gebhart/patrepeval huggingface dataset:
Obesity drugs and their targets: correlation of mouse knockout phenotypes with drug effects <i>in vivo</i> (2006)

Sequencing of the human genome has yielded thousands of potential drug targets. The difficulty now is in determining which targets have real therapeutic value and should be the focus of a drug discovery effort. The available evidence suggests that knockout technology can be used prospectively to identify targets that are amenable to drug development for the treatment of a variety of diseases. This review compares the knockout phenotypes of 21 potential obesity targets with the effects of therapeutics designed for those targets on rodents and, when data were available, on humans. The phenotypes of obesity target knockouts model the effects seen when therapeutics designed for those obesity targets are delivered to rodents; of the 21 obesity targets reviewed, 16 showed a correspondence between knockout phenotype and drug effect in mice and/or rats. This suggests that, at least in terms of evaluating obesity targets, it is rare for compensatory developmental changes caused by the gene knockout to prevent detection of the relevant phenotype. In the majority of cases, the knockout phenotypes also modelled the effects seen when the relevant therapeutics were delivered to humans. Thus, it seems rational to use mouse knockout technology prospectively to identify genes that regulate body fat in vivo, and then to develop anti-obesity therapeutics by targeting the human protein products of these genes. Ultimately, the value of using this approach to identify novel targets for human anti-obesity therapies will be judged by future studies examining the anti-obesity effect, in humans, of the therapeutics that result from this approach.
Flat packaging of magnetic bubble devices (1974)

This paper describes a new method of packaging of a bubble device using, "flat-faced-coil (FFC)" drive coils, which simplify bubble device construction and facilitate easy heat radiation from the coils. The construction of the bubble drive coils is very important, because it determines the bubble device assembly process and the thermal dissipation of the coils. The FFCs sandwich the bubble chips. On the other hand, solenoid coils usually wrap around the bubble chips. As the FFC creates no large obstacles, it is easy to remove bubble chips from the coils as required. There is also excellent accessibility when wiring from the bubble chips to the electronic circuits.
A seismic swarm as a dynamic ergodic stochastic process: a case study of the L’Aquila’s earthquake in 2009 (2011)

The lethal earthquake of 6 April 2009 in L’Aquila, Central Italy, re-opened the discussion about the earthquake prediction due to the several precursory phenomena described in association to the event. One of the most important precursors that preceded L’Aquila main-shock was the foreshock activity. Papadopoulos et al. (NHESS, 2010) reported that a foreshock activity was there in the last months before the main-shock but the foreshock signal became very strong in the last 10 days with drastic changes in space time-size domains of local seismicity. The importance of shortterm foreshocks for the prediction of the main-shock was noted since the 1960’s. However, foreshocks appear to precede only some main shocks and not others, while there are also foreshocks too small to detect by routine seismic analysis. In this context, the aim of the paper is to analyse the phenomenon of swarm as a dynamic ergodic stochastic process with particular reference to mean time of transition of a certain class of earthquake swarms (belonging to a certain state) to other classes of varying intensity. This kind of analysis can be referred to some indicators such as the mean first passage time and the mean time to return with their respective probabilities, that constitute an important interpretive tool in forecasting.
Lipoproteins: Structure and Function (1975)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
A high dynamic range current-mode amplifier for computed tomography (2006)

In this paper, we show a high dynamic range current-mode detector for computed tomography application. A regulated current mirror structure has been implemented at pixel level that provides with 17 bits dynamic range and a noise floor below 3 pARMS. Nonlinearity is kept below 2% and signal bandwidth is higher than 10 kHz. A test structure with 4times4 pixel array is presented is this paper. Both photodiode and current mode amplifier have been integrated into the same CMOS standard process
Perindopril reduced cardiac events in stable coronary artery disease (2004)

Source Citation Fox KM. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet. 2003;362:782-8. 13678872
High-Performance Transparent Conducting Oxide Nanowires (2006)

We report the growth and characterization of single-crystalline Sn-doped In2O3 (ITO) and Mo-doped In2O3 (IMO) nanowires. Epitaxial growth of vertically aligned ITO nanowire arrays was achieved on ITO/yttria-stabilized zirconia (YSZ) substrates. Optical transmittance and electrical transport measurements show that these nanowires are high-performance transparent metallic conductors with transmittance of approximately 85% in the visible range, resistivities as low as 6.29 x 10(-5) Omega x cm and failure-current densities as high as 3.1 x 10(7) A/cm2. Such nanowires will be suitable in a wide range of applications including organic light-emitting devices, solar cells, and field emitters. In addition, we demonstrate the growth of branched nanowire structures in which semiconducting In2O3 nanowire arrays with variable densities were grown epitaxially on metallic ITO nanowire backbones.
Occupation hand book for youth (OHBY) Profile and use (2006)

Introduction Against the backdrop of the current severe employment situation, major changes in the industrial economy and its employment style and other trends in Japan over recent years, efforts to provide career and vocational guidance to the younger generation has become increasingly essential. Within this environment, occupational information plays an extremely important role in supporting the vocational-based education of young people who have yet to develop awareness about the future, and encouraging them to think in terms of personal career development. The Occupation Hand Book for Youth (OHBY) was developed in 2002 as a PC-based guidance system to help empower young people from junior high school to college age launch independent and productive searches for occupation-related information. It is designed for use in combination with psychological testing to facilitate effective career-based education. By targeting these goals, the OHBY has emerged as one of the leading occupational information tools available in Japan today. In this article, we profile the policy behind the development and design of the OHBY. We also provide guidelines to serve as a reference for group counseling, individual use or other applications of the system at the junior and senior high school career education classes, counseling centers, which serve as the primary venues for its use.
Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. (1996)

T-helper 1 (Th1) Th2 kinetics were studied by immunohistochemistry and molecular biology techniques (reverse transcriptase polymerase chain reaction. RT PCR, Southern-blot) during the course of pulmonary tuberculosis induced in BALB/c mice by the intratracheal instillation of the live and virulent strain H-37Rv. The histopathological study clearly showed two phases of the disease. The first one was an acute phase which was characterized by inflammatory infiltrate in the alveolar capillary interstitium, blood vessel and bronchial wall with formation of granulomas. In this acute phase which lasted from 1 to 28 days, a clear predominance of Th1 cells was observed, manifested by a high percentage of interleukin-2 (IL-2) positive cells in the inflammatory infiltrate and granulomas demonstrated by immunohistology, as well as a gradual increment of interferon-gamma (INF-gamma) m-RNA. This was followed by a chronic or advanced phase characterized by pneumonia, focal necrosis and fibrosis, with a Th0 balance due to an equivalent proportion of IL-2 and IL-4 positive cells in the lung lesions, that coincided with the highest level of INF-gamma and IL-4 mRNA. The cytofluorometric analysis of bronchial lavage cells, showed a predominance of CD4 T cells during the acute phase and CD8 T lymphocytes in the chronic phase, gamma-delta T lymphocytes showed two peaks, at the beginning (3 days) and at the end (4 months) of the infection. These results suggest that T-lymphocyte subset kinetics and the pattern of cytokines produced in the lung during tuberculosis infection changed over time and correlate with the type and magnitude of tissue injury.
A Low-Ripple Fast-Settling CMOS Envelope Detector (2006)

The design of a high performance envelope detector is made in this work. Proposed circuit does not need the traditional compensation between keeping and tracking required in these circuits due to a system by what the signal peaks are held in two periods and combined to obtain the envelope of the signal. Simulation results are offered comparing both the conventional and the proposed envelope detector and it is shown the superior performance of this circuit obtaining for a signal at 10MHZ smaller ripple (<1%), faster settling (0.4mus) and using smaller silicon area
Reaction Dynamics, Molecular Clusters, and Aqueous Geochemistry (2006)

Earth scientists will come to rely heavily upon computational chemistry because our environments are so difficult to sample. Essential geochemical information can often be better acquired by simulation than by either experiment or field sampling. No reactions are more essential to geochemistry than those involving water. Considerable advances are being made in understanding these hydrolytic reactions by close coupling of simulation to experiments on 1–5-nm-sized metal-hydroxide clusters. These clusters are sufficiently small that experiments can identify reaction properties at specific metal-oxygen sites that can then be treated using high-level methods of simulation. This twofold approach shows that some reaction classes at mineral surfaces are surprisingly robust and treatable using kinetic information in hand. Pathways for other reactions, such as dissociation of the oxygens that bridge metals and that hold the structure together, are enormously sensitive to details that neither experiment, nor simulation, alone can fully uncover. New efforts are needed to synthesize 1–5 nm experimental molecules to predict rate parameters for these aqueous reactions.
Evidence for Organosulfates in Secondary Organic Aerosol (2006)

Recent work has shown that particle-phase reactions contribute to the formation of secondary organic aerosol (SOA), with enhancements of SOA yields in the presence of acidic seed aerosol. In this study, the chemical composition of SOA from the photooxidations of alpha-pinene and isoprene, in the presence or absence of sulfate seed aerosol, is investigated through a series of controlled chamber experiments in two separate laboratories. By using electrospray ionization-mass spectrometry, sulfate esters in SOA produced in laboratory photooxidation experiments are identified for the first time. Sulfate esters are found to account for a larger fraction of the SOA mass when the acidity of seed aerosol is increased, a result consistent with aerosol acidity increasing SOA formation. Many of the isoprene and alpha-pinene sulfate esters identified in these chamber experiments are also found in ambient aerosol collected at several locations in the southeastern U.S. It is likely that this pathway is important for other biogenic terpenes, and may be important in the formation of humic-like substances (HULIS) in ambient aerosol.
A compact board-mounted power supply module for telecommunications systems (2003)

The authors describe the circuit and components of a compact board-mounted power supply module. A single-ended forward converter without a reset circuit reduces transformer size and circuit power dissipation. A simple, wideband optoisolation circuit extends the feedback loop bandwidth and reduces the size of the output smoothing filter. A low-profile surface-mounted transformer allows the power supply module to be mounted on a 15 mm-pitch circuit board. The 10 W power supply module can be reduced to 20 cm/sup 3/, which is half the conventional size.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Three-Dimensional Electron Microscopic Imaging of Membrane Invaginations in <i>Escherichia coli</i> Overproducing the Chemotaxis Receptor Tsr (2004)

Electron tomography is a powerful method for determining the three-dimensional structures of large macromolecular assemblies, such as cells, organelles, and multiprotein complexes, when crystallographic averaging methods are not applicable. Here we used electron tomographic imaging to determine the molecular architecture of Escherichia coli cells engineered to overproduce the bacterial chemotaxis receptor Tsr. Tomograms constructed from fixed, cryosectioned cells revealed that overproduction of Tsr led to formation of an extended internal membrane network composed of stacks and extended tubular structures. We present an interpretation of the tomogram in terms of the packing arrangement of Tsr using constraints derived from previous X-ray and electron-crystallographic studies of receptor clusters. Our results imply that the interaction between the cytoplasmic ends of Tsr is likely to stabilize the presence of the membrane networks in cells overproducing Tsr. We propose that membrane invaginations that are potentially capable of supporting axial interactions between receptor clusters in apposing membranes could also be present in wild-type E. coli and that such receptor aggregates could play an important role in signal transduction during bacterial chemotaxis.
Crystallization and preliminary X-ray analysis of the complex between human CTLA-4 and B7-2 (2001)

CTLA-4 is a dimeric T-cell surface receptor responsible for transducing signals that down-regulate activated T cells upon binding B7 ligands. The disulfide-linked homodimer of the extracellular segment of human CTLA-4 and the receptor-binding domain of human B7-2 were purified and cocrystallized. Diffraction from these crystals is consistent with the monoclinic space group P2(1) (unit-cell parameters a = 47.85, b = 54.56, c = 103.09 A, beta = 91.63); native data have been collected to 3.2 A resolution.
Dynamic tags for dynamic data web services (2010)

Service descriptions play a crucial role in Service-oriented Computing (SOC), especially with respect to service discovery and selection, service composition, and service replacement. Service providers have been the primary source of these descriptions, such as WSDL, WADL, WSMO. However, it has been observed that service providers tend to release poor service descriptions about their offered web services, because they focus on the implementation aspects of their web services. However, efficient service discovery requires rich service descriptions.
Semantic query optimization for XQuery over XML streams (2005)

We study XML stream-specific schema-based optimization. We assume a widely-adopted automata-based execution model for XQuery evaluation. Criteria are established regard-ing what schema constraints are useful to a particular query. How to apply multiple opti-mization techniques on an XQuery is then ad-dressed. Finally we present how to correctly and efficiently execute a plan enhanced with our SQO techniques. Our experimentation on both real and synthetic data illustrates that these techniques bring significant performance improvement with little overhead. 1
Aerosol backscattering of a laser beam (1983)

The backscattering of a laser beam from a particulate medium is studied by means of the radiative transfer equation, taking into account the effect of multiple scattering. An analytical expression for the backscattered power is obtained. From this the widely used single scattered lidar equation is recovered as an asymptotic form. Numerical results are discussed for the case of laser power returned from an advective fog.
Mechanistic Studies of Pd(II)−α-Diimine-Catalyzed Olefin Polymerizations<sup>1</sup> (2000)

Mechanistic studies of olefin polymerizations catalyzed by aryl-substituted α-diimine−Pd(II) complexes are presented. Syntheses of several cationic catalyst precursors, [(N∧N)Pd(CH3)(OEt2)]BAr‘4 (N∧N = aryl-substituted α-diimine, Ar‘ = 3,5-(CF3)2C6H3), are described. X-ray structural analyses of [ArNC(H)C(H)NAr]Pd(CH3)(Cl) and [ArNC(Me)C(Me)NAr]Pd(CH3)2 (Ar = 2,6-(iPr)2C6H3) illustrate that o-aryl substituents crowd axial sites in these square planar complexes. Low-temperature NMR studies show that the alkyl olefin complexes, (N∧N)Pd(R)(olefin)+, are the catalyst resting states and that the barriers to migratory insertions lie in the range 17−19 kcal/mol. Following migratory insertion, the cationic palladium alkyl complexes (N∧N)Pd(alkyl)+ formed are β-agostic species which exhibit facile metal migration along the chain (“chain walking”) via β-hydride elimination/readdition reactions. Model studies using palladium−n-propyl and −isopropyl systems provide mechanistic details of this process, which is responsible for introducing branching in the polyethylenes made by these systems. Decomposition of the cationic methyl complexes (ArN∧NAr)Pd(CH3)(OEt2)+ (Ar = 2,6-(iPr)2C6H3, 2-tBuC6H4) occurs by C−H activation of β-C−H bonds of the ortho isopropyl and tert-butyl substituents and loss of methane. The rate of associative exchange of free ethylene with bound ethylene in (N∧N)Pd(CH3)(C2H4)+ is retarded by bulky substituents. The relationship of these exchange experiments to chain transfer is discussed.
Automatic fare collection in transit: a synthesis of current practice (1987)

Abstract Many industries are keeping pace with changing technology in an effort to improve operating efficiency and attract consumers with innovations. The transit industry is no exception, one example being the installation and operation of automatic fare‐collection (AFC) systems. There are many issues to consider in implementing an AFC system, including the type of equipment required and the expected quality of system performance. This article presents a synthesis of several sources of information pertaining to AFC operations. It includes a discussion of system requirements, and the advantages and disadvantages of system operation. Performance measures of reliability and maintainability are also defined, and AFC systems are evaluated using these measures. Several conclusions are reached concerning current AFC practice.
Liquid chromatographic studies with immobilized neuronal nicotinic acetylcholine receptor stationary phases: effects of receptor subtypes, pH and ionic strength on drug–receptor interactions (1999)

Nicotinic acetylcholine receptor (nAChR) alpha3-subunits, beta4-subunits, alpha3/beta4-subunit combination and alpha4/beta2-subunit combination were immobilized on chromatographic stationary phases and the binding affinities of the different nAChR subtypes were chromatographically evaluated. The observed relative binding affinities of epibatidine were alpha4/beta2>alpha3/beta4 and epibatidine did not bind at alpha3-subunits and beta4-subunits. No significant difference in binding affinities was observed on the alpha4/beta2 nAChRs immobilized in immobilized artificial membrane (IAM) particles and those sterically immobilized on Superdex 200 beads. The effects of mobile phase pH and ionic strength on the binding affinities of the alpha3/beta4 nAChRs support were also investigated. The results are consistent with the proposed ligand-nAChR binding model in which a cationic center exists at the binding site.
Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma (2009)

Lenalidomide plus dexamethasone is effective for the treatment of relapsed and refractory multiple myeloma (MM); however, toxicities from dexamethasone can be dose limiting. We evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed and refractory MM. Patients (N = 222) received lenalidomide 30 mg/day once daily (days 1-21 every 28 days) until disease progression or intolerance. Response, progression-free survival (PFS), overall survival (OS), time to progression (TTP), and safety were assessed. Overall, 67% of patients had received 3 or more prior treatment regimens. Partial response or better was reported in 26% of patients, with minimal response 18%. There was no difference between patients who had received 2 or fewer versus 3 or more prior treatment regimens (45% vs 44%, respectively). Median values for TTP, PFS, and OS were 5.2, 4.9, and 23.2 months, respectively. The most common grade 3 or 4 adverse events were neutropenia (60%), thrombocytopenia (39%), and anemia (20%), which proved manageable with dose reduction. Grade 3 or 4 febrile neutropenia occurred in 4% of patients. Lenalidomide monotherapy is active in relapsed and refractory MM with acceptable toxicities. These data support treatment with single-agent lenalidomide, as well as its use in steroid-sparing combination approaches. The study is registered at http://www.clinicaltrials.gov as NCT00065351.
On-chip evaluation, compensation and storage of scan diagnosis data (2007)

Technology and product ramp-up suffers increasingly from systematic production defects. Diagnosis of scan-test fail data plays an important role in yield enhancement, as diagnosis of scan fail data helps to understand and overcome systematic production defects. Acquisition of scan fail data during high-volume production may lead to significant test time overhead. A new on-chip architecture is presented that evaluates scan-test results and stores relevant scan diagnostic information on chip. Scan diagnostic data is unloaded for offline analysis after the scan test has been finished. Unloading scan diagnostic data from chip requires only very little test time overhead. Moreover, the proposed technique is automatic test equipment independent and accelerates test program development. A detailed implementation example, based on a state-of-the-art SoC device, is given.
Large-Scale Production of Therapeutic Antibodies: Considerations for Optimizing Product Capture and Purification (2004)

The first therapeutic proteins produced by fermentation of genetically engineered bacteria emerged two decades ago. With the notable exception of insulin, most of the initial wave of biotechnology products launched in the 1980s and 1990s were peptide hormones and enzymes licensed for indications with relatively small patient populations and for short-term rather than chronic use. Consequently, the market requirement for these products was frequently in the low kilogram range.