gebhart/patrepeval huggingface dataset:
Principles of Data Conversion System Design (1994)

This advanced text and reference covers the design and implementation of integrated circuits for analog-to-digital and digital-to-analog conversion. It begins with basic concepts and systematically leads the reader to advanced topics, describing design issues and techniques at both circuit and system level. Gain a system-level perspective of data conversion units and their trade-offs with this state-of-the art book. Topics covered include: sampling circuits and architectures, D/A and A/D architectures; comparator and op amp design; calibration techniques; testing and characterization; and more!
Case 5-1996 (1996)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 5-1996 — A 25-Year-Old Man with Hemopericardium, Bilateral Hemothorax, and Hemoptysis after Chest Trauma
Slow Radio-Frequency Processing of Large Oil Shale Volumes to Produce Petroleum-Like Shale Oil (2003)

A process is proposed to convert oil shale by radio frequency heating over a period of months to years to create a product similar to natural petroleum. Electrodes would be placed in drill holes, either vertical or horizontal, and a radio frequency chosen so that the penetration depth of the radio waves is of the order of tens to hundreds of meters. A combination of excess volume production and overburden compaction drives the oil and gas from the shale into the drill holes, where it is pumped to the surface. Electrical energy for the process could be provided initially by excess regional capacity, especially off-peak power, which would generate {approx}3 x 10{sup 5} bbl/day of synthetic crude oil, depending on shale grade. The electricity cost, using conservative efficiency assumptions, is $4.70 to $6.30/bbl, depending on grade and heating rate. At steady state, co-produced gas can generate more than half the electric power needed for the process, with the fraction depending on oil shale grade. This would increase production to 7.3 x 10{sup 5} bbl/day for 104 l/Mg shale and 1.6 x 10{sup 6} bbl/day for 146 l/Mg shale using a combination of off-peak power and power from co-produced gas.
[Validation of the hospital anxiety and depression scale in a gastro-intestinal clinic]. (1996)

This study examined the validity of the Japanese version of the hospital anxiety and depression scale (HAD) in a gastro-intestinal outpatient clinic. One hundred and twenty-three men and 142 women consulting a gastro-intestinal outpatient clinic at a primary care hospital in Kyoto during 1995 were surveyed. Item-remainder correlation and internal consistency were examined for reliability. Concurrent validities were examined using the stait-trait anxiety inventory (STAI) and Zung's self-rating depression scale (SDS). The prevalence of psychiatric disorder in this population ranged from 27% to 39%. Cronbach's coefficients were greater than 0.8 for the anxiety subscale and more than 0.7 for the depression subscale. Spearman's correlation of the anxiety subscale scores and the STAI were r = 0.678 for men, and r = 0.717 for women. The correlation of depression subscale scores and SDS were r = 0.457 for men, and r = 0.565 for women. It is suggested that the use of the HAD to general hospital outpatients clinic would facilitate detecting emotional disorders in outpatients.
DNA microarray analysis ofBacillus subtilissigma factors of extracytoplasmic function family (2003)

Target gene candidates of the seven extracytoplasmic function (ECF) sigma factors of Bacillus subtilis have been surveyed using DNA microarray analysis of mRNA extracted from cells grown in Luria^Bertani broth, in which an ECF sigma factor gene was placed under the control of the spac promoter on multicopy plasmid pDG148 and overexpressed. The number of target candidates for each of the sigma factors varied greatly, and a total of 278 genes were selected. Interestingly, the above target gene candidates shared only one gene out of 94 target genes of the general stress sigma B that have been reported in the literature thus far. Furthermore, lacZ-fusion experiments based on the results of DNA microarray analysis indicated that each ECF sigma factor directs transcription of its own operon, with the exception of sigZ. The DNA microarray data collected in this study are available at the KEGG Expression Database web site (http://www.genome.ad.jp/kegg/expression/).
Perspective on the Road toward Gene Therapy for Parkinson’s Disease (2017)

Many therapeutic strategies aimed at relieving symptoms of Parkinson's disease (PD) are currently used for treatment of this disease. With a hallmark of progressive degeneration of dopaminergic neurons, the absence of properly operational dopaminergic circuitry becomes a therapeutic target. Following diagnosis, dopamine replacement can be given in the form of L-DOPA (L-3,4-dihydroxyphenylalanine). Even though it is recognized as standard of care, this treatment strategy does not prevent the affected neurons from degenerating. Therefore, studies have been performed using gene therapy (GT) to make dopamine (DA) available from within the brain using an artificial DA circuitry. One approach is to administer a GT aimed at delivering the key enzymes for DA synthesis using a lentiviral vector system (Palfi et al., 2014). A similar approach has been investigated with adeno-associated virus (AAV) expressing aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP-cyclohydrolase I (Bankiewicz et al., 2000), which are downregulated in PD. Another GT approach to mitigate symptoms of PD used AAV-mediated delivery of GAD-67 (glutamate decarboxylase) (Kaplitt et al., 2007). This approach mimics the inhibitory effect of DA neurons on their targets, in reducing motor abnormalities. Finally, disease modifying strategies have been undertaken using neurotrophic factors such as neurturin (NTN) (Marks et al., 2008; Bartus et al., 2013a) or are ongoing with the closely related Glial cell line-derived neurotrophic factor. Those approaches are aiming at rescuing the degenerating neurons. All of the above mentioned strategies have their own merits, but also some disadvantages. So far, none of clinical applied GT studies has resulted in significant clinical benefit, although some clinical studies are ongoing and results are expected over the next few years.
Importance of Hydrophobic Apoproteins as Constituents of Clinical Exogenous Surfactants (1992)

The biophysical properties and physiologic effects of a series of clinical exogenous pulmonary surfactants was compared to determine the importance of the hydrophobic apoproteins (SP-B and C) as constituents of these preparations. The three exogenous surfactants studied, calf lung surfactant extract (CLSE), Survanta (Surfactant-TA), and Exosurf, all contain dipalmitoyl phosphatidylcholine (DPPC) as their major constituent. CLSE and Survanta also contain 1 to 2% of SP-B,C but Exosurf has the additives hexadecanol and tyloxapol instead to enhance the activity of DPPC. In adsorption experiments, CLSE reached a final surface tension of 22 mN/m, and Survanta and Exosurf reached 28 and 38 mN/m, respectively. Addition of 1% by weight of an apoprotein isolate containing both SP-B and C to Exosurf slightly improved its adsorption. In oscillating bubble studies, CLSE and Survanta decreased surface tension to low values of less than 1 and 2 mN/m, respectively, but Exosurf achieved a minimum value of only 29 mN/m. Addition of SP-B,C to Exosurf improved this minimum to 1 mN/m and approached the behavior of mixtures of synthetic DPPC with SP-B,C. In both adsorption and pulsating bubble experiments, the minimum surface tensions found for Exosurf were almost identical to those generated by tyloxapol alone. In studies of physiologic activity, 20 mg of CLSE or Survanta restored the pressure-volume mechanics of lavaged, surfactant-deficient excised rat lungs to 95 and 50%, respectively, of normal prelavage levels. Instillation of Exosurf (37.5 mg) produced a minimal improvement of only 10% compared to 70% for mixtures containing 1% SP-B,C with either Exosurf or DPPC.(ABSTRACT TRUNCATED AT 250 WORDS)
MTM1 mutations in X-linked myotubular myopathy (2000)

X-linked myotubular myopathy (XLMTM; MIM# 310400) is a severe congenital muscle disorder caused by mutations in the MTM1 gene. This gene encodes a dual-specificity phosphatase named myotubularin, defining a large gene family highly conserved through evolution (which includes the putative anti-phosphatase Sbf1/hMTMR5). We report 29 mutations in novel cases, including 16 mutations not described before. To date, 198 mutations have been identified in unrelated families, accounting for 133 different disease-associated mutations which are widespread throughout the gene. Most point mutations are truncating, but 26% (35/133) are missense mutations affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. Three recurrent mutations affect 17% of the patients, and a total of 21 different mutations were found in several independent families. The frequency of female carriers appears higher than expected (only 17% are de novo mutations). While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).
Multiple-Color Optical Activation, Silencing, and Desynchronization of Neural Activity, with Single-Spike Temporal Resolution (2007)

The quest to determine how precise neural activity patterns mediate computation, behavior, and pathology would be greatly aided by a set of tools for reliably activating and inactivating genetically targeted neurons, in a temporally precise and rapidly reversible fashion. Having earlier adapted a light-activated cation channel, channelrhodopsin-2 (ChR2), for allowing neurons to be stimulated by blue light, we searched for a complementary tool that would enable optical neuronal inhibition, driven by light of a second color. Here we report that targeting the codon-optimized form of the light-driven chloride pump halorhodopsin from the archaebacterium Natronomas pharaonis (hereafter abbreviated Halo) to genetically-specified neurons enables them to be silenced reliably, and reversibly, by millisecond-timescale pulses of yellow light. We show that trains of yellow and blue light pulses can drive high-fidelity sequences of hyperpolarizations and depolarizations in neurons simultaneously expressing yellow light-driven Halo and blue light-driven ChR2, allowing for the first time manipulations of neural synchrony without perturbation of other parameters such as spiking rates. The Halo/ChR2 system thus constitutes a powerful toolbox for multichannel photoinhibition and photostimulation of virally or transgenically targeted neural circuits without need for exogenous chemicals, enabling systematic analysis and engineering of the brain, and quantitative bioengineering of excitable cells.
The Journal of Inflammation. (2004)

Welcome to the Journal of Inflammation, the first open-access, peer-reviewed, online journal to focus on all aspects of the study of inflammation and inflammatory conditions. While research into inflammation has resulted in great progress in the latter half of the 20th century, the rate of progress is rapidly accelerating. Thus there is a need for a vehicle through which this very diverse research can be made readily available to the scientific community. The Journal of Inflammation, a peer reviewed journal, provides the ideal vehicle for such rapid dissemination of information. The Journal of Inflammation covers the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. This includes molecular, cellular, animal and clinical studies related to the study of inflammatory conditions and responses, and all related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments, etc. All articles published in the Journal of Inflammation are immediately listed in PubMed, and access to published articles is universal and free through the internet.
Biochemical Investigations and Mapping of the Calcium-binding Sites of Heparinase I from Flavobacterium heparinum (1999)

The heparinases from Flavobacterium heparinum are lyases that specifically cleave heparin-like glycosaminoglycans. Previously, amino acids located in the active site of heparinase I have been identified and mapped. In an effort to further understand the mechanism by which heparinase I cleaves its polymer substrate, we sought to understand the role of calcium, as a necessary cofactor, in the enzymatic activity of heparinase I. Specifically, we undertook a series of biochemical and biophysical experiments to answer the question of whether heparinase I binds to calcium and, if so, which regions of the protein are involved in calcium binding. Using the fluorescent calcium analog terbium, we found that heparinase I tightly bound divalent and trivalent cations. Furthermore, we established that this interaction was specific for ions that closely approximate the ionic radius of calcium. Through the use of the modification reagents N-ethyl-5-phenylisoxazolium-3'-sulfonate (Woodward's reagent K) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, we showed that the interaction between heparinase I and calcium was essential for proper functioning of the enzyme. Preincubation with either calcium alone or calcium in the presence of heparin was able to protect the enzyme from inactivation by these modifying reagents. In addition, through mapping studies of Woodward's reagent K-modified heparinase I, we identified two putative calcium-binding sites, CB-1 (Glu207-Ala219) and CB-2 (Thr373-Arg384), in heparinase I that not only are specifically modified by Woodward's reagent K, leading to loss of enzymatic activity, but also conform to the calcium-coordinating consensus motif.
Hydrogen Peroxide Is Involved in Collagen-Induced Platelet Activation (1998)

Abstract In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.
Three‐dimensional structure of acyl carrier protein in solution determined by nuclear magnetic resonance and the combined use of dynamical simulated annealing and distance geometry (1988)

The solution conformation of acyl carrier protein from Escherichia coli (77 residues) has been determined on the basis of 423 interproton-distance restraints and 32 hydrogen-bonding restraints derived from NMR measurements. A total of nine structures were computed using a hybrid approach combining metric matrix distance geometry and dynamic simulated annealing. The polypeptide fold is well defined with an average backbone atomic root-mean-square difference of 0.20 +/- 0.03 nm between the final nine converged structures and the mean structure obtained by averaging their coordinates. The principal structural motif is composed of three helices: 1 (residues 3-12), 2 (residues 37-47) and 4 (residues 65-75) which line a hydrophobic cavity. Helices 2 and 4 are approximately parallel to each other and anti-parallel at an angle of approximately equal to 150 degrees to helix 1. The smaller helix 3 (residues 56-63) is at an angle of approximately equal to 100 degrees to helix 4.
Transgenic Technology and Laboratory Animal Science (1997)

Transgenic technology allows the introduction of new and functional genetic material into the germ line. The first advanced eukaryotes to prove amenable to such genetic modifications were mice (Gordon and others 1980; Gordon and Ruddle 1981); subsequently, a variety of species including fish and fruit flies have been subject to transgenic manipulation. Germline gene transfer has enormously increased the rate of progress in understanding mammalian development. As a consequence of this improved knowledge, important insights into many disease processes have been gained, and new strategies for genetic engineering of livestock have been devised. These many advances have been comprehensively reviewed elsewhere (Palmiter and Brinster 1986; Gordon 1989). A related publication has also previously appeared in this ILAR News (Gordon 1988). In this paper transgenic technology will be discussed with the issues of laboratory animal sciences as a reference point. The extant approaches to gene transfer will first be discussed, after which some representative examples of transgenic experiments for studying gene regulation and creating models of disease will be presented. Throughout this article, issues of reproductive management, aspects of colony maintenance that require special emphasis, and IACUC review of transgenic protocols will serve as themes. However, in the last segment of the manuscript, direct focus on specific aspects of laboratory animal management will be provided.
Induced hypothermia by central venous infusion: Saline ice slurry versus chilled saline (2004)

Cold intravenous fluids rapidly induce hypothermia in swine with intact circulation. A two-phase (liquid plus ice) saline slurry cools more rapidly than an equal volume of cold saline at 0 degrees C. Ice-slurry could be a significant improvement over other cooling methods when rate of cooling and limited infusion volumes are important to the clinician.
Mutation of the PIK3CA Gene in Ovarian and Breast Cancer (2004)

Phosphatidylinositol 3'-kinases are lipid kinases with important roles in neoplasia. Recently, a very high frequency of somatic mutations in PIK3CA has been reported among a large series of colorectal cancers. However, the relevance of PIK3CA mutation in other cancer types remains unclear because of the limited number of tumors investigated. We have screened a total of 284 primary human tumors for mutations in all coding exons of PIK3CA using a combination of single stranded conformational polymorphism and denaturing high-performance liquid chromatography analysis. Among 70 primary breast cancers, 40% (28 of 70) harbored mutations in PIK3CA, making it the most common mutation described to date in this cancer type. Mutations were not associated with histologic subtype, estrogen receptor status, grade or presence of tumor in lymph nodes. Among the primary epithelial ovarian cancers only 11 of 167 (6.6%) contain somatic mutations, but there was a clear histologic subtype bias in their distribution. Only 2 of 88 (2.3%) of serous carcinomas had PIK3CA mutations compared with 8 of 40 (20.0%) endometrioid and clear cell cancers, which was highly significant (P = 0.001). In contrast, PIK3CA gene amplification (>7-fold) was common among all histologic subtypes (24.5%) and was inversely associated with the presence of mutations. Overall, PIK3CA mutation or gene amplification was detected in 30.5% of all ovarian cancers and 45% of the endometrioid and clear cell subtypes. Our study is the first direct evidence that PIK3CA is an oncogene in ovarian cancer and greatly extends recent findings in breast cancer.
Nerve growth factor and receptor expression in rheumatoid arthritis and spondyloarthritis (2009)

Abstract Introduction We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). Methods mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant. Results SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro . Conclusions Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthritis.
Studies on equine recurrent uveitis. II: The role of infection withLeptospira interrogansserovarpomona (1985)

An enzyme linked immunosorbent assay was developed for the detection of immunoglobulin class specific antibodies to Leptospira interrogans serovar pomona in the serum and aqueous humor of horses. Serum antibody was also assayed by microscopic agglutination tests. Although higher levels of antibody were found in sera from horses with signs of uveitis, the association was not statistically significant. Antibodies to pomona were detected in the aqueous of 12 eyes from the 101 horses sampled at a slaughterhouse, and in most instances, a comparison of the aqueous/serum antibody level with that of the total aqueous/serum IgG level indicated intraocular antibody synthesis. Antibodies were also found in 4 aqueous (or vitreous) samples out of 9 obtained from horses with clinically documented uveitis and the above comparison again indicated intraocular antibody synthesis. The data point to an important role for pomona as an etiology of equine recurrent uveitis but also emphasize that the initiating cause for this disease is often obscure in that association with leptospirosis cannot be shown in many instances.
Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity (2017)

In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity.