gebhart/patrepeval huggingface dataset:
Abstract 5109: Somatic CRISPR/Cas9-mediated gene editing enables versatile brain tumor modeling (2018)

Abstract Despite substantial advances in the molecular classification of pediatric brain tumors over the last decade, many tumors are still incurable, have a poor prognosis or therapy-related detrimental long term effects. To develop innovative and modern therapy approaches, sophisticated mouse models, faithfully reflecting the human disease are urgently needed. However, the development of transgenic mouse lines is a time consuming process that is confronted with an increasing number of candidate genes resulting from next generation sequencing of tumor specimens. To cope with this discrepancy, more adaptable animal models are needed. Using somatic gene transfer to manipulate cells in situ holds great advantages in terms of speed and flexibility. We therefore established a system in which we are using the CRISPR/Cas9 system for somatic disruption of candidate tumor suppressor genes (TSGs) in combination with transposon-mediated overexpression of candidate oncogenes to induce murine brain tumors. By deleting Ptch1 in murine cerebella, we induced Sonic Hedgehog (SHH) subgroup medulloblastoma with high penetrance and short latency. We characterized the induced mutations in depth and did not detect recurrent off-targets using unsupervised whole genome sequencing. We further demonstrated that this method is suited to induce other brain tumor entities by targeting multiple TSGs at the same time or by combining TSG targeting with overexpression of certain oncogenes. To date we established five novel mouse models using this system. Two of these resulted from simultaneous deletion of Nf1, Pten and Trp53 or from combining overexpression of a MET fusion with a loss of Trp53, respectively. Both of these combinations led to efficient glioblastoma induction in the murine forebrain. Our results demonstrate a fast and flexible system for validating novel candidate genes and for generating faithful animal models of human cancer. Citation Format: Marc Zuckermann, Britta Ismer, Volker Hovestadt, Christiane B. Knobbe-Thomsen, Marc Zapatka, Paul A. Northcott, Martine F. Roussel, Guido Reifenberger, Peter Lichter, Stefan M. Pfister, Daisuke Kawauchi, Jan Gronych, David T. Jones. Somatic CRISPR/Cas9-mediated gene editing enables versatile brain tumor modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5109.
Formation and reactions of active five-membered phosphane/borane frustrated Lewis pair ring systems (2018)

The reactive five-membered frustrated P/B Lewis pair 6a was generated from Tipp-P(vinyl)2 (Tipp: 2,4,6-triisopropylphenyl) by a series of anti-Markovnikov and Markovnikov hydroboration reactions. The in situ generated compound dimerized to give 7a under kinetic control and the dimer pair 8a/9a under thermodynamic control. The Mes*-P(vinyl)2 analogue (Mes*: 2,4,6-tri-tert-butylphenyl) reacts in a similar way, but in this case the thermodynamic dimers are observed at r.t. whereas the monomer 6b is the dominant species at 80 °C in solution. It is an active dihydrogen splitting reagent. The in situ generated monomeric five-membered P/B FLPs undergo addition reactions to various organic π-reagents. With benzaldehyde or phenylacetylene this gave the respective zwitterionic heteronorbornene or -norbornadiene type products, the latter with liberation of ethylene.
Generation of Zwitterionic Water Channels: Biszwitterionic Imidazolium Carboxylates as Hydrogen-Bonding Acceptors (2011)

Organic crystals containing several types of water channels are generated by clipping water molecules with biszwitterionic imidazolium carboxylates as hydrogen-bonding acceptors. The types of water channels to be generated depend on the size and the shape of the aromatic spacers tethered with two imidazolium carboxylates moieties. Clusters of water tetramers and dimers were obtained from imidazolium carboxylates with phenylene (1) and naphthalene (2) linkers, respectively. The latter showed pseudopolymorphism, affording layers of water hexamers. Imidazolium carboxylate possessing biphenylene linker (3) afforded channels of discrete water tetramers.
Lack of a role for creatine phosphate kinase in sulphur mustard-induced cytotoxicity (2007)

Several compounds involved in the creatine phosphate kinase (CPK) pathway were evaluated for their protective effects against the chemical warfare (CW) agent sulphur mustard (HD), in primary chick embryo neuron and first passage human skin keratinocyte cultures. High concentrations of both creatine and creatine phosphate were found to be protective under all culture conditions and increased the LC(50) of HD in both culture systems up to approximately 250%. Little difference was observed in the protective activity of these compounds in undifferentiated versus differentiated neuronal culture, or in proliferating versus differentiating cultures of keratinocytes. The protective effect of these compounds was found to be strictly prophylactic in nature. Although a modest decline in HD half-life was measured in buffer containing creatine phosphate, this did not account for the protective effects of this compound. In contrast to historical literature reporting 90-100% HD-induced CPK inhibition of purified enzyme, less than 30% of CPK activity was found to be inhibited by HD in both human keratinocytes and in swine blood plasma. Incubation of keratinocyte cultures with creatine or creatine phosphate prior to HD exposure did not alter CPK activity, compared with HD-only treated cultures. Although high mM concentrations of both creatine and creatine phosphate exert significant protective effects against HD, these results do not support a role for CPK in its toxicity or in the development of medical countermeasures against this CW agent.
A 40 nm CMOS analog front end with enhanced audio for HSPA/EDGE multimedia applications (2012)

A 40 nm CMOS analog front end (AFE) supporting HSPA/EDGE multimedia and enhanced audio applications is reported. The AFE consists of hi-fi audio and high-performance peripheral and auxiliary subsystems. Circuit techniques that enable a 200 μA audio RX path and a Class-AB driver with −80 dB THD are discussed. Audio playback and capture paths achieve 105 dB and 85 dB SNR, respectively.
Interfacial structure and ferroelectric properties of PZT/SrRuO<sub>3</sub> heterostructures on miscut (001)SrTiO<sub>3</sub> (1999)

Abstract A heterostructure of (001)PZT(53/47)/(110)SrRuO3(SRO) was deposited on a miscut (001)SrTiO3(ST) substrate by a magnetron sputtering. The film thickness of the PZT and SRO ranged from 100nm to 200nm. The miscut angles were typically 1.7°. The heterostructure was grown on the miscut ST substrates under a step-flow growth. The heterostructure was tightly bonded to the ST substrate without an interfacial layer. The sputtered PZT thin films were tetragonally deformed with c=4.16 Å (bulk c-lattice parameter, 4.14 Å). A room temperature dielectric constant of the PZT thin films was 200 to 300 at 1kHz. The P/E hysteresis measurements indicated that the saturation polarization Ps was 40 μ C/cm2 with a coercive field Ec of 400 kV/cm to 500 kV/cm. The Ec observed was one order of magnitude higher than a bulk value for PZT. The high values of Ec were observed in a perfect c-domain orientation without an interfacial layer or 90° domains. Key Words: ferroelectric thin filmsPZT thin filmssingle domain/single crystal
Improving the efficiencies of small molecule solar cells by solvent vapor annealing to enhance J-aggregation (2019)

The enhanced J-aggregation increases the crystallinity of the small molecules and forms a favorable film morphology with a fiber-like structure.
Identifying Implicit Quotes for Unsupervised Extractive Summarization of Conversations (2020)

Ryuji Kano, Yasuhide Miura, Tomoki Taniguchi, Tomoko Ohkuma. Proceedings of the 1st Conference of the Asia-Pacific Chapter of the Association for Computational Linguistics and the 10th International Joint Conference on Natural Language Processing. 2020.
Schedule generation and reconfiguration for parallel machines (2003)

The authors present a methodology for scheduling independent jobs with due dates on identical parallel machines. The jobs have different levels of importance and various processing times on the machines, and the objective is to minimize the total weighted job tardiness of the schedule. Since the problem is NP-hard, the goal is not to obtain the optimal schedule. Rather, an efficient near-optimal algorithm based on Lagrangian relaxation is presented. A nice feature of this approach is that it provides a lower bound on the cost, which can be used as a measure of suboptimality. On most problems tested, results are within 1% of the optima and have reasonable CPU times. Furthermore, the method provides job interaction information, which is then used to provide quick answers to 'what if' questions, to reconfigure the schedule to accommodate dynamic changes, and also to schedule jobs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genome-wide scan for quantitative trait loci influencing spatial navigation and social recognition memory in Dahl rats (2006)

The genetic determinants of learning and memory have been difficult to unravel because of the complex inheritance of these forms of cognitive behavior encompassing multiple genetic and environmental factors. Indeed, genes that can account for strain and individual variations in learning and memory are largely unknown. Here we report a genome-wide scan for quantitative trait loci (QTLs) affecting spatial learning and memory and social recognition memory in an F2 population derived from Dahl rats. We detected five QTLs on chromosomes 1, 8, 11, 17, and 20 affecting spatial acquisition performance and five QTLs on chromosomes 2, 3, 9, and 20 influencing spatial accuracy (once information about the target location had been acquired). None of these QTLs overlap, indicating the existence of independent genetic determinants for these two distinct behavioral components of spatial navigation. Moreover, five QTLs affecting social recognition memory were detected, two on chromosome 9 and three on chromosome X. The chromosomal regions linked to social recognition memory performance in the rat are syntenic to regions that have been linked to autism in humans. Thus our results could have paradigmatic value in guiding the experimental investigation of similar pathways in genetic susceptibility to this disorder, which results in profound impairments in social behavior.
Identification and characterization of a fungal-selective glutaminyl tRNA synthetase inhibitor with potent activity against Candida albicans (2021)

Candida albicans is the leading cause of systemic candidiasis. Effective treatment is threatened by a dearth of antifungal options and the emergence of resistance. Thus, there is an urgent need to identify novel therapeutic targets to expand our antifungal armamentarium. A promising approach is the discovery of essential genes, as most antimicrobials target essential bioprocesses. Despite detailed characterization of gene essentiality in Saccharomyces cerevisiae,defining essential targets in the pathogen of interest is necessary due to the high level of divergence between these organisms. Thus, using a machine learning algorithm we generated a comprehensive prediction of all genes essential in C. albicans . We leveraged our essentiality predictions with high-throughput screening and chemogenomic datasets to assign the mechanism of action of a previously uncharacterized compound. We identified T-035897 as a molecule with potent bioactivity against C. albicans . Prior chemogenomic profiling in S. cerevisiae suggested that T-035897 targets the glutaminyl tRNA synthetase Gln4, whose homolog in C. albicans was predicted and verified to be required for viability. To confirm the mechanism of T-035897 in C. albicans , we performed haploinsufficiency profiling,which supported Gln4as the target. In parallel, selection of resistant mutants and targeted sequencing uncovered substitutions in the Gln4 catalytic domain. Moreover, T-035897 inhibited translation in afluorescence-based reporter assay. Finally, T-035897 selectively abrogated fungal cell growth in a co-culture model with mammalian cells. Thus, we highlight the power of leveraging essentiality datasets in order to characterize compounds with potent antifungal activity in an effort to unveil novel therapeutic strategies.
Transferts de chaleur dans les milieux poreux - Conduction, convection, rayonnement (2019)

D’une très grande variété, aussi bien de structure que de nature, les milieux poreux occupent une large place dans de nombreux secteurs industriels et phénomènes naturels. Cependant, les transferts de chaleur dans ces milieux de forte complexité géométrique s’avèrent difficilement prévisibles.
<sup>19</sup>F NMR‐Based Fragment Screening for 14 Different Biologically Active RNAs and 10 DNA and Protein Counter‐Screens (2020)

Abstract We report here the nuclear magnetic resonance 19 F screening of 14 RNA targets with different secondary and tertiary structure to systematically assess the druggability of RNAs. Our RNA targets include representative bacterial riboswitches that naturally bind with nanomolar affinity and high specificity to cellular metabolites of low molecular weight. Based on counter‐screens against five DNAs and five proteins, we can show that RNA can be specifically targeted. To demonstrate the quality of the initial fragment library that has been designed for easy follow‐up chemistry, we further show how to increase binding affinity from an initial fragment hit by chemistry that links the identified fragment to the intercalator acridine. Thus, we achieve low‐micromolar binding affinity without losing binding specificity between two different terminator structures.
Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer (2022)

Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46-75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.
Remote Sensing Ontology Development for Earth Observation Data (2009)

Many standardization organizations are working for syntactic level of interoperability, but in the same time, semantic interoperability of data must be considered for earth observation data. Remote sensing ontology is developed for not only integrating global observation data, but also knowledge sharing and transfer. Ontological information is used for data sharing and data service such as support of metadata design, structuring of data contents, and support of data mining. Semantic network dictionary is constructed based on Semantic MediaWiki. Ontological information are added to the dictionary by digitalizing text based dictionaries, developing “knowledge writing tool” for experts, and extracting semantic relations from authoritative documents with natural language processing technique.
ALCOHOL DRINKING AND WITHDRAWAL IN MICE LACKING A FUNCTIONAL CRH RECEPTOR 1 (1998)

Behavioural Pharmacology publishes original research reports in diverse areas, ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Topics include drug, chemical, and hormonal effects on behaviour, the neurochemical mechanisms underlying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are published. Studies reporting neurochemical data have a predominantly behavioural focus, and human studies do not consist exclusively of clinical trials or case reports. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems.
High-affinity binding to staphylococcal protein A by an engineered dimeric Affibody molecule (2013)

Affibody molecules are engineered binding proteins, in which the three-helix bundle motif of the Z domain derived from protein A is used as a scaffold for sequence variation. We used phage display to select Affibody binders to staphylococcal protein A itself. The best binder, called ZpA963, binds with similar affinity and kinetics to the five homologous E, D, A, B and C domains of protein A, and to a five-domain protein A construct with an average dissociation constant, K(D), of ~20 nM. The structure of ZpA963 in complex with the Z domain shows that it interacts with a surface on Z that is identical in the five protein A domains, which explains the multi-domain affinity. This property allows for high-affinity binding by dimeric Affibody molecules that simultaneously engage two protein A domains in a complex. We studied two ZpA963 dimers in which the subunits were linked by a C-terminal disulfide in a symmetric dimer or head-to-tail in a fusion protein, respectively. The dimers both bind protein A with high affinity, very slow off-rates and with saturation-dependent kinetics that can be understood in terms of dimer binding to multiple sites. The head-to-tail (ZpA963)2htt dimer binds with an off-rate of k(off) ≤ 5 × 10(-6) s(-1) and an estimated K(D) ≤ 16 pM. The results illustrate how dimers of selected monomer binding proteins can provide an efficient route for engineering of high-affinity binders to targets that contain multiple homologous domains or repeated structural units.
ChemInform Abstract: STRUCTURAL APPROACH TO THE BEHAVIOR OF PERCHLORATE AS A LIGAND IN TRANSITION‐METAL COMPLEXES USING EXAFS, IR AND RAMAN SPECTROSCOPY. 1. A PERCHLORATE‐BRIDGED COPPER CHAIN WITH SHORT COPPER‐COPPER DISTANCES IN COPPER(II) PERCHLORATE (1984)

Abstract Der unter großem Überschuß an ClzOö (II) erhaltene orangefarbene Feststoff (III) ergab bei thermischer Zers. wasserfreies (hygroskopisches) Cu(Il)‐perchlorat als hellblauen Festkörper (IV).
The 100 Most-cited Articles in the Imaging Literature (2013)

Preclinical articles, primarily in the field of neurologic MR imaging, were highly represented in the top 100 cited articles in the medical imaging literature.
eNOS3 Genetic Polymorphism Is Related to Post-Ablation Early Recurrence of Atrial Fibrillation (2015)

The rs1799983 variant of the eNOS3 gene was associated with ERAF, but not with CR, after RFCA. eNOS3 gene variants may have a potential role for stratification of post-ablation management.
OXA-60, a Chromosomal, Inducible, and Imipenem-Hydrolyzing Class D β-Lactamase from<i>Ralstonia pickettii</i> (2004)

A chromosomally encoded oxacillinase, OXA-22, had been characterized from Ralstonia pickettii PIC-1 that did not explain by itself the resistance profile of this strain to beta-lactams. Thus, further analysis of the genetic background of this species led to the identification of another oxacillinase, OXA-60, that was expressed only after beta-lactam induction. This chromosomally encoded oxacillinase shared 19% amino acid identity with OXA-22. It has a narrow-spectrum hydrolysis profile that includes imipenem. OXA-60-like enzymes were identified in several R. pickettii strains. Gene inactivation and induction studies of the bla(OXA-60) and bla(OXA-22) genes in R. pickettii identified the relative contribution of each oxacillinase to the resistance profile of R. pickettii to beta-lactams.
Dynamic Biochemical Information Recovery in Spontaneous Human Seminal Fluid Reactions via <sup>1</sup>H NMR Kinetic Statistical Total Correlation Spectroscopy (2008)

Human seminal fluid (HSF) is a complex mixture of reacting glandular metabolite and protein secretions that provides critical support functions in fertilization. We have employed 600-MHz (1)H NMR spectroscopy to compare and contrast the temporal biochemical and biophysical changes in HSF from infertile men with spinal cord injury compared to age-matched controls. We have developed new approaches to data analysis and visualization to facilitate the interpretation of the results, including the first application of the recently published K-STOCSY concept to a biofluid, enhancing the extraction of information on biochemically related metabolites and assignment of resonances from the major seminal protein, semenogelin. Principal components analysis was also applied to evaluate the extent to which macromolecules influence the overall variation in the metabolic data set. The K-STOCSY concept was utilized further to determine the relationships between reaction rates and metabolite levels, revealing that choline, N-acetylglucosamine, and uridine are associated with higher peptidase activity. The novel approach adopted here has the potential to capture dynamic information in any complex mixture of reacting chemicals including other biofluids or cell extracts.
A Twist‐Bend Nematic Phase Driven by Hydrogen Bonding (2014)

Abstract The liquid crystalline phase behavior of 4‐[6‐(4′‐cyanobiphenyl‐4‐yl)hexyloxy]benzoic acid (CB6OBA) and 4‐[5‐(4′‐cyanobiphenyl‐4‐yloxy)pentyloxy]benzoic acid (CBO5OBA) is described. Both acids show an enantiotropic nematic phase attributed to the formation of supramolecular complexes by hydrogen bonding between the benzoic acid units. In addition, CB6OBA provides the first example of hydrogen bonding driving the formation of the twist‐bend nematic phase. The observation of the twist‐bend nematic phase for CB6OBA, but not CBO5OBA, is attributed to the more bent molecular shape of the complexes formed by the former, reinforcing the view that shape is a key factor in stabilizing this new phase. Temperature‐dependent FTIR spectroscopy reveals differences in hydrogen bonding between the two nematic phases shown by CB6OBA which suggest that the open hydrogen‐bonded complexes may play an important role in stabilizing the helical arrangement found in the twist‐bend nematic phase.