gebhart/patrepeval huggingface dataset:
Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic Control of the Membrane Metallo-Endopeptidase (2016)

Neuroendocrine tumors (NET) often harbor loss-of-function mutations in the MEN1 and DAXX tumor suppressor genes. Here, we report that the products of these genes, menin and Daxx, interact directly with each other to suppress the proliferation of NET cells, to a large degree by inhibiting expression of the membrane metallo-endopeptidase (MME). Menin and Daxx were required to enhance histone H3 lysine9 trimethylation (H3K9me3) at the MME promoter, as mediated partly by the histone H3 methyltransferase SUV39H1. Notably, the menin T429K mutation associated with a NET syndrome reduced Daxx binding, MME repression, and proliferation of NET cells. Conversely, inhibition of MME in NET cells repressed proliferation and tumor growth in vivo Our findings reveal a previously unappreciated cross-talk between two crucial tumor suppressor genes thought to work by independent pathways, focusing on MME as a common target of menin/Daxx to treat NET. Cancer Res; 77(2); 401-11. ©2016 AACR.
Raloxifene inhibits bone turnover and prevents further cancellous bone loss in adult ovariectomized rats with established osteopenia. (1996)

Estrogen (E) treatment has proven to be effective in preventing bone loss after menopause with, however, some undesirable side effects. Many of these side effects are related to the hormone's actions on reproductive tissues. Raloxifene is an organ-selective estrogen agonist that prevents acute cancellous osteopenia in ovariectomized (OVX'd) growing rats. The effects of raloxifene on adult rats with established bone loss are not known. We now compare the dose response effects of 4 months of treatment with raloxifene and estrogen in 8-month-old rats that had been OVX'd 2 months before treatment. OVX resulted in increased body weight, uterine atrophy and severe cancellous bone loss. Estrogen resulted in a dose-dependent increase in uterine weight in OVX'd rats whereas raloxifene did not promote uterine growth. Both treatments reduced body weight and serum cholesterol. Raloxifene and estrogen were each effective in stabilizing cancellous bone by preventing additional cancellous bone loss, but neither treatment replaced lost bone. These findings provide further evidence that raloxifene is a much more potent estrogen agonist on the skeleton and liver than on the uterus.
Data from Immunization with a Plasmid DNA Vaccine Encoding the N-Terminus of Insulin-like Growth Factor Binding Protein-2 in Advanced Ovarian Cancer Leads to High-level Type I Immune Responses (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Cancer vaccines targeting nonmutated proteins elicit limited type I T-cell responses and can generate regulatory and type II T cells. Class II epitopes that selectively elicit type I or type II cytokines can be identified in nonmutated cancer-associated proteins. In mice, a T-helper I (Th1) selective insulin-like growth factor binding protein-2 (IGFBP-2) N-terminus vaccine generated high levels of IFNγ secreting T cells, no regulatory T cells, and significant antitumor activity. We conducted a phase I trial of T-helper 1 selective IGFBP-2 vaccination in patients with advanced ovarian cancer.&lt;/p&gt;Patients and Methods:&lt;p&gt;Twenty-five patients were enrolled. The IGFBP-2 N-terminus plasmid-based vaccine was administered monthly for 3 months. Toxicity was graded by NCI criteria and antigen-specific T cells measured by IFNγ/IL10 ELISPOT. T-cell diversity and phenotype were assessed.&lt;/p&gt;Results:&lt;p&gt;The vaccine was well tolerated, with 99% of adverse events graded 1 or 2, and generated high levels of IGFBP-2 IFNγ secreting T cells in 50% of patients. Both Tbet&lt;sup&gt;+&lt;/sup&gt; CD4 (&lt;i&gt;P&lt;/i&gt; = 0.04) and CD8 (&lt;i&gt;P&lt;/i&gt; = 0.007) T cells were significantly increased in immunized patients. There was no increase in GATA3&lt;sup&gt;+&lt;/sup&gt; CD4 or CD8, IGFBP-2 IL10 secreting T cells, or regulatory T cells. A significant increase in T-cell clonality occurred in immunized patients (&lt;i&gt;P&lt;/i&gt; = 0.03, pre- vs. post-vaccine) and studies showed the majority of patients developed epitope spreading within IGFBP-2 and/or to other antigens. Vaccine nonresponders were more likely to have preexistent IGFBP-2 specific immunity and demonstrated defects in CD4 T cells, upregulation of PD-1, and downregulation of genes associated with T-cell activation, after immunization.&lt;/p&gt;Conclusions:&lt;p&gt;IGFBP-2 N-terminus Th1 selective vaccination safely induces type I T cells without evidence of regulatory responses.&lt;/p&gt;&lt;/div&gt;
Atherosclerosis and Peripheral Vascular Disease (2006)

Over the past 10 yr, the disease of obesity has been described as an “epidemic” and a “pathogen.” The increase in populations of the developed world exceeding a body mass index (BMI) of 25, rendering them overweight, is alarming. In 1999, in the United States 61% of adults fell into the first category and 27% were considered obese (1). The medical ramifications of obesity include, but are certainly not limited to, conditions such as type 2 diabetes mellitus, hypertension, osteoarthritis, ischemic heart disease, cardiomyopathy, and dyslipidemia, as well as peripheral vascular disease (PVD). There are approx 14 million individuals with type 2 diabetes in the United States, and the risk of developing type 2 diabetes is directly proportional to an increasing BMI (1–3). PVD in the diabetic population can be more advanced at the time of presentation than in the nondiabetic patient. The effects of sensory and motor neuropathy may mask subtle changes in perfusion and underlying infections secondary to advanced atherosclerosis. In fact, the diabetic patient population has a rate of lower-extremity amputation that is 15 times higher than that of the nondiabetic population (4). Currently, no data exist regarding the rates of PVD for patients harboring both comorbidities of obesity and diabetes concomitantly. Using the obese and diabetic patient as a paradigm, this chapter discusses the pathophysiology of atherosclerosis and the clinical presentation, diagnosis, and treatment of PVD.
Innate Response Activator B Cells Aggravate Atherosclerosis by Stimulating T Helper-1 Adaptive Immunity (2014)

Granulocyte macrophage colony-stimulating factor-producing IRA B cells alter adaptive immune processes and shift the leukocyte response toward a T helper-1-associated milieu that aggravates atherosclerosis.
Les réseaux hybrides satellites et terrestres (2015)

Cet ouvrage présente différentes approches permettant une intégration réussie des systèmes de communication par satellite dans les réseaux terrestres de prochaine génération. Les solutions proposées ont été développées et testées au cours de plusieurs projets de recherche européens et nationaux. Ces challenges techniques sont notamment illustrés par l’utilisation en exemple de systèmes de la famille DVB-S/RCS. S’appuyant sur l’étude des composants systèmes et leurs interactions, Les réseaux hybrides satellites et terrestresanalyse la complexité des réseaux de télécommunication terrestres et satellites par une approche haut niveau. Plusieurs scénarios proposent différentes voies pour réaliser cette intégration avec succès. Les principes de gestion de la qualité de service dans les réseaux terrestres et satellites ainsi que les solutions pour les faire interopérer sont décrits. La gestion de la mobilité inter-systèmes et les problèmes de performance sont également détaillés.
5-Acetyl-3-(5-phenyl-1H-pyrazol-3-yl)-1,3,4-thiadiazol-2(3H)-one monohydrate (2013)

In the title hydrate, C13H10N4O2S·H2O, the dihedral angles between the central pyrazole ring and its pendant phenyl and thia-diazole rings are 9.93 (8) and 4.56 (7)°, respectively. In the crystal, the components are linked by N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds, generating [100] chains incorporating R 4 (4)(10) loops. A weak C-H⋯O inter-action helps to consolidate the packing.
β‐Catenin transcriptional activity is inhibited downstream of nuclear localisation and is not influenced by IGF signalling in oesophageal cancer cells (2007)

Aberrant expression/localisation of beta-catenin has been implicated in the progression of oesophageal cancer. As a member of the Wnt-signalling pathway, activated beta-catenin translocates into the nucleus and drives gene transcription. Insulin-like growth factors (IGFs) have been implicated in modulation of beta-catenin localisation and transcriptional activity. We have demonstrated that beta-catenin is abundantly expressed by oesophageal cancer cells, and is both cytoplasmic and nuclear in location. beta-catenin was transcriptionally inactive in 4 of 5 cell lines. All cells expressed the IGF-1 receptor. Addition of exogenous IGFs activated the PI-3 kinase pathway but did not enhance beta-catenin/T-cell factor- (TCF) mediated transcription. Activation of Wnt signalling by lithium induced beta-catenin stabilisation in 2 cell lines but this did not increase transcriptional activity. In contrast 2 cell lines without lithium-enhanced stabilisation or re-distribution of beta-catenin did exhibit beta-catenin/TCF-mediated transcriptional activity. This study shows that beta-catenin accumulation and nuclear localisation is not indicative of transcriptional activity, and therefore is not supportive of a major role in these oesophageal cancer cells. It also questions the value of immunohistochemical studies that examine only expression. Co-operative signalling from other growth factors or adhesive molecules is likely to be required to relieve nuclear inhibition of transcriptional activity, and the nature of this is currently unknown.
Abstract 14722: Dual-Targeted Microbubbles Improve the Detection of Previously Ischemic Myocardium by Echocardiography (2014)

Introduction: Echocardiography using targeted microbubbles (MB) has been shown to detect previously-ischemic regions of myocardium by molecularly targeting cell adhesion molecules that are displayed on the activated endothelial surface after ischemia/reperfusion injury. We hypothesized that the accuracy and sensitivity of detection could be improved by constant infusion and dual-targeting, respectively. Methods: Ischemia/reperfusion injury was induced in 8 male C57BL/6 mice with 15-min LAD occlusions. After 2h of reperfusion, hearts of the closed-chest mice were imaged in long-axis with a Sequoia 15L8 transducer at 14 MHz. Each mouse received 3 of 4 MB preparations in random order: Sialyl Lewis X MB (MBX), anti-VCAM MB (MBV), Sialyl Lewis X + anti-VCAM MB (MBD), and isotype control MB (MBI). MB concentrations were approximately 200x10^6/mL, and 100 μL were infused at a constant rate of 25 μL/min via tail vein catheter. After imaging, mouse hearts were excised and stained with TTC/Phthalo blue dye to assess area at risk, and compared to regional time intensity curve (RTIC) retrieved from video data (Panel A). Results: Example RTIC for MBD shows enhanced MB signals during and after MB infusion in the anterior apical region of the heart (Panel A). In Panel B, normalized intensities are significantly higher for MBD, MBX, and MBV, compared to MBI (p&lt;0.05). Furthermore, normalized intensity for MBD is higher than both MBX and MBV (p&lt;0.05). Receiver operating curve analysis using blue dye as the gold standard showed accurate detection of both ischemic and non-ischemic regions using MBD (AUC = 0.90), MBX (AUC = 0.89), and MBV (AUC = 0.97). Conclusions: Molecular imaging of endothelial cell adhesion molecules in closed-chest mice is possible using constant infusion of MB. Dual-targeted MB yield greater MB signals than single-targeted MB when delivered using constant infusion, improving both the sensitivity and accuracy of this technique to measure risk regions in intact mice.
Chromatin interactome mapping at 139 independent breast cancer risk signals (2019)

ABSTRACT Genome-wide association studies have identified 196 high confidence independent signals associated with breast cancer susceptibility. Variants within these signals frequently fall in distal regulatory DNA elements that control gene expression. We designed a Capture Hi-C array to enrich for chromatin interactions between the credible causal variants and target genes in six human mammary epithelial and breast cancer cell lines. We show that interacting regions are enriched for open chromatin, histone marks for active enhancers and transcription factors relevant to breast biology. We exploit this comprehensive resource to identify candidate target genes at 139 independent breast cancer risk signals, and explore the functional mechanism underlying altered risk at the 12q24 risk region. Our results demonstrate the power of combining genetics, computational genomics and molecular studies to rationalize the identification of key variants and candidate target genes at breast cancer GWAS signals.
Measurements of multijet event isotropies using optimal transport with the ATLAS detector (2024)

A measurement of novel event shapes quantifying the isotropy of collider events is performed in 140 fb<sup>-1</sup> of proton-proton collisions with $\sqrt{s}$ = 13 TeV centre-of-mass energy recorded with the ATLAS detector at CERN’s Large Hadron Collider. These event shapes are defined as the Wasserstein distance between collider events and isotropic reference geometries. This distance is evaluated by solving optimal transport problems, using the ‘Energy-Mover’s Distance’. Isotropic references with cylindrical and circular symmetries are studied, to probe the symmetries of interest at hadron colliders. The novel event-shape observables defined in this way are infrared- and collinear-safe, have improved dynamic range and have greater sensitivity to isotropic radiation patterns than other event shapes. The measured event-shape variables are corrected for detector effects, and presented in inclusive bins of jet multiplicity and the scalar sum of the two leading jets’ transverse momenta. The measured distributions are provided as inputs to future Monte Carlo tuning campaigns and other studies probing fundamental properties of QCD and the production of hadronic final states up to the TeV-scale.
Electrical-performance and reliability improvement of flexible low-temperature polycrystalline silicon thin-film transistors via post-annealing process (2022)

Abstract We investigated the improvement methods of the electrical characteristics and reliability of flexible low-temperature polycrystalline silicon (LTPS) thin-film transistors (TFTs) by optimizing the annealing process. We investigated the effect of annealing on the device properties via electrical measurement and density-of-state (DOS) analysis. The annealing temperature should be reduced for flexible LTPS TFTs compared to rigid devices because the range of the thermal stability of flexible substrate is narrower than that of the glass substrate. As the activation annealing temperature ( T a ) decreased, the threshold voltage and field-effect mobility ( μ FE ) decreased, and the subthreshold swing (SS) increased. When the post-annealing temperature ( T pa ) decreased, μ FE increased, and the changes in the other parameters were negligible. The DOS decreased with an increase in T a and a reduction in T pa . These results originated from ineffective dopant activation and defect curing due to the lower T a and the enhanced hydrogen defect passivation at the lower T pa . Therefore, flexible LTPS TFTs with reduced T a values exhibited similar μ FE values and lower SS values when the post-annealing process was omitted. Furthermore, removing the post-annealing process improved the reliability of the flexible LTPS TFTs with reduced T a values under electrical stress. According to a hot-carrier instability analysis, defect passivation by hydrogen was more stable than defect curing with a higher T a . Consequently, although T a was low for flexible LTPS TFTs, the electrical performance and reliability could be improved by optimizing the post-annealing process.
In situ and ex situ optical characterization of electro deposited magneto-optic materials (1996)

Electrodeposition is being investigated as a novel and low-cost method to prepare magneto-optic thin film and nanostructured materials. This deposition method allows precise control over thin-film properties and permits deposition of novel magnetic geometries. Multilayers and alloys can be deposited and controlled by adjusting deposition potentials and ion concentrations in the bath. Nickel/cobalt alloys have been electrodeposited from sulfamate, sulfate, and chloride solutions onto Au substrates. The optical properties were monitored in situ with a real-time spectroscopic ellipsometer measuring simultaneously at 44 wavelengths in the 410–750 nm spectral range. In situ measurements have the advantage of determining the material microstructural properties (thickness, density, and roughness) before the films are oxidized in the air ambient. Ex situ variable angle spectroscopic ellipsometry measurements were taken over the spectral range from 205 to 1000 nm.
Memory hierarchy usage estimation for global loop transformations (2005)

Major parts of the power dissipation for data dominated embedded system is due to huge amounts of data transfers to and from large consuming data memories. Global loop transformations play a crucial role in optimizing the memory accesses. By improving regularity and temporal locality of these memory accesses using loop transformations, data can be potentially stored closer to the datapath in smaller less power consuming memories. To steer the selection of which loop transformations to perform, high level memory estimation is used. In state of the art memory estimation techniques the mapping of data to different parts of the memory hierarchy are not considered since these decisions are made in later system design phases. However, estimates of these mapping decisions is crucial, since they greatly influence the consequences of different transformations. In this paper we propose a systematic methodology for hierarchical memory usage estimation which considers also future data mapping decisions for a memory hierarchy. The goal of the estimation is to evaluate global loop transformation decisions for different platforms and keep only the optimal decision (in terms of energy) for each platform. We demonstrate our methodology on a real- life multimedia video coder (QSD PCM) which shows that for 1k layer one memory, a factor of 2 improvement in total energy can be achieved.
Keggin-type Polyoxometalates as Bidirectional Redox Mediators for Rechargeable Batteries (2016)

Keggin-type polyoxometalates (POMs), which possess multiple redox centers, were investigated as bidirectional redox mediators in rechargeable batteries. A series of POMs have been synthesized and employed in sulfur electrodes where neither the active material nor the discharge product were electrically conductive. POMs were found to have multiple redox potentials covering the range of the equilibrium potentials of the redox reactions of sulfur, which consequently facilitated both charge and discharge reactions. In particular, [SiMo12O40]4− offered a large discharge capacity of 1270 mAh g−1 by accelerating the reduction of shorter, less soluble polysulfides, leading to a higher cycling performance. The mediator role was confirmed via an X-ray photoelectron spectroscopy study on the cycled cathodes. Density functional theory calculations showed that the redox potentials of POMs are tunable, allowing selective design of suitable POM molecules for specific battery electrodes.
Targeting small GTPases and their downstream pathways with intracellular macromolecule binders to define alternative therapeutic strategies in cancer (2021)

The RAS superfamily of small GTPases regulates major physiological cellular processes. Mutation or deregulation of these small GTPases, their regulators and/or their effectors are associated with many diseases including cancer. Hence, targeting these classes of proteins is an important therapeutic strategy in cancer. This has been recently achieved with the approval of the first KRASG12C covalent inhibitors for the clinic. However, many other mutants and small GTPases are still considered as 'undruggable' with small molecule inhibitors because of a lack of well-defined pocket(s) at their surface. Therefore, alternative therapeutic strategies have been developed to target these proteins. In this review, we discuss the use of intracellular antibodies and derivatives - reagents that bind their antigen inside the cells - for the discovery of novel inhibitory mechanisms, targetable features and therapeutic strategies to inhibit small GTPases and their downstream pathways. These reagents are also versatile tools used to better understand the biological mechanisms regulated by small GTPases and to accelerate the drug discovery process.
BIOMETRIC RECOGNITION SYSTEM BASED ON THE MOTION OF THE HUMAN BODY GRAVITY CENTRE ANALYSIS (2010)

In this paper we present a novel approach that enables the determination and measurement of important features associated with the human body movement. This information can be used in the construction of a biometric personal identification system. Biometrics is, essentially, a pattern recognition system based on measurements of unique physiological or behavioural features as acquired from an individual. The domain of biometric techniques is currently placed within recently developed disciplines of science. Biometry or biometrics is simply defined as automatically recognizing a person using distinguishing traits and is widely used in various security systems. Biometry can be defined as a method of personal identification based on individuals &amp;apos; physical and behavioural features. Physiological biometrics covers data coming directly from a measurement of part of a human body, for example a fingerprint, the shape of the face, or from the retina. Behavioural biometrics analyses data obtained on the basis of an activity performed by a given person, for example speech and the handwritten signature. The system of biometrics defined above can now be expanded, and a new biometrics system can be considered. In our approach, human foot pressure on a surface is measured and the pressure data retrieved. The pressure parameters are collected without the necessity of any movements of the feet. 1.
Eulerian simulations to assess dispersion for transport through 2D correlated porous media (2019)

International audience
Characterization and plant expression of a glyphosate‐tolerant enolpyruvylshikimate phosphate synthase (2008)

These data suggest that aroA(1398) is a suitable candidate for conferring glyphosate tolerance in transgenic crop plants.