gebhart/patrepeval huggingface dataset:
In Vivo Cardiac Myosin Binding Protein C Gene Transfer Rescues Myofilament Contractile Dysfunction in Cardiac Myosin Binding Protein C Null Mice (2012)

This proof-of-concept study demonstrates that gene therapy designed to increase expression of cMyBPC in the cMyBPC-deficient myocardium can improve myofilament and in vivo contractile function, suggesting that cMyBPC gene therapy may be a viable approach for treatment of cardiomyopathies because of mutations in cMyBPC.
Prediction of ATP-binding motifs: a comparison of a perceptron-type neural network and a consensus sequence method (1993)

The wording of the original paper has lead to some confusion as to the motif used in the study, and some of the original data was incorrecdy classified (Leberman, 1993). We have repeated the work with the revised classifications, and would like to re-title the article thus:
Th17 Cells in Airway Diseases (2008)

Chronic inflammation is a key feature of many airway diseases. Leukocyte accumulation in the lung has the capacity to mediate many aspects of the pathophysiology of such diseases including asthma and chronic obstructive pulmonary disease (COPD). Until recently, the CD4+ lymphocyte component of these inflammatory influxes was thought to consist of Th1 or Th2 type cells, however a third group of cells termed Th17 have been identified. These cells follow a distinct differentiation profile requiring TGFbeta and IL-6 leading to the expression of the Th17 selective transcription factor, RORgammat. Differentiation of these cells is restricted by Th1 and Th2 cytokines including IFNgamma and IL-4 which attenuate Th17 cell differentiation. The presence of Th17 cells in the airway has yet to be confirmed, yet IL-17 is expressed in both asthma and COPD. Many of the inflammatory effects of Th17 cells are attributed to the expression of this cytokine. For example, IL-17 up-regulates the expression of a number of CXCR2 chemokines including CXCL1, CXCL6 and CXCL8 together with neutrophil survival factors GM-CSF and G-CSF from the airway epithelium. This would suggest that Th17 cells are important in promoting and sustaining neutrophilic inflammation as observed in severe asthma and COPD. In addition, IL-17 can act synergistically with viral infection or other inflammatory mediators including TNF-alpha to potentiate these responses. Confirmation of the presence of Th17 cells in the airways in disease warrants further investigation since these cells would present a novel therapeutic opportunity to reduce neutrophilic inflammation in the lung.
Analysis of the nucleotide sequence of the guinea pig cytomegalovirus (GPCMV) genome (2008)

In this report we describe the genomic sequence of guinea pig cytomegalovirus (GPCMV) assembled from a tissue culture-derived bacterial artificial chromosome clone, plasmid clones of viral restriction fragments, and direct PCR sequencing of viral DNA. The GPCMV genome is 232,678 bp, excluding the terminal repeats, and has a GC content of 55%. A total of 105 open reading frames (ORFs) of > 100 amino acids with sequence and/or positional homology to other CMV ORFs were annotated. Positional and sequence homologs of human cytomegalovirus open reading frames UL23 through UL122 were identified. Homology with other cytomegaloviruses was most prominent in the central approximately 60% of the genome, with divergence of sequence and lack of conserved homologs at the respective genomic termini. Of interest, the GPCMV genome was found in many cases to bear stronger phylogenetic similarity to primate CMVs than to rodent CMVs. The sequence of GPCMV should facilitate vaccine and pathogenesis studies in this model of congenital CMV infection.
Predicting clinical response to anticancer drugs using an ex vivo platform that captures tumour heterogeneity (2015)

Predicting clinical response to anticancer drugs remains a major challenge in cancer treatment. Emerging reports indicate that the tumour microenvironment and heterogeneity can limit the predictive power of current biomarker-guided strategies for chemotherapy. Here we report the engineering of personalized tumour ecosystems that contextually conserve the tumour heterogeneity, and phenocopy the tumour microenvironment using tumour explants maintained in defined tumour grade-matched matrix support and autologous patient serum. The functional response of tumour ecosystems, engineered from 109 patients, to anticancer drugs, together with the corresponding clinical outcomes, is used to train a machine learning algorithm; the learned model is then applied to predict the clinical response in an independent validation group of 55 patients, where we achieve 100% sensitivity in predictions while keeping specificity in a desired high range. The tumour ecosystem and algorithm, together termed the CANScript technology, can emerge as a powerful platform for enabling personalized medicine.
Identification of Two Novel Human Acyl-CoA Wax Alcohol Acyltransferases (2005)

The esterification of alcohols such as sterols, diacylglycerols, and monoacylglycerols with fatty acids represents the formation of both storage and cytoprotective molecules. Conversely, the overproduction of these molecules is associated with several disease pathologies, including atherosclerosis and obesity. The human acyl-CoA:diacylglycerol acyltransferase (DGAT) 2 gene superfamily comprises seven members, four of which have been previously implicated in the synthesis of di- or triacylglycerol. The remaining 3 members comprise an X-linked locus and have not been characterized. We describe here the expression of DGAT2 and the three X-linked genes in Saccharomyces cerevisiae strains virtually devoid of neutral lipids. All four gene products mediate the synthesis of triacylglycerol; however, two of the X-linked genes act as acyl-CoA wax alcohol acyltransferases (AWAT 1 and 2) that predominantly esterify long chain (wax) alcohols with acyl-CoA-derived fatty acids to produce wax esters. AWAT1 and AWAT2 have very distinct substrate preferences in terms of alcohol chain length and fatty acyl saturation. The enzymes are expressed in many human tissues but predominate in skin. In situ hybridizations demonstrate a differentiation-specific expression pattern within the human sebaceous gland for the two AWAT genes, consistent with a significant role in the composition of sebum.
DEVELOPMENTAL MORPHOLOGY AND CYTOLOGY OF THE YOUNG MAIZE EMBRYO (ZEA MAYS L.) (1986)

Young embryos of maize were analyzed with light and electron microscopical techniques to determine the sequence of morphological, anatomical and cytological events resulting in the onset and initial development of the embryo axis and the scutellum. The proembryo stage ends at 5 days after pollination (DAP). The radial symmetry of the proembryo changes into a bilateral symmetry, probably caused by the excentric position of the embryo apex within the endosperm. Scutellum formation starts at the apex and posterior side of the embryo proper and is characterized cytologically by different types of cell growth and multiplication in epidermis and mesophyl. From anatomical observations it is concluded that the coleoptile arises as a protuberance of the scutellum. Shoot meristem formation initiates in the protoderm at the anterior side of the embryo and is characterized cytologically by decreasing cell sizes, by vacuolation and by an increase of cytoplasm. The lateral orientation of the shoot meristem is likely caused by the failure of a second cotyledon to develop. Root meristem formation is somewhat retarded. Only vacuolized cells at the base of the embryo proper were detected at 5 DAP but at 7 to 8 DAP the root meristem was identified as a group of dividing cells with few vacuoles and much cytoplasm. The meristem is not located at the exterior of the embryo but at the base of the embryo proper, in direct line with the suspensor. The coleorhiza is formed adjacent to the seminal root. Its exogenous character was not established. The new axis from root to shoot meristem deviates from the axis of the proembryo as a result of the lateral position of the shoot meristem. Lateral outgrowth of the shoot is, however, restricted by mechanical forces from outside and growth of tissues inside the embryo. In the determination of the location of the meristems next to morphological, also physiological and genetical factors are important. Metabolic gradients and physiological sinks are established already before the zygote divides and expression of polarity is present in all cormophyta.
Crosslinking treatment of progressive keratoconus: new hope (2006)

Collagen crosslinking by the photosensitzer riboflavin and ultraviolet A-light is an effective means for stabilizing the cornea in keratoconus. Collagen crosslinking might become the standard therapy for progressive keratoconus in the future diminishing significantly the need for corneal transplantation. Preoperative pachymetry and individual control of the ultraviolet A-irradiance before each treatment are mandatory. The treatment parameters must not be varied.
Strain- and age-dependent transplacental carcinogenesis by 1-ethyl-1-nitrosourea in inbred strains of mice. (1974)

Summary Pregnant AKR/J, SWR/J, DBA/2J, C57BL/6J, and C57L/J mice were given a single i.p. injection of ENU, 0.5 mmole/kg, in trioctanoin on either Day 12, 14, 16, or 18 of gestation. Tumors developed in offspring of all strains, but the incidence, type, and latency period depended on both the inbred strain and the specific day of gestation. The most common tumors were single or multiple pulmonary adenomas and leukemias after exposure to ENU on Days 16 and 18, respectively. These two types of tumor were frequently concurrent, but each was found simultaneously with other tumor types as well. Aside from thymic or splenic leukemias and pulmonary adenomas, other tumor types were hepatomas, Harderian gland adenomas, tumors of endocrine glands, particularly the ovary, and even neurogenic tumors. Hepatomas occurred preferentially in males, and certain tumors appeared more frequently in some strains than in others.
Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse (2000)

Hearing in mammals relies on the highly synchronous synaptic transfer between cochlear inner hair cells (IHCs) and the auditory nerve. We studied the presynaptic function of single mouse IHCs by monitoring membrane capacitance changes and voltage-gated Ca(2+) currents. Exocytosis initially occurred at a high rate but then slowed down within a few milliseconds, despite nearly constant Ca(2+) influx. We interpret the observed secretory depression as depletion of a readily releasable pool (RRP) of about 280 vesicles. These vesicles are probably docked close to Ca(2+) channels at the ribbon-type active zones of the IHCs. Continued depolarization evoked slower exocytosis occurring at a nearly constant rate for at least 1 s and depending on "long-distance" Ca(2+) signaling. Refilling of the RRP after depletion followed a biphasic time course and was faster than endocytosis. RRP depletion is discussed as a mechanism for fast auditory adaptation.
Comparison of the Binax Legionella Urinary Antigen Enzyme Immunoassay (EIA) with the Biotest Legionella Urin Antigen EIA for Detection of Legionella Antigen in both Concentrated and Nonconcentrated Urine Samples (1998)

We evaluated a newly commercial enzyme immunoassay (EIA) (Biotest Legionella Urin Antigen EIA; Biotest AG, Dreieich, Germany) for detection of antigens of all Legionella pneumophila serogroups with a relatively wide spectrum of cross-reactivity as well as antigens of other Legionella spp. by comparing its sensitivity and specificity with those of an EIA for detection of L. pneumophila serogroup 1 antigen (Legionella urinary antigen EIA; Binax, Portland, Maine). Both tests were performed with both concentrated and nonconcentrated urine samples. We also evaluated the capabilities of both EIAs to detect extracted soluble antigens of American Type Culture Collection (ATCC) Legionella strains (L. pneumophila serogroups 1 to 14, L. bozemanii, and L. longbeachae). The sensitivity of the Biotest EIA was 66.66% in nonconcentrated urine and 86.66% in concentrated urine. The sensitivity of the Binax EIA was 63.76% and 88.88% in nonconcentrated and concentrated urine, respectively. The specificity was 100% in nonconcentrated and concentrated urine for both assays. The Binax EIA and Biotest EIA detected extracted soluble antigens of L. pneumophila serogroups 1 to 14 and L. bozemanii ATCC strains. The cross-reactions observed with the Binax EIA were probably due to common epitopes directly related to lipopolysaccharide. Further studies are required to determine the usefulness of the Binax EIA for detection of urinary antigens from Legionella species and serogroups other than L. pneumophila serogroup 1. The Biotest EIA proved to be as rapid, sensitive, and specific as the Binax EIA for the diagnosis of legionellosis. Concentration of antigen present in urine increased the sensitivities of both techniques with no reduction in specificity.
Effect of Antibiotic Therapy on the Density of Vancomycin-Resistant Enterococci in the Stool of Colonized Patients (2000)

For patients with vancomycin-resistant enterococci in stool, treatment with antianaerobic antibiotics promotes high-density colonization. Limiting the use of such agents in these patients may help decrease the spread of vancomycin-resistant enterococci.
Differential Distribution of Burst and Single-Spike Responses in Auditory Thalamus (2002)

The medial geniculate body (MGB) of the auditory thalamus comprises lemniscal and nonlemniscal neurons that project to the primary auditory cortex and limbic structures, respectively. Here we show that in anesthetized guinea pigs, MGB responses to a noise-burst stimulus exhibit distinct and synaptic pathway-specific firing patterns. The majority of nonlemniscal MGB cells exhibited bursting responses, whereas lemniscal neurons discharged mainly single or spike doublets. The burst firing is delayed in nonlemniscal neurons and exhibited several features that are characteristics of those mediated by low-threshold Ca(2+) spikes. Such a synaptic pathway-specific allocation of bursting and single-spike firing patterns is consistent with the notion of parallel processing of auditory information in thalamocortical system.
A null mutation at the c-jun locus causes embryonic lethality and retarded cell growth in culture. (1993)

The AP-1 transcription factors are considered immediate-early response genes and are thought to be involved in a wide range of transcriptional regulatory processes linked to cellular proliferation and differentiation. To study one of the key members of this family, the proto-oncogene c-jun, we have used homologous recombination-mediated gene targeting to produce mice with a c-jun null mutation. c-jun null embryos die at mid-gestation, with an average time of death of 12.5 days postcoitus. Homozygous mutant embryos are indistinguishable from wild-type littermates both grossly and histologically until the time of death. However, primary fibroblasts derived from live heterozygous and homozygous mutant embryos show greatly reduced growth rates in culture. The subnormal mitogenic response of these cells cannot be overcome by the addition of a number of purified mitogens. These studies indicate that although c-jun is not required for cellular proliferation and differentiation up to mid-gestation, it is required for survival past that stage as well as for the mitogenic response of embryonic fibroblasts in culture.
In vivo effects of fenpropimorph on the yeast Saccharomyces cerevisiae and determination of the molecular basis of the antifungal property (1990)

The effects of fenpropimorph on sterol biosynthesis and growth of Saccharomyces cerevisiae were examined to pinpoint the mode of action of fungicides that inhibit ergosterol biosynthesis. Taking advantage of sterol auxotrophy and sterol permeability in mutant strains, we show that growth inhibition is strongly correlated with inhibition of sterol biosynthesis. We confirm that in vivo and at low concentrations, fenpropimorph inhibits delta 8----delta 7-sterol isomerase, and in addition, when it is used at higher concentrations, it inhibits delta 14-sterol reductase. We show also that the fungistatic effect of fenpropimorph is not due to the accumulation of abnormal sterols in treated cells but is linked to the specific inhibition of ergosterol biosynthesis, leading to the arrest of cell proliferation in the unbudded G1 phase of the cell cycle.
A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium (1990)

A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid.
Continuous Separations of Suspensions by Nonuniform Electric Fields in Liquid Dielectrics (1960)

Suspensions of various solids in organic dielectric liquids can be separated continuously into their components by pulsating direct or alternating current electric fields of modest strength. The method and its important variables are described, together with the results observed for several systems. It is found,for example, that there exists a critical lower voltage and a critical upper voltage between which the operation must take place if appreciable separation is to take place. Best results are obtained if the dielectric constant exceeds that of the liquid. Among other separations possible, it is shown that zircon‐rutile particle mixtures readily separate under conditions of dielectrophoresis. These materials cannot be separated by density or magnetic methods. A simple theory for the forces exerted on the particles sitting in combined gravitational and nonuniform electric fields is given.
Comparison of Stability for All-trans Retinoic Acid Nanosuspensions and Lipid Nanoparticle Formulations (2007)

The principal aim of this study was to compare the stability of different nanoparticle formulations with lipophilic and chemically unstable model drug nW-trans retinoic acid (ATRA). ATRA nanoparticles (ATRA-NP) and ATRA-loaded solid lipid nanoparticles (ATRA-SLN, palmitic acid as solid lipid matrix) were prepared by solvent injection method, whilst ATRA-loaded nanostructured lipid carriers (ATRA-NLC, glyceryl monostearate and palmitic acid (3:1 w/w) as solid lipid matrix, soybean oil as liquid lipid material), ATRA-SLN (glyceryl monostearate as solid lipid matrix), and ATRA-loaded nanoemulsions (ATRA-NE, soybean oil as liquid lipid material) were successfully prepared by melt high pressure homogenization method. The chemical stability of ATRA was determined by HPLC analysis. It was found that ATRA in all tested colloidal carriers was more stable than that in methanol solution. The type of colloidal carries systems, preparation method, lipid phase state, concentration of lipid and drug had a strong influence on the chemical stability of ATRA. ATRA was more stable in SLN than in NP, which were both produced by solvent injection method. However, ATRA-NP produced by solvent injection method showed higher stability than ATRA-SLN produced by melt high pressure homogenization method. Additionally, ATRA was more stable when it was incorporated in SLN than that entrapped in NLC or NE. The concentration of lipid or drug also influenced the stability of ATRA. We conclude that ATRA-NP or ATRA-loaded lipid nanoparticle formulations can satisfy the needs for improving both the solubility and stability limitations of ATRA.
The carboxy-terminal region of the glycoprotein hormone alpha-subunit: contributions to receptor binding and signaling in human chorionic gonadotropin. (1992)

The glycoprotein hormones are heterodimeric and contain a common alpha-subunit, which is noncovalently associated with a hormone-specific beta-subunit. The alpha-subunit has been highly conserved throughout evolution; for example, the five amino acid residues of the carboxy-terminus, Tyr-Tyr-His-Lys-Ser-COOH, are identical in nine of the 10 available amino acid sequences. It has been shown that enzymatic removal of these five amino acid residues, while not affecting holoprotein formation, results in a heterodimer that exhibits very little, if any, binding to the CG/LH receptor. Using site-directed mutagenesis on the human alpha-subunit, we have prepared two deletion mutants, Des-(88-92)alpha and Des-(89-92)alpha, and two point mutants, where each of the two tyrosines, 88 and 89, was replaced with phenylalanine, in order to delineate more specifically the contributions of these aromatic side-chains to receptor binding. The cDNAs for wild-type hCG alpha and mutants were introduced into a pcDNAINEO expression vector, and the cDNA for hCG beta was inserted into a pRSV plasmid; both were transiently cotransfected into DUXB-11 cells. The media were collected, and RIAs showed that all mutants formed heterodimers; moreover, there was no discernable difference in subunit assembly between wild-type hCG alpha and the various mutant alpha-subunits. The gonadotropin mutants were assayed in vitro using a competitive binding assay with [125I]hCG and stimulation of progesterone production in the transformed murine Leydig cell line MA-10.(ABSTRACT TRUNCATED AT 250 WORDS)