gebhart/patrepeval huggingface dataset:
Inhibition of human factor VIIIa by anti-A2 subunit antibodies. (1994)

Human inhibitory alloantibodies and autoantibodies to Factor VIII (FVIII) are usually directed toward the A2 and/or C2 domains of the FVIII molecule. Anti-C2 antibodies block the binding of FVIII to phospholipid, but the mechanism of action of anti-A2 antibodies is not known. We investigated the properties of a patient autoantibody, RC, and a monoclonal antibody, 413, that bind to the region which contains the epitopes of all anti-A2 alloantibodies or autoantibodies studied to date. mAb 413 and RC were noncompetitive inhibitors of a model intrinsic Factor X activation complex (intrinsic FXase) consisting of Factor IXa, activated FVIII (FVIIIa), and synthetic phospholipid vesicles, since they decreased the Vmax of intrinsic FXase by > 95% at saturating concentrations without altering the Km. This indicates that RC and mAb 413 either block the binding of FVIIIa to FIXa or phospholipid or interfere with the catalytic function of fully assembled intrinsic FXase, but they do not inhibit the binding of the substrate Factor X. mAb 413 did not inhibit the increase in fluorescence anisotropy that results from the binding of Factor VIIIa to fluorescein-5-maleimidyl-D-phenylalanyl-prolyl-arginyl-FIXa (Fl-M-FPR-FIXa) on phospholipid vesicles in the absence of Factor X, indicating it does not inhibit assembly of intrinsic FXase. Addition of Factor X to Fl-M-FPR-FIXa, FVIIIa, and phospholipid vesicles produced a further increase in fluorescence anisotropy and a decrease in fluorescence intensity. This effect was blocked completely by mAb 413. We conclude that anti-A2 antibodies inhibit FVIIIa function by blocking the conversion of intrinsic FXase/FX complex to the transition state, rather than by interfering with formation of the ground state Michaelis complex.
Cone Survival Despite Rod Degeneration in XOPS-mCFP Transgenic Zebrafish (2005)

The XOPS-mCFP transgene causes selective degeneration of rods without secondary loss of cones in animals up to 7 months of age. This raises important questions about the significance of rod-cone interactions in zebrafish and their potential as a model of human inherited retinal degenerations.
[Sleep disorders in patients with chronic renal insufficiency]. (2012)

Sleep disorders, especially insomnia, daytime sleepiness, sleep apnea syndrome and restless legs syndrome are very frequently encountered in patients with chronic renal failure whether or not they undergo renal replacement therapy. The causes of sleep disorders are multifactorial and not only linked to the renal disease itself, but also to its treatment and its associated psychosocial factors. This article discusses the prevalence and physiopathology of the most frequently encountered sleep disorders in chronic renal failure patients, and highlights the actually available therapeutic options.
Evaluation of Ebola Virus Inhibitors for Drug Repurposing (2015)

A systematic screen of FDA-approved drugs was performed to identify compounds with in vitro antiviral activities against Ebola virus (EBOV). Compounds active (>50% viral inhibition and <30% cellular toxicity) at a single concentration were tested in dose-response assays to quantitate the antiviral activities in replication and viral entry assays as well as cytotoxicity in the Vero cell line used to conduct these assays. On the basis of the approved human dosing, toxicity/tolerability, and pharmacokinetic data, seven of these in vitro hits from different pharmacological classes (chloroquine (CQ), amiodarone, prochlorperazine, benztropine, azithromycin, chlortetracycline, and clomiphene) were evaluated for their in vivo efficacy at a single dose and were administered via either intraperitoneal (ip) or oral route. Initially, azithromycin (100 mg/kg, twice daily, ip), CQ (90 mg/kg, twice daily, ip), and amiodarone (60 mg/kg, twice daily, ip) demonstrated significant increases in survival in the mouse model. After repeat evaluation, only CQ was found to reproducibly give significant efficacy in the mouse model with this dosing regimen. Azithromycin and CQ were also tested in a guinea pig model of EBOV infection over a range of doses, but none of the doses increased survival, and drug-related toxicity was observed at lower doses than in the mouse. These results show the benefits and specific challenges associated with drug repurposing and highlight the need for careful evaluation of approved drugs as rapidly deployable countermeasures against future pandemics.
PCS number portability (2002)

Intelligent network (IN) and non-IN architectures are described that support personal communications services (PCS) number portability independent of the service provider (SP) that is used. Database query rates and call setup times are computed for selected architectures. To attain number portability, it is concluded that Common Channel Signaling System 7 is the principal ingredient for successful operation no matter which architecture is selected.
Combined Diffusion and Perfusion MRI With Correlation to Single-Photon Emission CT in Acute Ischemic Stroke (1999)

Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.
Ultrasound induced increase in excitability of single neurons (2008)

The aim of this study was to carefully assess the level of modulation in electrical excitability of single neurons with the application of high frequency ultrasound. High frequency tone bursts of ultrasound have been shown to dramatically increase the spike frequency of primary hippocampal neurons in culture. In addition, these ultrasonic bursts also induce silent or still developing neurons to fire. Results indicate that the increase in excitability is largely mediated by mechanical effects and not thermal effects of ultrasound. Future studies on culture models exposed to varying ultrasound protocols may provide insight into the feasibility of using ultrasound as a means for neurostimulation studies conducted on brain slice and in vivo models.
Yarrowia lipolytica (2012)

The yeast Yarrowia lipolytica presents specific physiological, metabolic and genomic characteristics, which differentiate it from the model yeast Saccharomyces cerevisiae. These properties have led several research groups to use this yeast as a model for basic knowledge. Thanks to the development of advanced genetic tools and -omic approaches, significant progress has been achieved in the understanding of specific biological processes. This review, after a short presentation of this model yeast, will briefly highlight the different use of Y. lipolytica for basic knowledge and the advantages gained by exploiting this non-conventional yeast. Future perspectives in employing this yeast for basic knowledge in the field of RNA splicing and genome evolution, and for the study of lipid metabolism, are also discussed.
Sensitivity by combination: immuno-PCR and related technologies (2008)

The versatility of immunoassays for the detection of antigens can be combined with the signal amplification power of nucleic acid amplification techniques in a broad range of innovative detection strategies. This review summarizes the spectrum of both, DNA-modification techniques used for assay enhancement and the resulting key applications. In particular, it focuses on the highly sensitive immuno-PCR (IPCR) method. This technique is based on chimeric conjugates of specific antibodies and nucleic acid molecules, the latter of which are used as markers to be amplified by PCR or related techniques for signal generation and read-out. Various strategies for the combination of antigen detection and nucleic acid amplification are discussed with regard to their laboratory analytic performance, including novel approaches to the conjugation of antibodies with DNA, and alternative pathways for signal amplification and detection. A critical assessment of advantages and drawbacks of these methods for a number of applications in clinical diagnostics and research is conducted. The examples include the detection of viral and bacterial antigens, tumor markers, toxins, pathogens, cytokines and other targets in different biological sample materials.
IS EQUITY FINANCED BUDGET DEFICIT STABLE IN AN INTEREST FREE ECONOMY (1994)

The purpose of this paper is to analyze the stability of an equity financed budget deficit in an interest free Islamic economy. To this effect a small closed economy theoretical macroeconomic model broadly consistent with the Islamic tenets is developed. This study found that under a strong wealth effect an equity financed deficit is not necessarily unstable and that government expenditure policies may contribute positively in terms of enhancing the output of the economy.
Rapid Identification of Methicillin-ResistantStaphylococcus aureusand Simultaneous Species Confirmation Using Real-Time Fluorescence PCR (2000)

A duplex LightCycler PCR assay targeting the mecA gene and a Staphylococcus aureus-specific marker was used to test 165 S. aureus strains and 80 strains of other bacterial species. Within an assay time of 60 min plus 10 min for sample preparation, S. aureus as well as the presence or absence of the mecA gene was correctly identified.
Degranulation of human eosinophils induced by Paragonimus westermani-secreted protease (2005)

Eosinophil degranulation is considered to be a key effector function for the killing of helminthic worms and tissue inflammation at worm-infected lesion sites. However, relatively little data are available with regard to eosinophil response after stimulation with worm-secreted products which contain a large quantity of cysteine proteases. In this study, we attempted to determine whether the degranulation of human eosinophils could be induced by the direct stimulation of the excretory-secretory products (ESP) of Paragonimus westermani, which causes pulmonary paragonimiasis in human beings. Incubation of eosinophils for 3 hr with Paragonimus-secreted products resulted in marked degranulation, as evidenced by the release of eosinophil-derived neurotoxin (EDN) in the culture supernatants. Moreover, superoxide anion was produced by eosinophils after stimulation of the ESP. The ESP-induced EDN release was found to be significantly inhibited when the ESP was pretreated with protease inhibitor cocktail or the cysteine protease inhibitor, E-64. These findings suggest that human eosinophils become degranulated in response to P. westermani-secreted proteases, which may contribute to in vivo tissue inflammation around the worms.
TGFα can act as a chemoattractant to perioptic mesenchymal cells in developing mouse eyes (1995)

Growth factors are believed to play an important role in regulating cell fate and cell behavior during embryonic development. Transforming growth factor alpha (TGF alpha), a member of the epidermal growth factor (EGF) superfamily, is a small polypeptide growth factor. Upon binding to its receptor, the EGF receptor (EGFR), TGF alpha can exert diverse biological activities, such as induction of cell proliferation or differentiation. To explore the possibility that TGF alpha might regulate cell fate during murine eye development, we generated transgenic mice that express human TGF alpha in the lens under the control of the mouse alpha A-crystallin promoter. The transgenic mice displayed multiple eye defects, including corneal opacities, cataracts and microphthalmia. At early embryonic stages TGF alpha induced the perioptic mesenchymal cells to migrate abnormally into the eye and accumulate around the lens. In situ hybridization revealed that the EGFR mRNA is highly expressed in the perioptic mesenchyme, suggesting that the migratory response is mediated by receptor activation. In order to test this model, the TGF alpha transgenic mice were bred to EGFR mutant waved-2 (wa-2) mice. We found that the eye defects of the TGF alpha transgenic mice are significantly abated in the wa-2 homozygote background. Because the EGFR mutation in the wa-2 mice is located in the receptor kinase domain, this result indicates that the receptor tyrosine kinase activity is critical for signaling the migratory response. Taken together, our studies demonstrate that TGF alpha is capable of altering the migratory decisions and behavior of perioptic mesenchyme during eye development.
A High-Throughput Assay for Evaluating State Dependence and Subtype Selectivity of Cav2 Calcium Channel Inhibitors (2008)

Cav2.2 channels play a critical role in pain signaling by controlling synaptic transmission between dorsal root ganglion neurons and dorsal horn neurons. The Cav2.2-selective peptide blocker ziconotide (Prialt, Elan Pharmaceuticals, Dublin, Ireland) has proven efficacious in pain relief, but has a poor therapeutic index and requires intrathecal administration. This has provided impetus for finding an orally active, state-dependent Cav2.2 inhibitor with an improved safety profile. Members of the Cav2 subfamily of calcium channels are the main contributors to central and peripheral synaptic transmission, but the pharmacological effects of blocking each subtype is not yet defined. Here we describe a high-throughput fluorescent assay using a fluorometric imaging plate reader (FLIPR [Molecular Devices, Sunnyvale, CA]) designed to quickly evaluate the state dependence and selectivity of inhibitors across the Cav2 subfamily. Stable cell lines expressing functional Cav2 channels (Ca(V)alpha, beta(3), and alpha(2)delta subunits) were co-transfected with an inward rectifier (Kir2.3) so that membrane potential, and therefore channel state, could be controlled by external potassium concentration. Following cell incubation in drug with varying concentrations of potassium, a high potassium trigger was added to elicit calcium influx through available, unblocked channels. State-dependent inhibitors that preferentially bind to channels in the open or inactivated state can be identified by their increased potency at higher potassium concentrations, where cells are depolarized and channels are biased towards these states. Although the Cav2 channel subtypes differ in their voltage dependence of inactivation, by adjusting pre-trigger potassium concentrations, the degree of steady-state inactivation can be more closely matched across Cav2 subtypes to assess molecular selectivity.
Signaling Aptamers for Monitoring Enzymatic Activity and for Inhibitor Screening (2004)

Real-time action: The conversion of adenosine 5′-monophosphate (AMP) into adenosine by alkaline phosphatase was monitored in real time by exploiting a signaling DNA aptamer as a reporter. The aptamer has a higher affinity for adenosine than for AMP and releases readily distinguishable fluorescence signals upon complexation with AMP and after conversion of AMP into adenosine (see figure). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2004/z400026_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide (1999)

Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer.
Removal of Escherichia coli from water by systems based on insoluble polystyrene–poly(ethylene glycol)s, –polyethylenimines, and –polyethylenepolyamines quaternized (1991)

Abstract Insoluble polymers adsorbing bacterial cells were prepared by reactions of chloromethylated, divinylbenzene crosslinked polystyrene (CMPS) beads with poly(ethylene glycol) 600 (PEG600), PEG monolaurate (PEGLE), polyethylenimines (PEIs, MW = ca. 300. 600. and 1200, referred to as PEI300, PEI600, and PEI1200, respectively), as well as ethylenediamine (ED) and tetraethylenepentamine (TEP) as polyethylenepolyamines. CMPS‐ED and CMPS‐TEP were further quaternized with 1‐iodooctane (IO) and 1‐iodododecane (IDD), respectively. These polymers were brought into contact with Escherichia coli by stirring in sterilized, distilled, and deionized water. Although CMPS‐PEG and CMPS‐PEGLE did not adsorb the cells, they caused a decrease in the number of viable cells. The decrease seemed to result from the bactericidal action of substances leached from the polymers. CMPS‐PEI300, CMPS‐PEI600, and CMPS‐PEI1200, CMPS‐ED‐IO, and CMPS‐TEP‐IDD caused a decrease in the viable cell number by adsorption of the cells to their surfaces. It was observed with a scanning electron microscope that the cells were present on the surfaces of CMPS‐PEI600 beads. The decrease coefficient for decrease in viable cell number of E. coli caused by the polymer increased with nitrogen content of the polymer. The adhesion of the cells to CMPS‐PEI300, CMPS‐PEI600, and CMPS‐PEI1200, CMPS‐ED‐IO, and CMPS‐TEP‐IDD was due mainly to electrostatic interaction between them.
RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication. (1990)

Replication of the Chinese hamster dihydrofolate (dhfr) gene initiates near a 281-bp HaeIII fragment of stably bent DNA that binds RIP60, a 60-kDa origin-specific DNA-binding protein that has been purified from HeLa cell nuclear extract (L. Dailey, M. S. Caddle, N. Heintz, and N. H. Heintz, Mol. Cell. Biol. 10:6225-6235, 1990). Circular permutation assays showed that stable DNA bending in the dhfr origin region fragment was due to the presence of five oligo (dA)3-4 tracts, designated bend elements B1 to B5, that are spaced 10 bp apart. DNA bending directed by elements B1 to B5, as assessed by anomolous migration of DNA fragments on polyacrylamide gels, was accentuated at 4 degrees C. Bend element B5, which is in inverse orientation relative to elements B1 to B4, overlaps an ATT-rich motif that comprises the RIP60 protein-binding site. Gel mobility shift assays with circularly permuted bent DNA fragments and purified RIP60 showed that RIP60 markedly enhanced DNA bending of the dhfr origin region sequences. These results suggest that, as in many plasmids, bacteriophages, and eucaryotic viruses, mammalian DNA-binding proteins may enhance DNA bending near origins of replication during initiation of DNA synthesis.
Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. (1994)

The extended interaction of aldoses with proteins or lipids results in nonenzymatic glycation and oxidation, ultimately forming AGEs, the presence of which in the plasma and vessel wall is associated with diabetic vascular complications. We show here that AGE albumin in the intravascular space interacts with the vessel wall via binding to an integral membrane protein, receptor for AGE (RAGE), a member of the immunoglobulin superfamily, resulting in clearance from the plasma and induction of interleukin 6 mRNA. Intravenously infused 125I-AGE albumin showed a rapid phase of plasma clearance with deposition in several organs. Rapid removal of 125I-AGE albumin from the plasma was prevented by administration of a soluble, truncated form of RAGE, which blocked binding of 125I-labeled AGE albumin to cultured endothelial cells and mononuclear phagocytes, as well as by pretreatment with anti-RAGE IgG. Ultrastructural studies with AGE albumin-colloidal gold conjugates perfused in situ showed that in murine coronary vasculature this probe was taken up by endothelial plasmalemmal vesicles followed by transport either to the abluminal surface or by accumulation in intracellular vesicular structures reminiscent of endosomes and lysosomes. Consequences of AGE-RAGE interaction included induction of interleukin 6 mRNA expression in mice. These data indicate that RAGE mediates the interaction of AGEs with the vessel wall, both for removal of these glycated proteins from the plasma and for changes in gene expression.
Reconstitution of a human immune system in immunodeficient mice: models of human alloreaction in vivo (2005)

Rodents have been widely used for studies in transplantation immunology because of their short reproduction period and the relative ease of generating inbred mutant or transgenic strains. However, although many biological mechanisms are similar between rodents and humans, several features clearly distinguish the immune system in these species. Consequently, it is rarely possible to extrapolate observations from rodent models directly into clinical practice. In vitro studies with human cells are useful for elucidation of basic mechanisms, but in order to study complex biological phenomena, in vivo studies are indispensable. In later years, a number of interesting models have been described where immunodeficient mice have been reconstituted with human cells, so-called humanized mice, in order to study human immune responses in vivo. This has opened a new field of experimental immunology that has been applied to areas such as cancer, autoimmunity, allergy, infections, and transplantation biology. In this review, we shall concentrate on the use of severe combined immunodeficient mice reconstituted with human immune or stem cells for studies of human alloreaction in vivo.
Producer-cell modification of human immunodeficiency virus type 1: Nef is a virion protein (1996)

Type 1 human immunodeficiency viruses encoding mutated nef reading frames are 10- to 30-fold less infectious than are isogenic viruses in which the nef gene is intact. This defect in infectivity causes nef-negative viruses to grow at an attenuated rate in vitro. To investigate the mechanism of Nef-mediated enhancement of viral growth rate and infectivity, a complementation analysis of nef mutant viruses was performed. To provide Nef in trans upon viral infection, a CEM derivative cell line (designated CLN) that expresses Nef under the control of the viral long terminal repeat was constructed. When nef-negative virus was grown in CLN cells, its growth rate was restored to wild-type levels. However, the output of nef-negative virus during the first 72 h after infection of CLN cells was not restored, suggesting that provision of Nef within the newly infected cell does not enhance the productivity of a nef-negative provirus. The genetically nef-negative virions produced by the CLN cells, however, were restored to wild-type levels of infectivity as measured in a syncytium formation assay in which CD4-expressing HeLa cells were targets. These trans-complemented, genetically nef-negative virions yielded wild-type levels of viral output following a single cycle of replication in primary CD4 T cells as well as in parental CEM cells. To define the determinants for producer cell modification of virions by Nef, the role of myristoylation was investigated. Virus that encodes a myristoylation-negative nef was as impaired in infectivity as was virus encoding a deleted nef gene. Because myristoylation is required for both membrane association of Nef and optimal viral infectivity, the possibility that Nef protein is included in the virion was investigated. Wild-type virions were purified by filtration and exclusion chromatography. A Western blot (immunoblot) of the eluate fractions revealed a correlation between peak Nef signal and peak levels of p24 antigen. Although virion-associated Nef was detected in part as the 27-kDa full-length protein, the majority of immunoreactive protein was detected as a 20-kDa isoform. nef-negative virus lacked both 27- and 20-kDa immunoreactive species. Production of wild-type virions in the presence of a specific inhibitor of the human immunodeficiency virus type 1 protease resulted in virions which contained only 27-kDa full-length Nef protein. These data indicate that Nef is a virion protein which is processed by the viral protease into a 20-kDa isoform within the virion particle.