gebhart/patrepeval huggingface dataset:
Effect of enzyme supplementation at moderate cellulase loadings on initial glucose and xylose release from corn stover solids pretreated by leading technologies (2008)

Moderate loadings of cellulase enzyme supplemented with beta-glucosidase were applied to solids produced by ammonia fiber expansion (AFEX), ammonia recycle (ARP), controlled pH, dilute sulfuric acid, lime, and sulfur dioxide pretreatments to better understand factors that control glucose and xylose release following 24, 48, and 72 h of hydrolysis and define promising routes to reducing enzyme demands. Glucose removal was higher from all pretreatments than from Avicel cellulose at lower enzyme loadings, but sugar release was a bit lower for solids prepared by dilute sulfuric acid in the Sunds system and by controlled pH pretreatment than from Avicel at higher protein loadings. Inhibition by cellobiose was observed to depend on the type of substrate and pretreatment and hydrolysis times, with a corresponding impact of beta-glucosidase supplementation. Furthermore, for the first time, xylobiose and higher xylooligomers were shown to inhibit enzymatic hydrolysis of pure glucan, pure xylan, and pretreated corn stover, and xylose, xylobiose, and xylotriose were shown to have progressively greater effects on hydrolysis rates. Consistent with this, addition of xylanase and beta-xylosidase improved performance significantly. For a combined mass loading of cellulase and beta-glucosidase of 16.1 mg/g original glucan (about 7.5 FPU/g), glucose release from pretreated solids ranged from 50% to75% of the theoretical maximum and was greater for all pretreatments at all protein loadings compared to pure Avicel cellulose except for solids from controlled pH pretreatment and from dilute acid pretreatment by the Sunds pilot unit. The fraction of xylose released from pretreated solids was always less than for glucose, with the upper limit being about 60% of the maximum for ARP and the Sunds dilute acid pretreatments at a very high protein mass loading of 116 mg/g glucan (about 60 FPU).
Regulation of Cytokine Production in T-Cell Responses to Inhalant Allergen:GATA-3 Expression Distinguishesbetween Th1- and Th2-Polarized Immunity (2001)

Upregulation of GATA-3 expression in PBMC is a hallmark of the early phase of Th2 recall responses to specific allergen in atopics. The reciprocal expression pattern observed in HDM-specific recall responses of non-atopics provides independent confirmation of the presence of underlying Th1-like immunity in these subjects. The parallel findings in neonatal T cells suggest that the same approach may be utilized for monitoring the progress of allergen-specific Th1/Th2 memory development during early childhood, and hence in assessment of risk for future allergic disease.
Translation and the stability of mRNAs encoding the transferrin receptor and c-fos. (1991)

Turnover of the full-length human transferrin receptor (TfR) mRNA is regulated by iron, and this regulation is mediated by the transcript's 3' untranslated region. Alterations in the sequence of the TfR mRNA regulatory region have been identified that render the mRNA unregulated by iron and intrinsically unstable. When cells expressing this unstable mRNA are treated with inhibitors of protein synthesis (cycloheximide or puromycin), the steady-state level of the encoded human TfR mRNA is increased due to a stabilization of the transcript. A similar set of observations has been made using a chimeric mRNA in which the rapid turnover determinant of the TfR mRNA is replaced by the (A+U)-rich region from the 3' untranslated region of c-fos mRNA. To distinguish between a labile protein participant in the degradation of these mRNAs and a requirement for their translation per se, we introduced a ferritin iron-responsive element into the 5' untranslated region of each of these mRNAs. The presence of the 5' iron-responsive element allowed us to use iron availability to alter the translation of the mRNAs in question without global effects on cellular protein synthesis. Although specific translation of these mRNAs could be inhibited by iron chelation to a degree comparable to that seen with cycloheximide (approximately 95% inhibition), no effects on mRNA turnover were observed. These data support a model in which a trans-acting labile protein is necessary for the turnover of these mRNAs rather than there being a requirement for the translation of the mRNAs themselves.
Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and recurrent infections (2005)

A boy with developmental delay, particularly of speech, a distinct face, antineutrophil cytoplasmic antibodies, and recurrent infections was found to have an apparently balanced de novo t(1;6)(q32.3;q22.3) translocation. Fluorescent in situ hybridisation with BAC/PAC clones and long range polymerase chain reaction products assessed in the human genome sequence localised the chromosome 1 breakpoint to a 9.8 kb segment within a hypothetical gene, LOC388735, and the chromosome 6 breakpoint to a 12.8 kb segment in intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene. Disruption and/or formation of TCBA1 fusion genes in T cell lymphoma and leukaemia cell lines suggests a role for this gene in tumorigenesis. The isolated mouse Tcba1 gene shows 91% amino acid sequence similarity with human TCBA1. It is expressed in fetal and adult brain and with lower levels in liver and testis. The human gene has been reported to be expressed exclusively in brain and thymus. Reduced TCBA1 expression in brain and thymus may explain at least some of the symptoms in this patient. It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features.
THE PYROLYSIS OF OXIMES OF SOME GAMMA CYANO-AND GAMMA NITRO-KETONES (1965)

Oximes of gamma cyano- and gamma nitro-ketones are decomposed by heat as well as by acids. From the very complex mixtures resulting there have been isolated arylated pyrroles, arylated 2-aminopyridines, and the corresponding pyridones, as well as several minor products. This behavior constitutes a new synthesis of these heterocyclic compounds. In a Beckmann rearrangement γ-benzoyl-α,β-diphenylbutyronitrile gave an anilide, the structure of which was confirmed by an independent synthesis. By physical methods both structures of gamma ketonic amides are confirmed.
PPAR Modulators and PPAR Pan Agonists for Metabolic Diseases: The Next Generation of Drugs Targeting Peroxisome Proliferator-Activated Receptors? (2008)

The Peroxisome Proliferator-Activated Receptors-PPAR alpha, PPAR gamma, and PPAR delta--are members of the nuclear receptor gene family that have emerged as therapeutic targets for the development of drugs to treat human metabolic diseases. The discovery of high affinity, subtype-selective agonists for each of the three PPAR subtypes has allowed elucidation of the pharmacology of these receptors and development of first-generation therapeutic agents for the treatment of diabetes and dyslipidemia. However, despite proven therapeutic benefits of selective PPAR agonists, safety concerns and dose-limiting side effects have been observed, and a number of late-stage development failures have been reported. Scientists have continued to explore ligand-based activation of PPARs in hopes of developing safer and more effective drugs. This review highlights recent efforts on two newer approaches, the simultaneous activation of all three PPAR receptors with a single ligand (PPAR pan agonists) and the selective modulation of a single PPAR receptor in a cell or tissue specific manner (selective PPAR modulator or SPPARM) in order to induce a subset of target genes and affect a restricted number of metabolic pathways.
Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia (2011)

This pilot study supports the hypothesis that extracorporeal apheresis can lower circulating sFlt-1 in very preterm preeclampsia. Further studies are warranted to determine whether this intervention safely and effectively prolongs pregnancy and improves maternal and fetal outcomes in this setting.
Acute hyperglycemia induces rapid, reversible increases in glomerular permeability in nondiabetic rats (2010)

This study was performed to investigate the impact of acute hyperglycemia (HG) on the permeability of the normal glomerular filtration barrier in vivo. In anesthetized Wistar rats (250-280 g), the left ureter was catheterized for urine collection, while simultaneously blood access was achieved. Rats received an intravenous (iv) infusion of either 1) hypertonic glucose to maintain blood glucose at 20-25 mM (G; n = 8); 2) hypertonic glucose as in 1) and a RhoA-kinase inhibitor (Y-27632; Rho-G; n = 8); 3) 20% mannitol (MANN; n = 7) or 4) hypertonic (12%) NaCl to maintain plasma crystalloid osmotic pressure (pi(cry)) at approximately 320-325 mosmol/l (NaCl; n = 8) or 5) physiological saline (SHAM; n = 8). FITC-Ficoll 70/400 was infused iv for at least 20 min before termination of the experiments, and plasma and urine were collected to determine the glomerular sieving coefficients (theta) for polydisperse Ficoll (molecular radius 15-80 A) by high-performance size-exclusion chromatography. In G there was a marked increase in for Ficoll(55-80A) at 20 min, which was completely reversible within 60 min and abrogated by a Rho-kinase (ROCK) inhibitor, while glomerular permeability remained unchanged in MANN and NaCl. In conclusion, acute HG caused rapid, reversible increases in for large Ficolls, not related to the concomitant hyperosmolarity, but sensitive to ROCK inhibition. The changes observed were consistent with the formation of an increased number of large pores in the glomerular filter. The sensitivity of the permeability changes to ROCK inhibition strongly indicates that the cytoskeleton of the cells in the glomerular barrier may be involved in these alterations.
Prophylaxis against ampicillin-associated diarrhea with a lactobacillus preparation (1979)

The efficacy of a lactobacillus preparation (Lactinex) in preventing ampicillin-associated diarrhea in adult inpatients was studied. In a double-blind procedure, 98 patients were assigned randomly to receive one packet of Lactinex (Lactobacillus acidophilus and L bulgaricus) or placebo four times daily for the first five days of ampicillin therapy. Cases of diarrhea were reviewed independently and classified according to etiology. Complete data were obtained for 79 patients--43 received placebo and 36 received Lactinex. Diarrhea occurred in nine (21%) patients receiving placebo and in three (8.3%) patients receiving Lactinex; the difference was not statistically significant (p = 0.21, Fisher's Exact Test). When the patients with diarrhea unrelated to ampicillin were excluded (50%), the incidence of ampicillin-induced diarrhea in the placebo group (14%) was significantly greater (p = 0.03, Fisher's Exact Test) than in the Lactinex group (0%). Prophylactic administration of lactobacillus preparations may be effective in preventing ampicillin-induced diarrhea; however, prophylactic administration appears to be justified, on a cost/benefit basis, only in patients with a history of antibiotic-induced diarrhea.
A Population Pharmacokinetic and Pharmacodynamic Evaluation of Pralatrexate in Patients With Relapsed or Refractory Non-Hodgkin's or Hodgkin's Lymphoma (2009)

In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B(12) might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B(12) administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B(12) pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.
Investigation of current densities produced by surface electrodes using finite element modeling and current density imaging (2005)

Designers of gel-type surface electrodes, used in medical applications such as pain relief and neuromuscular stimulation, require a more thorough understanding of current pathways in tissue in order to design more effective electrical stimulation systems. To investigate these pathways, a finite element model (FEM) was used to compute current density distributions produced by an electrode placed on the surface of a homogeneous, tissue-mimicking gel slab. The gel slab phantom was constructed and the current densities were measured using a recently developed technique called current density imaging (CDI). CDI uses the phase data produced by magnetic resonance imaging (MRI) as a measure of the magnetic fields produced by the externally applied current. The results of the FEM simulation and CDI measurements compare well. CDI has several potential advantages over conventional FEM techniques including: no requirement for knowledge of local tissue conductivities, low and constant computational overhead regardless of tissue complexity, and the potential to perform in-vivo measurements.
Variational Data Assimilation with an Adiabatic Version of the NMC Spectral Model (1992)

Variational four-dimensional (4D) data assimilation is performed using an adiabatic version of the National Meteorological Center (NMC) baroclinic spectral primitive equation model with operationally analyzed fields as well as simulated datasets. Two limited-memory quasi-Newton minimization techniques were used to iteratively find the minimum of a cost function, with the NMC forecast as a constraint. The cost function consists of a weighted square sum of the differences between the model forecast and observations over a time interval. In all the experiments described in this paper, observations are available for all degrees of freedom of the model. The derivation of the adjoint of the discretized adiabatic NMC spectral model is presented. The creation of this adjoint model allows the gradient of the cost function with respect to the initial conditions to be computed using a single backward-in-time integration of the adjoint equations. As an initial evaluation of the variational data-assimilation procedure, an assimilation system with a low-resolution version of the NMC spectral model was tested using fields from a Rossby-Haurwitz-wave solution as observations. The results were encouraging, with a significant reduction in the magnitudes of both the cost function and the norm of its gradient during the minimization process. In particular, the high-frequency noise exhibited in the rms of the divergence field, produced by random perturbation in the initial conditions, is largely eliminated after the variational data assimilation. The performance of the assimilation scheme was examined in a more realistic configuration using the adiabatic NMC spectral model truncated at T40. Both operationally analyzed observations, consisting of vorticity, divergence, temperature, surface pressure and moisture fields (distributed at two time levels separated by a 6-h time interval), and model-generated data were variationally assimilated. The effect of the number of observation fields in time on the convergence rate of the minimization and the impacts due to the inclusion of the horizontal diffusion and the surface drag in the model and its adjoint on the convergence rate and the accuracy of the retrieval are addressed.
Separation of Long DNA Molecules by Quartz Nanopillar Chips under a Direct Current Electric Field (2003)

We have established the nanofabrication technique for constructing nanopillars with high aspect ratio (100-500 nm diameter and 500-5000 nm tall) inside a microchannel on a quartz chip. The size of pillars and the spacing between pillars are designed as a DNA sieving matrix for optimal analysis of large DNA fragments over a few kilobase pairs (kbp). A chip with nanopillar channel and simple cross injector was developed based on the optimal design and applied to the separation of DNA fragments (1-38 kbp) and large DNA fragments (lambda DNA, 48.5 kbp; T4 DNA, 165.6 kbp) that are difficult to separate on conventional gel electrophoresis and capillary electrophoresis without a pulsed-field technique. DNA fragments ranging from 1 to 38 kbp were separated as clear bands, and furthermore, the mixture of lambda DNA and T4 DNA was successfully separated by a 380-microm-long nanopillar channel within only 10 s even under a direct current (dc) electric field. Theoretical plate number N of the channel (380-1450 microm long) was 1000-3000 (0.7 x 10(6)-2.1 x 10(6) plates/m). A single DNA molecule observation during electrophoresis in a nanopillar channel revealed that the optimal nanopillars induced T4 DNA to form a narrow U-shaped conformation during electrophoresis whereas lambda DNA kept a rather spherical conformation. We demonstrated that, even under a dc electric field, the optimal nanopillar dimensions depend on a gyration radius of DNA molecule that made it possible to separate large DNA fragments in a short time.
Response of satellite cells to focal skeletal muscle injury (1985)

The time course and pattern of the initiation of satellite cell mitoses was studied following a crush injury of the distal third of the 30-day-old rat extensor digitorum longus, a muscle in which myofibers run the entire length of the belly. Satellite cell mitotic activity was monitored using autoradiography after injection of 3H-thymidine. Satellite cell labeling rose above control values by 15 hours post injury at the injured site and by 20 hours in the middle third or adjacent undamaged portion of the muscle. Labeling decreased in the proximal third of the muscle, so that by 25 hours post injury, a gradient of labeling was established along the muscle length. Electron microscopy (EM) quantitation showed that the reduced labeling in the proximal third resulted from a reduction in satellite cell numbers. The results suggest that mitotic activity of satellite cells after localized injury occurs mainly at or near the site of injury, but that many of the dividing cells have migrated from undamaged areas distant from the lesion site.
Expression cloning of a human B1 bradykinin receptor. (1994)

A cDNA clone encoding a human B1 bradykinin receptor was isolated from a human embryonic lung fibroblast cDNA library by expression cloning. The photoprotein aequorin was utilized as an indicator of the ability of the B1 receptor agonist [des-Arg10]kallidin to mediate Ca2+ mobilization in Xenopus laevis oocytes injected with RNA. A clone was isolated with a 1307-nucleotide insert which contains an open reading frame encoding a 353-amino acid protein with the characteristics of a G-protein-coupled receptor. The amino acid sequence of the B1 bradykinin receptor is 36% identical to the amino acid sequence of the B2 bradykinin receptor. The cloned B1 bradykinin receptor expressed in mammalian cells exhibits high affinity binding for 3H-labeled [des-Arg10]kallidin and low affinity for bradykinin. The B1 receptor antagonist [des-Arg10,Leu9]kallidin effectively displaces 3H-labeled [des-Arg10]kallidin from the cloned receptor, whereas the B2 receptor antagonist Hoe-140 (D-Arg0-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, where Thi is L-[3-(2-thienyl)alanyl], Tic is D-(1,2,3,4-tetrahydroisoquinolin-3-yl-carbonyl), and Oic is L-[(3aS, 7aS)-octahydroindol-2-yl-carbonyl]) does not. Therefore, the expressed receptor has the pharmacological characteristics of the B1 receptor subtype. The availability of both the cloned human B1 and B2 bradykinin receptors should allow the elucidation of the relative contributions of these two receptor subtypes in acute and chronic inflammatory processes.
Efficient site-directed mutagenesis by simultaneous use of two primers (1983)

A rapid and efficient procedure for site specific mutagenesis is described. A double primed synthesis with a 17-mer mismatch primer and a "universal" 15-mer M13 sequencing primer was used to introduce a T to A transversion into an ompF signal peptide gene cloned in the M13mp8 vector. The two primers were annealed to the circular single stranded M13 template. After a short extension and ligation reaction, a double stranded restriction fragment containing the mismatch (ompF*/EcoR1-SalI) was cut out of the partly single stranded circular DNA and inserted into pBR322. 42% of the E.coli transformants harboured plasmid with the desired mutation, which could be detected by the appearance of a new restriction site (MboII) and by dot blot hybridization of plasmid DNA with the 32P-labeled 17-mer.
Reversibility of Covalent Electrophile−Protein Adducts and Chemical Toxicity (2008)

The biotin-tagged electrophiles 1-biotinamido-4-(4'-[maleimidoethylcyclohexane]-carboxamido)butane (BMCC) and N-iodoacetyl-N-biotinylhexylenediamine (IAB) have been used as model electrophile probes in complex proteomes to identify protein targets associated with chemical toxicity. Whereas IAB activates stress signaling and apoptosis in HEK293 cells, BMCC does not. Cysteine Michael adducts formed from BMCC and nonbiotinylated analogues rapidly disappeared in the intact cells, whereas the adducts were stable in BMCC-treated subcellular fractions, even in the presence of the cellular reductants reduced glutathione, NADH, and NADPH. In contrast, cysteine thioether adducts formed from IAB and its nonbiotinylated analogues were stable in intact cells. Loss of the BMCC adduct in cells was reduced at 4 degrees C, which suggests the involvement of a metabolic process in adduct removal. Model studies with a glutathione-BMCC conjugate indicated rapid hydrolysis of the adducted imide ring, but neither the conjugate nor its hydrolysis product dissociated to release the electrophile in neutral aqueous buffer at significant rates. The results suggest that low BMCC toxicity reflects facile repair that results in transient adduction, which fails to trigger damage-signaling pathways.
A Review of Acute Cyanide Poisoning With a Treatment Update (2011)

Cyanide causes intracellular hypoxia by reversibly binding to mitochondrial cytochrome oxidase a(3). Signs and symptoms of cyanide poisoning usually occur less than 1 minute after inhalation and within a few minutes after ingestion. Early manifestations include anxiety, headache, giddiness, inability to focus the eyes, and mydriasis. As hypoxia progresses, progressively lower levels of consciousness, seizures, and coma can occur. Skin may look normal or slightly ashen, and arterial oxygen saturation may be normal. Early respiratory signs include transient rapid and deep respirations. As poisoning progresses, hemodynamic status may become unstable. The key treatment is early administration of 1 of the 2 antidotes currently available in the United States: the well-known cyanide antidote kit and hydroxocobalamin. Hydroxocobalamin detoxifies cyanide by binding with it to form the renally excreted, non-toxic cyanocobalamin. Because it binds with cyanide without forming methemoglobin, hydroxocobalamin can be used to treat patients without compromising the oxygen-carrying capacity of hemoglobin.