gebhart/patrepeval huggingface dataset:
Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals (1994)

Antigen-driven tolerance is an effective method for suppression of autoimmune diseases. Adult animals can be tolerized against the induction of experimental autoimmune encephalomyelitis (EAE) by both oral and parenteral administration of myelin basic protein (MBP). We have found that in contrast to previous studies of neonatal tolerance in which parenterally administered autoantigens induced tolerance, the oral administration of MBP in neonatal rats did not result in tolerization to MBP, but instead, primed for immunologic responses. Proliferative responses to MBP and its encephalitogenic epitope were present in animals fed with MBP as neonates and co-culture of encephalitogenic T cells with cells from neonatal rats fed with MBP were associated with enhanced MBP responses rather than the suppression observed with cells from adult rats fed with MBP. Furthermore, neonates fed with MBP and immunized 6-8 weeks later with MBP in adjuvant to induce EAE revealed enhancement of disease severity, and were not protected from a second attack upon active reinduction of EAE. Subcutaneous injection of soluble MBP into neonates had no effect on EAE induction as adults, whereas intraperitoneal injection of MBP in neonates was associated with marked suppression of disease in adults. Suppression of EAE began to appear in animals fed with MBP at 4 weeks of age, and was similar to oral tolerance in adult animals when animals were fed at 6 weeks of age. These results suggest that immaturity of the immunoregulatory network associated with oral tolerance and sensitization to autoantigens via the gut in the neonatal period may contribute to the pathogenesis of autoimmune diseases.
Cut-wire pairs and plate pairs as magnetic atoms for optical metamaterials (2005)

We study the optical properties of metamaterials made from cut-wire pairs or plate pairs. We obtain a more pronounced optical response for arrays of plate pairs, a geometry that also eliminates the undesirable polarization anisotropy of the cut-wire pairs. The measured optical spectra agree with simulations, revealing negative magnetic permeability in the range of telecommunications wavelengths. Thus nanoscopic plate pairs might serve as an alternative to the established split-ring resonator design.
Noncontact measurement of breathing function (2006)

This paper aims to open a new line of research by demonstrating the feasibility of monitoring breathing function in a highly automated and noncontact fashion. The method is based on the statistical modeling of dynamic thermal data captured through a highly sensitive infrared imaging system. This method achieved an accuracy of 96.43% on a small set of subjects during rest and after brief exercise. It has the potential to provide a unique capability for sustained monitoring of chronic or acute breathing problems and in sleep studies by overcoming the deficiencies of the existing measurement modalities. The method also opens the way for the next generation contact-free polygraphy that will not affect the subject's psychophysiology.
NMR structure reveals intramolecular regulation mechanism for pheromone binding and release (2001)

Odorants are transmitted by small hydrophobic molecules that cross the aqueous sensillar lymph surrounding the dendrites of the olfactory neurons to stimulate the olfactory receptors. In insects, the transport of pheromones, which are a special class of odorants, is mediated by pheromone-binding proteins (PBPs), which occur at high concentrations in the sensillar lymph. The PBP from the silk moth Bombyx mori (BmPBP) undergoes a pH-dependent conformational transition between the forms BmPBP(A) present at pH 4.5 and BmPBP(B) present at pH 6.5. Here, we describe the NMR structure of BmPBP(A), which consists of a tightly packed arrangement of seven alpha-helices linked by well defined peptide segments and knitted together by three disulfide bridges. A scaffold of four alpha-helices that forms the ligand binding site in the crystal structure of a BmPBP-pheromone complex is preserved in BmPBP(A). The C-terminal dodecapeptide segment, which is in an extended conformation and located on the protein surface in the pheromone complex, forms a regular helix, alpha(7), which is located in the pheromone-binding site in the core of the unliganded BmPBP(A). Because investigations by others indicate that the pH value near the membrane surface is reduced with respect to the bulk sensillar lymph, the pH-dependent conformational transition of BmPBP suggests a novel physiological mechanism of intramolecular regulation of protein function, with the formation of alpha(7) triggering the release of the pheromone from BmPBP to the membrane-standing receptor.
Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity (2004)

Glycosaminoglycans have been implicated in the binding and activation of a variety of growth factors, cytokines, and chemokines. In this way, glycosaminoglycans are thought to participate in events such as development and wound repair. In particular, heparin and heparan sulfate have been well studied, and specific aspects of their structure dictate their participation in a variety of activities. In contrast, although dermatan sulfate participates in many of the same biological processes as heparin and heparan sulfate, the interactions of dermatan sulfate have been less well studied. Dermatan sulfate is abundant in the wound environment and binds and activates growth factors such as fibroblast growth factor-2 (FGF-2) and FGF-7, which are present during the wound repair process. To determine the minimum size and sulfation content of active dermatan sulfate oligosaccharides, dermatan sulfate was first digested and then separated by size exclusion high pressure liquid chromatography, and the activity to facilitate FGF-2 and FGF-7 was assayed by the cellular proliferation of cell lines expressing FGFR1 or FGFR2 IIIb. The minimum size required for the activation of FGF-2 was an octasaccharide and for FGF-7 a decasaccharide. Active fractions were rich in monosulfated, primarily 4-O-sulfated, disaccharides and iduronic acid. Increasing the sulfation to primarily 2/4-O-sulfated and 2/6-O-sulfated disaccharides did not increase activity. Cell proliferation decreased or was abolished with higher sulfated dermatan sulfate preparations. This indicated a preference for specific dermatan sulfate oligosaccharides capable of promoting FGF-2- and FGF-7-dependent cell proliferation. These data identify critical oligosaccharides that promote specific members of the FGF family that are important for wound repair and angiogenesis.
Importance of the G protein γ subunit in activating G protein‐coupled inward rectifier K+ channels (1999)

The G protein-coupled inward rectifier K(+) channel (GIRK) is activated by direct interaction with the heterotrimeric GTP-binding protein betagamma subunits (Gbetagamma). However, the precise role of Gbeta and Ggamma in GIRK activation remains to be elucidated. Using transient expression of GIRK1, GIRK2, Gbeta1, and Ggamma2 in human embryonic kidney 293 cells, we show that C-terminal mutants of Gbeta1, which do not bind to Ggamma2, are still able to associate with GIRK, but these mutants are unable to induce activation of GIRK channels. In contrast, other C-terminal mutants of Gbeta1 that bind to Ggamma2, are capable of activating the GIRK channel. These results suggest that Ggamma plays a more important role than that of an anchoring device for the Gbetagamma-induced GIRK activation.
Purification and partial characterization of 3-hydroxyisobutyryl-coenzyme A hydrolase of rat liver. (1994)

An unusual feature of valine catabolism is a reaction in which an intermediate of its catabolic pathway, (S)-3-hydroxyisobutyryl-CoA, is hydrolyzed to give the free acid and CoA-SH. The enzyme responsible for this reaction, 3-hydroxyisobutyryl-CoA hydrolase (EC 3.1.2.4), was purified 7200-fold from rat liver in this study. The purified enzyme consists of a single polypeptide with an M(r) of 36,000 in the native and denatured forms. The hydrolase is highly specific for (S)-3-hydroxyisobutyryl-CoA and 3-hydroxypropionyl-CoA (Km, 6 and 25 microM, respectively) with optimal activity around pH 8. The turnover rate of the enzyme for (S)-3-hydroxyisobutyryl-CoA is 270 s-1, which is high relative to other enzymes of the valine pathway. Likewise, activity of the enzyme expressed on a wet weight basis is also very high in the major tissues of the rat. These findings suggest that rapid destruction of (S)-3-hydroxyisobutyryl-CoA produced during valine catabolism is physiologically important. We propose that the need for a mechanism to protect cells against the toxic effects of methacrylyl-CoA, which is maintained in equilibrium with (S)-3-hydroxyisobutyryl-CoA by crotonase, explains why valine catabolism involves this enzyme and why its tissue activity is so high.
A Preliminary Study of Intravenous Surfactants in Paraplegic Dogs: Polymer Therapy in Canine Clinical SCI (2004)

Hydrophilic polymers, both surfactants and triblock polymers, are known to seal defects in cell membranes. In previous experiments using laboratory animals, we have exploited this capability using polyethylene glycol (PEG) to repair spinal axons after severe, standardized spinal cord injury (SCI) in guinea pigs. Similar studies were conducted using a related co-polymer Poloxamer 188 (P 188). Here we carried out initial investigations of an intravenous application of PEG or P 188 (3500 Daltons, 30% w/w in saline; 2 mL/kg I.V. and 2 mL/kg body weight or 300 mL P 188 per kg, respectively) to neurologically complete cases of paraplegia in dogs. Our aim was to first determine if this is a clinically safe procedure in cases of severe naturally occurring SCI in dogs. Secondarily, we wanted to obtain preliminary evidence if this therapy could be of clinical benefit when compared to a larger number of similar, but historical, control cases. Strict entry criteria permitted recruitment of only neurologically complete paraplegic dogs into this study. Animals were treated by a combination of conventional and experimental techniques within approximately 72 h of admission for spinal trauma secondary to acute, explosive disk herniation. Outcome measures consisted of measurements of voluntary ambulation, deep and superficial pain perception, conscious proprioception in hindlimbs, and evoked potentials (somatosensory evoked potentials [SSEP]). We determined that polymer injection is a safe adjunct to the conventional management of severe neurological injury in dogs. We did not observe any unacceptable clinical response to polymer injection; there were no deaths, nor any other problem arising from, or associated with, the procedures. Outcome measures over the 6-8-week trial were improved by polymer injection when compared to historical cases. This recovery was unexpectedly rapid compared to these comparator groups. The results of this pilot trial provides evidence consistent with the notion that the injection of inorganic polymers in acute neurotrauma may be a simple and useful intervention during the acute phase of the injury.
Screening of boronic acids for strong inhibition of the hydrolytic activity of α-chymotrypsin and for sugar sensing associated with a large fluorescence change (1996)

Abstract
Optimized Assembly and Covalent Coupling of Single-Molecule DNA Origami Nanoarrays (2014)

Artificial DNA nanostructures, such as DNA origami, have great potential as templates for the bottom-up fabrication of both biological and nonbiological nanodevices at a resolution unachievable by conventional top-down approaches. However, because origami are synthesized in solution, origami-templated devices cannot easily be studied or integrated into larger on-chip architectures. Electrostatic self-assembly of origami onto lithographically defined binding sites on Si/SiO2 substrates has been achieved, but conditions for optimal assembly have not been characterized, and the method requires high Mg2+ concentrations at which most devices aggregate. We present a quantitative study of parameters affecting origami placement, reproducibly achieving single-origami binding at 94±4% of sites, with 90% of these origami having an orientation within ±10° of their target orientation. Further, we introduce two techniques for converting electrostatic DNA-surface bonds to covalent bonds, allowing origami arrays to be used under a wide variety of Mg2+-free solution conditions.
Changes in Brain Natriuretic Peptide and Norepinephrine Over Time and Mortality and Morbidity in the Valsartan Heart Failure Trial (Val-HeFT) (2003)

Not only are plasma BNP and NE important predictors of heart failure M&M, but changes in these neurohormones over time are associated with corresponding changes in M&M. These data further reinforce their role as significant surrogate markers in HF and underscore the importance of including their measurement in HF trials.
Correlation between near‐infrared Raman spectroscopy and the histopathological analysis of atherosclerosis in human coronary arteries (2002)

An algorithm using PCA and discriminant analysis based on m-distance has been developed and successfully applied to diagnose coronary artery disease by NIRS obtaining good sensitivity and specificity for each tissue category.
Biochemical and amino acid sequence analysis of human eosinophil granule major basic protein. (1988)

Eosinophil granule major basic protein (MBP) is a relatively low molecular weight cationic (pI greater than 10) protein present in the crystalloid core of the eosinophil granule. Amino acid sequence analysis of this protein was undertaken as part of an analysis of the structural basis of the potent cytotoxic activities of MBP on parasites and mammalian cells. Many conventional sequencing strategies were unworkable because of the unusual amino acid composition of MBP and its insolubility in solutions buffered at neutral pH. Less conventional chemical reactions, including cyanogen bromide-induced cleavage at tryptophan and acid-induced cleavage at aspartic acid, were used successfully to obtain peptides which allowed definition of the amino acid sequence of MBP. Characterization of MBP by reverse-phase high pressure liquid chromatography and two-dimensional gel analysis showed no microheterogeneity that might be attributed to post-translational modifications. Comparison of the MBP sequence with a protein sequence data base showed that MBP has no significant sequence homology with other characterized proteins. The basicity (pI 10.9) and hydrophobicity predicted from the MBP sequence are likely responsible for the observed affinity of this cytotoxic molecule for cell surfaces and some serum proteins.
Side Effects of Ketamine in the Long-Term Treatment of Neuropathic Pain (2008)

Ketamine is evaluated as a nonoptimal, however, available NMDA blocker suitable for clinical use. Studying its effects in clinics can be expected to increase our knowledge necessary for the development of new, effective, and safe "antineuralgic drug."
Combinatorial RNAi for quantitative protein network analysis (2007)

The elucidation of cross-talk events between intersecting signaling pathways is one main challenge in biological research. The complexity of protein networks, composed of different pathways, requires novel strategies and techniques to reveal relevant interrelations. Here, we established a combinatorial RNAi strategy for systematic single, double, and triple knockdown, and we measured the residual mRNAs and proteins quantitatively by quantitative real-time PCR and reverse-phase protein arrays, respectively, as a prerequisite for data analysis. Our results show that the parallel knockdown of at least three different genes is feasible while keeping both untargeted silencing and cytotoxicity low. The technique was validated by investigating the interplay of tyrosine kinase receptor ErbB2 and its downstream targets Akt-1 and MEK1 in cell invasion. This experimental approach combines multiple gene knockdown with a subsequent quantitative validation of reduced protein expression and is a major advancement toward the analysis of signaling pathways in systems biology.
2009년 봄철 부산지역 황사 기간 중 에어로솔 농도 분포 (2013)

동아시아 지역 봄철에 주로 발생하는 황사의 물리적 특성을 알아보기 위하여 부산지역에서 발생한 2009년 황사기간의 종관 일기도와 자동기상관측장비(AWS)를 이용한 기상해석, PM10 샘플러와 레이저입자계수기(LPC)를 이용한 대기입자상 물질농도 분석, 위성영상과 역궤적분석 모델을 이용한 발생원을 조사하였다. 2009년 2월 20일의 경우 (사례1), PM10 농도가 급격히 증가할 때 0.3-1.0 μm의 작은 입자의 에어로솔 체적 농도 분포가 감소한 반면 1.0-10.0 μm의큰 입자의 농도는 증가하였다. 그 후 PM10 농도가 감소할 때 지상의 풍향은 북풍에서 남서풍으로 변하였으며, 전체 에어로솔 농도는 감소하였다. PM10과 1.0-10.0 μm의 큰 입자 농도의 상관계수는 0.9 이상으로 높은 양의 상관관계를 나타내었다. 이는 내몽골 지역에서 발달된 황사가 중국 고비 사막을 통과하여 한반도로 유입된 것으로 추측할 수 있었다. 2009년 4월 25일의 경우 (사례 2), PM10 농도가 급격히 증가할 때 0.3-0.5 μm의 작은 입자의 에어로솔 체적 농도 분포가 감소한 반면 0.5-10.0 μm의 큰 입자의 농도는 증가하였다. 그 후 PM10 농도가 감소할 때 0.3-0.5 μm의 작은 입자의 농도는 증가한 반면 0.5-10.0 μm의 큰 입자의 농도는 감소하였다. 이 때 지상의 풍향은 북동풍에서 남서풍으로 변한 후다시 북동풍으로 변하였다. PM10과 1.0-10.0 μm의 큰 입자의 농도의 상관계수는 약 0.9에 가까운 높은 양의 상관관계를 나타내었다. 입자의 역궤적 수송 모델 분석 결과, 만주지역과 중국 동쪽 해안으로부터 한반도로 유입된 것으로 추측할수 있었다.
A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium (2000)

Type III secretion systems (TTSS) are important virulence factors that Gram-negative bacteria use to translocate proteins into the cytoplasm of eukaryotic host cells. Salmonellae encode two virulence-associated TTSS. The Salmonella pathogenicity island 1 (SPI1)-encoded TTSS is active on contact with host cells, whereas the Salmonella pathogenicity island 2 (SPI2)-encoded TTSS is expressed after phagocytosis of bacteria by host cells. Previously, no consensus signal sequence for translocation has been identified among TTSS effector proteins. In this work, seven proteins, termed Salmonella-translocated effectors (STE), are described that contain conserved amino acid sequences that direct translocation by TTSS in Salmonella typhimurium. STE that are coordinately regulated with SPI2 gene expression contain translocation signals that are recognized by the SPI2 but not by the SPI1 TTSS. STE that are constitutively expressed contain signals that direct translocation through both SPI1 and SPI2 TTSS. Of the seven STE examined, SspH1 and SspH2 have been previously shown to be translocated and involved in virulence; SlrP and SifA were identified as virulence factors, but were not previously known to be associated with TTSS; and SseI, SseJ, and SifB were previously unidentified. Three STE genes (sspH1, sspH2, and sseI) are located within temperate bacteriophages, suggesting a common mechanism for the dissemination of more recently evolved STE.
Combination of the insulin sensitizer, pioglitazone, and the long‐acting GLP‐1 human analog, liraglutide, exerts potent synergistic glucose‐lowering efficacy in severely diabetic ZDF rats (2008)

Combination therapy with insulinotropic GLP-1 agonist liraglutide and insulin sensitizer, pioglitazone, improves glycaemic control above and beyond what would be expected from additive effects of the two antidiabetic agents.
Analysis of repetitive element DNA methylation by MethyLight (2005)

Repetitive elements represent a large portion of the human genome and contain much of the CpG methylation found in normal human postnatal somatic tissues. Loss of DNA methylation in these sequences might account for most of the global hypomethylation that characterizes a large percentage of human cancers that have been studied. There is widespread interest in correlating the genomic 5-methylcytosine content with clinical outcome, dietary history, lifestyle, etc. However, a high-throughput, accurate and easily accessible technique that can be applied even to paraffin-embedded tissue DNA is not yet available. Here, we report the development of quantitative MethyLight assays to determine the levels of methylated and unmethylated repeats, namely, Alu and LINE-1 sequences and the centromeric satellite alpha (Satalpha) and juxtacentromeric satellite 2 (Sat2) DNA sequences. Methylation levels of Alu, Sat2 and LINE-1 repeats were significantly associated with global DNA methylation, as measured by high performance liquid chromatography, and the combined measurements of Alu and Sat2 methylation were highly correlative with global DNA methylation measurements. These MethyLight assays rely only on real-time PCR and provide surrogate markers for global DNA methylation analysis. We also describe a novel design strategy for the development of methylation-independent MethyLight control reactions based on Alu sequences depleted of CpG dinucleotides by evolutionary deamination on one strand. We show that one such Alu-based reaction provides a greatly improved detection of DNA for normalization in MethyLight applications and is less susceptible to normalization errors caused by cancer-associated aneuploidy and copy number changes.
Glioblastoma Proto-oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress (2009)

Glioblastoma multiforme is the most prevalent type of adult brain tumor and one of the deadliest tumors known to mankind. The genetic understanding of glioblastoma multiforme is, however, limited, and the molecular mechanisms that facilitate glioblastoma multiforme cell survival and growth within the tumor microenvironment are largely unknown. We applied digital karyotyping and single nucleotide polymorphism arrays to screen for copy-number changes in glioblastoma multiforme samples and found that the most frequently amplified region is at chromosome 7p11.2. The high resolution of digital karyotyping and single nucleotide polymorphism arrays permits the precise delineation of amplicon boundaries and has enabled identification of the minimal region of amplification at chromosome 7p11.2, which contains two genes, EGFR and SEC61gamma. SEC61gamma encodes a subunit of a heterotrimeric protein channel located in the endoplasmic reticulum (ER). In addition to its high frequency of gene amplification in glioblastoma multiforme, SEC61gamma is also remarkably overexpressed in 77% of glioblastoma multiforme but not in lower-grade gliomas. The small interfering RNA-mediated knockdown of SEC61gamma expression in tumor cells led to growth suppression and apoptosis. Furthermore, we showed that pharmacologic ER stress agents induce SEC61gamma expression in glioblastoma multiforme cells. Together, these results indicate that aberrant expression of SEC61gamma serves significant roles in glioblastoma multiforme cell survival likely via a mechanism that is involved in the cytoprotective ER stress-adaptive response to the tumor microenvironment.
L-Sorbose metabolism in Klebsiella pneumoniae and Sor+ derivatives of Escherichia coli K-12 and chemotaxis toward sorbose (1984)

L-Sorbose degradation in Klebsiella pneumoniae was shown to follow the pathway L-sorbose leads to L-sorbose-1-phosphate leads to D-glucitol-6-phosphate leads to D-fructose-6-phosphate. Transport and phosphorylation of L-sorbose was catalyzed by membrane-bound enzyme IIsor of the phosphoenolpyruvate-dependent carbohydrate:phosphotransferase system, specific for and regulated by this ketose and different from all other enzymes II described thus far. Two soluble enzymes, an L-sorbose-1-phosphate reductase and a D-glucitol-6-phosphate dehydrogenase, were involved in the conversion of L-sorbose-1-phosphate to D-fructose-6-phosphate. This dehydrogenase was temperature sensitive, preventing growth of wild-type strains of K. pneumoniae at temperatures above 35 degrees C in the presence of L-sorbose. The enzyme was distinct from a second D-glucitol-6-phosphate dehydrogenase involved in the metabolism of D-glucitol. The sor genes were transferred from the chromosome of nonmotile strains of K. pneumoniae by means of a new R'sor+ plasmid to motile strains of Escherichia coli K-12. Such derivatives not only showed the temperature-sensitive Sor+ phenotype characteristic for K. pneumoniae or Sor+ wild-type strains of E. coli, but also reacted positively to sorbose in chemotaxis tests.