gebhart/patrepeval huggingface dataset:
Study of temperature-dependent ultrathin oxide growth on Si(111) using variable-angle spectroscopic ellipsometry (1990)

The monolayer-sensitive variable-angle spectroscopic ellipsometry technique was used to study the temperature-dependent growth mechanisms of an ultrathin oxide layer on top of silicon. The oxidation was done in atomic oxygen produced in a pure oxygen plasma and driven by an RF power source. The results have been compared with the recently proposed model of Murali and Murarka for ultrathin oxide growth on top of silicon. The activation energies of different growth parameters associated with the oxide growth have also been determined.
Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain (2010)

The novel analgesic tapentadol combines mu-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule and shows potent analgesia in various rodent models of pain. We analyzed the contribution of opioid and monoaminergic mechanisms to the activity of tapentadol in rat models of nociceptive and neuropathic pain. Antinociceptive efficacy was inferred from tail withdrawal latencies of experimentally naive rats using a tail flick test. Antihypersensitive efficacy was inferred from ipsilateral paw withdrawal thresholds toward an electronic von Frey filament in a spinal nerve ligation model of mononeuropathic pain. Dose-response curves of tapentadol (intravenous) were determined in combination with vehicle or a fixed dose (intraperitoneal) of the mu-opioid receptor antagonist naloxone (1mg/kg), the alpha2-adrenoceptor antagonist yohimbine (2.15 mg/kg), or the serotonin 5-HT(2A) receptor antagonist ritanserin (0.316 mg/kg). Tapentadol showed clear antinociceptive and antihypersensitive effects (>90% efficacy) with median effective dose (ED(50)) values of 3.3 and 1.9 mg/kg, respectively. While the antinociceptive ED(50) value of tapentadol was shifted to the right 6.4-fold by naloxone (21.2mg/kg) and only 1.7-fold by yohimbine (5.6 mg/kg), the antihypersensitive ED(50) value was shifted to the right 4.7-fold by yohimbine (8.9 mg/kg) and only 2.7-fold by naloxone (5.2mg/kg). Ritanserin did not affect antinociceptive or antihypersensitive ED(50) values of tapentadol. Activation of both mu-opioid receptors and alpha2-adrenoceptors contribute to the analgesic effects of tapentadol. The relative contribution is, however, dependent on the particular pain indication, as mu-opioid receptor agonism predominantly mediates tapentadol's antinociceptive effects, whereas noradrenaline reuptake inhibition predominantly mediates its antihypersensitive effects.
Functional Independence and Interdependence of the Src Homology Domains of Phospholipase C-γ1 in B-Cell Receptor Signal Transduction (1999)

B-cell receptor (BCR)-induced activation of phospholipase C-gamma1 (PLCgamma1) and PLCgamma2 is crucial for B-cell function. While several signaling molecules have been implicated in PLCgamma activation, the mechanism coupling PLCgamma to the BCR remains undefined. The role of PLCgamma1 SH2 and SH3 domains at different steps of BCR-induced PLCgamma1 activation was examined by reconstitution in a PLCgamma-negative B-cell line. PLCgamma1 membrane translocation required a functional SH2 N-terminal [SH2(N)] domain, was decreased by mutation of the SH3 domain, but was unaffected by mutation of the SH2(C) domain. Tyrosine phosphorylation did not require the SH2(C) or SH3 domains but depended exclusively on a functional SH2(N) domain, which mediated the association of PLCgamma1 with the adapter protein, BLNK. Forcing PLCgamma1 to the membrane via a myristoylation signal did not bypass the SH2(N) domain requirement for phosphorylation, indicating that the phosphorylation mediated by this domain is not due to membrane anchoring alone. Mutation of the SH2(N) or the SH2(C) domain abrogated BCR-stimulated phosphoinositide hydrolysis and signaling events, while mutation of the SH3 domain partially decreased signaling. PLCgamma1 SH domains, therefore, have interrelated but distinct roles in BCR-induced PLCgamma1 activation.
Exome sequencing and analysis of 454,787 UK Biobank participants (2021)

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing<sup>1</sup> to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study<sup>2</sup>. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10<sup>-11</sup>. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.
Power Split Supercharging: A Mild Hybrid Approach to Boost Fuel Economy (2020)

This work studies a novel low voltage (&amp;lt;60 V) hybrid system that supports engine boosting and downsizing in addition to start-stop, regenerative braking, and constrained torque assist/regeneration. The hybrid power split supercharger (PSS) shares a 9 kW motor between supercharging the engine or providing hybrid functionalities through a planetary gear set, a brake and a bypass valve. The PSS operation is limited to only one of the parallel hybrid or boosting modes at a time, necessitating a highly optimized decision making algorithm to select the device mode and power split ratio. In this work an adaptive equivalent consumption minimization strategy (A-ECMS) is developed for energy management of the PSS. The A-ECMS effectiveness is compared against a dynamic programming (DP) solution with full drive cycle preview through hardware-in-the-loop experiments on an engine dynamometer testbed. The experiments show that the PSS with A-ECMS reduces a vehicle fuel consumption by 18.4% over standard FTP75 cycle compared to a baseline turbocharged engine, while global optimal DP solution decreases the fuel consumption by 22.8% compared to baseline.
Comparative assessment of processes for the transportation of thermal energy over long distances (2012)

International audience
Membrane-bound full-length Sonic Hedgehog identifies cancer stem cells in human non-small cell lung cancer (2017)

The mechanism of Sonic Hedgehog (Shh) pathway activation in non-small cell lung cancer (NSCLC) is poorly described. Using an antibody against the Shh C-terminal domain, we found a small population of Shh-positive (Shh+) cells in NSCLC cells. The objective of this study was to characterize these Shh+ cells. Shh+ and Shh- cells were sorted by using Fluorescence Activated Cell Sorting (FACS) on 12 commercial NSCLC cell lines. Functional analyses on sorted cells were performed with gene expression assays (qRT-PCR and microarray) and cells were treated with cytotoxic chemotherapy and a targeted inhibitor of Shh signaling (GDC0449). We used <i>in vivo</i> models of nude mice inoculated with Shh+ and Shh- sorted cells and drug-treated cells. Finally, we confirmed our results in fresh human NSCLC samples (n=48) paired with normal lung tissue. We found that Shh+ cells produced an uncleaved, full-length Shh protein detected on the membranes of these cells. Shh+ cells exerted a paracrine effect on Shh- cells, inducing their proliferation and migration. Shh+ cells were chemo-resistant and showed features of cancer stem cells (CSCs) <i>in vitro</i> and <i>in vivo</i>. Pharmacological inhibition of the Shh pathway suppressed their CSC features. A high percentage of Shh+ cells was associated with poor prognosis in early-stage NSCLC patients. In conclusion, we describe for the first time the presence of an abnormal membrane-bound full-length Shh protein in human cancer cells that allows the identification of CSCs <i>in vitro</i> and <i>in vivo</i>.
Generalized size scaling of metabolic rates based on single-cell measurements with freshwater phytoplankton (2019)

Kleiber's law describes the scaling of metabolic rate with body size across several orders of magnitude in size and across taxa and is widely regarded as a fundamental law in biology. The physiological origins of Kleiber's law are still debated and generalizations of the law accounting for deviations from the scaling behavior have been proposed. Most theoretical and experimental studies of Kleiber's law, however, have focused on the relationship between the average body size of a species and its mean metabolic rate, neglecting intraspecific variation of these 2 traits. Here, we propose a theoretical characterization of such variation and report on proof-of-concept experiments with freshwater phytoplankton supporting such framework. We performed joint measurements at the single-cell level of cell volume and nitrogen/carbon uptake rates, as proxies of metabolic rates, of 3 phytoplankton species using nanoscale secondary ion mass spectrometry (NanoSIMS) and stable isotope labeling. Common scaling features of the distribution of nutrient uptake rates and cell volume are found to hold across 3 orders of magnitude in cell size. Once individual measurements of cell volume and nutrient uptake rate within a species are appropriately rescaled by a function of the average cell volume within each species, we find that intraspecific distributions of cell volume and metabolic rates collapse onto a universal curve. Based on the experimental results, this work provides the building blocks for a generalized form of Kleiber's law incorporating intraspecific, correlated variations of nutrient-uptake rates and body sizes.
Ruthenium‐Catalysed Hydrogenation of Aromatic Ketones using Monodentate Phosphoramidite Ligands (2010)

Abstract A ruthenium pre‐catalyst containing two equivalents of the bulky monodentate phosphoramidite 3,3′‐dimethyl‐PipPhos and one equivalent of a chiral diamine such as 1,2‐diphenylethylenediamine or 1,2‐diaminocyclohexane was used for the asymmetric hydrogenation of aromatic ketones. A range of substituted and unsubstituted aryl alkyl ketones was hydrogenated using only 0.1 mol% of this catalyst with full conversions and enantioselectivities up to 97%. The phosphoramidite and diamine ligands matched when both had the same configuration, i.e., S ‐phosphoramidite with S,S ‐diamine. In that case the product was obtained with high enantioselectivity and the R ‐configuration. The mismatched case produced the product in lower ee . The product configuration was determined by the configuration of the diamine ligand. A mechanistic proposal was made.
Ultrathin two-dimensional van der Waals asymmetric ferroelectric semiconductor junctions (2022)

Two-dimensional van der Waals ferroelectric semiconductors have attracted extensive research interest in both theoretical investigation and device applications due to their ferroelectricity and semiconducting nature. However, it is still not well understood how the ferroelectric phase is able to coexist with the semiconducting phase in this emerging material class. In this work, mm-scale continuous films of In2Se3 with a thickness of ∼3 nm were synthesized successfully by physical vapor deposition. Furthermore, we fabricated asymmetric ferroelectric semiconductor junctions (a-FSJs) from thick exfoliated and PVD-grown ultrathin In2Se3 films. A high read current density of ∼100 A/cm2 and a distinction ratio of over 102 at VRead = 0.5 V are achieved in devices fabricated by a 3 nm-thick In2Se3 film toward ultrahigh-density memory integration. Notably, the coercive voltage is constant, with In2Se3 film thickness decreasing from 200 to 3 nm. A qualitative model is proposed to elucidate the anomalous film-thickness-independent coercive voltage in this ultrathin a-FSJ, which can also be generalized to other emerging two-dimensional ferroelectric semiconductors.
Combinatorial chemistry in nematodes: modular assembly of primary metabolism-derived building blocks (2015)

The nematode Caenorhabditis elegans was the first animal to have its genome fully sequenced and has become an important model organism for biomedical research. However, like many other animal model systems, its metabolome remained largely uncharacterized, until recent investigations demonstrated the importance of small molecule-based signalling cascades for virtually every aspect of nematode biology. These studies have revealed that nematodes are amazingly skilled chemists: using simple building blocks from conserved primary metabolism and a strategy of modular assembly, C. elegans and other nematode species create complex molecular architectures to regulate their development and behaviour. These nematode-derived modular metabolites (NDMMs) are based on the dideoxysugars ascarylose or paratose, which serve as scaffolds for attachment of moieties from lipid, amino acid, carbohydrate, citrate, and nucleoside metabolism. Mutant screens and comparative metabolomics based on NMR spectroscopy and MS have so-far revealed several 100 different ascarylose ("ascarosides") and a few paratose ("paratosides") derivatives, many of which represent potent signalling molecules that can be active at femtomolar levels, regulating development, behaviour, body shape, and many other life history traits. NDMM biosynthesis appears to be carefully regulated as assembly of different modules proceeds with very high specificity. Preliminary biosynthetic studies have confirmed the primary metabolism origin of some NDMM building blocks, whereas the mechanisms that underlie their highly specific assembly are not understood. Considering their functions and biosynthetic origin, NDMMs represent a new class of natural products that cannot easily be classified as "primary" or "secondary". We believe that the identification of new variants of primary metabolism-derived structures that serve important signalling functions in C. elegans and other nematodes provides a strong incentive for a comprehensive re-analysis of metabolism in higher animals, including humans.
Integral quadratic constraint approach vs. multiplier approach (2004)

Integral quadratic constraints (IQC) arise in many optimal and/or robust control problems. The IQC approach can be viewed as a generalization of the classical multiplier approach in the absolute stability theory. In this paper, we study the relationship between the two approaches for robust stability analysis. The key result shows that for many applications, the existence of an IQC is equivalent to the existence of a multiplier. Because the multiplier approach is typically simpler and more intuitive, this result suggests that the multiplier approach may be more useful than the IQC approach in many applications.
Lattice instability and superconductivity in electron doped (3, 3) carbon nanotubes (2009)

We investigated the effect of electron doping on the phonon dispersion and electron-phonon coupling of a small diameter (3, 3) carbon nanotube using first principles density functional perturbation theory. Electron doping increases the number of nesting features in the electronic band structure, which is reflected in a wealth of phonon anomalies. We found that the overall electron-phonon coupling is substantially enhanced with respect to the pristine tube, which improves superconductivity. At the same time, the intrinsic Peierls instability remains similar, but the Peierls temperature still remains larger than the superconducting transition temperature.
Factor XI Regulates Pathological Thrombus Formation on Acutely Ruptured Atherosclerotic Plaques (2014)

Factor XI antisense oligonucleotides safely prevent thrombus formation on acutely ruptured atherosclerotic plaques in mice. Furthermore, perturbed carotid arteries from factor XI antisense-treated animals show a less severe inflammatory response.
Targeting cell cycle phase-specific drug sensitivity for melanoma therapy (2018)

The development of small molecule MAPK pathway inhibitors (MAPKi) and antagonists of the immune checkpoints has revolutionized melanoma therapy. However, MAPKi only work in approximately 40% of cases as a BRAFV600 mutation must be present; moreover, rapid development of resistance is common. Immune checkpoint inhibitors (ICi) show response rates up to 60%, depending on drug or combination, with durable effects but resistance can still occur. Thus there is a clear need to develop combination therapies to delay the onset of resistance.\n\nMany anti‐cancer drugs impact the cell cycle but are also dependent on specific cell cycle phases, which results in cell cycle phase‐specific drug insensitivity. The tumor microenvironment is characterized by cancer cell subpopulations with heterogeneous cell cycle profiles. For example, hypoxic tumor zones contain clusters of cancer cells that arrest in G1‐phase whereas actively cycling cells cluster around blood vessels. Importantly, neoplastic cells exhibit differential drug sensitivity based on their residence in specific cell cycle phases.\n\nWe have established a model to study the effects of the cell cycle on drug sensitivity in real‐time: Utilizing two‐ and three‐dimensional melanoma culture models in combination with fluorescent cell cycle indicators (FUCCI), we investigated the effect of G1‐arrest on drug sensitivity. G1‐arrested melanoma cells were more resistant to apoptosis induced by agents that selectively target S/G2/M phase cells, such as the proteasome inhibitor bortezomib or the alkylating agent temozolomide. In contrast, G1‐arrested cells were more sensitive to MAPKi‐induced cell death as this pathway is essential for G1‐phase progression. Of major clinical relevance, pretreatment of melanoma cells with sub‐lethal but G1‐arresting doses of a MAPKi resulted in resistance to temozolomide or bortezomib. We also found that changing environmental conditions, such as applying hypoxia, resulted in protective G1‐ arrest. However, hypoxia can also result in endoplasmic reticulum (ER) stress. If the level of ER stress is persistent or excessive it switches to an apoptotic response. We show that the protective effect of G1‐arrest can be overridden by the apoptotic effect of ER stress. This was then used as a therapeutic approach: Using the F‐XBP1ΔDBD‐venus reporter construct, to visualize ER stress, we showed that single agent low dose ER stress‐inducing agents, bortezomib and fenretinide, induced ER‐stress and cell cycle arrest but only limited cell death, while the combination resulted in synergistic apoptosis. Taken together, our data demonstrate that cell cycle‐tailored targeting of metastatic melanoma can improve therapy outcomes and that additional induction of ER stress is a strategy worth investigating to further improve melanoma therapy. Furthermore, we propose that our real‐time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches.
Electron microscopy and x-ray study of nanostructured titanium dioxidefilms (1992)

The structure of multilayered TiO<SUB>2</SUB> films formed by nano-structured colloidal particles was studied by scanning electron microscopy, x-ray powder diffraction, and other methods. The structure of the surface and inner layers of the films are discussed in relation to the methods of preparation and subsequent treatment of the films.
109: IgH Gene Rearrangements in PBPC Mononuclear Cells does not Influence Survival or Relapse following Autologous Transplantation for B-cell Lymphoproliferative Diseases (2008)

Background: Relapsed disease remains a major obstacle following autologous hematopoietic stem cell transplantation (HSCT) for non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Studies regarding the role of residual tumour cells collected in autografts in earlier relapse and reduced survival have been inconclusive. The impact of residual disease detected by sensitive molecular methods in autologous PBPCs remains uncertain and is addressed in this study. Methods: Patients undergoing autologous HSCT for NHL and MM at our institution between June 2001 and January 2006 were enrolled (n = 158). Aliquots of freshly collected PBPC collections were assessed for the presence of clonal IgH gene rearrangements using qualitative semi-nested PCR. Patients with detectable clonal IgH gene rearrangements were designated “positive” and compared with “negative” patients without detectable IgH gene rearrangements. Survival, progression-free survival, and time to next treatment were determined for all patients. All outcomes were compared using the method of Kaplan and Meier. Results: In comparison to patients with “positive” PBPC grafts, patients “negative” for detectable disease had no improvement in overall survival for MM (p = 0.91) and for NHL (p = 0.82). Further analysis based on tissue histology in patients with NHL revealed no significant difference in overall survival between patients with “positive” grafts compared with “negative” PBPC collections (aggressive histology NHL, p = 0.74; indolent NHL, p = 0.29). There was also no significant improvement in progression-free survival among patients with NHL (p = 0.85) or MM (p = 0.91). Conclusion: The use of autologous PBPCs “negative” for contaminating tumour cells does not lead to improved overall survival in MM or NHL. Furthermore, the absence of detectable clonal IgH rearrangements using sensitive PCR did not correlate with a reduction in progression-free survival. Our results suggest that disease relapse cannot be adequately explained by the reinfusion of PBPCs containing residual tumour cells. It is possible that high dose chemotherapy regimens used in autologous HSCT are not sufficiently eliminating residual tumour burden in some patients, including those with “negative” PBPC collections. Taken together, our results suggest that strategies aimed at removing tumour cells from autologous PBPC grafts in patients with MM and NHL may have marginal benefit.
Brachypodium as a Model for the Grasses: Today and the Future (2011)

International audience
A Mega-High-Throughput Screening Platform for the Discovery of Biologically Relevant Sequence-Defined Non-Natural Polymers (2021)

Combinatorial methods enable the synthesis of chemical libraries on scales of millions to billions of compounds, but the ability to efficiently screen and sequence such large libraries has remained a major bottleneck for molecular discovery. We developed a novel technology for screening and sequencing libraries of synthetic molecules of up to a billion compounds in size. This platform utilizes the Fiber-optic Array Scanning Technology (FAST) to screen bead-based libraries of synthetic compounds at a rate of 5 million compounds per minute (~83,000 Hz). This ultra-high-throughput screening platform has been used to screen libraries of synthetic “self-readable” non-natural polymers that can be sequenced at femtomole scale by chemical fragmentation and high-resolution mass spectrometry. The versatility and throughput of the platform was demonstrated by screening two libraries of non-natural polyamide polymers with sizes of 1.77M and 1B compounds against the protein targets K-Ras, asialoglycoprotein receptor 1 (ASGPR), IL-6, IL 6 receptor (IL-6R) and TNFα. Hits with low nanomolar binding affinities were found against all targets, including competitive inhibitors of K-Ras binding to Raf and functionally active uptake ligands for ASGPR facilitating intracellular delivery of a non-glycan ligand.