gebhart/patrepeval huggingface dataset:
Normalization and subtraction: two approaches to facilitate gene discovery. (1996)

Large-scale sequencing of cDNAs randomly picked from libraries has proven to be a very powerful approach to discover (putatively) expressed sequences that, in turn, once mapped, may greatly expedite the process involved in the identification and cloning of human disease genes. However, the integrity of the data and the pace at which novel sequences can be identified depends to a great extent on the cDNA libraries that are used. Because altogether, in a typical cell, the mRNAs of the prevalent and intermediate frequency classes comprise as much as 50-65% of the total mRNA mass, but represent no more than 1000-2000 different mRNAs, redundant identification of mRNAs of these two frequency classes is destined to become overwhelming relatively early in any such random gene discovery programs, thus seriously compromising their cost-effectiveness. With the goal of facilitating such efforts, previously we developed a method to construct directionally cloned normalized cDNA libraries and applied it to generate infant brain (INIB) and fetal liver/spleen (INFLS) libraries, from which a total of 45,192 and 86,088 expressed sequence tags, respectively, have been derived. While improving the representation of the longest cDNAs in our libraries, we developed three additional methods to normalize cDNA libraries and generated over 35 libraries, most of which have been contributed to our integrated Molecular Analysis of Genomes and Their Expression (IMAGE) Consortium and thus distributed widely and used for sequencing and mapping. In an attempt to facilitate the process of gene discovery further, we have also developed a subtractive hybridization approach designed specifically to eliminate (or reduce significantly the representation of) large pools of arrayed and (mostly) sequenced clones from normalized libraries yet to be (or just partly) surveyed. Here we present a detailed description and a comparative analysis of four methods that we developed and used to generate normalize cDNA libraries from human (15), mouse (3), rat (2), as well as the parasite Schistosoma mansoni (1). In addition, we describe the construction and preliminary characterization of a subtracted liver/spleen library (INFLS-SI) that resulted from the elimination (or reduction of representation) of -5000 INFLS-IMAGE clones from the INFLS library.
The endomembrane requirement for cell surface repair (2003)

The capacity to reseal a plasma membrane disruption rapidly is required for cell survival in many physiological environments. Intracellular membrane (endomembrane) is thought to play a central role in the rapid resealing response. We here directly compare the resealing response of a cell that lacks endomembrane, the red blood cell, with that of several nucleated cells possessing an abundant endomembrane compartment. RBC membrane disruptions inflicted by a mode-locked Ti:sapphire laser, even those initially smaller than hemoglobin, failed to reseal rapidly. By contrast, much larger laser-induced disruptions made in sea urchin eggs, fibroblasts, and neurons exhibited rapid, Ca(2+)-dependent resealing. We conclude that rapid resealing is not mediated by simple physiochemical mechanisms; endomembrane is required.
Neuronal migration in the murine rostral migratory stream requires serum response factor (2005)

The central nervous system is fundamentally dependent on guided cell migration, both during development and in adulthood. We report an absolute requirement of the transcription factor serum response factor (SRF) for neuronal migration in the mouse forebrain. Conditional, late-prenatal deletion of Srf causes neurons to accumulate ectopically at the subventricular zone (SVZ), a prime neurogenic region in the brain. SRF-deficient cells of the SVZ exhibit impaired tangential chain migration along the rostral migratory stream into the olfactory bulb. SVZ explants display retarded chain migration in vitro. Regarding target genes, SRF deficiency impairs expression of the beta-actin and gelsolin genes, accompanied by reduced cytoskeletal actin fiber density. At the posttranslational level, cofilin, a key regulator of actin dynamics, displays dramatically elevated inhibitory phosphorylation at Ser-3. Our studies indicate that SRF-controlled gene expression directs both the structure and dynamics of the actin microfilament, thereby determining cell-autonomous neuronal migration.
Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs (2005)

Hypercholesterolemia (HC), a major risk factor for onset and progression of renal disease, is associated with increased oxidative stress, potentially causing endothelial dysfunction. One of the sources of superoxide anion is xanthine oxidase (XO), but its contribution to renal endothelial function in HC remains unclear. We tested the hypothesis that XO modulates renal hemodynamics and endothelial function in HC pigs. Four groups ( n = 23) of female domestic pigs were studied 12 wk after either normal ( n = 11) or HC diet ( n = 12). Oxidative stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting and immunohistochemistry). Renal hemodynamics and function were studied with electron beam-computed tomography before and after endothelium-dependent (ACh) and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal infusion of either oxypurinol or saline ( n = 5–6 in each group). HC showed elevated oxidative stress, higher plasma uric acid (23.8 ± 3.8 vs. 6.2 ± 0.8 μM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO expression compared with normal. Inhibition of XO in HC significantly improved the blunted responses to ACh of cortical perfusion (13.5 ± 12.1 and 37.2 ± 10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood flow, and glomerular filtration rate; restored medullary perfusion; and improved the blunted cortical perfusion response to sodium nitroprusside. This study demonstrates that the endogenous XO system is activated in swine HC. Furthermore, it suggests an important role for XO in regulation of renal hemodynamics, function, and endothelial function in experimental HC.
Bilateral Subthalamic Nucleus Stimulation for Parkinson's Disease: A Systematic Review of the Clinical Literature (2005)

Bilateral subthalamic nucleus stimulation is effective in the treatment of PD. Further refinements in patient selection and surgical technique may lessen the incidence of complications associated with this procedure.
A Visual Model Weighted Cosine Transform for Image Compression and Quality Assessment (1985)

Utilizing a cosine transform in image compression has several recognized performance benefits, resulting in the ability to attain large compression ratios with small quality loss. Also, incorporation of a model of the human visual system into an image compression or quality assessment technique intuitively should (and has often proven to) improve performance. Clearly, then, it should prove highly beneficial to combine the image cosine transform with a visual model. In the past, combining these two has been hindered by a fundamental problem resulting from the scene alteration that is necessary for proper cosine transform utilization. A new analytical solution to this problem, taking the form of a straightforward multiplicative weighting function, is developed in this paper. This solution is readily applicable to image compression and quality assessment in conjunction with a visual model and the image cosine transform. In the development, relevant aspects of a human visual system model are discussed, and a refined version of the mean square error quality assessment measure is given which should increase this measure's utility.
A Search for Components in Human Body Odour that Attract Females of Aedes Aegypti (2007)

In a new type of wind tunnel, mosquitoes fly upwind towards host odour sources and towards human skin wash extracts obtained by rubbing the skin with a pad soaked in ethanol. We used this behavioural response as a bioassay to identify attractants in liquid chromatography fractions of such extracts. L-Lactic acid is a major constituent of skin wash extracts and it is a necessary component for the extract's effectiveness. As a single stimulus, however, L-lactic acid is only slightly effective. This indicates that the extract's high degree of effectiveness is based on a synergism of L-lactic acid and other odour components. The separation of the extract by liquid chromatography revealed three distinct regions of active fractions, only one of which contained L-lactic acid. The components of the other two regions have not yet been determined. A combination of fractions in these two regions together with L-lactic acid is as attractive as the complete extract.
Efficacy and safety of olopatadine hydrochloride 0.77% in patients with allergic conjunctivitis using a conjunctival allergen-challenge model (2015)

Olopatadine 0.77% is superior to both its vehicle and olopatadine 0.2% for the treatment of allergen-mediated ocular itching and conjunctival redness. Ocular itching symptom relief is maintained over 24 hours, supporting once-daily dosing and demonstrating a comparable safety profile to olopatadine 0.2%.
Developmentally regulated conversion of mesenchyme to epithelium (1989)

Polarized epithelial cells perform many critical physiological functions in multicellular organisms. Recent embryological studies of the conversion of nonpolar mesenchymal cells to epithelium in the developing mouse kidney have provided vital information on the molecular mechanisms that initiate epithelial cell polarization. To become polar, the cells first attach to the basement membrane that is produced by the developing epithelial cells themselves. Of the basement membrane components, laminin has a key role in the development of epithelial cell polarity. Laminin is a multidomain glycoprotein composed of three subunits: A, B1, and B2. One binding site for epithelial cells is found in the carboxyl-terminal part of the A chain of laminin. Antibodies reacting with this part of laminin inhibit polarization of developing epithelial cells in organ cultures of embryonic kidneys. Expression studies also suggest that the A chain of laminin is important for epithelial cell polarization; the A chain appears when the cells begin to polarize, whereas B chains are expressed at an earlier stage of development. The studies of conversion of mesenchyme to epithelium suggest that morphogenesis can be controlled by differential expression of laminin chains.
Physical and Chemical Properties of Drug Molecules Governing their Diffusion Through the Spinal Meninges (1992)

Drugs administered into the epidural space for selective spinal analgesia must diffuse through the spinal meninges to gain access to their sites of action in the spinal cord. Therefore, knowledge of the physical and chemical properties of drug molecules that govern their diffusion through the meninges is important for understanding the pharmacokinetics of epidural analgesia. To determine the physicochemical properties of drug molecules that govern the rate at which drugs diffuse through the spinal meninges, the authors measured the permeability coefficient of eight different drug molecules through the spinal meninges of the monkey using a previously established in vitro model. We previously reported permeability measurements for four of the molecules used in this study; the other four molecules' permeability measurements are new. The measured permeability coefficient was then correlated with the drugs' molecular weight, molecular surface area, molecular volume, length of the major molecular axis, and octanol:buffer distribution coefficient. We found no relationship between the drugs' permeability coefficients and any measure of drug mass, molecular shape, or molecular size. There was, however, a biphasic relationship between the octanol: buffer distribution coefficient and the drugs' measured permeability coefficients. Drugs that were either very hydrophilic or very hydrophobic had permeability coefficients that were significantly less than drugs of intermediate hydrophobicity. These data suggest that it should be possible to design novel analgesics for which meningeal permeability is maximal.
Variable diffraction gratings using nanoporous electrodes and electrophoresis of dye ions (2007)

Transparent electrically-conductive nanoporous thin films can be used as electrodes to attract dye ions from solution to modulate the reflectance of a surface. Here we demonstrate that this technique can be used to create diffraction gratings that can be modified by the application of a small electrical potential with a selected spatial distribution. Using nanoporous ITO films fabricated by Glancing Angle Deposition, we have produced variable diffraction gratings, fabricated by a variety of methods, including lithography combined with etching techniques or direct patterning using focused ion beam etching. We demonstrate modulation of the diffraction pattern by employing electric force to attract the dye ions into the nanoporous electrode, thereby introducing a substantial local change in the effective refractive index value and thus altering the resultant diffraction pattern and, in some cases, yielding diffractive orders that lie between those associated with the underlying grating. These new orders are easily distinguished and their intensity can be substantially modified by controlling the applied voltage. Because this technique can work with very small pitch gratings, this approach has the potential to enable new applications that may not be readily achieved using conventional liquid crystal technology.
Epitope-optimized alpha-fetoprotein genetic vaccines prevent carcinogen-induced murine autochthonous hepatocellular carcinoma (2013)

Epitope-optimization is required to break immune tolerance and potently activate AFP-specific CD8 T cells, generating effective antitumor effect to prevent clinically relevant carcinogen-induced autochthonous HCC in mice. Our study provides a practical roadmap to develop effective human HCC vaccines that may result in an improved outcome compared to the current HCC vaccines based on wild-type AFP.
A Convergent Enantioselective Route to Structurally Diverse 6-Deoxytetracycline Antibiotics (2005)

Complex antibiotics based on natural products are almost invariably prepared by semisynthesis, or chemical transformation of the isolated natural products. This approach greatly limits the range of accessible structures that might be studied as new antibiotic candidates. Here we report a short and enantioselective synthetic route to a diverse range of 6-deoxytetracycline antibiotics. The common feature of this class is a scaffold of four linearly fused rings, labeled A through D. We targeted not a single compound but a group of structures with the D ring as a site of structural variability. A late-stage, diastereoselective C-ring construction was used to couple structurally varied D-ring precursors with an AB precursor containing much of the essential functionality for binding to the bacterial ribosome. Five derivatives were synthesized from benzoic acid in yields ranging from 5 to 7% over 14 to 15 steps, and a sixth, (-)-doxycycline, was synthesized in 8.3% yield over 18 steps.
Self-Assembly of Molecular Prisms via an Organometallic “Clip” (2002)

[reaction: see text] Under the appropriate conditions, the combination of two tritopic pyridyl ligands with three metal-containing molecular "clips" spontaneously generates supramolecular coordination cages with trigonal prismatic frameworks.
Autotaxin/Lysopholipase D and Lysophosphatidic Acid Regulate Murine Hemostasis and Thrombosis (2009)

The lipid mediator lysophosphatidic acid (LPA) is a potent regulator of vascular cell function in vitro, but its physiologic role in the cardiovasculature is largely unexplored. To address the role of LPA in regulating platelet function and thrombosis, we investigated the effects of LPA on isolated murine platelets. Although LPA activates platelets from the majority of human donors, we found that treatment of isolated murine platelets with physiologic concentrations of LPA attenuated agonist-induced aggregation. Transgenic overexpression of autotaxin/lysophospholipase D (Enpp2), the enzyme necessary for production of the bulk of biologically active LPA in plasma, elevated circulating LPA levels and induced a bleeding diathesis and attenuation of thrombosis in mice. Intravascular administration of exogenous LPA recapitulated the prolonged bleeding time observed in Enpp2-Tg mice. Enpp2+/- mice, which have approximately 50% normal plasma LPA levels, were more prone to thrombosis. Plasma autotaxin associated with platelets during aggregation and concentrated in arterial thrombus, and activated but not resting platelets bound recombinant autotaxin/lysoPLD in an integrin-dependent manner. These results identify a novel pathway in which LPA production by autotaxin/lysoPLD regulates murine hemostasis and thrombosis and suggest that binding of autotaxin/lysoPLD to activated platelets may provide a mechanism to localize LPA production.
Gold and nano-gold in medicine: overview, toxicology and perspectives (2009)

Nano-technology has entered the field of medicine in recent decades and many of the nanomaterials developed have already had a high impact on health care. Among nanomaterials, gold nanoparticles (GNPs) and gold quantum dots (QDs) are receiving significant attention because their unique physical, chemical and biological properties are quite different from the bulk of their counterparts. In this article, after a brief historical overview, the use of gold and nano-gold in medicine is reviewed, analyzed, and discussed. The review particularly deals with the use of GNPs and bio-conjugated GNPs in cancer treatment, drug or gene delivery, DNA detection, biomedical imaging including that of brain activity, enhancement of gene regulation, the detection of toxic metals, immuno-assays, disease detection and diagnostics, therapy and also the toxicity of gold and GNPs, etc. A number of novel applications of GNPs in medicine and perspectives of nano-gold use in medicine are also discussed.
DNA synthesis-associated nuclear exclusion of p53 in normal human breast epithelial cells in culture. (1994)

Immunohistochemical staining using three monoclonal antibodies to p53 revealed that most normal human breast epithelial cells (HBEC) in the exponential growth phase, have p53 located in the nucleus but that some cells have the protein in the cytoplasm. Cytoplasmic staining of p53 with the monoclonal antibody PAb240 was inhibited by the specific oligopeptide, NTFRHSVVVP, that corresponds to the amino acids between 210 and 219 in p53 and which includes the epitope domain for PAb240. It was not inhibited by the control oligopeptide SPFVTVHNVR. Growth arrest of HBEC achieved by EGF depletion resulted in predominant nuclear location of p53 and stimulation of arrested cells with EGF induced transient nuclear exclusion of the protein when the induced DNA synthesis level was maximal. These observations suggest that p53 in normal HBEC becomes inactivated by nuclear exclusion during cellular DNA synthesis.
Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915-29 (1998)

This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.
Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity (1999)

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.
<title>Command-wide teleradiology for U.S. armed forces in Korea</title> (1992)

There are 17 U.S. military medical treatment facilities scattered in the Republic of Korea to provide health care for approximately 40,000 U.S. troops and their dependents. Only three Army and one Air Force radiologist are assigned for radiological diagnosis. In some areas, report turn-around time can be as long as two weeks. An extensive teleradiology network is planned as part of an MDIS implementation program to improve the quality of radiological service overcoming the distance and time barriers.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Minimum intron requirements for tRNA splicing and nuclear transport in Xenopus oocytes (1993)

The presence or absence of an intron defines two classes of eukaryotic nuclear tRNA genes whose transcripts differ in a requirement for splicing. Using quantitative nuclear microinjection, we have previously found that nucleocytoplasmic transport of these two classes of tRNAs involves pathways which differ in one or more limiting components. To examine substrate features which distinguish these two pathways, a series of variants of a Xenopus tRNA(Tyr) gene were constructed in which the intron size was altered. The splicing and transport properties of the resulting transcripts were examined in oocyte microinjection and in vitro processing assays. The addition of one or two nucleotides at the splice site equivalent in an intronless gene produced transcripts which could be transported without splicing. However, transport was reduced relative to the mature-sequence tRNA, suggesting the anticodon loop (interrupted in pre-tRNAs) may be recognized by the intronless tRNA transport apparatus. Transcripts with four- or six-nucleotide intervening sequences were incompletely spliced with cleavage at only the 3' splice site. Neither unspliced precursor nor partially processed intermediates were efficiently transported. The results of coinjection experiments using tRNA and pre-tRNA competitors suggest that simple retention by the splicing apparatus may not account for failure to export these RNAs. Finally, a requirement for splicing is not unique to transport of pre-tRNA(Tyr) since a pre-tRNA(3Leu) variant which was not spliced was also not exported.