gebhart/patrepeval huggingface dataset:
Acid-Dependent Electrophilicity of Cyclopropylpyrroloindoles. Nature's Masking Strategy for a Potent DNA Alkylator (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcid-Dependent Electrophilicity of Cyclopropylpyrroloindoles. Nature's Masking Strategy for a Potent DNA AlkylatorM. A. Warpehoski and D. E. HarperCite this: J. Am. Chem. Soc. 1994, 116, 17, 7573–7580Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ja00096a014https://doi.org/10.1021/ja00096a014research-articleACS PublicationsRequest reuse permissionsArticle Views99Altmetric-Citations45LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Continuous Versus Intermittent Portal Triad Clamping for Liver Resection (1999)

This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC, especially in patients with abnormal liver parenchyma.
Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. (1994)

In response to inflammatory stimuli, expression of a group of proteins that bind circulating leukocytes (endothelial-leukocyte adhesion molecules) are induced on the luminal surface of vascular endothelium. A series of phosphorothioate oligonucleotides 18 to 21 bases in length were designed and synthesized to hybridize selectively to the mRNA, which encodes three such endothelial-leukocyte adhesion molecules; human intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Antisense oligonucleotides were identified that selectively inhibited ICAM-1, VCAM-1, and E-selectin expression in HUVEC. Oligonucleotides that hybridized to the 3'-untranslated region of either ICAM-1, VCAM-1, or E-selectin mRNAs promoted a selective reduction in the respective mRNA levels. In contrast, oligonucleotides that hybridized to 5'-untranslated sequences did not significantly reduce target mRNA levels, although they did promote a reduction in protein expression. With the use of flow cytometry to measure cell surface expression, ICAM-1 and E-selectin were selectively inhibited by their respective antisense oligonucleotide. At low concentrations of oligonucleotides, only VCAM-1 antisense oligonucleotides inhibited VCAM-1 expression. However, at an oligonucleotide concentration of 50 nM or greater, phosphorothioate oligonucleotides not predicted to hybridize to VCAM-1 mRNA also reduced VCAM-1 expression. The sequence-independent inhibition of VCAM-1 expression by phosphorothioate oligonucleotides could be the result of a perturbation in the transcriptional regulation of the VCAM-1 gene. ICAM-1, VCAM-1, and E-selectin antisense oligonucleotides reduced adhesion of HL-60 cells to TNF-activated HUVEC. These data demonstrate that phosphorothioate oligonucleotides are capable of selectively inhibiting the expression of ICAM-1, VCAM-1, and E-selectin in HUVEC.
Cell Lysis Induced by Ricin D and Ricin E in Various Cell Lines (1997)

Ricin D, one of the two isolectins from small caster beans showed stronger cytotoxicity than another one, ricin E, based on the inhibition of colony formation and the inhibition of protein synthesis. Both ricin D and ricin E induced cell lysis to different extents in each cell line tested, albeit ricin E was slightly less effective than ricin D. DNA fragmentation, a characteristic feature of apoptosis, was also induced by ricin D and ricin E in Vero cells. Scatchard plot analysis showed that ricin D binds to cells with higher affinity than ricin E, while the number of binding sites per cell was not much different, suggesting that the differences in the cytotoxicity between ricin D and ricin E is mainly due to their differential binding affinity to cells. In Vero cells, the cytolytic activities of ricin D and ricin E were inhibited by brefeldin A (BFA), which is known to effect the Golgi apparatus, but not significant effect of BFA was observed in a BFA-resistant cell line, MDCK cells. These results suggest that the Golgi apparatus may be involved in ricin-induced cell lysis.
Modulation of in vitro splicing of the upstream intron by modifying an intra-exon sequence which is deleted from the dystrophin gene in dystrophin Kobe. (1995)

Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing 52-bp deletion was skipped during splicing, although the known consensus sequences at the 5' and 3' splice sites of exon 19 were maintained (Matsuo, M., T. Masumura, H. Nishio, T. Nakajima, Y. Kitoh, T. Takumi, J. Koga, and H. Nakamura. 1991. J. Clin. Invest. 87:2127-2131). These data suggest that the deleted sequence of exon 19 may function as a cis-acting element for exact splicing for the upstream and downstream introns. To investigate this potential role of exon 19, an in vitro splicing system using artificial dystrophin mRNA precursors (pre-mRNAs) was established. Pre-mRNA containing exon 18, truncated intron 18, and exon 19 was spliced precisely in vitro, whereas splicing of intron 18 was almost completely abolished when the wild-type exon 19 was replaced by the dystrophin Kobe exon 19. Splicing of intron 18 was not fully reactivated when dystrophin Kobe exon 19 was restored to nearly normal length by inserting other sequences into the deleted site. These results suggest that the presence of the exon 19 sequence which is lost in dystrophin Kobe is more critical for splicing of intron 18 than the length of the exon 19 sequence. Characteristically, the efficiency of splicing of this intron seemed to correlate with the presence of polypurine tracks within the downstream exon 19. Moreover, an antisense 31-mer 2'-O-methyl ribonucleotide complementary to the 5' half of the deleted sequence in dystrophin Kobe exon 19 inhibited splicing of wild-type pre-mRNA in a dose- and time-dependent manner. This first in vitro evidence that dystrophin pre-mRNA splicing can be modulated by an antisense oligonucleotide raises the possibility of a new therapeutic approach for Duchenne muscular dystrophy.
Generating Text with Recurrent Neural Networks (2011)

Recurrent Neural Networks (RNNs) are very powerful sequence models that do not enjoy widespread use because it is extremely difficult to train them properly. Fortunately, recent advances in Hessian-free optimization have been able to overcome the difficulties associated with training RNNs, making it possible to apply them successfully to challenging sequence problems. In this paper we demonstrate the power of RNNs trained with the new Hessian-Free optimizer (HF) by applying them to character-level language modeling tasks. The standard RNN architecture, while effective, is not ideally suited for such tasks, so we introduce a new RNN variant that uses multiplicative (or “gated”) connections which allow the current input character to determine the transition matrix from one hidden state vector to the next. After training the multiplicative RNN with the HF optimizer for five days on 8 high-end Graphics Processing Units, we were able to surpass the performance of the best previous single method for characterlevel language modeling – a hierarchical nonparametric sequence model. To our knowledge this represents the largest recurrent neural network application to date. 1.
Single nucleotide polymorphism detection by combinatorial fluorescence energy transfer tags and biotinylated dideoxynucleotides (2002)

Combinatorial fluorescence energy transfer (CFET) tags, constructed by exploiting energy transfer and combinatorial synthesis, allow multiple biological targets to be analyzed simultaneously. We here describe a multiplex single nucleotide polymorphism (SNP) assay based on single base extension (SBE) using CFET tags and biotinylated dideoxynucleotides (biotin-ddNTPs). A library of CFET-labeled oligonucleotide primers was mixed with biotin-ddNTPs, DNA polymerase and the DNA templates containing the SNPs in a single tube. The nucleotide at the 3'-end of each CFET-labeled oligonucleotide primer was complementary to a particular SNP in the template. Only the CFET-labeled primer that is fully complementary to the DNA template was extended by DNA polymerase with a biotin-ddNTP. We isolated the DNA extension fragments that carry a biotin at the 3'-end by capture with streptavidin-coated magnetic beads, while the unextended primers were eliminated. The biotinylated fluorescent DNA fragments were subsequently analyzed in a multicolor fluorescence electrophoresis system. The distinct fluorescence signature and electrophoretic mobility of each DNA extension product in the electropherogram coded the SNPs without the use of a sizing standard. We simultaneously distinguished six nucleotide variations in synthetic DNA templates and a PCR product from the retinoblastoma tumor suppressor gene. The use of CFET-labeled primers and biotin-ddNTPs coupled with the specificity of DNA polymerase in SBE offered a multiplex method for detecting SNPs.
High power, high efficiency diode pumped Raman fiber laser (2016)

We demonstrate a high power high efficiency Raman fiber laser pumped directly by a laser diode module at 976 nm. 80 Watts of CW power were obtained at a wavelength of 1020 nm with an optical-to-optical efficiency of 53%. When working quasi-CW, at a duty cycle of 30%, 85 W of peak power was produced with an efficiency of 60%. A commercial graded-index (GRIN) core fiber acts as the Raman fiber in a power oscillator configuration, which includes spectral selection to prevent generation of the 2nd Stokes. In addition, significant brightness enhancement of the pump beam is attained due to the Raman gain distribution profile in the GRIN fiber. To the best of our knowledge, this is the highest power Raman fiber laser directly pumped by laser diodes, which also exhibits a record efficiency for such a laser. In addition, it is the highest power Raman fiber laser (regardless of pumping source) demonstrated based on a GRIN fiber.
The treatment of osteoarthritis of the knee with pulsed electrical stimulation. (1995)

The improvements in clinical measures for pain and function found in this study suggest that pulsed electrical stimulation is effective for treating OA of the knee. Studies for longterm effects are warranted.
The mechanism of proton pumping by cytochrome c oxidase (1998)

Cytochrome c oxidase catalyzes the reduction of oxygen to water that is accompanied by pumping of four protons across the mitochondrial or bacterial membrane. Triggered by the results of recent x-ray crystallographic analyses, published data concerning the coupling of individual electron transfer steps to proton pumping are reanalyzed: Conversion of the conventional oxoferryl intermediate F to the fully oxidized form O is connected to pumping of only one proton. Most likely one proton is already pumped during the double reduction of O, and only three protons during conversion of the "peroxy" forms P to O via the oxoferryl form F. Based on the available structural, spectroscopic, and mutagenesis data, a detailed mechanistic model, carefully considering electrostatic interactions, is presented. In this model, each of the four reductions of heme a during the catalytic cycle is coupled to the uptake of one proton via the D-pathway. These protons, but never more than two, are temporarily stored in the regions of the heme a and a3 propionates and are driven to the outside ("pumped") by electrostatic repulsion from protons entering the active site during turnover. The first proton is pumped by uptake of one proton via the K-pathway during reduction, the second and third proton during the P --> F transition when the D-pathway and the active site become directly connected, and the fourth one upon conversion of F to O. Atomic structures are assigned to each intermediate including F' with an alternative route to O.
Differential effects of over-expressed neural cell adhesion molecule isoforms on myoblast fusion. (1993)

We have used a transfection based approach to analyze the role of neural cell adhesion molecule (NCAM) in myogenesis at the stage of myoblast fusion to form multinucleate myotubes. Stable cell lines of myogenic C2 cells were isolated that express the transmembrane 140- or 180-kD NCAM isoforms or the glycosylphosphatidylinositol (GPI) linked isoforms of 120 or 125 kD. We found that expression of the 140-kD transmembrane isoform led to a potent enhancement of myoblast fusion. The 125-kD GPI-linked NCAM also enhanced the rate of fusion but less so when a direct comparison of cell surface levels of the 140-kD transmembrane form was carried out. While the 180-kD transmembrane NCAM isoform was effective in promoting C2 cell fusion similar to the 140-kD isoform, the 120-kD isoform did not have an effect on fusion parameters. It is possible that these alterations in cell fusion are associated with cis NCAM interactions in the plane of the membrane. While all of the transfected human NCAMs (the transmembrane 140- and 180-kD isoforms and the 125- and 120-kD GPI isoforms) could be clustered in the plane of the plasma membrane by species-specific antibodies there was a concomitant clustering of the endogenous mouse NCAM protein in all cases except with the 120-kD human isoform. These studies show that different isoforms of NCAM can undergo specific interactions in the plasma membrane which are likely to be important in fusion. While the transmembrane and the 125-kD GPI-anchored NCAMs are capable of enhancing fusion the 120-kD GPI NCAM is not. Thus it is likely that interactions associated with NCAM intracellular domains and also the muscle specific domain (MSD) region in the extracellular domain of the GPI-linked 125-kD NCAM are important. In particular this is the first role ascribed to the O-linked carbohydrate containing MSD region which is specifically expressed in skeletal muscle.
The Three Es of Cancer Immunoediting (2004)

After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models--together with compelling data from human patients--indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting--elimination, equilibrium, and escape.
Recombinant human B cell stimulatory factor 2 (BSF‐2/IFN‐β2) regulates β‐fibrinogen and albumin mRNA levels in Fao‐9 cells (1987)

Conditioned medium from human monocytes contains a partially characterized hepatocyte-stimulating factor that simultaneously elevates the mRNA levels of the acute-phase protein beta-fibrinogen and decreases albumin mRNA in rat hepatoma cells. We demonstrate that recombinant human B-cell stimulatory factor 2, which is identical to interferon-beta 2/26 kDa protein and interleukin-HP1, exhibits the same activity as hepatocyte-stimulating factor. Furthermore, a specific antibody against B-cell stimulatory factor 2 was able to inhibit hepatocyte-stimulating factor in conditioned medium from human monocytes. Our data show that hepatocyte-stimulating factor and B-cell stimulatory factor 2 are functionally and immunologically related proteins.
Animation space (2006)

Skeletal subspace deformation (SSD), a simple method of character animation used in many applications, has several shortcomings; the best-known being that joints tend to collapse when bent. We present animation space , a generalization of SSD that greatly reduces these effects and effectively eliminates them for joints that do not have an unusually large range of motion.While other, more expensive generalizations exist, ours is unique in expressing the animation process as a simple linear transformation of the input coordinates. We show that linearity can be used to derive a measure of average distance (across the space of poses), and apply this to improving parametrizations.Linearity also makes it possible to fit a model to a set of examples using least-squares methods. The extra generality in animation space allows for a good fit to realistic data, and overfitting can be controlled to allow fitted models to generalize to new poses. Despite the extra vertex attributes, it is possible to render these animation-space models in hardware with no loss of performance relative to SSD.
The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus (1998)

In Staphylococcus aureus, in addition to mutations in the grl and gyr gene loci, multidrug efflux pumps like NorA contribute to decreased fluoroquinolone susceptibility. Efflux pumps can be inhibited by the plant alkaloid reserpine, which, at 20 mg/L, reduced sparfloxacin, moxifloxacin and ciprofloxacin IC50s and MICs by up to four-fold in 11, 21 and 48 of the 102 unrelated clinical isolates tested, respectively. The effect was less pronounced with the hydrophobic drugs sparfloxacin and moxifloxacin than with the hydrophilic drug ciprofloxacin and was stable in all 25 clonally related isolates tested.
Droplet microfluidic technology for single-cell high-throughput screening (2009)

We present a droplet-based microfluidic technology that enables high-throughput screening of single mammalian cells. This integrated platform allows for the encapsulation of single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil and enables the digital manipulation of these reactors at a very high-throughput. Here, we validate a full droplet screening workflow by conducting a droplet-based cytotoxicity screen. To perform this screen, we first developed a droplet viability assay that permits the quantitative scoring of cell viability and growth within intact droplets. Next, we demonstrated the high viability of encapsulated human monocytic U937 cells over a period of 4 days. Finally, we developed an optically-coded droplet library enabling the identification of the droplets composition during the assay read-out. Using the integrated droplet technology, we screened a drug library for its cytotoxic effect against U937 cells. Taken together our droplet microfluidic platform is modular, robust, uses no moving parts, and has a wide range of potential applications including high-throughput single-cell analyses, combinatorial screening, and facilitating small sample analyses.
The Jasmonate Signal Pathway (2002)

Plant responses to many biotic and abiotic stresses are orchestrated locally and systemically by signaling molecules known as the jasmonates (JAs). JAs also regulate such diverse processes as pollen maturation and wound responses in Arabidopsis. Here we review recent advances in our understanding of
Polymorphisms in glutathione S-transferases (GSTM1 and GSTT1) and survival after treatment for breast cancer. (2001)

The response to treatment for breast cancer is likely predicted by a number of disease and tumor tissue characteristics, many of which are under active investigation. One area that has received little attention is that of endogenous capabilities to respond to reactive oxygen species and subsequent byproducts resulting from radiation therapy and a number of chemotherapeutic agents, preventing cytotoxicity toward tumor cells. The glutathione S-transferases are key conjugating enzymes in this response, and GSTM1 and GSTT1 have deletion polymorphisms that result in no enzyme activity. In this retrospective study, we evaluated the role of GSTM1- and GSTT1-null genotypes on disease-free and overall survival among 251 women who received treatment for incident, primary breast cancer. Women were identified through Tumor Registry records and normal archived tissue retrieved for genotyping. Adjusting for age, race, and stage at diagnosis, women with null genotypes for GSTM1 and GSTT1 had reduced hazard of death [adjusted hazard ratio (HR), 0.59; 95% confidence interval (CI), 0.36-0.97; and HR, 0.51; CI, 0.29-0.90, respectively] in relation to those with alleles present. Furthermore, women who were null for both GSTM1 and GSTT1 had one-third the hazard of death of those with alleles for both genes present (adjusted HR, 0.28; 95% CI, 0.11-0.70). Similar relationships were noted for risk of recurrence. These data indicate that interindividual differences in activity of enzymes that prevent therapy-generated reactive oxidant damage may have an important impact on disease recurrence and overall survival.
Analysis of a charge-pump PLL: a new model (1994)

A new model for the analysis of a second-order charge-pump phase-locked loop (PLL) is described. This model uses a set of difference equations in two well-chosen state variables. It allows one to model exactly the transient behavior of the PLL, even if the loop is out of lock. Theoretical stability and overload limits are determined. A continuous-time approximation is derived. Its validity is verified by simulation examples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>