gebhart/patrepeval huggingface dataset:
Elevated Plus Maze for Mice (2008)

Although the mouse genome is now completely sequenced, the functions of most of the genes expressed in the brain are not known. The influence of a given gene on a specific behavior can be determined by behavioral analysis of mutant mice. If a target gene is expressed in the brain, behavioral phenotype of the mutant mice could elucidate the genetic mechanism of normal behaviors. The elevated plus maze test is one of the most widely used tests for measuring anxiety-like behavior. The test is based on the natural aversion of mice for open and elevated areas, as well as on their natural spontaneous exploratory behavior in novel environments. The apparatus consists of open arms and closed arms, crossed in the middle perpendicularly to each other, and a center area. Mice are given access to all of the arms and are allowed to move freely between them. The number of entries into the open arms and the time spent in the open arms are used as indices of open space-induced anxiety in mice. Unfortunately, the procedural differences that exist between laboratories make it difficult to duplicate and compare results among laboratories. Here, we present a detailed movie demonstrating our protocol for the elevated plus maze test. In our laboratory, we have assessed more than 90 strains of mutant mice using the protocol shown in the movie. These data will be disclosed as a part of a public database that we are now constructing. Visualization of the protocol will promote better understanding of the details of the entire experimental procedure, allowing for standardization of the protocols used in different laboratories and comparisons of the behavioral phenotypes of various strains of mutant mice assessed using this test.
Immunoenhancing property of dietary whey protein in mice: role of glutathione. (1989)

The spleen cells immune response to sheep red blood cells of C3H/HeJ mice fed a 20 g whey protein/100 g diet is substantially higher than that of mice fed an equivalent casein diet of similar nutritional efficiency. The present study indicates that the observed immunoenhancing effect of the whey protein mixture is dependent on the overall amino acid pattern resulting from the contribution of all its protein components. Whey protein contains substantially more cysteine than casein. Dietary cysteine is considered to be a rate limiting substrate for the synthesis of glutathione which is necessary for lymphocyte proliferation. Our studies show that enhancement of host humoral immune response is associated with greater and more sustained production of splenic glutathione during the antigen driven clonal expansion of the lymphocyte in whey protein fed mice in comparison to mice fed the equivalent casein or the cysteine-enriched casein diet. Hence the efficiency of dietary cysteine in inducing supernormal glutathione levels is greater when it is delivered in the whey protein than as free cysteine. Administration of S-(n-butyl) homocysteine sulfoximine, which reduces splenic glutathione level by half, produces a 4-5 fold drop in the humoral immune response of whey protein diet-fed mice. This is further evidence of the important role of glutathione in the immunoenhancing effect of dietary whey protein.
Piglets produced from cloned blastocysts cultured in vitro with GM‐CSF (2012)

In general, pig embryos established by somatic cell nuclear transfer (SCNT) are transferred at the one-cell stage because of suboptimal embryo culture conditions. Improvements in embryo culture can increase the practical application of late embryo transfer. The goal of this study was to evaluate embryos cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro, and to track the in vivo developmental competency of SCNT-derived blastocysts from these GM-CSF embryos. The receptor for GM-CSF was up-regulated in in vitro-produced embryos when compared to in vivo-produced cohorts, but the level decreased when GM-CSF was present. In vitro fertilized (IVF) embryos, supplemented with GM-CSF (2 or 10 ng/ml), showed a higher frequency of development to the blastocyst stage compared to controls. The total cell numbers of the blastocysts also increased with supplementation of GM-CSF. Molecular analysis demonstrates that IVF-derived blastocysts cultured with GM-CSF exhibit less apoptotic activity. Similarly, an increase in development to the blastocyst stage and an increase in the average total-cell number in the blastocysts were observed when SCNT-derived embryos were cultured with either concentration of GM-CSF (2 or 10 ng/ml). When SCNT-derived embryos, cultured with 10 ng/ml GM-CSF, were transferred into six surrogates at Day 6, five of the surrogates became pregnant and delivered healthy piglets. Our findings suggest that supplementation of GM-CSF can provide better culture conditions for IVF- and SCNT-derived embryos, and pig SCNT-derived embryos cultured with GM-CSF in vitro can successfully produce piglets when transferred into surrogates at the blastocyst stage. Thus, it may be practical to begin performing SCNT-derived embryo transfer at the blastocyst stage.
Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach. (1983)

Ten permanent clones derived from a single biopsy specimen of an untreated human adenocarcinoma of the stomach were established and characterized in vitro. Tissue culture growth properties, doubling times, plating efficiencies, growth fractions, cell cycle phase distributions, DNA indices, modal chromosome numbers, and ploidies were determined. Growth fractions were nearly 100%, and doubling times ranged from 23 to 37 hr. The plating efficiencies were generally high for tumor cells in culture, ranging up to 70%. Modal chromosome numbers varied from 45 to 48, with a wider range of variability in about 25% of the cells studied in each clone. In addition, the parent cell line (from which the clones were isolated) was shown to grow in athymic mice and to have the same histochemical and cytological characteristics as the specimen taken from the patient. It is important to characterize human tumor cells in vitro in this detailed manner, since they serve as excellent model systems for other studies involving the heterogeneous responses to drugs and radiation. The identification of mechanisms of drug sensitivity and resistance and the testing of drug and radiation combination treatment schedules in such in vitro systems can provide valuable insight into the design of clinical protocols for treatment of stomach cancer in humans.
In Vivo Gene Expression Dynamics of Tumor-Targeted Bacteria (2012)

The engineering of bacteria to controllably deliver therapeutics is an attractive application for synthetic biology. While most synthetic gene networks have been explored within microbes, there is a need for further characterization of in vivo circuit behavior in the context of applications where the host microbes are actively being investigated for efficacy and safety, such as tumor drug delivery. One major hurdle is that culture-based selective pressures are absent in vivo, leading to strain-dependent instability of plasmid-based networks over time. Here, we experimentally characterize the dynamics of in vivo plasmid instability using attenuated strains of S. typhimurium and real-time monitoring of luminescent reporters. Computational modeling described the effects of growth rate and dosage on live-imaging signals generated by internal bacterial populations. This understanding will allow us to harness the transient nature of plasmid-based networks to create tunable temporal release profiles that reduce dosage requirements and increase the safety of bacterial therapies.
Colorimetric detection of specific DNA segments amplified by polymerase chain reactions. (1989)

The polymerase chain reaction (PCR) procedure has many potential applications in mass screening. We describe here a general assay for colorimetric detection of amplified DNA. The target DNA is first amplified by PCR, and then a second set of oligonucleotides, nested between the first two, is incorporated by three or more PCR cycles. These oligonucleotides bear ligands: for example, one can be biotinylated and the other can contain a site for a double-stranded DNA-binding protein. After linkage to an immobilized affinity reagent (such as a cloned DNA-binding protein, which we describe here) and labeling with a second affinity reagent (for example, avidin) linked to horseradish peroxidase, reaction with a chromogenic substrate allows detection of the amplified DNA. This amplified DNA assay (ADA) is rapid, is readily applicable to mass screening, and uses routine equipment. We show here that it can be used to detect human immunodeficiency virus sequences specifically against a background of human DNA.
The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. (1990)

We have isolated the gene for a novel growth regulator, amphiregulin (AR), that is evolutionarily related to epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). AR is a bifunctional growth modulator: it interacts with the EGF/TGF-alpha receptor to promote the growth of normal epithelial cells and inhibits the growth of certain aggressive carcinoma cell lines. The 84-amino-acid mature protein is embedded within a 252-amino-acid transmembrane precursor, an organization similar to that of the TGF-alpha precursor. Human placenta and ovaries were found to express significant amounts of the 1.4-kilobase AR transcript, implicating AR in the regulation of normal cell growth. In addition, the AR gene was localized to chromosomal region 4q13-4q21, a common breakpoint for acute lymphoblastic leukemia.
Bioavailability and its assessment (2004)

Bioavailability is a key pharmacokinetic parameter which expresses the proportion of a drug administered by any nonvascular route that gains access to the systemic circulation. Presented in this review are the different approaches to measurement of bioavailability (absolute and relative), including the case in which intravenous administration is impossible. The rate of drug absorption is also discussed with special emphasis on the possible difficulties encountered using C(max) and T(max) or curve fitting to evaluate the rate of drug absorption.
Distributed Restoration of the Transport Network (2009)

This chapter contains sections titled: Introduction Restoration Speed and Network Capacity Theory and Concepts Alternative Routing Criteria Performance Measures for Distributed Restoration The Capacity Consistency Problem in DRAs Overview of Distributed Restoration Algorithms DRA Properties Distributed Preplanning with a DRA Implementation Considerations for Distributed Restoration Looking Ahead This chapter contains sections titled: References
A bipartite DNA-binding domain in yeast Reb1p. (1993)

The REB1 gene encodes a DNA-binding protein (Reb1p) that is essential for growth of the yeast Saccharomyces cerevisiae. Reb1p binds to sites within transcriptional control regions of genes transcribed by either RNA polymerase I or RNA polymerase II. The sequence of REB1 predicts a protein of 809 amino acids. To define the DNA-binding domain of Reb1p, a series of 5' and 3' deletions within the coding region was constructed in a bacterial expression vector. Analysis of the truncated Reb1p proteins revealed that nearly 400 amino acids of the C-terminal portion of the protein are required for maximal DNA-binding activity. To further define the important structural features of Reb1p, the REB1 homolog from a related yeast, Kluyveromyces lactis, was cloned by genetic complementation. The K. lactis REB1 gene supports active growth of an S. cerevisiae strain whose REB1 gene has been deleted. The Reb1p proteins of the two organisms generate almost identical footprints on DNA, yet the K. lactis REB1 gene encodes a polypeptide of only 595 amino acids. Comparison of the two Reb1p sequences revealed that within the region necessary for the binding of Reb1p to DNA were two long regions of nearly perfect identity, separated in the S. cerevisiae Reb1p by nearly 150 amino acids but in the K. lactis Reb1p by only 40 amino acids. The first includes a 105-amino-acid region related to the DNA-binding domain of the myb oncoprotein; the second bears a faint resemblance to myb. The hypothesis that the DNA-binding domain of Reb1p is formed from these two conserved regions was confirmed by deletion of as many as 90 amino acids between them, with little effect on the DNA-binding ability of the resultant protein. We suggest that the DNA-binding domain of Reb1p is made up of two myb-like regions that, unlike myb itself, are separated by as many as 150 amino acids. Since Reb1p protects only 15 to 20 nucleotides in a chemical or enzymatic footprint assay, the protein must fold such that the two components of the binding site are adjacent.
A Conducting‐Polymer Platform with Biodegradable Fibers for Stimulation and Guidance of Axonal Growth (2009)

A biosynthetic platform composed of a conducting polypyrrole sheet embedded with unidirectional biodegradable polymer fibers is described (see image; scale bar = 50 µm). Such hybrid systems can promote rapid directional nerve growth for neuro-regenerative scaffolds and act as interfaces between the electronic circuitry of medical bionic devices and the nervous system.
First light for the Bowen fluorescence spatial heterodyne spectrometer at Millstone Hill Observatory (2007)

Neutral oxygen (O I) is a dominant species between about 250 and 500 km in the thermosphere. A complete thermospheric model requires measurements of the species density ([O]) to incorporate into forward models. One way to measure [O] is to detect Bowen fluorescence at triplet 844.6 nm. Bowen fluorescence is generated when thermospheric oxygen absorbs Solar Lyman-&beta; and de-excites through a path eventually leading to 844.6 nm emission. This emission must be distinguished from the brighter 844.6 nm emission caused by photoelectron (PE) impact, which can be done by measuring the intensity ratio between two branches of the 844.6 triplet. An instrument to measure Mid-latitude Bowen fluorescence has been installed at Millstone Hill Observatory. The instrument is a Spatial Heterodyne Spectrometer (SHS), a novel type of Fourier transform spectrometer. This SHS was first used to observe Na Fraunhofer lines from dayglow at 589 nm, and is to be turned to the 844.6 region. With simple readjustments, it can also be reset for other visible and near IR wavelengths.
Automatic detection of cerebral microbleeds via deep learning based 3D feature representation (2015)

Clinical identification and rating of the cerebral microbleeds (CMBs) are important in vascular diseases and dementia diagnosis. However, manual labeling is time-consuming with low reproducibility. In this paper, we present an automatic method via deep learning based 3D feature representation, which solves this detection problem with three steps: candidates localization with high sensitivity, feature representation, and precise classification for reducing false positives. Different from previous methods by exploiting low-level features, e.g., shape features and intensity values, we utilize the deep learning based high-level feature representation. Experimental results validate the efficacy of our approach, which outperforms other methods by a large margin with a high sensitivity while significantly reducing false positives per subject.
Circular Dichroism Studies of the Interaction between Synthetic Peptides Corresponding to Intracellular Loops of β-Adrenergic Receptors and Phospholipid Vesicles1 (1994)

We previously showed that peptides corresponding to the N-terminal parts of the third intracellular loops of turkey and hamster beta-adrenergic receptors (tu beta I3N and ha beta I3N, respectively) can activate the GS protein (one of the GTP-binding regulatory proteins which couples to the beta-adrenergic receptor) reconstituted in phospholipid vesicles, and also that such activation can be greatly enhanced by a modification which increases the hydrophobicity of the peptides. These observed phenomena suggest that the interaction with phospholipid membranes is important for the activity of these peptides; hence, in the present study we employed circular dichroism to analyze the interaction of the synthetic peptides corresponding to the intracellular loops of G protein-coupled receptors with phosphatidylserine/phosphatidylcholine mixed vesicles. The tu beta I3N and ha beta I3N peptides were subsequently found to take on an alpha-helical conformation upon binding with the vesicles, whereas those corresponding to the intracellular loops of m1 and m2 muscarinic acetylcholine receptors in contrast did not interact with the vesicles. The positions of several side chains of the membrane-bound loop peptides were also determined. Our results show for the first time the interaction occurring between the intracellular loops of beta-adrenergic receptors and a phospholipid membrane.
Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. (1987)

Antigen-specific, Ia-restricted helper/inducer T lymphocytes consist of subsets that can be distinguished by lymphokine secretion. One, called Th1, secretes IL-2 and the other, termed Th2, produces BSF-1/IL-4 in response to stimulation by lectin or antigen receptor signals, and each uses the respective lymphokine as its autocrine growth factor. Cloned lines representing Th2 cells proliferate in response to both IL-2 and their autocrine lymphokine, BSF-1/IL-4, but this proliferation is dependent on the synergistic costimulator activity of the monokine, IL-1. In contrast, Th1 clones proliferate only in response to IL-2, are unresponsive to BSF-1/IL-4, and their growth is unaffected by IL-1. These response patterns are not attributable to variations in culture conditions but apparently reflect intrinsic properties of the two T cell subsets. Moreover, the unresponsiveness of Th1 cells to BSF-1/IL-4 may be related to lower levels of expression of surface receptors for this lymphokine. These results may explain the observed heterogeneity among bulk populations of T cells in terms of lymphokine responsiveness and requirement for accessory factors (costimulators). In addition, our findings suggest that IL-2, unlike BSF-1/IL-4, is a fully competent growth factor that is potentially involved in antigen-independent expansion of bystander T cells present at sites of immune stimulation.
Exogenous hyaluronidases and degradation of hyaluronic acid in the rabbit eye. (1984)

The infusion of two enzymes that degrade hyaluronic acid--testicular hyaluronidase and Streptomyces hyaluronidase--was evaluated by quantitative aqueous perfusion of rabbit eyes and by analyses of glycosaminoglycans (GAGs) isolated from the enzyme-treated eyes. The infusion of 1 and 10 units of Streptomyces hyaluronidase (SH) was considerably more effective than the infusion of 10 and 100 units of testicular hyaluronidase (TH) in reducing aqueous outflow resistance. As a result of the infusion of heat-inactivated enzymes, only a moderate decrease of hyaluronic acid in the aqueous outflow pathway was observed. There was no significant "wash-out" of other GAG material, ie, keratan sulfate, heparan sulfate, and hybrid dermatan sulfate-chondroitin sulfate. The SH enzyme, tested by infusion and isolation of GAGs or by in vitro analyses of the rate and extent of degradation of GAGs, completely removed all hyaluronic acid and did not alter the other GAGs. In contrast, the TH enzyme was only partially effective in degrading susceptible GAGs. The results of these studies indicate that SH is more effective than TH in decreasing aqueous outflow resistance and that hyaluronic acid is an important GAG contributor to aqueous outflow resistance in the normal rabbit eye.
Serum Tryptase Measurements in Patients with Myelodysplastic Syndromes (2002)

Abnormal differentiation and maturation of hemopoietic cells are characteristic features of myelodysplastic syndromes (MDS). Tryptases (alpha- and beta-type) are lineage-restricted serine proteases primarily expressed in mast cells (MC). We have analyzed expression of tryptase in 89 de novo MDS patients (refractory anemia (RA), n = 30; RA with ringed sideroblasts (RARS), n = 21; RA with excess of blasts (RAEB/RAEB-t), n = 27; chronic myelomonocytic leukemia (CMML), n = 11). Serum levels of total tryptase (alpha - protryptase + beta - tryptase) were measured by FIA. The numbers of tryptase+ cells were determined in paraffin-embedded bone marrow (bm) sections by immunohistochemistry and morphometry. In healthy individuals, serum total tryptase levels ranged between < 1 and 15 ng/ml (5.6 +/- 2.8 ng/ml). Tryptase levels of > 20 ng/ml were detected in 5/22 patients with RA (22.7%), 4/17 with RARS (23.5%), 0/16 with RAEB/RAEB-t, and 3/8 with CMML (37.5%). Thus, serum tryptase concentrations were higher in RA (16.6 +/- 14.3 ng/ml), RARS (12.9 +/- 8.2), and CMML (16.5 +/- 7.6) compared to RAEB/-t (8.7 +/- 3.8). By morphometry, elevated numbers of tryptase+ bm cells were detected in all MDS groups (RA: 139 +/- 131; RARS: 118 +/- 98; RAEB/RAEB-t: 80 +/- 79; CMML: 105 +/- 114 cells/mm2) compared to controls (54 +/- 51 cells/mm2). As assessed by Northern blotting and protein analysis, bm cells in MDS primarily produced alpha-(pro)tryptase, but little or no beta-tryptase. Together, our data show that elevated levels of tryptase are detectable in a group of patients with MDS probably because of an increase in neoplastic (mast) cells producing the enzyme(s). In addition, serum tryptase levels appear to correlate with MDS variants. Follow up studies should clarify whether an elevated tryptase concentration in MDS is of prognostic significance.
All About Albumin: Biochemistry, Genetics, and Medical Applications (1995)

A Historical Perspective. The Albumin Molecule: Its Structure and Chemical Properties. Ligand Binding by Albumin. Genetics: The Albumin Gene. Metabolism: Albumin in the Body. Clinical Aspects: Albumin in Medicine. Practical Aspects: Albumin in the Laboratory. Subject Index.
The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer (2003)

The cell cycle is controlled by numerous mechanisms ensuring correct cell division. This review will focus on these mechanisms, i.e. regulation of cyclin-dependent kinases (CDK) by cyclins, CDK inhibitors and phosphorylating events. The quality checkpoints activated after DNA damage are also discussed. The complexity of the regulation of the cell cycle is also reflected in the different alterations leading to aberrant cell proliferation and development of cancer. Consequently, targeting the cell cycle in general and CDK in particular presents unique opportunities for drug discovery. This review provides an overview of deregulation of the cell cycle in cancer. Different families of known CDK inhibitors acting by ATP competition are also discussed. Currently, at least three compounds with CDK inhibitory activity (flavopiridol, UCN-01, roscovitine) have entered clinical trials.
C‐CAM (cell‐CAM 105) – a member of the growing immunoglobulin superfamily of cell adhesion proteins (1991)

Cell recognition and adhesion, being of prime importance for the formation and integrity of tissues, are mediated by cell adhesion molecules, which can be divided into several distinct protein superfamilies. The cell adhesion molecule C-CAM (cell-CAM 105) belongs to the immunoglobulin superfamily, and more specifically is a member of the carcinoembryonic antigen (CEA) gene family. C-CAM can mediate adhesion between hepatocytes in vitro in a homophilic, calcium-independent binding reaction. The molecule, which occurs in various isoforms, is expressed in liver, several epithelia, vessel endothelia, platelets and granulocytes and its expression is dynamically regulated under various physiological and pathological conditions. It is proposed that C-CAM in different cells and tissues plays different functional roles, where the common denominator is membrane-membrane binding.