gebhart/patrepeval huggingface dataset:
BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor (2022)

[Image: see text] Despite advances in the treatment of heart failure in recent years, options for patients are still limited and the disease is associated with considerable morbidity and mortality. Modulating cyclic guanosine monophosphate levels within the natriuretic peptide signaling pathway by inhibiting PDE9A has been associated with beneficial effects in preclinical heart failure models. We herein report the identification of BAY-7081, a potent, selective, and orally bioavailable PDE9A inhibitor with very good aqueous solubility starting from a high-throughput screening hit. Key aspect of the optimization was a switch in metabolism of our lead structures from glucuronidation to oxidation. The switch proved being essential for the identification of compounds with improved pharmacokinetic profiles. By studying a tool compound in a transverse aortic constriction mouse model, we were able to substantiate the relevance of PDE9A inhibition in heart diseases.
IgA proteases of two distinct specificities are released by Neisseria meningitidis. (1980)

Strains of Neisseria meningitidis produce two distinct extracellular IgA proteases that cleave the human IgA1 heavy chain at different points within the hinge region. Type 1 protease cleaves the prolyl-seryl peptide bond at position 237-238; type type 2 protease cleaves the prolyl-threonyl bond two residues amino terminal to that bond attacked by type 1 enzyme. Each meningococcal isolate elaborates only one of these two enzymes, and the type of protease produced correlates with certain serogroups: group A yielding only type 1, and groups X and Y only type 2 enzyme. In addition, analysis of amino acid sequences of human alpha-chain proteins reveals that the repeating octapeptide characteristic of the IgA1 hinge region is actually triplicated.
Repurposing dasatinib for diffuse large B cell lymphoma (2019)

To repurpose compounds for diffuse large B cell lymphoma (DLBCL), we screened a library of drugs and other targeted compounds approved by the US Food and Drug Administration on 9 cell lines and validated the results on a panel of 32 genetically characterized DLBCL cell lines. Dasatinib, a multikinase inhibitor, was effective against 50% of DLBCL cell lines, as well as against in vivo xenografts. Dasatinib was more broadly active than the Bruton kinase inhibitor ibrutinib and overcame ibrutinib resistance. Tumors exhibiting dasatinib resistance were commonly characterized by activation of the PI3K pathway and loss of PTEN expression as a specific biomarker. PI3K suppression by mTORC2 inhibition synergized with dasatinib and abolished resistance in vitro and in vivo. These results provide a proof of concept for the repurposing approach in DLBCL, and point to dasatinib as an attractive strategy for further clinical development in lymphomas.
Graphical definitions (1998)

In the past, attempts to extend the spreadsheet paradigm to support graphical objects, such as colored circles or user-defined graphical types, have led to approaches featuring either a direct way of creating objects graphically or strong compatibility with the spreadsheet paradigm, but not both. This inability to conveniently go beyond numbers and strings without straying outside the spreadsheet paradigm has been a limiting factor in the applicability of spreadsheet languages. In this article we present graphical definitions, an approach that removes this limitation, allowing both simple and complex graphical objects to be programmed directly using direct manipulation and gestures, in a manner that fits seamlessly within the spreadsheet paradigm. We also describe an empirical study, in which subjects programmed such objects faster and with fewer errors using this approach than when using a traditional approach to formula specification. Because the approach is expressive enough to be used with both built-in and user-defined types, it allows the directness of demonstrational and spreadsheet techniques to be used in programming a wider range of applications than has been possible before.
PDB_ISL (2000)

For large scale structural assignment to sequences, as in computational structural genomics, a fast yet sensitive homology search procedure is essential. A new approach using intermediate sequences was tested as a shortcut to iterative multiple sequence search methods such as PSI-BLAST and hidden Markov models. A library containing potential intermediate sequences for proteins of known structure (PDB_ISL) was constructed. The sequences in the library were collected from a large sequence database using the sequences of the domains of proteins of known structure as the query sequences and the program PSI-BLAST. Sequences of proteins of unknown structure can be matched to distantly related proteins of known structure by using any pairwise sequence comparison methods to find homologues in PDB_ISL. Searches of PDB_ISL were calibrated, and the number of correct matches found at a given error rate was the same as that found by PSI_BLAST. The advantage of this library is that it uses pairwise sequence comparison methods, such as FASTA or BLAST2, and can, therefore, be searched easily and, in many cases, much more quickly than an iterative multiple sequence comparison method. The procedure is roughly twenty times faster than PSI-BLAST for small genomes and several hundred times for large genomes such as C. elegans.
Capacitive power transfer for slip ring replacement in wound field synchronous machines (2011)

Permanent magnet synchronous machines are utilized in a wide variety of applications due to their many desirable characteristics, including high torque density capability and high efficiency. In the near future, however, the demand for the permanent magnet rare earth materials is projected to exceed world production. As a result, electric machines which do not rely on rare earth materials, such as wound field synchronous machines (WFSMs), are receiving renewed attention for use in traction and wind energy applications. However, WFSMs require a current delivery mechanism to the rotor such as mechanical slip rings whose components require periodic replacement and generate adverse debris within the machine enclosure. Rotary transformers may replace slip rings but also introduce rotor speed dependencies and magnetic coupling difficulties. This paper proposes a capacitive non-contact power transfer technique to eliminate the need for mechanical slip rings while also avoiding the pitfalls of rotating transformer technologies. The capacitive power transfer system is compared to traditional rotor power coupling techniques and its performance is validated with experimental results.
Peer Review Certifies Quality and Innovation in Clinical Pharmacology & Therapeutics (2017)

Clinical Pharmacology & Therapeutics (CPT) is an established voice of the discipline, a trusted source of new knowledge showcasing discovery, translation, and application of novel therapeutic paradigms to advance the management of patients and populations. Identifying, evaluating, prioritizing, and disseminating the best science along the discovery-development-regulatory-utilization continuum are responsibilities shared through peer review. To enhance the uniformity of this essential component of quality assurance and innovation, and maximize the value of the journal and its contents to authors, reviewers, and the readership, we review key concepts concerning peer review as it specifically relates to CPT.
Microfluidic Devices for Energy Conversion:  Planar Integration and Performance of a Passive, Fully Immersed H2−O2 Fuel Cell (2004)

We describe the fabrication and performance of a passive, microfluidics-based H2-O2 microfluidic fuel cell using thin film Pt electrodes embedded in a poly(dimethylsiloxane) (PDMS) device. The electrode array is fully immersed in a liquid electrolyte confined inside the microchannel network, which serves also as a thin gas-permeable membrane through which the reactants are fed to the electrodes. The cell operates at room temperature with a maximum power density of around 700 microW/cm(2), while its performance, as recorded by monitoring the corresponding polarization curves and the power density plots, is affected by the pH of the electrolyte, its concentration, the surface area of the Pt electrodes, and the thickness of the PDMS membrane. The best results were obtained in basic solutions using electrochemically roughened Pt electrodes, the roughness factor, R(f), of which was around 90 relative to a smooth Pt film. In addition, the operating lifetime of the fuel cell was found to be longer for the one using higher surface area electrodes.
The Formation of Ultrafine Particles of Metal Sulfide by the Electrostatic Spray Pyrolysis Method [Translated]<sup>†</sup> (1997)

In the preparation of fine particles of metal sulfide such as zinc sulfide and cadmium sulfide using the spray pyrolysis method, the electrostatic spray method was applied to atomize the starting solutions. The optimum operation conditions where the droplets could be generated from a Taylor cone were examined experimentally. It was shown that the use of the electrostatic spray pyrolysis method is available for preparing the several dozens nanometer-sized fine particles, in comparison with a typical ultrasonic spray pyrolysis method that produced the several hundreds nanometer size.† This report was originally printed in J. Soc. Powder Technology, Japan. 33(3), 192-198 (1996) in Japanese, before being translated into English by KONA Editorial Committee with the permission of the editorial committee of the Soc. Powder Technology, Japan.
Preparative separaton of plasmid and bacterial artificial chromosome DNA by density gradient electrophoresis in the presence of linear polymers (1998)

A density gradient apparatus was used to examine the separation of different physical forms and sizes of DNA. A gradient of sucrose was used to stabilize thermal convection during electrophoresis in the column (2.2 cm in diameter). Linear polymers were added to the density gradient and screened for their ability to separate the supercoiled, nicked circular, and linear forms of the plasmid pBR 322. The influence of different concentrations and molecular weights of the polymers was examined on the separation. Polyethylene oxide with a molecular weight of 5,000,000 and a concentration of 0.2% w/v achieved the best separation results for the different physical forms of the plasmid. The order of separation of the different physical forms of the plasmid were linear (fastest), supercoiled, and nicked circular (slowest). These conditions were also used to separate a preparation of bacterial artificial chromosome (BAC) DNA. A rapidly moving form, presumably the supercoiled form, was resolved from a large amount of E. coli genomic DNA and from sheared forms of the BAC DNA.
Dynamic flux of microvesicles modulate parasite-host cell interaction ofTrypanosoma cruziin eukaryotic cells (2016)

Extracellular vesicles released from pathogens may alter host cell functions. We previously demonstrated the involvement of host cell-derived microvesicles (MVs) during early interaction between Trypanosoma cruzi metacyclic trypomastigote (META) stage and THP-1 cells. Here, we aim to understand the contribution of different parasite stages and their extracellular vesicles in the interaction with host cells. First, we observed that infective host cell-derived trypomastigote (tissue culture-derived trypomastigote [TCT]), META, and noninfective epimastigote (EPI) stages were able to induce different levels of MV release from THP-1 cells; however, only META and TCT could increase host cell invasion. Fluorescence resonance energy transfer microscopy revealed that THP-1-derived MVs can fuse with parasite-derived MVs. Furthermore, MVs derived from the TCT-THP-1 interaction showed a higher fusogenic capacity than those from META- or EPI-THP-1 interaction. However, a higher presence of proteins from META (25%) than TCT (12%) or EPI (5%) was observed in MVs from parasite-THP-1 interaction, as determined by proteomics. Finally, sera from patients with chronic Chagas disease at the indeterminate or cardiac phase differentially recognized antigens in THP-1-derived MVs resulting only from interaction with infective stages. The understanding of intracellular trafficking and the effect of MVs modulating the immune system may provide important clues about Chagas disease pathophysiology.
Development of Methodology to Assess the Effect of Stem Surface Finish on Implant Loosening (2010)

Joint replacement surgery is a common orthopaedic procedure used for the treatment of diseased or damaged joints. The majority of these replacement systems incorporate a stemmed portion which is inserted into the bone canal, either with or without bone cement, to achieve fixation to the host bone. Although this procedure has proven effective, relative displacement at the bone-cement and/or cement-stem interfaces (i.e., implant loosening) is a common complication, leading to pain and the need for revision surgery.
Policy Processing: Don't Take it for Granted (2009)

The new advanced services and limitations of current Internet have driven a lot of initiatives in architectures for future Internet. Ambient networks is one of these initiatives, focused in providing a seamless cooperation of resources in an environment with a multitude of access technologies, network operators and business actors. There are many efforts using policy based management as a practical solution for addressing the challenges for the management of future Internet such as cross-domain management, integration and manipulation of data across the world, seamless mobility, reliability, performance and heterogeneity support. However, not much attention has been given to the policy processing itself. In this paper we present our policy processing system, currently used in the PBMAN project, a policy based management architecture and prototype for Ambient Networks. The primary contribution of this paper is to give real attention to the components of policy systems that can determine its performance as well as its successful adoption.
Bendability optimization of flexible optical nanoelectronics via neutral axis engineering (2012)

The enhancement of bendability of flexible nanoelectronics is critically important to realize future portable and wearable nanoelectronics for personal and military purposes. Because there is an enormous variety of materials and structures that are used for flexible nanoelectronic devices, a governing design rule for optimizing the bendability of these nanodevices is required. In this article, we suggest a design rule to optimize the bendability of flexible nanoelectronics through neutral axis (NA) engineering. In flexible optical nanoelectronics, transparent electrodes such as indium tin oxide (ITO) are usually the most fragile under an external load because of their brittleness. Therefore, we representatively focus on the bendability of ITO which has been widely used as transparent electrodes, and the NA is controlled by employing a buffer layer on the ITO layer. First, we independently investigate the effect of the thickness and elastic modulus of a buffer layer on the bendability of an ITO film. Then, we develop a design rule for the bendability optimization of flexible optical nanoelectronics. Because NA is determined by considering both the thickness and elastic modulus of a buffer layer, the design rule is conceived to be applicable regardless of the material and thickness that are used for the buffer layer. Finally, our design rule is applied to optimize the bendability of an organic solar cell, which allows the bending radius to reach about 1 mm. Our design rule is thus expected to provide a great strategy to enhance the bending performance of a variety of flexible nanoelectronics.
Group-10 π-hole⋯dz2[MII] interactions: a theoretical study of model systems inspired by CSD structures (2023)

In recent years Pd(II) and Pt(II) cases have been reported wherein metals in square planar complexes were used as nucleophilic partners to construct supramolecular assemblies with electrophilic molecules like σ-hole and π-hole donors. The formation of such assemblies is based on the nucleophilicity and accessibility of the d<sub><i>z</i><sup>2</sup></sub> orbital (in group-10 elements) in the square-planar complexes. This opens new avenues in inorganic chemistry and crystal engineering as it enriches the current toolbox of noncovalent interactions and supramolecular synthons thus allowing the design of new types of architectures in the solid state. This manuscript reports a comprehensive theoretical study characterizing π-hole⋯d<sub><i>z</i><sup>2</sup></sub>[M<sup>II</sup>] (M = group 10 element) interactions from an energetic point of view. Several computational tools based on the topology of the electron density are used. Examined systems had been identified by considering structures in the Cambridge Structural Database where this interaction was used to construct supramolecular assemblies. Several aromatic rings have been used, varying from π-basic to π-acid rings by adjusting the number of fluorine substituents. Moreover, the influence of metal⋯metal interactions on the nucleophilicity of the d<sub><i>z</i><sup>2</sup></sub> orbital has been studied using MEP surface analysis. The π-hole energies are moderately strong (from -5 to -10 kcal mol<sup>-1</sup>) and the crucial role of dispersion forces is revealed.
FEBS Open Bio (2018)

FEBS Open Bio is an open access journal for the rapid publication of research articles across the molecular and cellular life sciences. The journal’s rigorous peer review process focusses on the technical and ethical quality of papers, rather than objective judgements of significance. We also welcome papers that report confirmatory or negative results.
Maskless Laser Patterning for Gold Plating of Microelectronic Materials (1983)

The authors have developed a method for producing small area patterns using any one of several organic coatings, including photoresist in conjunction with a Q‐switched Nd‐YAG laser. The laser removes the coating locally leaving a clean metal surface which can then be plated by conventional means. The authors have laser patterned coated substrates of copper, nickel, nickel‐plated Be‐Cu, and gold plated the patterned diam regions. These areas are typical of those required on microelectronic connector parts and serve to demonstrate the potential of this simple technique for conserving precious metals. Laser and coating parameters are described together with details of the patterning method.
A derivative of a rigid glutamate analog protects the retina from excitotoxicity (1994)

In the retina, the activation of metabotropic glutamate receptors (mGluRs) reduces the toxic effect of N-methyl-D-aspartate (NMDA). We have induced NMDA-mediated excitotoxicity in the adult rat retina by a single intraocular injection of NMDA. The damage that resulted was estimated by assessing the NMDA-induced loss of retinal choline acetyltransferase (ChAT) activity. The new rigid glutamate analog, dimethyl ester of (+/-)-trans-azetidine-2,4-dicarboxylic acid (t-DMADA), with a putative mGluR-agonistic activity, protected the retina from NMDA-induced loss of ChAT activity. This study demonstrated that t-DMADA can be considered a prototype of new retino-protective agents.
Nanopatterning with tailored molecules (2014)

Star block copolymer synthesis was performed in a controlled fashion by an in-situ core first ATRP route. The obtained resist materials on the basis of industrial used monomers with tailored star block copolymer architecture were systematically characterized and patterned. In dissolution investigations an excellent dissolution contrast between exposed and unexposed state was identified for this new resist material type. Additionally, the materials show an excellent sensitivity, which surpass the reference linear copolymer by a factor of eight. By a combinatorial resist optimization realized high resolution features are presented. Finally, preliminary results utilizing a further improved resist material design are shown.
OHMIC HEATING OF SOLID‐LIQUID MIXTURES: A COMPARISON OF MATHEMATICAL MODELS UNDER WORST‐CASE HEATING CONDITIONS1 (1998)

ABSTRACT A critical issue in the modeling of ohmic heating of solid‐liquid mixtures is the understanding of worst‐case scenarios, and in particular, the reliability of mathematical models under such conditions. This study involves examination of two alternative published formulations, one involving the use of circuit theory and a well‐mixed fluid assumption, against another formulation, involving the solution to Laplace's equation, but without convective effects. As expected, the models (and an analytical solution) yield identical results under situations where solid and fluid electrical conductivity are equal. However, when the solid is of lower electrical conductivity than the fluid, the Circuit Analogy, Mixed Fluid (CAMF) approach is shown to be more conservative than the Laplace Equation, No Convection (LENC) approach. This prediction is borne out by experimental studies, which confirm that the worst‐case scenario in ohmic heating is not necessarily associated with a stationary fluid situation. Under the less likely conditions where the solid is more conductive than the fluid, the LENC approach is more conservative than the CAMF approach. Models are also compared with respect to other features, such as practicality of use, and computational cost.
ShiftsReduce (2019)

Racetrack memories (RMs) have significantly evolved since their conception in 2008, making them a serious contender in the field of emerging memory technologies. Despite key technological advancements, the access latency and energy consumption of an RM-based system are still highly influenced by the number of shift operations. These operations are required to move bits to the right positions in the racetracks. This article presents data-placement techniques for RMs that maximize the likelihood that consecutive references access nearby memory locations at runtime, thereby minimizing the number of shifts. We present an integer linear programming (ILP) formulation for optimal data placement in RMs, and we revisit existing offset assignment heuristics, originally proposed for random-access memories. We introduce a novel heuristic tailored to a realistic RM and combine it with a genetic search to further improve the solution. We show a reduction in the number of shifts of up to 52.5%, outperforming the state of the art by up to 16.1%.
Sumi-supervised deep autoencoder network for graph-based dimensionality reduction in hyperspectral imagery (2018)

Nonlinear graph-based dimensionality reduction algorithms have been shown to be very effective at yielding low-dimensional representations of hyperspectral image data. However, the steps of graph construction and eigenvector computation often suffer from prohibitive computational and memory requirements. In the paper, we develop a semi-supervised deep auto-encoder network (SSDAN) that is capable of generating mappings that approximate the embeddings computed by the nonlinear DR methods. The SSDAN is trained with only a small subset of the original data and enables an expert user to provide constraints that can bias data points from the same class towards being mapped closely together. Once the SSDAN is trained on a small subset of the data, it can be used to map the rest of the data to the lower dimensional space, without requiring complicated out-of-sample extension procedures that are often necessary in nonlinear DR methods. Experiments on publicly available hyperspectral imagery (Indian Pines and Salinas) demonstrate that SSDANs compute low-dimensional embeddings that yield good results when input to pixel-wise classification algorithms.