gebhart/patrepeval huggingface dataset:
Bernard Lerer: Recipient of the 2014 Inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine (Pacific Rim Association for Clinical Pharmacogenetics) (2014)

This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.
Complexes of DNA with cationic peptides: Conditions of formation and factors effecting internalization by mammalian cells (2006)

This work was devoted to the study of conditions of the formation of DNA/K8 complex and analysis of factors effecting the entry of DNA/K8 complex into mammalian cells in comparison with DNA complexes with arginine-rich fragment (47-57) of human immunodeficiency virus (type 1) transcription factor Tat (Tat peptide). The stoichiometry of positively charged DNA/K8 complexes has been studied for the first time. Non-cooperative character of DNA-K8 interaction was revealed. It has been shown that along with the positive charge of such complexes, the presence of an excess of free K8 peptide in the culture medium is a necessary condition for maximal efficiency of cell transfection with DNA/K8 complexes. A stimulatory effect of free K8 peptide on the efficiency of mammalian cell transfection by DNA/K8 complexes is likely to be mediated by the interactions of cationic peptide K8 with negatively charged proteoglycans on the cell surface, which leads to protection of DNA/K8 complexes from disruption by cellular heparan sulfates. However, the protective role of free cationic peptides depends not only on their positive charge, but also on the primary structure of the peptide. In contrast with the results obtained for DNA complexes with molecular conjugates based on poly-L-lysine, the aggregation of DNA/K8 complexes leads to a significant increase in the expression of transferred gene.
The proteasome regulator PI31 is required for protein homeostasis, synapse maintenance and neuronal survival in mice (2019)

Abstract Proteasome-mediated degradation of intracellular proteins is essential for cell function and survival. The proteasome-binding protein PI31 (Proteasomal Inhibitor of 31kD) promotes 26S assembly and functions as an adapter for proteasome transport in axons. As localized protein synthesis and degradation is especially critical in neurons, we generated a conditional loss of PI31 in spinal motor neurons (MNs) and cerebellar Purkinje cells (PCs). A cKO of PI31 in these neurons caused axon degeneration, neuronal loss and progressive spinal and cerebellar neurological dysfunction. For both MNs and PCs, markers of proteotoxic stress preceded axonal degeneration and motor dysfunction, indicating a critical role for PI31 in neuronal homeostasis. The time course of the loss of MN and PC function in developing mouse CNS suggests a key role for PI31 in human developmental neurological disorders. Statement of Significance The conserved proteasome-binding protein PI31 serves as an adapter to couple proteasomes with cellular motors to mediate their transport to distal tips of neurons where protein breakdown occurs. We generated global and conditional PI31 knockout mouse strains and show that this protein is required for protein homeostasis, and that its conditional inactivation in neurons disrupts synaptic structures and long-term survival. This work establishes a critical role for PI31 and local protein degradation in the maintenance of neuronal architecture, circuitry and function. Because mutations that impair PI31 function cause neurodegenerative diseases in humans, reduced PI31 activity may contribute to age-related neurodegenerative diseases.
Decentralized real-time monitoring and diagnosis (2002)

Real time monitoring of complex systems requires a smart and efficient inference engine. TEAMS-RT is capable of monitoring up to 1000 tests in real-time. Even so, for larger systems, a centralized solution will be computationally infeasible. Here, we present a lattice architecture of multiple collaborative TEAMS-RTs that can be embedded in the different subsystems of an interconnected system. A signal processing toolkit has been developed to facilitate data acquisition, filtering, feature extraction and test decisions.
Scaling Considerations for Thermal and Pressure-Sensitive Paint Methods Used to Determine Adiabatic Effectiveness (2020)

Abstract To be representative of engine conditions, a measurement of film cooling behavior with an experiment must involve matching certain nondimensional parameters, such as freestream Reynolds number. However, the coolant flowrate must also be scaled between the experiments and engine conditions to accurately predict film cooling effectiveness. This process is complicated by gas property variation with temperature. Additionally, selection of the appropriate coolant flowrate parameter to scale from low to high temperatures is a topic of continued uncertainty. Furthermore, experiments are commonly conducted using thermal measurement techniques with infrared thermography (IR), but the use of pressure-sensitive paints (PSPs) implementing the heat-mass transfer analogy is also common. Thus, the question arises of how the adiabatic effectiveness distributions compare between mass transfer experimental methods and thermal experimental methods and whether these two methods are sensitive to coolant flowrate parameters in different ways. In this study, a thermal technique with IR was compared with a heat-mass transfer method with a PSP on a flat plate model with a 7-7-7 film cooling hole. While adiabatic effectiveness is best scaled by accounting for specific heats with the advective capacity ratio (ACR) using thermal techniques, results revealed that PSP measurements are scaled best with the mass flux ratio (M). The difference in these methods has significant implications for engine designers that rely on PSP experimental data to predict engine thermal behavior as PSP is fundamentally not sensitive to the same relevant physical mechanisms to which thermal methods are sensitive.
Use of statins in the elderly according to age and indication—a cross-sectional population-based register study (2019)

In the oldest old (≥ 80 years), statin users were fewer and had more often an established indication, suggesting that physicians extrapolate scientific evidence for beneficial effects in younger age groups to the oldest, but require a more solid ground for treatment. As the oldest old, nursing home residents, and those with multi-dose drug-dispensing were statin users to a lesser extent, physicians may often refrain from treatment in those with lower life expectancy, either due to age or to severely reduced health status. In both age groups, our results however also indicate some over- as well as undertreatment.
TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells (2014)

TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.
3C-, 4H- and 6H-SiC Bulks Studied by Silicon <i>K</i>-Edge X-Ray Absorption (2013)

High-resolution synchrotron radiation X-ray absorption of Si K-edge have been employed to investigate 6H-, 4H- and 3C-SiC. Detailed analyses of the extended x-ray absorption fine structure are taken by using the IFEFFIT program, and significant results on the atomic bonding are obtained from these comparative studies. The x-ray absorption near-edge structures of the Si K-edge are investigated, and the electronic structure of 3C-, 4H- and 6H-SiC are studied. In order to investigate the angular dependence, the x-ray absorption near-edge spectra were operated at 55o and 90o of the angle between the surface and the X-ray direction.
Establishment of an Embryotoxicity Assay with Green Fluorescence Protein-expressing Embryonic Cell-derived Cardiomyocytes (1999)

Transgenic embryonic stem cells were used to determine the embryotoxic effects of chemicals on the development of embryonic tissues. This investigation supports an ongoing validation study, aimed at reducing the time-consuming procedure currently in use, and at providing more-objective and more-detailed information on the embryotoxic potentials of chemicals. Green fluorescence protein (GFP) was used as a reporter gene and was linked to a human α-cardiac-specific promoter. The expression of GFP was switched on after specific activation of the human α-actin promoter. This permitted the easy quantification of cardiac cells by using a fluorescence-activated cell sorter (FACS). The percentage of cardiac precursor cells was calculated from the FACS-distribution pattern of cells which fluoresced versus the total number of cells. The percentage of cardiac precursor cells increased from 25% in embryoid bodies on day 3, to 86% on day 7. However, in 11-day-old embryoid bodies, the percentage decreased to 35%. Five chemicals with known embryotoxic potentials were compared with respect to the IC50 (concentration causing 50% inhibition of measured effect) values obtained by various in vitro endpoints (for example, cytotoxicity, morphology). The results showed a higher sensitivity of endpoints used for the analysis of specific effects on the selected target tissue. The data also showed the need to develop in vitro methods with specific endpoints which account for the complexity of embryotoxicology.
ETS-Mediated Cooperation between Basic Helix-Loop-Helix Motifs of the Immunoglobulin μ Heavy-Chain Gene Enhancer (1998)

The muE motifs of the immunoglobulin mu heavy-chain gene enhancer bind ubiquitously expressed proteins of the basic helix-loop-helix (bHLH) family. These elements work together with other, more tissue-restricted elements to produce B-cell-specific enhancer activity by presently undefined combinatorial mechanisms. We found that muE2 contributed to transcription activation in B cells only when the muE3 site was intact, providing the first evidence for functional interactions between bHLH proteins. In vitro assays showed that bHLH zipper proteins binding to muE3 enhanced Ets-1 binding to muA. One of the consequences of this protein-protein interaction was to facilitate binding of a second bHLH protein, E47, to the muE2 site, thereby generating a three-protein-DNA complex. Furthermore, transcriptional synergy between bHLH and bHLH zipper factors also required an intermediate ETS protein, which may bridge the transcription activation domains of the bHLH factors. Our observations define an unusual form of cooperation between bHLH and ETS proteins and suggest mechanisms by which tissue-restricted and ubiquitous factors combine to generate tissue-specific enhancer activity.
Comparative Studies of Anionic Molecular Assemblies as Mediums for Electron Transfer Quenching of Excited Ru[(bpy)3]2+ by Cationic Quenchers (1985)

Abstract Behaviors of excited [Ru(bpy)3]2+ bound to anionic molecular assemblies such as polymer electrolytes, vesicles and micelles together with electron-acceptor quencher MV2+ have been investigated by measurements of [Ru(bpy)3]2+ luminescence quenching and radical yields in electron-transfer quenching using a dye laser photolysis apparatus. Quenching behavior characteristic to each molecular assembly has been observed. A remarkable enhancement of quenching was observed in the presence of poly(vinyl sulfate). Such an effect was observed also in sodium dihexadecyl phosphate solution though it is less pronounced. However, no such specific quenching behavior was observed in sodium dodecyl sulfate micellar solution.
The Creation Process of Chinese Calligraphy and Emulation of Imagery Thinking (2008)

Chinese calligraphy is both an art form and the embodiment of imagery thinking. The process of calligraphy involves studying tablets or documents, remembering the contents, and creating new artwork with calligraphic images from memory. All these steps are related to simulation intelligence, thought patterns, and cognition models. Ancient tablets were damaged by human hands and eroded by the environment, thus considerably degrading their original appearance. Automated reconstruction of the characters represented in the tablets, completed in the past by an experienced expert, is a necessary preprocessing stage that simulates the imagery thinking of calligraphy creation. Following reconstruction, a stroke-reforming approach based on statistical models generates new calligraphic styles. We present the results of this approach and discuss ongoing problems. This article is part of a special issue on AI in China.
UK election: Cameron clutches surprise second term (2015)

The Conservative Party remaining in government after this year's general election may not have been a surprise to some, but it's fair to say that the scale of the victory caught many people, pundits, pollsters - and perhaps even the Prime Minister - unawares.
Double-Strand Break Repair in Tandem Repeats During Bacteriophage T4 Infection (2000)

Recombinational repair of double-strand breaks in tandemly repeated sequences often results in the loss of one or more copies of the repeat. The single-strand annealing (SSA) model for repair has been proposed to account for this nonconservative recombination. In this study we present a plasmid-based physical assay that measures SSA during bacteriophage T4 infection and apply this assay to the genetic analysis of break repair. SSA occurs readily in broken plasmid DNA and is independent of the strand exchange protein UvsX and its accessory factor UvsY. We use the unique features of T4 DNA metabolism to examine the link between SSA repair and DNA replication and demonstrate directly that the DNA polymerase and the major replicative helicase of the phage are not required for SSA repair. We also show that the Escherichia coli RecBCD enzyme can mediate the degradation of broken DNA during early, but not late, times of infection. Finally, we consider the status of broken ends during the course of the infection and propose a model for SSA during T4 infections.
Recursed Is Not Recursive: A Jarring Result (2020)

Recursed is a 2D puzzle platform video game featuring treasure chests that, when jumped into, instantiate a room that can later be exited (similar to function calls), optionally generating a jar that returns back to that room (similar to continuations). We prove that Recursed is RE-complete and thus undecidable (not recursive) by a reduction from the Post Correspondence Problem. Our reduction is "practical": the reduction from PCP results in fully playable levels that abide by all constraints governing levels (including the 15x20 room size) designed for the main game. Our reduction is also "efficient": a Turing machine can be simulated by a Recursed level whose size is linear in the encoding size of the Turing machine and whose solution length is polynomial in the running time of the Turing machine.
Laparoscopic Ovarian Drilling for Clomiphene-Resistant Polycystic Ovary Syndrome (2011)

Laparoscopic ovarian drilling (LOD) is an alternative to ovulation induction with gonadotropins for polycystic ovarian syndrome (PCOS) patients unresponsive to clomiphene. It is quick and easy to perform, although the number of punctures and energy doses has not been standardized. The mechanism of LOD is unclear, but it is likely mediated by a reduction in intraovarian androgen production. Serum luteinizing hormone and testosterone levels are rapidly normalized, and these changes are sustained over long-term follow-up. Studies have shown that ovulation and pregnancy rates are comparable between ovulation induction with gonadotropins and LOD, but LOD avoids the risks of multiple pregnancy and ovarian hyperstimulation syndrome. LOD is also more cost effective and better tolerated than gonadotropin therapy. Concerns regarding clinically significant adhesion formation and premature ovarian failure are not supported by the available data. Transvaginal hydrolaparoscopy and ultrasound guidance are less invasive techniques for performing ovarian drilling and may encourage LOD earlier in the course of treatment for PCOS.
Development and application of microarray-based comparative genomic hybridization : analysis of neurofibromatosis type-2, schwannomatosis and related tumors. (2005)

Neurofibromatosis type-2 (NF2) is an autosomal dominant disorder with the clinical hallmark of bilateral eighth cranial nerve schwannomas. However, the diagnostic criterion is complicated by the presence of a variable phenotype, with the severe form presenting with additional tumors such as peripheral schwannoma, meningioma and ependymoma. We constructed a microarray spanning 11Mb of 22q, encompassing the NF2 gene, to detect deletions in schwannoma. Forty seven patients were analyzed and heterozygous deletions were detected in 45% of tumors. Using this array-based approach, we also detected genetic heterogeneity in a number of samples studied. Despite the high sensitivity and the comprehensive series of studied schwannomas, no homozygous deletions affecting the NF2 gene were detected <b>(paper I)</b>. In order to detect more subtle deletions within the NF2 locus, a higher-resolution gene-specific array was developed, for the detection of disease-causing<b> </b>deletions using a PCR-based non-redundant strategy. This novel approach for array construction significantly increased the reliability and resolution of deletion-detection within the NF2 locus <b>(paper II)</b>. To further expand the coverage of the 11 Mb microarray, we constructed the first comprehensive microarray representing a human chromosome for analysis of DNA copy number. This 22q array covers 34.7 Mb, representing 1.1% of the genome, with an average resolution of 75 kb <b>(paper III)</b>. Using this array, we analyzed sporadic and familial schwannomatosis samples, which revealed two commonly deleted regions within the immunoglobulin lambda locus and the GSTT1/CABIN1 locus. These regions were further characterized using higher-resolution non-redundant arrays, bioinformatic tools, positional cloning and mutational screening. Missense mutations were detected in the CABIN1 gene, which may contribute to the pathogenesis of schwannomatosis and therefore requires further study <b>(paper IV)</b>. Meningioma is the second most common NF2-associated tumor and loss of 1p has been previously established as a major genetic factor for disease initiation/progression and also correlates with increased morbidity. We analyzed 82 meningiomas using a chromosome 1 tiling-path genomic microarray. The distribution of aberrations detected supports the existence of at least four regions on chromosome 1, which are important for meningioma tumorigenesis <b>(paper V)</b>.
UxTh1-x(C2O4)2 Solid Characterisation Studies (2016)

Many advanced reprocessing schemes under development are aimed at co-processing and co-conversion of actinides, unlike current reprocessing plants that produce separate uranium and plutonium products. The most well developed option for the co-conversion stage is probably oxalate co-precipitation, followed by the thermal co-conversion to a mixed oxide product. It is thus envisaged that future processes will avoid separation of plutonium from uranium and instead allow part of the uranium to flow with the plutonium, resulting in co-precipitation as the oxalate, and finally co-conversion to a mixed uranium-plutonium oxide (MOX), which can be fabricated into recycled nuclear fuel for further energy generation. The co-crystallisation of uranium (IV) and plutonium (III) into a single oxalate structure ensures the homogenous distribution of the two actinides at the molecular scale. The joint conversion of uranium and plutonium to the oxide form makes it possible to remove the complicated step of blending and grinding the two distinct oxide powders, as currently employed for the purposes of MOX fuel fabrication. This concept can also be extended to other actinides, including minor actinides from partitioning processes such as SANEX (Selective Actinide Extraction) and GANEX (Grouped Actinide Extraction) processes or even a thorium containing product from recycle of thorium based fuels. A selection of UxTh1-x(C2O4)2 solids at varying concentrations of uranium and thorium were prepared by oxalate co-precipitation. Uranium (VI) was conditioned electrochemically at -0.7 V to uranium (IV), in the presence of hydrazine. The reduced uranium (IV) in nitric acid was mixed with thorium nitrate solutions at different concentration ratios with oxalic acid. The mixed tetravalent uranium-thorium oxalate solid products have been characterised by Raman and IR spectroscopies. The influence of thorium substituted into the uranium oxalate structure was evaluated. Several vibrational modes were found to be affected by the variation in ionic radius appearing to be metal sensitive and therefore, provide the initial indication in the evaluation of the chemical composition.