gebhart/patrepeval huggingface dataset:
Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana (2014)

Several genes positively influence final leaf size in Arabidopsis when mutated or overexpressed. The connections between these growth regulators are still poorly understood although such knowledge would further contribute to understand the processes driving leaf growth. In this study, we performed a combinatorial screen with 13 transgenic Arabidopsis lines with an increased leaf size. We found that from 61 analyzed combinations, 39% showed an additional increase in leaf size and most resulted from a positive epistasis on growth. Similar to what is found in other organisms in which such an epistasis assay was performed, only few genes were highly connected in synergistic combinations as we observed a positive epistasis in the majority of the combinations with samba, BRI1(OE) or SAUR19(OE). Furthermore, positive epistasis was found with combinations of genes with a similar mode of action, but also with genes which affect distinct processes, such as cell proliferation and cell expansion.DOI: http://dx.doi.org/10.7554/eLife.02252.001.
A Practical Ion Trap Mass Spectrometer for the Analysis of Peptides by Matrix-Assisted Laser Desorption/Ionization (1996)

The present paper describes the performance of a newly configured matrix-assisted laser desorption/ionization quadrupole ion trap mass spectrometer (MALDI-ITMS), designed for biological applications that require the determination of the primary structures of proteins, e.g., the rapid identification of proteins and the elucidation of posttranslational modifications. The strategy used for solving problems of this type involves enzymatic digestion of the protein, followed by MALDI ion trap mass spectrometric analysis of the components of the resulting complex mixture of peptide ions. The new instrument is demonstrated to be a highly practical tool for analyzing proteins. In particular, mixtures containing as many as 30 peptide components can be rapidly and sensitively analyzed without prior chromatographic separation of the components. Informative tandem mass spectra can be obtained from the peptide components with m/z values up to 3500. A single subpicomole sample loading of a complex peptide mixture is more than sufficient for a complete set of experiments that includes both low- and high-resolution molecular mass determinations as well as a complete MS/MS study of the various components present in the sample. Extensive use is made of improved methods for trapping, isolating, fragmenting, and detecting ions in the ITMS (details are to be provided in two future papers).
Synergic antiproliferative effect of DNA methyltransferase inhibitor in combination with anticancer drugs in gastric carcinoma (2006)

Epigenetic alterations of DNA methylation play an important role in the regulation of gene expression associated with chemosensitivity of gastric carcinomas. With the aim of improving the chemotherapeutic efficacy of gastric carcinoma, the effect of DNA methyltransferase inhibitor, 5-aza-CdR, on the chemosensitivity of five anticancer drugs was investigated. Human gastric cancer cell lines, OCUM-2M and MKN-74, and five anticancer drugs, 5-FU, PTX, OXA, SN38, and GEM, were used. In both gastric cancer cell lines, a synergistic antiproliferative effect by a combination of 5-aza-CdR at 5 microM was found in SN38 and GEM. 5-Aza-CdR at 5 microM increased apoptosis induced by SN38 and GEM in both cell lines. 5-Aza-CdR increases the expression of DAPK-2 and DAPK-3, RASSF1, and THBS1 genes in both OCUM-2M and MKN-74 cells, but not that of hMLH1, p16, MGMT, E-cadherin, and p53 genes. These findings suggest that 5-aza-CdR is a promising chemotherapeutical agent for gastric carcinomas, in combination with the anticancer drugs SN38 and GEM, in apoptosis signaling. The upregulation of DAPK-2 and DAPK-3, RASSF1, and THBS1 genes by 5-aza-CdR might be associated with the synergistic effect.
Hormone Conjugated with Antibody to CD3 Mediates Cytotoxic T Cell Lysis of Human Melanoma Cells (1988)

Cytotoxic T lymphocytes can be activated by antibodies to their antigen-specific receptor complex (TCR-CD3) to destroy target cells, regardless of the specificity of the cytotoxic T cells. A novel hormone-antibody conjugate, consisting of an analog of melanocyte-stimulating hormone chemically coupled to a monoclonal antibody to CD3, the invariant component of the T cell receptor complex, was used to target human melanoma cells for destruction by human cytotoxic T lymphocytes that bear no specificity for the tumor cells. As targeting components of such anti-CD3 conjugates, hormones or growth factors are expected to prove more effective than antibodies to tumor-associated antigens in focusing the destructive activity of cytotoxic T cells on tumor target cells.
Effect of dislocations in strained Si/SiGe on electron mobility (1996)

In this article the presence of threading and misfit dislocations in strained modulation-doped Si/SiGe heterostructures and their effect on electron mobility are investigated. It is found that the low-temperature electron mobility is sensitive to threading dislocations when their density exceeds 3×108 cm−2, and decreases by two orders of magnitude when the threading dislocation density is 1×1011 cm−2. The room-temperature mobility is reduced under the same conditions by 10% and 50%, respectively. Misfit segments in the graded Ge-content buffer limit the mobility when the Si channel is 0.4 μm or less away from that buffer. Misfit dislocations at the Si-channel bottom interface very strongly scatter the electrons in the channel once a continuous network of misfit segments is created.
Targeting phosphoinositide 3‐kinase δ for the treatment of respiratory diseases (2013)

Asthma and chronic obstructive pulmonary disease (COPD) are characterized in their pathogenesis by chronic inflammation in the airways. Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase expressed predominantly in leukocytes, is thought to hold much promise as a therapeutic target for such inflammatory conditions. Of particular interest for the treatment of severe respiratory disease is the observation that inhibition of PI3Kδ may restore steroid effectiveness under conditions of oxidative stress. PI3Kδ inhibition may also prevent recruitment of inflammatory cells, including T lymphocytes and neutrophils, as well as the release of proinflammatory mediators, such as cytokines, chemokines, reactive oxygen species, and proteolytic enzymes. In addition, targeting the PI3Kδ pathway could reduce the incidence of pathogen-induced exacerbations by improving macrophage-mediated bacterial clearance. In this review, we discuss the potential and highlight the unknowns of targeting PI3Kδ for the treatment of respiratory disease, focusing on recent developments in the role of the PI3Kδ pathway in inflammatory cell types believed to be critical to the pathogenesis of COPD.
Stimulatory effect of lysophosphatidic acids on uterine smooth muscles of non-pregant rats. (1980)

Lysophosphatidic acids stimulated isolated uterine smooth muscle dose-dependently. The contractions were not reduced by pretreatment with atropine or an anti-5-hydroxytryptaminic agent. The potency depended on the nature of the acyl chain in the molecule. Of the compounds with a saturated fatty acyl group tested, the most effective were myristoyl- and lauroyl-lysophosphatidic acid. In a series of unsaturated lysophosphatidic acids, the potency increased with the number of cis double bonds in the acyl chain, and linolenoyl-lysophosphatidic acid was the most active. When injected intravenously, these compounds induced an immediate rise in blood pressure and intrauterine pressure, like prostaglandin F2 alpha: The order of potency of their effects on the intact uterus was consistent with that of their effects on isolated uterine smooth muscle, but not with that of their hypertensive effects in rats.
Improved Method for the Determination of Tobacco-specific Nitrosamines (TSNA) in Tobacco Smoke (1989)

Abstract The method used to determine tobacco-specific nitrosamines [TSNA], N’ -nitrosonornicotine [NNN], 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK], N’ -nitrosoanabasine [NAB] and N’ -nitrosoanatabine [NAT], in mainstream smoke was modified. The methodology included trapping mainstream smoke in a buffer solution and on a Cambridge filter, extracting TSNA from the buffer solution and the filter with dichloromethane, clean-up procedures and analysis by GC/TEA. Extracts from both the buffer solution and the filter were cleaned up and analysed individually. The clean-up procedure included column chromatography on basic alumina and the removal of nicotine. N-Nitrosodibenzylamine [NDBenzA] which had suitable chromatographic properties was used as internal standard. N’ -Nitrosopentylpicolylamine [NPePicA], a newly synthesized nitrosamine with physicochemical properties similar to the TSNA, could also be used as an internal standard. The recoveries for the buffer solution were as follows: NDBenzA 89 %, NPePicA 83 %, NNN 85 %, NNK 88 %, NAB/NAT 85 %. For the TSNA trapped on the filter the following recoveries were determined: NDBenzA 81 %, NPePicA 75 %, NNN 77 %, NNK 78 %, NAB/NAT 75 %. Parameters influencing the TSNA values in the mainstream smoke were investigated. Artifact formation of TSNA during mainstream smoke collection did not occur under standard conditions. TSNA values were greatly influenced by the puff volume, they increased with increasing puff volume. Reproducible and reliable results can be achieved in a relatively short time with the method reported.
Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels (2008)

The dielectrophoresis (DEP) phenomenon is used to separate platelets directly from diluted whole blood in microfluidic channels. By exploiting the fact that platelets are the smallest cell type in blood, we utilize the DEP-activated cell sorter (DACS) device to perform size-based fractionation of blood samples and continuously enrich the platelets in a label-free manner. Cytometry analysis revealed that a single pass through the two-stage DACS device yields a high purity of platelets (approximately 95%) at a throughput of approximately 2.2 x 10(4) cells/second/microchannel with minimal platelet activation. This work demonstrates gentle and label-free dielectrophoretic separation of delicate cells from complex samples and such a separation approach may open a path toward continuous screening of blood products by integrated microfluidic devices.
The Helix−Coil Transition of DNA Duplexes and Hairpins Observed by Multiple Fluorescence Parameters (1998)

The thermal denaturation of 8-20-bp DNA duplexes labeled with fluorescein and tetramethylrhodamine at opposing 5'-ends was investigated by monitoring the fluorescence intensity of the dyes, the fluorescence anisotropy of tetramethylrhodamine, the fluorescence resonance energy transfer between fluorescein and rhodamine, and, for the 20-bp duplex, the UV absorption. Melting experiments with the single strands of the duplexes revealed that the single strands can form hairpins stabilized by only a few base pairs. The thermal denaturation curves of the duplexes were fitted well to an extended all-or-none model assuming that only the fully base-paired duplex, the maximally base-paired hairpin, and the random coil conformations are present simultaneously. The extent-of-melting versus temperature curves derived from the different spectroscopic parameters are nearly identical, provided that the analysis of the baselines is carried out correctly; the DeltaH and DeltaS of the dissociation compare well with predictions based on nearest neighbor interaction values available in the literature. Our results imply that for all the oligonucleotides other than the 34-bp oligomer, no partially melted intermediates other than hairpins are present in the reaction mixture in amounts that can be detected by our methods. The melting of the hairpins was also studied directly using single-stranded oligonucleotides. The melting of a 34-bp duplex can be accounted for by a statistical zipper model.
Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk (2020)

Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity for stable gene expression and the lack of preexisting immunity in most human subjects. However, the use of integrating vectors may raise some concerns about the potential risk of insertional mutagenesis. Here we investigated liver gene transfer by integrase-defective lentiviral vectors (IDLVs) containing an inactivating mutation in the integrase (D64V). Hepatocyte-targeted expression using IDLVs resulted in the sustained and robust induction of immune tolerance to both intracellular and secreted proteins, despite the reduced transgene expression levels in comparison with their integrase-competent vector counterparts. IDLV-mediated and hepatocyte-targeted coagulation factor IX (FIX) expression prevented the induction of neutralizing antibodies to FIX even after antigen rechallenge in hemophilia B mice and accounted for relatively prolonged therapeutic FIX expression levels. Upon the delivery of intracellular model antigens, hepatocyte-targeted IDLVs induced transgene-specific regulatory T cells that contributed to the observed immune tolerance. Deep sequencing of IDLV-transduced livers showed only rare genomic integrations that had no preference for gene coding regions and occurred mostly by a mechanism inconsistent with residual integrase activity. Conclusion: IDLVs provide an attractive platform for the tolerogenic expression of intracellular or secreted proteins in the liver with a substantially reduced risk of insertional mutagenesis. (hepatology 2011;)
Microsoft CEP server and online behavioral targeting (2009)

In this demo, we present the Microsoft Complex Event Processing (CEP) Server, Microsoft CEP for short. Microsoft CEP is an event stream processing system featured by its declarative query language and its multiple consistency levels of stream query processing. Query composability, query fusing, and operator sharing are key features in the Microsoft CEP query processor. Moreover, the debugging and supportability tools of Microsoft CEP provide visibility of system internals to users. Web click analysis has been crucial to behavior-based online marketing. Streams of web click events provide a typical workload for a CEP server. Meanwhile, a CEP server with its processing capabilities plays a key role in web click analysis. This demo highlights the features of Microsoft CEP under a workload of web click events.
Genome-wide loss-of-function analysis of deubiquitylating enzymes for zebrafish development (2009)

Abstract Background Deconjugation of ubiquitin and/or ubiquitin-like modified protein substrates is essential to modulate protein-protein interactions and, thus, signaling processes in cells. Although deubiquitylating (deubiquitinating) enzymes (DUBs) play a key role in this process, however, their function and regulation remain insufficiently understood. The "loss-of-function" phenotype studies can provide important information to elucidate the gene function, and zebrafish is an excellent model for this goal. Results From an in silico genome-wide search, we found more than 90 putative DUBs encoded in the zebrafish genome belonging to six different subclasses. Out of them, 85 from five classical subclasses have been tested with morpholino (MO) knockdown experiments and 57 of them were found to be important in early development of zebrafish. These DUB morphants resulted in a complex and pleiotropic phenotype that, regardless of gene target, always affected the notochord. Based on the huC neuronal marker expression, we grouped them into five sets (groups I to V). Group I DUBs ( otud7b, uchl3 and bap1 ) appear to be involved in the Notch signaling pathway based on the neuronal hyperplasia, while group IV DUBs ( otud4, usp5, usp15 and usp25 ) play a critical role in dorsoventral patterning through the BMP pathway. Conclusion We have identified an exhaustive list of genes in the zebrafish genome belonging to the five established classes of DUBs. Additionally, we performed the corresponding MO knockdown experiments in zebrafish as well as functional studies for a subset of the predicted DUB genes. The screen results in this work will stimulate functional follow-up studies of potential DUB genes using the zebrafish model system.
The Subunit Structure of Potato Tuber ADPglucose Pyrophosphorylase (1990)

ADPglucose pyrophosphorylase has been extensively purified from potato (Solanum tuberosum L.) tuber tissue to study its structure. By employing a modified published procedure (JR Sowokinos, J Preiss [1982] Plant Physiol 69: 1459-1466) together with Mono Q chromatography, a near homogeneous enzyme preparation was obtained with substantial improvement in enzyme yield and specific activity. In single dimensional sodium dodecyl sulfate polyacrylamide gels, the enzyme migrated as a single polypeptide band with a mobility of about 50,000 daltons. Analysis by two-dimensional polyacrylamide gel electrophoresis, however, revealed the presence of two types of subunits which could be distinguished by their slight differences in net charge and molecular weight. The smaller potato tuber subunit was recognized by antiserum prepared against the smaller spinach leaf 51 kilodalton ADPglucose pyrophosphorylase subunit. In contrast, the anti-54 kilodalton raised against the spinach leaf subunit did not significantly react to the tuber enzyme subunits. The results are consistent with the hypothesis that the potato tuber ADPglucose pyrophosphorylase is not composed of a simple homotetramer as previously suggested, but is a product of two separate and distinct subunits as observed for the spinach leaf and maize enzymes.
Influence of electromagnetic fields on the efflux of calcium ions from brain tissue in vitro: A three‐model analysis consistent with the frequency response up to 510 Hz (1988)

The frequency dependence of electromagnetic field-induced calcium-ion efflux from chicken brain tissues has been examined at 15-Hz intervals over the range 1-510 Hz. The electric field component was 15 Vrms/m and the magnetic component varied between 59 and 69 nTrms. No patterns of response as a function of frequency could be readily discerned when the differences in mean efflux values between exposed and sham samples were compared. However, the calculated P-value, a function that combines at each frequency the difference between the means of the exposed and sham groups with the variance of each group, does provide a basis for hypothesizing the existence of three frequency-dependent patterns in the data. One pattern includes all the highly significant (P less than .01) responses which occur between 15 and 315 Hz, at 30-Hz intervals; two independent trials at 165 Hz, giving nonsignificant responses (P greater than .5), break this pattern into two groups of five frequencies each, which is contrary to the expected result for a simple Lorentz-force interaction. However, another pattern of significant results at 60, 90, and 180 Hz, but not at 300 Hz, is consistent with a Lorentz-force model. A third pattern, composed of only one significant response at 405 Hz, is very close to the resonance predicted on a linear extrapolation from high-frequency data for 13carbon atoms. This hypothetical ordering of the frequency-response profile provides the basis for future experimental designs to test each possible interaction model and for their connection to the calcium-ion efflux endpoint.
<title>Scenic classification methods for image and video databases</title> (1995)

The problem of scenic image classification is presented in the paper. On considering the specific nature of this problem, we propose a statistically data-based method, the Hidden Markov Model, to solve this problem. We segment an image and use the sequence of segments as the definition of the image; we then train a HMM on a test set of sequences/images to establish a classification. We present preliminary results on the use of a 1D HMM for classification of images as either indoor or outdoor.
Synthesis of 1-Aryl-1H-indazoles via Palladium-Catalyzed Intramolecular Amination of Aryl Halides (2004)

Palladium-catalyzed cyclization of arylhydrazones of 2-bromoaldehydes and 2-bromoacetophenones to give 1-aryl-1H-indazoles has been studied in detail. The cyclization of arylhydrazone of 2-bromobenzaldehydes can be performed with good to high yields using Pd(dba)2 and chelating phosphines, of which the most effective are rac-BINAP, DPEphos, and dppf, in the presence of Cs2CO3 or K3PO4 as a base. Electron-rich, bulky ligands commonly employed for intermolecular amination such as PtBu3 and o-PhC6H4PtBu2 were shown to be ineffective for cyclization and to lead instead to extensive oligomerization and tarring. The method developed is applicable for preparation of a wide scope of indazoles bearing electron-donating or electron-withdrawing substituents, among them, unprotected carboxyl, as well as various indazole heteroanalogues. The cyclization of arylhydrazones of less reactive halides such as 2-chlorobenzaldehyde, as well as 2-bromoacetophenone and bromotetralone, has been achieved. The purity of the starting hydrazone has been shown to be a critical parameter, as various impurities inhibit the cyclization.
Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2Deficiency in Mice: A Model of Human Neurodegenerative Disease (2008)

Calcium-independent group VIA phospholipase A2 (iPLA2beta) is considered to play a role in signal transduction and maintenance of homeostasis or remodeling of membrane phospholipids. A role of iPLA2beta has been suggested in various physiological and pathological processes, including immunity, chemotaxis, and cell death, but the details remain unclear. Accordingly, we investigated mice with targeted disruption of the iPLA2beta gene. iPLA2beta-/- mice developed normally and grew to maturity, but all showed evidence of severe motor dysfunction, including a hindlimb clasping reflex during tail suspension, abnormal gait, and poor performance in the hanging wire grip test. Neuropathological examination of the nervous system revealed widespread degeneration of axons and/or synapses, accompanied by the presence of numerous spheroids (swollen axons) and vacuoles. These findings provide evidence that impairment of iPLA2beta causes neuroaxonal degeneration, and indicate that the iPLA2beta-/- mouse is an appropriate animal model of human neurodegenerative diseases associated with mutations of the iPLA2beta gene, such as infantile neuroaxonal dystrophy and neurodegeneration with brain iron accumulation.
Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement (2003)

We evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran, two new direct thrombin inhibitors, was an optimal regimen for thromboprophylaxis in major orthopaedic surgery. In a double-blind study, 2788 patients undergoing total hip or knee replacement were randomly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4-12 h postoperatively, followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. The primary efficacy endpoint was venous thromboembolism (deep-vein thrombosis detected by mandatory venography, pulmonary embolism or unexplained death). The main safety endpoint was bleeding. Venous thromboembolism occurred in 355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatran and enoxaparin group, respectively, a difference in risk of 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparable between the two groups.