gebhart/patrepeval huggingface dataset:
A Flexible Multiwell Format for Immunofluorescence Screening Microscopy of Small-Molecule Inhibitors (2010)

Large-scale screens in mammalian cells demand for flexible high-throughput screening platforms that allow to analyze cellular traits on a genome-wide level or to identify small-molecule inhibitors (SMIs) from complex compound libraries. In this study we developed and tested high-density cell arrays made out of polydimethylsiloxane (PDMS) that support cell growth directly on standard glass microscope objective slides. We analyzed the effect of 3 reference inhibitors (MLN-8054, VX-680, and flavopiridol) and 4 exploratory, cell permeable small-molecule kinase inhibitors (two benzothiophene-based and two 4-amino-6-arylpyrimidine-based compounds) on different cell lines, using prototype 5 × 5 and 9 × 9 array carpets. We found that high-density PDMS cell arrays support growth of a broad range of cell types, are well suited for compound screens, and are compatible with high-content screening platforms. This novel array format is of particular advantage for compound screening to identify SMIs, when a combination of flexibility with respect to culture volume, well density, and high-resolution imaging is required. In addition, we demonstrated the suitability of this format for reverse transfection and siRNA experiments.
Genomic analysis of circulating cell-free DNA (cfDNA) to investigate mechanisms of resistance to enzalutamide (ENZ) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts). (2015)

157 Background: Factors driving clinical resistance to ENZ are poorly understood. Genomic analysis of cfDNA is a promising and minimally invasive approach for investigating mechanisms of therapeutic resistance in mCRPC. Methods: Baseline plasma samples were collected from 53 mCRPC pts commencing ENZ. In 31 of these pts, 12-week and treatment cessation samples were also obtained. DNA was extracted and subjected to array Comparative Genomic Hybridization (aCGH) for chromosome copy number (CN) analysis and androgen receptor (AR) gene sequencing (MiSeq) for mutation analysis. Endpoints were i) PSA50 or PSA30 response rates (RR) (PSA decline ≥ 50% or 30% for ≥ 3 weeks); and ii) radiographic/clinical progression-free survival (PFS). Results: CN changes on baseline aCGH included 8p loss (26%), 8q gain (32%), MYC gain (28%), CCND1 gain/amplification (amp) (11%), MET gain (13%), RB1 loss (21%) and AR gain/amp (30%). Correlation of clinical and genomic data showed multiple links between AR CN status and outcomes on ENZ. Firstly, compared to no AR gain/amp, pts with pre-treatment AR gain/amp had lower PSA50 (41% vs. 19%, P=0.12; Χ 2 ) and PSA30 RR (54% vs. 25%, P=0.051; Χ 2 ) and shorter median PFS (4.6 vs. 2.3 months, P&lt;0.001; log-rank). Secondly, on multivariate analysis, pre-treatment AR gain/amp (HR 3.42, P=0.002) together with prior abiraterone (HR 4.72, P=0.001) was confirmed as an independent prognostic factor for PFS. Thirdly, in pts with serial plasma samples, 16% (5/31) had a change in AR CN status from baseline with 3 pts converting from no AR gain to AR gain and 2 pts from AR gain to AR amp. Of note, median PFS in these 5 pts was only 2.8 months. Finally, AR gain/amp at baseline or emergence of AR gain/amp on-treatment was associated with decreased median PFS compared with no AR CN increase at any timepoint (2.3 months vs. 6.5 months, P&lt;0.001; log-rank). Conclusions: Detection of AR gain/amp in pre- or on-treatment cfDNA samples correlated with adverse outcomes on ENZ. These data indicate that AR gain/amp may be a biomarker of primary and acquired resistance to ENZ in mCRPC pts. Updated data including AR gene sequencing will be presented.
Interleukin-17A and Neutrophils in a Murine Model of Bird-Related Hypersensitivity Pneumonitis (2015)

Hypersensitivity pneumonitis (HP) is an immune mediated lung disease induced by the repeated inhalation of a wide variety of antigens. Bird-related hypersensitivity pneumonitis (BRHP) is one of the most common forms of HP in human and results from the inhalation of avian antigens. The findings of a recent clinical analysis suggest that in addition to Th1 factors, the levels of interleukin(IL)-17 and IL-17-associated transcripts are increased in the setting of HP, and that both IL-17A and neutrophils are crucial for the development of pulmonary inflammation in murine models of HP. Our objectives were to investigate the roles of IL-17A and neutrophils in granuloma-forming inflammation in an acute HP model. We developed a mouse model of acute BRHP using pigeon dropping extract. We evaluated the process of granuloma formation and the roles of both IL-17A and neutrophils in a model. We found that the neutralization of IL-17A by the antibody attenuated granuloma formation and the recruitment of neutrophils, and also decreased the expression level of chemokine(C-X-C motif) ligand 5 (CXCL5) in the acute HP model. We confirmed that most of the neutrophils in the acute HP model exhibited immunoreactivity to the anti-IL-17 antibody. We have identified the central roles of both IL-17A and neutrophils in the pathogenesis of granuloma formation in acute HP. We have also assumed that neutrophils are an important source of IL-17A in an acute HP model, and that the IL-17A-CXCL5 pathway may be responsible for the recruitment of neutrophils.
Structural and molecular determinants of CCS-mediated copper activation of MEK1/2 (2020)

Summary Normal physiology relies on the precise coordination of intracellular signal transduction pathways that respond to nutrient availability to balance cell growth and cell death. We recently established a critical mechanistic function for the redox-active micronutrient copper (Cu) in the canonical mitogen activated protein kinase (MAPK) pathway at the level of MEK1 and MEK2. Here we report the X-ray crystal structure of Cu-MEK1 and reveal active site chemical ligands and oxidation state specificity for MEK1 Cu coordination. Mechanistically, the Cu chaperone CCS selectively bound to and facilitated Cu transfer to MEK1. Mutations in MEK1 that disrupt Cu(I) affinity or a CCS small molecule inhibitor reduced Cu-stimulated MEK1 kinase activity. These atomic and molecular level data provide the first mechanistic insights of Cu kinase signaling and could be exploited for the development of novel MEK1/2 inhibitors that either target the Cu structural interface or blunt dedicated Cu delivery mechanisms via CCS.
Heterogeneous Power Delivery for 7nm High-Performance Chiplet-Based Processors using Integrated Passive Device and In-Package Voltage Regulator (2020)

We demonstrate two heterogeneous solutions to improve power delivery to High-Performance Computing (HPC) processors. The scalable HPC vehicle integrates two 7nm CMOS processor chiplets, each with four ARM¯ Cortex¯-A72 cores, that are mounted on a Chip-on-Wafer-on-Substrate (CoWoS¯) silicon interposer [1]. In the first solution, Integrated Passive Device (IPD) capacitors are placed directly beneath the interposer to provide more accessible and effective supply noise decoupling. The result is 3.9% higher maximum clock frequency at a core supply of 1.135V. In the second solution, the processor is powered by a laterally mounted in-Package Voltage Regulator (PVR) built in 28nm CMOS augmented with high-permeability on-die inductors. The processor performance provided by the buck converter-based PVR matches that by an off-package External Voltage Regulator (EVR). As processor power increases with higher core counts, PVRs with on-die inductors will be increasingly compelling for efficient system power delivery.
ChemInform Abstract: Catenanes, Rotaxanes, and Pretzelanes‐Template Synthesis and Chirality (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Entrevista a Colum McCann (2004)

El escritor irlandes Colum McCann nos visito para presentar El bailarin (RBA), su biografia novelada del gran Rudolf Nureiev.
CryoProtect: A Web Server for Classifying Antifreeze Proteins from Nonantifreeze Proteins (2017)

Antifreeze protein (AFP) is an ice-binding protein that protects organisms from freezing in extremely cold environments. AFPs are found across a diverse range of species and, therefore, significantly differ in their structures. As there are no consensus sequences available for determining the ice-binding domain of AFPs, thus the prediction and characterization of AFPs from their sequence is a challenging task. This study addresses this issue by predicting AFPs directly from sequence on a large set of 478 AFPs and 9,139 non-AFPs using machine learning (e.g., random forest) as a function of interpretable features (e.g., amino acid composition, dipeptide composition, and physicochemical properties). Furthermore, AFPs were characterized using propensity scores and important physicochemical properties via statistical and principal component analysis. The predictive model afforded high performance with an accuracy of 88.28% and results revealed that AFPs are likely to be composed of hydrophobic amino acids as well as amino acids with hydroxyl and sulfhydryl side chains. The predictive model is provided as a free publicly available web server called CryoProtect for classifying query protein sequence as being either AFP or non-AFP. The data set and source code are for reproducing the results which are provided on GitHub.
Assessment and Management of Acute Volar Rim Fractures (2021)

The volar rim of the distal radius is the only bony restraint to volar carpal subluxation. Higher loads across the volar rim require stable and rigid fixation to maintain reduction and allow healing while rehabilitation begins. Volar marginal fragments are not amenable to buttressing by fixed angle volar locking plates. Appropriate management of volar marginal fragments comprises two steps-recognition of their presence and rigid anatomical repair. The best opportunity for success in the presence of a volar marginal fragment is its adequate initial treatment. The purpose of this review is to reinforce the importance of a complete preoperative and intraoperative evaluation of distal radius fractures. Volar marginal fragments can easily be overlooked even following initial reduction and fixation. Understanding the relevant anatomy and loading parameters can facilitate intraoperative decisions on approach and fixation, which are integral to achieving optimal clinical outcomes.
Automatic Detection of Sensitive Data Using Transformer- Based Classifiers (2022)

The General Data Protection Regulation (GDPR) has allowed EU citizens and residents to have more control over their personal data, simplifying the regulatory environment affecting international business and unifying and homogenising privacy legislation within the EU. This regulation affects all companies that process data of European residents regardless of the place in which they are processed and their registered office, providing for a strict discipline of data protection. These companies must comply with the GDPR and be aware of the content of the data they manage; this is especially important if they are holding sensitive data, that is, any information regarding racial or ethnic origin, political opinions, religious or philosophical beliefs, trade union membership, data relating to the sexual life or sexual orientation of the person, as well as data on physical and mental health. These classes of data are hardly structured, and most frequently they appear within a document such as an email message, a review or a post. It is extremely difficult to know if a company is in possession of sensitive data at the risk of not protecting them properly. The goal of the study described in this paper is to use Machine Learning, in particular the Transformer deep-learning model, to develop classifiers capable of detecting documents that are likely to include sensitive data. Additionally, we want the classifiers to recognize the particular type of sensitive topic with which they deal, in order for a company to have a better knowledge of the data they own. We expect to make the model described in this paper available as a web service, customized to private data of possible customers, or even in a free-to-use version based on the freely available data set we have built to train the classifiers.
SmartGraph: A Network Pharmacology Investigation Platform (2019)

Abstract Motivation Drug discovery investigations need to incorporate network pharmacology concepts while navigating the complex landscape of drug-target and target-target interactions. This task requires solutions that integrate high-quality biomedical data, combined with analytic and predictive workflows as well as efficient visualization. SmartGraph is an innovative platform that utilizes state-of-the-art technologies such as a Neo4j graph-database, Angular web framework, RxJS asynchronous event library and D3 visualization to accomplish these goals. Results The SmartGraph framework integrates high quality bioactivity data and biological pathway information resulting in a knowledgebase comprised of 420,526 unique compound-target interactions defined between 271,098 unique compounds and 2,018 targets. SmartGraph then performs bioactivity predictions based on the 63,783 Bemis-Murcko scaffolds extracted from these compounds. Through several use-cases, we illustrate the use of SmartGraph to generate hypotheses for elucidating mechanism-of-action, drug-repurposing and off-target prediction. Availability https://smartgraph.ncats.io/
A further characterization of acridine-photosensitized inhibition of mast cell degranulation. (1990)

The purpose of this study was to further characterize acridine-photosensitized inhibition of mast cell degranulation. Acridine plus UVA radiation (320-400 nm) inhibited degranulation in response to antigen in IgE-sensitized rat serosal mast cells and in response to concanavalin A, which acts by a mechanism similar to antigen-IgE challenge. Removing oxygen from the incubation medium prevented the acridine-photosensitized inhibition of mast cell degranulation in response to 48/80. Acridine plus UVA radiation did not decrease mast cell ATP content, thus excluding inhibition of ATP production as a mechanism for photosensitized inhibition of mast cell degranulation. Although the viability of mast cells, as determined by uptake of trypan blue, was not affected 3 h after treatment with acridine plus UVA radiation, viability decreased by 6 h, and by 22 h 44% of the cells were nonviable. These results indicate that degranulation of mast cells by a variety of agents is inhibited by UVA plus acridine treatment, and that photosensitization requires oxygen and occurs before cytotoxicity.
Quasi-guided-optical-waveguide VCSELs for single-mode high-power applications (2006)

Novel quasi-guided optical waveguide (QGOW) VCSELs is presented and analyzed for lateral mode control in large-aperture single-mode high-power VCSELs, with large modal discrimination in excess of 20 cm−1 and low fundamental mode loss.
Biallelic Loss of Function of SORL1 in an Early Onset Alzheimer’s Disease Patient (2018)

Heterozygous SORL1 protein truncating variants (PTV) are a strong risk factor for early-onset Alzheimer's disease (EOAD). In case control studies performed at the genome-wide level, PTV definition is usually straightforward. Regarding splice site variants, only those affecting canonical sites are typically included. Some other variants, not annotated as PTV, could, however, affect splicing and hence result in a loss of SORL1 function. We took advantage of the whole exome sequencing data from the 9/484 patients with a previously reported SORL1 PTV in the French EOAD series and searched for a second variant which may affect splicing and eventually result in more than 50% loss of function overall. We found that one patient, known to carry a variant predicted to disrupt the canonical 5' splice site of exon 8, also carried a second novel intronic variant predicted to affect SORL1 splicing of exon 29. Segregation analysis showed that the second variant was located in trans from the known PTV. We performed ex vivo minigene splicing assays and showed that both variants led to the generation of transcripts containing a premature stop codon. This is therefore the first evidence of a human carrying biallelic SORL1 PTV. This patient had a family history of dementia in both maternal and paternal lineages with later ages of onset than the proband himself. However, his 55 years age at onset was in the same ranges as previously published SORL1 heterozygous PTV carriers. This suggests that biallelic loss of SORL1 function is an extremely rare event that was not associated with a dramatically earlier age at onset than heterozygous SORL1 loss-of-function variant carriers, in this single patient.
Inorganic Overgrowth of Aragonite on Molluscan Nacre Examined by Atomic Force Microscopy (1995)

The nacre (mother-of-pearl) that forms the irridescent inner layers of mollusc shells is a highly ordered microlaminate composite of aragonite crystals and biopolymers with a strength and fracture resistance that far exceed those of the mineral crystals themselves. The processes governing the biofabrication of this material by the secretory cells of the mantle are complex and only partially understood. We have used the atomic force microscope (AFM) to investigate the aqueous solution conditions under which mineral growth can occur on the nacreous layer of the shell of the bivalve mollusc Atrina sp. In situ imaging of the mature nacre surface exposed to a pH-controlled environment of natural seawater with added carbonate ions reveals that inorganic overgrowth of aragonite can occur within the ranges of pH and inorganic ion concentrations found in the molluscan extrapallial fluid from which the mineral is produced during biological shell growth. Thus, we posit that once nucleation has occurred, nacreous tablets could grow inorganically in the extrapallial space; the role of proteins and other macromolecules may be limited to initiating growth or controlling morphology through selective adsorption and spatial constraint on the growing crystal.
Calcium Phosphate Cements: Structure-related Properties (2021)

Calcium phosphate cements (CPCs) are commonly used as bone void fillers and to reinforce hardware in fracture repair. They are injectable, mouldable and self-setting in vivo, and in addition to being osteoconductive they can also be both bioactive and resorbable, which makes them interesting as bone regenerative biomaterials. The cement sets through a dissolution–precipitation process, and cement hardening occurs via the entanglement of the precipitated crystals. This type of setting reaction leads to an intricate microstructure, ranging from the nano- to the micrometre scale. Moreover, different types of porogens can be added to the cement paste, which changes the macrostructure of the hardened material. This chapter provides an overview of the structural organisation of CPCs at different length scales, which parameters influence it and also how this affects the characteristics of the cement. The structure and the porosity of the cement are dependent on the chemistry behind the setting reaction, as well as the size and size distribution of the starting powders, the choice of aqueous solution and the liquid-to-powder ratio. The structure of the cement, in turn, influences several important parameters of the cement. The microstructure can be correlated to the surface area, where a change in which affects both the resorbability and the bioactivity of the material. The mechanical properties of the cement can not only be strongly correlated to the structure and the porosity of the cement, but also to the efficacy of the crystal entanglement. Furthermore, CPCs can be used as drug delivery systems, where the structure of the cement influences both the amount of drug that can be loaded as well as the release rate.
Towards temporal characterization of intense isolated attosecond pulses from relativistic surface high harmonics (2018)

Relativistic surface high harmonics have been considered a unique source for the generation of intense isolated attosecond pulses in the extreme ultra-violet (XUV) and X-ray spectral range. However, its experimental realization is still a challenging task requiring identification of the optimum conditions for the generation of isolated attosecond pulses as well as their temporal characterization. Here, we demonstrate measurements in both directions. Particularly, we have made a first step towards the temporal characterization of the emitted XUV radiation by adapting the attosecond streak camera concept to identify the time domain characteristics of relativistic surface high harmonics. The results, supported by PIC simulations, set the upper limit for the averaged (over many shots) XUV duration to &lt;6 fs, even when driven by not CEP controlled relativistic few-cycle optical pulses. Moreover, by measuring the dependence of the spectrum of the relativistic surface high harmonics on the carrier envelope phase (CEP) of the driving infrared laser field, we experimentally determined the optimum conditions for the generation of intense isolated attosecond pulses.
Phase transitions from semiconductive amorphous to conductive polycrystalline in indium silicon oxide thin films (2016)

The enhancement in electrical conductivity and optical transparency induced by a phase transition from amorphous to polycrystalline in lightly silicon-doped indium oxide (InSiO) thin films is studied. The phase transition caused by simple thermal annealing transforms the InSiO thin films from semiconductors to conductors. Silicon atoms form SiO4 tetrahedra in InSiO, which enhances the overlap of In 5s orbitals as a result of the distortion of InO6 octahedral networks. Desorption of weakly bonded oxygen releases electrons from deep subgap states and enhances the electrical conductivity and optical transparency of the films. Optical absorption and X-ray photoelectron spectroscopy measurements reveal that the phase transition causes a Fermi energy shift of ∼0.2 eV.
A rover for the JAXA MMX Mission to Phobos (2019)

The Martian Moons eXploration (MMX) is a mission by the Japan Aerospace Exploration Agency, JAXA,to the Martian moons Phobos and Deimos. It will primarily investigate the origin of this moon by bringing samples back from Phobos to Earth and deliver a small (about 25 kg) Rover to the surface. The Rover is a contribution by the Centre National d’Etudes Spatiales (CNES) and the German Aerospace Center (DLR). Its currently considered scientific payload consists of a thermal mapper (miniRAD), a Raman spectrometer (RAX) a stereo pair of cameras looking forward (NavCAM)and two cameras looking at the interface wheel-surface (WheelCAM) and consequent Phobos’ regolith mechanical properties.The cameras will serve for both, technological and scientific needs. The MMX rover will be delivered from an altitude of <100 m and start uprighting and deploying wheels and a solar generator after having come to rest on the surface. It is planned to operate for three months on Phobos and provide unprecedented science while moving for a few meters to hundreds of meters. MMX will be launched in September 2024 and inserted into Mars orbit in 2025, the Rover delivery and operations are planned for 2026-2027.