gebhart/patrepeval huggingface dataset:
A Simple RNA Target Capture NGS Strategy for Fusion Genes Assessment in the Diagnostics of Pediatric B‐cell Acute Lymphoblastic Leukemia (2019)

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. Fusion genes are hallmarks of ALL, and they are used as biomarkers for risk stratification as well as targets for precision medicine. Hence, clinical diagnostics pursues broad and comprehensive strategies for accurate discovery of fusion genes. Currently, the gold standard methodologies for fusion gene detection are fluorescence in situ hybridization and polymerase chain reaction; these, however, lack sensitivity for the identification of new fusion genes and breakpoints. In this study, we implemented a simple operating procedure (OP) for detecting fusion genes. The OP employs RNA CaptureSeq, a versatile and effortless next-generation sequencing assay, and an in-house as well as a purpose-built bioinformatics pipeline for the subsequent data analysis. The OP was evaluated on a cohort of 89 B-cell precursor ALL (BCP-ALL) pediatric samples annotated as negative for fusion genes by the standard techniques. The OP confirmed 51 samples as negative for fusion genes, and, more importantly, it identified known (<i>KMT2A</i> rearrangements) as well as new fusion events (<i>JAK2</i> rearrangements) in the remaining 38 investigated samples, of which 16 fusion genes had prognostic significance. Herein, we describe the OP and its deployment into routine ALL diagnostics, which will allow substantial improvements in both patient risk stratification and precision medicine.
CRISPR /Cas9 recombineering‐mediated deep mutational scanning of essential genes in Escherichia coli (2020)

Deep mutational scanning can provide significant insights into the function of essential genes in bacteria. Here, we developed a high-throughput method for mutating essential genes of Escherichia coli in their native genetic context. We used Cas9-mediated recombineering to introduce a library of mutations, created by error-prone PCR, within a gene fragment on the genome using a single gRNA pre-validated for high efficiency. Tracking mutation frequency through deep sequencing revealed biases in the position and the number of the introduced mutations. We overcame these biases by increasing the homology arm length and blocking mismatch repair to achieve a mutation efficiency of 85% for non-essential genes and 55% for essential genes. These experiments also improved our understanding of poorly characterized recombineering process using dsDNA donors with single nucleotide changes. Finally, we applied our technology to target rpoB, the beta subunit of RNA polymerase, to study resistance against rifampicin. In a single experiment, we validate multiple biochemical and clinical observations made in the previous decades and provide insights into resistance compensation with the study of double mutants.
Psychophysiology-Based QoE Assessment: A Survey (2016)

We present a survey of psychophysiology-based assessment for quality of experience (QoE) in advanced multimedia technologies. We provide a classification of methods relevant to QoE and describe related psychological processes, experimental design considerations, and signal analysis techniques. We summarize multimodal techniques and discuss several important aspects of psychophysiology-based QoE assessment, including the synergies with psychophysical assessment and the need for standardized experimental design. This survey is not considered to be exhaustive but serves as a guideline for those interested to further explore this emerging field of research.
Identification of a Ca 2+ -Binding Domain in the Rubella Virus Nonstructural Protease (2007)

The rubella virus (RUB) nonstructural protein (NS) open reading frame (ORF) encodes a polypeptide precursor that is proteolytically self cleaved into two replicase components involved in viral RNA replication. A putative EF-hand Ca(2+)-binding motif that was conserved across different genotypes of RUB was predicted within the nonstructural protease that cleaves the precursor by using bioinformatics tools. To probe the metal-binding properties of this motif, we used an established grafting approach and engineered the 12-residue Ca(2+)-coordinating loop into a non-Ca(2+)-binding scaffold protein, CD2. The grafted EF-loop bound to Ca(2+) and its trivalent analogs Tb(3+) and La(3+) with K(d)s of 214, 47, and 14 microM, respectively. Mutations (D1210A and D1217A) of two of the potential Ca(2+)-coordinating ligands in the EF-loop led to the elimination of Tb(3+) binding. Inductive coupled plasma mass spectrometry was used to confirm the presence of Ca(2+) ([Ca(2+)]/[protein] = 0.7 +/- 0.2) in an NS protease minimal metal-binding domain, RUBCa, that spans the EF-hand motif. Conformational studies on RUBCa revealed that Ca(2+) binding induced local conformational changes and increased thermal stability (Delta T(m) = 4.1 degrees C). The infectivity of an RUB infectious cDNA clone containing the mutations D1210A/D1217A was decreased by approximately 20-fold in comparison to the wild-type (wt) clone, and these mutations rapidly reverted to the wt sequence. The NS protease containing these mutations was less efficient at precursor cleavage than the wt NS protease at 35 degrees C, and the mutant NS protease was temperature sensitive at 39 degrees C, confirming that the Ca(2+)-binding loop played a structural role in the NS protease and was specifically required for optimal stability under physiological conditions.
Phase 2a Study of Ataluren-Mediated Dystrophin Production in Patients with Nonsense Mutation Duchenne Muscular Dystrophy (2013)

ClinicalTrials.gov NCT00264888.
Availability requirement for a fault-management server in high-availability communication systems (2003)

This paper investigates the availability requirement for the fault management server in high-availability communication systems. This study shows that the availability of the fault management server does not need to be 99.999% in order to guarantee a 99.999% system availability, as long as the fail-safe ratio (the probability that the failure of the fault management server does not bring down the system) and the fault coverage ratio (probability that the failure in the system can be detected and recovered by the fault management server) are sufficiently high. Tradeoffs can be made among the availability of the fault management server, the fail-safe ratio, and the fault coverage ratio to optimize system availability. A cost-effective design for the fault management server is proposed.
Sentence Level Machine Translation Evaluation as a Ranking (2007)

The paper proposes formulating MT evalu-ation as a ranking problem, as is often done in the practice of assessment by human. Un-der the ranking scenario, the study also in-vestigates the relative utility of several fea-tures. The results show greater correlation with human assessment at the sentence level, even when using an n-gram match score as a baseline feature. The feature contributing the most to the rank order correlation be-tween automatic ranking and human assess-ment was the dependency structure relation rather than BLEU score and reference lan-guage model feature. 1
An effective imaging condition for reverse-time migration using wavefield decomposition (2011)

Abstract Reverse-time migration (RTM) exhibits great superiority over other imaging algorithms in handling steeply dipping structures and complicated velocity models. However, low-frequency, high-amplitude noises commonly seen in a typical RTM image have been one of the major concerns because they can seriously contaminate the signals in the image if they are not handled properly. We propose a new imaging condition to effectively and efficiently eliminate these specific noises from the image. The method works by first decomposing the source and receiver wavefields to their one-way propagation components, followed by applying a correlation-based imaging condition to the appropriate combinations of the decomposed wavefields. We first give the physical explanation of the principle of such noises in the conventional RTM image. Then we provide the detailed mathematical theory for the new imaging condition. Finally, we propose an efficient scheme for its numerical implementation. It replaces the computationally intensive decomposition with the cost-effective Hilbert transform, which significantly improves the efficiency of the imaging condition. Applications to various synthetic and real data sets demonstrate that this new imaging condition can effectively remove the undesired low-frequency noises in the image.
Harnessing human dendritic cell subsets for medicine (2010)

Immunity results from a complex interplay between the antigen-non-specific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors, and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. In this article, we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines.
A microelectromechanically controlled cavity optomechanical sensing system (2012)

Microelectromechanical systems (MEMS) have been applied to many measurement problems in physics, chemistry, biology and medicine. In parallel, cavity optomechanical systems have achieved quantum-limited displacement sensitivity and ground state cooling of nanoscale objects. By integrating a novel cavity optomechanical structure into an actuated MEMS sensing platform, we demonstrate a system with high quality-factor interferometric readout, electrical tuning of the optomechanical coupling by two orders of magnitude, and a mechanical transfer function adjustable via feedback. The platform separates optical and mechanical components, allowing flexible customization for specific scientific and commercial applications. We achieve displacement sensitivity of 4.6 fm/Hz^1/2 and force sensitivity of 53 aN/Hz^1/2 with only 250 nW optical power launched into the sensor. Cold-damping feedback is used to reduce the thermal mechanical vibration of the sensor by 3 orders of magnitude and to broaden the sensor bandwidth by approximately the same factor, to above twice the fundamental frequency of \approx 40 kHz. The readout sensitivity approaching the standard quantum limit is combined with MEMS actuation in a fully integrated, compact, low power, stable system compatible with Si batch fabrication and electronics integration.
Gut expression and regulation of FAT/CD36: possible role in fatty acid transport in rat enterocytes (2001)

Fatty acid translocase (FAT)/CD36 is one of several putative plasma membrane long-chain fatty acid (LCFA) transport proteins; however, its role in intestinal absorption of LCFA is unknown. We hypothesized that FAT/CD36 would be differentially expressed along the longitudinal axis of the gut and during intestinal development, suggesting specificity of function. We found that intestinal mucosal FAT/CD36 mRNA levels varied by anatomic location along the longitudinal gut axis: stomach 45 +/- 7, duodenum 173 +/- 29, jejunum 238 +/- 17, ileum 117 +/- 14, and colon 9 +/- 1% (means +/- SE with 18S mRNA as control). FAT/CD36 protein levels were also higher in proximal compared with distal intestinal mucosa. Mucosal FAT/CD36 mRNA was also regulated during intestinal maturation, with a fourfold increase from neonatal to adult animals. In addition, FAT/CD36 mRNA levels and enterocyte LCFA uptake were rapidly downregulated by intraduodenal oleate infusion. These findings suggest that FAT/CD36 plays a role in the uptake of LCFA by small intestinal enterocytes. This may have important implications in understanding fatty acid absorption in human physiological and pathophysiological conditions.
Metrology of Quantum Control and Measurement in Superconducting Qubits (2018)

Quantum computers have the potential to solve problems which are classically intractable. Superconducting qubits present a promising path to building such a computer. Recent experiments with these qubits have demonstrated the principles of quantum error correction, quantum simulation, quantum annealing, and more. Current research with superconducting qubits is focused on two primary goals: creating a fully fault tolerant logical qubit out of many physical qubits using surface code error correction, and demonstrating an exponential speedup over any classical computer for a well-defined computational problem. To achieve either of these goals requires high precision control of three components: single qubit gates, two qubit gates, and qubit measurement. In this thesis, we use randomized benchmarking to characterize single qubit gates with 99.95\\% fidelity and two qubit gates wiht 99.5\\% fidelity in superconducting transmon qubits. In addition, we use standard decoherence measurements as well as newly developed extensions of randomized benchmarking to determine the limiting sources of error. Finally, we explore the surprisingly complicated dynamics of measuring the transmon state through a coupled resonator, and show that fully understanding this process requires breaking a few "standard" assumptions.
Susceptibility to Genital Herpes as a Biomarker Predictive of Increased HIV Risk: Expansion of a Murine Model of Microbicide Safety (2009)

These findings indicate that disruption of the epithelium contributes to increased HSV-2 susceptibility and might provide a biomarker predictive of increased risk for HIV acquisition. The results are consistent with the safety outcomes of the recently completed Phase IIb clinical trial with 0.5% PRO 2000 gel, and predict that tenofovir gel will not adversely affect the genital tract.
DELINEATION OF CYSTINE AND CYSTEINE TRANSPORT SYSTEMS IN RAT KIDNEY CORTEX BY DEVELOPMENTAL PATTERNS (1969)

The impaired ability of neonatal rat kidney cortex slices to take up L-cystine at a time when the ability to accumulate cysteine is similar to that of adult tissues indicates the separate nature of the transport processes for these amino acids. Dissimilarities in dependence on oxygen and temperature are also indicative of different transport systems. The intracellular form of the amino acid was largely cysteine when either cystine or cysteine was the transported substrate although significant amounts of both were incorporated into reduced glutathione. No difference in intracellular forms was found between neonatal and adult tissue.
In vitro activities of two oxazolidinone antimicrobial agents, DuP 721 and DuP 105 (1988)

The antibacterial activities of DuP 105 and DuP 721, new oxazolidinone antimicrobial agents, were compared with those of beta-lactams and glycopeptides. Ninety percent of Staphylococcus aureus and Staphylococcus epidermidis isolates, including methicillin-resistant isolates, were inhibited by 4 micrograms of DuP 105 and 1 microgram of DuP 721 per ml. DuP 721 inhibited hemolytic streptococcus groups A, B, C, F, and G at a concentration of less than or equal to 1 microgram/ml, and it inhibited viridans group streptococci at a concentration of 2 micrograms/ml. Both agents inhibited Listeria monocytogenes, Corynebacterium group JK species, anaerobic cocci, and Clostridium spp. including Clostridium difficile. They did not inhibit members of the family Enterobacteriaceae or Pseudomonas aeruginosa, but the MIC for 90% of Bacteroides fragilis isolates was 8 micrograms of DuP 721 per ml.
Lipase-catalyzed resolution of acyclic amino alcohol precursors (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLipase-catalyzed resolution of acyclic amino alcohol precursorsEva Foelsche, Andrea Hickel, Helmut Hoenig, and Peter Seufer-WasserthalCite this: J. Org. Chem. 1990, 55, 6, 1749–1753Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/jo00293a015https://doi.org/10.1021/jo00293a015research-articleACS PublicationsRequest reuse permissionsArticle Views532Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Genetic Variables That Influence Phenotype (2006)

Characterization of genetically engineered mice requires consideration of the gene of interest and the genetic background on which the mutation is maintained. A fundamental prerequisite to deciphering the genetic factors that influence the phenotype of a mutant mouse is an understanding of genetic nomenclature. Mutations and transgenes are often maintained on segregating or mixed backgrounds of often-unspecified origin. Minimizing the importance of strain and substrain differences, especially among 129 strains, can lead to poor experimental design or faulty interpretations of data. Genetic factors that influence phenotype can be categorized as traits that are unique to the background strain, unique to the gene of interest, or an interaction of both the background strain and the gene of interest. The commonly used inbred strains are generally well characterized and understood; however, specific genetic alterations combined with genes unique to the background inbred strain may lead to unexpected results. Genetic background effects can be analyzed and controlled for by using specific targeting and breeding strategies. Selection of appropriate experimental controls is critical. Ideally, mutations or transgenes should be characterized on more than one genetic background and in hybrids of the two progenitor strains. This approach may lead to the identification of novel genetic modifiers of the "gene of interest." Conditional mutagenesis technologies increase the options for controlling genetic background effects in addition to permitting the study of developmental and temporal changes in gene and protein expression and thus phenotype.
Dielectric permittivity of Si/sub 3/N/sub 4/ and SiO/sub 2/ increased by electrode profile and material (2003)

The dielectric permittivity of thin films of silicon nitride and silicon oxide deposited on a silicon wafer can considerably be increased by the geometrical form and the material of the counter (gate) electrode. A conventional disc-like electrode either consisting of Pd or Au results in the well known permittivity data for both dielectrics. However, the use of a Pd electrode with a Gaussian-like profile yields an increase of the permittivity from /spl epsi//sub r/'/spl ap/7 to /spl epsi//sub r/'/spl ap/22 for silicon nitride at the low frequency side of the spectrum. Similar results are obtained for silicon oxide. The increase of /spl epsi//sub r/' is assumed to be due to an enhanced absorption of hydrogen (protons) from the atmosphere by the thin and scattered edges of the Gaussian-like Pd electrode. The protons diffuse into the dielectric film and contribute directly or indirectly to the permittivity.
T‐DNA recombination and replication in maize cells (2003)

T-DNA recombination and replication was analyzed in 'black mexican sweet' (BMS) cells transformed with T-DNAs containing the replication system from wheat dwarf virus (WDV). Upon recombination between the T-DNA ends, a promoterless marker gene (gusA) was activated. Activation of the recombination marker gene was delayed and increased exponentially over time, suggesting that recombination and amplification of the T-DNA occurred in maize cells. Mutant versions of the viral initiator gene (rep), known to be defective in the replication function, failed to generate recoverable recombinant T-DNA molecules. Circularization of T-DNA by the FLP/FRT site-specific recombination system and/or homologous recombination was not necessary to recover circular T-DNAs. However, replicating T-DNAs appeared to be suitable substrates for site-specific and homologous recombination. Among 33 T-DNA border junctions sequenced, only one pair of identical junction sites was found implying that the population of circular T-DNAs was highly heterogenous. Since no circular T-DNA molecules were detected in treatments without rep, it suggested that T-DNA recombination was linked to replication and might have been stimulated by this process. The border junctions observed in recombinant T-DNA molecules were indicative of illegitimate recombination and were similar to left-border recombination of T-DNA into the genome after Agro-mediated plant transformation. However, recombination between T-DNA molecules differed from T-DNA/genomic DNA junction sites in that few intact right borders were observed. The replicating T-DNA molecules did not enhance genomic random integration of T-DNA in the experimental configuration used for this study.
First Downhole Application of Distributed Acoustic Sensing (DAS) for Hydraulic Fracturing Monitoring and Diagnostics (2011)

Abstract The first E&amp;P downhole field trial of Distributed Acoustic Sensing (DAS) fibre optic technology was conducted by Shell Canada during the completion of a tight gas well in February 2009. DAS is a novel technology that allows the detection, discrimination and location of acoustic events on a standard telecom single-mode fibre of several kilometres in length. Using a combination of the measurement of backscattered light and advanced signal processing, the DAS interrogator system segregates the fibre into an array of individual "microphones". To date the technology has been mainly applied in the defense and security industries. One of the most exciting applications for downhole application of DAS is in the area of hydraulic fracturing of tight sand and shale gas reservoirs. Balancing the cost of hydraulic fracture stimulation versus the production benefit is crucial in a tight sand and shale gas developments as, after drilling costs, the completion is the largest single cost component of the well. Recordings were made while tools were run in hole, bridge plugs set, perforations shot and during the fracture stimulation treatment(s). The technology proved sufficiently reliable and sensitive to detect and monitor these in-well activities. The fidelity of the recordings made during hydraulic fracturing and flow back operations, provided a step-change improvement in the ability to perform real-time and post-job diagnostics &amp; analyses of the stimulation. The different case studies presented in this paper will illustrate how, even in its earliest form, DAS has the potential to enhance the capability of monitoring and understanding in-wellbore activities. The technology enables the optimization of hydraulic fracturing design and execution, which could drive down completion costs and lead to increased well productivity and ultimate recovery.