gebhart/patrepeval huggingface dataset:
Novel γ-secretase modulators for the treatment of Alzheimer's disease: a review focusing on patents from 2010 to 2012 (2013)

Introduction: γ-Secretase is the enzyme responsible for the final step of amyloid precursor protein proteolysis to generate Aβ peptides including Aβ42 which is believed to be a toxic species involved in Alzheimer's disease (AD) progression. γ-Secretase modulators (GSMs) have been shown to selectively lower Aβ42 production without affecting total Aβ levels or the formation of γ-secretase substrate intracellular domains such as APP intracellular domain and Notch intracellular domain. Therefore, GSMs have emerged as an important therapeutic strategy for the treatment of AD. Areas covered: The literature covering novel GSMs will be reviewed focusing on patents from 2010 to 2012. Expert opinion: During the last review period (2008 – 2010) considerable progress was made developing GSMs with improved potency for lowering Aβ42 levels, but most of the compounds resided in unfavorable central nervous system (CNS) drug space. In this review period (2010 – 2012), there is a higher percentage of potent GSM chemical matter that resides in favorable CNS drug space. It is anticipated that clinical candidates will emerge out of this cohort that will be able to test the GSM mechanism of action in the clinic.
High electron doping to a wide band gap semiconductor 12CaO∙7Al2O3 thin film (2007)

High-density electrons (∼1.9×1021cm−3) were doped into a polycrystalline film of a wide band gap (∼7eV) semiconductor 12CaO∙7Al2O3 (C12A7) by an in situ postdeposition reduction treatment using an oxygen-deficient C12A7 overlayer. The resultant film exhibits metallic conduction with a Hall mobility of ∼2.5cm2V−1s−1 and a conductivity of ∼800Scm−1. Optical analyses indicate that most of the doped electrons behave as free carriers with an effective mass of 0.82me and the estimated in-grain mobility is 5.2cm2V−1s−1, which agrees reasonably with the value obtained for high-quality single crystals.
The Practical Application Value of a Sustainable Water Purification Process Is Crucial (2023)

sponsorship: Q.G. acknowledges the support provided by the China Scholarship Council (CSC) of the Ministry of Education, P. R. China (CSC 202006420004). (China Scholarship Council (CSC) of the Ministry of Education, P. R. China|CSC 202006420004)
Expression of Neonatal Fc Receptor in the Eye (2014)

Our results demonstrate that FcRn has the potential to interact with IgG-Fc domains in the ciliary epithelium and retinal and choroidal vasculature, which might affect the half-life and distribution of intravitreally injected Fc-carrying molecules.
Base excision repair of DNA in mammalian cells (2000)

Base excision repair (BER) of DNA corrects a number of spontaneous and environmentally induced genotoxic or miscoding base lesions in a process initiated by DNA glycosylases. An AP endonuclease cleaves at the 5' side of the abasic site and the repair process is subsequently completed via either short patch repair or long patch repair, which largely require different proteins. As one example, the UNG gene encodes both nuclear (UNG2) and mitochondrial (UNG1) uracil DNA glycosylase and prevents accumulation of uracil in the genome. BER is likely to have a major role in preserving the integrity of DNA during evolution and may prevent cancer.
Suppression of Zn diffusion due to hydrogen passivation in p -AlGaInP (1994)

The behaviors of Zn acceptors in p-AlGaInP layer during thermal annealing in AsH3+H2 mixture gas have been investigated. The electrical activities of Zn acceptors were greatly affected by the hydrogen atoms originating from AsH3 during thermal annealing. In addition, from observation of the atomic disordering, hydrogen passivation of Zn acceptors was found to suppress the atomic diffusion. These phenomena can be consistently explained by a simple hydrogen passivation model, which is the termination of dangling bonds by hydrogen atoms.
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma (2020)

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 - a component of the transcription elongation complex P-TEFb - bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.
Compétitivité nationale : lorsque les États européens misent sur les villes (Interview) (2013)

Les villes, et en particulier les capitales régionales, sont sorties renforcées de la décentralisation généralisée en Europe. Ces porte-drapeaux de la compétitivité resisteront?elles à la crise économique ? \nLes réponses par l’analyse de Patrick Le Galès, politiste et sociologue.
Pathogenic Acanthamoeba castellanii Secretes the Extracellular Aminopeptidase M20/M25/M40 Family Protein to Target Cells for Phagocytosis by Disruption (2017)

<i>Acanthamoeba</i> is free-living protist pathogen capable of causing a blinding keratitis and granulomatous encephalitis. However, the mechanisms of <i>Acanthamoeba</i> pathogenesis are still not clear. Here, our results show that cells co-cultured with pathogenic <i>Acanthamoeba</i> would be spherical and floated, even without contacting the protists. Then, the <i>Acanthamoeba</i> protists would contact and engulf these cells. In order to clarify the contact-independent pathogenesis mechanism in <i>Acanthamoeba</i>, we collected the <i>Acanthamoeba</i>-secreted proteins (Asp) to incubate with cells for identifying the extracellular virulent factors and investigating the cytotoxicity process. The Asps of pathogenic <i>Acanthamoeba</i> express protease activity to reactive Leu amino acid in ECM and induce cell-losing adhesion ability. The M20/M25/M40 superfamily aminopeptidase protein (ACA1_264610), an aminopeptidase be found in Asp, is upregulated after <i>Acanthamoeba</i> and C6 cell co-culturing for 6 h. Pre-treating the Asp with leucine aminopeptidase inhibitor and the specific antibodies of <i>Acanthamoeba</i> M20/M25/M40 superfamily aminopeptidase could reduce the cell damage during Asp and cell co-incubation. These results suggest an important functional role of the <i>Acanthamoeba</i> secreted extracellular aminopeptidases in the <i>Acanthamoeba</i> pathogenesis process. This study provides information regarding clinically pathogenic isolates to target specific molecules and design combined drugs.
Quantifying Volume Change in Porous Electrodes via the Multi-Species, Multi-Reaction Model (2023)

Automotive manufacturers are working to improve individual cell and overall pack design by increasing their performance, durability, and range, while reducing cost; and active material volume change is one of the more complex aspects that needs to be considered during this process. As the time from initial design to manufacture of electric vehicles is decreased, design work that used to rely solely on testing needs to be supplemented or replaced by virtual methods. As electrochemical engineers drive battery and system design using model-based methods, the need for coupled electrochemical/mechanical models that take into account the active material change utilizing physics based or semi-empirical approaches is necessary. In this study, we illustrated the applicability of a mechano-electrochemical coupled modeling method considering the multi-species, multi-reaction model as popularized by Verbrugge and Baker. To do this, validation tests were conducted using a computer-controlled press apparatus that can control the press displacement and press force with precision. The coupled MSMR volume change model was developed and its applicability to graphite and NMC cells was illustrated. The increased accuracy of the model considering the coupled MSMR volume change approach shows in the importance of accounting for individual gallery volume change behavior on cell level predictions.
GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer (2020)

Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors.
Qualitative and Quantitative Knowledge in Classical Mechanics (1975)

This thesis investigates what knowledge is necessary to solve mechanics problems. A program NEWTON is described which understands and solves problems in a mechanics mini-world of objects moving on surfaces. Facts and equations such as those given in a mechanics text need to be represented. However, this is far from sufficient to solve problems. Human problem solvers rely on 'common sense' and 'qualitative' knowledge which the physics text tacitly assumes to be present. A mechanics problem solver must embody such knowledge. Quantitative knowledge given by equations and more qualitative common sense knowledge are the major research points exposited in this thesis. The major issue in solving problems is planning. Planning involves tentatively outlining a possible path to the solution without actually solving the problem. Such a plan needs to be constructed and debugged in the process of solving the problem. Envisionment, or qualitative simulation of the event, plays a central role in this planning process. (Author)
Experimental Demonstration of AlN Heat Spreaders for the Monolithic Integration of Inline Phase-Change Switches (2018)

Inline phase-change switch (IPCS) devices were fabricated on top of an AlN heat spreading layer deposited on a thick SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> layer. The thick SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> emulates the inter-layer dielectric thermal properties that prevent direct integration of IPCS devices at the end of a back-end-of-line CMOS process. The AlN acts as a heat spreading layer, enabling the proper thermal quench rate despite the low thermal conductivity of the oxide underneath. Multiple AlN thicknesses were examined and shown to properly quench the device. Use of this heat spreading layer experimentally demonstrates a substrate agnostic monolithic integration scheme, where IPCS devices can be integrated at the end of any microfabrication process—regardless of the substrate or materials underneath. This is attractive for many CMOS applications, where wafer real-estate is expensive, or in III–V applications, where the wafer thermal properties are poor and vary among different technologies.
DWWA, a Novel Protein Containing Two WW Domains and an IQ Motif, Is Required for Scission of the Residual Cytoplasmic Bridge during Cytokinesis inDictyostelium (2003)

We have identified a novel gene, dwwA, which is required for cytokinesis of Dictyostelium cells on solid surfaces. Its product, Dd WW domain containing protein A (DWWA), contains several motifs, including two WW domains, an IQ motif, a C2 domain, and a proline-rich region. On substrates, cells lacking dwwA were multinucleated and larger and flatter than wild-type cells due to their frequent inability to sever the cytoplasmic bridge connecting daughter cells after mitosis. When cultured in suspension, however, dwwA-null cells seemed to carry out cytokinesis normally via a process not driven by the shearing force arising from agitation of the culture. GFP-DWWA localized to the cell cortex and nucleus; analysis of the distributions of various truncation mutants revealed that the N-terminal half of the protein, which contains the C2 domain, is required for the cortical localization of DWWA. The IQ motif of DWWA binds calmodulin in vitro. Given that the scission process is also defective in calmodulin knockdown cells cultured on substrates (Liu et al., 1992), we propose that DWWA's multiple binding domains enable it to function as an adaptor protein, facilitating the scission process through the regulation of Ca(2+)/calmodulin-mediated remodeling of the actin cytoskeleton and/or modulation of membrane dynamics.
The control system for the Honda humanoid robot (2006)

To avoid tipping over either during walking or on standing up, humans will first push down hard on the ground with a part of the sole of the foot. Then, when the tipping force can no longer be resisted, a change in body position or an extra step (stepping out) may be required to stabilise the posture. Our biped robot's control system attempts to reproduce and execute the same postural control operations carried out by humans. In this article, we present the history of robot development at Honda, fundamental dynamics for robots and the principles of posture control.
Synthesis and activity of potent 3-(isoxazolidin-5-yl)- and 3-(isoxazolidinium-5-yl) cephalosporins. (1992)

The syntheses and in vitro antibacterial activities of 3-(isoxazolidin-5-yl)- and 3-(isoxazolidinium-5-yl)cephalosporins are described. 1,3-Dipolar cycloaddition of 3-vinylcephalosporin with nitrone gave diastereomeric isomers of 3-(isoxazolidin-5-yl)cephalosporin. The antibacterial activities of 3'-(S)-isomers were superior to those of 3'-(R)-isomers. The quaternarization of isoxazolidine ring increased the antibacterial activity. Among them, compound 10b with a hydroxyimino group in the C-7 side chain showed potent activities against staphylococci and compound 10f with an N-hydroxypyridone exhibited an excellent antipseudomonal activity.
Muscarinic acetylcholine receptors in the etiology and treatment of schizophrenia (2020)

Although the etiology of schizophrenia is unclear, considerable neuroimaging, pharmacology, genetic, postmortem, and preclinical studies point to a key role for muscarinic acetylcholine receptors (mAChRs) in the pathophysiology and treatment of psychosis. Unlike currently available antipsychotics, which mostly provide symptomatic relief for positive symptoms of schizophrenia, mAChRs show immense potential in the treatment of all schizophrenia symptom domains, and could provide a major advance in the clinical treatment and prognosis of patients. Unfortunately, clinical use of drugs targeting mAChRs are limited, despite their utility, due to the side-effect profile of non-subtype-selective mAChR agents. However, recent major advances in the development of subtype-selective mAChR pharmacological agents as well as development of individual mAChR knockout mice have allowed for the roles of each mAChR in schizophrenia to begin to be elucidated, and have reinforced the clinical utility of especially the M<sub>1</sub> and M<sub>4</sub> mAChR subtypes in the treatment schizophrenia.
Optomechanical coupling in a two-dimensional photonic crystal defect cavity (2011)

We experimentally investigate the optomechanical properties of a conventional two-dimensional suspended photonic crystal defect cavity. Particularly, we measure localized mechanical modes in the GHz regime exhibiting high values of the optomechanical vacuum coupling rate exceeding 250 kHz.
Learning curve analysis of concentrated photovoltaic systems (2014)

Abstract Price declines and volume growth of concentrated photovoltaic (CPV) systems are analysed using the learning curve methodology and compared with other forms of solar electricity generation. Logarithmic regression analysis determines a learning rate of 18% for CPV systems with 90% confidence of that rate being between 14 and 22%, which is higher than the learning rates of other solar generation systems (11% for CSP and 12 to 14% for PV). Current CPV system prices are competitive with PV and CSP, which, when combined with the higher learning rate, indicates that CPV is likely to further improve its marketability. A target price of 1 $/W in 2020 could be achieved with a compound growth rate of 67% for the total deployed volume between 2014 and 2020, which would realize a cumulative deployed volume of 7900 MW. Other projections of deployment volumes from commercial sources are converted using the learning rate into future price scenarios, resulting in predicted prices in the range of 1.1 to 1.3 $/W in 2020. © 2014 The Authors. Progress in Photovoltaics: Research and Applications published by John Wiley &amp; Sons Ltd.
Manipulation of fluids in three-dimensional porous photonic structures with patterned surface properties (2023)

A three-dimensional porous photonic structure, whose internal pore surfaces can be provided with desired surface properties in a spatially selective manner with arbitrary patterns, and methods for making the same are described. When exposed to a fluid (e.g., via immersion or wicking), the fluid can selectively penetrate the regions of the structure with compatible surface properties. Broad applications, for example in security, encryption and document authentication, as well as in areas such as simple microfluidics and diagnostics, are anticipated.
Identification of Breast Cancer Specific Proteolytic Activities for Targeted Prodrug Activation (2004)

Abstract : The underlying hypothesis of this proposal is that a breast tissue/cancer proteolytic activity can be identified by screening the extracellular fluid from human breast cancers with a fluorescence quenched random peptide library. The peptide substrate(s) identified from this screening could be used to produce prodrugs that are targeted for specific activation by proteolytic activity present in extracellular fluid of breast cancers while avoiding systemic toxicity. In the first year we developed methods to synthesize large fluorescently quenched peptide libraries as outlined in task 1. In preliminary studies, we incubated these libraries with a purified serine protease, human glandular kallikrein 2, and identified a series of putative substrates. These substrates were resynthesized as soluble peptides and peptides were then identified that were excellent hK2 substrates but unstable to non-specific hydrolysis in human plasma. Coupling these peptides to the thapsigargin analog, Ll2ADT, however, produced a prodrug that was readily hydrolyzed by hK2, stable in human plasma in vitro and mouse plasma both in vitro and in vivo, and was selectively cytotoxic to cancer cells in the presence of enzymatically active hK2. These studies demonstrated the feasibility of the approach to identification of protease substrates outlined in tasks 1-3 of the proposal. However, incubation of breast cancer homogenates or concentrated media from breast cancer cell lines did not yield any hydrolyzed peptides. This lack of hydrolys is most likely is due to a combination of ng/ml concentrations of protease in the extracellular fluid and the need to dilute samples to cover entire bead library (i.e. 10-40 mls). A new approach for combinatorial screening is required that would yield libraries of small physical volume to screen small volume of extracellular fluid from breast cancers without requiring substantial dilution.
Resolution Assessment of an Aberration Corrected 1.2-MV Field Emission Transmission Electron Microscope (2015)

Journal Article Resolution Assessment of an Aberration Corrected 1.2-MV Field Emission Transmission Electron Microscope Get access Yoshio Takahashi, Yoshio Takahashi Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Tetsuya Akashi, Tetsuya Akashi Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Tomokazu Shimakura, Tomokazu Shimakura Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Toshiaki Tanigaki, Toshiaki Tanigaki Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Takeshi Kawasaki, Takeshi Kawasaki Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroyuki Shinada, Hiroyuki Shinada Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Nobuyuki Osakabe Nobuyuki Osakabe Central Research Laboratory, Hitachi, Ltd., Hatoyama 350-0395, Japan Search for other works by this author on: Oxford Academic Google Scholar Microscopy and Microanalysis, Volume 21, Issue S3, 1 August 2015, Pages 1865–1866, https://doi.org/10.1017/S1431927615010107 Published: 23 September 2015