gebhart/patrepeval huggingface dataset:
Systemic siRNA delivery to leukocyte-implicated diseases (2009)

Short interfering RNA (siRNA), a small duplex of RNA fragment, has proved as an extremely useful research tool to interrogate gene functions in test tubes. However, the transformation of siRNAs from a functional genomic tool into a new therapeutic modality has been hindered by ineffective delivery methods for systemic administration. In this review, we will discuss the recent advances in formulating new delivery strategies that target siRNAs to specific cells following systemic administration. Special emphasis will be given to leukocytes, since siRNA delivery remains exceptionally challenging here due to the unavailability of effective delivery technologies. We will not only detail new platforms that utilize leukocyte integrins as receptor targets for siRNAs delivery, but also show how one of these strategies has been utilized for in vivo drug target validation of a novel anti-inflammatory target, cyclin D1, for inflammatory bowel diseases.
The Role of MeCP2 in the Brain (2011)

Methyl-CpG binding protein 2 (MeCP2) was first identified in 1992 as a protein that binds specifically to methylated DNA. Mutations in the MECP2 gene were later found to be the cause of an autism spectrum disorder, Rett syndrome. Despite almost 20 years of research into the molecular mechanisms of MeCP2 function, many questions are yet to be answered conclusively. This review considers several key questions and attempts to evaluate the current state of evidence. For example, is MeCP2 just a methyl-CpG binding protein? Is it a multifunctional protein or primarily a transcriptional repressor? We also consider whether MeCP2, as a chromosome-binding protein, acts at specific sites within the genome or more globally, and in which cell types it is functionally important. Finally, we consider two alternative views of MeCP2 in the brain: as a regulator of brain development or as a factor that helps maintain neuronal/glial function.
APOBEC3G expression is correlated with poor prognosis in colon carcinoma patients with hepatic metastasis. (2014)

Increased expression of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) in human primary colorectal tumors and hepatic metastasis has been detected. However, the clinical relevance of APOBEC3G in colon carcinoma hepatic metastasis remains uncertain. The aim of this study was to assess the prognostic value of APOBEC3G in colon carcinoma patients with hepatic metastasis after hepatic resection. APOBEC3G expression was evaluated by immunohistochemistry in paraffin-embedded primary colon carcinoma and paired hepatic metastasis tissues from 136 patients with liver metastasis from colon carcinoma that underwent hepatic resection. The relation between APOBEC3G expression and clinicopathologic factors and long-term prognosis in these 136 patients was retrospectively examined. The prognostic significance of negative or positive APOBEC3G expression in colon carcinoma hepatic metastasis was assessed using Kaplan-Meier survival analysis and log-rank tests. Positive expression of APOBEC3G was correlated with liver metastasis of colon cancer. Univariate analysis indicated significantly worse overall survival (OS) for patients with a positive APOBEC3G expression in colon carcinoma hepatic metastasis than for patients with a negative APOBEC3G expression. Multivariate analysis showed positive-APOBEC3G in colon carcinoma hepatic metastasis to be an independent prognostic factor for OS after hepatic resection (P = 0.000). Positive expression of APOBEC3G was statistically significantly associated with poor prognosis of colon carcinoma patients with hepatic metastasis. APOBEC3G could be a novel predictor for poor prognosis of colon carcinoma patients with hepatic metastasis after hepatic resection.
Hyperspectral Raman Microscopic Imaging Using Powell Lens Line Illumination (1998)

The design and characterization of a simple and robust hyperspectral Raman line imaging illumination system with the use of a Powell lens is reported. The generated line uniformity is ±5% of total intensity with a laser power density of 12 mW/μm 2 at the sample with a 50×/0.8 NA (numerical aperture) objective. Similar results were obtained by using other objectives. Linewidths remained near the diffraction limit for all objectives tested. Significant decreases in image acquisition time are also reported with the use of a Powell lens-illuminated hyperspectral Raman line imaging microscope equipped with an intensified charge-coupled device (CCD) detector. Hyperspectral images (100 × 350 pixels) were acquired in as little as 8 with a corresponding signal-to-noise ratio of 24.
Homogeneous buoyancy-generated turbulence (1991)

If a random and statistically homogeneous density distribution is created in a fluid, a random motion of the fluid is subsequently generated by buoyancy forces. This motion is resisted by viscous stresses, while the density variation is smoothed by molecular diffusion of the relevant scalar property of the fluid. Furthermore, advective mixing generates smaller-scale components of the scalar quantity, increasing the rate of smoothing. If the Reynolds number of the motion is sufficiently large, the motion becomes turbulent in the ordinary sense. Such turbulence may be said to be generated by an ‘‘active’’ conserved scalar quantity. To elucidate the nature of this buoyancy-driven turbulence, we consider an infinite fluid that is initially at rest everywhere, with a given distribution of the conserved scalar quantity. In order to have a well-defined initial state specified by a manageably small number of parameters, the initial distribution of the scalar is assumed to be statistically homogeneous and isotropic, and to be characterized by a single length L, and a measure of the magnitude of the scalar variations, say, the initial root-mean-square scalar fluctuation θ0. The other parameters on which the field of buoyancy-driven turbulence depends are the kinematic viscosity ν, the diffusivity of the conserved scalar quantity D, and the gravitational constant g. Dimensionless variables are constructed by choosing L as the unit of length and [L/gθ0]1/2 as the unit of time. The choice of these units introduces two dimensionless parameters into the problem, a Reynolds number R=[gθ0L3]1/2/ν and a Schmidt number σ=ν/D. Since analytical treatment of the problem is limited to the special cases where the nonlinear interactions may be neglected (e.g., R and σR≪1), the primary means of inquiry is a numerical simulation of the flow field. We have performed numerical simulations (using a subgrid model) which sample the entire parameter space of the flow. Of particular interest is the asymptotic behavior of the flow as R and σR increase. One observes that a competition arises between the increase in magnitude of the fluid velocity according to the linear equations and the nonlinear generation of small-scale density and velocity fluctuations. The linear analysis predicts that, in dimensionless units, the time tm at which the mean-square velocity fluctuations reach a maximum, as well as the value of this maximum 〈uiui〉m, increases without limit as R and σR increase. In contrast, the results of the numerical simulation show that tm and 〈uiui〉m become independent of R and σR for sufficiently large values of these parameters. The linear amplification of the flow is thus checked by nonlinear effects. Buoyancy-generated turbulence at high Reynolds number has a period of growth from an initial state of rest, lives for a time in which there is a burst of activity, and then dies in consequence of this activity. This example of self-induced mixing can be given a quantitative description which may be useful in other contexts.
Proteinaceous Molecules Mediating Bifidobacterium-Host Interactions (2016)

Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs.
An Arg/Ser Substitution in the Second Epidermal Growth Factor–Like Module of Factor IX Introduces an O-Linked Carbohydrate and Markedly Impairs Activation by Factor XIa and Factor VIIa/Tissue Factor and Catalytic Efficiency of Factor IXa (1999)

Factor IXR94S is a naturally occurring hemophilia B defect, which results from an Arg 94 to Ser mutation in the second epidermal growth factor (EGF)-like module of factor IX. Recombinant factor IXR94S was activated by factor XIa/calcium with an approximately 50-fold reduced rate and by factor VIIa/tissue factor/phospholipid/calcium with an approximately 20-fold reduced rate compared with wild-type factor IX. The apparent molecular mass of the light chain of factor IXaR94S was approximately 6 kD higher than that of plasma or wild-type factor IX, which was not corrected by N-glycosidase F digestion. This result indicated the presence of additional O-linked carbohydrate in the mutant light chain, probably at new Ser 94. The initial rate of activation of factor X by factor IXaR94S in the presence of polylysine was 7% +/- 1% of the initial rate of activation of factor X by plasma factor IXa, and the kc/Km for activation of factor X by factor IXaR94S/factor VIIIa/phospholipid/calcium was 4% +/- 1% of the kc/Km for activation of factor X by plasma factor IXa/factor VIIIa/phospholipid/calcium. The reduced efficiency of activation of factor X by factor IXaR94S in the tenase enzyme complex was due to a 58-fold +/- 12-fold decrease in kcat with little effect on Km. In conclusion, the R94S mutation had introduced an O-linked carbohydrate, which markedly impaired both activation by factor XIa and turnover of factor X in the tenase enzyme complex.
Inhibition of radiation-induced neoplastic transformation by beta-lapachone. (1989)

Beta-lapachone is a potent inhibitor of DNA repair in mammalian cells and activates topoisomerase I. We show that beta-lapachone can prevent the oncogenic transformation of CHEF/18A cells by ionizing radiation. Potentially lethal DNA damage repair (PLDR) occurs while x-irradiated cells are held in medium containing low serum prior to replating. PLDR processes permitted survival recovery but also drastically increased the number of foci per plate (i.e., transformation) of CHEF/18A cells. By blocking PLDR with beta-lapachone, both survival recovery and enhanced transformation were prevented. At equivalent survival levels, exposure of x-irradiated cells to beta-lapachone resulted in an 8-fold decrease in the number of foci per dish as compared to the number of transformants produced after PLDR. Early PLDR-derived increases in transformation may be the result of error-prone genetic rearrangements dependent on topoisomerase I, which are thereby prevented by beta-lapachone. Beta-lapachone exposure decreased the rejoining of DNA strand breaks and produced additional double-strand breaks in x-irradiated cells during PLDR. The activation of topoisomerase I by beta-lapachone may convert repairable single-strand DNA breaks into the more repair-resistant double-strand breaks, thereby preventing PLDR and neoplastic transformation. These results suggest a new direction for the development of anticarcinogenic agents.
Gene Structure of a New Cardiac Peptide Hormone: A Model for Heart-Specific Gene Expression (2000)

Volume excess and mechanical load lead to the induction of the endocrine activity of the heart. The increased production and secretion of A- and B-type natriuretic peptides (ANP and BNP), in turn, unload the heart due to their physiological effects. To find out the mechanisms of cardiac-specific expression and sensitivity to mechanical stimuli of the natriuretic peptide genes, we have used salmon (Salmo salar) as our model organism, because osmoregulating fish have a particularly well developed defense mechanism against volume excess. We have previously cloned a complementary DNA from salmon heart encoding a novel vasorelaxant cardiac hormone, salmon cardiac peptide (sCP). Its production is restricted to the heart, and its release is very sensitive to mechanical load. We have now cloned the gene encoding sCP. The structure of the gene suggests that sCP may represent an ancestral form of the mammalian natriuretic peptides. Remarkably, despite the large phylogenetic distance, the sCP promoter is as effective as mammalian ANP promoters in cultured neonatal rat atrial cardiomyocytes. Therefore, structural and functional comparisons of the promoters of sCP and ANP provide an excellent means of identifying the elements and transcription factors required for atrial-specific gene expression and the regulation of the endocrine function of the heart. Isolation of the protein product of sCP gene from salmon atrium demonstrated that the storage form of sCP is the prohormone of 126 amino acids. The final processing of the prohormone appears to take place during exocytosis of the secretory granules, as the released and circulating form is the biologically active 29-amino acid sCP.
The blood DNA virome in 8,000 humans (2017)

The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.
[Peer education's effects on preventing accidental injuries in middle school students]. (2009)

Peer education plays a important role on preventing accidental injuries in the middle school students.
Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy (2005)

We have shown previously that the glucagon-like peptide-1 (GLP-1)-(7-36) amide increases myocardial glucose uptake and improves left ventricular (LV) and systemic hemodynamics in both conscious dogs with pacing-induced dilated cardiomyopathy (DCM) and humans with LV systolic dysfunction after acute myocardial infarction. However, GLP-1-(7-36) is rapidly degraded in the plasma to GLP-1-(9-36) by dipeptidyl peptidase IV (DPP IV), raising the issue of which peptide is the active moiety. By way of methodology, we compared the efficacy of a 48-h continuous intravenous infusion of GLP-1-(7-36) (1.5 pmol.kg(-1).min(-1)) to GLP-1-(9-36) (1.5 pmol.kg(-1).min(-1)) in 28 conscious, chronically instrumented dogs with pacing-induced DCM by measuring LV function and transmyocardial substrate uptake under basal and insulin-stimulated conditions using hyperinsulinemic-euglycemic clamps. As a result, dogs with DCM demonstrated myocardial insulin resistance under basal and insulin-stimulated conditions. Both GLP-1-(7-36) and GLP-1-(9-36) significantly reduced (P < 0.01) LV end-diastolic pressure [GLP-1-(7-36), 28 +/- 1 to 15 +/- 2 mmHg; GLP-1-(9-36), 29 +/- 2 to 16 +/- 1 mmHg] and significantly increased (P < 0.01) the first derivative of LV pressure [GLP-1-(7-36), 1,315 +/- 81 to 2,195 +/- 102 mmHg/s; GLP-1-(9-36), 1,336 +/- 77 to 2,208 +/- 68 mmHg] and cardiac output [GLP-1-(7-36), 1.5 +/- 0.1 to 1.9 +/- 0.1 l/min; GLP-1-(9-36), 2.0 +/- 0.1 to 2.4 +/- 0.05 l/min], whereas an equivolume infusion of saline had no effect. Both peptides increased myocardial glucose uptake but without a significant increase in plasma insulin. During the GLP-1-(9-36) infusion, negligible active (NH2-terminal) peptide was measured in the plasma. In conclusion, in DCM, GLP-1-(9-36) mimics the effects of GLP-1-(7-36) in stimulating myocardial glucose uptake and improving LV and systemic hemodynamics through insulinomimetic as opposed to insulinotropic effects. These data suggest that GLP-1-(9-36) amide is an active peptide.
Objective assessment of cough (1995)

Cough is a primitive reflex typically consisting of an initiating deep inspiration, glottal closure, and an explosive expiration accompanied by a sound. The flow characteristics of cough have been shown to differ between different pulmonary diseases. Cough sounds are generated at the larynx and in the lungs. Modern analysing techniques have also been applied in cough sound studies, and differences in cough sound duration and spectra have been found in pulmonary diseases with different bronchopulmonary pathophysiology. Since the objective assessment of cough is clinically important, automatic cough detectors and counters have been constructed, e.g. to assess the efficacy of antitussive drugs. Also, ambulatory methods for assessment of cough have been reported. This review includes a brief history of cough research and present methods available for objective assessment of cough.
Paired Stat6 C-Terminal Transcription Activation Domains Required Both for Inhibition of an IFN-Responsive Promoter and Trans- Activation (1999)

The cytokines IL-4 and IFN-gamma exert biologically antagonistic effects that in part reflect opposing influences on gene transcription. While the molecular mechanisms for IL-4-mediated transcription activation have been extensively studied, little is known about molecular mechanisms required for IL-4 inhibition of IFN-gamma signaling. We have investigated IL-4 inhibition of the IFN-gamma-inducible promoter for IFN regulatory factor-1 (IRF-1). In a cell line with low endogenous Stat6, increasing levels of activated Stat6 at constant doses of IFN-gamma and IL-4 leads to inhibition of the IRF-1 promoter. The Stat1-dependent IFN-gamma activation sequence element of the IRF-1 promoter is a target for Stat6-mediated inhibition despite apparently normal Stat1 DNA binding. However, our data are inconsistent with competition between Stat1 and Stat6 for access to the IRF-1 IFN-gamma activation sequence or for an essential coactivator as a mechanism for this Stat6-mediated inhibition. Instead, the data demonstrate that a threshold of Stat6 transcription activation domains is required for IL-4-dependent inhibition. The findings provide evidence of a novel mechanism in which the Stat6 transcription activation domains play a critical role in the IL-4-mediated inhibition of an IFN-gamma-inducible promoter.
Bearing Fault Detection Via Stator Current Noise Cancellation and Statistical Control (2008)

This paper proposes a new approach to detect <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">situ</i> bearing faults via stator current monitoring. For <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">situ</i> bearing faults, the characteristic bearing fault frequencies may not exist, particularly at an early stage. In addition, the bearing fault signatures are usually subtle compared to the dominant components in the sampled stator current. Therefore, in this paper, a noise cancellation technique is used to suppress those dominant components that are not related to a potential bearing fault. The remaining components, i.e., the noise-cancelled stator current, are then closely related to the health condition of the bearing. Furthermore, it is observed that under the presence of a bearing fault, the noise-cancelled stator current displays a significant amount of degrees of uncontrolled variation in its magnitude. The uncontrolled variation is detected by observing the samples falling outside the three-sigma limits on Shewhart's control charts. Therefore, it is possible to detect <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in</i> <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">situ</i> bearing faults by detecting the variation in magnitude of the noise-cancelled stator current, as verified by online experiments performed in this paper.
Multicenter Prospective Investigation on Efficacy and Safety of Carperitide for Acute Heart Failure in the 'Real World' of Therapy (2005)

The clinical condition improved in 82% of patients treated with carperitide. Based on these findings, minute strategy will be established for carperitide therapy within the strata of patient characteristics that may predict the prognosis.