gebhart/patrepeval huggingface dataset:
Visualization of Dynamics of Single Endogenous mRNA Labeled in Live Mouse (2014)

The transcription and transport of messenger RNA (mRNA) are critical steps in regulating the spatial and temporal components of gene expression, but it has not been possible to observe the dynamics of endogenous mRNA in primary mammalian tissues. We have developed a transgenic mouse in which all β-actin mRNA is fluorescently labeled. We found that β-actin mRNA in primary fibroblasts localizes predominantly by diffusion and trapping as single mRNAs. In cultured neurons and acute brain slices, we found that multiple β-actin mRNAs can assemble together, travel by active transport, and disassemble upon depolarization by potassium chloride. Imaging of brain slices revealed immediate early induction of β-actin transcription after depolarization. Studying endogenous mRNA in live mouse tissues provides insight into its dynamic regulation within the context of the cellular and tissue microenvironment.
IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response (2002)

All eukaryotic cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded protein response (UPR). In yeast, a type-I ER transmembrane protein kinase, Ire1p, is the proximal sensor of unfolded proteins in the ER lumen that initiates an unconventional splicing reaction on HAC1 mRNA. Hac1p is a transcription factor required for induction of UPR genes. In higher eukaryotic cells, the UPR also induces site-2 protease (S2P)-mediated cleavage of ER-localized ATF6 to generate an N-terminal fragment that activates transcription of UPR genes. To elucidate the requirements for IRE1alpha and ATF6 for signaling the mammalian UPR, we identified a UPR reporter gene that was defective for induction in IRE1alpha-null mouse embryonic fibroblasts and S2P-deficient Chinese hamster ovary (CHO) cells. We show that the endoribonuclease activity of IRE1alpha is required to splice XBP1 (X-box binding protein) mRNA to generate a new C terminus, thereby converting it into a potent UPR transcriptional activator. IRE1alpha was not required for ATF6 cleavage, nuclear translocation, or transcriptional activation. However, ATF6 cleavage was required for IRE1alpha-dependent induction of UPR transcription. We propose that nuclear-localized IRE1alpha and cytoplasmic-localized ATF6 signaling pathways merge through regulation of XBP1 activity to induce downstream gene expression. Whereas ATF6 increases the amount of XBP1 mRNA, IRE1alpha removes an unconventional 26-nucleotide intron that increases XBP1 transactivation potential. Both processing of ATF6 and IRE1alpha-mediated splicing of XBP1 mRNA are required for full activation of the UPR.
Therapy with hydroxyurea is associated with reduced adhesion molecule gene and protein expression in sickle red cells with a concomitant reduction in adhesive properties (2006)

Propagation of the vaso-occlusive process in sickle cell anaemia (SCA) is a complex process involving the adhesion of steady-state SCA patients red cells and reticulocytes to the vascular endothelium. The effect of hydroxyurea therapy (HUT) on the adhesive properties of sickle cells and the expression of adhesion molecule genes by erythroid cells of SCA individuals is not yet fully understood. The expressions of the CD36 gene and the VLA-4-integrin subunit genes, CD49d (alpha-subunit) and CD29 (beta-subunit), were compared in the reticulocytes of steady-state SCA patients and patients on HUT using real-time PCR. Basal adhesion of red cells from these subjects was also compared using static adhesion assays, as was surface protein expression, using flow cytometry. Basal sickle red cell adhesion to fibronectin was significantly greater than that of normal cells (P < 0.01); in contrast, HUT was associated with significantly lower levels (P < 0.01) of red cell adhesion that were similar to those of control cells; this decrease could not be justified solely by altered reticulocyte numbers in this population. Accordingly, flow cytometry demonstrated that reticulocytes from patients on HUT had significantly lower CD36 and CD49d surface expressions (P < 0.01) and, importantly, significantly lower expressions of the CD36, CD49d and CD29 genes (P < 0.05) than reticulocytes of SCA patients not on HUT. Taken together, data support the hypothesis that HUT reduces the adhesive properties of sickle cells and that this decrease appears to be mediated, at least in part, by a decrease in the gene and, consequently, surface protein expression of adhesion molecules such as VLA-4 and CD36.
Competitive Exclusion of Salmonella Enteritidis by Salmonella Gallinarum in Poultry (2000)

Salmonella Enteritidis emerged as a major egg-associated pathogen in the late 20th century. Epidemiologic data from England, Wales, and the United States indicate that S. Enteritidis filled the ecologic niche vacated by eradication of S. Gallinarum from poultry, leading to an epidemic increase in human infections. We tested this hypothesis by retrospective analysis of epidemiologic surveys in Germany and demonstrated that the number of human S. Enteritidis cases is inversely related to the prevalence of S. Gallinarum in poultry. Mathematical models combining epidemiology with population biology suggest that S. Gallinarum competitively excluded S. Enteritidis from poultry flocks early in the 20th century.
Process Execution Controls: revisited (2002)

In late 1989 the Government of Canada contracted with Thompson-Foss Inc. to implement integrity controls into Trusted Tunis. This paper discusses the Thompson-Foss implementation of Process Execution Controls. In an attempt to better understand the mechanism as well as examine its usefulness as an integrity control the Canadian System Security Centre contracted with Thompson-Foss Incorporated to implement PECs. This paper is an account of the implementation, how well PECs can be implemented on a UNIX-like operating system kernel extensions required to more fully implement PECs, and extensions to Process Execution Controls.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Metabolites of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers' urine. (1993)

Metabolites of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a potent pulmonary carcinogen, have been quantified in the urine of 11 smokers. They were not detected in nonsmokers' urine. The metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide, were detected in quantities of 0.23-1.0 and 0.57-6.5 micrograms/24 h, respectively. The results of this study provide the first evidence for metabolites of tobacco-specific nitrosamines in human urine.
Spontaneous Slow Hemodynamic Oscillations are Impaired in Cerebral Microangiopathy (2005)

Small-vessel disease or cerebral microangiopathy (CMA) is a common finding in elderly people. It is related to a variety of vascular risk factors and may finally lead to subcortical ischemic vascular dementia. Because vessel stiffness is increased, we hypothesized that slow spontaneous oscillations are reduced in cerebral hemodynamics. Accordingly, we examined spontaneous oscillations in the visual cortex of 13 patients suffering from CMA, and compared them with 14 age-matched controls. As an imaging method we applied functional near-infrared spectroscopy, because it is particularly sensitive to the microvasculature. Spontaneous low-frequency oscillations (LFOs) (0.07 to 0.12 Hz) were specifically impaired in CMA in contrast to spontaneous very-low-frequency oscillations (0.01 to 0.05 Hz), which remained unaltered. Vascular reagibility was reduced during visual stimulation. Interestingly, changes were tightly related to neuropsychological deficits, namely executive dysfunction. Vascular alterations had to be attributed mainly to the vascular risk factor arterial hypertension. Further, results suggest that the impairments might be, at least partly, reversed by medical treatment such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Results indicate that functional near-infrared spectroscopy may detect changes in the microvasculature due to CMA, namely an impairment of spontaneous LFOs, and of vascular reagibility. Hence, CMA accelerates microvascular changes due to aging, leading to impairments of autoregulation.
Power deposition in whole-body NMR imaging (1981)

The surface radio frequency (rf) power absorption in human head and torso nuclear magnetic resonance (NMR) imaging experiments is estimated. The results are expressed as a function of the NMR frequency, the rf pulse length, and the pulse duty cycle, which are varied over six orders of magnitude for general applicability. The results are compared with average metabolic levels and the limits advised by the National Radiological Protection Broad of the United Kingdom. Heating due to time-dependent magnetic field gradients is discussed.
The Challenge of Asian Law (1995)

Several years ago, when U.S. trade across the Pacific finally surpassed that across the Atlantic, a small group of U.S. lawyers were already responding to the challenge of representing clients in transactions in Asia. While few had had the opportunity to take courses dealing with Asian law during their law school years, many entered the field because of undergraduate language and area studies courses. A few had taught courses dealing with Asia before beginning their law studies.
Mutual capacitance of liquid conductors in deformable tactile sensing arrays (2016)

Advances in highly deformable electronics are needed in order to enable emerging categories of soft computing devices ranging from wearable electronics, to medical devices, and soft robotic components. The combination of highly elastic substrates with intrinsically stretchable conductors holds the promise of enabling electronic sensors that can conform to curved objects, reconfigurable displays, or soft biological tissues, including the skin. Here, we contribute sensing principles for tactile (mechanical image) sensors based on very low modulus polymer substrates with embedded liquid metal microfluidic arrays. The sensors are fabricated using a single-step casting method that utilizes fine nylon filaments to produce arrays of cylindrical channels on two layers. The liquid metal (gallium indium alloy) conductors that fill these channels readily adopt the shape of the embedding membrane, yielding levels of deformability greater than 400%, due to the use of soft polymer substrates. We modeled the sensor performance using electrostatic theory and continuum mechanics, yielding excellent agreement with experiments. Using a matrix-addressed capacitance measurement technique, we are able to resolve strain distributions with millimeter resolution over areas of several square centimeters.
A New Approach to Reducing Postsurgical Cancer Recurrence: Perioperative Targeting of Catecholamines and Prostaglandins (2012)

Surgery is a crucial intervention in most cancer patients, but the perioperative period is characterized by increased risks for future outbreak of preexisting micrometastases and the initiation of new metastases-the major cause of cancer-related death. Here we argue that the short perioperative period is disproportionately critical in determining long-term recurrence rates, discuss the various underlying risk factors that act synergistically during this period, and assert that this time frame presents an unexplored opportunity to reduce long-term cancer recurrence. We then address physiologic mechanisms that underlie these risk factors, focusing on excess perioperative release of catecholamines and prostaglandins, which were recently shown to be prominent in facilitating cancer recurrence through their direct impact on the malignant tissue and its microenvironment, and through suppressing antimetastatic immunity. The involvement of the immune system is further discussed in light of accumulating evidence in cancer patients, and given the recent identification of endogenously activated unique leukocyte populations which, if not suppressed, can destroy autologous "immune-resistant" tumor cells. We then review animal studies and human correlative findings, suggesting the efficacy of blocking catecholamines and/or prostaglandins perioperatively, limiting metastasis and increasing survival rates. Finally, we propose a specific perioperative pharmacologic intervention in cancer patients, based on simultaneous β-adrenergic blockade and COX-2 inhibition, and discuss specific considerations for its application in clinical trials, including our approved protocol. In sum, we herein present the rationale for a new approach to reduce long-term cancer recurrence by using a relatively safe, brief, and inexpensive intervention during the perioperative period.
Fibrin Sealant in the United States: Clinical Use at the University of Virginia (1995)

Fibrin sealant use in the United States has been limited because of the lack of a commercially available, government approved product. However, the significant need and usefulness of this material at the time of surgical operations has stimulated alternative sources of production. At the University of Virginia, the Blood Bank produces concentrated single donor or autologous fibrinogen for use with commercially available bovine thrombin in order to make fibrin sealant. The hemostatic and adhesive properties of fibrin sealant have been used since 1985 at this Center in a wide variety of operations with over 90% effectiveness. This chapter will review the development and role of this material in modern clinical surgery at this institution. The advantages, disadvantages, and never applications of this substance in various forms will be assessed. The role of fibrin sealant is increasing in this country and additional developmental work is continuing. The era of a commercially available product in the United States appears to be on the horizon.
Cutting Edge: MHC Class II-Restricted Peptides Containing the Inflammation-Associated Marker 3-Nitrotyrosine Evade Central Tolerance and Elicit a Robust Cell-Mediated Immune Response (2003)

Nitrotyrosine is widely recognized as a surrogate marker of up-regulated inducible NO synthase expression at sites of inflammation. However, the potential immunogenicity of autologous proteins containing nitrotyrosine has not previously been investigated. Herein, we used the I-E(K)-restricted T cell epitope of pigeon/moth cytochrome c (PCC/MCC(88-103)) to assess the ability of T cells to recognize ligands containing nitrotyrosine. Substitution of the single tyrosine (Y97) in PCC/MCC(88-103) with nitrotyrosine abrogates recognition by the MCC(88-103)-specific T cell hybridoma 2B4. CBA (H2(K)) mice immunized with MCC(88-103) or nitrated MCC(88-103) peptides produce T cell responses that are mutually exclusive. Transgenic mice that constitutively express PCC under the control of an MHC class I promoter are tolerant toward immunization with MCC(88-103), but exhibited a robust immune response against nitrated MCC(88-103). Analysis of T cell hybridomas specific for nitrated-MCC(88-103) indicated that subtle differences in TCR VDJ gene usage are sufficient to allow nitrotyrosine-specific T cells to escape the processes of central tolerance.
Serotonin 5-HT3-receptor Antagonist GR 38032F Suppresses Sleep Apneas in Rats (1998)

The effects of administration of GR38032F, a 5-HT3 receptor antagonist, on spontaneous sleep apneas were studied in adult Sprague-Dawley rats by monitoring sleep, respiration and blood pressure for 6 hours. Intraperitoneal injection of GR38032F (1 mg/kg) suppressed spontaneous central apneas during non-rapid-eye-movement (NREM) and especially during rapid-eye-movement (REM) sleep. This effect was associated with increased respiratory drive but did not cause cardiovascular changes at the dose tested. The suppressive action of GR38032F on spontaneous sleep apneas is analogous to findings in anesthetized rats in which 5-HT and 2-methyl-5-HT provoked central apneas that were antagonized by GR38032 (Yoshioka et al, JPET 1992; 260:917-924). Our data implicate 5-HT3 receptor systems in determining sleep-related respiratory drive and apnea expression in rats, effects which are most probably mediated by vagal afferents.
Bind-n-Seq: high-throughput analysis of in vitro protein–DNA interactions using massively parallel sequencing (2009)

Transcription factor-DNA interactions are some of the most important processes in biology because they directly control hereditary information. The targets of most transcription factor are unknown. In this report, we introduce Bind-n-Seq, a new high-throughput method for analyzing protein-DNA interactions in vitro, with several advantages over current methods. The procedure has three steps (i) binding proteins to randomized oligonucleotide DNA targets, (ii) sequencing the bound oligonucleotide with massively parallel technology and (iii) finding motifs among the sequences. De novo binding motifs determined by this method for the DNA-binding domains of two well-characterized zinc-finger proteins were similar to those described previously. Furthermore, calculations of the relative affinity of the proteins for specific DNA sequences correlated significantly with previous studies (R(2 )= 0.9). These results present Bind-n-Seq as a highly rapid and parallel method for determining in vitro binding sites and relative affinities.
Androgen receptors frequently are expressed in breast carcinomas (2003)

Androgen receptors are commonly expressed in DCIS and in invasive breast carcinoma. A significant number of poorly differentiated carcinomas are ER-negative and PR-negative but AR-positive. Immunohistochemical examination of AR would be desirable because it would provide additional information about steroid receptors in breast carcinomas.
The Fatty Liver and Insulin Resistance (2005)

Obesity is not necessary to observe insulin resistance in humans since severe insulin resistance also characterizes patients lacking subcutaneous fat such as those with HAART (highly-active antiretroviral therapy) - associated lipodystrophy. Both the obese and the lipodystrophic patients have, however, an increase in the amount of fat hidden in the liver. Liver fat content can be non-invasively accurately quantified by proton magnetic resonance spectroscopy. It is closely correlated with fasting insulin and direct measures of hepatic insulin sensitivity while the amount of subcutaneous adipose tissue is not. The causes of interindividual variation in liver fat content independent of obesity are largely unknown but could involve differences in signals from adipose tissue such as in the amount of adiponectin produced and differences in fat intake. Adiponectin deficiency characterizes both lipodystrophic and obese insulin resistant individuals, and serum levels correlate with liver fat content. Liver fat content can be decreased by weight loss. In addition, treatment of both lipodystrophic and type 2 diabetic patients with PPARgamma agonists but not metformin decreases liver fat and increases adiponectin levels. Markers of liver fat such as serum alanine aminotransferase activity have been shown to predict type 2 diabetes in several studies independent of obesity. The fatty liver thus may help to explain why some but not all obese individuals are insulin resistant and why even lean individuals may be insulin resistant, and thereby at risk of developing type 2 diabetes and cardiovascular disease.
Classification of virulent and temperate bacteriophages of Listeria spp. on the basis of morphology and protein analysis (1992)

A set of 22 phages of Listeria species (listeriaphages) (21 temperate and 1 virulent) were compared on the basis of morphology and protein composition. All 22 phages had icosahedral heads and exhibited either contractile or noncontractile tails. They represented two different morphotypes. Twenty phages belonged to the Siphoviridae family and could be differentiated only on the basis of tail length. Accordingly, they could be assigned to previously defined listeriaphage species. Two other phages were classified as members of the Myoviridae family, one of which (A511) should be regarded as a new species. It was found to be substantially different from all other known listeriaphages. All phages exhibited typical protein profiles, which were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent laser densitometrical analysis of the gels. It was then possible to distinguish eight protein subgroups on the basis of unique protein patterns. This classification corresponds well to the previous groupings based on host range. Most of the phages revealed two or three major proteins ranging from 21 to 24 kDa and 30 to 36 kDa. In addition, at least 10 minor proteins could be observed for each phage. Our results indicate that the major proteins are structural proteins of the capsid and tail, and the protein band ranging from 30 to 35 kDa could clearly be assigned to the proteins of the phage capsid.
Formation of cross-reacting antibodies against cellular and extracellular lipoteichoic acid of Streptococcus mutans BHT (1976)

Antisera prepared against strains of Streptococcus mutans, particularly strain BHT, contain antibodies to the membrane lipoteichoic acid component that will cross-react with lipoteichoic acids from three species of lactobacilli. A more detailed study of the antibodies to strain BHT confirmed that the antibodies are specific for the polyglycerol phosphate component common to the lipoteichoic acids. Sera with a higher hemagglutinating titer could be obtained by injecting disrupted organisms. The partially purified lipoteichoic acid isolated from the culture fluid of S. mutans BHT was also immunogenic antibodies; antibodies were also formed against another unidentified component in this extracellular fraction.
MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders (2009)

Understanding complex diseases such as sporadic Alzheimer disease (AD) has been a major challenge. Unlike the familial forms of AD, the genetic and environmental risks factors identified for sporadic AD are extensive. MicroRNAs are one of the major noncoding RNAs that function as negative regulators to silence or suppress gene expression via translational inhibition or message degradation. Their discovery has evoked great excitement in biomedical research for their promise as potential disease biomarkers and therapeutic targets. Key microRNAs have been identified as essential for a variety of cellular events including cell lineage determination, proliferation, apoptosis, DNA repair, and cytoskeletal organization; most, if not all, acting to fine-tune gene expression at the post-transcriptional level in a host of cellular signaling networks. Dysfunctional microRNA-mediated regulation has been implicated in the pathogenesis of many disease states. Here, the current understanding of the role of miRNAs in the central nervous system is reviewed with emphasis on their impact on the etiopathogenesis of sporadic AD.