gebhart/patrepeval huggingface dataset:
COMPUTATIONAL STRATEGY FOR DISCOVERING DRUGGABLE GENE NETWORKS FROM GENOME-WIDE RNA EXPRESSION PROFILES (2005)

We propose a computational strategy for discovering gene networks affected by a chemical compound. Two kinds of DNA microarray data are assumed to be used: One dataset is short time-course data that measure responses of genes following an experimental treatment. The other dataset is obtained by several hundred single gene knock-downs. These two datasets provide three kinds of information; (i) A gene network is estimated from time-course data by the dynamic Bayesian network model, (ii) Relationships between the knocked-down genes and their regulatees are estimated directly from knock-down microarrays and (iii) A gene network can be estimated by gene knock-down data alone using the Bayesian network model. We propose a method that combines these three kinds of information to provide an accurate gene network that most strongly relates to the mode-of-action of the chemical compound in cells. This information plays an essential role in pharmacogenomics. We illustrate this method with an actual example where human endothelial cell gene networks were generated from a novel time course of gene expression following treatment with the drug fenofibrate, and from 270 novel gene knock-downs. Finally, we succeeded in inferring the gene network related to PPAR-alpha, which is a known target of fenofibrate.
Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA. (1977)

Glucocorticoid hormones specifically increase the intracellular concentration of mouse mammary tumor virus (MMTV) RNA in a cultured cell line from a GR mouse mammary carcinoma (GR) and in an MMTV-infected rat hepatoma cell line (M1.19). In contrast, these steroids have no effect on the concentration of MMTV RNA in a lymphoma line, S49, from a Balb/c mouse. Using a molecular hybridization procedure to detect newly synthesized RNA, we have directly measured the effect of dexamethasone, a synthetic glucocorticoid, on the rate of MMTV RNA synthesis. In GR cells the hormone causes a 10-fold increase in the rate of synthesis of viral RNA without appreciably affecting the overall rate of cellular RNA synthesis. The transition from the basal to the maximally stimulated rate of MMTV RNA synthesis occurs within the earliest labeling period, 0-15 min after addition of the hormone. Thus, it appears that glucocorticoids regulate MMTV genes principally by this rapid and specific alteration of their rate of transcription. Similar results are obtained in M1.19 rat hepatoma cells. In contrast, dexamethasone does not affect the rate of viral RNA synthesis in S49 lymphoma cells.
Analysis of Sperm Cell Viability, Acrosomal Integrity, and Mitochondrial Function Using Flow Cytometry1 (1990)

A triple staining procedure was developed to evaluate bull spermatozoa using flow cytometry. Flow cytometric estimates of cell viability, measured by propidium iodide (PI) exclusion, and acrosomal integrity, measured by Pisum sativum agglutinin (PSA) binding acrosomal contents, were equivalent to estimates made by using standard laboratory assays. Mitochondrial function, measured by rhodamine 123 (R123) fluorescence, was depressed by the mitochondrial inhibitors rotenone (64%) or monensin (52%), establishing that mitochondrial damage can be detected. Dilauroylphosphatidylcholine (PC12) or lysophosphatidylcholine (LPC) was used to destabilize sperm membranes. When challenged with 15-30 microM PC12, selective exposure of PSA binding sites occurred without induction of PI uptake or loss of R123 staining. However, PC12 concentrations greater than 60 microM resulted in a loss of R123 fluorescence intensity. In contrast, greater than 1200 microM LPC was required to expose PSA binding sites, which also resulted in PI uptake. By using flow cytometry, these three stains in combination can be used to correlate three different features simultaneously on individual spermatozoa and assay thousands of cells per sample without extensive preparation.
A leakage current model for SOI based floating body memory that includes the Poole-Frenkel effect (2008)

The leakage current of SOI based Floating Body Memory (FBM) has been modeled. The model takes into account oxide/SOI interface traps (D <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">it</sub> ) and Electric Field Enhanced (EFE) generation of electron hole pairs (EHPs) from trap states via the Poole-Frenkel Effect (PFE). This model has been used to improve the retention time of Z-RAM by a reduction of both D <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">it</sub> and electric field. It can also be extended to SOI based low power devices.
Conditional Dicer Substrate Formation via Shape and Sequence Transduction with Small Conditional RNAs (2013)

RNA interference (RNAi) mediated by small interfering RNAs (siRNAs) enables knockdown of a gene of choice, executing the logical operation: silence gene Y. The fact that the siRNA is constitutively active is a significant limitation, making it difficult to confine knockdown to a specific locus and time. To achieve spatiotemporal control over silencing, we seek to engineer small conditional RNAs (scRNAs) that mediate 'conditional RNAi' corresponding to the logical operation: if gene X is transcribed, silence independent gene Y. By appropriately selecting gene X, knockdown of gene Y could then be restricted in a tissue- and time-specific manner. To implement the logic of conditional RNAi, our approach is to engineer scRNAs that, upon binding to mRNA 'detection target' X, perform shape and sequence transduction to form a Dicer substrate targeting independent mRNA 'silencing target' Y, with subsequent Dicer processing yielding an siRNA targeting mRNA Y for destruction. Toward this end, here we design and experimentally validate diverse scRNA mechanisms for conditional Dicer substrate formation. Test tube studies demonstrate strong OFF/ON conditional response, with at least an order of magnitude increase in Dicer substrate production in the presence of the cognate mRNA detection target. By appropriately dimensioning and/or chemically modifying the scRNAs, only the product of signal transduction, and not the reactants or intermediates, is efficiently processed by Dicer, yielding siRNAs. These mechanism studies explore diverse design principles for engineering scRNA signal transduction cascades including reactant stability vs metastability, catalytic vs noncatalytic transduction, pre- vs post-transcriptional transduction, reactant and product molecularity, and modes of molecular self-assembly and disassembly.
Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity (2003)

Experimental work during the past 15 years has demonstrated that endothelial cells in the heart play an obligatory role in regulating and maintaining cardiac function, in particular, at the endocardium and in the myocardial capillaries where endothelial cells directly interact with adjacent cardiomyocytes. The emerging field of targeted gene manipulation has led to the contention that cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal cardiac development and growth. Some of the molecular mechanisms and cellular signals governing this interaction, such as neuregulin, vascular endothelial growth factor, and angiopoietin, continue to maintain phenotype and survival of cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular endothelial cells, also express and release a variety of auto- and paracrine agents, such as nitric oxide, endothelin, prostaglandin I(2), and angiotensin II, which directly influence cardiac metabolism, growth, contractile performance, and rhythmicity of the adult heart. The synthesis, secretion, and, most importantly, the activities of these endothelium-derived substances in the heart are closely linked, interrelated, and interactive. It may therefore be simplistic to try and define their properties independently from one another. Moreover, in relation specifically to the endocardial endothelium, an active transendothelial physicochemical gradient for various ions, or blood-heart barrier, has been demonstrated. Linkage of this blood-heart barrier to the various other endothelium-mediated signaling pathways or to the putative vascular endothelium-derived hyperpolarizing factors remains to be determined. At the early stages of cardiac failure, all major cardiovascular risk factors may cause cardiac endothelial activation as an adaptive response often followed by cardiac endothelial dysfunction. Because of the interdependency of all endothelial signaling pathways, activation or disturbance of any will necessarily affect the others leading to a disturbance of their normal balance, leading to further progression of cardiac failure.
Direct monitoring of coronary artery motion with cardiac fat navigator echoes (2003)

Navigator echoes (NAVs) provide an effective means of monitoring physiological motion in magnetic resonance imaging (MRI). Motion artifacts can be suppressed by adjusting the data acquisition accordingly. The standard pencil-beam NAV has been used to detect diaphragm motion; however, it does not monitor cardiac motion effectively. Here we report a navigator approach that directly measures coronary artery motion by exciting the surrounding epicardial fat and sampling the signal with a k-space trajectory sensitized to various motion parameters. The present preliminary human study demonstrates that superior-inferior (SI) respiratory motion of the coronary arteries detected by the cardiac fat NAV highly correlates with SI diaphragmatic motion detected by the pencil-beam NAV. In addition, the cardiac fat navigator gating is slightly more effective than the diaphragmatic navigator gating in suppressing motion artifacts in free-breathing 3D coronary MR angiography (MRA).
Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs (2003)

MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield approximately 65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, approximately 22-nt miRNAs. Here, we demonstrate that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5. Exportin-5 can bind pre-miRNAs specifically in vitro, but only in the presence of the Ran-GTP cofactor. Short hairpin RNAs, artificial pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin-5 for nuclear export. Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function.
Mitral Valve Repair is Feasible Following Extensive Decalcification and Reconstruction of the Atrioventricular Groove. (2015)

After aggressive decalcification of the posterior MV annulus, both MV repair and replacement were feasible, with acceptable procedure-related mortality. It was clear however, that decalcification increased both complexity and risk. In well-selected patients, an aggressive approach to MV repair might facilitate a high rate of repair with acceptable midterm outcome in this patient population.
Listening for effective HIV/AIDS interventions application of the beneficiary assessment approach to preparation of the Niger Multi-country AIDS Program (MAP) (2005)

This report describes the Beneficiary Assessment (BA) study done to support the Multi-Country AIDS Program (MAP) in Niger in 2002. BA was chosen as a key research tool largely due to a drive for responsive and culturally appropriate communications strategies to improve health service. In the case discussed in this paper, the World Bank and the Government of Niger's Intersectoral Coordination for the fight against AIDS (CISLS) chose to use BA in order to discover the: (1) present level of knowledge of HIV and attitudes toward those with the disease; (2) perceptions of existing services; (3) constraints on stemming spread; and (4) what measures might be indicated to prevent the spread of the disease. As the most widely-used qualitative assessment tool in Bank operations, BA has produced important policy changes in a range of sectors and countries. The MAP BA brought out crucial information on felt needs and informed the MAP plan. For example, it revealed: (1) the necessity of targeting messages (and, more vitally, precisely how to do so) rather than lumping all high risk populations together and disregarding their very different perspectives, (2) the importance of using community institutions to communicate prevention messages, and (3) the need to integrate HIV Prevention and mitigation efforts with anti-poverty measures in a basic needs context.
The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes (2015)

Mass spectrometry (MS) is a powerful tool for determining the mass of biomolecules with high accuracy and sensitivity. MS performed under so-called "native conditions" (native MS) can be used to determine the mass of biomolecules that associate noncovalently. Here we review the application of native MS to the study of protein-ligand interactions and its emerging role in elucidating the structure of macromolecular assemblies, including soluble and membrane protein complexes. Moreover, we discuss strategies aimed at determining the stoichiometry and topology of subunits by inducing partial dissociation of the holo-complex. We also survey recent developments in "native top-down MS", an approach based on Fourier Transform MS, whereby covalent bonds are broken without disrupting non-covalent interactions. Given recent progress, native MS is anticipated to play an increasingly important role for researchers interested in the structure of macromolecular complexes.
Glycerol monooleate/solvents systems for progesterone transdermal delivery: In vitro permeation and microscopic studies (2002)

Transdermal delivery of most drugs is precluded by the barrier characteristics of the stratum corneum (SC). Chemical penetration enhancers are capable of interacting with SC constituents, inducing a temporary reversible increase in the skin permeability. The aim of this work was to assess the influence of glycerol monooleate (GMO)/solvents systems on percutaneous absorption across hairless mouse SC of a lipophilic drug, progesterone (PG), as well as its effect on the SC structural characteristics, by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The morphological changes observed in the hairless mouse SC suggest a GMO effect on the skin barrier. In addition, the increase in the In vitro PG flux and in vivo penetration of a fluorescent label point towards GMO as a potential absorption enhancer. The results obtained showed that GMO/solvents systems provoked changes in the SC that could be causing increased permeation of PG across hairless mouse skin, optimising in this way the transdermal delivery of this drug.
Diagnostic Value of Recombinant Human Thyrotropin–Stimulated 123I Whole-Body Scintigraphy in the Follow-Up of Patients With Differentiated Thyroid Cancer (2012)

In DTC, rhTSH-aided ¹²³I DxWBS achieves comparable results in diagnostic follow-up with those of rhTSH-aided ¹³¹I DxWBS. Future studies should address the preablation setting and scan activity and timing.
Spontaneous formation of nanospiked microstructures in germanium by femtosecond laser irradiation (2007)

We report a novel phenomenon of spontaneous formation of nearly regular arrays of nanospikes atop conical microstructures by exposing a germanium surface to femtosecond laser pulses in an environment of SF6. Silicon laser texturing has been reported, but no information has been published on laser microtexturing of Ge and in particular the observation of nanospikes atop conical microstructures. The nanospikes are around 2 µm high having a tip radius of 100 nm and are formed atop conical microstructures that are around 5 µm wide and 10 µm tall. The tip radius could be sharpened down to ∼10 nm by brief chemical etching. A higher laser fluence and fewer shots favour the formation of nanospikes. By increasing the number of shots at higher fluence the surface morphology changes from conical microstructures to tall straight-walled pillar-like structures and the nanospikes disappear. The surface morphology of germanium has been compared with silicon. The germanium samples turn completely black after laser processing, i.e. they exhibit greatly reduced reflectivity throughout the visible spectrum.
Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules (1995)

Fusion regulatory protein (FRP)-1 regulates virus-mediated cell fusion and fusion of monocytes. Eleven of fifteen N-terminal amino acids of FRP-1 were the same as the amino acid sequence of 4F2/CD98 heavy chain. FRP-1 molecules were detected in Con A- or IL-2-stimulated lymphocytes, while FRP-1 was rare on resting lymphocytes. These properties of FRP-1 are similar to those of 4F2/CD98. Treatment of monocytes with anti-4F2/CD98 mAbs resulted in cell fusion, and other mAbs directed against 4F2/CD98 induced formation of multinucleated giant cells of Cd+U2ME-7 cells, a CD4+U937 cell line transfected with the HIV gp160 gene. Both anti-4F2/CD98 and anti-FRP-1 mAbs reacted with murine L929 cells expressing human 4F2/CD98 transiently or constitutively. When Newcastle disease virus (NDV)-infected L929 cells expressing human FRP-1/CD98 were incubated with mAb 4-5-1, an anti-FRP-1 mAb, multinucleated giant cells were induced; thus, FRP-1/CD98 molecules expressed in L929 cells are functional for fusion regulatory activity.
Antibodies to the IL-12 receptor beta 2 chain mark human Th1 but not Th2 cells in vitro and in vivo. (1999)

Great attention has been placed on the possibility of distinguishing Th1 from Th2 cells on the basis of differential expression of surface receptors. We have recently shown that the differential expression of the IL-12R beta 2 chain in Th1 and Th2 cells, as measured at the mRNA level, accounts for an important regulatory mechanism in the differentiation of the two cell subsets. In this study, we identify IL-12R expression at the protein level. We have generated an anti-IL-12R beta 2-specific mAb and analyzed IL-12R beta 2 expression on polarized Th cell populations generated in vitro and on T cells derived from patients with Th1- or Th2-mediated inflammatory conditions. Although IL-12R beta 2 was absent in freshly isolated PBMC and in cord blood cells, we were able to detect IL-12R beta 2 expression selectively in differentiated Th1 and T cytotoxic 1, but not Th2 or T cytotoxic 2 cells. In the presence of IL-12, cell surface expression of the IL-12R beta 2 subunit was readily detected on T cells after 24 h, reached the maximum at day 5, and declined thereafter. Most importantly, the anti-IL-12R beta 2 mAb recognizes lung T cells from patients with sarcoidosis, a disease characterized by a typical cell-mediated, Th1-type inflammatory response. In contrast, IL-12R beta 2 was absent in lung T cells from patients with allergic asthma, a disease characterized by a Th2-type inflammatory response. The mAb reported in this study should represent a powerful tool to investigate the role of Th1 and Th2 cells in inflammatory conditions and to monitor therapies aimed at altering the balance of Th cell subsets.
Occurrence of the New Tetracycline Resistance Gene tet (W) in Bacteria from the Human Gut (2000)

Members of our group recently identified a new tetracycline resistance gene, tet(W), in three genera of rumen obligate anaerobes. Here, we show that tet(W) is also present in bacteria isolated from human feces. The tet(W) genes found in human Fusobacterium prausnitzii and Bifidobacterium longum isolates were more than 99.9% identical to those from a rumen isolate of Butyrivibrio fibrisolvens.
Arabidopsis EIN3-binding F-box 1 and 2 form ubiquitin-protein ligases that repress ethylene action and promote growth by directing EIN3 degradation (2004)

Ubiquitination of various intracellular proteins by ubiquitin-protein ligases (or E3s) plays an essential role in eukaryotic cell regulation primarily through its ability to selectively target proteins for degradation by the 26S proteasome. Skp1, Cullin, F-box (SCF) complexes are one influential E3 class that use F-box proteins to deliver targets to a core ligase activity provided by the Skp1, Cullin, and Rbx1 subunits. Almost 700 F-box proteins can be found in Arabidopsis, indicating that SCF E3s likely play a pervasive role in plant physiology and development. Here, we describe the reverse genetic analysis of two F-box proteins, EBF1 and -2, that work coordinately in SCF complexes to repress ethylene action. Mutations in either gene cause hypersensitivity to exogenous ethylene and its precursor 1-aminocyclopropane-1-carboxylic acid. EBF1 and -2 interact directly with ethylene insensitive 3 (EIN3), a transcriptional regulator important for ethylene signaling. Levels of EIN3 are increased in mutants affecting either EBF1 or -2, suggesting that the corresponding SCF complexes work together in EIN3 breakdown. Surprisingly, double ebf1 ebf2 mutants display a substantial arrest of seedling growth and have elevated EIN3 levels, even in the absence of exogenous ethylene. Collectively, our results show that the SCF(EBF1/EBF2)-dependent ubiquitination and subsequent removal of EIN3 is critical not only for proper ethylene signaling but also for growth in plants.
Antidepressants in the treatment of premature ejaculation (1996)

The SSRI antidepressants have emerged as effective new treatment for patients with premature ejaculation whether or not these patients suffer from depression. Clomipramine, fluoxetine, paroxetine, and sertraline seem to be a safe treatment option for patients with premature ejaculation, especially in cases of failed psychological treatment, in rejection of psychological treatment, and when partners are unwilling to cooperate in treatment. Further controlled and larger studies that focus on clinically relevant issues such as dose, length of treatment, maintenance of beneficial effects after treatment discontinuation, and the combination of pharmaco- and behavior therapy for premature ejaculation are warranted. Other medications, such as benzodiazepines, may be useful in some cases of premature ejaculation.
Multicast routing in datagram internetworks and extended LANs (1990)

Multicasting, the transmission of a packet to a group of hosts, is an important service for improving the efficiency and robustness of distributed systems and applications. Although multicast capability is available and widely used in local area networks, when those LANs are interconnected by store-and-forward routers, the multicast service is usually not offered across the resulting internetwork . To address this limitation, we specify extensions to two common internetwork routing algorithms—distance-vector routing and link-state routing—to support low-delay datagram multicasting beyond a single LAN. We also describe modifications to the single-spanning-tree routing algorithm commonly used by link-layer bridges, to reduce the costs of multicasting in large extended LANs. Finally, we discuss how the use of multicast scope control and hierarchical multicast routing allows the multicast service to scale up to large internetworks.