gebhart/patrepeval huggingface dataset:
Measurement of energy expenditure in humans by doubly labeled water method (1982)

The utility of the doubly labeled water method for the determination of energy expenditure and water output was investigated in humans. Approximately 10 g of 18O and 0.5 g of 2H as water was orally administered to four healthy adults. Total body water was determined from the isotope dilution, and the ensuing 18O and 2H disappearance rates from body water were determined for 13 days by mass spectrometric isotope ratio analysis of the urinary water. During this period, subjects were maintained on a measured diet to determine energy and water intake. The energy expenditure from the doubly labeled water method differed from dietary intake plus change in body composition by an average of 2%, with a coefficient of variation of 6%. The water outputs determined by the two methods differed by 1%, with a coefficient of variation of 7%. The doubly labeled water method is noninvasive, and the subjects could maintain their daily activities without restriction.
Control of vascular smooth muscle cell growth and its implication in atherosclerosis and restenosis (review). (1998)

Abnormal proliferation of vascular smooth muscle cells (SMCs) is thought to contribute to neointimal thickening during spontaneous atherosclerosis and vessel renarrowing (restenosis) after angioplasty. This review will focus on the mechanisms underlying cell-cycle control in SMCs and its implication in atherosclerosis and restenosis. Therapeutic approaches that targeted specific cell-cycle control genes or growth regulatory molecules which effectively inhibited neointimal lesion formation will also be discussed.
Analysis of the Human Factor VIII A2 Inhibitor Epitope by Alanine Scanning Mutagenesis (1997)

Antibodies directed to the A2 domain of factor VIII (fVIII) are usually an important component of the polyclonal response in patients who have clinically significant inhibitory antibodies to fVIII. A major determinant of the A2 epitope has been located by homolog scanning mutagenesis using recombinant hybrid human/porcine fVIII molecules to a sequence bounded by Arg484-Ile508 (Healey, J. F. , Lubin, I. M., Nakai, H., Saenko, E. L., Hoyer, L. W., Scandella, D. , and Lollar, P. (1995) J. Biol. Chem. 270, 14505-14509). Within this region, human residues Arg484, Pro485, Tyr487, Ser488, Arg489, Pro492, Val495, Phe501, and Ile508 differ from porcine fVIII. We stably expressed in mammalian cells nine active B-domainless human fVIII molecules containing single alanine substitutions at these sites. Their inhibition by a murine anti-A2 monoclonal antibody, monoclonal antibody (mAb) 413, and by three A2-specific alloimmune and two A2-specific autoimmune human inhibitor plasmas was measured by the Bethesda assay. The inhibition of Arg484 --> Ala, Tyr487 --> Ala, Arg489 --> Ala, and Arg492 --> Ala by mAb413 was reduced by greater than 90% compared with wild-type, B-domainless human fVIII. mAb413 inhibited the most severely affected mutant, Arg489 --> Ala, 0.01% as well as wild-type fVIII. For all five patient plasmas, the Tyr487 --> Ala mutant displayed the greatest reduction in inhibition. The inhibition of the Tyr487 --> Ala mutant by these antibodies ranged from 10% to 20% that of wild-type fVIII. The inhibition of the Ser488 --> Ala, Arg489 --> Ala, Pro492 --> Ala, Val495 --> Ala, Phe501 --> Ala, and Ile508 --> Ala mutants by most of the plasmas also was significantly reduced. In contrast, the Arg484 --> Ala and Pro485 --> Ala mutants were relatively unaffected. Thus, although mAb413 binds to the same region as human A2 inhibitors, it recognizes a different set of amino acid side chains. The side chains recognized by human A2 inhibitors appear to be similar, despite the differing immune settings that give rise to fVIII alloantibodies and autoantibodies.
Taxonomic aspects of Peronosporaceae inferred from Bayesian molecular phylogenetics (2003)

We present the results of a Bayesian phylogenetic analysis of parts of the nuclear 28S rDNA of a representative sample of the Peronosporales. Peronospora s.l. is shown to be paraphyletic. Based on molecular and morphological evidence, several species of the genus Peronospora are transferred to Hyaloperonospora. Plasmopara oplismeni appears to be related only distantly to the other Plasmopara species, and is transferred to the new genus Viennotia based on molecular, morphological, and ecological evidence. The remaining Plasmopara species are likely to be paraphyletic with respect to Bremia, Paraperonospora, and Basidiophora. Phytophthora is shown to be paraphyletic with respect to the obligatory biotrophic genera. Evidence for the assumption that obligatory biotrophism arose independently at least twice in Peronosporales is demonstrated.Key words: LSU rDNA, Straminipila, Peronosporomycetes, Peronosporales, downy mildews, Bayesian phylogenetic analysis.
The role of the neurovascular scalp structures in migraine (2012)

The data reported suggest a role for neurovascular scalp structures in at least some patients with migraine. It would be of interest to find a clinical distinction between patients according to the prevalence of an intracranial or extracranial peripheral pain mechanism. This could lead to more efficacious treatments.
MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation (2018)

Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro. Further, combination treatment resulted in delayed tumor growth and improved survival in mouse models. Tumor regression was dependent on activated CD8<sup>+</sup> T cells and Batf3<sup>+</sup> dendritic cells. We also observed antigen spreading and induction of an inflammatory gene signature, including increased expression of PD-L1. Triple therapy with the combination of T-VEC, MEK inhibition, and anti-PD-1 antibody further augmented responses. These data support clinical development of combination oncolytic viruses, MEK inhibitors, and checkpoint blockade in patients with melanoma.
Potency estimates for recombinant factor IX in the one‐stage clotting assay are influenced by more than just the choice of activated partial thromboplastin time reagent (2018)

The activated partial thromboplastin time (APTT) one-stage clotting (OSC) assay is used to potency label factor IX (FIX) therapeutics and to monitor the treatment of deficient patients. Studies have highlighted differences in potency estimates for FIX therapeutics depending on what activator type the APTT reagent contains. During the study to replace the 4th International Standard (IS) for FIX Concentrate, it was noted that for the recombinant FIX (rFIX) candidates, a potency difference of 20% was obtained by some between laboratories using the reagent DAPTTIN. This study was designed to investigate this discrepancy. Two plasma-derived (pdFIX) and 2 rFIX materials were assayed against the 4th IS for FIX concentrate (07/182) using the OSC assay. Three different APTT reagents were used (DAPTTIN, SynthAFax and SynthASil), plus 4 different activation times. The pdFIX samples were not affected by activation time or APTT reagent, with expected potencies recovered in all assays and at all activation times. For rFIX, expected potencies were recovered using SynthASil, but SynthAFax generated potencies around 20% lower. This was consistent across the activation times. For DAPTTIN, potencies for rFIX dropped progressively and by up to 30% as activation time increased from 120 to 300 seconds. This study demonstrates that activation time as well as choice of APTT reagent can result in discrepancies in the potency estimation of rFIX. These factors should be taken into account when assaying rFIX.
[Prognostic importance of beta-2-microglobulin in multiple myeloma]. (1992)

Beta 2 microglobulin is a low molecular weight protein found on the surface of all nucleated cells: it is the light chain of the HL-A histocompatibility complex. The increased levels of serum beta 2 microglobulin in patients with multiple myeloma have been associated with a poor prognosis. Pretreatment levels of serum beta 2 microglobulin were estimated in 70 previously untreated patients with multiple myeloma. In a multivariate analysis, serum beta 2 microglobulin levels and stage were the most significant prognostic factors for survival independent of other risk factors associated with a worse prognosis. There was a clear difference in survival duration observed between the patients with a high pretreatment level of beta 2 microglobulin and stage III (none alive at 5 years) compared with patients with normal levels and stage I (80% alive at five years) (p less than .001). We conclude that pretreatment-beta 2 microglobulin level is one of the most useful prognostic factors in patients with multiple myeloma.
166. Kationoid reactivity of aromatic compounds. Part I (1932)

W. Bradley and R. Robinson, J. Chem. Soc., 1932, 1254 DOI: 10.1039/JR9320001254
Conversion of aminoacylation specificity from tRNATyrto tRNASerin vitro (1990)

The discrimination mechanism between tRNA(Ser) and tRNA(Tyr) was studied using various in vitro transcripts of E. coli tRNATyr variants. The insertion of only two nucleotides into the variable stem of tRNA(Tyr) generates serine charging activity. The acceptor activities of some of the tRNA(Tyr) mutants with insertions in the long variable arm were enhanced by changes in nucleotides at positions 9 and/or 20B, which are possible elements for dictating the orientation of the long variable arm. These findings suggest that the long variable arm is involved in recognition by seryl-tRNA synthetase in spite of sequence and length variations shown within tRNA(Ser) isoacceptors, and eventually serves as a determinant for selection from other tRNA species. Changing the anticodon from GUA to the serine anticodon GGA resulted in a marked decrease in tyrosine charging activity, but this mutant did not show any serine charging activity. The discriminator base, the fourth base from the 3' end of tRNA, was also important for aminoacylation with tyrosine. Complete specificity change in vitro was facilitated by insertion of three nucleotides into the variable arm plus two nucleotide changes at positions 9 and 73.
Human cytokines, tumor necrosis factor, and interferons: Gene cloning, animal studies, and clinical trials (1988)

Presented is a comprehensive program designed to isolate human cytokine genes and investigate their relative induction, and to analyze cytokine activities in cell culture, animal tumor models, and human clinical trials. Human cytokine cDNAs have been isolated from a cDNA library made from normal human peripheral blood leukocytes (PBLs) treated with Sendai virus and the relative induction of tumor necrosis factor (TNF), alpha and gamma interferons (IFN-alpha, IFN-gamma), and interleukin-1 beta IL-1 beta) genes has been analyzed. In the Sendai virus-induced PBL system, IL-1 beta mRNA was shown to be approximately twofold higher than TNF or IFN-alpha mRNA whereas IFN-gamma mRNA was 50-100-fold lower than TNF or IFN-alpha mRNA. The cytotoxic activity of TNF was analyzed on several cell lines and IFN-alpha and IFN-gamma were shown to potentiate TNF cytotoxicity about 2-200-fold depending on cell lines. The LD50 for recombinant TNF in BALB/c mice was determined to be 6 X 10(7) U/kg and the therapeutic dose of recombinant TNF in sarcoma 180 bearing BALB/c mice was 3 X 10(5) U/kg, indicating a wide therapetic index. Phase I clinical trials of recombinant TNF given I.V. indicated a tolerated dose of 150,000 U/kg with biphasic half-life (T-1/2) of 2 and 31 min following TNF injection. Phase II trials of TNF and trials of TNF combined with IFN-alpha are in progress. These studies indicate that cytokines such as TNF and IFN-alpha are subject to similar induction systems, potentiate each other's activities, and can be tolerated at specific doses for potential therapeutic use.
Prolonging Storage Life of Betel Leaves (1977)

Mature leaves (3rd to 6th leaves from the tip) were found to be the best material for prolonged storage and distant transport, since they had minimum climacteric peak, senescence, reduction of chlorophyll and spoilage with, greater build up of carotenoids. Compared with CCC and lodo-acetic acid, with BA treatment chlorophyll destruction was minimum with greater build up of carotenoids and yellowing was delayed by about 3 days. Ventilation was found to be very important, in the absence of which, there was moist discoloration and fermentation, while with too much aeration, there was dry discoloration. The methods of packing leaves in baskets normally practised is found to give minimum spoilage. When a mixture of sodium bicarbonate and tartaric acid was also included in the packing, the storage life of the leaves was further extended. Disinfecting the packing material with sodium hypochlorite or aureofungin is found to be beneficial for reducing of spore load and for development of yellow colour. No wide differences in spoilage were noticed between the bulk and small packs among the leaves of three stages of maturity.
A logic of authentication (1990)

Authentication protocols are the basis of security in many distributed systems, and it is therefore essential to ensure that these protocols function correctly. Unfortunately, their design has been extremely error prone. Most of the protocols found in the literature contain redundancies or security flaws. A simple logic has allowed us to describe the beliefs of trustworthy parties involved in authentication protocols and the evolution of these beliefs as a consequence of communication. We have been able to explain a variety of authentication protocols formally, to discover subtleties and errors in them, and to suggest improvements. In this paper we present the logic and then give the results of our analysis of four published protocols, chosen either because of their practical importance or because they serve to illustrate our method.
Serum Interleukin-18 Concentrations Are Increased in the Polycystic Ovary Syndrome: Relationship to Insulin Resistance and to Obesity (2004)

Low-grade chronic inflammation is involved in the pathogenesis of the metabolic syndrome and atherosclerosis, and serum levels of inflammatory cytokines are useful cardiovascular risk markers. We have studied serum IL-18 concentrations in women with polycystic ovary syndrome (PCOS), focusing on its relationship with obesity and indexes of insulin resistance. Sixty consecutive women with PCOS and 34 healthy women were recruited. Serum levels of IL-18 and lipid and hormone profiles were measured. The insulin sensitivity index was calculated from glucose and insulin concentrations during an oral glucose tolerance test. Data were submitted to a multivariate general linear model introducing age as a covariate. Serum IL-18 levels were increased in PCOS patients compared with controls (P = 0.031) and in obese women compared with lean women (P = 0.018). No interaction between PCOS and obesity was found, suggesting that the influence of PCOS on serum IL-18 concentrations studied here was not different in lean women compared with obese women and that the influence of obesity on serum IL-18 concentrations was the same in the PCOS and control groups. Serum IL-18 levels correlated, after logarithmic transformation, with body mass index (r = 0.38; P < 0.0002), waist-to-hip ratio (r = 0.33; P < 0.001), and total testosterone levels (r = 0.24; P < 0.02), and inversely with the insulin sensitivity index (r = -0.23; P < 0.03). In conclusion, PCOS and obesity induce an increase in serum IL-18 levels, which are also associated with several indexes of global and visceral adiposity and with insulin resistance.
The Possible Role of Endothelin-1 in the Pathogenesis of Coronary Vasospasm (1989)

We investigated the in vivo vasoconstrictor effects of endothelin-1 (ET-1) on canine coronary arteries and the regulation of ET-1 gene expression with special reference to the pathogenesis of coronary vasospasm. ET-1, administered into the coronary arteries of anesthetized dogs, produced a profound and long-lasting reduction in coronary blood flow with myocardial ischemia. Coronary angiography revealed delayed filling of the distal branches and, in some cases, total occlusion in the epicardial portions of coronary arteries. The coronary vasoconstriction induced by ET-1 subsided after intracoronary administration of nitroglycerin. Pretreatment with the Ca2+-channel antagonist, nitrendipine, suppressed ET-1-induced vasoconstriction. In cultured porcine aortic endothelial cells, ET-1 gene expression was induced by agents related to thrombus formation, such as thrombin and transforming growth factor beta (TGF beta). These findings suggest that ET-1, produced by vascular endothelial cells, may contribute to the regulation of coronary circulation and the pathogenesis of coronary vasospasm with respect to intimal injury and subsequent thrombus formation.
Prognostic factors in severe community‐acquired pneumonia in patients without co‐morbid illness (2001)

Markers of disease severity appear to be the most important predictors of outcome in patients with severe community-acquired pneumonia.
Oxidative/reductive conjugation of mannan to antigen selects for T1 or T2 immune responses. (1995)

The induction of CD8+ cytotoxic T lymphocytes (CTLs) is desirable for immunization against many diseases, and recombinant-synthetic peptide antigens are now favored agents to use. However, a major problem is how to induce CTLs, which requires a T1-type response to such synthetic antigens. We report that T1-type (generating high CTL, low antibody) or T2-type (the reciprocal) responses can be induced by conjugation of the antigen to the carbohydrate polymer mannan: T1 responses are selected by using oxidizing conditions; T2 responses are selected by using reducing conditions for the conjugation. Using human MUC1 as a model antigen in mice, immunization with oxidized mannan-MUC1 fusion protein (ox-M-FP) led to complete tumor protection (challenge up to 5 x 10(7) MUC1+ tumor cells), CTLs, and a high CTL precursor (CTLp) frequency (1/6900), whereas immunization with reduced mannan-MUC1 FP (red-M-FP) led to poor protection after challenge with only 10(6) MUC1+ tumor cells, no CTLs, and a low CTLp frequency (1/87,800). Ox-M-FP selects for a T1 response (mediated here by CD8+ cells) with high interferon gamma (IFN-gamma) secretion, no interleukin 4 (IL-4), and a predominant IgG2a antibody response; red-M-FP selects for a T2-type response with IL-4 production and a high predominant IgG1 antibody response but no IFN-gamma.
Accelerated proton echo planar spectroscopic imaging (PEPSI) using GRAPPA with a 32‐channel phased‐array coil (2008)

Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5-fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32-channel coil array, 1.5 cm(3) voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8-channel array, the smaller RF coil elements in this 32-channel array provided a 3.1-fold and 2.8-fold increase in signal-to-noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity-encoding (SENSE) and GRAPPA reconstruction using an 8-channel array showed that both methods yielded similar quantitative metabolite measures (P > 0.1). Concentration values of N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (mI), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32-channel array coil the mean Cramer-Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for mI and Glx at 2-fold acceleration. At 4-fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11%. In conclusion, the use of a 32-channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites.
6.7-Dihydroxycumarin (Aesculetin) als Substrat der Catechol-O-Methyltransferase / 6,7-Dihydroxycoumarin (Aesculetin) as a Substrate for Catediol-O-methyltransferase (1976)

6,7-Dihydroxycoumarin (Aesculetin) was found to be a substrate of rat liver Catechol-O-methylfransferase (COMT) (EC 2.1.1.6). Incubation of this substrate with S-Adenosyl-ʟ-[methyl- 14 C] methionine and/or S-Adenosyl- methionin-hydrogensulfate in the presence of COMT yields the highly fluorescent compounds 7-hydroxy-6-methoxycoumarin (Scopoletin) and 6-hydroxy-7-methoxycoumarin (Isoscopoletin) in the ration of about 2:1. The O-methylated products obtained from Aesculetin were identified after separation by thin layer chromatographpy mainly by the reversed isotope dilution technique. The fluorescence of the isolated methylethers was proportional to concentration within the range from 10 -5 - 10 -7 M. A reciprocal plot of activity versus substrate concentration gives a K m of 1 × 10 -6 M.
Gadolinium Chelates: Chemistry, Safety and Behavior (2007)

The sections in this article are 1 Introduction 2 Chemistry of Gadolinium-Based Contrast Agents 3 Tolerance and Pharmacology of Gadolinium Chelates 4 Principles of Contrast Enhanced MRI 5 Tissue-Specific Gadolinium Complexes 6 Biographical Sketches Related Articles
The facial dysmorphy in the newly recognised microdeletion 2p15–p16.1 refined to a 570 kb region in 2p15 (2008)

In this journal, Rajcan-Separovic et al 1 characterised a new microdeletion syndrome involving chromosome 2p15–16.1 in two patients with an autistic disorder (AD) and multiple congenital anomalies (MCA) with recognisable dysmorphic features. While screening for genomic copy number variations with a 1 Mb resolution bacterial artificial chromosome (BAC) array-based comparative genomic hybridisation (aCGH) in patients referred for the aetiological diagnosis of mental retardation and MCA (MR/MCA), a 570 kb de novo microdeletion at 2p15 was detected. We compare our findings with those of Rajcan-Separovic et al 1 and we discuss the phenotype–genotype correlations.

The patient is a 16-year-old boy born to healthy and non-consanguineous Belgian parents. 

He was first referred at the age of 9½ years (fig 1A) for school difficulties secondary to mild mental retardation (IQ of 50), MCA with ectomorphic habitus (height 147 cm (>P97), weight 25.7 kg (P3) and a normal occipito-frontal circumference of 54.2 cm). He has characteristic dysmorphic features including high forehead, fine hair, telecanthus, antimongoloid palpebral fissures, large ears, broad and high nasal root with prominent tip, high palate with nasal speech, everted lower lip, long fingers, pectus excavatum, kyphoscoliosis (>20°), congenital heart defect consisting of a bicuspid aortic valve with mild aortic valve insufficiency without stenosis and a prolapsed mitral valve with a first grade mitral …