gebhart/patrepeval huggingface dataset:
A high throughput screen for inhibitors of nematode detoxification genes (2014)

Nematodes parasitize ∼1/3 of humans world-wide. Although current anthelmintics are effective against many nematode infections, there is growing concern that resistance could threaten this mode of treatment. Pharmacological compounds that target xenobiotic detoxification pathways, which lead to multidrug resistance can greatly increase the useful life of current and future anthelmintics. The transcription factor SKN-1 is essential for the development of nematode embryos and activates the expression of ∼65 genes predicted to promote modification, conjugation, or export of drugs [1]. We have identified a major pathway regulating SKN-1 that is distinct from the major pathway regulating xenobiotic detoxification in mammals. SKN-1 also binds to target DNA by a unique monomeric mechanism relative to all other known basic leucine zipper factors [2,3]. Hence, SKN-1 is a promising target for the development of inhibitors that disrupt embryonic development, decrease stress resistance, and inhibit xenobiotic detoxification in nematodes without affecting homologous pathways in humans. We have successfully carried out a HTS screening of the MLSMR library to identify inhibitors of the transcriptional activation of the SKN-1 pathway in C. elegans through use of promoters of the SKN-1 target gene gst-4 (Pgst-4::GFP), which can be detected through simple fluorescence measurements. We report for the first time a small molecule inhibitor of the SKN-1 pathway, ML358, which resulted from a vanillamine derived scaffold identified from the HTS program and advanced through analog synthesis and structure-activity studies. ML358 is a potent (IC50 = 0.24□μM, Emax = 100%) and selective inhibitor of the SKN-1 pathway in C. elegans. ML358 is non-toxic to both C. elegans (LC50 > 64 μM) and Fa2N-4 immortalized human hepatocytes (LC50 > 50μM). In addition, ML358, has good solubility, permeability, chemical and metabolic stability in human and mouse liver microsomes. ML358 is a valuable probe to study the function and relevance of the transcription factor SKN-1 in drug detoxification and resistance in parasitic nematodes. Currently available drugs target only a specific enzyme or enzyme class and/or affect homologous human targets. By selective targeting of the SKN-1 pathway present in diverse nematode clades, ML358 can potentially lead to drug candidates that could be used as adjuvants to increase the efficacy of current anthelmintics.
Tailored and anisotropic dielectric constants through porosity in ceramic components (2005)

In this paper, different densities within a ceramic are used to provide a wide continuous range of dielectric constants for high-frequency applications. Cofiring different ceramic materials together to make a single unified structure to obtain different dielectric constant combinations is quite difficult due to phase stability issues and shrinkage mismatches. However, using various levels of porosity in order to alter the effective dielectric constant in the same material allows patterning different dielectric constants into a single unit. Since the structure is made from a single material, the varying porosity regions can be made compatible. Glassy-carbon-assisted and microcellular-structure-based porous titania allow for an extremely wide range of dielectric constants, ranging from 12 to 90, while maintaining a low loss tangent. Highly anisotropic materials are demonstrated herein to achieve a dielectric constant contrast of 90/9.6 using large-range aligned microcellular structure. Dielectric-resonator antennas are shown as an application of adjusting the bandwidth between 0.5% and 2.5% by tailoring the ceramic dielectric constant. A stratified-medium-loaded cavity resonator and a buried dielectric ring resonator internal to a microcellular substrate are used to demonstrate both the cofiring and variable dielectric constant capabilities of structured porosity.
Efficient handling of concept drift and concept evolution over Stream Data (2016)

To decide if an update to a data stream classifier is necessary, existing sliding window based techniques monitor classifier performance on recent instances. If there is a significant change in classifier performance, these approaches determine a chunk boundary, and update the classifier. However, monitoring classifier performance is costly due to scarcity of labeled data. In our previous work, we presented a semi-supervised framework SAND, which uses change detection on classifier confidence to detect a concept drift. Unlike most approaches, it requires only a limited amount of labeled data to detect chunk boundaries and to update the classifier. However, SAND is expensive in terms of execution time due to exhaustive invocation of the change detection module. In this paper, we present an efficient framework, which is based on the same principle as SAND, but exploits dynamic programming and executes the change detection module selectively. Moreover, we provide theoretical justification of the confidence calculation, and show effect of a concept drift on subsequent confidence scores. Experiment results show efficiency of the proposed framework in terms of both accuracy and execution time.
Conditioned immune response associated with allogeneic skin grafts in mice. (1982)

Groups of CBA mice were given sham skin grafts (conditioned stimulus, CS) or alloantigen only (unconditioned stimulus, US; C57BL/6 lymphoid cells inoculated i.p.). A further group of animals received simultaneous US and CS (alloantigen (US), in this case actually given in the context of a C57BL/6 skin graft). The peripheral blood leukocyte (PBL) pool of all animals was analyzed in tissue culture for the frequency of cytotoxic T lymphocyte precursors (CTLp) specific for alloantigens on the grafted tissue. After three "conditioning" trials, spaced at intervals to allow recovery in all groups of the CTLp frequency to that of naive control mice, individuals in all groups were sham-grafted (given CS alone). PBL of these mice were tested 2 days after removal of the casts. Only group CS + US, and only some 50 to 60% of these, were able to show a "conditioned" increase in the CTLp frequency specific for alloantigens of the grafted tissue after sham-grafting. When these "responder" mice were subdivided into two groups that were subsequently given two trials of CS only or CS + US, followed by retesting with CS alone, either extinction or reinforcement of the previously conditioned response was observed.
Abstract 8877: Redefining the Role of Angiotensin II Type 1 and Type 2 Receptors in Cardiomyocyte Apoptosis (2011)

Purpose of the study: Angiotensin II exerts its effects by activating its receptors, primarily type 1 (AT1R) and type 2 (AT2R). The role of AT1R and AT2R in cardiomyocyte apoptosis remains controversial. To define the precise role of AT1R and AT2R on cardiomyocyte biology, we studied the apoptotic response of AT1R or AT2R overexpression in HL-1 cardiomyocytes. Materials and Methods: HL-1 cells were transfected with AT1R and AT2R cDNA, and cell apoptosis and the expressions of apoptotic genes, NADPH oxidase, ROS, iNOS and eNOS were detected in this study. Results: We observed that AT1R overexpression increased endogenous AT2R expression, but AT2R overexpression did not affect endogenous AT1R expression. Caspase-3 staining, cell cycle analysis and Bax/Bcl2 Western analysis indicated that overexpression of AT1R or AT2R resulted in cardiomyocyte apoptosis (Fig A). Further, we observed that AT1R overexpression significantly increased Nox2, p47 phox and p67 phox (subunits of NADPH oxidase) and ROS generation; in contrast, AT2R overexpression decreased p67 phox expression without significant effect on other NADPH oxidase subunits or ROS generation (Fig B). Both AT1R and AT2R overexpression markedly increased iNOS expression (AT2R&gt;AT1R) (Fig B). To delineate the contribution of upregulation of AT2R by AT1R overexpression and subsequent increase in iNOS resulting in apoptosis in cardiomyocytes; AT1R over-expressing cells were treated with AT2R blocker PD133319; this treatment significantly inhibited AT1R overexpression-induced iNOS and apoptosis. Conclusion: These findings suggest that AT2R overexpression induces cardiomyocyte apoptosis via iNOS upregulation; AT1R overexpression induces cardiomyocyte apoptosis at least in part via endogenous AT2R increase and resultant upregulation of iNOS.
Novel Hybrid Quadrupole-Multireflecting Time-of-Flight Mass Spectrometry System (2023)

A novel mass spectrometry system is described here comprising a quadrupole-multireflecting time-of-flight design. The new multireflecting time-of-flight analyzer has an effective path length of 48 m and employs planar, gridless ion mirrors providing fourth-order energy focusing resulting in resolving power over 200 000 fwhm and sub-ppm mass accuracy. We show how these attributes are maintained with relatively fast acquisition speeds, setting the system apart from other high resolution mass spectrometers. We have integrated this new system into both liquid chromatography-mass spectrometry and mass spectrometry imaging workflows to demonstrate how the instrument characteristics are of benefit to these applications.
Fatty acid synthase is a metabolic marker of cell proliferation rather than malignancy in ovarian cancer and its precursor cells (2014)

Ovarian cancer (OC) is caused by genetic aberrations in networks that control growth and survival. Importantly, aberrant cancer metabolism interacts with oncogenic signaling providing additional drug targets. Tumors overexpress the lipogenic enzyme fatty acid synthase (FASN) and are inhibited by FASN blockers, whereas normal cells are FASN-negative and FASN-inhibitor-resistant. Here, we demonstrate that this holds true when ovarian/oviductal cells reside in their autochthonous tissues, whereas in culture they express FASN and are FASN-inhibitor-sensitive. Upon subculture, nonmalignant cells cease growth, express senescence-associated β-galactosidase, lose FASN and become FASN-inhibitor-resistant. Immortalized ovarian/oviductal epithelial cell lines—although resisting senescence—reveal distinct growth activities, which correlate with FASN levels and FASN drug sensitivities. Accordingly, ectopic FASN stimulates growth in these cells. Moreover, FASN levels and lipogenic activities affect cellular lipid composition as demonstrated by thin-layer chromatography. Correlation between proliferation and FASN levels was finally evaluated in cancer cells such as HOC-7, which contain subclones with variable differentiation/senescence and corresponding FASN expression/FASN drug sensitivity. Interestingly, senescent phenotypes can be induced in parental HOC-7 by differentiating agents. In OC cells, FASN drugs induce cell cycle blockade in S and/or G2/M and stimulate apoptosis, whereas in normal cells they only cause cell cycle deceleration without apoptosis. Thus, normal cells, although growth-inhibited, may survive and recover from FASN blockade, whereas malignant cells get extinguished. FASN expression and FASN drug sensitivity are directly linked to cell growth and correlate with transformation/differentiation/senescence only indirectly. FASN is therefore a metabolic marker of cell proliferation rather than a marker of malignancy and is a useful target for future drug development.
Genotyping‐by‐sequencing through transcriptomics: implementation in a range of crop species with varying reproductive habits and ploidy levels (2017)

The application of genomics in crops has the ability to significantly improve genetic gain for agriculture. Many marker-dense tools have been developed, but few have seen broad adoption in plant genomics due to issues of significant variations of genome size, levels of ploidy, single nucleotide polymorphism (SNP) frequency and reproductive habit. When combined with limited breeding activities, small research communities and scant sequence resources, the suitability of popular systems is often suboptimal and routinely fails to effectively balance cost-effectiveness and sample throughput. Genotyping-by-sequencing (GBS) encompasses a range of protocols including resequencing of the transcriptome. This study describes a skim GBS-transcriptomics (GBS-t) approach developed to be broadly applicable, cost-effective and high-throughput while still assaying a significant number of SNP loci. A range of crop species with differing levels of ploidy and degree of inbreeding/outbreeding were chosen, including perennial ryegrass, a diploid outbreeding forage grass; phalaris, a putative segmental allotetraploid outbreeding forage grass; lentil, a diploid inbreeding grain legume; and canola, an allotetraploid partially outbreeding oilseed. GBS-t was validated as a simple and largely automated, cost-effective method which generates sufficient SNPs (from 89 738 to 231 977) with acceptable levels of missing data and even genome coverage from c. 3 million sequence reads per sample. GBS-t is therefore a broadly applicable system suitable for many crops, offering advantages over other systems. The correct choice of subsequent sequence analysis software is important, and the bioinformatics process should be iterative and tailored to the specific challenges posed by ploidy variation and extent of heterozygosity.
Organic Solar Cells Using Transparent SnO2–F Anodes (2006)

Copper phthalocyanine/C60/2,9- dimethyl-4,7-diphenyl-1,10-phenanthroline/Ag heterojunction organic solar cells are grown on low-cost SnO2–F-coated glass using organic vapor-phase deposition (see figure). The bulk heterojunction (BHJ) solar cell with nanoscale CuPc protrusions shows a 2.5 % power-conversion efficiency under 1 sun illumination. The high efficiency in BHJ solar cells is attributed to the increased exciton dissociation efficiency at the CuPc/C60 interface.
New 40kV / 300kVA Quasi-2-Level Operated 5-Level Flying Capacitor SiC “Super-Switch” IPM (2019)

Emerging applications, e.g., traction systems and utility scale renewable energy systems, demand for Medium Voltage (MV)power electronic switches with blocking capabilities above 20kV, which cannot be provided with today's 10kV or 15kV SiC power semiconductors. Therefore, this work investigates different concepts for the realization of a MV half-bridge, i.e., a series connection of 10kV SiC MOSFETs, a JFET Super Cascode arrangement, and Modular Multilevel Converter (MMCs)and Flying Capacitor Converter (FCCs)topologies. The FCC topology features several advantages such as reduced switching losses, reduced chip area, lower dv/dt of the switching transitions, and robust voltage balancing. Moreover, the volume of the flying capacitors can be reduced with Quasi-2-Level (Q2L) operation of the half-bridge, where the intermediate voltage levels are only used during very short time intervals, i.e., during the switching transitions. This paper analyzes the design, the switching behavior, and the voltage balancing of the Q2L-FCC bridge-leg and confirms its suitability as a versatile MV switch. Finally, the integration of a complete bridge-leg, including gate drivers, isolated cooling interfaces, measurements, and Q2L control into a 300 kVA/40 kV SiC Super-Switch Intelligent Power Module (SiC-SS-IPM)is presented.
CRAC channel inhibitors block cytokine production with a pattern distinguishable from cyclosporine (P5216) (2013)

Abstract Engagement of the T cell receptor (TCR) triggers complex signaling cascades that result in various effector T cell responses. A critical component of TCR signaling is store-operated calcium entry (SOCE) that occurs through the activation of calcium release-activated calcium (CRAC) channels. Activated CRAC channels cause an increase in cytoplasmic calcium, which results in the transcription of calcineurin/NFAT-dependent genes involved in T cell proliferation and cytokine production. Both CRAC channel inhibitors and calcineurin inhibitors are known to inhibit T cell function. However, the relative impact of CRAC channel inhibitors and calcineurin inhibitors on Th1, Th2, Th17, and Treg functions are not known. Using anti-CD3/anti-CD28 to stimulate cytokine production by peripheral blood mononuclear cells (PBMCs), we demonstrate that novel CalciMedica CRAC channel inhibitors have a pattern of cytokine inhibition that is different from the calcineurin inhibitor cyclosporine (CsA). CRAC channel inhibitors inhibit Th1 and Th17 cytokines (IFNγ and IL-17) more potently than Treg and Th2 cytokines (IL-10 and IL-4), while CsA inhibits IL-10 more potently than IFNγ, IL-4, and IL-17. These results suggest that CRAC channel inhibitors and CsA have different potencies against different effector T cell subsets, and that CRAC channel inhibitors may achieve a more favorable balance of effects on pro- versus anti-inflammatory pathways in immune disorders.
Kagome-fiber-based pulse compression of mid-infrared picosecond pulses from a Ho:YLF amplifier: publisher’s note (2016)

This publisher’s note identifies an error in the published version of Fig. 1 of Optica3, 816 (2016)10.1364/OPTICA.3.000816.
Dealloying Silver/Gold Alloys in Neutral Silver Nitrate Solution: Porosity Evolution, Surface Composition, and Surface Oxides (2008)

The electrochemistry of dealloying silver/gold alloys in neutral pH silver nitrate solution to form nanoporous gold (NPG) is discussed. At pH 7, porosity evolution was observed to occur at high potentials, above that required for oxygen evolution, and within the nominal domain of the Pourbaix diagram where silver would be expected to form a passivating oxide. Electron microscopy shows that a small pore NPG is formed over a potential regime of vs normal hydrogen electrode, but electrochemical measurements show that the specific capacitance of samples over the same voltage range rises nearly threefold. The observations are explained in terms of residual surface oxides passivating the pores behind the dissolution front, which is itself acidified (and thus corrosive) due to an accumulation of protons associated with oxide formation and water dissociation. A model is proposed that is consistent with the electrochemical and microscopy results. This method of fabricating NPG has advantages of simplicity and safety, and the porosity formation mechanism may be extended to other systems.
Discriminatively trained Bayesian speaker comparison of i-vectors (2013)

This paper presents a framework for fully Bayesian speaker comparison of i-vectors. By generalizing the train/test paradigm, we derive an analytic expression for the speaker comparison log-likelihood ratio (LLR), as well as solutions for model training and Bayesian scoring. This framework is useful for enrollment sets of any size. For the specific case of single-cut enrollment, it is shown to be mathematically equivalent to probabilistic linear discriminant analysis (PLDA). Additionally, we present discriminative training of model hyper-parameters by minimizing the total cross entropy between LLRs and class labels. When applied to speaker recognition, significant performance gains are observed for various NIST SRE 2010 extended evaluation tasks.
Cloud-enabled privacy-preserving collaborative learning for mobile sensing (2012)

In this paper, we consider the design of a system in which Internet-connected mobile users contribute sensor data as training samples, and collaborate on building a model for classification tasks such as activity or context recognition. Constructing the model can naturally be performed by a service running in the cloud, but users may be more inclined to contribute training samples if the privacy of these data could be ensured. Thus, in this paper, we focus on privacy-preserving collaborative learning for the mobile setting, which addresses several competing challenges not previously considered in the literature: supporting complex classification methods like support vector machines, respecting mobile computing and communication constraints, and enabling user-determined privacy levels. Our approach, Pickle, ensures classification accuracy even in the presence of significantly perturbed training samples, is robust to methods that attempt to infer the original data or poison the model, and imposes minimal costs. We validate these claims using a user study, many real-world datasets and two different implementations of Pickle.
Internal Mammary Artery Anomalies (1990)

The internal mammary arteries (IMA) are considered to be the superior conduit in coronary bypass grafting (CABG). Anomalies of an IMA can influence the surgical technique and results; their true incidence is not well known. The IMA's were visualised angiographically in 262 consecutive patients undergoing cardiac catheterisation prior to CABG. Satisfactory visualisation was possible of 459/524 IMA's studied (88%). A total of 118/459 (26%) surgically significant anomalies was observed in 79/262 patients (30%): common origin of another large artery in 48/459 (11%), large side branches in 41/459 (9%), tortuosity in 21/459 (5%), atypical course or origin in 5/459 (1%), atherosclerotic lesions in 2/459 (0.4%) and spasticity of an IMA in 1/459 (0.2%). Angiographic visualisation of the IMA's resulted in modification of surgical strategy in 11/262 patients (4%); meticulous preparation because of difficult or atypical IMA anatomy was necessary in 68/262 patients (26%). These results demonstrate that significant anomalies of the IMA which might--when unrecognized--jeopardize IMA-flow after CABG are relatively common; they might escape detection during IMA take-down but can be diagnosed by angiography during catheterisation.
Flow Characteristics and Spillage Mechanisms of an Inclined Quad-Vortex Range Hood Subject to Influence from Draft (2014)

The flow and spillage characteristics of an inclined quad-vortex (IQV) range hood subject to the influence of drafts from various directions were studied. The laser-assisted smoke flow visualization technique was used to reveal the flow characteristics, and the tracer-gas (sulfur hexafluoride) concentration detection method was used to indicate the quantitative values of the capture efficiency of the hood. It was found that the leakage mechanisms of the IQV range hood are closely related to the flow characteristics. A critical draft velocity of about 0.5 m/s and a critical face velocity of about 0.25 m/s for the IQV range hood were found. When the IQV range hood was influenced by a draft with a velocity larger than the critical draft velocity, the spillage of pollutants became significant and the pollutant spillage rate increased with increasing draft velocity. At draft velocities less than or equal to the critical value, no containment leakages induced by the turbulence diffusion, reverse flow, or boundary-layer separation were observed, and the capture efficiency was about 100%. The IQV range hood exhibited a high ability to resist the influences of lateral and frontal drafts. The capture efficiency of the IQV range hood operated at the suction flow rate 5 to 9 m(3)/min is higher than that of the conventional range hood operated at 11 to 15 m(3)/min.