cancer, incorporation of integrative clinical sequencing data into clinical management was feasible, revealed potentially actionable findings in 46% of patients, and was associated with change in treatment and family genetic counseling for a small proportion of patients. The lack of a control group limited assessing whether better clinical outcomes resulted from this approach than outcomes that would have occurred with standard care.
Extraction of choriocapillaris hemodynamic data from ICG fluorescence angiograms. (1993)

It is possible to extract information related to choriocapillaris blood flow from high-speed ICG angiograms when a fairly well-defined dye bolus wavefront is present. Interpretation of the results suggests that the choriocapillaris lobules fill in a pulsatile manner, out of phase with each other, and may act thereby to dissipate the blood volume entering the choroid during each cardiac cycle in such a way that the retinal macular is not significantly displaced by expansion of the choroidal vascular volume. Depending upon the distribution of pressure gradients across a group of lobules, blood may flow from one lobule into or even through an adjacent one.
Pulmonary diffusing capacities for nitric oxide and carbon monoxide determined by rebreathing in dogs (1990)

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ("normoxia," PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.
Estimation of Gadolinium-induced T1-shortening with Measurement of Simple Signal Intensity Ratio between the Cochlea and Brain Parenchyma on 3D-FLAIR: Correlation with T1 Measurement by TI Scout Sequence (2010)

Measurement of the simple signal intensity ratio between the cochlea and the medulla can be used for semi-quantitative analysis of 3D-FLAIR. The results of this study may facilitate clinical research of inner-ear disease using 3D-FLAIR.
Model-based classification of nonstationary vocal fold vibrations (2006)

Classification of vocal fold vibrations is an essential task of the objective assessment of voice disorders. For historical reasons, the conventional clinical examination of vocal fold vibrations is done during stationary, sustained phonation. However, the conclusions drawn from a stationary phonation are restricted to the observed steady-state vocal fold vibrations and cannot be generalized to voice mechanisms during running speech. This study addresses the approach of classifying real-time recordings of vocal fold oscillations during a nonstationary phonation paradigm in the form of a pitch raise. The classification is based on asymmetry measures derived from a time-dependent biomechanical two-mass model of the vocal folds which is adapted to observed vocal fold motion curves with an optimization procedure. After verification of the algorithm performance the method was applied to clinical problems. Recordings of ten subjects with normal voice and ten dysphonic subjects have been evaluated during stationary as well as nonstationary phonation. In the case of nonstationary phonation the model-based classification into "normal" and "dysphonic" succeeds in all cases, while it fails in the case of sustained phonation. The nonstationary vocal fold vibrations contain additional information about vocal fold irregularities, which are needed for an objective interpretation and classification of voice disorders.
Is the Increase in Serum Cystathionine Levels in Patients with Liver Cirrhosis a Consequence of Impaired Homocysteine Transsulfuration at the Level of ?-Cystathionase? (2000)

Our data provides indirect evidence for two hitherto unrecognized alterations of methionine metabolism in cirrhotics, i.e. impairment of the transsulfuration of homocysteine at the level of cystathionine degradation and a shift in remethylation of homocysteine towards the betaine-homocysteine-methyltransferase reaction.
A human monoclonal antibody specific for the N terminus of the hepatitis C virus nucleocapsid protein. (1993)

PBMC from a patient with chronic hepatitis C virus (HCV) infection were immortalized with EBV and plated by limiting dilution. Cultures secreting antibodies reactive in a commercial HCV II generation ELISA, which incorporates Ag derived from the nucleocapsid, NS3, and NS4 regions, were repeatedly cloned in the presence of feeder cells and growth factors. Of 23 initially immunoreactive cultures, only one cloned line, designated B12.F8, secreted HCV nucleoprotein-specific IgG1(kappa), whereas no reaction with recombinant polypeptides derived from NS3, NS4, and NS5 regions were documented. Human mAb (hmAb) B12.F8 was shown to recognize the native HCV nucleoprotein expressed in eukaryotic cells transfected with a core cDNA construct by immunofluorescence. The fine specificity of this hmAb was evaluated using synthetic oligopeptides covering the entire HCV nucleocapsid region. A weak but consistent reactivity was observed by PEPSCAN using a 12-mer encompassing residues 34-45 of the HCV-deduced amino acid sequence. Such weak reactivity is indicative for conformational epitopes and, in concurrence with this assumption, we found that longer peptides from the region containing residues 27-59 were more efficiently recognized and effectively inhibited binding of hmAb B12.F8 to recombinant nucleocapsid protein. Several overlapping immunoreactive fragments from the nucleocapsid region were selected from a random cDNA library consisting of DNase I fragments of recombinant core Ag. Best reactive recombinants were identified within residues 1-78 of the HCV sequence, in agreement with the results obtained using synthetic peptides. Comparative experiments on the fine specificity of sera from HCV-infected patients with anticore antibodies invariably showed recognition of peptides 8-40 and 27-59, as well as recombinant fragments spanning from residues 1 to 73, suggesting that hmAb B12.F8 identifies a major B cell epitope within the immunodominant nucleoprotein amino terminal subregion.
Lack of Behavioral Effects in Non-Human Primates after Exposure to Ultrawideband Electromagnetic Radiation in the Microwave Frequency Range (1995)

The effect of acute exposure to ultrawideband (UWB) electromagnetic radiation on the Primate Equilibrium Platform (PEP) task, where the monkey's task is to manipulate a joystick control to compensate for the random perturbations in the pitch plane that are generated by a computer at unpredictable intervals, was examined. The duration of the UWB exposure was 2 min at a pulse repetition rate of 60 Hz (total of 7200 pulses). The bandwidth of the pulse was 100 MHz to 1.5 GHz (peak power between 250-500 MHz) with a peak E-field strength of 250 kV/m. Each monkey was exposed twice. The interval between exposures was 6 days. The exposure to UWB electromagnetic radiation had no effect on PEP performance when tested immediately after exposure.
Reproducible and inexpensive probe preparation for oligonucleotide arrays (2001)

We present a new protocol for the preparation of nucleic acids for microarray hybridization. DNA is fragmented quantitatively and reproducibly by using a hydroxyl radical-based reaction, which is initiated by hydrogen peroxide, iron(II)-EDTA and ascorbic acid. Following fragmentation, the nucleic acid fragments are densely biotinylated using a biotinylated psoralen analog plus UVA light and hybridized on microarrays. This non-enzymatic protocol circumvents several practical difficulties associated with DNA preparation for microarrays: the lack of reproducible fragmentation patterns associated with enzymatic methods; the large amount of labeled nucleic acids required by some array designs, which is often combined with a limited amount of starting material; and the high cost associated with currently used biotinylation methods. The method is applicable to any form of nucleic acid, but is particularly useful when applying double-stranded DNA on oligonucleotide arrays. Validation of this protocol is demonstrated by hybridizing PCR products with oligonucleotide-coated microspheres and PCR amplified cDNA with Affymetrix Cancer GeneChip microarrays.
Electroporation of the heart (2005)

Defibrillation shocks are commonly used to terminate life-threatening arrhythmias. According to the excitation theory of defibrillation, such shocks are aimed at depolarizing the membranes of most cardiac cells resulting in resynchronization of electrical activity in the heart. If shock-induced changes in transmembrane potential are large enough, they can cause transient tissue damage due to electroporation. In this review evidence is presented that (a) electroporation of the heart tissue can occur during clinically relevant intensities of the external electrical field, and (b) electroporation can affect the outcome of defibrillation therapy; being both pro- and anti-arrhythmic.
Evolution of legume seed storage proteins--a domain common to legumins and vicilins is duplicated in vicilins. (1989)

We examined the primary sequence of canavalin, the major storage protein of jack beans, and found that an ancient sequence duplication accounts for 80% of the amino acid residues. Evidence for such a duplication was also found in the orthologous proteins phaseolin and pea vicilin. This sequence duplication presumably accounts for a structural duplication in the canavalin monomer observed by crystallographic analysis. One copy of this repeat was found in a second storage-protein family, the legumins, where it encompasses almost the entire B-chain of the mature molecule. We propose that the vicilin and legumin families of legume seed proteins evolved from a common precursor, which consisted of one copy of the repeat in the vicilins.
Experimental investigation of the polarization properties of a hollow core photonic bandgap fiber for 1550 nm (2005)

The properties of a hollow core photonic bandgap fiber designed for 1.55 um transmission are investigated with special emphasis on polarization issues. Large and strongly wavelength dependent phase and group delays are found. At the same time the principle states of polarization move strongly and erratically as a function of wavelength, leading to strong mode coupling. Wavelength regions with high polarization dependent loss coincide with depolarization due to a polarization dependent coupling to surface modes at these wavelengths.
The use of phrases and structured queries in information retrieval (1991)

Both phrases and Boolean queries have a long history in information retrieval, particularly in commercial systems. In previous work, Boolean queries have been used as a source of phrases for a statistical retrieval model, This work, like the majority of research on phrases, resulted in little improvement in retrieval effectiveness, In this paper, we describe an approach where phrases identified in natural language queries are used to build structured queries for a probabilistic retrieval model. Our results show that using phrases in this way can improve performance, and that phrases that are automatically extracted from a natural language query perform nearly as well as manually selected phrases.