gebhart/patrepeval huggingface dataset:
Peptide YY Inhibits Nutrient-, Hormonal-, and Vagally-Stimulated Pancreatic Exocrine Secretion (1987)

Peptide YY (PYY) is a recently isolated gut peptide that is found primarily in the mucosal endocrine cells of the terminal ileum, colon, and rectum of several mammalian species, including humans. The purpose of this study was to characterize the effect of PYY on pancreatic exocrine secretion in six conscious dogs prepared with pancreatic and gastric fistulas. In control experiments, pancreatic exocrine secretion was stimulated by either intravenous (i.v.) administration of secretin (100 ng/kg/h), cholecystokinin-8 (50 ng/kg/h), neurotensin (5 micrograms/kg/h), or 2-deoxy-D-glucose (75 mg/kg); or by the intraduodenal infusion of hydrochloric acid (4 mEq/h), a mixture of amino acids (phenylalanine + tryptophan at 5 mmol/h), sodium oleate (9 mmol/h), or a liquid meal. On separate days, PYY (12.5, 25, 50, 100, 200, or 400 pmol/kg/h) was given intravenously in combination with one of the above pancreatic secretagogues. Intravenous PYY at 200 and 400 pmol/kg/h inhibited secretin-stimulated pancreatic bicarbonate output significantly (p less than 0.05). Pancreatic bicarbonate and protein responses to all pancreatic secretagogues were reduced significantly (p less than 0.05) by PYY at 400 pmol/kg/h. Intravenous administration of atropine (0.6 mg bolus, followed by 0.02 mg/kg/h) did not abolish the ability of PYY to inhibit secretin-stimulated pancreatic bicarbonate secretion. This study demonstrates that PYY can inhibit nutrient-, hormonal-, and vagally-stimulated pancreatic exocrine secretion in the dog; its mechanism of action appears to be independent of cholinergic innervation.
L-lysine production at 50 degrees C by mutants of a newly isolated and characterized methylotrophic Bacillus sp (1990)

The amino acid L-lysine was produced from homoserine auxotrophic and S-(2-aminoethyl)-L-cysteine-resistant mutants of a newly isolated gram-positive methylotrophic bacterium, capable of growth on methanol at 60 degrees C. The temperature optimum for growth was between 50 and 53 degrees C. These aerobic, gram-positive, endospore-forming, rod-shaped bacteria required biotin and vitamin B12 for growth. Extracts of the bacteria grown on methanol lacked hydroxypyruvate reductase and contained hexulose 6-phosphate synthase activity. Therefore, these bacteria were considered to be type I methylotrophic bacteria of the genus Bacillus. Fed-batch fermentations resulted in cell densities of 50 g of cell dry weight per liter. Biomass yields on carbon, nitrogen, phosphate, and sulfate were determined. Generation of homoserine auxotrophic and amino acid analog-resistant mutants resulted in L-lysine concentrations of nearly 20 g/liter in fed-batch fermentations.
Somatic comorbidity in anorexia nervosa: First results of a 21-year follow-up study on female inpatients (2012)

Somatic comorbidity seems to be an important factor for anorexia nervosa outcome and should be included in multivariate analyses on the long-term course of anorexia nervosa as an independent variable. Further investigations are needed in order to understand in which way anorexia nervosa and a somatic disease can interact.
Template/Primer Requirements and Single Nucleotide Incorporation by Hepatitis C Virus Nonstructural Protein 5B Polymerase (2000)

Nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) possesses an RNA-dependent RNA polymerase activity responsible for viral genome RNA replication. Despite several reports on the characterization of this essential viral enzyme, little is known about the reaction pathway of NS5B-catalyzed nucleotide incorporation due to the lack of a kinetic system offering efficient assembly of a catalytically competent polymerase/template/primer/nucleotide quaternary complex. In this report, specific template/primer requirements for efficient RNA synthesis by HCV NS5B were investigated. For intramolecular copy-back RNA synthesis, NS5B utilizes templates with an unstable stem-loop at the 3' terminus which exists as a single-stranded molecule in solution. A template with a stable tetraloop at the 3' terminus failed to support RNA synthesis by HCV NS5B. Based on these observations, a number of single-stranded RNA templates were synthesized and tested along with short RNA primers ranging from two to five nucleotides. It was found that HCV NS5B utilized di- or trinucleotides efficiently to initiate RNA replication. Furthermore, the polymerase, template, and primer assembled initiation-competent complexes at the 3' terminus of the template RNA where the template and primer base paired within the active site cavity of the polymerase. The minimum length of the template is five nucleotides, consistent with a structural model of the NS5B/RNA complex in which a pentanucleotide single-stranded RNA template occupies a groove located along the fingers subdomain of the polymerase. This observation suggests that the initial docking of RNA on NS5B polymerase requires a single-stranded RNA molecule. A unique beta-hairpin loop in the thumb subdomain may play an important role in properly positioning the single-stranded template for initiation of RNA synthesis. Identification of the template/primer requirements will facilitate the mechanistic characterization of HCV NS5B and its inhibitors.
Optical amplification of photothermal therapy with gold nanoparticles and nanoclusters (2006)

Recently, several groups (Anderson, Halas, Zharov, and their co-workers, 2003; El-Sayed and co-workers, 2006) demonstrated, through pioneering results, the great potential of photothermal (PT) therapy for the selective treatment of cancer cells, bacteria, viruses, and DNA targeted with gold nanospheres, nanoshells, nanorods, and nanosphere clusters. However, the current understanding of the relationship between the nanoparticle/cluster parameters (size, shape, particle/cluster structure, etc) and the efficiency of PT therapy is limited. Here, we report theoretical simulations aimed at finding the optimal single-particle and cluster structures to achieve its maximal absorption, which is crucial for PT therapeutic effects. To characterize the optical amplification in laser-induced thermal effects, we introduce relevant parameters such as the ratio of the absorption cross section to the gold mass of a single-particle structure and absorption amplification, defined as the ratio of cluster absorption to the total absorption of non-interacting particles. We consider the absorption efficiency of single nanoparticles (gold spheres, rods, and silica/gold nanoshells), linear chains, 2D lattice arrays, 3D random volume clusters, and the random aggregated N-particle ensembles on the outer surface of a larger dielectric sphere, which mimic aggregation of nanosphere bioconjugates on or within cancer cells. The cluster particles are bare or biopolymer-coated gold nanospheres. The light absorption of cluster structures is studied by using the generalized multiparticle Mie solution and the T-matrix method. The gold nanoshells with (silica core diameter)/(gold shell thickness) parameters of (50–100)/(3–8) nm and nanorods with minor/major sizes of (15–20)/(50–70) nm are shown to be more efficient PT labels and sensitizers than the equivolume solid single gold spheres. In the case of nanosphere clusters, the interparticle separations and the short linear-chain fragments are the main structural parameters determining the absorption efficiency and its spectral shifting to the red. Although we have not found a noticeable dependence of absorption amplification on the cluster sphere size, 20–40 nm particles are found to be most effective, in accordance with our experimental observations. The long-wavelength absorption efficiency of random clusters increases with the cluster particle number N at small N and reveals a saturation behaviour at N>20.
Cytotoxic T lymphocyte response against multiple simian immunodeficiency virusA (SIV) proteins in SIV-infected macaques (1992)

To identify the target proteins of CD8+ T lymphocytes we have explored the cytolytic immune responses of 12 rhesus macaques experimentally infected with the simian immunodeficiency virus (SIVmac). Target cells were autologous B cell lines presenting SIVmac proteins after infection with recombinant vaccinia viruses. The eight following proteins were studied: ENV, POL, GAG, NEF, VIF, REV, TAT, and VPX. Macaque PBMC stimulated with Con A and expanded in T cell growth factor-containing medium produced cell lines with cytolytic activity in the majority of infected animals (9/12). The structural proteins ENV, POL, and GAG were recognized by cell lines derived from nine, eight, and six macaques, respectively. The small regulatory proteins also represented efficient CTL targets, a specific activity being detected against NEF (8/12), REV (7/12), VPX (7/12), TAT (6/12), and VIF (5/12). Most cytotoxic responses (except those directed against ENV) were mediated by CD8 cells and were MHC class I restricted. Limiting dilution analysis allowed us to quantify the frequency of CTL precursors and confirmed the high immunogenicity of multiple SIV proteins. Three different patterns of response could be defined: six animals were able to recognize at least six of the eight tested target proteins, two of them reacting with all eight target proteins. The other three responder macaques reacted only against a few SIV proteins, whereas no cytotoxic activity was detected in the three remaining infected macaques and in the nine negative controls. The six animals responding against multiple proteins were still healthy 12 to 22 mo after infection with two of them presenting a decrease in circulating CD4 cells concurrently to the disappearance of the CTL response. Conversely, three nonresponder or low responder macaques developed an overt disease after 4 to 12 mo, and two other presented a very low level of CD4 cells, suggesting that the pattern of response may be of prognostic value.
Field-deployable viral diagnostics using CRISPR-Cas13 (2018)

Mitigating global infectious disease requires diagnostic tools that are sensitive, specific, and rapidly field deployable. In this study, we demonstrate that the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENV detection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015-2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.
Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors (2009)

The pathogenicity of many bacteria depends on the injection of effector proteins via type III secretion into eukaryotic cells in order to manipulate cellular processes. TAL (transcription activator-like) effectors from plant pathogenic Xanthomonas are important virulence factors that act as transcriptional activators in the plant cell nucleus, where they directly bind to DNA via a central domain of tandem repeats. Here, we show how target DNA specificity of TAL effectors is encoded. Two hypervariable amino acid residues in each repeat recognize one base pair in the target DNA. Recognition sequences of TAL effectors were predicted and experimentally confirmed. The modular protein architecture enabled the construction of artificial effectors with new specificities. Our study describes the functionality of a distinct type of DNA binding domain and allows the design of DNA binding domains for biotechnology.
Etomidate Inhibits Adrenocortical Function in Surgical Patients (1984)

Postoperative adrenocortical function was compared in 23 out-patients receiving either thiopental, 4 mg/kg, for induction and a thiopental infusion, 0.26 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance of anesthesia (control); etomidate, 0.4 mg/kg, for induction followed by an etomidate infusion, 0.02 mg . kg-1 . min-1, and nitrous oxide 70% for maintenance (etomidate I); or etomidate, 0.4 mg/kg, for induction and a thiopental infusion, 0.22 mg . kg-1 . min-1, in combination with nitrous oxide 70% for maintenance (etomidate II). The norepinephrine response to anesthesia and surgery did not differ significantly between the three groups. The postoperative cortisol response to ACTH stimulation was normal in the control group (maximum rise in plasma cortisol was 20.1 +/- 2.9 micrograms/dl [mean +/- SEM] ), however, it was decreased in all patients receiving etomidate, whether by a short infusion (mean change in plasma cortisol was -3.8 +/- 1.9 micrograms/dl) or as a single induction dose (mean change in plasma cortisol was -4.0 +/- 2.0 micrograms/dl). Similarly, the postoperative aldosterone levels in the control group increased normally in response to ACTH (+ 10.2 +/- 3.0 ng/dl) but decreased in both the etomidate I and etomidate II groups (-3.0 +/- 0.7 ng/dl and -3.3 +/- 1.0 ng/dl, respectively). Because ACTH was administered exogenously, etomidate-induced suppression of adrenocortical response appeared to be a direct effect on the adrenal gland, which was present at a time when the serum etomidate levels were in the subhypnotic range.(ABSTRACT TRUNCATED AT 250 WORDS)
Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing nanoparticle-mediated Drug Delivery (2010)

The use of peptides to mediate the delivery and uptake of nanoparticle (NP) materials by mammalian cells has grown significantly over the past 10 years. This area of research has important implications for the development of new therapeutic materials and for the emerging field of NP-mediated drug delivery. In this review, we highlight recent advances in the delivery of various NPs by some of the more commonly employed cellular delivery peptides and discuss important related factors such as NP-peptide bioconjugation, uptake efficiency, intracellular fate and toxicity. We also highlight various demonstrations of therapeutic applications of NP-peptide conjugates where appropriate. The paper concludes with a brief forward-looking perspective discussing what can be expected as this field develops in the coming years.
Escherichia coli K-12 structural kdgT mutants exhibiting thermosensitive 2-keto-3-deoxy-D-gluconate uptake (1977)

A specific method is described for selecting thermosensitive mutants of Escherichia coli K-12 able to grow on 2-keto-3-deoxy-D-gluconate (KDG) and D-glucuronate at 2, but not at 42 degrees C. The extensive analysis of one such mutant is consistent with the conclusion that the carrier molecule responsible for KDG and glucuronate uptake becomes thermolabile. (i) Growth on a variety of carbon sources is perfectly normal at 28 and 42 degrees C, whereas in the same temperature range it gradually diminishes on KDG and glucuronate. (ii) The apparent Km value for KDG is about twofold in the range 25 to 40 degrees C. In the same temperature range, the Vmax values for KDG influx are higher for the mutant compared with those of the wild-type strain, but the optimum temperature is 34 degrees C instead of 38 degrees C. On the contrary, the Vmax values for glucuronate influx are lower for the mutant than for the parental strain, and the optimum temperature for both strains is shifted beyond 40 degrees C. (iii) The activation energies for KDG and glucuronate uptake are about twofold higher in the mutant than in the wild-type strain. (iv) Kinetics of counterflow under deenergized conditions (overshoot) at different temperatures indicate that the defect is located in the translocation step rather than in the processes involved in energy coupling. (v) The first-order rate constants for thermal denaturation are, respectively, 2.5- and 5-fold higher at 40 and 30 degrees C in the mutant than in the wild-type strain, and the activation energy for thermal denaturation is lower. (vi) The carrier molecule in the mutant is also much more sensitive to denaturation by N-ethylmaleimide. (vii) Four independent thermosensitive mutations and one revertatn were located by transduction in or near the kdgT locus, defined previously as the site of nonconditional KDG transport-negative mutations. These results support the conclusion that kdgT represents the structural gene coding for the KDG transport system.
Polarity of Liquid Interfaces by Second Harmonic Generation Spectroscopy (1997)

A spectroscopic method, based on the interface selectivity of second-harmonic generation, is used to obtain the polarity of liquid interfaces. In this paper the second-harmonic measurement of the spectrum of the polarity indicator molecule N,N‘-diethyl-p-nitroaniline (DEPNA) at the air/water interface demonstrates the method. Two different approaches are used to measure the intramolecular charge transfer (CT) absorption band position of DEPNA at the air/water interface. The DEPNA CT band blue-shifts from 429 nm in bulk water (polar solvent) to 359 nm in bulk hexane (nonpolar solvent) and 329 nm in the gas phase (no solvent). At the air/water interface, the charge transfer peak band maximum occurs at 373 nm, which indicates that the polarity of the air/water interface is similar to those of the bulk solvents carbon tetrachloride and butyl ether. The DEPNA results together with the results from another solvatochromic polarity indicator molecule, ET(30), which will be reported elsewhere, show that the polarity results of the air/water interface are general.
Microarray analysis reveals that TP53- and ATM-mutant B-CLLs share a defect in activating proapoptotic responses after DNA damage but are distinguished by major differences in activating prosurvival responses (2003)

The ATM/p53-dependent DNA damage response pathway plays an important role in the progression of lymphoid tumors. Inactivation of the ATM or TP53 gene is frequent in B-cell lymphocytic leukemia (B-CLL) and leads to aggressive disease. Although the ATM and p53 pathways overlap, they are not congruent, and it is unclear how the mechanism of tumor progression differs between ATM- and p53-deficient tumors. Using microarray analysis of ATM-mutant, TP53-mutant, and ATM/TP53 wild-type B-CLLs, we show that after exposure to DNA damage transcriptional responses are entirely dependent on ATM function. The p53 proapoptotic responses comprise only a part of ATM-regulated transcription; additionally, ATM regulates prosurvival responses independently of p53. Consequently, the greater severity of the TP53-mutant B-CLLs compared with ATM-mutant B-CLLs is consistent with the additive effect of defective apoptotic and elevated survival responses after DNA damage in these tumors. We also show that transcription expression profiles of ATM-deficient, TP53-deficient, and wild-type B-CLLs are indistinguishable before irradiation. Therefore, damage-induced transcriptional fingerprinting can be used to stratify tumors according to their biologic differences and simultaneously identify potential targets for treating refractory tumors.
Early Retinal Function Deficit without Prominent Morphological Changes in the R6/2 Mouse Model of Huntington’s Disease (2014)

Huntington's disease (HD) is an inherited neurodegenerative disorder that primarily affects the medium-size GABAergic neurons of striatum. The R6/2 mouse line is one of the most widely used animal models of HD. Previously the hallmarks of HD-related pathology have been detected in photoreceptors and interneurons of R6/2 mouse retina. Here we aimed to explore the survival of retinal ganglion cells (RGCs) and functional integrity of distinct retinal cell populations in R6/2 mice. The pattern electroretinography (PERG) signal was lost at the age of 8 weeks in R6/2 mice in contrast to the situation in wild-type (WT) littermates. This defect may be attributable to a major reduction in photopic ERG responses in R6/2 mice which was more evident in b- than a-wave amplitudes. At the age of 4 weeks R6/2 mice had predominantly the soluble form of mutant huntingtin protein (mHtt) in the RGC layer cells, whereas the aggregated form of mHtt was found in the majority of those cells from the 12-week-old R6/2 mice and onwards. Retinal astrocytes did not contain mHtt deposits. The total numbers of RGC layer cells, retinal astrocytes as well as optic nerve axons did not differ between 18-week-old R6/2 mice and their WT controls. Our data indicate that mHtt deposition does not cause RGC degeneration or retinal astrocyte loss in R6/2 mice even at a late stage of HD-related pathology. However, due to functional deficits in the rod- and cone-pathways, the R6/2 mice suffer progressive deficits in visual capabilities starting as early as 4 weeks; at 8 weeks there is severe impairment. This should be taken into account in any behavioral testing conducted in R6/2 mice.
Control of the electrode work function and active layer morphology via surface modification of indium tin oxide for high efficiency organic photovoltaics (2007)

Indium tin oxide (ITO) substrates modified with self-assembled monolayers (SAMs) were used to control the anode work function and active layer morphology of organic solar cells based on poly(3-hexylthiophene)/[6:6]-phenyl-C61 butyric acid methyl ester heterojunctions. By using SAMs with the terminal groups –NH2, –CH3, and –CF3, the authors were able to control the hole injection barrier of the ITO closer to the highest occupied molecular orbital level of active layer and surface energy of the ITO substrate. A solar cell device with CF3 SAM treated ITO was found to exhibit high efficiency performance, about 3.15%.
"Covalent affinity" purification of ubiquitin-activating enzyme. (1982)

We have previously described an enzyme that activates ubiquitin, the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes (Ciechanover, A., Heller, H., Katz-Etzion, R., and Hershko, A. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 761-765). It carries out ubiquitin-dependent PPi-ATP and AMP-ATP exchange reactions and binds to the activated polypeptide by a thiolester linkage. We describe here a procedure for the purification of this enzyme by its binding to ubiquitin-Sepharose. Binding of the enzyme to the affinity column requires ATP and Mg2+, and bound enzyme cannot be displaced by high salt but can be eluted by raising the pH, by increased concentrations of a thiol compound, or by the joint supplementation of AMP and pyrophosphate. Another form of the enzyme that cannot carry out AMP-ATP exchange (but catalyzes ubiquitin-dependent PPi-ATP exchange) does not bind to the affinity column. These data indicate that a covalent, possibly thiolester intermediate, is formed between the activating enzyme and Sepharose-bound ubiquitin. It is suggested designating this procedure of enzyme isolation "covalent affinity" chromatography. The purified enzyme has an apparent Mr = 210,000 and appears to be composed of two subunits of Mr = 105, 000. ATP-dependent binding of ubiquitin to the purified enzyme and to its subunit is demonstrated.
Experiments on the rise of air bubbles in clean viscous liquids (1996)

A number of new experiments have been performed on the rise of air bubbles in clean mixtures of distilled water and pure, reagent grade, glycerine covering a range of the relevant parameter, the Morton number, Mo = gv 4 ρ 3 /σ 3 , of 10 13 . Here g is the acceleration due to gravity, v the kinematic viscosity, ρ the density and σ the surface tension of the mixture. In these careful measurements several scaling regimes have been found that have not been discussed before in the extensive literature on the subject. The transitions between these regimes have been delineated and attempts made to discuss the dynamical processes that might be important in each of them.