gebhart/patrepeval huggingface dataset:
Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure (2015)

Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42 95% CI 0.18-0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p = 0.04, OR 4.45 95% CI 1.2-16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was positively associated with both outcomes (OR 4.2, 95% CI 1.07-16.1, P = 0.04; OR 4.45, 95% CI 1.2-16.6, P = 0.026, respectively). All other variables, including IBD type, sex, weight, age, smoking status, and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn disease patients, a nonstricturing nonpenetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, P = 0.04).Jewish Ashkenazi ethnicity is protective of ATI formation and infliximab therapy failure. These findings suggest a role for ethnicity, and implicitly for genetic predisposition, in modulating the risk of anti-TNF immunogenicity and treatment unresponsiveness.
COMMD1-Deficient Dogs Accumulate Copper in Hepatocytes and Provide a Good Model for Chronic Hepatitis and Fibrosis (2012)

New therapeutic concepts developed in rodent models should ideally be evaluated in large animal models prior to human clinical application. COMMD1-deficiency in dogs leads to hepatic copper accumulation and chronic hepatitis representing a Wilson's disease like phenotype. Detailed understanding of the pathogenesis and time course of this animal model is required to test its feasibility as a large animal model for chronic hepatitis. In addition to mouse models, true longitudinal studies are possible due to the size of these dogs permitting detailed analysis of the sequence of events from initial insult to final cirrhosis. Therefore, liver biopsies were taken each half year from five new born COMMD1-deficient dogs over a period of 42 months. Biopsies were used for H&E, reticulin, and rubeanic acid (copper) staining. Immunohistochemistry was performed on hepatic stellate cell (HSC) activation marker (alpha-smooth muscle actin, α-SMA), proliferation (Ki67), apoptosis (caspase-3), and bile duct and liver progenitor cell (LPC) markers keratin (K) 19 and 7. Quantitative RT-PCR and Western Blots were performed on gene products involved in the regenerative and fibrotic pathways. Maximum copper accumulation was reached at 12 months of age, which coincided with the first signs of hepatitis. HSCs were activated (α-SMA) from 18 months onwards, with increasing reticulin deposition and hepatocytic proliferation in later stages. Hepatitis and caspase-3 activity (first noticed at 18 months) increased over time. Both HGF and TGF-β1 gene expression peaked at 24 months, and thereafter decreased gradually. Both STAT3 and c-MET showed an increased time-dependent activation. Smad2/3 phosphorylation, indicative for fibrogenesis, was present at all time-points. COMMD1-deficient dogs develop chronic liver disease and cirrhosis comparable to human chronic hepatitis, although at much higher pace. Therefore they represent a genetically-defined large animal model to test clinical applicability of new therapeutics developed in rodent models.
The structure of C-polysaccharide from the walls of <i>Streptococcus pneumoniae</i> (1978)

The well-known immologically active component of pneumococci, C-polysaccharide, is a teichoic acid that can be isolated from the cell walls and purified by Sephadex and ion-exchange chromatography. Further details of the structure of C-teichoic acid were established by chemical degradation, including hydrolysis in acid and alkali, treatment with HF, periodate oxidation and methylation. In addition, the use of 13C n.m.r. has confirmed some of these structural features and resulted in a proposal for the order of substituents, the location of positions of substitution and the configuration of anomeric centres in the repeating unit of the polymer.
Signal Processing Aspects of Real-Time DNA Microarrays (2007)

Data acquisition in conventional fluorescent-based microarrays takes place after the completion of a hybridization phase. During the hybridization phase, target analytes bind to their corresponding capturing probes on the array. The conventional microarrays attempt to detect presence and quantify amounts of the targets by collecting a single data point, supposedly taken after the hybridization process has reached its steady-state. Recently, so-called real-time microarrays capable of acquiring not only the steady-state data but the entire kinetics of hybridization have been proposed in [1]. The richness of the information obtained by the real-time microarrays promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to the conventional microarrays. In the current paper, we study the signal processing aspects of the real-time microarray data acquisition.
Differential virulence of camel <i>Trypanosoma evansi</i> isolates in mice (2018)

This study assessed the virulence of Trypanosoma evansi, the causative agent of camel trypanosomiasis (surra), affecting mainly camels among other hosts in Africa, Asia and South America, with high mortality and morbidity. Using Swiss white mice, we assessed virulence of 17 T. evansi isolates collected from surra endemic countries. We determined parasitaemia, live body weight, packed cell volume (PCV) and survivorship in mice, for a period of 60 days' post infection. Based on survivorship, the 17 isolates were classified into three virulence categories; low (31-60 days), moderate (11-30 days) and high (0-10 days). Differences in survivorship, PCV and bodyweights between categories were significant and correlated (P < 0.05). Of the 10 Kenyan isolates, four were of low, five moderate and one (Type B) of high virulence. These findings suggest differential virulence between T. evansi isolates. In conclusion, these results show that the virulence of T. evansi may be region specific, the phenotype of the circulating parasite should be considered in the management of surra. There is also need to collect more isolates from other surra endemic regions to confirm this observation.
Gold and Hydroxyapatite Nano-Composite Scaffolds for Anterior Cruciate Ligament Reconstruction: <i>In Vitro</i> Characterization (2015)

Current anterior cruciate ligament (ACL) graft replacement materials often fail due to the lack of biological integration. While many newly developed extracellular matrix based scaffolds show good biocompatibility they often do not entice cellular remodeling and the rebuilding of a functional ligament. We have proposed the conjugation of gold nanoparticles (AuNP) and hydroxyapatite nanoparticles (nano-HAp) to acellular tissue to enhance cell attachment and proliferation while maintaining an improved degradation resistance and open microstructure. We are the first to investigate the double conjugation of AuNP and nano-HAp onto decellularized tissue to improve the tissue remodeling response. Decellularized porcine diaphragm was crosslinked with two types of nano-HAp and amine-functionalized AuNP with 1-ethyl-3-(3-dimethlaminopropyl) carbodiimide (EDC) crosslinker. Scaffolds were characterized using electron microscopy, differential scanning calorimetry, and fibroblast assays. Results demonstrated that scaffolds with nano-HAp have increased thermal stability at low levels of crosslinking. The open microstructure of the scaffold was not compromised allowing for cell migration while still providing increased degradation resistance. The addition of < 200 nm nano-HAp decreased cell viability compared to scaffolds without nanoparticles, but the addition of AuNP to scaffolds showed enhanced cell viability in the presence of < 200 nm nano-HAp. The addition of < 40 nm nano-HAp showed an increase in cell viability compared to scaffolds crosslinked without nanoparticles. It is concluded that attaching AuNP and < 40nm nano-HAp to extracellular matrices may improve overall properties.
Evaluation of Corrosion Preventive Compounds for Aviation Materials Applications (2005)

Abstract : Corrosion preventive compounds (CPCs) were evaluated using substrates comprised of five commonly used rotary wing aviation materials. The materials used were magnesium alloy AZ31B-H24 aluminum alloy 2024-T3, 4130 low alloy steel. 4340 high strength steel, and AM-355 stainless steel. The relative performance of each CPC was assessed in combination with the materials under several different tests. These tests consisted of general corrosion resistance. resistance to crevice corrosion attack. stress corrosion cracking (4340 only). and surface wetting characteristics. The commercially available CPCs examined were Carwell AR500 CorrosionX Aviation, and CorrosionX general purpose formula. Additionally. Mercon Dexron III automatic transmission fluid was tested for comparison. Baseline data for the test materials with no CPC applied was also collected. Product physical characteristics and properties with respect to application and removal, as well as Materials Safety Data Sheet information, are also included and discussed.
TURBULENT FRICTION-DRAG REDUCTION CONTROL-SCHEME REQUIRING ONLY STREAMWISE WALL SHEAR SIGNAL (2003)

We propose a new algebraic control scheme for drag reduction in wall-turbulence, which requires the streamwise wall-shear signal only. By assuming continuously distributed sensors and actuators, the controller is designed to reduce the near-wall Reynolds shear stress that is directly responsible for the turbulent skin friction drag. Intuitive and suboptimal control schemes are considered. The derived control laws are assessed by means of direct numerical simulation of turbulent pipe flow at Reτ ~ 180. A clear drag reduction symptom associated with a negative near-wall Reynolds stress is observed when the control scheme derived by the suboptimal control theory is applied.
ChemInform Abstract: New Poly(ethylene Oxide)‐Cu(CF3SO3)2 Polymer Electrolytes. (1988)

Abstract The electrochemical characteristics are determined for polymer electrolytes formed by complexes of poly(ethylene oxide), PEO, and Cu(CF 3 SO 3 ) 2 with varying molar ratio.
The Contribution of Intelligent System in Forming Trust and Competitiveness during Online Transactions (2007)

This paper uncovers concealed relationships between trust and competitiveness. This study analyzes the effect of these factors on human online decision process and how they influence the business-to-consumer (B2C) outcome when they are used collectively. This research provides a toolset for users to gauge the level of trust and competitiveness of a Web site prior to their engagement in online decision-making process.
Further characterization of IgE‐binding antigens from guinea pig hair as new members of the lipocalin family (2003)

These studies provide important information on the isoallergen character of two relevant guinea pig allergens Cav p 1 and Cav p 2 as well as on their cross-reactive properties.
Transmural Dispersion of Repolarization as a Preclinical Marker of Drug-induced Proarrhythmia (2012)

Torsade de Pointes (TdP) proarrhythmia is a major complication of therapeutic drugs that block the delayed rectifier current. QT interval prolongation, the principal marker used to screen drugs for proarrhythmia, is both insensitive and nonspecific. Consequently, better screening methods are needed. Drug-induced transmural dispersion of repolarization (TDR) is mechanistically linked to TdP. Therefore, we hypothesized that drug-induced enhancement of TDR is more predictive of proarrhythmia than QT interval. High-resolution transmural optical action potential mapping was performed in canine wedge preparations (n = 19) at baseline and after perfusion with 4 different QT prolonging drugs at clinically relevant concentrations. Two proarrhythmic drugs in patients (bepridil and E4031) were compared with 2 nonproarrhythmic drugs (risperidone and verapamil). Both groups prolonged the QT (all P < 0.02), least with the proarrhythmic drug bepridil, reaffirming that QT is a poor predictor of TdP. In contrast, TDR was enhanced only by proarrhythmic drugs (P < 0.03). Increased TDR was due to a preferential prolongation of midmyocardial cell, relative to epicardial cell, APD, whereas nonproarrhythmic drugs similarly prolonged both cell types. In contrast to QT prolongation, augmentation of TDR was induced by proarrhythmic but not nonproarrhythmic drugs, suggesting TDR is a superior preclinical marker of proarrhythmic risk during drug development.
Practical Olefin Aziridination with a Broad Substrate Scope (2002)

The present study illustrates the possibility of a rational approach that bypasses the requirement for stoichiometric amounts of toxic oxidants and metal additives (including reagents and catalysts) in organic redox reactions. We describe an aziridination process that delivers a nitrene functionality to olefins from a readily available N-aminophthalimide. Remarkably, both electron-rich and electron-poor olefins are converted to aziridines with high efficiency. The continuum of applied potentials and the heterogeneous nature of reactions at electrode surfaces allow for the electrochemical discrimination of substrates which have similar redox potentials and therefore cannot be selectively reduced or oxidized using soluble reagents. This selectivity is due to the phenomenon of overpotential, the kinetic inhibition of electron transfer on a particular electrode surface.
Quantitative analysis of SILCs (stress-induced leakage currents) based on the inelastic trap-assisted tunneling model (1999)

We have successfully developed a new quantitative analytical ITAT-based SILC model which can explain both of the two field dependencies, i.e. Fowler-Nordheim (FN)-field and the direct tunneling (DT)-field dependent of A-mode and B-mode SILCs. While DT-field dependence of A-mode comes from the single trap assisted tunneling, FN-field dependence of B- mode originates at the tunneling via the multi-trap leakage path. We have also developed an analytical model for the anomalous SILC of the flash memory cell and investigate the properties of retention lifetime of failure bits. The anomalous SILC shows the DT-field dependence because of the tunneling via the incomplete multi-trap path. A remarkable behavior of retention characteristics predicted by our models is a nearly logarithmic time dependence. The Fowler- Nordheim tunneling model leads to an overestimation of lifetime at low Vth region. To take into account a position of each trap and clarify the detail characteristics of SILC, we have proposed a new Monte Carlo like approach for hopping conduction and successfully explained the anomalous SILC using only physical based parameters.
Simple theory of steam oxidation of AlAs (1999)

Kinetics of AlAs steam oxidation process is investigated theoretically in cylindrically symmetric mesa structures. Under the assumption of a steady-state process, compact analytical formulae are obtained for time evolution of the oxidation front and for the oxidation rate. Values of main oxidation process parameters are extracted from existing experimental data for T = 350 °C and the layer thickness d = 250 nm. The oxidation rate is found to first decrease from its initial value of B/A and remain almost constant for a large range of intermediate sizes of unoxidized region. When the unoxidized region becomes very small, a rapid increase in this rate up to the value of B/[A(1-β)] is predicted. This renders the process control of fabricating miniature oxide apertures with diameters < 2 μm extremely difficult. Comparison with 1D model of oxidation process in cartesian geometry reveals significant differences in time evolution of the oxidation front. Understanding these differences is important for achieving a good control of the oxidation process in cylindrical structures.
Efficient Synthesis and Host−Guest Properties of a New Class of Calix[6]azacryptands (2006)

Two members of a new class of calix[6]azacryptands, namely, calix[6]tampo and calix[6]tamb, have been synthesized through an efficient [1 + 1] macrocyclization reaction--reduction sequence. One of them has been obtained in a remarkably high overall yield from the known X(6)H(3)Me(3). In comparison to all the other calix[6]azacryptands, they possess unique conformational properties since they present a rigidified cone conformation with a partial filling of the cavity by the methoxy groups. In contrast to calix[6]tampo, the fully protonated derivative of calix[6]tamb behaves as a remarkable molecular receptor toward polar neutral guests. NMR studies have shown that the intracavity binding process is governed by a conformational flip of the aromatic walls of the calixarene core.
Assessment of the Consistency of Medicinal Chemists in Reviewing Sets of Compounds (2004)

Medicinal chemists are frequently asked to review lists of compounds to assess their drug- or leadlike nature and to evaluate the suitability of lead compounds based on their "attractiveness" and/or synthetic feasibility as a basis for launching a drug-discovery campaign. It is often felt that one medicinal chemist's opinion is as good as any other, but is it? In an attempt to answer this question, an experiment was performed in conjunction with a recent compound acquisition program (CAP) conducted at Pharmacia. Historically, the CAP included a review of many thousands of compounds by medicinal chemists who eliminate anything deemed undesirable for any reason. In a review conducted in 2002, about 22 000 compounds requiring review by medicinal chemists were broken down into 11 lists of approximately 2000 compounds each. Unknown to the medicinal chemists, a subset of 250 compounds, previously rejected by a very experienced senior medicinal chemist, was added to each of the lists. Most of the 13 medicinal chemists who participated in this process reviewed two lists, although some only reviewed a single list and one reviewed three lists. Those compounds that were deemed unacceptable were recorded and tabulated in various ways to assess the consistency of the reviews. It was found that medicinal chemists were not very consistent in the compounds they rejected as being undesirable. The inconsistency arises from the subjective analysis that all humans utilize when considering "data sets" of any kind. This has important implications for pharmaceutical project teams where individual medicinal chemists review lists of primary screening hits to identify those compounds suitable for follow-up. Once a compound is removed from a list, it and other structurally similar compounds are effectively removed from further consideration. This can also have an impact on computational chemists who are developing models for assessing the desirability or attractiveness of different classes of compounds for lead discovery.
Communications, Information, and Cyber Security in Systems-of-Systems: Assessing the Impact of Attacks through Interdependency Analysis (2014)

The analysis of risks associated with communications, and information security for a system-of-systems is a challenging endeavor. This difficulty is due to the complex interdependencies that exist in the communication and operational dimensions of the system-of-systems network, where disruptions on nodes and links can give rise to cascading failure modes. In this paper, we propose the modification of a functional dependency analysis tool, as a means of analyzing system-of-system operational and communication architectures. The goal of this research is to quantify the impact of attacks on communications, and information flows on the operability of the component systems, and to evaluate and compare different architectures with respect to their reliability and robustness under attack. Based on the topology of the network, and on the properties of the dependencies, our method quantifies the operability of each system as a function of the availability and correctness of the required input, and of the operability of the other systems in the network. The model accounts for partial capabilities and partial degradation. Robustness of the system-of-systems is evaluated in terms of its capability to maintain an adequate level of operability following a disruption in communications. Hence, different architectures can be compared based on their sensitivity to attacks, and the method can be used to guide decision both in architecting the system-of-systems and in planning updates and modifications, accounting for the impact of interdependencies on the robustness of the system-of-systems. Synthetic examples show conceptual application of the method.
A fully automated hot-wall multiplasma-monochamber reactor for thin film deposition (1991)

We present a study on the development and the evaluation of a fully automated radio-frequency glow discharge system devoted to the deposition of amorphous thin film semiconductors and insulators. The following aspects were carefully addressed in the design of the reactor: (1) cross contamination by dopants and unstable gases, (2) capability of a fully automated operation, (3) precise control of the discharge parameters, particularly the substrate temperature, and (4) high chemical purity. The new reactor, named ARCAM, is a multiplasma-monochamber system consisting of three separated plasma chambers located inside the same isothermal vacuum vessel. Thus, the system benefits from the advantages of multichamber systems but keeps the simplicity and low cost of monochamber systems. The evaluation of the reactor performances showed that the oven-like structure combined with a differential dynamic pumping provides a high chemical purity in the deposition chamber. Moreover, the studies of the effects associated with the plasma recycling of material from the walls and of the thermal decomposition of diborane showed that the multiplasma-monochamber design is efficient for the production of abrupt interfaces in hydrogenated amorphous silicon (a-Si:H) based devices. Also, special attention was paid to the optimization of plasma conditions for the deposition of low density of states a-Si:H. Hence, we also present the results concerning the effects of the geometry, the substrate temperature, the radio frequency power and the silane pressure on the properties of the a-Si:H films. In particular, we found that a low density of states a-Si:H can be deposited at a wide range of substrate temperatures (100 °C≤Ts≤300 °C).