gebhart/patrepeval huggingface dataset:
Targeted gene modification for gene therapy of stem cells (1990)

Ideally, gene therapy would correct the specific gene defect without adding potentially harmful extraneous DNA sequences. Such correction can be obtained with homologous recombination between input DNA sequences and identical (homologous) sequences in the genomic target gene. The development of techniques for obtaining virtually pure populations of hematopoietic stem cells should permit the use of the highly efficient nuclear microinjection methods for transfer of DNA. These techniques combined with new highly sensitive methods for detecting cells with the specified genetic modification of nonexpressed genes would make homologous recombination-mediated gene therapy feasible for hematopoietic stem cells. These advances are reviewed with particular emphasis on approaches to targeted gene modification of hematopoietic stem cells and speculation on directions for future research.
High Performance Liquid Chromatographic Method for Prostaglandin E2Determination in Human Gastric Juice Without Derivatization (1984)

Abstract A rapid and practical method for the separation and quantitation of PGE2 in human gastric juice by high performance liquid chromatography is described. Separation on a reversed-phase column and UV detection allows quantities as little as 20 nanograms of PGE2 to be detected. Specificity, sensitivity, high yield and reproducibility make this method particularly suitable for prostaglandin determination in human gastric juice.
Use of Concentrations of Progesterone and Estradiol-17β in Milk in Monitoring Postpartum Ovarian Function in Dairy Cows (1987)

Data from artificial insemination, rectal palpation, and hormone assays were used to characterize postpartum reproductive activity in 54 dairy cows. Progesterone and estradiol-17 beta were measured in milk samples collected for 120 d (Trial 1) or 65 d (Trial 2). Progesterone was higher and estradiol was lower in milk than in serum. Values for both hormones in milk were highly correlated with those in serum. Most cows (64%) had short first luteal phases (less than or equal to 12 d). First rise (28 d) in progesterone was later (33.4 vs. 24.9 d) for cows having short rather than normal (greater than 12 d) luteal phases. Cows were classified as having a short luteal phase followed by a normal luteal phase or as having normal luteal phases for the first two estrous cycles. Estradiol for the 6 d prior to each luteal phase was higher preceding the second phase than the short phase or those preceding both phases of cows with normal phases. Follicular function prior to ovulation, as measured by estradiol, was not responsible for short-lived corpora lutea. Concentrations of progesterone in milk in the late luteal phase prior to insemination were related to fertility.
Channelrhodopsin2 expression in cardiomyocytes: A new tool for light-induced depolarization with high spatio-temporal resolution in vitro and in vivo (2011)

Objectives: Electrical pacing of cardiomyocytes is widely used in clinics as well as in cardiac research. However, because of side effects, longer lasting or sub-threshold depolarization are not possible. We thought to overcome these limitations by using illumination of channelrhodopsin 2 (ChR2), a genetically targetable, light-gated cation channel.
Visualization of molecular interactions using bimolecular fluorescence complementation analysis: Characteristics of protein fragment complementation (2009)

Investigations of the molecular processes that sustain life must include studies of these processes in their normal cellular environment. The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells. This assay is based on the facilitated association of complementary fragments of a fluorescent protein that are fused to interaction partners. Complex formation by the interaction partners tethers the fluorescent protein fragments in proximity to each other, which can facilitate their association. The BiFC assay enables sensitive visualization of protein complexes with high spatial resolution. The temporal resolution of BiFC analysis is limited by the time required for fluorophore formation, as well as the stabilization of complexes by association of the fluorescent protein fragments. Many modifications and enhancements to the BiFC assay have been developed. The multicolor BiFC assay enables simultaneous visualization of multiple protein complexes in the same cell, and can be used to investigate competition among mutually exclusive interaction partners for complex formation in cells. The ubiquitin-mediated fluorescence complementation (UbFC) assay enables visualization of covalent ubiquitin family peptide conjugation to substrate proteins in cells. The BiFC assay can also be used to visualize protein binding to specific chromatin domains, as well as other molecular scaffolds in cells. BiFC analysis therefore provides a powerful approach for the visualization of a variety of processes that affect molecular proximity in living cells. The visualization of macromolecular interactions and modifications is of great importance owing to the central roles of proteins, nucleic acids and other macromolecular complexes in the regulation of cellular functions. This tutorial review describes the BiFC assay, and discusses the advantages and disadvantages of this experimental approach. The review will be of interest to scientists interested in the investigation of macromolecular interactions or modifications who need exquisite sensitivity for the detection of their complexes or conjugates of interest.
Interferon-mediated fatigue (2001)

Fatigue is a common side effect of interferon (IFN) therapy, reported in 70-100% of patients treated with IFN. The etiology of IFN-mediated fatigue (IMF) is multifactorial, with endocrine failure, neuropsychiatric disturbance, autoimmunity, and cytokine dysregulation potentially being contributors. Thyroid dysfunction, associated with the development of autoantibodies, is seen in 8-20% of patients receiving IFN-alpha. IFN-alpha also suppresses the hypothalamic-pituitary-adrenal axis. In addition, IFN-alpha therapy leads to depression and cognitive slowing, and depressed patients are predisposed to develop fatigue. Clinical management of IMF is challenging because the syndrome is variable in onset and severity and the pathophysiology is poorly understood. Current management typically centers on dose reduction, but ancillary nonpharmacologic measures may help improve symptoms. Other strategies include antidepressant or anxiolytic therapy and treatment of coexisting hypothyroidism. Future studies utilizing IFN should include quantitative guidelines for grading and managing IMF.
Effect of Rituximab on the Peripheral Blood and Cerebrospinal Fluid B Cells in Patients With Primary Progressive Multiple Sclerosis (2005)

The effect(s) of rituximab on the cerebrospinal fluid B-cell compartment is limited in comparison with the effect(s) on the B cells in the periphery, but this finding will need to be confirmed in a larger group of MS patients.
The Study on Brain Targeting of the Amphotericin B Liposomes (2003)

To improve transporting drugs across the Blood Brain Barrier (BBB) into the brain, RMP-7 was conjugated to the surface of liposomes containing Amphotericin B (AmB) for cerebral inflammation, because it can selectively bound to the B2 receptors on the capillary blood vessel. First, RMP-7 was conjugated to DSPE-PEG-NHS [1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-n-[poly (ethylenegly-col)]-hydroxy succinamide, PEG M 3400] under mild condition to obtain a predominantly 1:1 conjugate (DSPE-PEG-RMP-7), as evidenced by the Matrix-Assisted Laser Desorption-Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF-MS). The second, endothelium cell was cultured on the cell insert to form an in vitro BBB model and the stereoscan microscope, electric resistance and permeation of horse-radish peroxidase (HRP) across the endothelium cell monolayer were used as indicators to evaluate the integrality of the monolayer, and then the in vitro BBB model was used to determine the bioactivity of DSPE-PEG-RMP-7 "opening" BBB. The results demonstrated the in vitro BBB model was set up, RMP-7 and DSPE-PEG-RMP-7 could improve the transporting of HRP across the BBB. The third, the liposomes containing AmB (AmB-L-PEG) was prepared by modified Film-sonication method and DSPE-PEG-RMP-7 was used to modify the AmB-L-PEG to obtain AmB-L-PEG-RMP-7. The fourth, tissue distribution of AmB in the rats of three groups was determined: Group I, AmB-L-PEG; Group II, AmB-L-PEG+RMP-7 (the physical mixture of AmB-L-PEG and RMP-7); Group III, AmB-PEG-RMP-7. The drugs were transfused into the rats through the femoral vein. The concentration of AmB in the tissue was checked using High-Performance Liquid Chromatography (HPLC) method. The rank of AmB concentration in the brain were as follows: III>II>I. The AmB concentration in the liver, spleen, lung and kidney had no significant difference. The concentration of AmB in the brain of the group III was raised several times higher than that in the other two groups, because the DSPE-PEG-RMP-7 had been inserted in the surface of AmB-L-PEG. Both the RMP-7 and AmB-L-PEG could reach BBB at the same time. When RMP-7 selectively reacted with the B2 receptor, the BBB is "opened" and AmB was transported into the brain at the same time. While in group II, the RMP-7 could improve the AmB concentration in the brain a little, because the RMP-7 and liposomes could not reach BBB at the same time. The distribution of AmB in the tissues demonstrated that the RMP-7 and its derivative had selectivity to the brain.
Thyroid autoantibodies in euthyroid non-pregnant women with recurrent spontaneous abortions (1995)

This study was undertaken to evaluate the incidence of thyroid autoantibodies in women with a history of recurrent (three or more consecutive) spontaneous abortions. A total of 22 euthyroid non-pregnant habitual aborters were analysed for thyreoglobulin and thyroid peroxidase antibodies; 22 nulligravidae and 22 multigravidae without endocrine dysfunction served as controls. Both thyroid antibodies were assayed using highly sensitive, commercially available enzyme-linked immunosorbent assay kits. Eight of the 22 women with recurrent spontaneous abortions (36%) but only two of the 22 nulligravidae controls (9%; chi 2 test, P = 0.03) and one of 22 multigravidae subjects (5%; chi 2 test, P < 0.01) demonstrated positive titres (> 100 IU/ml, as recommended by the manufacturer) of thyreoglobulin, thyroid peroxidase or both antibodies. The mean +/- SD antibody concentrations were 102.5 +/- 226.5 in the study versus 20.9 +/- 68.8 in the nulligravidae (U-test, P = 0.057) and 26.4 +/- 60.2 IU/ml (P = 0.097) in the multigravidae population for thyroid peroxidase, and 47.7 +/- 57.9 versus 24.1 +/- 31.9 (U-test, P = 0.051) and 28.1 +/- 27.9 IU/ml (P = 0.059) for thyreoglobulin. In conclusion, the incidence of thyroid antibodies in euthyroid women with habitual abortions appears to be significantly increased compared with the controls of reproductive age without previous abortions. Although the important issue of cause and effect has not been fully clarified, this finding suggests that thyroid antibodies may be a marker for autoimmune-mediated recurrent spontaneous abortions, not dissimilar to, for example, anticardiolipin.
Engaging students in active learning: The case for personalized multimedia messages. (2000)

The authors tested the hypothesis that personalized messages in a multimedia science lesson can promote deep learning by actively engaging students in the elaboration of the materials and reducing processing load. Students received a multimedia explanation of lightning formation (Experiments 1 and 2) or played an agent-based computer game about environmental science (Experiments 3, 4, and 5). Instructional messages were presented in either a personalized style, where students received spoken or written explanations in the 1st- and 2nd-person points of view, or a neutral style, where students received spoken or written explanations in the 3rd-person point of view. Personalized rather than neutral messages produced better problem-solving transfer performance across all experiments and better retention performance on the computer game. The theoretical and educational implications of the findings are discussed. Classic research in psychology has shown that people react differently to situations that involve personal reference. This is the case of the well-known cocktail party effect, in which a person who is attending to one conversation is able to detect his or her own name in a separate conversation that is taking place simultaneously in the same room (Cherry, 1953). Another robust phenomenon is the self-referential effect, in which retention is facilitated by having people process information by relating it to aspects of themselves (Rogers, Kuiper, & Kirker, 1977). As with other factors in human learning and memory, the question arises as to whether personal reference effects can be extended and used in the area of multimedia learning. For example, it is possible to teach a computer-based science lesson with higher or lower levels of self-referenc ing by varying the communication style used in the explanations (Turco, 1996). In the studies reported in the literature, high self-referencing has been created by
Comparative toxicity and proliferation testing of aflibercept, bevacizumab and ranibizumab on different ocular cells (2013)

In our experiments, aflibercept did not lead to any negative effects on retinal cell lines and might therefore be used safely in clinical applications.
Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713). (1993)

The c-fes proto-oncogene product is expressed predominantly in hematopoietic cells of the myeloid lineage and has been implicated in the regulation of myeloid differentiation. The c-fes locus encodes a 93-kDa protein tyrosine kinase (p93c-fes) that possesses several structural features characteristic of the cytoplasmic class of protein tyrosine kinases, including a consensus sequence for autophosphorylation surrounding Tyr-713 and a src homology 2 (SH2) domain. To assess the effect of each of these potential regulatory sites on p93c-fes protein tyrosine kinase activity, we specifically deleted the c-fes SH2 domain using the polymerase chain reaction and replaced Tyr-713 with phenylalanine by oligonucleotide-directed mutagenesis (Y713F mutant). The resulting mutants were expressed in Escherichia coli and assayed for changes in protein tyrosine kinase activity using an immune complex kinase assay. Both mutations produced a marked decrease in the rate and extent of autophosphorylation and phosphorylation of the model substrate, enolase. To test whether the c-fes SH2 domain could interact with the autophosphorylated kinase domain, the SH2 domain was expressed as a fusion protein with glutathione S-transferase and immobilized on glutathione-agarose. The recombinant c-fes SH2 domain precipitated p93c-fes as readily as a monoclonal antibody. Binding of the SH2 domain to p93c-fes was completely dependent upon autophosphorylation, as a kinase-defective mutant of p93c-fes was not precipitated by the SH2 domain. High-affinity binding was also observed with recombinant SH2 domains from v-src and v-fps, raising the possibility of protein-protein interactions between various members of the cytoplasmic PTK family. These results indicate that the c-fes SH2 domain and consensus autophosphorylation site (Tyr-713) play major roles in the positive regulation of p93c-fes tyrosine kinase activity, possibly through intramolecular interaction.
Association of Temporal Changes in Gestational Age With Perinatal Mortality in the United States, 2007-2015 (2018)

Although the proportion of births at gestational age 39 to 40 weeks increased, perinatal mortality at this gestational age declined. This finding may be owing to pregnancies delivered at 39 to 40 weeks that previously would have been unnecessarily delivered earlier, leaving fetuses at higher risk for mortality at other gestational ages.
Introduction of a Chimeric Chalcone Synthase Gene into Petunia Results in Reversible Co-Suppression of Homologous Genes in trans. (1990)

We attempted to overexpress chalcone synthase (CHS) in pigmented petunia petals by introducing a chimeric petunia CHS gene. Unexpectedly, the introduced gene created a block in anthocyanin biosynthesis. Forty-two percent of plants with the introduced CHS gene produced totally white flowers and/or patterned flowers with white or pale nonclonal sectors on a wild-type pigmented background; none of hundreds of transgenic control plants exhibited such phenotypes. Progeny testing of one plant demonstrated that the novel color phenotype co-segregated with the introduced CHS gene; progeny without this gene were phenotypically wild type. The somatic and germinal stability of the novel color patterns was variable. RNase protection analysis of petal RNAs isolated from white flowers showed that, although the developmental timing of mRNA expression of the endogenous CHS gene was not altered, the level of the mRNA produced by this gene was reduced 50-fold from wild-type levels. Somatic reversion of plants with white flowers to phenotypically parental violet flowers was associated with a coordinate rise in the steady-state levels of the mRNAs produced by both the endogenous and the introduced CHS genes. Thus, in the altered white flowers, the expression of both genes was coordinately suppressed, indicating that expression of the introduced CHS gene was not alone sufficient for suppression of endogenous CHS transcript levels. The mechanism responsible for the reversible co-suppression of homologous genes in trans is unclear, but the erratic and reversible nature of this phenomenon suggests the possible involvement of methylation.
Turning it up a Notch: cross-talk between TGFβ and Notch signaling (2005)

Signaling through both the transforming growth factor beta (TGF beta) superfamily of growth factors and Notch play crucial roles during embryonic pattern formation and cell fate determination. Although both pathways are able to exert similar biological responses in certain cell types, a functional interaction between these two signaling pathways has not been described. Now, three papers provide evidence of both synergy and antagonism between TGF beta and Notch signaling. These reports describe a requirement for Notch signal transducers in TGF beta- and BMP-induced expression of Notch target genes, as well as in BMP-controlled cell differentiation and migration. These papers uncover a direct link between the Notch and TGF beta pathways and suggest a critical role for Notch in some of the biological responses to TGF beta family signaling.
Genetic map of Saccharomyces cerevisiae (1980)

Researchers present a compilation of most of the published yeast mapping data, as well as a large amount of unpublished data, according to chromosomes and intervals; the numbers of independent sets of data for the different intervals ranged from 1 to 12. These data have been analyzed and a new genetic map has been constructed. Although all of the data presented in this article are from tetrad analyses, many other techniques have been used to assign genes to chromosomes or to specific chromosome arms. These techniques include aneuploid analysis, mitotic recombination analysis, mitotic chromosome loss or nondisjunction, and random spore analysis.
CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells (1995)

The selective A1-adenosine-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), has been reported to activate Cl- efflux from cystic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bearing the cystic fibrosis transmembrane regulator(delta F508) mutation, but has little effect on the same process in cells repaired by transfection with wild-type cystic fibrosis transmembrane regulator (O. Eidelman, C. Guay-Broder, P. J. M. van Galen, K. A. Jacobson, C. Fox, R. J. Turner, Z. I. Cabantchik, and H. B. Pollard. Proc. Natl. Acad. Sci. USA 89: 5562-5566, 1992). We report here that CPX downregulates Na+/H+ exchange activity in CFPAC-1 cells but has a much smaller effect on cells repaired with the wild-type gene. CPX also mildly decreases resting intracellular pH. In CFPAC-1 cells, this downregulation is dependent on the presence of adenosine, since pretreatment of the cells with adenosine deaminase blocks the CPX effect. We also show that, by contrast, CPX action on these cells does not lead to alterations in intracellular free Ca2+ concentration. We conclude that CPX affects pH regulation in CFPAC-1 cells, probably by antagonizing the tonic action of endogenous adenosine.
Molecular biology of graft occlusion (1995)

Whatever the method, the biologic price of restitution of arterial flow through or around an obstructed artery is injury to the arterial wall. The artery mounts a healing response that in 30% to 60% of procedures exceeds the need. The result is formation of a lumen-narrowing lesion composed of smooth muscle cells and extracellular matrix with varying amounts of atherosclerotic components. The primary player appears to be the smooth muscle cell. For four decades the standard model for studying these events has been catheter denudation of arterial endothelium in small animals. Molecular biology has provided an enormous amount of new information including growth factors, adhesion molecules, receptor binding sites, and molecules that up- or down-regulate or maintain a steady state of expression of numberless genes in the arterial wall. Predictably, means of inhibiting these molecular events have been found. That their clinical trials have been universally disappointing should not be surprising given that the animal in which the discoveries were made--the rat--is not normally susceptible to atherosclerosis and the histology of the rat artery only approximates that of the human. Nevertheless, reason for optimism exists because of our increasing understanding of the injury response. Recent developments include the use of blocking antisense oligonucleotides, blocking antibodies, gene transfer trials, and early investigations into the role of the immune system.