gebhart/patrepeval huggingface dataset:
Role of the Virus Nucleoprotein in the Regulation of Lymphocytic Choriomeningitis Virus Transcription and RNA Replication (2003)

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has a bisegmented negative-strand RNA genome. Each segment carries two viral genes in opposite orientation and separated by an intergenic region (IGR). The RNA-dependent RNA polymerase (RdRp) L of LCMV produces subgenomic mRNA and full-length genomic and antigenomic RNA species in two different processes termed transcription and replication, respectively. It is widely accepted that intracellular nucleoprotein (NP) levels regulate these two processes. Intracellular NP levels increase during the course of the infection, resulting in the unfolding of secondary RNA structures within the IGR. Structure-dependent transcription termination at the IGR is thereby attenuated, promoting replication of genome and antigenome RNA species. To test this hypothesis, we established a helper-virus-free minigenome (MG) system where intracellular synthesis of an S segment analogue from a plasmid is driven by RNA polymerase I. Cotransfection with two additional plasmids expressing the minimal viral trans-acting factors L and NP under control of RNA polymerase II allowed for RNA synthesis mediated by the intracellularly reconstituted LCMV polymerase. Both processes, transcription and replication, were strictly dependent on NP. However, both were equally enhanced by incrementally increasing amounts of NP up to levels in the range of those in LCMV-infected cells. Our data are consistent with a central role for NP in transcription and replication of the LCMV genome, but they do not support the participation of NP levels in balancing the two processes.
Variational sensitivity analysis, data requirements, and parameter identification in a leaky aquifer system (1990)

The adjoint state sensitivity method is developed to aid the analysis of a pumping test design for parameter identification in a leaky aquifer system. The system considered consists of an unconfined aquifer overlaying an aquitard which overspreads a confined aquifer. The adjoint equations are derived in the continuous form without discretizing the governing equations and are expressed in terms of “convection‐diffusion” equations with time dependent coefficients. The multiple cell balance (MCB) method is used to solve the nonlinear governing equations as well as their adjoint equations. Algorithms are developed for calculating sensitivity coefficients of heads in each layer of an aquifer with respect to various parameters. A concept called “contribution of an observation” is introduced which can be used to measure the usefulness of an observation in connection with data requirements for parameter identification. It links experimental design with observation errors and the requirement of model application. The sufficiency of an observation system for parameter identification can be evaluated at the design stage before extensive resources are committed to data collection. A numerical example is given to verify the proposed method and to explain its applicability to the design of a pumping test.
Damage-free separation of GaN thin films from sapphire substrates (1998)

Gallium nitride thin films grown on sapphire substrates were successfully separated and transferred onto Si substrates using single 38 ns KrF excimer laser pulses directed through the transparent substrate at fluences in the range of 400–600 mJ/cm2. The absorption of the 248 nm radiation by the GaN at the interface induces rapid thermal decomposition of the interfacial layer, yielding metallic Ga and N2 gas. The substrate is easily removed by heating above the Ga melting point of 30 °C. Scanning electron microscopy and x-ray diffraction of the GaN films before and after lift-off demonstrate that the structural quality of the GaN films is not altered by the separation and transfer process.
Activation of Toll-like Receptor 5 on Breast Cancer Cells by Flagellin Suppresses Cell Proliferation and Tumor Growth (2011)

Increasing evidence showed that Toll-like receptors (TLR), key receptors in innate immunity, play a role in cancer progression and development but activation of different TLRs might exhibit the exact opposite outcome, antitumor or protumor effects. TLR function has been extensively studied in innate immune cells, so we investigated the role of TLR signaling in breast cancer epithelial cells. We found that TLR5 was highly expressed in breast carcinomas and that TLR5 signaling pathway is overly responsive in breast cancer cells. Interestingly, flagellin/TLR5 signaling in breast cancer cells inhibits cell proliferation and an anchorage-independent growth, a hallmark of tumorigenic transformation. In addition, the secretion of soluble factors induced by flagellin contributed to the growth-inhibitory activity in an autocrine fashion. The inhibitory activity was further confirmed in mouse xenografts of human breast cancer cells. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy.
Typical Weather Years and the Effect of Urban Microclimate on the Energy Behaviour of Buildings and HVAC Systems (2007)

Abstract Building simulation programs require climate information in the form of hourly based typical weather years assembled from meteorological measurements. A thorough description of these weather data sets is presented in this paper followed by a classification based on the way they are derived from monitored data and a comparison between the different types. Finally, we analyse the efforts made to deliver urban specific climatic data to assess the effect of urban microclimate on buildings.
Direct Comparison of Insulin Lispro and Aspart Shows Small Differences in Plasma Insulin Profiles After Subcutaneous Injection in Type 1 Diabetes (2001)

Two rapid-acting insulin analogs, lispro and aspart, are now available for clinical use (1).

The aim of our study was to compare the plasma-insulin profiles of these analogs after subcutaneous injection in patients with type 1 diabetes.

Fourteen patients with type 1 diabetes (six men and eight women, [mean ± SEM] 35.4 ± 3.3 years of age [range 22–59], HbA1c 7.3 ± 0.3% [reference range 3.2–5.4], BMI 24.7 ± 1.1 kg/m2, and diabetes duration 22.9 ± 2.6 years) were recruited for the study. Only two patients had measurable C-peptide levels (0.04 and 0.11 nmol/l). All patients were on multiple-injection therapy with a breakfast insulin dose of 11.1 ± 0.7 U (range 6–14) and no intermediate-acting insulin in the morning.

The study was designed as a single blind randomized crossover study. On the first day, seven patients were randomized to insulin lispro (Humalog, U-100; Eli Lilly, Indianapolis, IN), and the other seven were randomized to insulin aspart (NovoRapid, U-100; Novo-Nordisk, Bagsveard, Denmark). On the second study day (5–21 days later), the patients received the alternative insulin analog. The patients continued their usual insulin treatment between the study days.

All patients arrived to the clinic fasting. After an initial blood sampling, they were given 10 U s.c. of one of the insulins in the abdominal wall at 7:30 a.m. A standardized breakfast, which had an energy content of 418 kcal and a nutrient content of 21 g protein, 11 g …
Networks of Ultrasmall Pd/Cr Nanowires as High Performance Hydrogen Sensors (2011)

The newly developed hydrogen sensor, based on a network of ultrasmall pure palladium nanowires sputter-deposited on a filtration membrane, takes advantage of single palladium nanowires' characteristics of high speed and sensitivity while eliminating their nanofabrication obstacles. However, this new type of sensor, like the single palladium nanowires, cannot distinguish hydrogen concentrations above 3%, thus limiting the potential applications of the sensor. This study reports hydrogen sensors based on a network of ultrasmall Cr-buffered Pd (Pd/Cr) nanowires on a filtration membrane. These sensors not only are able to outperform their pure Pd counterparts in speed and durability but also allow hydrogen detection at concentrations up to 100%. The new networks consist of a thin layer of palladium deposited on top of a Cr adhesion layer 1-3 nm thick. Although the Cr layer is insensitive to hydrogen, it enables the formation of a network of continuous Pd/Cr nanowires with thicknesses of the Pd layer as thin as 2 nm. The improved performance of the Pd/Cr sensors can be attributed to the increased surface area to volume ratio and to the confinement-induced suppression of the phase transition from Pd/H solid solution (α-phase) to Pd hydride (β-phase).
Activation of the Bacillus subtilis global regulator CodY by direct interaction with branched‐chain amino acids (2004)

CodY, a GTP-activated global transcriptional regulator of early stationary phase genes, is conserved in many Gram-positive bacterial species. Recently, a number of novel targets regulated by CodY have been identified, including three Bacillus subtilis operons involved in branched-chain amino acid (BCAA) biosynthesis (Molle, V., et al., 2003, J Bacteriol 185: 1911-1922). The mechanism of involvement of CodY in regulating the ilvB operon was investigated here using in vivo transcriptional fusions, in vitro gel mobility shift assays and DNase I footprinting assays. CodY was found to mediate regulation of the ilvB operon by GTP and BCAAs and to bind to the ilvB promoter region. BCAAs increased the affinity of CodY for the ilvB promoter and for all other CodY targets tested. This effect of BCAAs in vitro was additive with the effect of GTP on CodY DNA-binding activity.
Diagnosis and management of rheumatoid arthritis. (2005)

Rheumatoid arthritis is a chronic inflammatory disease characterized by uncontrolled proliferation of synovial tissue and a wide array of multisystem comorbidities. Prevalence is estimated to be 0.8 percent worldwide, with women twice as likely to develop the disease as men. Untreated, 20 to 30 percent of persons with rheumatoid arthritis become permanently work-disabled within two to three years of diagnosis. Genetic and environmental factors play a role in pathogenesis. Although laboratory testing and imaging studies can help confirm the diagnosis and track disease progress, rheumatoid arthritis primarily is a clinical diagnosis and no single laboratory test is diagnostic. Complications of rheumatoid arthritis may begin to develop within months of presentation; therefore, early referral to or consultation with a rheumatologist for initiation of treatment with disease-modifying antirheumatic drugs is recommended. Several promising new disease-modifying drugs recently have become available, including leflunomide, tumor necrosis factor inhibitors, and anakinra. Nonsteroidal anti-inflammatory drugs, corticosteroids, and nonpharmacologic modalities also are useful. Patients who do not respond well to a single disease-modifying drug may be candidates for combination therapy. Rheumatoid arthritis is a lifelong disease, although patients can go into remission. Physicians must be aware of common comorbidities. Progression of rheumatoid arthritis is monitored according to American College of Rheumatology criteria based on changes in specific symptoms and laboratory findings. Predictors of poor outcomes in early stages of rheumatoid arthritis include low functional score early in the disease, lower socioeconomic status, early involvement of many joints, high erythrocyte sedimentation rate or C-reactive protein level at disease onset, positive rheumatoid factor, and early radiologic changes.
The Significance of Adhesion Molecules in Nephrology (1996)

Our knowledge of adhesion molecules has exploded over the last 5 years and has swamped most fields of medicine including nephrology. This is not surprising because adhesion molecules play a pivotal role in all aspects of cell to cell contact. Thus, they are involved in important issues, such as fetal development, in any kind of inflammatory or immune response including allograft rejection, as well as thrombus formation, and in tumor growth and metastasis (1-3). This short overview briefly reports some aspects of the biology of relevant adhesion molecules and their significance in inflammatory kidney diseases and in hemodialysis and renal allograft rejection. Finally, new therapeutic opportunities that arise by blocking adhesion molecule function are discussed.
Ophthalmic Drug Delivery system - A Review (2010)

Ocular drug delivery has been a major challenge to pharmacologists and drug delivery scientists due to its unique anatomy and physiology. Static barriers (different layers of cornea, sclera, and retina including blood aqueous and bloodâÂÂretinal barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution), and efflux pumps in conjunction pose a significant challenge for delivery of a drug alone or in a dosage form, especially to the posterior segment. Identification of influx transporters on various ocular tissues and designing a transporter-targeted delivery of a parent drug has gathered momentum in recent years. Parallelly, colloidal dosage forms such as nanoparticles, nanomicelles, liposomes, and micro emulsions have been widely explored to overcome various static and dynamic barriers. Novel drug delivery strategies such as bioadhesive gels and fibrin sealant-based approaches were developed to sustain drug levels at the target site. Designing noninvasive sustained drug delivery systems and exploring the feasibility of topical application to deliver drugs to the posterior segment may drastically improve drug delivery in the years to come. Current developments in the field of ophthalmic drug delivery promise a significant improvement in overcoming the challenges posed by various anterior and posterior segment diseases.
Replacement of intervertebral discs in chimpanzees by silicone‐Dacron implants: A preliminary report (1973)

Abstract We have developed a prosthetic replacement for the intervertebral disc. Although current management of a patient with degenerative disc disease is usually effective, certain inadequacies in permanent pain relief do exist. Most of the persistent symptoms seem to occur because of vertebral settling with subsequent posterior joint incongruities followed by arthritic changes. Theoretically, the replacement of a diseased intervertebral disc, prior to the onset of irrevocable changes, with a spacer would maintain anatomical congruity and physiologic function. This study is the preliminary report of the development of a silicone‐Dacron prosthesis and its experimental trials in chimpanzees. Our early evaluation shows that the prosthesis allows motion, maintains the intervertebral space, and absorbs the compressive stresses placed on the spine. The artificial disc has a biomechanical behavior comparable to the normal chimp disc. Resorption of adjacent bone, reactive bone formation, and infection are complications that we have experienced. Continued evaluation is necessary.
Mitochondrial ADP/ATP Carrier Can Be Reversibly Converted into a Large Channel by Ca2+ (1996)

Single-channel current measurements of excised patches with reconstituted purified mitochondrial ADP/ATP carrier (AAC) indicates the presence of a large low cation selective (PK+/PCl− = 4.3 ± 0.6) channel. The channel conductance has multiple sublevels and varies from 300 to 600 pS. It has low probability of current fluctuations at Vhold up to 80−100 mV of both signs and is reversibly gated at Vhold > 150 mV. The opening of the channel is Ca2+-dependent (1 mM Ca2+) and can be reversibly closed on removal of Ca2+. It is strongly pH dependent and closes completely at pHex 5.2. The AAC-specific inhibitor bongkrekate inhibits the channel partially and completely in combination with ADP, whereas carboxyatractylate did not affect the conductance. The effects of these AAC-specific ligands prove that the channel activity belongs to AAC. The AAC-linked conductance can clearly be differentiated from the porin channel, rarely detected in our preparations. The properties of the AAC-linked channel coincide with the mitochondrial permeability transition pore (MTP), which is also affected by the AAC ligands [Hunter, D. R., & Haworth, R. A. (1979) Arch. Biochem. Biophys. 195, 453−459] and resembles the mitochondrial "multiconductance channel" [Kinnally, K. W., Campo, M. L., & Tedeschi, H. T. (1989) J. Bioenerg. Biomembr. 21, 497−506] or "megachannel" [Petronilli, V., Szabo, I., & Zoratti, M. (1989) FEBS Lett. 259, 137−143]. Therefore we conclude that the AAC, when converted into a large unselective channel, is a key component in the MTP and thus is involved in the ischemia-reperfusion damage and cytosolic Ca2+ oscillations. The channel opening in AAC is proposed to be caused by binding of Ca2+ to the cardiolipin, tightly bound to AAC, thus releasing positive charges within the AAC which open the gate.
Antitumor activity of trioxacarcin C. (1983)

The novel antitumor antibiotic, trioxacarcin C, was studied for antitumor activities against murine tumor systems. When mice with i.p.-inoculated B16 melanoma were given intraperitoneal injections of trioxacarcin C, the maximal T/C% was 164 by successive administration of 0.125 mg/kg/day (day 1 approximately 10). It also gave the prolongation of life span of mice bearing i.p. P388 leukemia (T/C 141%) by i.p. injection for 10 days, and inhibited the growth of sarcoma 180 (T/C 42%) and Lewis lung carcinoma implanted s.c. (T/C 23%) by i.v. administration for 6 or 7 days. It inhibited the growth of P388 leukemia cells in vitro and showed significant inhibition on the colony formation of HeLa S3 cells. DNA and RNA synthesis were more strongly inhibited than protein synthesis by trioxacarcin C. Also, it induced strand scission of PM-2 DNA without reducing agents or metals. It did not effect the number of white blood cells and blood urea nitrogen value of the peripheral blood.
Sequential changes of gap-junctional intercellular communications during multistage rat liver carcinogenesis: direct measurement of communication in vivo (1991)

We have developed a simple method to measure gap-junctional intercellular communication (GJIC), by means of microinjection/dye transfer assay, in liver slices freshly removed from the rat. Using this method and immunostaining of connexin 32 (cx32), the major liver gap junction protein, we studied sequential changes of GJIC during chemical hepatocarcinogenesis in male Fischer-344 rats under a modified Solt-Farber protocol (3 weeks 4 day exposure regimen). Four weeks after commencement of the protocol, there was a substantial decrease in GJIC in the liver parenchyma, which was free from focal lesions. The decrease in GJIC persisted up to at least the 15th week of treatment, while a decrease in the number of immunoreactive cx32 spots was evident only at 4 weeks of post-protocol commencement. Most enzyme-altered (GST-P-positive) focal lesions showed markedly lower GJIC and a significantly lower number of cx32-positive spots than surrounding hepatocytes. Most GST-P-positive foci showed a selective lack of GJIC with surrounding heptocytes. Hepatocellular carcinomas arising 1 year after the carcinogenic regimen had significantly reduced communicational capacity accompanied by a large decrease in cx32 expression. These results suggest that a progressive decrease in homologous as well as heterologous GJIC in preneoplastic lesions occurs during rat hepatocarcinogenesis, and that preneoplastic lesions with the most prominent disorders in GJIC may be more likely to develop into carcinomas.
Relationship between colonial morphology and adherence of Streptococcus pneumoniae (1995)

Phase variants in colonial opacity of pneumococci differ in the ability to colonize the nasopharynx of infant rats. To explain this observation at a cellular level, we compared the ability of opacity variants to adhere to buccal epithelial cells, type II pneumocytes, or vascular endothelial cells and to the glycoconjugates that represent the cognate receptors at each of these sites. The transparent phenotype was associated with enhanced adherence to buccal cells (approximately 100%) and their receptor relative to that of the opaque variants. Only modest differences in adherence (&lt; 45%) were demonstrated to resting lung and vascular cells. In contrast, adherence of transparent variants increased by 90% to lung cells stimulated with interleukin-1 and by 130% to endothelial cells stimulated with tumor necrosis factor. In contrast, cytokine stimulation did not influence the adherence of opaque pneumococci. This difference correlated with the unique ability of transparent variants to adhere to immobilized GlcNAc and to cells bearing transfected platelet-activating factor receptors. These results suggest that the mechanism of enhanced colonization of the nasopharynx in vivo by transparent as compared with opaque phase variants involves a greater ability to adhere to both GlcNAc beta 1-3Gal on buccal epithelial cells and GlcNAc and PAF receptors on cytokine-activated, as opposed to resting, lung and endovascular cells.
Empirically supported psychosocial treatments for attention deficit hyperactivity disorder (1998)

Reviews and evaluates psychosocial treatments for attention deficit hyperactivity disorder (ADHD) in children and adolescents according to Task Force Criteria (Lonigan, Elbert, & Johnson, this issue). It is concluded that behavioral parent training and behavioral interventions in the classroom meet criteria for well-established treatments. Cognitive interventions do not meet criteria for well-established or probably efficacious treatments. Issues regarding the evaluative process are discussed and future directions for psychosocial treatment for ADHD are outlined.
Electrochemical Test to Evaluate Passivation Layers: Overcoats of Si in Ink (1982)

A potentiodynamic polarization technique was used to assess the quality of passivating overcoats on Si nozzle plates for continuous stream ink jet printing. These include , , and films deposited by various methods. The worst overcoats dissolved under an anodic potential. The others were electrochemically inert or nearly so. Even among these the protection provided differed widely. Overcoat rankings using the polarization technique compared favorably with microscopic examinations. The best was plasma‐assisted CVD from an discharge. Some overcoats and combinations were pinhole free over the 1 cm2 tested.
Induction of a mitogen-responsive gene after expression of the Ha-ras oncogene in NIH 3T3 fibroblasts. (1989)

A cDNA clone, T1, has been isolated whose corresponding mRNA was transiently expressed at highly elevated levels after conditional expression of the Ha-ras(EJ) gene and after mitogenic activation of quiescent NIH 3T3 cells. Glucocorticoid hormone stimulated substantial T1 expression as well but only in proliferating cells. At least two different signaling pathways participate in the regulation of the T1 gene: a protein kinase C-dependent signal is involved in the response of proliferating NIH 3T3 cells to glucocorticoid in the absence but not the presence of p21ras, whereas a protein kinase C-independent mechanism mediates the response to serum factors. Treatment of cells with the protein kinase inhibitor 2-aminopurine blocked induction of expression of the T1 gene. T1 mRNA accumulation is regulated at the transcriptional level.
Methylation Linear Discriminant Analysis (MLDA) for identifying differentially methylated CpG islands (2008)

MLDA has advantages for analyzing methylation data from CpG island microarrays, since there is a clear rational for the definition of methylation status, it uses DMH data without between-group normalisation and is less influenced by cross-hybridisation of loci. The MLDA algorithm successfully identified differentially methylated loci between two classes of samples analysed by DMH using CpG island microarrays.