gebhart/patrepeval huggingface dataset:
Triaryl Pyrazoline Compound Inhibits Flavivirus RNA Replication (2006)

Triaryl pyrazoline {[5-(4-chloro-phenyl)-3-thiophen-2-yl-4,5-dihydro-pyrazol-1-yl]-phenyl-methanone} inhibits flavivirus infection in cell culture. The inhibitor was identified through high-throughput screening of a compound library using a luciferase-expressing West Nile (WN) virus infection assay. The compound inhibited an epidemic strain of WN virus without detectable cytotoxicity (a 50% effective concentration of 28 microM and a compound concentration of >or=300 microM required to reduce 50% cell viability). Besides WN virus, the compound also inhibited other flaviviruses (dengue, yellow fever, and St. Louis encephalitis viruses), an alphavirus (Western equine encephalitis virus), a coronavirus (mouse hepatitis virus), and a rhabdovirus (vesicular stomatitis virus). However, the compound did not suppress an orthomyxovirus (influenza virus) or a retrovirus (human immunodeficiency virus type 1). Mode-of-action analyses in WN virus showed that the compound did not inhibit viral entry or virion assembly but specifically suppressed viral RNA synthesis. To examine the mechanism of inhibition of dengue virus, we developed two replicon systems for dengue type 1 virus: (i) a stable cell line that harbored replicons containing a luciferase reporter and a neomycin phosphotransferase selection marker and (ii) a luciferase-expressing replicon that could differentiate between viral translation and RNA replication. Analyses of the compound in the dengue type 1 virus replicon systems showed that it weakly suppressed viral translation but significantly inhibited viral RNA synthesis. Overall, the results demonstrate that triaryl pyrazoline exerts a broad spectrum of antiflavivirus activity through potent inhibition of viral RNA replication. This novel inhibitor could be developed for potential treatment of flavivirus infection.
The role of calcium in the organization of fibrillin microfibrils (1993)

The microfibrillar glycoprotein fibrillin has a multidomain structure which contains forty-three epidermal growth factor-like motifs with calcium-binding consensus sequences. We have utilized intact microfibrils isolated from human dermal fibroblast cultures to investigate the putative influence of bound calcium on microfibrillar organization and integrity. Incubation with EDTA or EGTA rapidly resulted in gross disruption of microfibril morphology. The treatment induced disorganization of the interbead domains although the regular beaded arrangement was always apparent. These changes were readily reversible on replacing calcium, indicating that the treatment had not compromised microfibrillar integrity. The data localize calcium binding EGF-like repeats to the interbead domains and indicate that lateral packing of fibrillin monomers is calcium-dependent. This arrangement suggests how mutations in epidermal growth factor-like domains of fibrillin might cause the disruption in microfibril organization and interactions which underlies the clinical symptoms of some Marfan syndrome patients.
High-efficiency transformation and gene inactivation in Streptococcus suis type 2 (1995)

An efficient electrotransformation system for Streptococcus suis type 2 is described. It is demonstrated that vectors based on the broad-host-range plasmid pWVO1 replicate in S. suis type 2. Transformation efficiencies of about 10(7) transformants per micrograms of plasmid DNA could be obtained. Derivatives of plasmid pBR322 containing S. suis chromosomal DNA did not replicate but integrated into the chromosome. Southern hybridization analysis revealed that double as well as single cross-over integration events had occurred. Double cross-over events occurred at a frequency of about 15%. With these transformation and integration systems, recombinant DNA technology can now be applied to this important pathogenic species.
Mass spectrometry in diagnosis of metabolic disorders (1988)

Mass spectrometry is an important part of multicomponent analytical systems designed for diagnosis of metabolic disorders. In our laboratory capillary gas chromatography/mass spectrometry (GC/MS) with computerized library search is used primarily to separate and identify urinary organic acids. About 50 different diseases with increased excretion of organic acids are recognized today. Other techniques, including thin-layer chromatography, high-performance liquid chromatography with diode array detector, automatic amino acid analysis and two-dimensional electrophoresis are used to detect other compounds of diagnostic significance. The diagnostic use of GC/MS is exemplified by studies on two siblings. One died of his disease at approximately 1 year old. Both excreted 3-hydroxydicarboxylic acids (C8-C12) as identified by mass spectrometry. These metabolites are secondary to systemic carnitine deficiency. Low-fat diet normalized the clinical condition of the surviving sibling. GC/MS is now used to monitor the efficacy of dietary treatment by analysing the dicarboxylic acid excretion in this patient. Modern DNA technology is rapidly becoming increasingly important for diagnosis, particularly prenatal diagnosis, of metabolic diseases. It is suggested, however, that mass spectrometry will continue to be an important diagnostic tool for many years ahead.
BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008)

Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid beta precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer's disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Abeta1-40 transgenes in APP mouse models. Expression of BRI2-Abeta1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild-type human BRI2 reduces cerebral Abeta deposition in an AD mouse model. Additional data indicate that the 23 aa peptide, Bri23, released from BRI2 by normal processing, is present in human CSF, inhibits Abeta aggregation in vitro and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Abeta deposition in vivo.
The Duffy antigen receptor for chemokines: structural analysis and expression in the brain (1996)

The Duffy antigen receptor for chemokines (DARC) is expressed in human erythrocytes and on endothelial cells lining postcapillary venules in kidney and spleen. DARC is a promiscuous chemokine receptor and a binding protein for the malarial parasite Plasmodium vivax. The expression of DARC by subsets of endothelial cells and neurons in discrete anatomic sites in the brain suggests that this enigmatic receptor may have multiple roles in normal and pathological physiology. Conservation of this promiscuous chemokine binding function is evident from the similarity in nucleotide sequence of DARC homologues from multiple species, as well as the high-affinity binding of human chemokines to murine and avian erythrocytes. Analysis of the functional domains of DARC using chimeric receptors and and monoclonal antibodies to multiple extracellular domains localized chemokine binding to structures in the amino terminal extracellular domain (E1). Scatchard analysis demonstrated that a chimeric DARC receptor, composed of the E1 domain of DARC and the predicted hydrophobic helices and loops of interleukin-8RB (IL-8RB), bound IL-8, and MGSA with KD values almost identical to the wild type receptors and bound a repertoire of C-X-C and C-C chemokines characteristic of DARC. Although numerous reports have demonstrated that chemokines such as IL-8 are expressed in the brain, presumably by glial cells, little insight into the nature of their role in normal or pathological physiology in the nervous system has developed because the target cells that express the corresponding receptors have not yet been identified. Northern blotting experiments suggest that mRNA encoding DARC are expressed in the central nervous system, however, interpretation of this is unclear because of the ubiquitous expression of DARC lining postcapillary venules. This study provides direct evidence to localize expression of DARC in the central nervous system. Immunohistochemical examination of human archival sections of the brain with monoclonal antibodies specific for DARC localize expression of DARC to cell bodies and processes of Purkinjie cells in the cerebellum. The immunohistochemical findings were supported by analysis of chemokine binding and radioligand crosslinking with membranes made from various brain fractions. The hierarchical expression of DARC in neurons in the cerebellum suggest that chemokines may play an important role in the modulation of neuronal activity by glial cells.
Recovery of Calcium Carbonate and Hydrogen Sulfide from Waste Calcium Sulfide (1997)

The removal of H2S from hot coal gas using a limestone-based sorbent generates a large quantity of calcium sulfide waste (e.g., 67 tons/day from the gasification of 1000 tons/day of 3% S coal) that cannot be landfilled because of potential H2S evolution and sulfide leaching. In the process proposed here, the CaS is dissolved by reaction with H2S complexed with aqueous methyldiethanolamine (MDEA) or other alkanolamines. In the second step, the highly soluble Ca(HS)2 reacts readily with CO2, also complexed with aqueous MDEA, to precipitate pure CaCO3 of uniform crystal size and to form MDEA-complexed H2S in solution. The solution from step 2 is splithalf is recycled to step 1 and half is sent to a stripper to recover H2S and from there to a column where the needed CO2 is absorbed from a combustion gas.
Public issues on projected user interface (2010)

What will happen when pocket projectors become mainstream personal display channels? What will be affected when numerous projections intrude our living space without proper control? Today's technology in projection has promised a big screen viewing experience from mobile devices, pushing us toward a truly ubiquitous display environment. But, is our society prepared for the next projection-generation?
A Newfound Cancer-Activating Mutation Reshapes the Energy Landscape of Estrogen-Binding Domain (2014)

The ligand-binding domain (LBD) of an estrogen receptor undergoes a large conformational switching from an inactive to active state in response to hormone stimuli. Very recently, a novel D538G mutant has been identified to be active in advanced breast cancer tumors. Here, we ask if molecular simulations can provide insight on its mechanistic impact on the receptor's activation status. It has been challenging for ab initio modeling to identify two distinct conformations of a single amino acid sequence as large as that of the LBD. Using a coarse-grained (CG) model, we are able to correctly reproduce this LBD conformational switching. Furthermore, we found that the D538G mutation reshapes the energy landscape by stabilizing both active and inactive conformations, but preferring the active by 1.5 kcal/mol. This observation is consistent with the concept of a mutation-shifting landscape and provides a structural explanation for the oncogenic D538G mutation at the detailed conformational level.
Cystemustine induces redifferentiation of primary tumors and confers protection against secondary tumor growth in a melanoma murine model. (2001)

N'-(2-Chloroethyl)-N-(2-(methylsulfonyl)-ethyl)-N'-nitrosourea (cystemustine) is a chloroethylnitrosourea that has been used in the treatment of human melanoma. Its main antitumor effect is DNA damage to malignant melanocytes. Although unreported at present, other effects may also account for its cytotoxicity, some of them could be more or less delayed with respect to its administration. In this report, we have developed a model of secondary tumor with B16 melanoma in syngeneic C57B16 recipients to investigate the impact of cystemustine treatment of primary B16 melanoma tumors on the fate of secondary implanted untreated tumors. The data presented in this report indicate that cystemustine-treated cells or the administration of cystemustine provoke an important growth delay of primary melanoma tumors, together with an increase in cell pigmentation and cell morphology changes. Data also show that prime treatment induces a dramatic decrease in tumor weight of secondary untreated tumors accompanied by an increase in melanin content and an alteration of cell morphology. Finally, 1H-NMR spectroscopy was performed on treated B16 cells, showing an alteration in the phospholipid derivatives of melanocytes, suggesting subsequent modifications of membrane phospholipid composition. In conclusion, the data highlight two important findings: (a) cystemustine produces modifications other than DNA damage, i.e., cell morphology changes, pigmentation, and phospholipid metabolism alterations, indicating an interference with cell cycle, cell redifferentiation, and proliferation programs; and (b) cystemustine-treated tumors appear to confer a protective effect against the development of secondary untreated tumors that may be mediated by cytokines or an immune response.
Parallel interference cancellation techniques for synchronous carrier interferometry/MC-CDMA uplink (2005)

In this paper, we investigate the performance of various parallel interference cancellation (PIC) techniques for a synchronous carrier interferometry/MC-CDMA uplink. Specifically, we compare the performance of the system with conventional PIC, TPIC (PIC with threshold) and block-PIC. While TPIC does not offer any performance gain relative to conventional PIC, a significant improvement in performance and capacity is seen with block-PIC relative to conventional PIC (at the cost of a slight increase in complexity). We demonstrate that the block-PIC method provides the best performance with a BER of 10/sup -3/ at 12 dB which is 1 dB off the single user performance.
Signal Transduction During Activation and Inhibition of Natural Killer Cells (2010)

Natural killer (NK) cells are important for early immune responses to viral infections and cancer. Upon activation, NK cells secrete cytokines and chemokines, and kill sensitive target cells by releasing the content of cytolytic granules. This unit is focused on the signal transduction pathways that regulate NK cell activities in response to contact with other cells. We will highlight signals regulating NK cell adhesion to target cells and describe the induction of cellular cytotoxicity by the engagement of different NK cell activation receptors. Negative signaling induced by inhibitory receptors opposes NK cell activation and provides an important safeguard from NK cell reactivity toward normal, healthy cells. We will discuss the complex integration of the different signals that occur during interaction of NK cells with target cells.
Dissolution of ZnO Nanoparticles at Circumneutral pH: A Study of Size Effects in the Presence and Absence of Citric Acid (2011)

Understanding size-dependent processes, including dissolution, of engineered nanoparticles is essential in addressing the potential environmental and health impacts of these materials as well as their long-term stability. In this study, experimental measurements of size-dependent dissolution of well-characterized zinc oxide (ZnO) nanoparticles with particle diameters in the range of 4 to 130 nm have been measured at circumneutral pH (pH 7.5) and compared. Dissolution was found to be enhanced with smaller ZnO nanoparticles compared to larger-sized particles, even though the nanoparticles were present in solution as aggregates with hydrodynamic diameters on the order of 1-3 μm in size. The presence of citric acid significantly enhanced the extent of ZnO dissolution for all sizes, and the greatest enhancement was observed for the 4 nm particles. Although these results are found to be in qualitative agreement with theoretical predictions, a linearized form of the Kelvin equation to calculate a surface free energy yielded quantities inconsistent with expected values from the literature. Reasons for this inconsistency are discussed and include potential deviations of solubility behavior from classical thermodynamics as a result of a lack of detailed knowledge of surface structure and surface properties, including the presence of different surface crystal facets, and the aggregation state.
Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Disease: Different Syndromes? (1998)

To assess the possible differences in respiratory mechanics between the acute respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDSp) and that originating from extrapulmonary disease (ARDSexp) we measured the total respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0, 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with ARDSp and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and EELV were similar in both groups of patients. The Est,L, however, was markedly higher in the ARDSp group than in the ARDSexp group (20.2 +/- 5.4 versus 13.8 +/- 5.0 cm H2O/L, p < 0.05), whereas Est,w was abnormally increased in the ARDSexp group (12.1 +/- 3.8 versus 5.2 +/- 1.9 cm H2O/L, p < 0.05). The IAP was higher in ARDSexp than in ARDSp (22.2 +/- 6.0 versus 8.5 +/- 2.9 cm H2O, p < 0.01), and it significantly correlated with Est,w (p < 0. 01). Increasing PEEP to 15 cm H2O caused an increase of Est,rs in ARDSp (from 25.4 +/- 6.2 to 31.2 +/- 11.3 cm H2O/L, p < 0.01) and a decrease in ARDSexp (from 25.9 +/- 5.4 to 21.4 +/- 55.5 cm H2O/L, p < 0.01). The estimated recruitment at 15 cm H2O PEEP was -0.031 +/- 0.092 versus 0.293 +/- 0.241 L in ARDSp and ARDSexp, respectively (p < 0.01). The different respiratory mechanics and response to PEEP observed are consistent with a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar collapse in ARDSexp.
Monoclonal and specific polyclonal antibodies for immunoassay of Clostridium difficile toxin A (1985)

Monoclonal antibody, affinity-purified antibody, and monospecific antiserum against toxin A were produced. The monoclonal antibody was an immunoglobulin G2a kappa chain isotype that immunoprecipitated toxin A, as shown by crossed immunoelectrophoresis. These antibodies were compared by counterimmunoelectrophoresis, latex agglutination, and indirect enzyme-linked immunosorbent assay for their sensitivity in detecting toxin A. Our findings indicate that these antibodies may be useful as immunodiagnostic reagents for Clostridium difficile disease.
Kinetics of regulated protein–protein interactions revealed with firefly luciferase complementation imaging in cells and living animals (2004)

Signaling pathways regulating proliferation, differentiation, and apoptosis are commonly mediated through protein-protein interactions as well as reversible phosphorylation of proteins. To facilitate the study of regulated protein-protein interactions in cells and living animals, we optimized firefly luciferase protein fragment complementation by screening incremental truncation libraries of N- and C-terminal fragments of luciferase. Fused to the rapamycin-binding domain (FRB) of the kinase mammalian target of rapamycin and FK506-binding protein 12 (FKBP), respectively, the optimized FRB-N-terminal luciferase fragment (NLuc)/C-terminal luciferase fragment (CLuc)-FKBP luciferase complementation imaging (LCI) pair reconstituted luciferase activity in cells upon single-site binding of rapamycin in an FK506-competitive manner. LCI was used in three independent applications. In mice bearing implants of cells expressing the FRB-NLuc/CLuc-FKBP LCI pair, dose- and time-dependent luciferase activity allowed target-specific pharmacodynamic analysis of rapamycin-induced protein-protein interactions in vivo. In cells expressing a Cdc25C-NLuc/CLuc-14-3-3epsilon LCI pair, drug-mediated disruption of cell cycle regulated protein-protein interactions was demonstrated with the protein kinase inhibitor UCN-01 in a phosphoserine-dependent manner. When applied to IFN-gamma-dependent activation of Janus kinase/signal transducer and activator of transcription 1 (STAT1), LCI revealed, in the absence of ligand-induced phosphorylation, STAT1 proteins existing in live cells as preformed dimers. Thus, optimized LCI provides a platform for near real-time detection and characterization of regulated and small molecule-induced protein-protein interactions in intact cells and living animals and should enable a wide range of novel applications in drug discovery, chemical genetics, and proteomics research.
DOUBLE-BALLOON TRAPPING TECHNIQUE FOR EMBOLIZATION OF A LARGE WIDE-NECKED SUPERIOR CEREBELLAR ARTERY ANEURYSM (2008)

Double-balloon trapping is a novel endovascular technique that can be used to treat wide-necked aneurysms and maintain patency of side branches incorporated into the aneurysm neck.
Design of recombinant antibody microarrays for complex proteome analysis: Choice of sample labeling‐tag and solid support (2007)

Antibody-based microarray is a novel technology with great potential within high-throughput proteomics. The process of designing high-performing antibody (protein) microarrays has, however, turned out to be a challenging process. In this study, we have developed further our human recombinant single-chain variable-fragment (scFv) antibody microarray methodology by addressing two crucial technological issues, choice of sample labeling-tag and solid support. We examined the performance of a range of dyes in a one- or two-color approach on a selection of solid supports providing different surface and coupling chemistries, and surface structures. The set-ups were evaluated in terms of sensitivity, specificity, and selectivity. The results showed that a one-color approach, based on NHS-biotin (or ULS-biotin) labeling, on black polymer Maxisorb slides (or Nexterion slide H) was the superior approach for targeting low-abundant (pg/mL) analytes in nonfractionated, complex proteomes, such as human serum or crude cell supernatants. Notably, microarrays displaying adequate spot morphologies, high S/Ns, minimized nonspecific binding, and most importantly a high selectivity, specificity, and sensitivity (>or=fM range) were obtained. Taken together, we have designed the first generation of a high-performing recombinant scFv antibody microarray technology platform on black polymer Maxisorb slides for sensitive profiling of low-abundant analytes in nonfractionated biotinylated complex proteomes.