gebhart/patrepeval huggingface dataset:
Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer (2011)

Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10)) and BMP2 (rs4813802, P = 4.65×10(-11)). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8)) and rs11632715 (P = 2.30×10(-10)). As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.
Singing voice conversion method based on many-to-many eigenvoice conversion and training data generation using a singing-to-singing synthesis system (2012)

Abstract—The voice quality (identity) of singing voices is usually fixed in each singer. To overcome this limitation and enable singers to freely change their voice quality using signalprocessing technologies, we propose a singing voice conversion method based on many-to-many eigenvoice conversion (EVC) that can convert the voice quality of an arbitrary source singer into that of another arbitrary target singer. Previous EVC-based methods required parallel data consisting of song pairs of a single reference singer and many prestored target singers for training a voice conversion model, but it was difficult to record such data. Our proposed method therefore uses a singing-to-singing synthesis system called VocaListener to generate parallel data by imitating singing voices of many prestored target singers with the system’s singing voices. Experimental results show that our method succeeded in enabling people to sing a song with the voice quality of a different target singer even if only an extremely small amount of the target singing voice is available. I.
Does Obstructive Sleep Apnea Worsen During REM Sleep? (2013)

Although it is thought that obstructive sleep apnea (OSA) is worse during rapid eye movement (REM) sleep than in non-REM (NREM) sleep there are some uncertainties, especially about apnoe-hypopnoe-index (AHI). Several studies found no significant difference in AHI between both sleep stages. However, REM sleep is associated more with side sleeping compared to NREM sleep, which suggests that body position is a possible confounding factor. The main purpose of this study was to compare the AHI in REM and NREM sleep in both supine and lateral body position. A retrospective study was performed on 422 consecutive patients who underwent an overnight polysomnography. Women had higher AHI in REM sleep than NREM sleep in both supine (46.05+/-26.26 vs. 23.91+/-30.96, P<0.01) and lateral (18.16+/-27.68 vs. 11.30+/-21.09, P<0.01) body position. Men had higher AHI in REM sleep than NREM sleep in lateral body position (28.94+/-28.44 vs. 23.58+/-27.31, P<0.01), however, they did not reach statistical significance in supine position (49.12+/-32.03 in REM sleep vs. 45.78+/-34.02 in NREM sleep, P=0.50). In conclusion, our data suggest that REM sleep is a contributing factor for OSA in women as well as in men, at least in lateral position.
Enzyme which specifically adds tyrosine to the α chain of tubulin (1977)

A posttranslational modification of tubulin with potential significance for the regulation of microtubule assembly or function has been revealed by the discovery of an enzyme (tubulin--tyrosine ligase) which can add a tyrosine residue to the alphachain, apparently through peptide bond linkage to a C-terminal glutamate or glutamine. The ability to add tyrosine in the presence of ATP and to release it agiain in the presence of ADP and inorganic phosphate (or arsenate) appear to be functions of the same enzyme, as judged by the relative rates at which these reactions are catalyzed over a 20-fold enzyme purification. The apparent size of the enzyme from bovine brain is 150 000 daltons in extracts and after ammonium sulfate fractionation, but 35 000 after elution from anion-exchange columns. Addition of pure dimeric tubulin to the latter species converts it back to the larger form, which is apparently a stoichiometric 1:1 complex of tubulin and the 35 000-dalton enzyme. Tubulin--tyrosine ligase is specific for tubulin; other proteins with C-terminal glutamate or glutamine do not substratesmate or glutamine do not act as substrates or inhibitors. It is less specific for tyrosine; five out of six tyrosine dipeptides were inhibitors and competed with tyrosine.
The mechanism of polymer alignment of liquid-crystal materials (1987)

Smetic and nematic liquid-crystal materials can be homogeneously aligned by buffed thin films of appropriate polymers. We propose that the buffing process orients the polymer’s molecular chains in a manner similar to cold drawing of bulk polymer samples. Experimental verification of this theory is obtained by measuring buffing-induced birefringence in thin films of various polymers coated on glass. Further experiments establish that the oriented state of the polymer chains, and not scratching or grooving of the surface, is necessary to produce alignment. Alignment is found to occur when the polymer is both oriented and crystalline. A picture of alignment is presented in which the formation of a liquid-crystal phase on the crystalline,oriented polymer surface is analogous to the epitaxial growth of conventional solid crystals.
ELECTRIC CONDUCTANCE OF BIOLOGICAL SYSTEMS (1933)

Since the time of Galvani, the electrical phenomena associated with the physiological prooesses of growth, stimulation, injury, recovery and death have received an enormous amount of experimental and theoretical attention. Certain of these phenomena, such as action potentials resulting from some physiological activity, and physiological activity, resulting from an externally applied electric field, may be considered as "active" from the physiological point of view. From the investigations of these activities, much evidence has been accumulated which indicates that in general the living cell may be considered to have an electrically conducting interior enclosed by a comparatively non-conducting membrane—or sheath. There is, furthermore, hoth direct and indirect evidence of the existence of an electric potential difference across this membrane in the normal resting cell. Also, almost any change of the physiological condition of the cell is accompanied by an alteration of this potential difference. Conversely, when the potential difference is changed...
A secretory system for bacterial production of high‐profile protein targets (2011)

Escherichia coli represents a robust, inexpensive expression host for the production of recombinant proteins. However, one major limitation is that certain protein classes do not express well in a biologically relevant form using standard expression approaches in the cytoplasm of E. coli. To improve the usefulness of the E. coli expression platform we have investigated combinations of promoters and selected N-terminal fusion tags for the extracellular expression of human target proteins. A comparative study was conducted on 24 target proteins fused to outer membrane protein A (OmpA), outer membrane protein F (OmpF) and osmotically inducible protein Y (OsmY). Based on the results of this initial study, we carried out an extended expression screen employing the OsmY fusion and multiple constructs of a more diverse set of human proteins. Using this high-throughput compatible system, we clearly demonstrate that secreted biomedically relevant human proteins can be efficiently retrieved and purified from the growth medium.
Why isoEthernet will change the voice and video worlds (1996)

The answers to many of the communications problems businesses face lie in the integration of telephony, data collaboration, and video communications with the desktop computer, doing it inexpensively, doing it seamlessly with the local area and wide area networks. The adoption of isochronous Ethernet (isoEthernet) by the IEEE 802.9 committee as the new multimedia standard in LANs has given rise to new technology that converges voice, collaborative video, and data at the desktop. The official name for isoEthernet is ISLAN16-T, and it is sponsored by the IEEE 802.9 committee. IEEE 802.9a, the document specifying the isoEthernet standard, became an official standard at the end of 1995. The intent behind the ISLAN16-T standard is to define a LAN transport capable of handling synchronous services such as voice and video while retaining compatibility with 10Base-T. ISLAN16-T opens the door to a multitude of new applications that can reshape work and communications habits to make businesses more productive, responsive, and profitable.
Hardware and software requirements for quantitative analysis of comparative genomic hybridization (1995)

Recommendations are made for hardware and software capabilities that will permit a level of performance of comparative genomic hybridization (CGH) analysis on metaphase chromosomes that is comparable to the best current practice. Guidelines for interpreting the results of CGH analysis in terms of chromosomal gains or losses are also presented.
Practical recording materials (1996)

The ideal recording material for holography should have a spectral sensitivity well matched to available laser wavelengths, a linear transfer characteristic, high resolution, and low noise. In addition, it should either be indefinitely recyclable or relatively inexpensive.
Swinholide A Is a Microfilament Disrupting Marine Toxin That Stabilizes Actin Dimers and Severs Actin Filaments (1995)

Swinholide A, isolated from the marien sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of swinholide A. They also suggest that swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities.
Epigenetic biomarkers in urothelial bladder cancer (2009)

Bladder cancers comprise heterogeneous cell populations, and numerous factors are likely to be involved in dictating recurrence, progression and patient survival. While several molecular markers that are used to evaluate the development and prognosis of bladder cancer have been studied, the limited value of these established markers has created the need for new molecular indicators of bladder cancer prognosis. Of particular interest is the silencing of tumor-suppressor genes by epigenetic alteration. Recent progress in understanding epigenetic modification and gene silencing has led to new opportunities for the understanding, detection, treatment and prevention of cancer. Moreover, epigenetic silencing of tumor-suppressor genes is interesting from a clinical standpoint, because of the possibility of reversing epigenetic changes and restoring gene function in a cell. This review focuses on the prognostic relevance of epigenetic markers in bladder cancer.
Computer aided design of square spiral transformers and inductors (MIC application) (2003)

A simple, yet accurate, lumped-element model for four-port planar rectangular spiral structures has been developed. Closed-form expressions were used to generate frequency-dependent parameter values, resulting in an equivalent circuit which is easily incorporated into existing analysis packages. The method can easily be implemented in a commercial microwave computer-aided design program, allowing its use in the optimization of various types of active circuits. The technique was applied to standard and center-tapped transformer configurations, as well as to spiral inductors to 20 GHz. Comparison with measured results shows good agreement up to the first resonant frequency of the structures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Privacy preserving database application testing (2003)

Traditionally, application software developers carry out their tests on their own local development databases. However, such local databases usually have only a small number of sample data and hence cannot simulate satisfactorily a live environment, especially in terms of performance and scalability testing. On the other hand, the idea of testing applications over live production databases is increasingly problematic in most situations primarily due to the fact that such use of live production databases has the potential to expose sensitive data to an unauthorized tester and to incorrectly update information in the underlying database. In this paper, we investigate techniques to generate mock databases for application software testing without revealing any confidential information from the live production databases. Specifically, we will design mechanisms to create the deterministic rule set R, non-deterministic rule set N R, and statistic data set S for a live production database. We will then build a security Analyzer which will process the triplet <R',N R',S'> together with security requirements (security policy) and output a new triplet <R',N R',S'> The security Analyzer will guarantee that no confidential information could be inferred from the new triplet <R',N R',S'> The mock database generated from this new triplet can simulate the live environment for testing purpose, while maintaining the privacy of data in the original database.
Design of waveguide-grating filters with symmetrical line shapes and low sidebands (1994)

We show that ideal reflection filters can be designed by combining guided-mode resonance effects in waveguide gratings with antireflection effects of thin-film structures. Since the guided-mode resonance effect overrides the antireflection effect this filter provides a symmetrical line shape with near-zero reflectivity over appreciable wavelength bands adjacent to the resonance wavelength. In the single-layer filter the same layer functions as the waveguide grating supporting the resonance and as the antireflection layer suppressing reflection around the resonance. A multilayer design allows the filter resonance peak to have a wide surrounding region of low reflectance. The central resonance wavelength, the filter linewidth, the range of the low sidebands, and the resonance line shape are all under the control of the designer.
Attenuation of Serum Inducibility of Immediate early Genes by Oncoproteins in Tyrosine Kinase Signaling Pathways (1993)

Immediate early genes involved in controlling cell proliferation are rapidly and transiently induced following stimulation of susceptible cells with serum. To study how oncoproteins regulate immediate early genes, we examined serum inducibility of these genes in cells transformed by various oncoproteins. We found that induction of the immediate early gene, c-fos, by serum stimulation was markedly attenuated in four independent cell lines stably transformed by the v-Src tyrosine kinase. Cells chronically transformed by other oncoproteins implicated in tyrosine kinase signaling pathways, including v-Sis, v-Ras, and v-Raf, showed the same pattern of attenuation. In contrast, serum inducibility of c-fos was not attenuated in cells transformed by simian virus 40, which is thought to transform cells through a different pathway. Cell cycle analyses showed that proliferation of these transformed cell lines could be arrested effectively in 0.1% serum, demonstrating that the attenuation was not simply due to continuous cycling of transformed cells after serum deprivation. Moreover, serum inducibility of other immediate early genes, including c-jun, junB, egr-1, and NGFI-B, also was strikingly attenuated by these same oncoproteins. Nuclear run-on transcription assays established that this attenuation of serum inducibility occurred at the transcriptional level. Finally, flow cytometric analysis demonstrated that serum-starved v-Src-transformed cells were viable and able to progress into S phase of the cell cycle after serum stimulation, even though the induction of immediate early genes was greatly attenuated in these cells. Our results suggest that activation of immediate early genes is repressed by chronic stimulation of tyrosine kinase signaling pathways in transformed cells.
An in vitro screening technique for DNA polymerases that can incorporate modified nucleotides. Pseudo-thymidine as a substrate for thermostable polymerases (1999)

DNA polymerases are desired that incorporate modified nucleotides into DNA with diminished pausing, premature termination and infidelity. Reported here is a simple in vitro assay to screen for DNA polymerases that accept modified nucleotides based on a set of primer extension reactions. In combination with the scintillation proximity assay (SPA[trade]), this allows rapid and simple screening of enzymes for their ability to elongate oligonucleotides in the presence of unnatural nucleotides. A proof of the concept is obtained using pseudo-thymidine (psiT), the C-nucleoside analog of thymidine, as the unnatural substrate. The conformational properties of psiT arising from the carbon-carbon bond between the sugar and the base make it an interesting probe for the importance of conformational restraints in the active site of polymerases during primer elongation. From a pool of commercially available thermostable polymerases, the assay identified Taq DNA polymerase as the most suitable enzyme for the PCR amplification of oligonucleotides containing psiT. Subsequent experiments analyzing PCR performance and fidelity of Taq DNA polymerase acting on psiT are presented. This is the first time that PCR has been performed with a C-nucleoside.
Spectrum, energy content and relaxation mechanism of the photoisomer of the laser dye 3,3'-diethyloxadicarbocyanine iodide. Laser-induced optoacoustic studies (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpectrum, energy content and relaxation mechanism of the photoisomer of the laser dye 3,3'-diethyloxadicarbocyanine iodide. Laser-induced optoacoustic studiesGabriel M. Bilmes, Jorge O. Tocho, and Silvia E. BraslavskyCite this: J. Phys. Chem. 1988, 92, 21, 5958–5962Publication Date (Print):October 1, 1988Publication History Published online1 May 2002Published inissue 1 October 1988https://pubs.acs.org/doi/10.1021/j100332a024https://doi.org/10.1021/j100332a024research-articleACS PublicationsRequest reuse permissionsArticle Views111Altmetric-Citations35LEARN 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 options Get e-Alerts
Activity-based protein profiling: The serine hydrolases (1999)

With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. To date, proteomics efforts have primarily been confined to recording variations in protein level rather than activity. The ability to profile classes of proteins on the basis of changes in their activity would greatly accelerate both the assignment of protein function and the identification of potential pharmaceutical targets. Here, we describe the chemical synthesis and utility of an active-site directed probe for visualizing dynamics in the expression and function of an entire enzyme family, the serine hydrolases. By reacting this probe, a biotinylated fluorophosphonate referred to as FP-biotin, with crude tissue extracts, we quickly and with high sensitivity detect numerous serine hydrolases, many of which display tissue-restricted patterns of expression. Additionally, we show that FP-biotin labels these proteins in an activity-dependent manner that can be followed kinetically, offering a powerful means to monitor dynamics simultaneously in both protein function and expression.
Genome engineering using the CRISPR-Cas9 system (2013)

Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.