gebhart/patrepeval huggingface dataset:
Dirlotapide: a review of its properties and role in the management of obesity in dogs (2007)

Dirlotapide is a microsomal triglyceride transfer protein (MTP) inhibitor developed specifically for canine weight reduction. MTP catalyzes the assembly of triglyceride-rich apolipoprotein-B containing lipoproteins to form chylomicrons in the intestinal mucosa and very low-density lipoproteins in the liver. Following oral administration, dirlotapide has in vivo selectivity for intestinal MTP compared with hepatic MTP. In addition to reducing intestinal fat absorption, dirlotapide also reduces food intake in a dose-dependent manner, probably via increased release of peptide YY into the circulation. The decrease in food intake is responsible for the majority of the weight reduction effect. In clinical use, it is recommended to adjust the dose according to the observed weight loss of each individual. The initial dose of 0.05 mg/kg is doubled after 14 days and then adjusted monthly, the maximum permitted daily dose is 1.0 mg/kg, although doses as high as 10 mg/kg have been administered to dogs without severe adverse experience in safety studies. Dirlotapide can be used without necessitating changes to the current feeding or exercise regimens, but it is desirable to monitor the food intake during weight-stabilization to establish revised feeding and exercise routines that will minimize the risk of weight regain post-treatment. The drug offers a novel approach that is applicable in cases where dietary management alone has proved to be unsuccessful.
Bile acid metabolism in early life: studies of amniotic fluid. (1990)

Bile acid metabolism of the human fetus was examined in early gestation (weeks 13-19) and compared with the full-term fetus from the analysis of amniotic fluid collected from healthy pregnant women. Total individual bile acids were determined by gas-liquid chromatography-mass spectrometry after solvolysis and hydrolysis of bile acid conjugates. Additionally, bile acids were separated according to their mode of conjugation by lipophilic anion exchange chromatography. Qualitatively the bile acid profiles of amniotic fluid in early gestation were similar and markedly different from those of full-term fetuses. Chenodeoxycholic acid was the major bile acid identified in early gestation and concentrations exceeded those of cholic acid, but by full term this relationship was reversed. Over 50 bile acids were identified in the amniotic fluids, these included C-1, C-4, and C-6 hydroxylated species and reflected primary hepatic synthesis by the fetus. At full term, 7 alpha,12 alpha-dihydroxy-3-oxo-4-cholenoic acid was one of the major bile acids identified in amniotic fluid. The monohydroxy bile acids lithocholic and 3 beta-hydroxy-5-cholenoic acids were present in significant proportions during early gestation, but by full term these accounted for only a few percent of the total bile acids. Quantitatively the total bile acid concentration of amniotic fluid was less than 4 mumol/l. The majority of bile acids were found to be glyco-, tauro-, and sulfate-conjugates. The more hydrophobic bile acids tended to be preferentially sulfated. These data indicate that significant and major changes in bile acid metabolism take place between early and late gestation in the human fetus.
Generation of Solution and Surface Gradients Using Microfluidic Systems (2000)

This paper describes a simple, versatile method of generating gradients in composition in solution or on surfaces using microfluidic systems. This method is based on controlled diffusive mixing of species in solutions that are flowing laminarly, at low Reynolds number, inside a network of microchannels. We demonstrate the use of this procedure to generate (1) gradients in the compositions of solutions, measured directly by colorimetric assays and (2) gradients in topography of the surfaces produced by generating concentration gradients of etching reagents, and then using these gradients to etch profiles into the substrate. The lateral dimensions of the gradients examined here, which went from 350 to 900 μm, are determined by the width of the microchannels. Gradients of different size, resolution, and shape have been generated using this method. The shape of the gradients can be changed continuously (dynamic gradients) by varying the relative flow velocities of the input streams of fluids. The method is experimentally simple and highly adaptable, and requires no special equipment except for an elastomeric relief structure that can be readily prepared by rapid prototyping. This technique provides a new platform with which to study phenomena that depend on gradients in concentration, especially dynamic phenomena in cell biology (chemotaxis and haptotaxis) and surface chemistry (nucleation and growth of crystals, etching, and Marangoni effects).
Evaluation of Relative Promoter Strength in Primary Hepatocytes Using Optimized Lipofection (1991)

For most genetic deficiencies manifested in the liver, maximization of gene expression in hepatocytes will be an important factor in achieving successful gene therapy. A rapid, highly efficient, and nontoxic method for transfecting DNA into hepatocytes was used to compare directly promoter strengths of various cellular and viral promoters. Conditions are described here for transfecting 5-10% of primary hepatocytes using the positively charged liposomes, Lipofectin. Cells are not damaged by this method as they continue to transcribe genes controlled by liver specific promoters and can survive for over 2 weeks in culture. We find that the cytomegalovirus, SR alpha, and beta-actin promoters are more active than the SV40, RSV, RNA polymerase II, albumin, alpha 1-antitrypsin, or phosphoenolpyruvate carboxykinase promoters. A simple TK promoter and a TK promoter with the polyoma enhancer (MCI) were almost completely inactive. This information will be useful in the construction of vectors designed to express genes efficiently in primary hepatocytes for purposes of gene therapy, although the stability of expression from these promoters will need to be demonstrated in hepatocytes in vivo.
Dispenser printing for prototyping microscale devices (2010)

Direct write dispenser printing technology is a versatile and scalable manufacturing technique for additive deposition of novel materials.We present a versatile prototyping dispenser printer capable of rapid fabrication of unique microscale devices.A theoretical error analysis of the printer is performed to evaluate the repeatability and accuracy of the system.Additionally, we demonstrate two microdevice applications manufactured using the dispenser printer, including an electrochemical energy storage device and a thermoelectric energy harvester.
The novel microtubule-interfering agent TZT-1027 enhances the anticancer effect of radiation in vitro and in vivo (2007)

TZT-1027 is a novel anticancer agent that inhibits microtubule polymerisation and manifests potent antitumour activity in preclinical models. We have examined the effect of TZT-1027 on cell cycle progression as well as the anticancer activity of this drug both in vitro and in vivo. With the use of tsFT210 cells, which express a temperature-sensitive mutant of Cdc2, we found that TZT-1027 arrests cell cycle progression in mitosis, the phase of the cell cycle most sensitive to radiation. A clonogenic assay indeed revealed that TZT-1027 increased the sensitivity of H460 cells to gamma-radiation, with a dose enhancement factor of 1.2. Furthermore, TZT-1027 increased the radiosensitivity of H460 and A549 cells in nude mice, as revealed by a marked delay in tumour growth and an enhancement factor of 3.0 and 2.2, respectively. TZT-1027 also potentiated the induction of apoptosis in H460 cells by radiation both in vitro and in vivo. Histological evaluation of H460 tumours revealed that TZT-1027 induced morphological damage to the vascular endothelium followed by extensive central tumour necrosis. Our results thus suggest that TZT-1027 enhances the antitumour effect of ionising radiation, and that this action is attributable in part to potentiation of apoptosis induction and to an antivascular effect. Combined treatment with TZT-1027 and radiation therefore warrants investigation in clinical trials as a potential anticancer strategy.
Immuno‐informatics: Mining genomes for vaccine components (2002)

The complete genome sequences of more than 60 microbes have been completed in the past decade. Concurrently, a series of new informatics tools, designed to harness this new wealth of information, have been developed. Some of these new tools allow researchers to select regions of microbial genomes that trigger immune responses. These regions, termed epitopes, are ideal components of vaccines. When the new tools are used to search for epitopes, this search is usually coupled with in vitro screening methods; an approach that has been termed computational immunology or immuno-informatics. Researchers are now implementing these combined methods to scan genomic sequences for vaccine components. They are thereby expanding the number of different proteins that can be screened for vaccine development, while narrowing this search to those regions of the proteins that are extremely likely to induce an immune response. As the tools improve, it may soon be feasible to skip over many of the in vitro screening steps, moving directly from genome sequence to vaccine design. The present article reviews the work of several groups engaged in the development of immuno-informatics tools and illustrates the application of these tools to the process of vaccine discovery.
Reticuloendothelial system (RES) hyperfunction and erythropoietin (Ep) production in the regenerating liver (1979)

Hepatic cells in rats were evaluated after subtotal hepatectomy using scintillation scanning with technetium sulfur colloid (TSC), autoradiography, and microstereology techniques. The ability of the liver to accumulate TSC increased during the course of the regeneration as did the labeling of Kupffer and parenchymal cells with tritiated thymidine (3H-tdR). Kupffer to parenchymal cell number ratios and Kupffer cell relative areas were also elevated, attaining peak values at 72 hours post-hepatectomy. This period corresponds to the time of peak erythropoietin (Ep) production in rats with regenerating livers after nephrectomy and exposure to hypoxia. These findings suggest that the Kupffer cell may function as a cellular site of Ep formation.
A Study On The Three Dimensional Road Simulation Technique Based on GSIS (2004)

Based on Geo-Spatial Information System(GSIS), we tried to develop three dimensional road simulation system of coastal region considering landscape in Jeju island. The 1:5000 digital map, microstation CAD and Inroads road design programs were used to design coastal road. To estimate landscape effect of the three dimensional road visual simulation we implemented three types road simulations that are the trees planted, the flowers planted and the trees and flowers planted road, respectively. From the study, we found that the three dimensional virtual technique was very useful tool to design the road considering landscape effect in ocean view terrain and to estimate the reasonable road characteristics.
Closed-form least-squares source location estimation from range-difference measurements (1987)

Three noniterative techniques are presented for localizing a single source given a set of noisy range-difference measurements. The localization formulas are derived from linear least-squares "equation error" minimization, and in one case the maximum likelihood bearing estimate is approached. Geometric interpretations of the equation error norms minimized by the three methods are given, and the statistical performances of the three methods are compared via computer simulation.
A Preliminary Observation of Weight Loss Following Left Gastric Artery Embolization in Humans (2014)

The current data suggest that body weight in humans may be modulated via LGA embolization. Continued research is warranted with prospective studies to further investigate this phenomenon.
Adenovirus type 5 E4 Orf3 protein targets promyelocytic leukaemia (PML) protein nuclear domains for disruption via a sequence in PML isoform II that is predicted as a protein interaction site by bioinformatic analysis (2008)

Human adenovirus type 5 infection causes the disruption of structures in the cell nucleus termed promyelocytic leukaemia (PML) protein nuclear domains or ND10, which contain the PML protein as a critical component. This disruption is achieved through the action of the viral E4 Orf3 protein, which forms track-like nuclear structures that associate with the PML protein. This association is mediated by a direct interaction of Orf3 with a specific PML isoform, PMLII. We show here that the Orf3 interaction properties of PMLII are conferred by a 40 aa residue segment of the unique C-terminal domain of the protein. This segment was sufficient to confer interaction on a heterologous protein. The analysis was informed by prior application of a bioinformatic tool for the prediction of potential protein interaction sites within unstructured protein sequences (predictors of naturally disordered region analysis; PONDR). This tool predicted three potential molecular recognition elements (MoRE) within the C-terminal domain of PMLII, one of which was found to form the core of the Orf3 interaction site, thus demonstrating the utility of this approach. The sequence of the mapped Orf3-binding site on PML protein was found to be relatively poorly conserved across other species; however, the overall organization of MoREs within unstructured sequence was retained, suggesting the potential for conservation of functional interactions.
Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: Epidemiological applications (1994)

A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.
Charge injection and transport in films of CdSe nanocrystals (2000)

We have studied charge injection and charge transport in thin disordered films of CdSe nanocrystals between metal electrodes. Current–voltage characteristics of these devices are investigated as a function of electrode material, nanocrystal size, and temperature. We measure the photocurrent response of these structures and find that the photocurrent action spectra follow the quantum-confined absorption spectra of the nanoparticles. For dissimilar top and bottom electrodes, we find that the devices are highly rectifying. High work function materials such as gold and indium-tin oxide are found to be poor electron injectors, consistent with the estimated conduction and valence band levels of the nanocrystals. We observe that the current–voltage characteristics exhibit a history and time dependence which is characteristic of persistent photoconductivity, with current at constant bias decaying with time according to a stretched exponential form. We propose a model based on space-charge limited current dominated by mobile electrons which slowly fill deep traps. Numerical simulations show that the model is able to describe the observed time dependence. We also find that the conductivity is strongly temperature dependent, and is qualitatively consistent with an activated hopping process at temperatures above 180 K. We use the data and simulations to estimate the electron mobilities to be in the range of ∼10−4–10−6 cm2 V−1 s−1 and the trap densities to be approximately 2×1016 cm−3.
Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies. (1993)

CD44 molecules are comprised of multiple alternatively spliced forms and are associated with diverse functions such as mediation of carcinoma metastasis and T cell coactivation. To study the function of individual CD44 isoforms, we have transfected CD44 isoforms into CD44-negative Jurkat T cells and produced cloned Jurkat cell lines that are stably transfected with either a CD44 isoform containing no alternatively spliced insert (CD44H) or a CD44 variant (CD44E) containing an insert of 132 amino acids derived from exons 12, 13, and 14 of the CD44 gene. We found that neither CD44H- nor CD44E-transfected Jurkat T cells constitutively bound hyaluronan (HA), whereas PMA treatment induced Jurkat cells transfected with CD44H but not CD44E to bind HA. CD44 mAb against noninsert regions of the CD44 extracellular domain (A3D8, A1G3) and polyclonal antisera against the COOH-terminal extracellular glycosaminoglycan region of CD44H (anti-6A serum) both induced CD44H-transfected cells to bind HA, whereas only one CD44 mAb (A1G3) induced CD44E-transfected Jurkat T cells to bind HA. Studies of Jurkat cells transfected with CD44H forms with truncations of the CD44 cytoplasmic domain demonstrated that the cytoplasmic COOH-terminal 52 amino acids were critical for binding of HA to the CD44 extracellular domain. Thus, these data underscore the importance of the CD44 cytoplasmic domain in the function of the extracellular portion of CD44H, and demonstrate a role for ligation of human CD44 isoforms at multiple distinct sites in regulation of expression of CD44 binding to HA.
A two-sensor voice activity detection and speech enhancement based on coherence with additional enhancement of low frequencies using pitch information (2000)

This report proposesa2 microphone VoiceActivityDetector(VAD)and a Speech Enhancer (ENH) adapted to car conditions. The two modules are derived from the well-known Magnitude Square Coherence (MSC) which expresses a normalized cross-correlation for each frequency band of the received signals by the two sensors. A global VAD is directly obtained from the MSC by adaptive threshold which ensures a quasi-constant behaviour in different environmental conditions and different relative microphones positions. The ENH filter is applied to one of the two microphones and is divided in two parts : 1. from a Modified Coherence Function including Power Cross-Spectral Subtraction of background noise estimation is based on the Wiener Filter that is used to enhance speech; the estimation of Power Spectral Densities (PSD) are optimized to prevent the emergence of musical noise as well as reverberant effect. 2. a second module extracts the pitch value of voiced sections of speech to enhance low frequency bands of main signal that are partially or even totally removed by Wiener Filtering.
Genetic Modification of Domestic Animals for Agriculture and Biomedical Applications (2012)

Transgenic technology has been applied mainly in the study of gene structure and function in model organisms and gene therapy for human diseases. Transgenic technology has potential for rapidly improving quantity and quality of agricultural products, compared to traditional selection and breeding methods in domestic animals that are time consuming when attempting to alter the desired allele frequency for specific traits. Additionally, transgenic animals can be used as biomedical research models or directly for human health, by producing recombinant pharmaceutical proteins and/or organs for xenotransplantation. Due to the advantage of bypassing the need of embryonic stem (ES) cells that are difficult to isolate in domestic animal species, cell-based method of transgenesis followed by somatic cell nuclear transfer (SCNT) is currently widely applied. However, due to the limitations in making genetic modifications and SCNT, producing genetically modified animals is still inefficient. Fortunately, the current advancement of new techniques and methods in both gene targeting (Urnov et al., 2010) and abilities to produce pluripotent stem cells (Voigt and Serikawa, 2009) holds great promises for this field. In this chapter, we will review the recent progress and technical route of the cell-based method of transgenesis by SCNT and discuss the newly emerging methods to enrich the gene targeting frequency of somatic cells. We will also discuss factors to improve the efficiency of SCNT and our future perspectives on the promises of this field.
Linkage of gut microbiome with cognition in hepatic encephalopathy (2011)

Hepatic encephalopathy (HE) has been related to gut bacteria and inflammation in the setting of intestinal barrier dysfunction. We aimed to link the gut microbiome with cognition and inflammation in HE using a systems biology approach. Multitag pyrosequencing (MTPS) was performed on stool of cirrhotics and age-matched controls. Cirrhotics with/without HE underwent cognitive testing, inflammatory cytokines, and endotoxin analysis. Patients with HE were compared with those without HE using a correlation-network analysis. A select group of patients with HE (n = 7) on lactulose underwent stool MTPS before and after lactulose withdrawal over 14 days. Twenty-five patients [17 HE (all on lactulose, 6 also on rifaximin) and 8 without HE, age 56 ± 6 yr, model for end-stage liver disease score 16 ± 6] and ten controls were included. Fecal microbiota in cirrhotics were significantly different (higher Enterobacteriaceae, Alcaligeneceae, and Fusobacteriaceae and lower Ruminococcaceae and Lachnospiraceae) compared with controls. We found altered flora (higher Veillonellaceae), poor cognition, endotoxemia, and inflammation (IL-6, TNF-α, IL-2, and IL-13) in HE compared with cirrhotics without HE. In the cirrhosis group, Alcaligeneceae and Porphyromonadaceae were positively correlated with cognitive impairment. Fusobacteriaceae, Veillonellaceae, and Enterobacteriaceae were positively and Ruminococcaceae negatively related to inflammation. Network-analysis comparison showed robust correlations (all P < 1E-5) only in the HE group between the microbiome, cognition, and IL-23, IL-2, and IL-13. Lactulose withdrawal did not change the microbiome significantly beyond Fecalibacterium reduction. We concluded that cirrhosis, especially when complicated with HE, is associated with significant alterations in the stool microbiome compared with healthy individuals. Specific bacterial families (Alcaligeneceae, Porphyromonadaceae, Enterobacteriaceae) are strongly associated with cognition and inflammation in HE.