gebhart/patrepeval huggingface dataset:
Cover Picture: Multifunctional Inorganic Nanocontainers for DNA and Drug Delivery into Living Cells (Chem. Eur. J. 35/2014) (2014)

Manufacturing porous particles to enable them to carry bioactive molecules into living cells is a target for the development of personalized nanomedicine. In their Communication on page 10900 ff., L. De Cola et al. describe using zeolite-L crystals as multifunctional nanocontainers to simultaneously deliver DNA oligonucleotides and organic molecules into living cells. Multifunctional zeolite-L was prepared by filling the pore system with guest molecules, whilst DNA was adsorbed electrostatically on their surface. Manufacturing porous particles to enable them to carry bioactive molecules into living cells is a target for the development of personalized nanomedicine. In their Communication on page 10900 ff., L. De Cola et al. describe using zeolite-L crystals as multifunctional nanocontainers to simultaneously deliver DNA oligonucleotides and organic molecules into living cells. Multifunctional zeolite-L was prepared by filling the pore system with guest molecules, whilst DNA was adsorbed electrostatically on their surface. Probe Design Mechanism-based retaining glycosidase inhibitors serve as starting point for the design of activity-based glycosidase probes. Retaining glycosidases employ a double displacement mechanism in the hydrolysis of glycosidic bonds with overall retention. In contrast to inverting glycosidases, retaining glycosidases form a covalent intermediate with their substrates during the catalytic process and are therefore amenable to activity-based protein profiling studies. In their Concept on page 10864 ff., H. Overkleeft et al. present the current progress and future directions in the design of activity-based probes targeting retaining glycosidases.1 Supramolecular Chemistry Recent developments on the synthesis of new macrocycles have strongly contributed to the progress in the fabrication of composites, yet, this field can still be considered to be in its infancy. The Minireview by J. Pérez-Juste, L. M. Liz-Marzán et al. on page 10874 ff. focuses on the synthesis of noble-metal nanoparticles with macrocycles acting as capping agents or/and reducing agents, as well as on the post-synthetic metal-nanoparticle modification with macrocycles (SERS = surface-enhanced Raman spectroscopy).1 Multitalented Glycerol The Minireview by M. Gómez and co-workers on page 10884 ff. discusses recent developments associated with using glycerol as a solvent in the synthesis of organometallic complexes and metallic nanoparticles. It mainly focuses on their catalytic applications and the ability of glycerol to immobilize nanometric species, which, in turn, enables a straightforward recycling of the catalytic phase.1
Studies towards the Synthesis of (–)-Pulvomycin: Construction of the C12–C40 Segment by a Stereoselective Aldol Reaction (2021)

Abstract A convergent strategy was developed for the synthesis of the C12–C40 segment of (–)-pulvomycin. Key step was a diastereoselective aldol reaction between a chiral ethyl ketone representing the C24–C40 fragment and a chiral aldehyde representing the C12–C23 fragment. Both compounds were prepared from enantiomerically pure building blocks in a convergent fashion. The longest linear sequence commenced with a known d-fucose-derived glycosyl donor and entailed a total number of 16 steps. The desired anti-aldol product was obtained in a total yield of 5% over these steps and contains 12 out of 13 stereogenic centers present in the natural product.
Gate controllability of HfSiOx/AlGaN/GaN MOS high-electron-mobility transistor (2020)

Hafnium silicate (HfSiOx) has been applied to AlGaN/GaN high-electron-mobility transistors (HEMTs) as a high κ gate dielectric. The (HfO2)/(SiO2) laminate structure was deposited on the AlGaN surface by a plasma-enhanced atomic layer deposition, followed by a post-deposition annealing at 800 °C. The HfSiOx-gate HEMT showed good transfer characteristics with a high transconductance expected from its κ value and a subthreshold swing of 71 mV/decade. For the metal–oxide-semiconductor (MOS) HEMT diode, we observed excellent capacitance–voltage (C–V) characteristics with negligible frequency dispersion. The detailed C–V analysis showed low state densities on the order of 1011 cm−2 eV−1 at the HfSiOx/AlGaN interface. In addition, excellent operation stability of the MOS HEMT was observed at high temperatures up to 150 °C.
Actin maturation requires the ACTMAP/C19orf54 protease (2022)

Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves noncanonical excision of the acetylated methionine by an unidentified enzyme after translation. Here, we identified C19orf54, named ACTMAP (actin maturation protease), as this enzyme. Its ablation resulted in viable mice in which the cytoskeleton was composed of immature actin molecules across all tissues. However, in skeletal muscle, the lengths of sarcomeric actin filaments were shorter, muscle function was decreased, and centralized nuclei, a common hallmark of myopathies, progressively accumulated. Thus, ACTMAP encodes the missing factor required for the synthesis of mature actin and regulates specific actin-dependent traits in vivo.
PTU-263 Profiling humoral immune responses to clostridium difficile-specific antigens by protein microarray (2015)

<h3>Introduction</h3> The main objective of this study was to develop, validate and implement a novel microarray platform to enable the simultaneous quantification of systemic IgG immune responses to a 7-plex panel of highly purified <i>C. difficile</i>-specific virulence factors, including whole toxins A and B (toxinotype 0, strain VPI10463, ribotype 087), recombinant fragments of toxin A and B, PCR ribotype-specific surface layer proteins (001, 002, 027) and control proteins (tetanus and candida). We evaluated the performance of the microarray technique against tradional ELISA. <h3>Method</h3> Microbial antigens were diluted to 200 μg/ml in printing buffer in a 384-well plate and spotted in quadruplicate onto poly-L-Lysine-coated slides using a Biorobotics MicroGridII arrayer. The slides were blocked with 5% BSA diluted in PBS-Tween-20 wash buffer. After washing, all slides were incubated with sera diluted 1:500 in antibody diluent. Following washing, slides were incubated with biotinylated anti-human IgG diluted 1:20,000, washed and then incubated with Streptavidin Cy5 diluted 1:2,000 in 5% BSA. After final washes, slides were dried by centrifugation and scanned using a GenePix 4200AL scanner. The resultant TIFF images were processed with Axon GenePix Pro-6 microarray image analysis software. Protein signals were finally determined with background subtraction using RPPanalyzer, a module within the R statistical language on CRAN (http://vran.r-project.org). Kruskall Wallis was used with Dunn’s post test. Correlation was evaluated using Spearman rank correlation coefficient. <i>P </i>values of &lt; 0.05 were considered statistically significant. <h3>Results</h3> A total of 327 serum samples from patients with <i>C. difficile </i>infection (CDI), cystic fibrosis (CF) and healthy controls (HC) were tested by microarray for the presence of specific IgG antibody. The microarray assay fell within acceptable limits of precision for both intra- and inter-assay variability for all antigens tested (&lt;10% CV). Additionally, there was significant correlation (<i>p &lt; 0</i>.0001) between antibody detection levels using the microarray system and the ELISA format. <h3>Conclusion</h3> This is the first reported use of protein microarray to assess serum immunoreactivities to <i>C. difficile</i>-specific antigens. Our results suggest that the microarray platform allows accurate, precise and reproducible specific antibody quantifcation. Additional modifications of this approach could be used to simultaneously study multiple isotype specificities to several <i>C. difficile</i>strain-specific antigens for large collections of patient sera. <h3>Disclosure of interest</h3> O. Negm: None Declared, M. Hamed: None Declared, E. Abbott: None Declared, P. Tighe: None Declared, C. Shone: None Declared, C. Loscher: None Declared, L. Edwards: None Declared, M. Wilcox Grant/ Research Support from: Multiple therapeutic and diagnostic companies, Consultant for: Multiple therapeutic and diagnostic companies, T. Monaghan: None Declared.
Evaluating Plasmonic Transport in Current-carrying Silver Nanowires (2013)

Plasmonics is an emerging technology capable of simultaneously transporting a plasmonic signal and an electronic signal on the same information support. In this context, metal nanowires are especially desirable for realizing dense routing networks. A prerequisite to operate such shared nanowire-based platform relies on our ability to electrically contact individual metal nanowires and efficiently excite surface plasmon polaritons in this information support. In this article, we describe a protocol to bring electrical terminals to chemically-synthesized silver nanowires randomly distributed on a glass substrate. The positions of the nanowire ends with respect to predefined landmarks are precisely located using standard optical transmission microscopy before encapsulation in an electron-sensitive resist. Trenches representing the electrode layout are subsequently designed by electron-beam lithography. Metal electrodes are then fabricated by thermally evaporating a Cr/Au layer followed by a chemical lift-off. The contacted silver nanowires are finally transferred to a leakage radiation microscope for surface plasmon excitation and characterization. Surface plasmons are launched in the nanowires by focusing a near infrared laser beam on a diffraction-limited spot overlapping one nanowire extremity. For sufficiently large nanowires, the surface plasmon mode leaks into the glass substrate. This leakage radiation is readily detected, imaged, and analyzed in the different conjugate planes in leakage radiation microscopy. The electrical terminals do not affect the plasmon propagation. However, a current-induced morphological deterioration of the nanowire drastically degrades the flow of surface plasmons. The combination of surface plasmon leakage radiation microscopy with a simultaneous analysis of the nanowire electrical transport characteristics reveals the intrinsic limitations of such plasmonic circuitry.
Catalytic 3D polymerization of C60 (2018)

The present study addresses the problems of catalytic synthesis of C60-based 3D polymers in the presence of carbon disulfide CS2. It is shown that CS2 lowers the pressure of fullerite 3D polymerization at room temperature. In particular, the pressure at which the 3D ultrahard fullerite C60 phase is formed decreases from 18 GPa to 7 GPa. The catalyst plays no significant role at room temperature and low pressures up to 6 GPa. When the C60 + CS2 is heated to 1200 K, the pressure of the 3D C60 polymerization is further reduced to 2–4 GPa. Based on the TEM data, we propose a 3D polymer structure based on C60 obtained by the catalytic synthesis.
Teaching an Old Molecule New Tricks: Drug Repositioning for Duchenne Muscular Dystrophy (2019)

<b>:</b> Duchenne muscular dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophies. The disease is caused by the lack of dystrophin, a structurally essential protein; hence, a definitive cure would necessarily have to pass through some form of gene and/or cell therapy. Cell- and genetic-based therapeutics for DMD have been explored since the 1990s and recently, two of the latter have been approved for clinical use, but their efficacy is still very low. In parallel, there have been great ongoing efforts aimed at targeting the downstream pathogenic effects of dystrophin deficiency using classical pharmacological approaches, with synthetic or biological molecules. However, as it is always the case with rare diseases, R&D costs for new drugs can represent a major hurdle for researchers and patients alike. This problem can be greatly alleviated by experimenting the use of molecules that had originally been developed for different conditions, a process known as drug repurposing or drug repositioning. In this review, we will describe the state of the art of such an approach for DMD, both in the context of clinical trials and pre-clinical studies<b>.</b>
SPAKE Pre-Authentication (2020)

This document defines a new pre-authentication mechanism for the
Kerberos protocol that uses a password authenticated key exchange.
This document has three goals. First, increase the security of
Kerberos pre-authentication exchanges by making offline brute-force
attacks infeasible. Second, enable the use of second factor
authentication without relying on FAST. This is achieved using the
existing trust relationship established by the shared first factor.
Third, make Kerberos pre-authentication more resilient against time
synchronization errors by removing the need to transfer an encrypted
timestamp from the client.
Model-based Approximate Query Processing (2018)

Interactive visualizations are arguably the most important tool to explore, understand and convey facts about data. In the past years, the database community has been working on different techniques for Approximate Query Processing (AQP) that aim to deliver an approximate query result given a fixed time bound to support interactive visualizations better. However, classical AQP approaches suffer from various problems that limit the applicability to support the ad-hoc exploration of a new data set: (1) Classical AQP approaches that perform online sampling can support ad-hoc exploration queries but yield low quality if executed over rare subpopulations. (2) Classical AQP approaches that rely on offline sampling can use some form of biased sampling to mitigate these problems but require a priori knowledge of the workload, which is often not realistic if users want to explore a new database. In this paper, we present a new approach to AQP called Model-based AQP that leverages generative models learned over the complete database to answer SQL queries at interactive speeds. Different from classical AQP approaches, generative models allow us to compute responses to ad-hoc queries and deliver high-quality estimates also over rare subpopulations at the same time. In our experiments with real and synthetic data sets, we show that Model-based AQP can in many scenarios return more accurate results in a shorter runtime. Furthermore, we think that our techniques of using generative models presented in this paper can not only be used for AQP in databases but also has applications for other database problems including Query Optimization as well as Data Cleaning.
A soluble, magnesium‐independent prenyltransferase catalyzes reverse and regular C‐prenylations and O‐prenylations of aromatic substrates (2007)

Fnq26 from Streptomyces cinnamonensis DSM 1042 is a new member of the recently identified CloQ/Orf2 class of prenyltransferases. The enzyme was overexpressed in E. coli and purified to apparent homogeneity, resulting in a soluble, monomeric protein of 33.2 kDa. The catalytic activity of Fnq26 is independent of the presence of Mg(2+) or other divalent metal ions. With flaviolin (2,5,7-trihydroxy-1,4-naphthoquinone) as substrate, Fnq26 catalyzes the formation of a carbon-carbon-bond between C-3 (rather than C-1) of geranyl diphosphate and C-3 of flaviolin, i.e. an unusual "reverse" prenylation. With 1,3-dihydroxynaphthalene and 4-hydroxybenzoate as substrates Fnq26 catalyzes O-prenylations.
Stream-Centric Stereo Matching and View Synthesis: A High-Speed Approach on GPUs (2009)

In this paper, we propose a real-time image-based rendering (IBR) system. It is specifically designed for photorealistic view synthesis at high-speed on the graphics processing unit (GPU). We steer the proposed IBR system design with two high-level ideas. First, for cost-effective IBR, as long as the synthesized views look visually plausible, the estimated disparity and occlusion need not be correct. Hence, we jointly optimize stereo matching and view synthesis for a favorable end-to-end performance. Second, for great real-time acceleration on GPUs, all functional modules need be shaped at an early design stage, fitting the massively parallel streaming architecture of GPUs. Based on these two guidelines, we first propose a stream-centric local stereo matching algorithm. The key idea is to construct a versatile set of variable support patterns in a highly efficient manner, and then an optimal local support pattern is selected to approximate varying image structures adaptively. Next, a low-complexity adaptive view synthesis technique is proposed. It efficiently tackles visual artifacts in synthesized images, using a novel photometric outlier detection and handling scheme. We evaluated both the disparity estimation accuracy and novel view synthesis quality of the proposed approach, based on the benchmark Middlebury stereo datasets. The experiments show that our local stereo method produces consistently reliable disparity estimates for both homogeneous regions and depth discontinuities, outperforming several previous GPU-based local methods. More importantly, visually plausible intermediate views are generated by our IBR approach at high-speed on the GPU. With stereo matching and view synthesis completely running on an NVIDIA GeForce 8800 GT graphics card, the proposed IBR system reaches about 100 f/s for 450times375 stereo images with 60 disparity levels.
A Method for Determining Load-Dependent Stiffness of Flexures (2015)

This paper explores strategies for static balancing of several flexure types. First, it describes a method for determining the load-dependent stiffness behavior of compliant flexures. Load-dependent stiffness means that the stiffness changes when a flexure is subjected to force loads perpendicular to its axis of rotation. A set of non-dimensional parameters is selected to describe the loads and the resulting stiffness. Finite element models of each joint are developed, and stiffness data is gathered for a range of horizontal and vertical loading regimes. The method is verified by comparing results to an analytic model for joints where such is available, and to results in the literature. The load-dependent stiffness behavior is then examined to identify new strategies for static balancing that have not yet appeared in the literature.
Purinergic receptor activation evokes neurotrophic factor NPY release from mouse olfactory epithelial slices (2007)

The signals for injury-evoked neuroregeneration are unknown; however previous studies implied that injured cells secrete neurotrophic factors which trigger neurogenesis. Extracellular purine nucleotides exert multiple neurotrophic actions in the CNS mediated via activation of purinergic (P2) receptors. Our previous work demonstrated that ATP acts as a neuromodulator and a stress signal in the olfactory epithelium (OE). To determine whether ATP and P2 receptor activation evokes neurotrophic factor secretion in the OE, we monitored release of NPY, a neuroproliferative factor known to be present and functional in the OE. Neonatal mouse OE slices were cultured on nitrocellulose paper to visualize NPY release. Immunoassaying the nitrocellulose resulted in NPY immunoreactivity in the region corresponding to the OE of the nasal septum. Exogenous ATP (10–500 mM) significantly increased the percentage of OE slices that released NPY from 22% to 46% (p<0.05). P2 receptor antagonists PPADS (25 mM) and suramin (100 mM) reduced the number of OE slices exhibiting NPY release evoked by ATP by 53%, suggesting that activation of P2 receptors mediates NPY release. This study directly verifies that neurotrophic factor ATP evokes neurotrophic factor NPY release in the OE and provides pharmacological targets to promote regeneration of damaged OE. Research supported by NIH NIDCD DC006897.
Postnatal signalling with homeoprotein transcription factors (2014)

Homeoprotein (HP) transcription factors were originally identified for their embryonic cell-autonomous developmental functions. In this review, we discuss their postnatal and adult physiological functions based on the study of Otx2, Engrailed-1 and Engrailed-2 (collectively Engrailed). For Engrailed, we discuss its function in the cell-autonomous regulation of ventral midbrain dopaminergic neuron survival and physiology and in the non-cell-autonomous maintenance of axons. For Otx2, we describe how the protein is expressed in the choroid plexus and transported into cortical parvalbumin cells where it regulates plasticity in the visual cortex. These two examples illustrate how the understanding of HP postnatal and adult functions, including signalling functions, may lead to the identification of disease-associated genetic pathways and to the development of original therapeutic strategies.
JAK inhibition with ruxolitinib in relapsed or refractory classical Hodgkin lymphoma: Final results of a phase II, open label, multicentre clinical trial (JeRiCHO) (2022)

Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1.
The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL (2020)

Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based on persistence of minimal residual disease (MRD). New insights into biological features that are associated with MRD are needed. Here, we identify the glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting the cell surface proteome of MRD very high-risk (HR) B-cell precursor (BCP) ALL using a chemoproteomics strategy. The correlation between VNN2 transcript and surface protein expression enabled a retrospective analysis (ALL-BFM 2000; N = 770 cases) using quantitative polymerase chain reaction to confirm the association of VNN2 with MRD and independent prediction of worse outcome. Using flow cytometry, we detected VNN2 expression in 2 waves, in human adult bone marrow stem and progenitor cells and in the mature myeloid compartment, in line with proposed roles for fetal hematopoietic stem cells and inflammation. Prospective validation by flow cytometry in the ongoing clinical trial (AIEOP-BFM 2009) identified 10% (103/1069) of VNN2+ BCP ALL patients at first diagnosis, primarily in the MRD MR (48/103, 47%) and HR (37/103, 36%) groups, across various cytogenetic subtypes. We also detected frequent mutations in epigenetic regulators in VNN2+ ALLs, including histone H3 methyltransferases MLL2, SETD2, and EZH2 and demethylase KDM6A. Inactivation of the VNN2 gene did not impair leukemia repopulation capacity in xenografts. Taken together, VNN2 marks a cellular state of increased resistance to chemotherapy that warrants further investigations. Therefore, this marker should be included in diagnostic flow cytometry panels.