gebhart/patrepeval huggingface dataset:
Identification and Characterization of alcR , a Gene Encoding an AraC-Like Regulator of Alcaligin Siderophore Biosynthesis and Transport in Bordetella pertussis and Bordetella bronchiseptica (1998)

A Bordetella bronchiseptica iron transport mutant was isolated following an enrichment procedure based on streptonigrin resistance. The mutant displayed a growth defect on iron-restricted medium containing ferric alcaligin as the sole iron source. In addition to the apparent inability to acquire iron from the siderophore, the mutant failed to produce alcaligin as well as two known iron-regulated proteins, one of which is the AlcC alcaligin biosynthesis protein. A 1.6-kb KpnI-PstI Bordetella pertussis DNA fragment mapping downstream of the alcaligin biosynthesis genes alcABC restored both siderophore biosynthesis and expression of the iron-regulated proteins to the mutant. Nucleotide sequencing of this complementing 1.6-kb region identified an open reading frame predicted to encode a protein with strong similarity to members of the AraC family of transcriptional regulators, for which we propose the gene designation alcR. Primer extension analysis localized an iron-regulated transcription initiation site upstream of the alcR open reading frame and adjacent to sequences homologous to the consensus Fur repressor binding site. The AlcR protein was produced by using an Escherichia coli expression system and visualized in electrophoretic gels. In-frame alcR deletion mutants of B. pertussis and B. bronchiseptica were constructed, and the defined mutants exhibited the alcR mutant phenotype, characterized by the inability to produce and transport alcaligin and express the two iron-repressed proteins. The cloned alcR gene provided in trans restored these siderophore system activities to the mutants. Together, these results indicate that AlcR is involved in the regulation of Bordetella alcaligin biosynthesis and transport genes and is required for their full expression.
An Integrated Hall Sensor Platform Design for Position, Angle and Current Sensing (2006)

A new platform design of a Hall sensor uses digital signal processing and digital 3rd order temperature compensation. The improved architecture of the front-end achieves low noise of <2 muT in a bandwidth of 400 Hz by using a 3rd-order multibit continuous-time DeltaSigma-ADC. By chopping the first stage of this ADC a low magnetic offset of <50 muT is realized in a typical automotive operating temperature range from -50 to 150degC. A novel circuit technique for a stress sensor is used to compensate stress and aging effects in the Hall sensor. All required digital calculations are done at low power and area with a new intelligent state machine, which also provides various digital interface protocols.
Unconventional Superconductivity on a Topological Insulator (2010)

We study proximity-induced superconductivity on the surface of a topological insulator (TI), focusing on unconventional pairing. We find that the excitation spectrum becomes gapless for any spin-triplet pairing, such that both subgap bound states and Andreev reflection is strongly suppressed. For spin-singlet pairing, the zero-energy surface state in the d(xy)-wave case becomes a Majorana fermion, in contrast with the situation realized in the topologically trivial high-T(c) cuprates. We also study the influence of a Zeeman field on the surface states. Both the magnitude and direction of this field are shown to strongly influence the transport properties, in contrast with the case without TI. We predict an experimental signature of the Majorana states via conductance spectroscopy.
VIPERdb2: an enhanced and web API enabled relational database for structural virology (2008)

VIPERdb (http://viperdb.scripps.edu) is a relational database and a web portal for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the virology community, with an emphasis on the description and comparison of derived data from structural and computational analyses of the virus capsids. In the current release, VIPERdb2, we implemented a useful and novel method to represent capsid protein residues in the icosahedral asymmetric unit (IAU) using azimuthal polar orthographic projections, otherwise known as Φ–Ψ (Phi–Psi) diagrams. In conjunction with a new Application Programming Interface (API), these diagrams can be used as a dynamic interface to the database to map residues (categorized as surface, interface and core residues) and identify family wide conserved residues including hotspots at the interfaces. Additionally, we enhanced the interactivity with the database by interfacing with web-based tools. In particular, the applications Jmol and STRAP were implemented to visualize and interact with the virus molecular structures and provide sequence–structure alignment capabilities. Together with extended curation practices that maintain data uniformity, a relational database implementation based on a schema for macromolecular structures and the APIs provided will greatly enhance the ability to do structural bioinformatics analysis of virus capsids.
Origins and Evolution of the Global RNA Virome (2018)

Viruses with RNA genomes dominate the eukaryotic virome, reaching enormous diversity in animals and plants. The recent advances of metaviromics prompted us to perform a detailed phylogenomic reconstruction of the evolution of the dramatically expanded global RNA virome. The only universal gene among RNA viruses is the gene encoding the RNA-dependent RNA polymerase (RdRp). We developed an iterative computational procedure that alternates the RdRp phylogenetic tree construction with refinement of the underlying multiple-sequence alignments. The resulting tree encompasses 4,617 RNA virus RdRps and consists of 5 major branches; 2 of the branches include positive-sense RNA viruses, 1 is a mix of positive-sense (+) RNA and double-stranded RNA (dsRNA) viruses, and 2 consist of dsRNA and negative-sense (-) RNA viruses, respectively. This tree topology implies that dsRNA viruses evolved from +RNA viruses on at least two independent occasions, whereas -RNA viruses evolved from dsRNA viruses. Reconstruction of RNA virus evolution using the RdRp tree as the scaffold suggests that the last common ancestors of the major branches of +RNA viruses encoded only the RdRp and a single jelly-roll capsid protein. Subsequent evolution involved independent capture of additional genes, in particular, those encoding distinct RNA helicases, enabling replication of larger RNA genomes and facilitating virus genome expression and virus-host interactions. Phylogenomic analysis reveals extensive gene module exchange among diverse viruses and horizontal virus transfer between distantly related hosts. Although the network of evolutionary relationships within the RNA virome is bound to further expand, the present results call for a thorough reevaluation of the RNA virus taxonomy.<b>IMPORTANCE</b> The majority of the diverse viruses infecting eukaryotes have RNA genomes, including numerous human, animal, and plant pathogens. Recent advances of metagenomics have led to the discovery of many new groups of RNA viruses in a wide range of hosts. These findings enable a far more complete reconstruction of the evolution of RNA viruses than was attainable previously. This reconstruction reveals the relationships between different Baltimore classes of viruses and indicates extensive transfer of viruses between distantly related hosts, such as plants and animals. These results call for a major revision of the existing taxonomy of RNA viruses.
Distinct receptors for cholecystokinin and gastrin on muscle cells of stomach and gallbladder (1990)

A technique of receptor protection that enables selective preservation of one receptor type was used in conjunction with preferential antagonists of cholecystokinin (L364,718) and gastrin (L365,260) to characterize cholecystokinin (CCK) and gastrin receptors on isolated single muscle cells of the guinea pig stomach and gallbladder. In gastric muscle cells, CCK-8 and gastrin-17 were equipotent and the concentration causing 50% inhibition of response (IC50) values of both antagonists were independent of the agonist, whereas in gallbladder muscle cells, CCK-8 was more potent than gastrin-17 and the IC50 values of the antagonists were dependent on the agonist. In gastric muscle cells, CCK-8, gastrin-17, and L364,718 protected completely the response to CCK-8 or gastrin-17, and L365,260 protected partially but equally the response to both agonists. In gallbladder muscle cells, CCK-8 and L364,718 protected completely and gastrin-17 and L365,260 protected partially the response to CCK-8; conversely, gastrin-17 and L365,260 protected completely and CCK-8 and L364,718 protected partially the response to gastrin-17. The patterns of response in muscle cells from the two regions indicate the presence of one receptor type in gastric muscle cells that interacts equally with gastrin and CCK, and of two receptor types in gallbladder muscle cells, one of which interacts preferentially with CCK and the other preferentially with gastrin.
Pathogenesis and mechanisms of inflammation in the childhood rheumatic diseases (1998)

The presence of CD4+ cells in the synovium of children with juvenile rheumatoid arthritis has led to the generally accepted hypothesis that aberrant activation or regulation of acquired immunity is central to the pathogenesis of this family of diseases; however, this hypothesis remains unproven, and, indeed, a specific role for T cells in the process of chronic synovitis in rheumatoid disease has yet to be identified for either adults or children. In contrast, processes associated with innate immunity are undeniably involved in the pathophysiology of chronic synovitis in both rheumatoid arthritis and juvenile rheumatoid arthritis. The presence of neutrophils in the synovial fluid, complement activation, and immune complex accumulation in the synovial fluid and serum all indicate an active inflammatory process. It is reasonable to hypothesize, therefore, that there are important clues to the cause of juvenile rheumatoid arthritis to be gleaned from a more careful study of inflammation or innate immunity. This review will focus on the roles of complement, immune complexes, and the vascular endothelium in the pathogenesis of juvenile rheumatoid arthritis. In so doing, it will reexamine the dogma of the central role of the T cell in juvenile rheumatoid arthritis disease pathogenesis and offer new paradigms with which to understand this and other rheumatic diseases of childhood.
Analysis of Advertising Effectiveness with Eye Tracking (2008)

Global business organizations as well as medium and small sized companies use increasingly different kinds of outdoor and indoor advertising like posters and billboards. Analysis of advertising effectiveness has become a more and more
Obinutuzumab plus Chlorambucil in Patients with CLL and Coexisting Conditions (2014)

Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions. In this patient population, obinutuzumab was superior to rituximab when each was combined with chlorambucil. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01010061.).
Influence of moderate alcohol consumption on obstructive sleep apnoea with and without AutoSet nasal CPAP therapy (1996)

Snoring worsens with high alcohol consumption. It is unclear whether moderate alcohol intake worsens sleep and breathing in subjects with obstructive sleep apnoea syndrome (OSAS), and whether alcohol increases the pressure requirement for nasal continuous positive airway pressure (CPAP). Fourteen adult males with untreated OSAS but without heart or lung disease were studied (age 53+/-9 yrs, body mass index (BMI) 33+/-5 kg x m(-2) (mean+/-SD). The subjects underwent overnight polysomnography on four occasions: control, alcohol, CPAP, and alcohol + CPAP. On the alcohol nights, the subjects drank 1.5 mL x kg(-1) body weight (BW) vodka (40% alcohol by volume) (blood alcohol with and without CPAP 0.45+/-0.1 and 0.47+/-0.2 mg x mL(-1) (mean+/-SD)). On the CPAP nights, the pressure required to prevent apnoea, snoring, and silent inspiratory airflow limitation was determined using an autotitrating nasal CPAP system (ResCare AutoSet). Alcohol and control nights were performed in random order. Without CPAP, alcohol produced a small non-significant decrease in the percentage of rapid eye movement (REM) sleep (control 11+/-2 vs alcohol 8+/-1% (mean+/-SEM)), but with CPAP there was no such effect (control 15+/-2 vs 17+/-2%; CPA x alcohol interaction p=0.015). With CPAP, slow-wave sleep in the first 2 h increased slightly with alcohol (control 39+/-6 vs alcohol 51+/-4%; p=0.004). Arousal index without CPAP increased slightly with alcohol (control 43+/-5 vs alcohol 49+/-6 events x h(-1); p=0.02). There was little or no effect of alcohol on other sleep stages, arousal index, apnoea index, apnoea/hypopnoea index, mean or longest event duration, mean or worst arterial oxygen saturation, with or without CPAP, either for the full night or for the first 2 h. There was no change in the pressure requirement for CPAP (full night: control 11.9+/-0.9 vs alcohol 12.5+/-0.9 cm H2O; first 2 h: 10.9+/-0.6 vs 11.1+/-0.8 cm H2O). Moderate alcohol intake (in the form of vodka) has little effect on breathing or saturation during sleep in subjects with mild-to-severe obstructive sleep apnoea, and no effect on the pressure required for continuous positive airway pressure in order to prevent apnoea, snoring, and flow limitation. These results cannot be extrapolated to other doses or forms of alcohol, or to subjects with concurrent heart or lung disease.
Genetic correction using engineered nucleases for gene therapy applications (2013)

Genetic mutations in humans are associated with congenital disorders and phenotypic traits. Gene therapy holds the promise to cure such genetic disorders, although it has suffered from several technical limitations for decades. Recent progress in gene editing technology using tailor‐made nucleases, such as meganucleases ( MN s), zinc finger nucleases ( ZFN s), TAL effector nucleases ( TALEN s) and, more recently, CRISPR /Cas9, has significantly broadened our ability to precisely modify target sites in the human genome. In this review, we summarize recent progress in gene correction approaches of the human genome, with a particular emphasis on the clinical applications of gene therapy.
Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans (2003)

Our results appear to demonstrate that the procedures of ex vivo expansion of autologous mesenchymal stem cells and of transplantation into the spinal cord of humans are safe and well tolerated by ALS patients.
The Structure of Zwitterionic Phosphocholine Surfactant Monolayers (2006)

The structure of a zwitterionic phosphocholine (PC) surfactant monolayer adsorbed on the surface of water has been determined using neutron reflectivity in combination with H/D isotopic substitution. The most significant results of this study are the level of hydration of the PC headgroup and the lack of dehydration with increasing temperature and salt addition. The fraction of the alkyl chain (f(c)) immersed in water for all three chain isomers studied was found to be around 0.15, suggesting that the PC headgroup geometries influenced not only the headgroup hydration but also the degree of immersion of the alkyl chain in water. At the critical micelle concentration (CMC), the number of water molecules associated with the PC headgroup in C(m)PC (m = 12, 14, 16) was on order of 15. This value was significantly greater than that obtained for nonionic and ionic surfactants with similar limiting area per molecule at the CMC (A(cmc)). However, the fraction of the chain immersed in water for the ionic and nonionic surfactants was much greater. This suggests that the unique surface biocompatibility of PC surfactants arises from their strong affinity for water, and the relatively low fraction of mixing with the alkyl chain arises from the higher structural order within the PC monolayer. As surface coverage decreased, the number of water molecules associated with each PC headgroup increased, but f(c) remained constant for all the surfactants. This observation was consistent with the small variation in the thickness of the headgroup region, and the entire layer changed little with surfactant concentration. This is attributed to the role of PC headgroup geometries to maintain the conformational order within the layer as packing density varies. Further structural analysis based on a kinematic approach showed that, as the chain length was increased from C12 to C14 to C16 at the CMC, the angle of tilt for the alkyl chain increased from 40 degrees to 48 degrees to 53 degrees , respectively, whereas the thickness of the whole layer and that of the PC head region was largely constant. The almost vertical projection of the PC headgroup from these single alkyl chain surfactants is in sharp contrast to its strongly tilted conformation, as reported for dichain phospholipids such as dipalmitoyl glycerol phosphocholine (DPPC).
Internal ribosome entry segment-mediated initiation of c-Myc protein synthesis following genotoxic stress (2001)

Initiation of translation of the proto-oncogene c-myc can occur by either the cap-dependent scanning mechanism or by internal ribosome entry. The latter mechanism requires a complex RNA structural element that is located in the 5′ untranslated region of c-myc, termed an internal ribosome entry segment (IRES). Recent work has shown that IRESs are used to maintain protein expression under conditions when cap-dependent translation initiation is compromised; for example, during mitosis, apoptosis and under conditions of cell stress, such as hypoxia or heat shock. Induction of genotoxic stress also results in a large reduction in global protein synthesis rates and therefore we investigated whether the c-myc IRES was active following DNA damage. As expected, in cells treated with either ethylmethane sulphonate or mitomycin C there was a large reduction in protein synthesis, although this was brought about by two different mechanisms. However, in each case the c-myc IRES was active and c-Myc protein expression was maintained. Finally we showed that the proteins required for this process are downstream of the p38 mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated protein kinase (ERK)/MEK(MAPK/ERK kinase) signalling pathways, since pre-treatment of cells with inhibitors of these pathways before DNA damage is initiated inhibits both c-myc IRES activity and expression of c-Myc protein.
SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice (2012)

Chronic obstructive pulmonary disease/emphysema (COPD/emphysema) is characterized by chronic inflammation and premature lung aging. Anti-aging sirtuin 1 (SIRT1), a NAD+-dependent protein/histone deacetylase, is reduced in lungs of patients with COPD. However, the molecular signals underlying the premature aging in lungs, and whether SIRT1 protects against cellular senescence and various pathophysiological alterations in emphysema, remain unknown. Here, we showed increased cellular senescence in lungs of COPD patients. SIRT1 activation by both genetic overexpression and a selective pharmacological activator, SRT1720, attenuated stress-induced premature cellular senescence and protected against emphysema induced by cigarette smoke and elastase in mice. Ablation of Sirt1 in airway epithelium, but not in myeloid cells, aggravated airspace enlargement, impaired lung function, and reduced exercise tolerance. These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes. Inhibition of lung inflammation by an NF-κB/IKK2 inhibitor did not have any beneficial effect on emphysema. Thus, SIRT1 protects against emphysema through FOXO3-mediated reduction of cellular senescence, independently of inflammation. Activation of SIRT1 may be an attractive therapeutic strategy in COPD/emphysema.
Global resource sharing for synthesis of control data flow graphs on FPGAs (2003)

In this paper we discuss the global resource sharing problem during synthesis of control data flow graphs for FPGAs. We first define the Global Resource Sharing (GRS) problem. Then, we introduce the Global Inter Basic Block Resource Sharing (GIBBS) technique to solve the GRS problem. We developed five heuristics to solve the GRS problem. The first tries to minimize the number of connections between modules, the second considers the area gain, the third uses the criticality of operations assigned to resources as a measure for deciding on merging any given pair of resources, the fourth tries to capture common resource chains and overlap those to minimize both area and delay, and the fifth is the combination of these heuristics. While applying resource sharing, we also consider the execution frequency of the basic blocks. Using our techniques we synthesized several CDFGs representing applications from MediaBench suite. Our results show that, we can reduce the total area requirement by 44% on average (up to 59%) while increasing the execution time by 6% on average.
BAY 43-9006: Early Clinical Data in Patients with Advanced Solid Malignancies (2002)

Various signalling pathways can confer the malignant phenotype to a cell. Ras signalling proteins have been found to play an important role in controlling cellular growth. Raf-1 is a protein kinase that exerts its effects downstream of Ras in the mitogen-activated protein kinase pathway and is thus likely to be crucial in the development of the malignant phenotype. BAY 43-9006 is an orally administered selective inhibitor of Raf-1 and the first compound of its class to enter clinical trials. This article describes the early clinical data of BAY 43-9006 in patients with advanced, refractory solid tumours. To date, over 60 patients have been treated as part of four Phase I clinical trials. Dose levels have ranged from 50mg once weekly to 200mg twice-daily in continuous administration. The drug has been generally well tolerated with no dose limiting toxicity yet encountered. The more common toxicities have involved the gastrointestinal tract (diarrhea, nausea, abdominal cramping) and the skin (pruritus, rash, cheilitis). Pharmacokinetic evaluations have found BAY 43-9006 to have considerable interpatient variability. However, there seems to be an increase in C(max) and AUC values with increasing dose. There is no clear effect of food on bioavailability. Splitting the dose to twice-daily administration has shown increases in C(max) and AUC values but is also accompanied by considerable interpatient variability.
Polymer Network-Stabilized Liquid Crystals (2000)

The fabrication and properties of polymer network–stabilized liquid crystals, formed by polymerization of a small amount of a bifunctional photoreactive monomer dissolved in a liquid-crystalline phase, are reviewed. The polymer network morphology is strongly related to preparation conditions such as monomer content, polymerization temperature, and ultraviolet (UV) curing conditions. The transfer of anisotropic liquid-crystalline order onto the network is discussed in detail. The electro-optical performance of network-stabilized nematics, cholesterics, and ferroelectric smectics is largely dependent on the morphology of the network, as will be demonstrated with an emphasis laid on polymer-stabilized cholesteric textures (PSCTs). A general correlation between polymerization conditions, network morphology, and electro-optical behavior will be outlined and aspects concerning applications discussed.