gebhart/patrepeval huggingface dataset:
Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators (2016)

Interferon-stimulated gene 15 (ISG15) encodes an ubiquitin-like protein that covalently conjugates protein. Protein modification by ISG15 (ISGylation) is known to inhibit the replication of many viruses. However, studies on the viral targets and viral strategies to regulate ISGylation-mediated antiviral responses are limited. In this study, we show that human cytomegalovirus (HCMV) replication is inhibited by ISGylation, but the virus has evolved multiple countermeasures. HCMV-induced ISG15 expression was mitigated by IE1, a viral inhibitor of interferon signaling, however, ISGylation was still strongly upregulated during virus infection. RNA interference of UBE1L (E1), UbcH8 (E2), Herc5 (E3), and UBP43 (ISG15 protease) revealed that ISGylation inhibits HCMV growth by downregulating viral gene expression and virion release in a manner that is more prominent at low multiplicity of infection. A viral regulator pUL26 was found to interact with ISG15, UBE1L, and Herc5, and be ISGylated. ISGylation of pUL26 regulated its stability and inhibited its activities to suppress NF-κB signaling and complement the growth of UL26-null mutant virus. Moreover, pUL26 reciprocally suppressed virus-induced ISGylation independent of its own ISGylation. Consistently, ISGylation was more pronounced in infections with the UL26-deleted mutant virus, whose growth was more sensitive to IFNβ treatment than that of the wild-type virus. Therefore, pUL26 is a viral ISG15 target that also counteracts ISGylation. Our results demonstrate that ISGylation inhibits HCMV growth at multiple steps and that HCMV has evolved countermeasures to suppress ISG15 transcription and protein ISGylation, highlighting the importance of the interplay between virus and ISGylation in productive viral infection.
A 14 Bit 500 MS/s CMOS DAC Using Complementary Switched Current Sources and Time-Relaxed Interleaving DRRZ (2014)

A 14 bit 500 MS/s current-steering digital-to-analog converter (DAC) was designed and fabricated in 0.13 μm CMOS process. For traditional wide-band current-steering DACs, the spurious-free dynamic range (SFDR) is limited by nonlinear distortions from the code-dependent load variations and the code-dependent switching glitches. They are analyzed in this paper and mitigated by the proposed complementary switched current sources (CSCS) and time-relaxed interleaving digital- random-return-to-zero (TRI-DRRZ), respectively. The proposed techniques are fabricated and measured, with an SFDR of 84.8 dB at 11 MHz signal frequency and 73.5 dB at 244 MHz. The DAC consumes 299 mW from a mixed power supply of 1.2 V and 2.5 V with an active area of 1.85×0.65 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> .
New region feature descriptor-based image registration method (2012)

Successful content-based image registration relies on the accurate identification of corresponding features across images. Geometric and photometric transformations between images may hinder an algorithm's ability to precisely match features. In this work, we propose a novel region descriptor detection and matching algorithm for use with image registration. The detection process utilizes invariant feature points, as well as their spatial relationships and textural characteristics to create a connected graph whose structure represents an invariant region descriptor. With such a framework, feature matching can be accomplished by graph matching with a defined similarity metric. Subsequent image registration steps are outlined that employ the invariant region descriptors. The results provide strong evidence of the region descriptor's effectiveness in applications involving image registration. Several scenarios are presented including the registration of general objects, aerial photography, as well as scenes before and after a disaster.
Modelling the sea level of the upper Bay of Fundy (2005)

Abstract A high resolution model of the upper Bay of Fundy was developed to simulate the tides and sea level. The model includes the wetting and drying (inundation) of the extensive tidal flats in Minas Basin. The model reproduces the dominant M2 tidal harmonic with an error on the order of 0.30 m, and the total water level in Minas Basin with an r.m.s. error of 0.30–0.50 m. Overall the system is capable of a sea level simulation with a relative error of ∼10%. The motivation for the model development was the simulation of the land/water interface (instantaneous coastline) to aid in the validation of coastline retrieval algorithms from remotely sensed observations. Comparison of observed and simulated coastlines showed that a high quality representation of the local topography/bathymetry is as important as the sea level simulation in the calculation of the coastline. For example, long narrow features such as dykes are difficult to resolve in a dynamical model but are important for the inundation of low lying areas.
Development of an ECB on computer networks based on WWW technologies, resources and usability criteria (2003)

According to Baas, van den Eijnde, and Junger (2001) an electronic course book (ECB) is a learning module consisting of menu-driven hyperdocuments with a functional use of interactivity and multimedia, presented on the WWW and/or CDROM. The main purpose of this paper is to propose a model for the development of a computer network ECB based on (a) the integration of several tools, which are dispersed in the WWW as university course materials and that for their multimedia nature could not be inserted in a paper book, and (b) on WWW usability criteria, which make the design of the book very different from that of a printed book. The ECB will be useful both to teachers (while giving their lectures) since they will take advantage of the slide-based presentation of the text and of the several simulation tools included in the ECB, and to students (while studying the material) since they will be able to learn by reading, by doing and by answering.
Anatomic Consideration for Sacral Screw Placement (1991)

Instrumentation of the lumbosacral spine increasingly involves screw fixation to the sacrum. Recommended locations and techniques for screw placement vary, particularly when bicortical purchase of the sacrum is performed. The purpose of this study was to describe the critical anatomy and potential injuries to neurovascular and visceral structures anterior to the sacrum. Lack of awareness can lead to life-threatening complications. The study included 22 fresh human cadavers with no prior spinal surgery. Specimens were placed in a prone position, and the lumbosacral spine was exposed. Two 6.5-mm screws were inserted using one of two techniques, respectively: Starting just inferior to the S1 facet one screw was angled 25 degrees caudally and 30 degrees laterally; in the second technique, lateral inclination was increased to 45 degrees. In addition, all specimens had screws placed in the S2 pedicles. An anterior dissection was performed to allow evaluation of the neurovascular and visceral structures at risk for injury by, or adjacent to, the screw tips. All significant neurovascular structures in the area of concern were constant in position. The internal iliac vein and the lumbosacral nerve trunk were most at risk for injury by the 30 and 45 degrees laterally directed screws. The sigmoid colon, though close to the S2 screw, was protected by its mesentery. Screws placed in the S1 pedicle were least likely to injure the neurovascular bundle. A lateral and a midline safe zone were identified.
Distinct Global DNA Methylation Status in B-Cell Lymphomas : Immunohistochemical Study of 5-Methylcytosine and 5-Hydroxymethylcytosine (2014)

Lymphomas are malignant neoplasms composed of lymphoid cells at various developmental stages and lineages. Recent advances in comprehensive genomic analyses in acute myeloid leukemia have revealed prevalent mutations in regulators of epigenetic phenomena including global DNA methylation status. The examples include mutations in isocitrate dehydrogenase 1 (IDH1), IDH2, and ten-eleven translocation 2. These mutations are proposed to inhibit conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), leading to global accumulation of 5 mC. These changes in global DNA methylation status can be visualized immunohistochemically using specific antibodies against 5 mC and 5 hmC. We examined the global DNA methylation status of B-cell lymphomas and that of their normal counterparts by immunohistochemistry for 5 mC and 5 hmC. Non-tumor lymphoid cells inside germinal centers (GC) in reactive lymphoid hyperplasia (RLH) were stained positive for 5 mC, but they were negative for 5 hmC. Similarly, follicular lymphomas, whose postulated normal counterparts are centrocytes in GCs, were 5 mC-positive but 5 hmC-negative by immunohistochemistry. This immunostaining pattern was also observed in Burkitt lymphoma. In contrast, non-tumor lymphoid cells in mantle zones were stained positive for 5 mC as well as for 5 hmC. Likewise, most mantle cell lymphomas, whose postulated normal counterparts are mantle zone B cells in RLH, were stained positive for 5 mC as well as for 5 hmC. This immunostaining pattern was also observed in chronic lymphocytic leukemia/small lymphocytic lymphoma. These results suggest that, in terms of 5 mC/5 hmC immunohistochemistry, B-cell lymphomas with different histological subtypes are associated with distinct global DNA methylation statuses that resemble those of their postulated normal counterparts.
Cloning of a second gene encoding 6‐phosphofructo‐2‐kinase in yeast, and characterization of mutant strains without fructose‐2,6‐bisphosphate (1996)

We have identified a new gene, PFK27, that encodes a second inducible 6-phosphofructo-2-kinase in the yeast Saccharomyces cerevisiae. Sequencing shows an open reading frame of 397 amino acids and 45.3 kDa. Amino acid sequence comparisons with other bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoenzymes of various organisms revealed similarities only to the kinase domains. Expression of PFK27 was induced severalfold by glucose and sucrose, but not by galactose or maltose, suggesting that sugar transport might be involved in triggering the induction signal. We have constructed a mutant strain devoid of any fructose-2,6-bisphosphate. The mutant strain grew well on several kinds and concentrations of carbon sources. The levels of hexose phosphates in the cells were increased, but flux rates for glucose utilization and ethanol production were similar to the wild-type strain. However, after the transfer of the mutant cells from respiratory to fermentative growth conditions, growth, glucose consumption and ethanol production were delayed in a transition phase. Our results show that fructose-2,6-bisphosphate is an important effector in vivo of the 6-phosphofructo-1-kinase/fructose-1 ,6-bisphosphatase enzyme pair, and is involved in the initiation of glycolysis during the transition to a fermentative mode of metabolism. Nevertheless, it can be effectively replaced by other effectors and regulatory mechanisms during growth on glucose.
Astrovirus and Breda virus infections of dome cell epithelium of bovine ileum (1984)

A bovine enteric virus antigenically related to the United Kingdom isolate of bovine astrovirus was isolated from diarrheic feces, also containing rotavirus, of a calf in Florida. The astrovirus infected cell cultures and the epithelial cells of domes in the ileum, and there was cross-immunofluorescence with antiserum to the United Kingdom astrovirus. Calves infected with astrovirus alone did not develop clinical disease, but when astrovirus was mixed with rotavirus or Breda virus 2, the calves developed severe diarrhea and more extensive astrovirus infection of the dome epithelium. The dome epithelial cells showed degeneration associated with astrovirus infection, and a few cells showed degeneration with Breda virus 2 infection. Virions with a 30-nm diameter were seen in astrovirus-infected dome cells, and Breda virus 2 virions were also observed either in separate cells or, on occasion, with both viruses in one cell.
Effects of depletion of neutrophils or macrophages on development of cigarette smoke-induced emphysema (1999)

The aim of this study was to ascertain the putative roles of neutrophils or macrophages in the pathogenesis of cigarette smoking-induced emphysema on the basis of effects of anti-neutrophil (anti-PMN) antibody or anti-monocyte/macrophage (anti-MoMac) antibody on the development of emphysema in cigarette smoke-exposed rats. Rats were treated with rabbit anti-PMN or anti-MoMac antibody and exposed 7 days/wk for 2 mo to cigarette smoke inhalation; rats treated with nonimmunized rabbit IgG (control antibody) and exposed to cigarette smoke or normal room air served as controls. Antibody treatments began 24 h before the start of smoke or air exposure and was continued with 1 treatment/wk. Total and differential cell counts in bronchoalveolar lavage fluid and collagenase-dissociated lung and determinations of the elastinolytic activity of lung neutrophils or macrophages in [(3)H]elastin-coated wells indicated specific suppression of neutrophil accumulation and neutrophil-related elastinolytic burden in the lungs of the anti-PMN antibody-treated smoke-exposed rats, in contrast to specific suppression of macrophage accumulation and macrophage-related elastinolytic burden in the lungs of the anti-MoMac antibody-treated smoke-exposed rats. Cigarette smoke exposure-induced lung elastin breakdown (quantitated by immunologic assay of levels of elastin-derived peptides and desmosine in lavage fluid) and emphysema in the lungs (based on morphometric analysis of alveolar mean linear intercepts and alveolar tissue density in fixed lungs) were not prevented in the lungs of anti-PMN antibody-treated smoke-exposed rats but was clearly prevented in lungs of the anti-MoMac antibody-treated smoke-exposed rats. These findings implicate macrophages rather than neutrophils as the critical pathogenic factor in cigarette smoke-induced emphysema.
Experiments in Active Control of Stall on an Aeroengine Gas Turbine (1997)

This paper describes work carried out between 1989 and 1994 to investigate the application of ‘Active Stall Control’ to a Rolls-Royce Viper turbojet. The results demonstrate that stall control is feasible and can increase the stable operating range by up to 25% of pressure rise. Stall disturbances were detected using rings of high response pressure transducers positioned at different axial planes along the compressor, and processed using a PC-based data acquisition and control system. Actuation was provided by six hydraulically operated sleeve valves positioned to recirculate air over all or part of the compressor. Stall was artificially induced using combinations of inbleed into the combustor outer casing, fuel spiking, hot gas ingestion and inlet pressure spoiling, thus replicating many of the transient conditions commonly observed to make a compressor prone to stall. Results are compared from a number of stall control strategies including those demonstrated at low speed by Paduano et al [1993] and Day [1993]. Best results were obtained with detection of non-axisymmetric disturbances coupled with axisymmetric control action. A control system of this type is demonstrated to be capable of extending the stable engine operating range at all speeds and with each method of inducing stall.
Novel inactivators of serine proteases based on 6-chloro-2-pyrone (1983)

The interaction of serine protease (esterases) with 6-chloro-2-pyrones was investigated. Time-dependent inactivation of chymotrypsin, alpha-lytic protease, pig liver elastase, and cholinesterase was found with 3- and 5-benzyl-6-chloro-2-pyrone, as well as 3- and 5-methyl-6-chloro-2-pyrone. No inactivation was observed with the unsubstituted 6-chloro-2-pyrone. The substituted pyrones did not inactivate papain or carboxypeptidase A, as well as a number of other nonproteolytic enzymes. The substituted chloropyrones, therefore, show considerable selectivity toward serine proteases. Analogues in which the 6-chloro substituent is replaced by H or OH do not inactivate. The presence of the halogen is, therefore, essential for inactivation. Chymotrypsin catalyzes the hydrolysis of 3-benzyl-6-chloro-2-pyrone. At pH 7.5, (E)-4-benzyl-2-pentenedioic acid is the major product, and 2-benzyl-2-pentenedioic anhydride is a minor product. The ration of hydrolysis product found to the number of enzyme molecules inactivated varies from 14 to 40. The enzyme inactivated with the 3-benzyl compound does not show a spectrum characteristic of the pyrone ring. This suggests that inactivation by 3-benzyl-6-chloro-2-pyrone occurs in a mechanism-based fashion after enzymatic lactone hydrolysis. When the enzyme is inactivated with the 5-benzyl compound, absorbance due to the pyrone ring is observed. We suggest that inactivation occurs through an active site directed mechanism involving a 1,6-conjugate addition of an active site nucleophile to the pyrone ring.
[Inhibition of hepatitis B viral gene expression by antisense phosphrothioate oligonucleotides]. (1994)

Hep G2 cells transfected with HBV genomes were used to study the inhibitory effect of antisense phosphrothiate oligodeoxynucleotides on HBsAg and HBeAg production. The synthetic antisense 15-s-oligomers against the cap site of mRNA transcribed from the SPII promoter and regions of the translational initiation site of the S gene showed a dose-dependent and sequence-specific inhibitory effect on HBV gene expression between concentrations of 1.0-5.0 mumol/L. But the oligomers directed on the middle site of the S gene exerted little effect on HBsAg and HBeAg expression as well as the non-complementary random sequence control. The cells remained viable throughout the experiments and no morphological abnormalities and cytotoxicity were observed with antisense S-oligomers at concentrations below 20.0 mumol/L. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically infected with HBV.
<i>Toxoplasma gondii</i> -Infected Cells Are Resistant to Multiple Inducers of Apoptosis (1998)

Infection with certain intracellular pathogens, including viruses and bacteria, may induce host cell apoptosis. On the other hand, infection with some viruses inhibits apoptosis. Complex protozoan parasites, including Toxoplasma gondii and members of Plasmodium, Leishmania, and Microsporidia, are also obligate intracellular pathogens, yet relatively little is known regarding their subversion of host cell functions. We now report that cells infected with T. gondii are resistant to multiple inducers of apoptosis, including Fas-dependent and Fas-independent CTL-mediated cytotoxicity, IL-2 deprivation, gamma irradiation, UV irradiation, and the calcium ionophore beauvericin. Inhibition of such a broad array of apoptosis inducers suggests that a mechanism common to many, or perhaps all, apoptotic pathways is involved. The inhibitory activity requires live intracellular parasite and ongoing protein synthesis. Despite T. gondii-mediated inhibition of DNA fragmentation, infected cells can still be lysed by CTL.
Inhibitory effects of berberine on the activation and cell cycle progression of human peripheral lymphocytes. (2005)

The immunosuppressive property of berberine, an isoquinoline alkaloid, has been well documented, but the mechanism of its action on lymphocytes has not been completely elucidated. The present study is to investigate the effect of berberine on the activation and proliferation of lymphocytes, in particular T lymphocytes. Whole peripheral blood from healthy donors was stimulated with phytohemagglutinin (PHA) alone or phorbol dibutyrate (PDB) plus ionomycin, and the expression of CD69 and CD25 on T lymphocytes was evaluated with flow cytometry. The distribution of cell cycles and cell viability were analyzed by staining with propidium iodide (PI) and 7-aminoactinomycin D (7-AAD), respectively. The results showed that 100 micromol/L and 50 micromol/L of berberine significantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA, whereas the effect of 25 micromol/L berberine was not significant. As the incubation time increased, the extent of inhibition decreased. Similarly, the expression of CD25 was also reduced by berberine in a dose-dependent manner over the concentration range of 25-100 micromol/L. Besides, this alkaloid could block lymphocyte cell cycle progression from G0/G1 phase to S and G2/M phase without phase specificity. Moreover, analysis following 7-AAD staining revealed that berberine had no significant cytotoxicity on lymphocytes. Taken together, berberine significantly inhibits the expression of activation antigens on T lymphocytes and also blocks the progression of cell cycles of lymphocytes, suggesting that berberine may exert immunosuppressive effect through inhibiting the activation and proliferation of T cells.
Electrothermal tuning of Al–SiC nanomechanical resonators (2006)

A highly effective electrothermal tuning method is demonstrated for Al–SiC nanomechanical resonators. Doubly clamped beam devices are actuated and read out using a magnetomotive technique under a moderate vacuum at room temperature. Direct current applied to a beam heats the structure and shifts the resonance frequency downward. Frequency shifts of 10% are easily achievable, and the thermal time constant of these structures is in the submicrosecond range. The initial frequency and frequency tunability are studied for beams of varying Al thickness, and the device performance can be accurately modelled using simple mechanical and thermal models. Because of the different mechanical properties of SiC and Al, both the initial frequency and the frequency tunability can be modified by varying the Al layer thickness. This approach has the potential to become an important tool for effective frequency tuning in deployable SiC-based nanoelectromechanical system devices and systems for applications that would benefit from SiC as the structural material.
Identification of cardiac myosin peptides capable of inducing autoimmune myocarditis in BALB/c mice. (1996)

Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease. This study was undertaken to identify pathogenic epitopes on the myosin molecule. Our approach was based on the comparison of the pathogenicity between cardiac (alpha-)myosin and soleus muscle (beta-)myosin. We show that alpha-myosin is the immunodominant isoform and induces myocarditis at high severity and prevalence whereas beta-myosin induces little disease. Therefore the immunodominant epitopes of alpha-myosin must reside in regions of different amino acid sequence between alpha- and beta-myosin isoforms. Cardiac myosin peptides corresponding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease. Three pathogenic peptides were identified. One peptide that is located in the head portion of the molecule induced severe myocarditis, whereas two others that reside in the rod portion possessed only minor pathogenicity. The identification of pathogenic epitopes on the cardiac myosin molecule will allow detailed studies on the recognition of this antigen by the immune system and might be used to downmodulate ongoing heart disease.