gebhart/patrepeval huggingface dataset:
Natural and Phosphorothioate-Modified Oligodeoxyribonucleotides Exhibit a Non-Random Cellular Distribution (1990)

Abstract Addition of specific antisense oligomers to LTK- cells infected with HSV-1 has been shown to decrease viral production (1,8). We have investigated the cellular components that contain these oligomers and a phosphorothioate derivative by Normarski light microscopy and gel analysis of sucrose gradient cell fractions. Fractionation analysis suggests that these oligomers are distributed throughout the cell in a non-random manner and gel analysis suggest that intact oligomers are not equally distributed in the cytosol, nuclear or membrane component. Information about the cellular location of antisense oligomers should aid in the understanding of their antiviral effect and in the design of more effective oligonucleotide derivatives as potential antiviral agents.
Measurement of the conductivity exponent in two-dimensional percolating networks: square lattice versus random-void continuum (1985)

Using an analog simulation technique, we have studied the conductivity transition in two-dimensional percolating networks. A computer-controlled x-y plotter scribes a percolating pattern on a sheet of aluminized plastic while the resistance of the sheet is continuously monitored. With this technique, we have measured the conductivity exponent t for two systems: site percolation on a square lattice and random-void continuum percolation. We find t=1.29\ifmmode\pm\else\textpm\fi{}0.03 for the lattice and t=1.34\ifmmode\pm\else\textpm\fi{}0.07 for the continuum, in agreement with a recent theoretical prediction that the conductivity exponents for these two systems are the same. We have also verified a theoretical estimate of the magnitude of conductance fluctuations due to finite-size effects.
Defibrillators and Sudden Death (2003)

Letters16 December 2003Defibrillators and Sudden DeathLawrence J. Cohn, MDLawrence J. Cohn, MDFrom New York, NY 10021.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-12-200312160-w1 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:An often-overlooked detail in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) was that many and perhaps most of the patients had to have frequent or repetitive ventricular ectopic beats (1). In their systematic review, Ezekowitz and colleagues (2) did not discuss this. Until the MADIT II authors reveal the arrhythmia profiles of the patients in this trial, it cannot be used to determine who will benefit from an implantable cardioverter defibrillator.Reference1. Moss AJ, Zareba W, Hall WJ, Klein H, Wilber DJ, Cannom DS, . Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med. 2002;346:877-83. [PMID: 11907286] CrossrefMedlineGoogle Scholar2. Ezekowitz JA, Armstrong PW, McAlister FA. Implantable cardioverter defibrillators in primary and secondary prevention: a systematic review of randomized, controlled trials. Ann Intern Med. 2003;138:445-52. [PMID: 12639076] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From New York, NY 10021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoImplantable Cardioverter Defibrillators in Primary and Secondary Prevention Justin A. Ezekowitz , Paul W. Armstrong , and Finlay A. McAlister Metrics 16 December 2003Volume 139, Issue 12Page: W-84KeywordsArrhythmiaImplantable cardioverter defibrillatorsSystematic reviews ePublished: 16 December 2003 Issue Published: 16 December 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Asymmetrische Synthese cyclischer α-Aminosäuren nach der Bislactimether-Methode (1987)

Methylprolin 1a sowie seine Ringhomologen 1b und 2 wurden ohne direkten Zugriff auf den „chiral pool”︁ synthetisiert. Die mehrstufige Synthese ging vom Bislactimether 3 und den Dibromiden 4a,b bzw. 5 aus (a, n = 1; b, n = 2).
Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration (2004)

Although Apc is well characterized as a tumor-suppressor gene in the intestine, the precise mechanism of this suppression remains to be defined. Using a novel inducible Ahcre transgenic line in conjunction with a loxP-flanked Apc allele we, show that loss of Apc acutely activates Wnt signaling through the nuclear accumulation of beta-catenin. Coincidentally, it perturbs differentiation, migration, proliferation, and apoptosis, such that Apc-deficient cells maintain a "crypt progenitor-like" phenotype. Critically, for the first time we confirm a series of Wnt target molecules in an in vivo setting and also identify a series of new candidate targets within the same setting.
Dynamic stability of grid-connected photovoltaic systems (2004)

A mathematical model of grid-connected photovoltaic energy sources suitable for stability studies is presented. The power electronic conditioning unit is modelled from basic power transfer relations. Using this model, it is demonstrated that there exist two solutions for a given power output, one of which is unstable. By doing eigenvalue and eigenvector analysis, dynamic orbits are presented that help visualize any potential problem that may occur under disturbances. Simulations are carried out showing instances where the voltage at the photovoltaic panel collapses, in particular when operating close to the maximum power point.
Interpretation and trust (2012)

Statistical topic models can help analysts discover patterns in large text corpora by identifying recurring sets of words and enabling exploration by topical concepts. However, understanding and validating the output of these models can itself be a challenging analysis task. In this paper, we offer two design considerations - interpretation and trust - for designing visualizations based on data-driven models. Interpretation refers to the facility with which an analyst makes inferences about the data through the lens of a model abstraction. Trust refers to the actual and perceived accuracy of an analyst's inferences. These considerations derive from our experiences developing the Stanford Dissertation Browser, a tool for exploring over 9,000 Ph.D. theses by topical similarity, and a subsequent review of existing literature. We contribute a novel similarity measure for text collections based on a notion of "word-borrowing" that arose from an iterative design process. Based on our experiences and a literature review, we distill a set of design recommendations and describe how they promote interpretable and trustworthy visual analysis tools.
Essential roles for four cytoplasmic intermediate filament proteins in Caenorhabditis elegans development (2001)

The structural proteins of the cytoplasmic intermediate filaments (IFs) arise in the nematode Caenorhabditis elegans from eight reported genes and an additional three genes now identified in the complete genome. With the use of double-stranded RNA interference (RNAi) for all 11 C. elegans genes encoding cytoplasmic IF proteins, we observe phenotypes for the five genes A1, A2, A3, B1, and C2. These range from embryonic lethality (B1) and embryonic/larval lethality (A3) to larval lethality (A1 and A2) and a mild dumpy phenotype of adults (C2). Phenotypes A2 and A3 involve displaced body muscles and paralysis. They probably arise by reduction of hypodermal IFs that participate in the transmission of force from the muscle cells to the cuticle. The B1 phenotype has multiple morphogenetic defects, and the A1 phenotype is arrested at the L1 stage. Thus, at least four IF genes are essential for C. elegans development. Their RNAi phenotypes are lethal defects due to silencing of single IF genes. In contrast to C. elegans, no IF genes have been identified in the complete Drosophila genome, posing the question of how Drosophila can compensate for the lack of these proteins, which are essential in mammals and C. elegans. We speculate that the lack of IF proteins in Drosophila can be viewed as cytoskeletal alteration in which, for instance, stable microtubules, often arranged as bundles, substitute for cytoplasmic IFs.
Enhanced in vitro cytotoxicity and cytostasis of the combination of onconase with a proteasome inhibitor. (1998)

In proliferating cells the turnover rate of proteins responsible for regulation of the cell cycle progression, namely cyclins and inhibitors of the cyclin-dependent kinases (CDKs) and phosphatases, is rapid and their cellular level is modulated at the transcriptional, translational and/or degradation (via proteasome pathway) stages. Inhibition of proteasome function results in accumulation of rapidly turning over proteins and, thus, causes an imbalance of the cell cycle regulatory components, and loss of their regulatory function. Indeed, it has been shown that proteasome inhibitors perturb the cell cycle progression. Onconase, a novel RNase which has anti-tumor activity and is in clinical trials, has previously been shown to suppress protein synthesis, presumably by degradation of intracellular RNA, preferentially tRNA. By interfering with regulation of expression of cyclins and/or CDK-inhibitors, onconase also may induce the imbalance of these proteins and potentiate the effect of proteasome inhibitors. In the present study, we observed that the combinations of onconase with peptide-aldehyde inhibitors of calpain and proteasome such as the N-acetyl-leucinyl-leucinyl-norleucinal (LLnL) and the N-acetyl-leucinyl-valinyl-phenylalaninal (LVP), but not N-acetyl-leucinyl-leucinyl-methioninal (LLM), were synergistic in suppressing cell proliferation and inducing apoptosis in three human tumor cell lines: A-549 lung adenocarcinoma, DU-145 prostatic carcinoma, and MDA-MB-231 breast carcinoma. The observed cytotoxicity may also be a result of prevention of the induction of the 'survival' genes by the nuclear factor kappaB (NFkappaB) by onconase and proteasome inhibitors. The data indicate that such combinations should be further tested as potential anti-cancer regimens.
Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity (2006)

Retroviral vectors with long terminal repeats (LTRs), which contain strong enhancer/promoter sequences at both ends of their genome, are widely used for stable gene transfer into hematopoietic cells. However, recent clinical data and mouse models point to insertional activation of cellular proto-oncogenes as a dose-limiting side effect of retroviral gene delivery that potentially induces leukemia. Self-inactivating (SIN) retroviral vectors do not contain the terminal repetition of the enhancer/promoter, theoretically attenuating the interaction with neighboring cellular genes. With a new assay based on in vitro expansion of primary murine hematopoietic cells and selection in limiting dilution, we showed that SIN vectors using a strong internal retroviral enhancer/promoter may also transform cells by insertional mutagenesis. Most transformed clones, including those obtained after dose escalation of SIN vectors, showed insertions upstream of the third exon of Evi1 and in reverse orientation to its transcriptional orientation. Normalizing for the vector copy number, we found the transforming capacity of SIN vectors to be significantly reduced when compared with corresponding LTR vectors. Additional modifications of SIN vectors may further increase safety. Improved cell-culture assays will likely play an important role in the evaluation of insertional mutagenesis.
A Cytosolic Phospholipase A2 from Potato Tissues Appears to Be Patatin (1996)

Phospholipase (PL) A2 is involved in signal transduction in the resistance reaction that is induced in potato by inoculation of an incompatible race of Phytophthora infestans, the late blight fungus, or by treatment with fungal elicitor hyphal wall components (Kawakita et al. 1993). In this study, PLA2 in the soluble fraction from potato tuber was purified. The following results suggested that the enzyme was, in fact, patatin: (1) the molecular mass of the purified enzyme was 40 kDa, the same as that of patatin; (2) the pI of the purified enzyme was approximately 4.75, which corresponds to that of patatin; and (3) the amino-terminal amino acid sequence of the purified enzyme showed a high degree of homology to that of patatin. Patatin is known as a storage protein of the potato tuber and it has been shown to have esterase activity. However, other enzymatic activities and the function(s) of patatin are unknown. We investigated the PLA activities of the purified patatin. The PLA2 activity of the patatin was much higher than the PLA1 activity, even though the protein exhibited both activities. The PLA2 activity of the enzyme was particularly apparent when phosphatidylcholine with linoleic acid at the sn-2 position was used as substrate. Lower activity was observed with phosphatidylcholine with palmitic acid, oleic acid and arachidonic acid at the sn-2 position.
A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene. (1994)

A severe immunodeficiency involving a complete loss of T lymphocytes and natural killer cells was observed in independent lines of transgenic mice containing > 30 copies of the human CD3E gene (pL12). T-cell- natural killer (NK)- mice could also be generated by using a gene fragment pL12 delta 1 (without exons 4A and 5) coding for the CD3-epsilon transmembrane region and its 55-amino acid nonenzymatic cytoplasmic tail. The abnormally small thymus gland in the homozygous transgenic animals, which was approximately 1% the size of a wild-type thymus, contained only a few (2-4%) prethymocytes with a Thy-1+Pgp-1+IL-2R alpha- CD3-4-8- phenotype. In mice with lower copy numbers of the transgene thymocyte development was blocked at the Thy-1+Pgp-1-IL-2R alpha+CD3-4-8- stage, and normal NK activity was detected. Mice generated with high-copy numbers of a transgene pL12 delta 2 (pL12 delta 1 minus exons 6), coding for a truncated protein from which the CD3-epsilon extracellular domain, its transmembrane region, and most of its cytoplasmic region were absent, contained normal numbers of T lymphocytes and NK cells. These transgene effects suggested that recruitment of signal-transduction molecules by the cytoplasmic tail of this protein played an important role in the abrogation of both lineages. Taken together these observations support the notion that T lymphocytes and NK cells stemmed from a common precursor.
Identification of NovelRPGRORF15 Mutations in X-linked Progressive Cone-Rod Dystrophy (XLCORD) Families (2005)

The cloning strategy for ORF15 facilitated comprehensive sequence analysis in patients. Two families were identified with nonsense mutations, and clinical evaluation revealed them both to have a similar phenotype. The presence of a parafoveal ring of increased AF was an early indicator of affected status in these families. No disease-causing mutations in ORF15 were detected in four other families, suggesting that ORF15 mutations may not be the most common cause of XLCORD.
Single-longitudinal mode operation of a semiconductor laser using a metal film reflection filter (1985)

Theoretical and experimental results are presented which show that a narrow-band reflection filter can be used for longitudinal mode selection in semiconductor lasers. Single-mode operation of 13 μm InGaAsP semiconductor lasers both under CW and pulsed operation has been demonstrated. CW mode discrimination of >30 dB has been obtained up to an output power of ∼10 mW. These results suggest a new scheme for single-mode injection laser sources.
Imaging Tumor Angiogenesis With Contrast Ultrasound and Microbubbles Targeted to α v β 3 (2003)

CEU with microbubbles targeted to alpha(v)beta3 can noninvasively detect early tumor angiogenesis. This technique, when coupled with changes in blood volume and velocity, may provide insights into the biology of tumor angiogenesis and be used for diagnostic applications.
Isolation and Functional Analysis of Homogentisate Phytyltransferase from Synechocystis sp. PCC 6803 and Arabidopsis (2001)

Tocopherols, collectively known as vitamin E, are lipid-soluble antioxidants synthesized exclusively by photosynthetic organisms and are required components of mammalian diets. The committed step in tocopherol biosynthesis involves condensation of homogentisic acid and phytyl diphosphate (PDP) catalyzed by a membrane-bound homogentisate phytyltransferase (HPT). HPTs were identified from Synechocystis sp. PCC 6803 and Arabidopsis based on their sequence similarity to chlorophyll synthases, which utilize PDP in a similar prenylation reaction. HPTs from both organisms used homogentisic acid and PDP as their preferred substrates in vitro but only Synechocystis sp. PCC 6803 HPT was active with geranylgeranyl diphosphate as a substrate. Neither enzyme could utilize solanesyl diphosphate, the prenyl substrate for plastoquinone-9 synthesis. In addition, disruption of Synechocystis sp. PCC 6803 HPT function causes an absence of tocopherols without affecting plastoquinone-9 levels, indicating that separate polyprenyltransferases exist for tocopherol and plastoquinone synthesis in Synechocystis sp. PCC 6803. It is surprising that the absence of tocopherols in this mutant had no discernible effect on cell growth and photosynthesis.
Ets-2 and Components of Mammalian SWI/SNF Form a Repressor Complex That Negatively Regulates the BRCA1Promoter (2003)

Ets-2 is a transcriptional activator that can be modulated by ras-dependent phosphorylation. Evidence is presented indicating that ets-2 can also act as a transcriptional repressor. In the breast cancer cell line MCF-7, exogenous ets-2 repressed the activity of a BRCA1 promoter-luciferase reporter dependent on a conserved ets-2-binding site in this promoter. Conditional overproduction of ets-2 in MCF-7 cells resulted in repression of endogenous BRCA1 mRNA expression. To address the mechanism by which ets-2 could act as a repressor, a biochemical approach was used to identify proteins that interacted with the ets-2 pointed domain. From this analysis, components of the mammalian SWI/SNF chromatin remodeling complex were found to interact with ets-2. Brg-1, the ATP-hydrolyzing component of the SWI/SNF complex, along with the BAF57/p50 and Ini1 subunits could be co-immunoprecipitated from cells with ets-2. The pointed domain of ets-2 directly interacted in vitro with the C-terminal region of Brg-1 in a phosphorylation-dependent manner. The combination of Brg-1 and ets-2 could repress the BRCA1 promoter reporter in transfection assays. These results support a role for ets-2 as a repressor and indicate that components of the mammalian SNF/SWI complex are required as co-repressors.
Magnesium Ion-dependent Activation of the RecA Protein Involves the C Terminus (2003)

Optimal conditions for RecA protein-mediated DNA strand exchange include 6-8 mm Mg(2+) in excess of that required to form complexes with ATP. We provide evidence that the free magnesium ion is required to mediate a conformational change in the RecA protein C terminus that activates RecA-mediated DNA strand exchange. In particular, a "closed" (low Mg(2+)) conformation of a RecA nucleoprotein filament restricts DNA pairing by incoming duplex DNA, although single-stranded overhangs at the ends of a duplex allow limited DNA pairing to occur. The addition of excess Mg(2+) results in an "open" conformation, which can promote efficient DNA pairing and strand exchange regardless of DNA end structure. The removal of 17 amino acid residues at the Escherichia coli RecA C terminus eliminates a measurable requirement for excess Mg(2+) and permits efficient DNA pairing and exchange similar to that seen with the wild-type protein at high Mg(2+) levels. Thus, the RecA C terminus imposes the need for the high magnesium ion concentrations requisite in RecA reactions in vitro. We propose that the C terminus acts as a regulatory switch, modulating the access of double-stranded DNA to the presynaptic filament and thereby inhibiting homologous DNA pairing and strand exchange at low magnesium ion concentrations.
Chemical Modification of Recombinant Human Granulocyte Colony-Stimulating Factor by Polyethylene Glycol Increases its Biological Activity in vivo. (1992)

Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in Escherichia coli was chemically modified by polyethylene glycol (PEG) of molecular weights 4,500 or 10,000. The neutrophils observed at 32 hours after intravenous injection of the rHuG-CSF modified with PEG (4,500) or PEG (10,000) to mice were, respectively, 2.5 times and 5 times more than that observed after the injection of the unmodified rHuG-CSF. These results show that the covalent attachment of PEG to rHuG-CSF enhanced its pharmacological activity in vivo and that the modification with the larger PEG molecule is more effective to enhance the in vivo activity of rHuG-CSF.
Needleless Melt‐Electrospinning of Polypropylene Nanofibres (2012)

Polypropylene (PP) nanofibres have been electrospun from molten PP using a needleless melt‐electrospinning setup containing a rotary metal disc spinneret. The influence of the disc spinneret (e.g., disc material and diameter), operating parameters (e.g., applied voltage, spinning distance), and a cationic surfactant on the fibre formation and average fibre diameter were examined. It was shown that the metal material used for making the disc spinneret had a significant effect on the fibre formation. Although the applied voltage had little effect on the fibre diameter, the spinning distance affected the fibre diameter considerably, with shorter spinning distance resulting in finer fibres. When a small amount of cationic surfactant (dodecyl trimethyl ammonium bromide) was added to the PP melt for melt‐electrospinning, the fibre diameter was reduced considerably. The finest fibres produced from this system were 400 ± 290 nm. This novel melt‐electrospinning setup may provide a continuous and efficient method to produce PP nanofibres.
d -Amino Acids Trigger Biofilm Disassembly (2010)

Bacteria form communities known as biofilms, which disassemble over time. In our studies outlined here, we found that, before biofilm disassembly, Bacillus subtilis produced a factor that prevented biofilm formation and could break down existing biofilms. The factor was shown to be a mixture of D-leucine, D-methionine, D-tyrosine, and D-tryptophan that could act at nanomolar concentrations. D-amino acid treatment caused the release of amyloid fibers that linked cells in the biofilm together. Mutants able to form biofilms in the presence of D-amino acids contained alterations in a protein (YqxM) required for the formation and anchoring of the fibers to the cell. D-amino acids also prevented biofilm formation by Staphylococcus aureus and Pseudomonas aeruginosa. D-amino acids are produced by many bacteria and, thus, may be a widespread signal for biofilm disassembly.