gebhart/patrepeval huggingface dataset:
A DNA Methylation Prognostic Signature of Glioblastoma: Identification of NPTX2-PTEN-NF-κB Nexus (2013)

Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal patient survival, yet the molecular determinants of patient survival are poorly characterized. Global methylation profile of GBM samples (our cohort; n = 44) using high-resolution methylation microarrays was carried out. Cox regression analysis identified a 9-gene methylation signature that predicted survival in GBM patients. A risk-score derived from methylation signature predicted survival in univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort. Multivariate analysis identified methylation risk score as an independent survival predictor in TCGA cohort. Methylation risk score stratified the patients into low-risk and high-risk groups with significant survival difference. Network analysis revealed an activated NF-κB pathway association with high-risk group. NF-κB inhibition reversed glioma chemoresistance, and RNA interference studies identified interleukin-6 and intercellular adhesion molecule-1 as key NF-κB targets in imparting chemoresistance. Promoter hypermethylation of neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2 transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2 overexpression induced apoptosis, inhibited proliferation and anchorage-independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2 repressed NF-κB activity by inhibiting AKT through a p53-PTEN-dependent pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF-κB-activated high-risk GBMs. Taken together, a 9-gene methylation signature was identified as an independent GBM prognosticator and could be used for GBM risk stratification. Prosurvival NF-κB pathway activation characterized high-risk patients with poor prognosis, indicating it to be a therapeutic target.
The Furin Protease Cleavage Recognition Sequence of Sindbis Virus PE2 Can Mediate Virion Attachment to Cell Surface Heparan Sulfate (1999)

Cell culture-adapted Sindbis virus strains attach to heparan sulfate (HS) receptors during infection of cultured cells (W. B. Klimstra, K. D. Ryman, and R. E. Johnston, J. Virol. 72:7357-7366, 1998). At least three E2 glycoprotein mutations (E2 Arg 1, E2 Lys 70, and E2 Arg 114) can independently confer HS attachment in the background of the consensus sequence Sindbis virus (TR339). In the studies reported here, we have investigated the mechanism by which the E2 Arg 1 mutation confers HS-dependent binding. Substitution of Arg for Ser at E2 1 resulted in a significant reduction in the efficiency of PE2 cleavage, yielding virus particles containing a mixture of PE2 and mature E2. Presence of PE2 was associated with an increase in HS-dependent attachment to cells and efficient attachment to heparin-agarose beads, presumably because the furin recognition site for PE2 cleavage also represents a candidate HS binding sequence. A comparison of mutants with partially or completely inhibited PE2 cleavage demonstrated that efficiency of cell binding was correlated with the amount of PE2 in virus particles. Viruses rendered cleavage defective due to deletions of portions or all of the furin cleavage sequence attached very poorly to cells, indicating that an intact furin cleavage sequence was specifically required for PE2-mediated attachment to cells. In contrast, a virus containing a partial deletion was capable of efficient binding to heparin-agarose beads, suggesting different requirements for heparin bead and cell surface HS binding. Furthermore, virus produced in C6/36 mosquito cells, which cleave PE2 more efficiently than BHK cells, exhibited a reduction in cell attachment efficiency correlated with reduced content of PE2 in particles. Taken together, these results strongly argue that the XBXBBX (B, basic; X, hydrophobic) furin protease recognition sequence of PE2 can mediate the binding of PE2-containing Sindbis viruses to HS. This sequence is very similar to an XBBXBX heparin-HS interaction consensus sequence. The attachment of furin protease cleavage sequences to HS may have relevance to other viruses whose attachment proteins are cleaved during maturation at positively charged recognition sequences.
Simulation-aided path planning of UAV (2007)

The problem of path planning for Unmanned Aerial Vehicles (UAV) with a tracking mission, when some a priori information about the targets and the environment is available can in some cases be addressed using simulation. Sequential Monte Carlo Simulation can be used to assess the state of the system and target when the UAV reaches the area of responsibility and during the tracking task. This assessment of the future is then used to compare the impact of choosing different alternative paths on the expected value of the detection time. A path with a lower expected value of detection time is preferred. In this paper the details of this method is described. Simulations are performed by a special purpose simulation tool to show the feasibility of this method and compare it with an exhaustive search.
A Double Regio‐ and Stereoselective Glycosylation Strategy for the Synthesis of N‐Glycans (2007)

A building block approach for biantennary N-linked oligosaccharides from glycoproteins (N-glycans) has been developed. Starting from a core trisaccharide (beta-mannosyl chitobiose) containing a benzylidene-protected beta-mannoside, the attachment of the disaccharide building blocks for the antennae can be performed in a double regio- and stereoselective manner. A short synthesis of a GlcNPhtbeta1,2Man donor was developed. The benzylidene acetal moiety, as a minimal protection of the beta-mannoside, allows selective alpha-glycosylation at OH-3 of the 2,3-diol with GlcNbeta1,2Man trichloroacetimidate donors. Subsequent debenzylidenation leads to a 4,6-diol, which can be selectively extended at OH-6. Overreaction at OH-4 was generally low when phthalimido-protected donors were used. This general strategy represents a modular synthesis of N-glycans and their glycoconjugates.
Treatment planning in cutaneous T-Cell lymphoma (2003)

Effective long-term management of cutaneous T-cell lymphoma (CTCL) requires administration of skin-directed therapies such as topically applied nitrogen mustard or photochemotherapy to achieve a complete response in clinically early disease (patch and thin-plaque-phase mycosis fungoides, MF) and often the concomitant administration of well-tolerated drugs with systemic effects such as interferon alfa, bexarotene, methotrexate or extracorporeal photopheresis in more advanced, but not highly aggressive/nontransformed disease (thick plaque or tumor phase MF or erythrodermic CTCL). The author's approach is provided as a guide for dermatologists in private practice.
Threshold switching in melanin (1975)

Threshold-switching measurements of synthetic melanin confirm that this organic semiconductor switches to a low-resistance state in low electric fields as reported by McGinness et al. Time-dependent current-vs-voltage curves show that the time to traverse the negative-differential-resistance (NDR) segment is much slower than would be expected from electronic-switching mechanisms. Double-pulse measurements add to the evidence that thermal effects dominate electronic effects in melanin. A pseudomemory effect was found in melanin.
Hepatocyte Growth Factor Activator Inhibitor, a Novel Kunitz-type Serine Protease Inhibitor (1997)

Hepatocyte growth factor (HGF) activator is a serine protease that is produced and secreted by the liver and circulates in the blood as an inactive zymogen. In response to tissue injury, the HGF activator zymogen is converted to the active form by limited proteolysis. The activated HGF activator converts an inactive single chain precursor of HGF to a biologically active heterodimer in injured tissue. The activated HGF may be involved in the regeneration of the injured tissue. In this study, we purified an inhibitor of HGF activator from the conditioned medium of a human MKN45 stomach carcinoma cell line and molecularly cloned its cDNA. The sequence of the cDNA revealed that the inhibitor has two well defined Kunitz domains, suggesting that the inhibitor is a member of the Kunitz family of serine protease inhibitors. The sequence also showed that the primary translation product of the inhibitor has a hydrophobic sequence at the COOH-terminal region. Inhibitory activity toward HGF activator was detected in the membrane fraction as well as in the conditioned medium of MKN45 cells. These results suggest that the inhibitor may be produced as a membrane-associated form and secreted by the producing cells as a proteolytically truncated form.
The Origin of the VM/370 Time-Sharing System (1981)

VM/370 is an operating system which provides its multiple users with seemingly separate and independent IBM System/370 computing systems. These virtual machines are simulated using IBM System/370 hardware and have its same architecture. In addition, VM/370 provides a single-user interactive system for personal computing and a computer network system for information interchange among interconnected machines. VM/370 evolved from an experimental operating system designed and built over fifteen years ago. This paper reviews the historical environment, design influences, and goals which shaped the original system.
A Comparison of 2D-3D Pose Estimation Methods (2008)

www.aau.dk This thesis describes pose estimation as an increasingly used area in augmen-tation and tracking with many different solutions and methods that constantly undergo optimization and each has drawbacks and benefits. But the aim is always speed, accuracy or both when it comes to real applications. Pose esti-mation is used in many areas but primarily tracking and augmentation issues, where another large area of finding 2D-2D correspondences is crucial research area today. Software like ARToolKit [11] tracks a flat marker and is able to draw 3D objects on top of it for augmentation purposes. It is very fast, because the accuracy is not the largest issue when the eye has to judge if it looks real or augmented. But the speed must be high for the eye to see it as real as the background. There is not really a common standard of how to compare methods for pose estimation and there is no standard method to compare with. In this thesis efford is made to get a fair comparison and there is included a simple very known method as comparator. In total there is 4 methods tested, they calculate the perspective from known 2D-3D correspondences from image to point cloud. All have different limitations such as minimum amount of 2D-3D correspondence pairs or sensitivity to noise that makes it unpredictable in noisy conditions. The benefits and drawbacks are listed for each method for easy comparison. The 3 methods are nonlinear CPC, PosIt and PosIt for coplanar points, while DLT is a linear method that is used because it is easy to implement and good for comparison. All tests are done on fictive data to allow some extreme cases and to have ground truth for accurate comparisons. In short the tests made are: Noise ii test, increased number of points, planarity issues, distance to object and initial guesses. The findings were many and shows that the methods are working very differently. So when choosing a method, one has to consider the application of it, and what data is available to the method.
Molecular and biomolecular optoelectronics (2001)

Abstract Reversible electronic transduction of photonic processes occurring on electrodes is the conceptual method to develop molecular and biomolecular optoelectronic systems. Cyclic photochemical activation of molecular or biomolecular monolayer redox-functions provides a general methodology for the amperometric transduction of photonic information that is recorded by the chemical assembly. Alternatively, photoisomerizable monolayers associated with electrodes act as "command interfaces" for controlling the interfacial electron transfer between molecular redox-species or redox-proteins. The systems use a photonic input for the generation of an electronic output and act as information processing assemblies. Programmed arrays of photosensitizer/electron acceptor cross-linked Au-nanoparticle arrays are assembled on indium tin oxide (ITO) for photoelectrochemical applications.
Brain Stem and Cerebellar Hyperintense Lesions in Migraine (2006)

We found an increased prevalence of infratentorial (mostly pontine) hyperintensities in migraineurs from the general population. This extends the knowledge about vulnerable brain regions and type of lesions in migraine brains. A hemodynamic ischemic pathogenesis is likely, but further research is needed.
Intramolecular triple-helix formation at (PunPyn).cntdot.(PunPyn) tracts: recognition of alternate strands via Pu.cntdot.PuPy and Py.cntdot.PuPy base triplets (1992)

Triple-helical DNA shows increasing potential for applications in the control of gene expression (including therapeutics) and the development of sequence-specific DNA-cleaving agents. The major limitation in this technology has been the requirement of homopurine sequences for triplex formation. We describe a simple approach that relaxes this requirement, by utilizing both Pu.PuPy and Py.PuPy base triplets to form a continuous DNA triple helix at tandem oligopurine and oligopyrimidine tracts. [Triplex formation at such a sequence has been previously demonstrated only with the use of a special 3'-3' linkage in the third strand [Horne, D. A., & Dervan, P. B. (1990) J. Am. Chem. Soc. 112, 2435-2437].] Supporting evidence is from chemical probing experiments performed on several oligonucleotides designed to form 3-stranded fold-back structures. The third strand, consisting of both purine and pyrimidine blocks, pairs with purines in the Watson-Crick duplex, switching strands at the junction between the oligopurine and oligopyrimidine blocks but maintaining the required strand polarity without any special linkage. Although Mg2+ ions are not required for the formation of Pu.PuPy base triplets, they show enhanced stability in the presence of Mg2+. In the sequences observed. A.AT triplets appear to be more stable than G.GC triplets. As expected, triplex formation is largely independent of pH unless C+.GC base triplets are required.
Raman Spectroscopic Investigation of Individual Single-Walled Carbon Nanotubes Helically Wrapped by Ionic, Semiconducting Polymers (2013)

Raman-active vibrational modes of (6,5) chirality-enriched single-walled carbon nanotubes (SWNTs), helically wrapped by semiconducting poly[2,6-{1,5-bis(3-propoxysulfonic acid sodium salt)}naphthylene]ethynylene (PNES), are described in great detail. At an irradiation wavelength of 568.2 nm, the extent to which the environment impacts the nanotube vibrational signature can be probed; in particular, the absence of a G band shift for PNES–[(6,5) SWNT] samples relative to benchmark surfactant-coated nanotubes indicates the lack of any significant charge transfer between the PNES strand and the SWNT skeleton, but electronic spectra provide compelling evidence for polymer-to-SWNT energy transfer. At an irradiation wavelength of 457.9 nm, vibrational modes associated with PNES chains that wrap (6,5) SWNTs are conspicuously enhanced. Under 514.5 nm irradiation, PNES–[(6,5) SWNTs] are not excited in resonance but G and G′ bands associated with these nanohybrids are strongly enhanced, reflecting the excitation of a multiphonon-mediated vibronic transition of the (6,5) SWNT backbone. At a 488.0 nm irradiation wavelength, Raman spectral signatures of both the PNES polymer and the vibronically excited (6,5) SWNT skeleton through one-phonon-assisted processes are pronounced, demonstrating that a specific SWNT chirality and the corresponding semiconducting polymer helically wrapped about its surface can be probed using an excitation wavelength that does not resonantly excite the SWNT structure.
Development of a functional HTS assay for the APJ receptor (2010)

Development of a functional HTS assay for the APJ receptor Angela Giddings1, Scott Runyon2, James Thomas2, Julianne Tajuba1, Katherine Bortoff1, Rangan Maitra11Center for Pharmacology and Toxicology, 2Center for Organic and Medicinal Chemistry, Division of Discovery Sciences, RTI International, Research Triangle Park, NC, USAAbstract: The apelin receptor (APJ) is rapidly emerging as an attractive therapeutic target for various diseases. To date, only one nonpeptide APJ agonist has been reported and new chemotypes having improved pharmacological properties are needed to expedite maturation of this receptor as a viable target. Therefore, the development of a high-throughput screening (HTS) assay for APJ should facilitate the discovery of novel ligands as in vivo probes of APJ function. In this report, an HTS compatible assay for the APJ is demonstrated. This assay takes advantage of functional coupling of APJ with the promiscuous G&alpha;q16 protein and consequent mobilization of intracellular calcium, which can be measured in a microplate format using a fluorescent calcium probe. The assay was developed and validated using several known peptides derived from preproapelin. Most of the apelin peptides tested activated APJ at subnanomolar concentrations in accordance with their reported median effective concentration values. The assay was deemed robust and reproducible with a Z-factor of &sim;0.6 and tolerance to ethanol, dimethyl sulfoxide or a mixture of these two commonly used solvents to a final concentration of 1%. The assay was further validated by screening a small library of compounds for APJ activity. A hit rate of &sim;0.5% was achieved and confirmed by counter-screening against parental G&alpha;q16 cells lacking APJ. In conclusion, an HTS assay has been established to rapidly identify new ligands for the APJ. Novel APJ ligands having suitable drug-like properties are greatly needed to probe the in vivo pharmacology of this emerging therapeutic target.Keywords: APJ, apelin, G&alpha;q16, GPCR, HTS, assay
Correspondence between the frequency domain characteristics of simultaneous surface and intra-atrial recordings of atrial fibrillation (2002)

Previous studies have shown a decrease in the median frequency of intra-atrial recordings of atrial fibrillation during the infusion of procainamide. This study determines if the changes in median frequency can be measured simultaneously in ECG leads. Remainder electrocardiograms were generated for lead II and VI before and after the administration of procainamide. The median frequency of the power spectrum of the remainder electrocardiograms as well as an intra-atrial lead were calculated. The average median frequency of the pre-procainamide segments ranged from 4.1-6.9 Hz for lead II; 4.1-6.9 Hz for lead VI; and 4.1-7.4 Hz for the intra-atrial lead. The average median frequency of the post-procainamide segments ranged from 4.2-5.8 Hz for lead II; 4.3-5.8 fit for lead VI; and 3.1-6.1 Hz for the intra-atrial lead. Considering each patient individually, correlation between the median frequency of the surface and intra-atrial leads ranged from 0.06 to 0.88.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Palladium-catalyzed cross-coupling reaction of organoboron compounds with organic triflates (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPalladium-catalyzed cross-coupling reaction of organoboron compounds with organic triflatesTakayuki Ohe, Norio Miyaura, and Akira SuzukiCite this: J. Org. Chem. 1993, 58, 8, 2201–2208Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/jo00060a041https://doi.org/10.1021/jo00060a041research-articleACS PublicationsRequest reuse permissionsArticle Views4987Altmetric-Citations275LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Expression of the p16 and p15 cyclin-dependent kinase inhibitors in lymphocyte activation and neuronal differentiation. (1995)

The cyclin-dependent kinase inhibitors p16INK4/MTS1 and p15INK4B/MTS2 have been mapped to a region in chromosome 9 (921) that is deleted frequently in acute lymphoblastic leukemias and malignant gliomas. To gain insight into the functions of these inhibitors in lymphocytes and neuronal cells, we studied the expression of p15 and p16 during lymphocyte mitogenesis and neuronal differentiation. Expression of p15 was extinguished during lymphocyte activation, concomitant with an increase in retinoblastoma kinase activity. The differentiation of the embryonic teratocarcinoma cell line NT2 into postmitotic neurons (hNT) was associated with enhanced expression of p15 and p16 proteins. These findings suggest that p15 and p16 play a role in maintaining cell quiescence in lymphocytes and neuronal cells, respectively. Deletions of these genes may thus promote unrestrained growth.
Chemokine gene activation in human bone marrow‐derived osteoblasts following exposure to particulate wear debris (2006)

Particulate wear debris induces the expression of pro-inflammatory cytokine and chemokine genes in various cell types of the periprosthetic region. We have previously reported that titanium particles stimulate the selective induction of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human osteoblast-like osteosarcoma cells. In this study, we characterize the human bone marrow-derived osteoblast chemokine response to titanium particles. We demonstrate that titanium particles result in enhanced IL-8 and MCP-1 protein secretion as well as differential chemokine gene activation. Osteoblast chemokine expression was regulated at the level of gene transcription, with a time-dependent induction of NF-kappaB activation. Inhibition studies with N-acetyl-L-cysteine (Nac) and MG-132 suggest that titanium particle activation of NF-kappaB activity and IL-8 chemokine expression involves oxidant signaling and IkappaBalpha-proteasomal degradation. Activation of the NF-kappaB transcription factor, as well as the IL-8 gene, are redox-regulated. We also demonstrate that while cytochalasin D, a potent inhibitor of phagocytosis, suppressed the titanium particle effect on IL-8 protein release in human bone marrow-derived osteoblasts, the inhibitor had no effect on IL-8 expression in MG-63 osteoblast-like cells. Collectively, these results provide insight into the potential mechanisms responsible for the particulate activation of osteoblast chemokine expression and suggest an important role for the osteoblast in the pathogenesis of periprosthetic osteolysis.