gebhart/patrepeval huggingface dataset:
Effect of Extracts form Hovenia dulcis Thunb. on Alcohol Concentration in Rats and Men Administered Alcohol. (1995)

Hdを各種溶媒で分画し, その分画物摂取後のアルコール代謝に及ぼす影響についてラットおよびヒトを用いてそれぞれ検討した。1) 各種溶媒により得られたHd分画物のうち, アルコール投与ラットの血中アルコールおよびアセトアルデヒド濃度を最も低下させた画分は2規定塩酸溶出画分であり, それぞれの低下率は40%, 37%であった。次に効果を示した画分はメタノール抽出物であり, それぞれ12%, 17%低下させた。2) ヒト試験において, 糖質, タンパク質等からなるHdのエタノール抽出物の摂取では, 飲酒後の唾液中アルコールおよびアセトアルデヒド濃度を低下させる傾向が見られ, 飲酒の2時間後においては, 被験者6名中4名の唾液中のアルコール濃度を有意に低下させた。3) エタノール抽出物はヒトの飲酒後の呼気アルコール濃度を有意に低下させ, 飲酒の1時間後においては, 被験者8名中5名で有意な濃度の低下を示した。以上の結果より, Hdには飲酒後の体内における血中アルコールやアセトアルデヒド濃度を低下させる効果があり, 飲酒による酔いの症状を軽減するとともに, 呼気中のアルコール濃度の消失を早めるものと思われる。
Human Monoclonal Antibody Combination against SARS Coronavirus: Synergy and Coverage of Escape Mutants (2006)

The combination of two noncompeting human mAbs CR3014 and CR3022 potentially controls immune escape and extends the breadth of protection. At the same time, synergy between CR3014 and CR3022 may allow for a lower total antibody dose to be administered for passive immune prophylaxis of SARS-CoV infection.
A comprehensive assay for targeted multiplex amplification of human DNA sequences (2008)

We developed a robust and reproducible methodology to amplify human sequences in parallel for use in downstream multiplexed sequence analyses. We call the methodology SMART (Spacer Multiplex Amplification Reaction), and it is based, in part, on padlock probe technology. As a proof of principle, we used SMART technology to simultaneously amplify 485 human exons ranging from 100 to 500 bp from human genomic DNA. In multiple repetitions, >90% of the targets were successfully amplified with a high degree of uniformity, with 70% of targets falling within a 10-fold range and all products falling within a 100-fold range of each other in abundance. We used long padlock probes (LPPs) >300 bases in length for the assay, and the increased length of these probes allowed for the capture of human sequences up to 500 bp in length, which is optimal for capturing most human exons. To engineer the LPPs, we developed a method that generates ssDNA molecules with precise ends, using an appropriately designed dsDNA template. The template has appropriate restriction sites engineered into it that can be digested to generate nucleotide overhangs that are suitable for lambda exonuclease digestion, producing a single-stranded probe from dsDNA. The SMART technology is flexible and can be easily adapted to multiplex tens of thousands of target sequences in a single reaction.
Lysosomal Storage Diseases and the Blood-Brain Barrier (2008)

The blood-brain barrier becomes a crucial issue in neuronopathic lysosomal storage diseases for three reasons. Firstly, the function of the blood-brain barrier may be compromised in many of the lysosomal storage diseases and this barrier dysfunction may contribute to the neuropathology seen in the diseases and accelerate cell death. Secondly, the substrate reduction therapies, which successfully reduce peripheral lysosomal storage, because of the blood-brain barrier may not have as free an access to brain cells as they do to peripheral cells. And thirdly, enzyme replacement therapy appears to have little access to the central nervous system as the mannose and mannose-6-phosphate receptors involved in their cellular uptake and transport to the lysosome do not appear to be expressed at the adult blood-brain barrier. This review will discuss in detail these issues and their context in the development of new therapeutic strategies.
Vegetative Incompatibility in the het-6 Region of Neurospora crassa Is Mediated by Two Linked Genes (2000)

Non-self-recognition during asexual growth of Neurospora crassa involves restriction of heterokaryon formation via genetic differences at 11 het loci, including mating type. The het-6 locus maps to a 250-kbp region of LGIIL. We used restriction fragment length polymorphisms in progeny with crossovers in the het-6 region and a DNA transformation assay to identify two genes in a 25-kbp region that have vegetative incompatibility activity. The predicted product of one of these genes, which we designate het-6(OR), has three regions of amino acid sequence similarity to the predicted product of the het-e vegetative incompatibility gene in Podospora anserina and to the predicted product of tol, which mediates mating-type vegetative incompatibility in N. crassa. The predicted product of the alternative het-6 allele, HET-6(PA), shares only 68% amino acid identity with HET-6(OR). The second incompatibility gene, un-24(OR), encodes the large subunit of ribonucleotide reductase, which is essential for de novo synthesis of DNA. A region in the carboxyl-terminal portion of UN-24 is associated with incompatibility and is variable between un-24(OR) and the alternative allele un-24(PA). Linkage analysis indicates that the 25-kbp un-24-het-6 region is inherited as a block, suggesting that a nonallelic interaction may occur between un-24 and het-6 and possibly other loci within this region to mediate vegetative incompatibility in the het-6 region of N. crassa.
Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice (1999)

Thymic atrophy is a prominent feature of malnutrition. Forty-eight hours' starvation of normal mice reduced the total thymocyte count to 13% of that observed in freely fed controls, predominantly because of a diminution in the cortical CD4(+)CD8(+) thymocyte subpopulation. Prevention of the fasting-induced fall in the level of the adipocyte-derived hormone leptin by administering exogenous recombinant leptin protected mice from these starvation-induced thymic changes. The ob/ob mouse, which is unable to produce functional leptin because of a mutation in the obese gene, has impaired cellular immunity together with a marked reduction in the size and cellularity of the thymus. We found that ob/ob mice had a high level of thymocyte apoptosis resulting in a ratio of CD4(+)CD8(+) (cortical) to CD4(-)CD8(-) (precursor) thymocytes that was 4-fold lower than that observed in wild-type mice. Peripheral administration of recombinant leptin to ob/ob mice reduced thymocyte apoptosis and substantially increased both thymic cellularity and the CD4(+)CD8(+)/CD4(-)CD8(-) ratio. In contrast, a comparable weight loss in pair-fed PBS-treated ob/ob mice had no impact on thymocyte number. In vitro, leptin protected thymocytes from dexamethasone-induced apoptosis. These data indicate that reduced circulating leptin concentrations are pivotal in the pathogenesis of starvation-induced lymphoid atrophy.
Considerations in Control and Treatment of Nosocomial Infections Due to Multidrug‐ResistantAcinetobacter baumannii (2003)

We sought to control infection due to multidrug-resistant Acinetobacter baumannii (MDR-Ab) by identifying isolates as clonally related, leading to enhanced infection-control measures, including cohorting, surveillance, contact precaution, initial therapy with ampicillin/sulbactam and local polymyxin B, and, more recently, therapy with synergistic antibiotic combinations. Class restriction of cephalosporins has been associated with a reduction in cephalosporins-cephamycin-carbapenem resistance among nosocomial Klebsiella isolates. This has been supplemented by restriction of carbapenem use after an initial 24-h period in an effort to reduce the selection of porin-deficient, carbapenem-resistant A. baumannii and Pseudomonas aeruginosa. Evidence is reviewed suggesting that eradication of MDR-Ab nosocomial colonization may prevent subsequent infection. Relatively few standard antibacterial drugs remain active against MDR-Ab. Published clinical results of therapy with these agents are reviewed, and in vitro evidence of synergy between them is presented that suggests that combination therapy should be studied for enhanced clinical activity.
Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression (2016)

The transcription factor LSF is highly expressed in hepatocellular carcinoma (HCC) and promotes oncogenesis. Factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity and exerts anti-proliferative activity. Here, we show that LSF binds directly to the maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1) and its accessory protein UHRF1 both in vivo and in vitro. Binding of LSF to DNMT1 stimulated DNMT1 activity and FQI1 negated the methyltransferase activation. Addition of FQI1 to the cell culture disrupted LSF bound DNMT1 and UHRF1 complexes, resulting in global aberrant CpG methylation. Differentially methylated regions (DMR) containing at least 3 CpGs, were significantly altered by FQI1 compared to control cells. The DMRs were mostly concentrated in CpG islands, proximal to transcription start sites, and in introns and known genes. These DMRs represented both hypo and hypermethylation, correlating with altered gene expression. FQI1 treatment elicits a cascade of effects promoting altered cell cycle progression. These findings demonstrate a novel mechanism of FQI1 mediated alteration of the epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression.
GaAs/GaAlAs power HBTs for mobile communications (2002)

GaAlAs/GaAs power HBTs (heterojunction bipolar transistors) are investigated for handsets in mobile cellular communication systems at 1.8 GHz. Different HBT operating classes are compared, and the choice of the optimum operating class is discussed. Experimental measurements on a small-chip-size HBT of 0.4*0.4 mm/sup 2/ have shown 1-W output power with a power-added efficiency of 45%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A high-speed resonance-type FET transceiver switch for millimeter-wave band wireless network (1996)

This paper concerns with the design consideration, fabrication process, and performance of a CPW monolithic AlGaAs/InGaAs HJFET switch for V-band wireless networks applications. The Switch utilizes a resonance concept in order to either pass, or to block a signal by presenting, respectively, a parallel, or a series resonant circuit to the signal. A developed T/R switch exhibits state-of the art switching-speed and isolation of 250psec and 41dB, respectively, and an insertion loss of 3.9dB ovr V-band frequencies.
The structure, expression, and properties of additional members of the protein kinase C family. (1988)

In rat brain three members of the protein kinase C family encoded by cDNAs termed delta, epsilon, and zeta were newly identified by molecular cloning and sequence analysis. The new members have a common structure that is closely related to but clearly distinct from the four members of the family previously isolated having alpha-, beta I-, beta II-, and gamma-sequences, although the zeta-cDNA available at present does not appear to contain a complete reading frame for protein kinase C. The delta-, epsilon-, and zeta-cDNAs all encode a characteristic cysteine-rich sequence and protein kinase domain sequence, both of which are highly homologous among the protein kinase C family. However, the new members lack one of the conserved regions that is present in alpha-, beta I-, beta II-, and gamma-sequences. An additional cDNA clone termed epsilon' was isolated, which is identical with epsilon-cDNA except for a short sequence at the 5'-terminal end region. The two members having delta- and epsilon-sequences were expressed in COS 7 cells, and partially purified and characterized. The enzymes having delta- and epsilon-sequences depend on phospholipid and diacylglycerol for the enzymatic activity, but their properties slightly differ from the previously known members of protein kinase C. Northern blot analysis suggests that the new members of protein kinase C exist in the brain and some other tissues.
The effect of midpolar regime mimics on anion transport mediated by amphiphilic heptapeptides (2007)

Nine amphiphilic heptapeptides, synthetic anion transporters (SATs) of the form (C18H37)2N–Y–(Gly)3-Pro-(Gly)3–OCH2Ph were prepared. The unit (OH2)Y represents the diacids succinic, glutaric, diglycolic, 3-thiaglutaric, N-methyliminodiglycine, isophthalic, and terephthalic acids. Additionally, Y was absent or present as acetic acid affording the structure (C18H37)2N–(Gly)3-Pro-(Gly)3–OCH2Ph or (C18H37)2N–(Gly)4-Pro-(Gly)3–OCH2Ph. The diglycolic acid derivative was reported previously but the remaining compounds are new. These nine peptides mediated release of Cl– from DOPC/DOPA vesicles with varying efficacy. Chloride release diminished for the Y-containing amphiphilic heptapeptides in the order glutaric, succinic > 3-thiaglutaric > terephthalic > acetic, N-methyliminodiacetic, > no Y, isophthalic. The release of Cl– was generally exponential over time but the curve shapes were distinctly sigmoidal for the more flexible diacids. Computational studies were undertaken to assess differences in conformation. Overall, it appeared that Cl– release for those SATs that could adopt a linear conformation on the N-terminal side of proline correlated best with the polarity of the diacid.
Calculation of the free energy of association for protein complexes (1992)

We have developed a method for calculating the association energy of quaternary complexes starting from their atomic coordinates. The association energy is described as the sum of two solvation terms and an energy term to account for the loss of translational and rotational entropy. The calculated solvation energy, using atomic solvation parameters and the solvent accessible surface areas, has a correlation of 96% with experimentally determined values. We have applied this methodology to examine intermediates in viral assembly and to assess the contribution isomerization makes to the association energy of molecular complexes. In addition, we have shown that the calculated association can be used as a predictive tool for analyzing modeled molecular complexes.
Disulfide Bonding Arrangements in Active Forms of the Somatomedin B Domain of Human Vitronectin (2004)

The N-terminal cysteine-rich somatomedin B (SMB) domain (residues 1-44) of the human glycoprotein vitronectin contains the high-affinity binding sites for plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR). We previously showed that the eight cysteine residues of recombinant SMB (rSMB) are organized into four disulfide bonds in a linear uncrossed pattern (Cys(5)-Cys(9), Cys(19)-Cys(21), Cys(25)-Cys(31), and Cys(32)-Cys(39)). In the present study, we use an alternative method to show that this disulfide bond arrangement remains a major preferred one in solution, and we determine the solution structure of the domain using NMR analysis. The solution structure shows that the four disulfide bonds are tightly packed in the center of the domain, replacing the traditional hydrophobic core expected for a globular protein. The few noncysteine hydrophobic side chains form a cluster on the outside of the domain, providing a distinctive binding surface for the physiological partners PAI-1 and uPAR. The hydrophobic surface consists mainly of side chains from the loop formed by the Cys(25)-Cys(31) disulfide bond, and is surrounded by conserved acidic and basic side chains, which are likely to contribute to the specificity of the intermolecular interactions of this domain. Interestingly, the overall fold of the molecule is compatible with several arrangements of the disulfide bonds. A number of different disulfide bond arrangements were able to satisfy the NMR restraints, and an extensive series of conformational energy calculations performed in explicit solvent confirmed that several disulfide bond arrangements have comparable stabilization energies. An experimental demonstration of the presence of alternative disulfide conformations in active rSMB is provided by the behavior of a mutant in which Asn(14) is replaced by Met. This mutant has the same PAI-1 binding activity as rVN1-51, but its fragmentation pattern following cyanogen bromide treatment is incompatible with the linear uncrossed disulfide arrangement. These results suggest that active forms of the SMB domain may have a number of allowed disulfide bond arrangements as long as the Cys(25)-Cys(31) disulfide bond is preserved.
The Human TREX2 3′ → 5′-Exonuclease Structure Suggests a Mechanism for Efficient Nonprocessive DNA Catalysis (2005)

The 3' --> 5'-exonucleases process DNA ends in many DNA repair pathways of human cells. Determination of the human TREX2 structure is the first of a dimeric 3'-deoxyribonuclease and indicates how this highly efficient nonprocessive enzyme removes nucleotides at DNA 3' termini. Symmetry in the TREX2 dimer positions the active sites at opposite outer edges providing open access for the DNA. Adjacent to each active site is a flexible region containing three arginines positioned appropriately to bind DNA and to control its entry into the active site. Mutation of these three arginines to alanines reduces the DNA binding capacity by approximately 100-fold with no effect on catalysis. The human TREX2 catalytic residues overlay with the bacterial DnaQ family of 3'-exonucleases confirming the structural conservation of the catalytic sites despite limited sequence identity, and mutations of these residues decrease the still measurable activity by approximately 10(5)-fold, confirming their catalytic role.
Immunoglobulin A mediation of murine nasal anti-influenza virus immunity (1991)

Most mice which have recovered from influenza virus infection are immune to reinfection with the same influenza virus. This immunity could be abrogated by the intranasal instillation of anti-immunoglobulin A (anti-IgA) but not of anti-IgG or anti-IgM antiserum. Thus, IgA is the major, if not the sole, mediator of nasal immunity to influenza virus in immunocompetent mice.
Alkali-metal ion/molecule association reactions and their applications to mass spectrometry (2000)

This review will be concerned primarily with thermal alkali-metal ion association reactions of the general type: A+ + M + N reversible (A + M)+ + N. Where A denotes a positively charged alkali metal ion, M is neutral species and N works as a third body. As indicated, most association reactions are reversible, and the A-M bond derives primarily from electrostatic forces whose energy (affinity) is typically 50 kcal/mol or less, often much less. The review includes reaction mechanism, instrumentation, and application to mass spectrometry, together with reaction rates and alkali ion affinities of the classified compounds.
High-efficiency oscillations in germanium avalanche diodes below the transit-time frequency (1968)

Pulsed operation of Ge avalanche diodes has produced oscillations with efficiencies exceeding 40 percent at frequencies of 2-3 GHz. Computer simulation of diode and circuit behavior has provided an explanation for the observed results.
Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu Oncogene (1985)

A novel potential cell surface receptor of the tyrosine kinase gene family has been identified and characterized by molecular cloning. Its primary sequence is very similar to that of the human epidermal growth factor receptor and the v-erbB oncogene product; the chromosomal location of the gene for this protein is coincident with the neu oncogene, which suggests that the two genes may be identical.
Comparison of the GDx VCC Scanning Laser Polarimeter, HRT II ConfocalScanning Laser Ophthalmoscope, and Stratus OCT Optical Coherence Tomographfor the Detection of Glaucoma (2004)

The AUCs and the sensitivities at high specificities were similar among the best parameters from each instrument. Abnormal results (as compared with each instrument's normative database) were associated with high likelihood ratios and large effects on posttest probabilities of having glaucomatous visual field loss. Calculation of likelihood ratios may provide additional information to assist the clinician in diagnosing glaucoma with these instruments.
Understanding the mechanism of IL-1β secretion (2011)

The cytokine interleukin-1β (IL-1β) is a key mediator of the inflammatory response. Essential for the host-response and resistance to pathogens, it also exacerbates damage during chronic disease and acute tissue injury. It is not surprising therefore that there is a huge level of interest in how this protein is produced and exported from cells. However, the mechanism of IL-1β release has proven to be elusive. It does not follow the conventional ER-Golgi route of secretion. A literature full of disparate observations arising from numerous experimental systems, has contributed to a complicated mix of diverse proposals. Here we summarise these observations and propose that secretion of IL-1β occurs on a continuum, dependent upon stimulus strength and the extracellular IL-1β requirement.
Mutagenesis and heterologous expression in yeast of a plant Δ6‐fatty acid desaturase (2001)

Membrane-bound microsomal fatty acid desaturases are known to have three conserved histidine boxes, comprising a total of up to eight histidine residues. Recently, a number of deviations from this consensus have been reported, with the substitution of a glutamine for the first histidine residue of the third histidine box being present in the so called 'front end' desaturases. These enzymes are also characterized by the presence of a cytochrome b5 domain at the protein N-terminus. Site-directed mutagenesis has been used to probe the functional importance of a number of amino acid residues which comprise the third histidine box of a 'front end' desaturase, the borage Delta6-fatty acid desaturase. This showed that the variant glutamine in the third histidine box is essential for enzyme activity and that histidine is not able to substitute for this residue.
Chiral N-Heterocyclic Carbenes with Restricted Flexibility in Asymmetric Catalysis (2006)

A chiral C2-symmetric diamine was prepared from (S)-3-phenyl-3,4-dihydroisoquinoline by the virtue of asymmetric transformation. Rhodium and iridium complexes of chiral N-heterocyclic carbenes with restricted flexibility derived from 3,3‘-substituted partially reduced biisoquinoline were obtained by transmetalation from the corresponding silver(I) complexes. Unexpected double-bond formation in the carbene ligand has occurred during a transmetalation step. The structures of these complexes were verified by X-ray diffraction. Metal complexes of these N-heterocyclic carbenes were applied to the asymmetric hydrogenation of methyl 2-acetamidoacrylate. Good enantioselectivities of up to 67% ee were achieved.
Microvascular Complications of Impaired Glucose Tolerance (2003)

Impaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both large- and small-vessel vascular complications, independent of a patient's progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known.