gebhart/patrepeval huggingface dataset:
Coagulation initiated on herpesviruses (1997)

Herpesviruses have been previously correlated to vascular disease and shown to cause thrombogenic and atherogenic changes to host cells. Herein we show that even in the absence of cells, purified cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can initiate thrombin production. Functional assays demonstrated that purified HSV-1 and HSV-2 provide the necessary phospholipid (proPL) for assembling the coagulation factors Xa and Va into prothrombinase, which is responsible for generating thrombin. These observations are consistent with our earlier studies involving CMV. The presence of proPL on all three herpesviruses was confirmed directly by flow cytometry and electron microscopy by using annexin V and factor Va, respectively, as proPL-specific probes. Of equal importance, we found that CMV, HSV-1, and HSV-2 were also able to facilitate factor Xa generation from the inactive precursor factor X, but only when factor VII/VIIa and Ca2+ were present. Monoclonal antibodies specific for tissue factor (TF), the coagulation initiator, inhibited this factor X activation and, furthermore, enabled identification of TF antigen on each virus type by flow cytometry and electron microscopy. Collectively, these data show that CMV, HSV-1, and HSV-2 can initiate the generation of thrombin by having essential proPL and TF activities on their surface. Unlike the normal cellular source, the viral activity is constitutive and, therefore, not restricted to sites of vascular injury. Thus cell-independent thrombin production may be the earliest event in vascular pathology mediated by herpesviruses.
Antigen persistence is required throughout the expansion phase of a CD4+ T cell response (2005)

For CD8+ T cells, a relatively short antigen pulse seems sufficient for antigen-presenting cells to drive clonal expansion and differentiation. It is unknown whether the requirement for antigen is similarly ephemeral for CD4+ T cells. To study the dependence of a CD4+ T cell response on antigen persistence in a quantitatively and temporally controlled manner in vivo, we engineered a mouse line expressing a major histocompatibility complex class II–restricted epitope in dendritic cells under the control of a tetracycline-inducible promoter. Experiments tracking the proliferation of CD4+ T cells exposed to their cognate antigen in various amounts for different time periods revealed that the division of such cells was contingent on the presence of antigen throughout their expansion phase, even in the presence of an inflammatory stimulus. This previously unrecognized feature of a CD4+ T cell response contrasts with the proliferative behavior of CD8+ T cells that has been documented, and it implies that the two T cell subsets might require different strategies for efficient vaccination.
Hydrogen Production in a PV Concentrator using III-V Multi-Junction Solar Cells (2006)

Multi-junction solar cells from III-V compound semiconductors can generate ideal voltages for the electrolysis of water. This paper presents results of a PV-concentrator HyConreg with Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.35</sub> In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.65</sub> P/Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.83</sub> In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.17</sub> As tandem solar cells which are directly connected to the electrodes of a local polymer electrolyte membrane electrolyser. This electrolyser is integrated into the base plate of a concentrator module. A prototype system with an area of 96 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> has been realized. The solar to hydrogen conversion efficiency of this system was measured outdoor in Freiburg to be 18.2% (based on the thermoneutral voltage of 1.485 V)
A Domain in TNF Receptors That Mediates Ligand-Independent Receptor Assembly and Signaling (2000)

A conserved domain in the extracellular region of the 60- and 80-kilodalton tumor necrosis factor receptors (TNFRs) was identified that mediates specific ligand-independent assembly of receptor trimers. This pre–ligand-binding assembly domain (PLAD) is physically distinct from the domain that forms the major contacts with ligand, but is necessary and sufficient for the assembly of TNFR complexes that bind TNF-α and mediate signaling. Other members of the TNFR superfamily, including TRAIL receptor 1 and CD40, show similar homotypic association. Thus, TNFRs and related receptors appear to function as preformed complexes rather than as individual receptor subunits that oligomerize after ligand binding.
Assessment of methylsulfonylmethane as a permeability enhancer for regional EDTA chelation therapy (2009)

Pharmacologic chelators do not effectively penetrate cell membranes and blood-brain barrier. This study assesses methylsulfonylmethane (MSM) as a permeability enhancer and an excipient to facilitate EDTA transport across biologic membranes, and to make possible localized, regional chelation. Topical application of MSM with C(14)EDTA onto the rat cornea led to uptake of the C(14)EDTA in all tested ocular tissues. Without MSM, EDTA did not penetrate the eye. The ability of MSM to deliver EDTA into an eye provides an opportunity for regional chelation therapy. Additionally, these studies suggest that MSM could also be an adjuvant for delivering ciprofloxacin and other chemical compounds to specific, local tissue sites.
Survivin: Role in Normal Cells and in Pathological Conditions (2003)

Survivin, an inhibitor of apoptosis (IAP) containing one baculovirus IAP repeat (BIR) domain, has been reported to be capable of regulating both cellular proliferation and apoptotic cell death. Survivin splice variants, survivin-DeltaEx3 and survivin-2B, have apparently retained and lost anti-apoptotic potential, respectively. As survivin was first discovered due to its high homology with effector cell protease receptor (EPR-1), a protein involved in blood coagulation, it has been suggested (but not proven) that EPR-1 may act as a natural anti-sense to survivin in cells. Survivin homologs have been found in non-human species. Survivin expression has been described during embryonic development and in adult cancerous tissues, with greatly reduced expression in adult normal differentiated tissues, particularly if their proliferation index is low. Survivin has been defined as a universal tumor antigen and as the fourth most significant transcriptosome expressed in human tumors. Although survivin is usually located in the cell cytoplasmic region and associated with poor prognosis in cancer, nuclear localisation, indicative of favorable prognosis, has also been reported. Survivin expression has also been reported in a number of proliferating normal adult tissues. Extensive research has been conducted, aimed at increasing our understanding of survivin, by determining its sub-cellular structure and location, mechanism(s) of action and control of expression. While much important information on this molecule has been accumulated, there are still many areas of controversy or limited information. Further research may enable exploitation of survivin overexpression in cancer compared to normal tissues, making survivin a potentially attractive target for cancer therapeutics.
High-NA optical CD metrology on small ln-cell targets, enabling improved higher order dose control and process control for logic (2017)

The logic manufacturing process requires small in-device metrology targets to exploit the full dose correction potential of the modern scanners and process tools. A high-NA angular resolved scatterometer (YieldStar S-1250D) was modified to demonstrate the possibility of OCD measurements on 5x5µm2 targets. The results obtained on test wafers in a logic manufacturing environment, measured after litho and after core etch, showed a good correlation to larger reference targets and AEI to ADI intra-field CDU correlation, thereby demonstrating the feasibility of OCD on such small targets. The data was used to determine a reduction potential of 55% for the intra-field CD variation, using 145 points per field on a few inner fields, and 33% of the process induced across wafer CD variation using 16 points per field full wafer. In addition, the OCD measurements reveal valuable information on wafer-to-wafer layer height variations within a lot.
The N8-(2'-deoxyribofuranoside) of 8-aza-7-deazaadenine: a universal nucleoside forming specific hydrogen bonds with the four canonical DNA constituents (2000)

The 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidin-4-amine) N(8)-(2'-deoxyribonucleoside) (2) which has an unusual glycosylation position was introduced as a universal nucleoside in oligonucleotide duplexes. These oligonucleotides were prepared by solid-phase synthesis employing phosphoramidite chemistry. Oligonucleotides incorporating the universal nucleoside 2 are capable of forming base pairs with the four normal DNA nucleosides without significant structural discrimination. The thermal stabilities of those duplexes are very similar and are only moderately reduced compared to those with regular Watson-Crick base pairs. The universal nucleoside 2 belongs to a new class of compounds that form bidentate base pairs with all four natural DNA constituents through hydrogen bonding. The base pair motifs follow the Watson-Crick or the Hoogsteen mode. Also an uncommon motif is suggested for the base pair of 2 and dG. All of the new base pairs have a different shape compared to those of the natural DNA but fit well into the DNA duplex as the distance of the anomeric carbons approximates those of the common DNA base pairs.
Component reliability importance indices for maintenance optimization of electrical networks (2005)

Maximum asset performance is one of the major goals for electric power system managers. To reach this goal minimal life cycle cost and maintenance optimization become crucial while meeting demands from customers and regulators. One of the fundamental objectives is therefore to relate maintenance and reliability in an efficiently and effectively way, which is the aim of several maintenance methods such as the Reliability Centered Maintenance method (RCM). Furthermore, this necessitates the determination of the optimal balance between preventive and corrective maintenance to obtain the lowest total cost. This thesis proposes methods for defining the importance of individual components in a network with respect to total interruption cost. This is a first step in obtaining an optimal maintenance solution. Since the methods consider several customer nodes simultaneously, they are especially suitable for network structures that serve many purposes/customers e.g. transmission and distribution networks with more than one load point. The major results are three component reliability importance indices, which are applied in two case studies. The first case study is based on a network in the Stockholm area. The second case study is performed for one overhead line system in the rural parts of Kristinehamn. The application studies demonstrate that the indices are possible to implement for existing electrical networks and that they can be used for maintenance prioritization. Consequently these indices constitute a first step in the overall objective of a maintenance optimization method. The computations of the indices are performed both with analytical and simulation based techniques. Furthermore, the indices can be used to calculate the component contribution to the total system interruption cost. The approach developed for the importance indices can be utilized in any multi-state network that can be measured with one performance indicator.
To Sleep or Not To Sleep: A Systematic Review of the Literature of Pharmacological Treatments of Insomnia in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder (2013)

There is a relative paucity of evidence for the pharmacological treatment of ADHD-related sleep disorders; therefore, further research should be conducted to replicate these findings and obtain reliable results.
Humanized M195 monoclonal antibody conjugated to recombinant gelonin: an anti-CD33 immunotoxin with antileukemic activity. (1998)

The recently characterized immunotoxin HuM195-gelonin consists of a humanized anti-CD33 monoclonal antibody conjugated to the single-chain plant toxin gelonin. Binding of the immunotoxin to hematopoietic cells that express the CD33 differentiation antigen has been demonstrated and results in cytotoxicity due to ribosomal inactivation by gelonin. Blast cells from most patients with acute myelogenous leukemia express CD33, whereas normal stem cells necessary for maintenance of hematopoiesis do not. We asked whether an immunoconjugate using recombinant gelonin rather than plant gelonin is toxic to acute myelogenous leukemia (AML) cell lines and primary AML blasts obtained from patients and exposed to the immunotoxin in vitro. The CD33pos cell lines HL60, OCI/AML2, and OCI/ AML5 showed decreased proliferation when exposed to immunotoxin for 24-72 h. The CD33neg cell line OCI/AML3 was relatively resistant to HuM195, and all cell lines were resistant to equimolar concentrations of unconjugated antibody and gelonin. Primary blast cultures from seven patients with AML had CD33 detectable on 75.7-99.8% of cells by flow cytometry, and all showed dose-dependent decreases in clonogenic cell survival during 24-h incubation with the immunotoxin. Cells selected for low CD33 expression by cell sorting or by prolonged incubation with immunotoxin could reexpress CD33 at baseline levels and remained sensitive to immunotoxin. We conclude that humanized M195 conjugated to recombinant gelonin has antileukemic activity and should be considered for clinical testing in Phase I trials.
Comorbidity of Migraine and Psychiatric Disorders—A National Population‐Based Study (2008)

Migraine is associated with major depressive disorder, bipolar disorder, panic disorder, and social phobia. Migraine in association with various mental health disorders results in poorer health-related outcomes compared with migraine or a psychiatric condition alone. Understanding the psychiatric correlates of migraine is important in order to adequately manage this patient population and to guide public health policies regarding health services utilization and health-care costs.
Modulation of Radiation-Induced Cytokine Elevation Associated with Esophagitis and Esophageal Stricture by Manganese Superoxide Dismutase-Plasmid/Liposome (SOD2-PL) Gene Therapy (2001)

Radiation of the esophagus of C3H/HeNsd mice with 35 or 37 Gy of 6 MV X rays induces significantly increased RNA transcription for interleukin 1 (Il1), tumor necrosis factor alpha (Tnf), interferon gamma inducing factor (Ifngr), and interferon gamma (Ifng). These elevations are associated with DNA damage that is detectable by a comet assay of explanted esophageal cells, apoptosis of the esophageal basal lining layer cells in situ, and micro-ulceration leading to dehydration and death. The histopathology and time sequence of events are comparable to the esophagitis in humans that is associated with chemoradiotherapy of non-small cell lung carcinoma (NSCLC). Intraesophageal injection of clinical-grade manganese superoxide dismutase-plasmid/liposome (SOD2-PL) 24 h prior to irradiation produced an increase in SOD2 biochemical activity in explanted esophagus. An equivalent therapeutic plasmid weight of 10 microgram ALP plasmid in the same 500 microliter of liposomes, correlated to around 52-60% of alkaline phosphatase-positive cells in the squamous layer of the esophagus at 24 h. Administration of SOD2-PL prior to irradiation mediated a significant decrease in induction of cytokine mRNA by radiation and decreased apoptosis of squamous lining cells, micro-ulceration, and esophagitis. Groups of mice receiving 35 or 37 Gy esophageal irradiation by a technique protecting the lungs and treating only the central mediastinal area were followed to assess the long-term effects of radiation. SOD2-PL-treated irradiated mice demonstrated a significant decrease in esophageal wall thickness at day 100 compared to irradiated controls. Mice with orthotopic thoracic tumors composed of 32D-v-abl cells that received intraesophageal SOD2-PL treatment showed transgenic mRNA in the esophagus at 24 h, but no detectable human SOD2 transgene mRNA in explanted tumors by nested RT-PCR. These data provide support for translation of this strategy of SOD2-PL gene therapy to studies leading to a clinical trial in fractionated irradiation to decrease the acute and chronic side effects of radiation-induced damage to the esophagus.
Catecholamines (1974)

Hypermetabolism characterizes the metabolic response to thermal injury and the extent of energy production is positively related to the rate of urinary catecholamine excretion. Alpha and beta adrenergic blockade decreased metabolism from 69.6 +/- 5.3 Kcal/m(2)/hr to 57.4 +/- 5.2 (p < 0.01), and infusion of 6 microgm epinephrine/minute in normal man significantly increased metabolic rate. Twenty noninfected burned adults with a mean burn size of 45% total body surface (range 7-84%) and four normal controls were studied in an environmental chamber at two or more temperatures between 19 and 33 C with vapor pressure constant at 11.88 mm Hg. All burn patients were hypermetabolic at all temperatures studied and their core and mean skin temperatures were significantly elevated above control values. Between 25 and 33 C ambient, metabolism was unchanged in controls and burns of less than 40% total body surface (48.9 +/- 4.6 Kcal/m(2)/hr vs. 48.9 +/- 4.5), but metabolic rate decreased in larger burns in the warmer environment (72.0 +/- 1.9 vs. 65.8 +/- 1.7, p < 0.001). At 21 C, metabolism and catecholamines increased, except in four nonsurvivors who became hypothermic with decreased catechol elaboration. Metabolic rate in ten patients with bacteremia was below predicted levels while catecholamines were markedly elevated suggesting interference with tissue uptake of the neurohormonal transmitters. Feeding burn patients or administering glucose and insulin improved nitrogen retention and altered substrate flow but did not significantly reduce urinary catecholamines or metabolic rate. Burned patients are internally warm, not externally cold, and catecholamines appear to mediate their increased heat production. Hypermetabolism may be modified by ambient temperature, infection, and pharmacologic means. Alterations in hypothalamic function due to injury, resulting in increased catecholamine elaboration, would explain the metabolic response to thermal injury.
Stimulation of erythropoietin gene transcription during hypoxia and cobalt exposure (1989)

Erythropoietin, a plasma glycoprotein produced primarily by the kidney, is a growth and differentiation factor for erythroid progenitor cells. Production of renal erythropoietin is regulated by modulation of mRNA levels in response to changes in tissue oxygenation. Exposure to cobalt, a nonphysiologic stimulus for erythropoietin production, also acts by inducing mRNA accumulation. To determine whether variations in erythropoietin mRNA levels result from enhanced transcription of the erythropoietin gene, in vitro transcription reactions were performed using isolated rat kidney cell nuclei. Quantitation of specific nuclear RNAs labeled during in vitro transcription revealed active erythropoietin gene transcription in kidney nuclei from anemic-hypoxic and cobalt-treated animals while erythropoietin transcriptional activity was undetectable in normal kidney nuclei. Time course studies showed that stimulation of transcription begins between two and four hours following cobalt treatment and parallels the kinetics of mRNA and plasma erythropoietin accumulation. These results indicate that tissue hypoxia and cobalt exposure specifically enhance erythropoietin gene expression. This increase in erythropoietin production is regulated at least in part at the level of gene transcription.
A liposome-based therapeutic vaccine against β-amyloid plaques on the pancreas of transgenic NORBA mice (2002)

Immune tolerance to beta-amyloid (Abeta) was broken in NORBA transgenic mice presenting Abeta plaques on their pancreases. Vaccination of Black C57, BALB/c, and NORBA mice with the synthetic Abeta(1-16) sequence modified by covalently attaching two palmitoyl residues at each end of the peptide, subsequently reconstituted in liposomes-Lipid A elicited titers of 1:5,000 of anti-Abeta(1-16) antibodies within 10 weeks after the first inoculation. On direct interaction, sera with antibody titers of 1:5,000 solubilized in vitro up to 80% of preformed Abeta(1-42) aggregates. Cryosections of pancreases of unvaccinated NORBA mice show, on staining with Thioflavin T, extensive areas of high-intensity fluorescence in the acinar cell fields. Quantitation of the average fluorescence intensity in each section indicated that: (i) whereas nonvaccinated NORBA mice develop plaques within 45-60 days after birth, vaccinated 8-week-old NORBA mice did not develop amyloid plaques on their pancreases over a period of 7 months; (ii) cryosections from pancreases of 9- and 15-month-old vaccinated NORBA mice showed less than 50% of the fluorescence shown by cryosections from unvaccinated animals of the same age. The results indicate that palmitoylated Abeta peptides, reconstituted in liposomes-lipid A, are highly immunogenic, eliciting "therapeutic" antibody titers within 3 months of the first inoculation and preventing amyloid plaque formation in young animals or significantly reducing existing plaques in older transgenic mice. Possible implications for the therapy of Alzheimer's disease are discussed.
Control of small inhibitory RNA levels and RNA interference by doxycycline induced activation of a minimal RNA polymerase III promoter (2006)

RNA interference (RNAi) mediated by expression of short hairpin RNAs (shRNAs) is a powerful tool for efficiently suppressing target genes. The approach allows studies of the function of individual genes and may also be applied to human therapy. However, in many instances regulation of RNAi by administration of a small inducer molecule will be required. To date, the development of appropriate regulatory systems has been hampered by the few possibilities for modification within RNA polymerase III promoters capable of driving efficient expression of shRNAs. We have developed an inducible minimal RNA polymerase III promoter that is activated by a novel recombinant transactivator in the presence of doxycycline (Dox). The recombinant transactivator and the engineered promoter together form a system permitting regulation of RNAi by Dox-induced expression of shRNAs. Regulated RNAi was mediated by one single lentiviral vector, blocked the expression of green fluorescent protein (GFP) in a GFP-expressing HEK 293T derived cell line and suppressed endogenous p53 in wild-type HEK 293T, MCF-7 and A549 cells. RNA interference was induced in a dose- and time-dependent manner by administration of Dox, silenced the expression of both target genes by 90% and was in particular reversible after withdrawal of Dox.