gebhart/patrepeval huggingface dataset:
Effects of bile salts on the plasma membranes of isolated rat hepatocytes (1980)

The conjugated trihydroxy bile salts glycocholate and taurocholate removed approx. 20--30% of the plasma-membrane enzymes 5'-nucleotidase, alkaline phosphatase and alkaline phosphodiesterase I from isolated hepatocytes before the onset of lysis, as judged by release of the cytosolic enzyme lactate dehydrogenase. The conjugated dihydroxy bile salt glycodeoxycholate similarly removed 10--20% of the 5'-nucleotidase and alkaline phosphatase activities, but not alkaline phosphodiesterase activity; this bile salt caused lysis of hepatocytes at approx. 10-fold lower concentrations (1.5--2.0mM) than either glycocholate or taurocholate (12--16mM). At low concentrations (7 mM), glycocholate released these enzymes in a predominantly particulate form, whereas at higher concentrations (15 mM) glycocholate further released these components in a predominantly 'soluble' form. Inclusion of 1% (w/v) bovine serum albumin in the incubations had a small protective effect on the release of enzymes from hepatocytes by glycodeoxycholate, but not by glycocholate. These observations are discussed in relation to the possible role of bile salts in the origin of some biliary proteins.
The Equation for Response to Selection and Its Use for Prediction (1997)

The Breeder Genetic Algorithm (BGA) was designed according to the theories and methods used in the science of livestock breeding. The prediction of a breeding experiment is based on the response to selection (RS) equation. This equation relates the change in a population's fitness to the standard deviation of its fitness, as well as to the parameters selection intensity and realized heritability. In this paper the exact RS equation is derived for proportionate selection given an infinite population in linkage equilibrium. In linkage equilibrium the genotype frequencies are the product of the univariate marginal frequencies. The equation contains Fisher's fundamental theorem of natural selection as an approximation. The theorem shows that the response is approximately equal to the quotient of a quantity called additive genetic variance, VA, and the average fitness. We compare Mendelian two-parent recombination with gene-pool recombination, which belongs to a special class of genetic algorithms that we call univariate marginal distribution (UMD) algorithms. UMD algorithms keep the genotypes in linkage equilibrium. For UMD algorithms, an exact RS equation is proven that can be used for long-term prediction. Empirical and theoretical evidence is provided that indicates that Mendelian two-parent recombination is also mainly exploiting the additive genetic variance. We compute an exact RS equation for binary tournament selection. It shows that the two classical methods for estimating realized heritability--the regression heritability and the heritability in the narrow sense--may give poor estimates. Furthermore, realized heritability for binary tournament selection can be very different from that of proportionate selection. The paper ends with a short survey about methods that extend standard genetic algorithms and UMD algorithms by detecting interacting variables in nonlinear fitness functions and using this information to sample new points.
Molecular beacons: trial of a fluorescence-based solution hybridization technique for ecological studies with ruminal bacteria (1997)

Molecular beacons are fluorescent probes developed for solution rather than membrane hybridization. We have investigated the utility of these probes to study rumen microbial ecology. Two cellulolytic species, Ruminococcus albus and Fibrobacter succinogenes, were tested. Membrane and solution hybridizations gave similar results in competition experiments with cocultures of R. albus 8 and F. succinogenes S85.
Designing multi-user MIMO for energy efficiency: When is massive MIMO the answer? (2014)

Assume that a multi-user multiple-input multiple-output (MIMO) communication system must be designed to cover a given area with maximal energy efficiency (bits/Joule). What are the optimal values for the number of antennas, active users, and transmit power? By using a new model that describes how these three parameters affect the total energy efficiency of the system, this work provides closed-form expressions for their optimal values and interactions. In sharp contrast to common belief, the transmit power is found to increase (not decrease) with the number of antennas. This implies that energy efficient systems can operate at high signal-to-noise ratio (SNR) regimes in which the use of interference-suppressing precoding schemes is essential. Numerical results show that the maximal energy efficiency is achieved by a massive MIMO setup wherein hundreds of antennas are deployed to serve relatively many users using interference-suppressing regularized zero-forcing precoding.
Global analysis of proteins synthesized during phosphorus restriction in Escherichia coli (1996)

The pattern of proteins synthesized in Escherichia coli during steady-state growth in media with ample inorganic phosphate (Pi), upon limitation for Pi (without an alternative phosphorous compound), and during steady-state growth in media containing phosphonate (PHN) as the sole P source was examined by two-dimensional gel electrophoresis. Of 816 proteins monitored in these experiments, all those with differential synthesis rates greater than 2.0 or less than 0.5 upon phosphate limitation (P limitation) or during growth on PHN compared with their rates in the cultures with Pi were classified as belonging to the PL or PHN stimulon, respectively. The PL stimulon included 413 proteins, 208 showing induced synthesis and 205 showing repressed synthesis. The PHN stimulon was smaller: it included 257 proteins; 227 showed induced synthesis and 30 showed repressed synthesis. The overlap of the two stimulons included 137 proteins: most (118) were ones showing induced synthesis. The promoter regions of genes for several of the proteins with induced or repressed synthesis contained sequences which resembled the consensus sequence for PhoB binding. The aggregate mass of proteins responding to P limitation or growth on PHN was 30 to 40% of the cells' total mass. By comparing the proteins responding to P limitation with those responding to growth on PHN, one can speculate which proteins are likely involved in adapting cells to new P sources or in preparing cells to survive stationary phase.
The topology of the 30 S ribosomal subunit and a proposal for the surface distribution of its RNA by dark field electron microscopy. (1982)

A three-dimensional model of the Escherichia coli 30 S ribosome has been derived from an extensive dark field electron microscopic investigation of unstained and unshadowed ribosomes. Subsequent studies of specimens lightly stained with uranyl acetate have added information on the location of regions that preferentially bind uranyl ions and may represent surface RNA. The model is an elongated cone-shaped structure 180-200 A long and is divided into identifiable sections: a "head" partly encircled by a collar-like structure, a middle section carrying a 20-A protuberance, and a "tail." A groove separates the middle section from the tail. Uranyl-binding regions can be seen on the protuberance and the collar's ridge, in two bands below the collar and parallel to it, and in a patch on the back of the head. The staining technique described may offer a method for mapping the external nucleic acid of nucleoprotein complexes.
Chronic Stress Induces a Selective Decrease in AMPA Receptor-Mediated Synaptic Excitation at Hippocampal Temporoammonic-CA1 Synapses (2013)

Chronic stress promotes depression, but how it disrupts cognition and mood remains unknown. Chronic stress causes atrophy of pyramidal cell dendrites in the hippocampus and cortex in human and animal models, and a depressive-like behavioral state. We now test the hypothesis that excitatory temporoammonic (TA) synapses in the distal dendrites of CA1 pyramidal cells in rats are altered by chronic unpredictable stress (CUS) and restored by chronic antidepressant treatment, in conjunction with the behavioral consequences of CUS. We observed a decrease in AMPAR-mediated excitation at TA-CA1 synapses, but not Schaffer collateral-CA1 synapses, after CUS, with a corresponding layer-specific decrease in GluA1 expression. Both changes were reversed by chronic fluoxetine. CUS also disrupted long-term memory consolidation in the Morris water maze, a function of TA-CA1 synapses. The decreases in TA-CA1 AMPAR-mediated excitation and performance in the consolidation test were correlated positively with decreases in sucrose preference, a measure of anhedonia. We conclude that chronic stress selectively decreases AMPAR number and function at specific synapses and suggest that this underlies various depressive endophenotypes. Our findings provide evidence that glutamatergic dysfunction is an underlying cause of depression and that current first-line antidepressant drugs act by restoring excitatory synaptic strength. Our findings suggest novel therapeutic targets for this debilitating disease.
Semiconductor Eutectic Solar Cell. (1986)

Two-phase semiconducting eutectics are potential device-materials. Of these, the SnSe-SnSe2 eutectic was chosen for studies in detail because it consists of multi-p/n-layers of SnSe and SnSe2 semiconductors. Since plasma frequency has not been detected in its infrared reflectance spectrum up to 40 micrometers of wavelength, it suggests that the SnSe-SnSe2 eutectic is a nondegenerate semiconductor. As-grown SnSe2 single crystals have hexagonal crystallographic structure and show n-type conductivity. Polycrystalline SnSe and SnSe2 films have been successfully prepared in vacuum using a close-space-vapor transport technique. Keywords include: In-situ Composite, Eutectic Composite, Semiconductor Eutectic, Multijunction Photovoltaic, Multijunction Solar Cell, and Tin Selenide Eutectic.
Prognostic significance of CD100 expression in soft tissue sarcoma (2007)

The results from this study indicated the demonstrated prognostic significance of CD100 expression in STS.
The murG gene of Escherichia coli codes for the UDP-N-acetylglucosamine: N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis (1991)

Physiological properties of the murG gene product of Escherichia coli were investigated. The inactivation of the murG gene rapidly inhibits peptidoglycan synthesis in exponentially growing cells. As a result, various alterations of cell shape are observed, and cell lysis finally occurs when the peptidoglycan content is 40% lower than that of normally growing cells. Analysis of the pools of peptidoglycan precursors reveals the concomitant accumulation of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) and, to a lesser extent, that of undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide (lipid intermediate I), indicating that inhibition of peptidoglycan synthesis occurs after formation of the cytoplasmic precursors. The relative depletion of the second lipid intermediate, undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)GlcNAc, shows that inactivation of the murG gene product does not prevent the formation of lipid intermediate I but inhibits the next reaction in which GlcNAc is transferred to lipid intermediate I. In vitro assays for phospho-MurNAc-pentapeptide translocase and N-acetylglucosaminyl transferase activities finally confirm the identification of the murG gene product as the transferase that catalyzes the conversion of lipid intermediate I to lipid intermediate II in the peptidoglycan synthesis pathway. Plasmids allowing for a high overproduction of the transferase and the determination of its N-terminal amino acid sequence were constructed. In cell fractionation experiments, the transferase is essentially associated with membranes when it is recovered.
Association between occupation and knee and hip replacement due to osteoarthritis: a case-control study (2010)

These results support an association in males between occupations with heavy physical load and both TKR and THR for OA.
Real-world dosing patterns of patients (pts) with metastatic pancreatic cancer (mPC) treated with liposomal irinotecan (nal-IRI) in US oncology clinics (2018)

Background: nal-IRI + 5FU/LV therapy demonstrated significant survival improvement in mPC pts previously treated with gemcitabine-based therapy (NAPOLI-1). The generally recommended nal-IRI initiation dose is 70 mg/m2 (free base, equivalent to 80 mg/m2 salt based dosing). This retrospective observational analysis describes the real-world dosing patterns of nal-IRI. Methods: Using the Flatiron Health® longitudinal database, data was extracted and analyzed for adult pts with mPC treated with nal-IRI between Nov 2015 to Aug 2017. Dose intensity (DI) over the first 6 weeks of treatment, dose modifications anytime (mods), and overall duration of exposure (DOE) to nal-IRI were assessed. All dosing is expressed in terms of the free base. Results: 257 mPC pts (median age: 67y; IQR 61–74) treated with nal-IRI were identified; DI was calculated for 231 pts with available dose, height, and weight data. Mean DI was 177.8 mg/m2 (SD: 74.9 mg/m2). Median DOE was 7.3 (IQR: 3.4 – 17.1) weeks (wks). Median dose at initiation was 69.4 (IQR 56.7–70.2) mg/m2. Stratified into groups based on median DI (190 mg/m2), more pts below median DI initiated at a lower dose (LD) (30 - 65 mg/m2) compared to the pts at/above the median DI (44.4% vs 13.8%). Pts below median DI were also older: median age 70y (IQR 63 - 76) vs 65y (IQR 61 - 72). Mean DI was similar for pts who initiated nal-IRI in 1st/2nd line (176.4 mg/m2; n = 131) vs later lines (179.6 mg/m2; n = 100). In 1st/2nd line pts, median DOE was 8.9 (IQR: 3.1 – 19) wks vs 6.3 (IQR :3.4 – 12.1) wks in 3rd+ line. Median DOE in pts initiated at the recommended dose of 65-75 mg/m2 (n = 152) was 8.1 wks. DOE in LD (n = 67) and higher dose (75–90 mg/m2; n = 11) pts was 7.1 and 6.1 wks, respectively. 27.2% of pts experienced a dose mod (18.3% in 1st/2nd line; 8.9% in 3rd+ line). Pts with dose mods had a median DOE of 13.1 vs 6.1 wks in pts without mods. Conclusions: This real-world analysis showed similar DI results to the NAPOLI-1 trial, while dose mods were slightly lower. Pts with higher DI had longer DOE. Pts who experienced a dose mod, initiated nal-IRI in 1st/2nd line, were at/above median DI had, on average, longer DOE. Larger pt cohort analyses will elucidate dosing patterns and outcomes in nal-IRI treated pts. Legal entity responsible for the study: Ipsen Biopharmaceuticals. Funding: Ipsen Biopharmaceuticals. Disclosure: D. Ahn: Advisory board: Eisai. A. Surinach, F.A. Corvino: Employee: Genesis Research that received funding from Ipsen Biopharmaceuticals to conduct study. A. Valderrama, S. Pulgar: Employee: Ipsen Biopharmaceuticals. K. Mamlouk: Consultant: Ipsen Biopharmaceuticals. All other authors have declared no conflicts of interest.
Evaluation of a Blocking ELISA Using Monoclonal Antibodies for the Detection of Porcine Epidemic Diarrhea Virus and Its Antibodies (1995)

Two blocking enzyme-linked immunosorbent assays (ELISAs) involving the use of monoclonal antibodies (MAb) as capture and detecting agents and an indirect fluorescence test (IFT) were used for the detection of porcine epidemic diarrhea virus (PEDV) antigen or its antibodies. In the ELISA for viral antigen detection, the blocking step is accomplished by incubation of fecal samples, in duplicate wells, with PEDV-specific positive or negative serum, whereas in the ELISA for antibody detection the blocking step is accomplished by incubation of serum samples with a gut-origin virus suspension. All the methods developed were used to monitor an experimental infection in piglets with the CV-777 strain of PEDV and a natural PED outbreak in a swine fattening unit. The antigen-detection ELISA was able to detect PEDV shedding for a longer time than have previously described methods. The blocking ELISA for antibody detection was able to detect the serum antibody response sooner after PEDV infection than did IFT.
Novel Procedure for Modeling Ligand/Receptor Induced Fit Effects (2005)

We present a novel protein-ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does not change substantially upon ligand binding, success is limited when the protein must be "induced" into the correct binding conformation for a given ligand. We provide an in-depth description of our novel methodology and present results for 21 pharmaceutically relevant examples. Traditional rigid-receptor docking for these 21 cases yields an average RMSD of 5.5 A. The average ligand RMSD for docking to a flexible receptor for the 21 pairs is 1.4 A; the RMSD is < or =1.8 A for 18 of the cases. For the three cases with RMSDs greater than 1.8 A, the core of the ligand is properly docked and all key protein/ligand interactions are captured.
Novel Virulence Gene and Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) Multilocus Sequence Typing Scheme for Subtyping of the Major Serovars ofSalmonella entericasubsp.enterica (2011)

Salmonella enterica subsp. enterica is the leading cause of bacterial food-borne disease in the United States. Molecular subtyping methods are powerful tools for tracking the farm-to-fork spread of food-borne pathogens during outbreaks. In order to develop a novel multilocus sequence typing (MLST) scheme for subtyping the major serovars of S. enterica subsp. enterica, the virulence genes sseL and fimH and clustered regularly interspaced short palindromic repeat (CRISPR) loci were sequenced from 171 clinical isolates from nine Salmonella serovars, Salmonella serovars Typhimurium, Enteritidis, Newport, Heidelberg, Javiana, I 4,[5],12:i:-, Montevideo, Muenchen, and Saintpaul. The MLST scheme using only virulence genes was congruent with serotyping and identified epidemic clones but could not differentiate outbreaks. The addition of CRISPR sequences dramatically improved discriminatory power by differentiating individual outbreak strains/clones. Of particular note, the present MLST scheme provided better discrimination of Salmonella serovar Enteritidis strains than pulsed-field gel electrophoresis (PFGE). This method showed high epidemiologic concordance for all serovars screened except for Salmonella serovar Muenchen. In conclusion, the novel MLST scheme described in the present study accurately differentiated outbreak strains/clones of the major serovars of Salmonella, and therefore, it shows promise for subtyping this important food-borne pathogen during investigations of outbreaks.
<title>Three-Dimensional Stereometric Measurement System Using Optical Scanners, Cylindrical Lenses, And Line Sensors</title> (1983)

A simple and low-cost 3-dimensional stereometric measurement system has been developed which measures the shape of object by means of trigonometry. This system is composed of an X-Y optical scanner, cylindrical lenses and line sensors. A laser beam is incident on an object and is scanned over the area of interest by the optical scanner. Cartesian coordinates of a laser spot hit by the laser beam in a three dimensional space are determined simply and at high speed through the combined use of cylindrical lenses and line sensors. The cylindrical lens makes a line focus and, therefore, the coordinates of a light spot is projected onto a line orthogonal to the axis of the cylindrical lens. The position of the line focus in a line sensor can easily be measured by detecting the photo-cell which indicates the maximum output. Preliminary experiments suggest that the shape of the human torso surface can be measured with fairly good accuracy.
A New Therapy for Eosinophilic Esophagitis in Adults (2008)

Purpose: Topical steroid therapy such as aerosolized fluticasone has been demonstrated to be an effective treatment of Eosinophilic Esophagitis (EE) but may have oral side effects. We hypothesized that delivery of a budesonide gel specifically formulated to increase the contact time of the gel to the esophageal mucosa will result in a greater reduction in clinical symptoms of dysphagia and less oral side effects. Methods: An oral gel combining budesonide with the mucosal adherent preparation Rincinol (BRG) was compounded. Patients with abnormal Mayo dysphagia questionnaires underwent EGD with biopsies. 16 patients with greater than 15 eos/HPF and solid food dysphagia were enrolled in the study and treated with BRG. Patients were instructed to take BRG 3 mg/10 cc BID. If patients noted marked improvement at one week, they were switched to once daily BRG for 6 weeks; otherwise they were continued on BID BRG for a total of 6 weeks. Dysphagia symptoms and BRG side effects over the last two weeks of treatment were assessed by personal interview. Symptoms were evaluated on a scale of dysphagia resolution: <25%, 25–49%, 50–74%, 75–99% or complete resolution. Those patients, who had previously utilized topical fluticasone for EE, were asked to compare BRG vs topical fluticasone with respect to treatment effect and tolerance. Results: See Table 1 regarding the baseline clinical features of our EE patients. After 6 weeks of BRG therapy, all patients reported at least a 75% improvement in dysphagia symptomatology. 56% (9/16) of patients reported complete dysphagia resolution and 44% (7/16) reported a 75–99% reduction in dysphagia symptoms. Patients who transitioned from BID to once daily BRG noted no increase in dysphagia symptomatology. There was no significant difference in treatment response observed between the dosing regimens (Table 2). With respect to side effects, 13% (2/16) reported hoarseness and 6% (1/16) unpleasant taste. No oral candidiasis was observed with BRG therapy. Of the patients who had previously received fluticasone for treatment of EE, 38% (3/8) felt BRG was more effective, 62% (5/8) had no preference and none preferred fluticasone. When asked about tolerance, 50% (4/8) of patients tolerated both preparations equally, whereas 25% (2/8) favored fluticasone and 25% (2/8) favored budesonide.Table 2: BRG Dosing Regimen and Patient Reported Treatment EffectTable 1: Baseline Clinical Characteristics of Study PatientsConclusion: BRG effectively relieved symptoms of dysphagia in patients with esophageal eosinophilia with minimal side effects in this study. BRG may also be effective in treating EE patients who have previously failed fluticasone. Further studies should be performed to validate these findings.
Dynamic and static behavior of piezoelectric bimorphs with extenders in optical scanners (2002)

We have investigated the fabrication method by MEMS techniques of a Double Monomorph Optical Scanner and with Double "J" Flexures. The monomorphs were piezoelectric benders made of silicon covered by PZT, which acted as the piezoelectric material used to bend the flexures. A one dimensional double monomorph optical scanner consisting of two piezoelectric monomorphs connected to a mirror by means of Double "J" Flexures, has a large product of angular rotation and resonance frequency, and therefore it is more powerful and more versatile than a current state-of the-art optical scanner. We investigated resonance frequency and static behavior. The resonance showed nonlinear characteristics, evident in the shifting of the resonance frequency as function of the driving voltages and curve skipping.
TRPV1 is involved in stretch‐evoked contractile changes in the rat autonomous bladder model: a study with piperine, a new TRPV1 agonist (2007)

We found evidence for acute and prolonged effects of PIP on bladder contractility, which seem to be mediated through TRPV1. Furthermore, we found evidence for involvement of TRPV1 in afferent signaling of mechanical stimuli.