gebhart/patrepeval huggingface dataset:
Analysis of Bladder Cancer Tumor CpG Methylation and Gene Expression within The Cancer Genome Atlas Identifies GRIA1 as a Prognostic Biomarker for Basal-Like Bladder Cancer (2019)

Increased methylation levels at cytosines proximal to guanines (CpG) in the promoter regions of tumor suppressor genes have been reported to play an important role in the development and progression of bladder cancer. In this study, we conducted a genome-wide analysis using data from The Cancer Genome Atlas to better characterize CpG methylation and mRNA expression patterns in urothelial carcinomas and to identify new epigenetic biomarkers of survival. Across 408 tumors, we identified 223 genes that displayed significant relationships between CpG methylation and mRNA expression levels. Hypermethylation within 200 base pairs upstream of the transcription start site and hypomethylation within the 3' untranslated region and body region were associated with gene silencing. These 223 genes were functionally enriched for their role in glutamate receptor signaling and among them was a novel, tumor-stage-independent epigenetic biomarker of overall mortality, <i>GRIA1. GRIA1</i> hypermethylation and elevated mRNA expression levels were associated with significantly worse survival outcomes in patients with basal-like urothelial carcinomas. Furthermore, 70 genes associated with glutamate receptor signaling were differentially expressed between basal (n = 203 tumors) and luminal (n = 205 tumors) subtypes of bladder cancer, including genes involved in glutamate receptor-mediated activation of the calmodulin, PI3K/Akt, and EGFR signaling pathways. The majority of genes displayed increased expression levels in basal-like subtypes. This research highlights glutamate receptors as targets for investigation in the development and pharmacological treatment of urothelial cancer.
Electroporation enables the efficient mRNA delivery into the mouse zygotes and facilitates CRISPR/Cas9-based genome editing (2015)

Abstract Recent use of the CRISPR/Cas9 system has dramatically reduced the time required to produce mutant mice, but the involvement of a time-consuming microinjection step still hampers its application for high-throughput genetic analysis. Here we developed a simple, highly efficient and large-scale genome editing method, in which the RNAs for the CRISPR/Cas9 system are electroporated into zygotes rather than microinjected. We used this method to perform single-stranded oligodeoxynucleotide (ssODN)-mediated knock-in in mouse embryos. This method facilitates large-scale genetic analysis in the mouse.
Interaction of Stat6 and NF-κB: Direct Association and Synergistic Activation of Interleukin-4-Induced Transcription (1998)

Signal transducer and activator of transcription 6 (Stat6) and NF-kappaB are widely distributed transcription factors which are induced by different stimuli and bind to distinct DNA sequence motifs. Interleukin-4 (IL-4), which activates Stat6, synergizes with activators of NF-kappaB to induce IL-4-responsive genes, but the molecular mechanism of this synergy is poorly understood. Using glutathione S-transferase pulldown assays and coimmunoprecipitation techniques, we find that NF-kappaB and tyrosine-phosphorylated Stat6 can directly bind each other in vitro and in vivo. An IL-4-inducible reporter gene containing both cognate binding sites in the promoter is synergistically activated in the presence of IL-4 when Stat6 and NF-kappaB proteins are coexpressed in human embryonic kidney 293 (HEK 293) cells. The same IL-4-inducible reporter gene is also synergistically activated by the endogenous Stat6 and NF-kappaB proteins in IL-4-stimulated I.29mu B lymphoma cells. Furthermore, Stat6 and NF-kappaB bind cooperatively to a DNA probe containing both sites, and the presence of a complex formed by their cooperative binding correlates with the synergistic activation of the promoter by Stat6 and NF-kappaB. We conclude that the direct interaction between Stat6 and NF-kappaB may provide a basis for synergistic activation of transcription by IL-4 and activators of NF-kappaB.
An Integrated Global Demining and Development Strategy (1999)

The German Agency for Technical Cooperation (GTZ) operates as a public service company. The development policy objective is to improve the survival chances of people in countries of the Southern and Eastern Hemisphere, and to stabilize their natural bases of existence. The most important financing organization of the GTZ is the German federal government, i.e. the Federal Ministry for Economic co-operation and Development (BMZ). Within the framework of the federal government’s guidelines and development policy objectives, the GTZ is responsible for the conception, planning and implementation of 2800 projects in 140 partner countries. In addition to federal ministries, the GTZ also operates as contractor of international institutions such as the European Commission, the World Bank, United Nations organizations and regional development banks.
A simulation approach to statistical evaluation of periodic task scheduling in a real-time computer system (2010)

The task schedulability theorem in the celebrated GRMS theory provides a sufficient condition only, specifying the upper bound on CPU utilization by scheduled periodic tasks. This paper presents a simulation study on real-time task scheduling for a specific case when the upper bound on processor utilization can be exceeded. The results are applied in a problem of multiprocessor task scheduling.
The natural electrical conductivity of organic liquids subjected to hydrostatic pressures (1974)

The natural electrical conductivity of several organic liquids has been measured using transformer-coupled ratio arm bridges over a range of temperatures and pressures. Among these, n-hexane, diethyl hexyl sebacate and several alcohols showed a tendency for conductivity to fall with pressure. However, diethyl ether, carbon disulphide and, above 2500 bar, castor oil showed a tendency for conductivity to rise with pressure.
HIVPCES: a WWW-based HIV patient care expert system (2003)

Diagnosing HIV-patients and prescribing the correct drug regimen can be a complex task whose outcome is dependent on a large number of variables. The cost of an incorrectly administered drug even for a very short time, can be enormous. In this paper, the implementation of an interactive expert system to diagnose HIV patients that runs on World Wide Web clients is discussed. The system is managed centrally and accessed either as part of an intranet, or as an Internet site. The issues related to the implementation of the expert system are presented, the interfacing of the original code to the WWW is briefly described, and the database interface used for maintaining patient records are discussed.
Subfoveal choroidal blood flow and central retinal function in early glaucoma (2012)

The results suggest a significant alteration of both ChBVel and ChBF in EMG, which does not appear to be associated with the severity of central retinal dysfunction. These findings may contribute to a better understanding of the pathophysiology of early glaucomatous damage in EMG and have implications for the treatment of this pathologic condition.
<i>Staphylococcus aureus</i> Mevalonate Kinase: Isolation and Characterization of an Enzyme of the Isoprenoid Biosynthetic Pathway (2003)

It has been proposed that isoprenoid biosynthesis in several gram-positive cocci depends on the mevalonate pathway for conversion of acetyl coenzyme A to isopentenyl diphosphate. Mevalonate kinase catalyzes a key reaction in this pathway. In this study the enzyme from Staphylococcus aureus was expressed in Escherichia coli, isolated in a highly purified form, and characterized. The overall amino acid sequence of this enzyme was very heterologous compared with the sequences of eukaryotic mevalonate kinases. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and analytical gel filtration chromatography suggested that the native enzyme is a monomer with a molecular mass of approximately 33 kDa. The specific activity was 12 U/mg, and the pH optimum was 7.0 to 8.5. The apparent K(m) values for R,S-mevalonate and ATP were 41 and 339 micro M, respectively. There was substantial substrate inhibition at millimolar levels of mevalonate. The sensitivity to feedback inhibition by farnesyl diphosphate and its sulfur-containing analog, farnesyl thiodiphosphate, was characterized. These compounds were competitive inhibitors with respect to ATP; the K(i) values were 46 and 45 micro M for farnesyl diphosphate and its thio analog, respectively. Parallel measurements with heterologous eukaryotic mevalonate kinases indicated that S. aureus mevalonate kinase is much less sensitive to feedback inhibition (K(i) difference, 3 orders of magnitude) than the human enzyme. In contrast, both enzymes tightly bound trinitrophenyl-ATP, a fluorescent substrate analog, suggesting that there are similarities in structural features that are important for catalytic function.
The optical and electrical properties of silver nanowire mesh films (2013)

We present experimental results for the transmission T, haze H, sheet resistance Rs, and its spatial fluctuations ΔRs for silver nanowire films. Mie light scattering theory of nanowires is developed to predict both T and H as a function of diameter D of wires and the surface fraction ϕs covered by the wires. Percolation theory is used to derive an equation for Rs in terms of D, the aspect ratio of wires D/L and ϕs. The critical exponent t for percolation of Rs is found to be 1.23 in close agreement with theoretical results for 2D random resistive networks (t = 1.3). These equations show the importance of both the distributions of diameter ⟨D⟩ and aspect ratio of wires ⟨D⟩⟨L⟩/⟨L2⟩ to predict the optical and electrical properties. Spatial fluctuations ΔRs/Rs can also be significant in these films and be greater than 10% as ϕs approaches the critical percolation concentration ϕc. We show that the calculated T versus Rs and H versus Rs curves are in good agreement with the experimental data. We propose figures of merit for percolating nanowire films in terms of high T, low H, and low Rs to order the quality of films for touch screen applications. The results show that D &lt; 50 nm and L &gt; 5 μm are needed to achieve low haze H &lt; 1%, high transmission T &gt; 90%, together with low Rs ∼ 100 Ω/sq for touch screen applications. Finally, we present experimental and theoretical results of the real and imaginary refractive indices of AgNW/polymer nanocomposites, and find that the Van De Hulst model is more accurate than the Maxwell Garnett models.
Crystal structure of the kinase domain of serum and glucocorticoid‐regulated kinase 1 in complex with AMP–PNP (2007)

Serum and glucocorticoid-regulated kinase 1 (SGK1) is a serine/threonine protein kinase of the AGC family which participates in the control of epithelial ion transport and is implicated in proliferation and apoptosis. We report here the 1.9 A crystal structure of the catalytic domain of inactive human SGK1 in complex with AMP-PNP. SGK1 exists as a dimer formed by two intermolecular disulfide bonds between Cys258 in the activation loop and Cys193. Although most of the SGK1 structure closely resembles the common protein kinase fold, the structure around the active site is unique when compared to most protein kinases. The alphaC helix is not present in this inactive form of SGK1 crystal structure; instead, the segment corresponding to the C helix forms a beta-strand that is stabilized by the N-terminal segment of the activation loop through a short antiparallel beta-sheet. Since the differences from other kinases occur around the ATP binding site, this structure can provide valuable insight into the design of selective and highly potent ATP-competitive inhibitors of SGK1 kinase.
Genetic inducible fate mapping in larval zebrafish reveals origins of adult insulin-producing β-cells (2011)

The Notch-signaling pathway is known to be fundamental in controlling pancreas differentiation. We now report on using Cre-based fate mapping to indelibly label pancreatic Notch-responsive cells (PNCs) at larval stages and follow their fate in the adult pancreas. We show that the PNCs represent a population of progenitors that can differentiate to multiple lineages, including adult ductal cells, centroacinar cells (CACs) and endocrine cells. These endocrine cells include the insulin-producing β-cells. CACs are a functional component of the exocrine pancreas; however, our fate-mapping results indicate that CACs are more closely related to endocrine cells by lineage as they share a common progenitor. The majority of the exocrine pancreas consists of the secretory acinar cells; however, we only detect a very limited contribution of PNCs to acinar cells. To explain this observation we re-examined early events in pancreas formation. The pancreatic anlage that gives rise to the exocrine pancreas is located in the ventral gut endoderm (called the ventral bud). Ptf1a is a gene required for exocrine pancreas development and is first expressed as the ventral bud forms. We used transgenic marker lines to observe both the domain of cells expressing ptf1a and cells responding to Notch signaling. We do not detect any overlap in expression and demonstrate that the ventral bud consists of two cell populations: a ptf1-expressing domain and a Notch-responsive progenitor core. As pancreas organogenesis continues, the ventral bud derived PNCs align along the duct, remain multipotent and later in development differentiate to form secondary islets, ducts and CACs.
mRNA processing by RNases J1 and J2 affects <i>Bacillus subtilis</i> gene expression on a global scale (2008)

Ribonucleases J1 and J2 of Bacillus subtilis are evolutionarily conserved enzymes combining an endoribonucleolytic and a 5'-3' exoribonucleolytic activity in a single polypeptide. Their endoribonucleolytic cleavage specificity resembles that of RNase E, a key player in the processing and degradation of RNA in Escherichia coli. The biological significance of the paralogous RNases J1 and J2 in Bacillus subtilis is still unknown. Based on the premise that cleavage of an mRNA might alter its stability and hence its abundance, we have analysed the transcriptomes and proteomes of single and double mutant strains. The absence or decrease of both RNases J1 and J2 together profoundly alters the expression level of hundreds of genes. By contrast, the effect on global gene expression is minimal in single mutant strains, suggesting that the two nucleases have largely overlapping substrate specificities. Half-life measurements of individual mRNAs show that RNases J1/J2 can alter gene expression by modulating transcript stability. The absence/decrease of RNases J1 and J2 results in similar numbers of transcripts whose abundance is either increased or decreased, suggesting a complex role of these ribonucleases in both degradative and regulatory processing events that have an important impact on gene expression.
Design of multi-phase DC-DC converter with master-slave current sharing control (2003)

A novel multi-phase PWM DC-DC converter is designed, in order to solve the problem of meeting the power supply requirements of the new generation microprocessor which requires 40-100 A currents, lower voltage and better current transient response. In multi-phase converter, how to balance the currents in each phase is most important, and master-slave current sharing is an effective way. The multi-phase converter, by distributing the power and load current results in smaller and lower cost transistor with fewer input and output capacitors. It meets the specifications of Intel's VRM9.0 design guideline for the power supply of high-performance Pentium IV central processing units.
Using the topology-preserving properties of SOFMs in speech recognition (1991)

Self-organizing feature maps (SOFMs) are used as speech feature extractors followed by a classifier based on multilayer feedforward networks. Usually SOFMs have been used in speech recognition as static pattern classifiers or vector quantizers, ignoring their property of preserving the local topology of input pattern space. Here, the topological ordering of the acoustic speech data in the SOFM is utilized to form trajectories in the map which are then fed into a classifier. Viewing the trajectories at multiple resolution levels, feature vectors are formed that take contextual information into account. Experiments with such feature vectors indicate that better accuracies can be obtained than by using a simple SOFM classifier based on instantaneous acoustic features.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Role of the influenza virus heterotrimeric RNA polymerase complex in the initiation of replication (2006)

Both transcription and replication of the influenza virus RNA genome are catalysed by a virus-specific RNA polymerase. Recently, an in vitro assay, based on the synthesis of pppApG, for the initiation of replication by recombinant RNA polymerase in the absence of added primer was described. Here, these findings are extended to show that adenosine, AMP and ADP can each substitute for ATP in reactions catalysed by either recombinant ribonucleoprotein or RNA polymerase complexes with either model virion RNA (vRNA) or cRNA promoters. The use of either adenosine or AMP, rather than ATP, provides a convenient, sensitive and easy assay of replication initiation. Moreover, no pppApG was detected when a PB1-PA dimer, rather than the trimeric polymerase, was used to catalyse synthesis, contrasting with a previous report using baculovirus-expressed influenza RNA polymerase. Overall, it is suggested that the heterotrimeric polymerase is essential for the initiation of replication.
Changes in crystal phases and morphologies of rare earth hydroxide nitrates with ionic radius (2017)

Rare earth hydroxide nitrates are prepared from rare earth nitrates by hydrothermal treatment. Three crystal phases, M(OH)3 (M1), M2(OH)5.14(NO3)0.86·H2O (M2), and M4O(OH)9NO3 (M4) are identified. The crystal phase systematically changes from M1 to M4 through M2 with decreasing radius of rare earth cation. Morphology of nanocrystal depends on the crystal phase. M1 and M4 phases grow to be nanorod, and M2 to nanoplate.
Non-contact inspection for inner surface of small-diameter pipes based on laser-PSD (2005)

A new non-contact inspection technique based on laser-PSD (position sensitive detector) to inspect the inner surface of small-diameter pipe is proposed,and the corresponding sensor has been developed.After being reflected by two mirrors in series,a laser beam is projected onto the inner wall of a pipe as a small light spot and is read by a two-dimensional PSD.Based on the signals from the PSD and the structure parameters of the sensor,the spot position on the wall can be calculated in a local 3D coordinate system.The spot controlled by the micro-motor driven mirrors will scan a closed section ring on the inner wall of the pipe to obtain the relative coordinates of all the sampled points.The data will be then processed through data segmentation and least square fitting,to reconstruct the section curve used for obtaining the radius and the defect description of the section.Driven by a micro-pipe robot,the sensor can inspect a long curved pipe and obtain its 3-D reconstruction.An inspection system based on this technique can detect the mini-diameter pipe with an inner diameter of 9.5 mm～10.5 mm and a curvature radius larger than 100 mm at a measurement accuracy of the inner surface defect of ±0.1 mm.
Complete Genomic Structure, DNA Polymorphisms, and Alternative Splicing of the Human AF-6 Gene (1998)

In our previous work, detailed deletion mapping of ovarian cancers indicated that a 300-kb region of chromosome 6q27 was likely to contain one or more putative tumor suppressor genes associated with development of this type of cancer. DNA sequencing in the region disclosed the presence of AF-6, a gene that had been identified as the ALL-1 fusion partner involved in acute myeloid leukemias with t(6;11)(q27;q23) translocations. In the work reported here, we determined the complete genomic sequence of the AF-6 gene, including exon-intron boundaries, and found six DNA polymorphisms. One of them, an insertion/deletion polymorphism, determined the presence or absence of seven amino acids in the AF-6 product. We also identified two alternatively spliced forms of the gene; the two novel transcripts would encode additional C-terminal peptides in comparison to the reported protein. Sequencing of seven cosmid clones that covered the entire gene revealed 32 exons (not including one exon involved in the insertion/deletion polymorphism), spanning approximately 140 kb of genomic DNA. These results may contribute to an understanding of the mechanism causing chromosomal translocations in leukemic cells.
Processing data where it makes sense: Enabling in-memory computation (2019)

Today’s systems are overwhelmingly designed to move data to computation. This design choice goes directly against at least three key trends in systems that cause performance, scalability and energy bottlenecks: (1) data access from memory is already a key bottleneck as applications become more data-intensive and memory bandwidth and energy do not scale well, (2) energy consumption is a key constraint in especially mobile and server systems, (3) data movement is very expensive in terms of bandwidth, energy and latency, much more so than computation. These trends are especially severely-felt in the data-intensive server and energy-constrained mobile systems of today. At the same time, conventional memory technology is facing many scaling challenges in terms of reliability, energy, and performance. As a result, memory system architects are open to organizing memory in different ways and making it more intelligent, at the expense of higher cost. The emergence of 3D-stacked memory plus logic as well as the adoption of error correcting codes inside DRAM chips, and the necessity for designing new solutions to serious reliability and security issues, such as the RowHammer phenomenon, are an evidence of this trend. In this work, we discuss some recent research that aims to practically enable computation close to data. After motivating trends in applications as well as technology, we discuss at least two promising directions for processing-in-memory (PIM): (1) performing massively-parallel bulk operations in memory by exploiting the analog operational properties of DRAM, with low-cost changes, (2) exploiting the logic layer in 3D-stacked memory technology to accelerate important data-intensive applications. In both approaches, we describe and tackle relevant cross-layer research, design, and adoption challenges in devices, architecture, systems, and programming models. Our focus is on the development of in-memory processing designs that can be adopted in real computing platforms at low cost.
Field Guide to Interferometric Optical Testing (2006)

Fundamentals of Interferometry 1 Two-Beam Interference EquationInterferometric optical testing is based on the phenomena of interference.Two-beam interference is the superposition of two waves, such as the disturbance of the surface of a pond by a small rock encountering a similar pattern from a second rock.When two wave crests reach the same point simultaneously, the wave height is the sum of the two individual waves.Conversely, a wave trough and a wave crest reaching a point simultaneously will cancel each other out.Water, sound, and light waves all exhibit interference, but for the purpose of optical testing, the focus will be the interference of light and its applications.