gebhart/patrepeval huggingface dataset:
Potential Sources of Spurious Associations and Batch Effects in Genome‐Wide Association Studies (2009)

Genome-wide association studies (GWAS) use dense maps of single nucleotide polymorphisms (SNPs) that cover the entire human genome to search for genetic markers with different allele frequencies between cases and controls. Given the complexity of GWAS, it is not surprising that only a small portion of associated SNPs in the initial GWAS results were successfully replicated in the same populations. Each of the steps in a GWAS has the potential to generate spurious associations. In addition, there are batch effects in the genotyping experiments and in genotype calling that can cause both Type I and Type II errors. Decreasing or eliminating the various sources of spurious associations and batch effects is vital for reliably translating GWAS findings to clinical practice and personalized medicine. Here we review and discuss the variety of sources of spurious associations and batch effects in GWAS and provide possible solutions to the problems.
Unified multi-scale feature abstraction for medical image segmentation (2020)

Multi-scale contextual information is effective for pixel-level label prediction, i.e. image segmentation. However, such important information is only partially exploited in the existing methods. In this paper, we propose a new network architecture for unified multi-scale feature abstraction. The proposed network performs multi-scale analysis to the input image by using spatial pyramid pooling to obtain scene context information and abstract multi-scale features hierarchically. In addition, we present a new skip pathways to learn context information by fusing semantically similar features and develop a deep supervision mechanism for outputs in different scales. The proposed mechanisms relieve the gradient vanishing problem and enforce semantic feature learning. We extensively evaluated our method on the MICCAI 2017 Liver Tumor Segmentation (LiTS) Challenge Dataset and demonstrate highly competitive performance with single step operation and lightweight 2D networks.
Development of Novel, CNS Penetrant Positive Allosteric Modulators for the Metabotropic Glutamate Receptor Subtype 1 (mGlu1), Based on an N-(3-Chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide Scaffold, That Potentiate Wild Type and Mutant mGlu1 Receptors Found in Schizophrenics (2015)

The therapeutic potential of selective mGlu1 activation is vastly unexplored relative to the other group I mGlu receptor, mGlu5; therefore, our lab has focused considerable effort toward developing mGlu1 positive allosteric modulators (PAMs) suitable as in vivo proof of concept tool compounds. Optimization of a series of mGlu1 PAMs based on an N-(3-chloro-4-(1,3-dioxoisoindolin-2-yl)phenyl)-3-methylfuran-2-carboxamide scaffold provided 17e, a potent (mGlu1 EC50 = 31.8 nM) and highly CNS penetrant (brain to plasma ratio (Kp) of 1.02) mGlu1 PAM tool compound, that potentiated not only wild-type human mGlu1 but also mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenic patients. Moreover, both electrophysiological and in vivo studies indicate the mGlu1 ago-PAMs/PAMs do not possess the same epileptiform adverse effect liability as mGlu5 ago-PAMs/PAMs and maintain temporal activity suggesting a broader therapeutic window.
PD-1hiCXCR5– T peripheral helper cells promote B cell responses in lupus via MAF and IL-21 (2019)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathologic T cell-B cell interactions and autoantibody production. Defining the T cell populations that drive B cell responses in SLE may enable design of therapies that specifically target pathologic cell subsets. Here, we evaluated the phenotypes of CD4+ T cells in the circulation of 52 SLE patients drawn from multiple cohorts and identified a highly expanded PD-1hiCXCR5-CD4+ T cell population. Cytometric, transcriptomic, and functional assays demonstrated that PD-1hiCXCR5-CD4+ T cells from SLE patients are T peripheral helper (Tph) cells, a CXCR5- T cell population that stimulates B cell responses via IL-21. The frequency of Tph cells, but not T follicular helper (Tfh) cells, correlated with both clinical disease activity and the frequency of CD11c+ B cells in SLE patients. PD-1hiCD4+ T cells were found within lupus nephritis kidneys and correlated with B cell numbers in the kidney. Both IL-21 neutralization and CRISPR-mediated deletion of MAF abrogated the ability of Tph cells to induce memory B cell differentiation into plasmablasts in vitro. These findings identify Tph cells as a highly expanded T cell population in SLE and suggest a key role for Tph cells in stimulating pathologic B cell responses.
Enhancement of resolution and linearity control of contact-hole resist patterns with surface-active developer (1994)

The resolution enhancement of contact-hole resist patterns featuring precise linear correlation between mask size and resist-pattern size by employing a surface-active developer is presented. The addition of surfactant improves the wettability of the developer, thus enabling the solution to penetrate narrow spaces. The optimum surfactant concentration in developer leads to superior resist performance. This technology for contact-hole patterning results in high resolution, high sensitivity, and a wide process margin for ULSI manufacturing.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Method for Measuring Short Crack R-Curve Behavior of Ferroelectric Ceramic (1999)

Abstract This work describes a method for measurement of R-curve behavior in ferroelectric ceramics using four point bending specimens with a controlled surface crack. A short surface crack is produced by a Knoop indentation and the damage zone is polished away. The results are compared for two compositions of lead lanthanum zirconate titanate (PLZT), an elastio-plastic ferroelectric composition and a linear elastic electrostrictive composition. R-curves are measured in the crack length regime of 0.1 to 0.8 mm. The ferroelastic composition displays a toughness increase from 0.7 to 1.4 MPam. The linear elastic composition displays a constant toughness of between 0.6 and 0.7 MPa√m. The R-curve behavior of PLZT 8/65/35 is attributed to ferroelastic toughening.
960 TT-816, a novel small molecule immune checkpoint inhibitor targeting cannabinoid CB2receptor, stimulates innate and adaptive immunity for cancer therapy (2022)

<h3>Background</h3> The endocannabinoid system is widely expressed in the human body, including the innate and adaptive immune system, where endocannabinoids, Δ9-tetrahydrocannabinol and synthetic ligands regulate immune response. The effects of endocannabinoids on immune regulation are primarily mediated by G-protein coupled cannabinoid CB<sub>2</sub> receptors (CB<sub>2</sub>R) via several mechanisms, including development, migration, proliferation and effector functions. The upregulated expression of CB<sub>2</sub>R and elevated levels of endocannabinoids have been observed in a variety of tumor microenvironments and are associated with the aggressiveness of cancer. <h3>Methods</h3> Membranes prepared from CHO-K1 cells stably expressing human CB<sub>2</sub>R were used for receptor binding assays in the presence of TT-816 and [3H]CP-55,940, and for GTPγS binding assay in the presence of TT-816, 10 μM GDP and 0.3 nM [35S]GTPγS. cAMP assay was performed by incubating the CHO-K-1 cells for 30 min with TT-816, 25 μM forskolin and 12 nM CP-55,940, or with TT-816 and 5 μM forskolin. NK cell function was determined by co-culturing TT-816 pretreated NK cells with K562 cancer cells for 24 hours. The mixed lymphocyte reaction assay was conducted by co-culturing human CD4+ T cells with monocyte-derived dendritic cells. Cell viability was measured by FACS and IFN-γ by MSD. <h3>Results</h3> TT-816 is a competitive and selective CB<sub>2</sub>R antagonist. It bound to human CB<sub>2</sub>R with an IC50 26.2 nM, showing greater than 380-fold selectivity over cannabinoid CB<sub>1</sub> receptors. The ability of TT-816 to inhibit the constitutive activity of CB<sub>2</sub>R was characterized in both GTPγS and cAMP assays. TT-816 concentration-dependently inhibited the basal GTPγS binding response, antagonized CB<sub>2</sub>R agonist-mediated cAMP production and enhanced the forskolin response on basal cAMP level. Consistent with its inhibition of CB<sub>2</sub>R function, TT-816 inhibited the growth of human breast, colorectal and lung cancer cells. In addition, TT-816 concentration-dependently enhanced the functions of NK cells, dendritic cells and T cells. It increased NK cell killing of the human cancer cells and IFN-γ production, significantly stimulated the expression of CD86, HLA-DR, IL-12 and TNF-a in monocyte-derived dendritic cells, and enhanced CD4+ T cell proliferation and IFN-γ production in a mixed lymphocyte reaction assay. <h3>Conclusions</h3> TT-816 is a novel, oral small molecule immune checkpoint inhibitor that selectively blocks CB<sub>2</sub>R on cancer cells and immune cells. Preclinical data have demonstrated that it stimulates antitumor innate and adaptive immune response and inhibits cancer cell proliferation. TT-816 is currently undergoing phase 1 clinical trials for the treatment of a broad range of solid tumors.
Near Optimal Broadcast with Network Coding in Large Sensor Networks (2007)

International audience
Micrometer-Scale Ballistic Transport of Electron Pairs inLaAlO3/SrTiO3Nanowires (2016)

High-mobility complex-oxide heterostructures and nanostructures offer new opportunities for extending the paradigm of quantum transport beyond the realm of traditional III-V or carbon-based materials. Recent quantum transport investigations with LaAlO_{3}/SrTiO_{3}-based quantum dots reveal the existence of a strongly correlated phase in which electrons form spin-singlet pairs without becoming superconducting. Here, we report evidence for the micrometer-scale ballistic transport of electron pairs in quasi-1D LaAlO_{3}/SrTiO_{3} nanowire cavities. In the paired phase, Fabry-Perot-like quantum interference is observed, in sync with conductance oscillations observed in the superconducting regime (at a zero magnetic field). Above a critical magnetic field B_{p}, the electron pairs unbind and the conductance oscillations shift with the magnetic field. These experimental observations extend the regime of ballistic electronic transport to strongly correlated phases.
Supraoptimal Peptide–Major Histocompatibility Complex Causes a Decrease in Bcl-2 Levels and Allows Tumor Necrosis Factor α Receptor II–mediated Apoptosis of Cytotoxic T Lymphocytes (1998)

Cytotoxic T lymphocytes (CTLs) are primary mediators of viral clearance, but high viral burden can result in deletion of antigen-specific CTLs. We previously reported a potential mechanism for this deletion: tumor necrosis factor (TNF)-alpha-mediated apoptosis resulting from stimulation with supraoptimal peptide-major histocompatibility complex. Here, we show that although death is mediated by TNF-alpha and its receptor (TNF-RII), surprisingly neither the antigen dose dependence of TNF-alpha production nor that of TNF-RII expression can account for the dose dependence of apoptosis. Rather, a previously unrecognized effect of supraoptimal antigen in markedly decreasing levels of the antiapoptotic protein Bc1-2 was discovered and is likely to account for the gain in susceptibility or competence to sustain the death signal through TNF-RII. This decrease requires a signal through the TCR, not just through TNF-RII. Although death mediated by TNF-RII is not as widely studied as that mediated by TNF-RI, we show here that it is also dependent on proteolytic cleavage by caspases and triggered by a brief initial encounter with antigen. These results suggest that determinant density can regulate the immune response by altering the sensitivity of CTLs to the apoptotic effects of TNF-alpha by decreasing Bc1-2 levels.
Evidence that bacteriophage λ lysogens may induce in response to the proton motive force uncoupler CCCP (2015)

We describe a genetic β-galactoside reporter system using a disk diffusion assay on MacConkey Lactose agar petri plates to monitor maintenance of the bacteriophage λ prophage state and viral induction in Escherichia coli K-12. Evidence is presented that the phage λ major lytic promoters, pL and pR, are activated when cells containing the reporters are exposed to the energy poison carbonyl cyanide m-chlorophenyl hydrazine, CCCP. This uncoupler of oxidative phosphorylation inhibits ATP synthesis by collapsing the proton motive force. Expression of the λ lytic promoters in response to CCCP requires host RecA function and an autocleavable CI repressor, as does SOS induction of the λ prophage that occurs by a DNA damage-dependent pathway. λ Cro function is required for CCCP-mediated activation of the λ lytic promoters. CCCP does not induce an sfi-lacZ SOS reporter.
Exploiting spatio-temporal characteristics of human vision for mobile video applications (2008)

Video applications on handheld devices such as smart phones pose a significant challenge to achieve high quality user experience. Recent advances in processor and wireless networking technology are producing a new class of multimedia applications (e.g. video streaming) for mobile handheld devices. These devices are light weight and have modest sizes, and therefore very limited resources - lower processing power, smaller display resolution, lesser memory, and limited battery life as compared to desktop and laptop systems. Multimedia applications on the other hand have extensive processing requirements which make the mobile devices extremely resource hungry. In addition, the device specific properties (e.g. display screen) significantly influence the human perception of multimedia quality. In this paper we propose a saliency based framework that exploits the structure in content creation as well as the human vision system to find the salient points in the incoming bitstream and adapt it according to the target device, thus improving the quality of new adapted area around salient points. Our experimental results indicate that the adaptation process that is cognizant of video content and user preferences can produce better perceptual quality video for mobile devices. Furthermore, we demonstrated how such a framework can affect user experience on a handheld device.
Screening of novel immunogenic cell death inducers within the NCI Mechanistic Diversity Set (2014)

Immunogenic cell death (ICD) inducers can be defined as agents that exert cytotoxic effects while stimulating an immune response against dead cell-associated antigens. When initiated by anthracyclines, ICD is accompanied by stereotyped molecular changes, including the pre-apoptotic exposure of calreticulin (CRT) on the cell surface, the lysosomal secretion of ATP during the blebbing phase of apoptosis, and the release of high mobility group box 1 (HMGB1) from dead cells. By means of genetically engineered human osteosarcoma U2OS cells, we screened the 879 anticancer compounds of the National Cancer Institute (NCI) Mechanistic Diversity Set for their ability to promote all these hallmarks of ICD in vitro. In line with previous findings from our group, several cardiac glycosides exhibit a robust propensity to elicit the major manifestations of ICD in cultured neoplastic cells. This screen pointed to septacidin, an antibiotic produced by <i>Streptomyces fibriatus</i>, as a novel putative inducer of ICD. In low-throughput validation experiments, septacidin promoted CRT exposure, ATP secretion and HGMB1 release from both U2OS cells and murine fibrosarcoma MCA205 cells. Moreover, septacidin-killed MCA205 cells protected immunocompetent mice against a re-challenge with living cancer cells of the same type. Finally, the antineoplastic effects of septacidin on established murine tumors were entirely dependent on T lymphocytes. Altogether, these results underscore the suitability of the high-throughput screening system described here for the identification of novel ICD inducers.
Clinical evaluation of a new block sequential regularized expectation maximization (BSREM) reconstruction algorithm in PET/CT studies (2014)

2097 Objectives To compare the properties of a new BSREM reconstruction algorithm to the clinically widespread ordered subset expectation maximization (OSEM) algorithm in oncologic PET/CT studies. Methods Forty-eight reconstructions of (18)F-FDG-PET/CT studies of 6 patients were analyzed. Images were reconstructed with BSREM or OSEM algorithm with/without Time of Flight (TOF) corrections. All reconstructions included Point Spread Function (PSF) correction. OSEM reconstruction post-filtering was 4.0mm FWHM, while BSREM did not utilize post-filtering. Evaluation of image quality (GIQ) was performed on a five-point scale. The other four categories by a four-point scale: artifacts (category 1), lesion detectability (category 2), noise (category 3), and image sharpness (category 4). In a first analysis, BSREM data sets with/without TOF correction and a regularization setting of 300, 350, and 400 were evaluated. In a second analysis, 40 data (10 pat.) sets using BSREM, with a regularization setting of 400, was compared with OSEM. Mean ± STD and Wilcoxon test were obtained. Results BSREM - TOF reconstruction sets showed best results in all categories (1.33 ± 0.58 in GIQ and 1.0 ± 0.0 in all other categories; p> 0.05 in category 2 for BSREM - TOF vs. OSEM - TOF and p Conclusions The BSREM reconstruction algorithm shows relevant improvement of image quality compared to OSEM reconstruction in PET-CT-studies, especially for TOF-PET data.
Nanospectroscopy of single quantum dots with local strain control using a phase-change mask (2017)

International audience
Force Sensor Integrated Surgical Forceps for Minimally Invasive Robotic Surgery (2015)

This paper presents a novel surgical instrument integrated with a four-degree-of-freedom (DOF) force sensor. By adopting the capacitive transduction principle, the sensor enables the direct sensing of normal and shear forces at surgical instrument tips. Thus, three-DOF pulling forces and a single-DOF grasping force can be measured for haptic feedback control of robotic minimally invasive surgery systems. The sensor consists of four capacitive transducers, and all the transducers including analog signal processing units are embedded in small surgical instrument tips. The four-DOF force sensing is enabled thanks to the four capacitive transducers by using the force transformation method. In this study, the instrument is designed and manufactured to be adaptable to the open-source surgical robot platform, called Raven-II. In addition, the sensing system is experimentally validated through its application to the Raven-II by using a reference force sensor.
Deep-Sequencing Method for Quantifying Background Abundances of Symbiodinium Types: Exploring the Rare Symbiodinium Biosphere in Reef-Building Corals (2014)

The capacity of reef-building corals to associate with environmentally-appropriate types of endosymbionts from the dinoflagellate genus Symbiodinium contributes significantly to their success at local scales. Additionally, some corals are able to acclimatize to environmental perturbations by shuffling the relative proportions of different Symbiodinium types hosted. Understanding the dynamics of these symbioses requires a sensitive and quantitative method of Symbiodinium genotyping. Electrophoresis methods, still widely utilized for this purpose, are predominantly qualitative and cannot guarantee detection of a background type below 10% of the total Symbiodinium population. Here, the relative abundances of four Symbiodinium types (A13, C1, C3, and D1) in mixed samples of known composition were quantified using deep sequencing of the internal transcribed spacer of the ribosomal RNA gene (ITS-2) by means of Next Generation Sequencing (NGS) using Roche 454. In samples dominated by each of the four Symbiodinium types tested, background levels of the other three types were detected when present at 5%, 1%, and 0.1% levels, and their relative abundances were quantified with high (A13, C1, D1) to variable (C3) accuracy. The potential of this deep sequencing method for resolving fine-scale genetic diversity within a symbiont type was further demonstrated in a natural symbiosis using ITS-1, and uncovered reef-specific differences in the composition of Symbiodinium microadriaticum in two species of acroporid corals (Acropora digitifera and A. hyacinthus) from Palau. The ability of deep sequencing of the ITS locus (1 and 2) to detect and quantify low-abundant Symbiodinium types, as well as finer-scale diversity below the type level, will enable more robust quantification of local genetic diversity in Symbiodinium populations. This method will help to elucidate the role that background types have in maximizing coral fitness across diverse environments and in response to environmental change.
Measurements of electroweak $$Wjj $$ W j j production and constraints on anomalous gauge couplings with the ATLAS detector (2017)

Measurements of the electroweak production of a <i>W</i> boson in association with two jets at high dijet invariant mass are performed using [Formula: see text] 7 and 8 [Formula: see text] proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb[Formula: see text] of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a <i>W</i> boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process.
Influenza A viruses and PI3K (2012)

Influenza A viruses activate the host phosphoinositide 3-kinase (PI3K) signaling pathway at several stages of their replication cycle, which depending upon the stage can have pro- or anti-viral consequences. For example, transient PI3K activation due to virion attachment appears to promote virus entry, while pathogen recognition receptor-mediated PI3K signaling may contribute to host innate immune defenses. In addition, the viral NS1 protein, a multifunctional virulence factor, directly binds and activates PI3K to enhance efficient virus replication. Here, we comment on the strain-specific viral requirement for NS1-activated PI3K in vitro and in vivo. Our observations with NS1 suggest that to clarify the complex interplay between PI3K signaling and viral activators, it is essential to understand the temporal and spatial patterns of kinase activation, as well as the specific PI3K subclass and enzyme isotypes involved. It is likely that each independent activation event regulates individual pathways with distinct biological outcomes.
Picosecond Electronic Relaxation in CdS/HgS/CdS Quantum Dot Quantum Well Semiconductor Nanoparticles (1996)

Subpicosecond photoexcitation of CdS/HgS/CdS quantum dot quantum well nanoparticles at wavelengths shorter than their interband absorption (390 nm) leads to a photobleach spectrum at longer wavelengths (440−740 nm). The photobleach spectrum changes and its maximum red-shifts with delay time. These results are explained by the rapid quenching of the initially formed laser-excited excitons by two types of energy acceptors (traps); one is proposed to be due to CdS molecules at the CdS/HgS interface, and the other trap is that present in the CdS/HgS/CdS well. The results of the excitation at longer wavelengths as well as the formation and decay of the bleach spectrum at different wavelengths support this description.