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See detailNTFD - A stand-alone application for the non-targeted detection of stable isotope labeled compounds in GC/MS data.
Hiller, Karsten UL; Wegner, André UL; Weindl, Daniel UL et al

in Bioinformatics (2013), 29(9), 1226-8

SUMMARY: Most current stable isotope-based methodologies are targeted and focus only on the well-described aspects of metabolic networks. Here, we present NTFD (non-targeted tracer fate detection), a ... [more ▼]

SUMMARY: Most current stable isotope-based methodologies are targeted and focus only on the well-described aspects of metabolic networks. Here, we present NTFD (non-targeted tracer fate detection), a software for the non-targeted analysis of all detectable compounds derived from a stable isotope-labeled tracer present in a GC/MS dataset. In contrast to traditional metabolic flux analysis approaches, NTFD does not depend on any a priori knowledge or library information. To obtain dynamic information on metabolic pathway activity, NTFD determines mass isotopomer distributions for all detected and labeled compounds. These data provide information on relative fluxes in a metabolic network. The graphical user interface allows users to import GC/MS data in netCDF format and export all information into a tab-separated format. AVAILABILITY: NTFD is C++- and Qt4-based, and it is freely available under an open-source license. Pre-compiled packages for the installation on Debian- and Redhat-based Linux distributions, as well as Windows operating systems, along with example data, are provided for download at http://ntfd.mit.edu/. CONTACT: gregstep@mit.edu. [less ▲]

Detailed reference viewed: 162 (5 UL)
See detailNüchterne Narrationen. Zum Realismus in Guy Helmingers "Etwas fehlt immer” (2005) und “Morgen war schon” (2007).
Amann, Wilhelm UL

in Parr, Rolf; Ernst, Thomas; Conter, Claude D. (Eds.) Guy Helminger. Ein Sprachanatom bei der Arbeit (2014)

Detailed reference viewed: 36 (1 UL)
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See detailNuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain
Simonetti, Manuela; Hagenston, Anna; Vardeh, Daniel et al

in Neuron (2013), 77(1), 43-57

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is ... [more ▼]

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleusspecific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics and functional analyses, we discovered a pain-associated, nuclear calciumregulated gene program in spinal excitatory neurons. This includes C1q, a novel modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity. [less ▲]

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See detailNuclear Energy for Peaceful Purposes:
Al Hajjaji, Shams Al Din UL

Presentation (2016, December)

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See detailNuclear localization and phosphorylation modulate pathological effects of Alpha-Synuclein
Pinho, Raquel; Paiva, Isabel; Jerčić, Kristina Gotovac et al

in Human Molecular Genetics (2018)

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See detailThe Nuclear Question, 1954-1982
Paravantis, Spero UL

in Centre Virtuel de la Connaissance sur L'europe (2016)

Franco-British Diplomatic games and issues within the Western European Union (WEU) (1954-1982) http://www.cvce.eu/en/recherche/unit-content/-/unit/e7c423ed-a376-4a57-a415-f8519344e558 2 of 4 texts, which ... [more ▼]

Franco-British Diplomatic games and issues within the Western European Union (WEU) (1954-1982) http://www.cvce.eu/en/recherche/unit-content/-/unit/e7c423ed-a376-4a57-a415-f8519344e558 2 of 4 texts, which were published to accompany the selection of WEU documents for the above-named project, to establish the relevant institutional and historical background to place these documents in their proper context. Published October 2016 by DEIS, (Formerly the CVCE) University of Luxembourg [less ▲]

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See detailNuclear receptors as controlling factors in chemical metabolism: Determination of regulatory signal network crucial for co-ordinating cellular response to chemicals
Kolodkin, Alexey UL; Phillips, Anna; Hood, Steve R. et al

in Drug Metabolism Reviews (2010), 42(1), 279-280

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See detailNuclear receptors in human immune cells: expressions and correlations
Muller, Claude P.; Schiltz, Jang UL; Turner, Jonathan D. et al

in Molecular Immunology (2007), 44

Nuclear receptors (NR) are key modulators of gene transcription. Their activity is ligand induced and modulates a large variety of tissue-specific cellular functions. However, for many NR little is known ... [more ▼]

Nuclear receptors (NR) are key modulators of gene transcription. Their activity is ligand induced and modulates a large variety of tissue-specific cellular functions. However, for many NR little is known about their role in cells of the immune system. In this study, expression patterns and distribution of 24 NR were investigated in human peripheral blood mononuclear cells.We provide the first evidence of the expression of the 12 receptors CAR, CoupTF , CoupTF , FXR, GCNF, HNF4 , PPAR / , PXR, RevErb , TR2, TR4 and TLX in highly purified CD4, CD8, CD19, CD14 cells. The expression profile of RevErb and LXR previously observed in B cell and macrophages, respectively, has been extended to CD4, CD8 and CD14 cells. Except for RAR , which was absence in any of the cells tested, our results suggest an almost ubiquitous expression of the NR in the different cell lineages of the immune system. The expression of CAR, CoupTF , FXR was also confirmed at a protein level and despite conspicuous mRNA levels of HNF4 , only low levels of this receptor were detectable in the nuclear fraction of PBMCs. Expression of the latter receptors was mostly only a fraction (4–20%) of their expression in the thyroid gland, the adrenal gland, the lung or subcutaneous adipose tissue. The Spearman rank order correlation test was performed to examine the correlation in expression between individual nuclear receptor pairs in the four cell types for several donors. Distinct correlation patterns were observed between receptor pairs in the individual cell types. In CD4 T cells four NR, GCNF, PPAR , PPAR 7 and RevErb are perfectly correlated with each other (P≥0.0167). In the other cell types correlations betweenNRpairs were more diverse, but also statistically highly significant. Interestingly, the relative expression level of a number of receptor pairs ranked identical or similar in at least three (CoupTF and PPAR / , CoupTF andHNF4 as well asROR and PXR) or four cell types (CoupTF and CoupTF , PPAR and RevErb ). Despite the variability of NR expression in immune cells, these results suggest that some of the NR may be co-regulated in human immune cells. [less ▲]

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See detailNucleation in Hard Spheres Systems
Dorosz, Sven UL

Presentation (2012, February 07)

I will be discussing the nucleation process in a system composed of mono-disperse hard spheres initially in an over-compressed fluid state. Molecular dynamics simulations are presented for the homogeneous ... [more ▼]

I will be discussing the nucleation process in a system composed of mono-disperse hard spheres initially in an over-compressed fluid state. Molecular dynamics simulations are presented for the homogeneous system and the dynamics and structure of the forming nucleus including the corresponding nucleation rates are discussed. In comparison to the studied homogenous nucleation event we will extend this system and introduce a substrate to study its influence onto nucleation within the fluid. In this case the substrate is made up of the same type of spheres held fixed in space throughout the simulation process on a triangular lattice modeling a crystalline surface. In general heterogenous nucleation, due to surfaces, walls as well as confinement are of great importancein experiments of colloidal suspensionsbecause strong effects are observed. In our case the substrates influence is studied by varying the substrate lattice constant as well as the fluid density. We observe qualitatively different dynamical regimes that will be discussed in detail. [less ▲]

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See detailNucleation in Hard Spheres Systems
Dorosz, Sven UL

Presentation (2011, August)

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See detailNucleation in liquid crystals
Schilling, Tanja UL

Presentation (2003)

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See detailNucleation in suspensions of anisotropic colloids
Schilling, Tanja UL; Frenkel, Daan

in Computer Physics Communications (2005), 169(1-3), 117-121

We report Monte Carlo studies of liquid crystal nucleation in two types of anisotropic colloidal systems: hard rods and hard ellipsoids. In both cases we find that nucleation pathways differ strongly from ... [more ▼]

We report Monte Carlo studies of liquid crystal nucleation in two types of anisotropic colloidal systems: hard rods and hard ellipsoids. In both cases we find that nucleation pathways differ strongly from the pathways in systems of spherical particles. Short hard rods show an effect of self-poisoning. This part of the article is based on a previous publication [T. Schilling, D. Frenkel, Self-poisoning of crystal nuclei in hard-rod liquids, Phys. Rev. Lett. 92 (2004) 085505]. When a crystallite forms, its surfaces are covered preferentially by rods which align perpendicular to the surface. Therefore subsequent growth is stunted. Hard, almost spherical ellipsoids can be compressed to very high densities without crystallization—in contrast to hard spheres, which crystallize easily. When forced to crystallize, ellipsoids form very loosely aggregated nuclei. In both cases nucleation pathways are complex and it is therefore difficult to define an appropriate reaction coordinate. The common strategies of investigation of nucleation problems (i.e. definition of a coordinate and then sampling barrier crossing with well-known techniques) fail in these systems. [less ▲]

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See detailNucleation in suspensions of anisotropic colloids
Schilling, Tanja UL

Presentation (2004)

Detailed reference viewed: 61 (0 UL)
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See detailNucleation in suspensions of anisotropic colloids
Schilling, Tanja UL

Scientific Conference (2005)

Detailed reference viewed: 60 (3 UL)
See detailNucleation of a liquid crystal
Schilling, Tanja UL

Presentation (2004)

Detailed reference viewed: 17 (1 UL)
See detailNucleation of a liquid crystal
Schilling, Tanja UL

Presentation (2004)

Detailed reference viewed: 13 (2 UL)
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See detailNucleocytoplasmic shuttling of persistently activated STAT3.
Herrmann, Andreas; Vogt, Michael; Monnigmann, Martin et al

in Journal of Cell Science (2007), 120(Pt 18), 3249-61

Persistent activation of the transcription factor STAT3 has been detected in many types of cancer and plays an important role in tumor progression, immune evasion and metastasis. To analyze persistent ... [more ▼]

Persistent activation of the transcription factor STAT3 has been detected in many types of cancer and plays an important role in tumor progression, immune evasion and metastasis. To analyze persistent STAT3 activation we coexpressed STAT3 with v-Src. We found that tyrosine phosphorylation of STAT3 by v-Src is independent of Janus kinases (Jaks), the canonical activators of STATs. The STAT3-induced feedback inhibitor, suppressor of cytokine signaling 3 (SOCS3), did not interfere with STAT3 activation by v-Src. However, the protein inhibitor of activated STAT3 (PIAS3) suppressed gene induction by persistently activated STAT3. We measured nucleocytoplasmic shuttling of STAT3 in single cells by bleaching the YFP moiety of double-labelled STAT3-CFP-YFP in the cytoplasm. Analysis of the subcellular distribution of CFP and YFP fluorescence over time by mathematical modeling and computational parameter estimation revealed that activated STAT3 shuttles more rapidly than non-activated STAT3. Inhibition of exportin-1-mediated nuclear export slowed down nucleocytoplasmic shuttling of v-Src-activated STAT3 resulting in reduced tyrosine phosphorylation, decreased induction of STAT3 target genes and increased apoptosis. We propose passage of persistently activated STAT3 through the nuclear pore complex as a new target for intervention in cancer. [less ▲]

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See detailThe nucleotide excision repair (NER) system of Helicobacter pylori: Roles of NER components in mutation prevention and chromosomal import patterns after natural transformation
Moccia, Claudia; Kulick, Stefan; Krebes, Juliane et al

in BMC Microbiology (2012), 6(12), 67

Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic ... [more ▼]

Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination. [less ▲]

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See detailNueva división internacional del trabajo, diferenciación y superpoblación relativa: un análisis de sus relaciones y determinaciones
Cazón, Fernando; Graña, Juan M.; Kozlowski, Diego UL et al

in VIII Jornadas de Economía Crítica, Río Cuarto (2015)

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See detailNuevas estrategias farmacológicas en el tratamiento de la psoriasis
Andres Ejarque, Rosa Maria UL

Doctoral thesis (2013)

La psoriasis es una enfermedad inflamatoria crónica caracterizada por la inflamación de la piel, que viene acompañada por hiperproliferación de los queratinocitos, infiltración leucocitaria dérmica y una ... [more ▼]

La psoriasis es una enfermedad inflamatoria crónica caracterizada por la inflamación de la piel, que viene acompañada por hiperproliferación de los queratinocitos, infiltración leucocitaria dérmica y una angiogénesis incrementada. Los mecanismos patológicos que dirigen esta patología incluyen tanto respuestas de la inmunidad innata como de la adaptativa. En la presente tesis doctoral se ha ahondado en el estudio de la respuesta fisiopatológica de los queratinocitos a los cambios que se producen en el entorno de una placa psoriásica, con el objetivo de aportar evidencia de relevancia para el desarrollo de nuevos tratamientos farmacológicos. De este modo, se ha puesto de manifiesto que los mediadores proinflamatorios presentes en el contexto psoriásico son capaces de alterar la expresión de los receptores de adenosina, nucleósido implicado en el efecto antiinflamatorio del metotrexato, produciéndose una disminución de los receptores A2B y un aumento de los A2A. Así mismo, se ha demostrado que en piel psoriásica lesional existe una sobreactivación de los transductores de señales y activadores de la transcripción (STAT) 1 y 3, pese a que se produce una disminución mayoritaria de la expresión de las Janus cinasas (Jak). Además, se ha caracterizado el papel de diversos mediadores proinflamatorios en la modulación de estas vías de señalización. Recientemente se ha puesto de manifiesto la importancia de STAT3, así como del factor de transcripción nuclear κB (NF-κB) en la patogénesis de la psoriasis. Por ello, y con el fin de obtener nuevos fármacos útiles para el tratamiento de la enfermedad, en la presente tesis hemos evaluado el potencial efecto antipsoriásico de diversos derivados de origen natural en base a su capacidad para inhibir la activación de estos dos factores de transcripción. Para ello, iniciamos nuestro estudio mediante un screening previo en la línea de macrófagos murinos RAW 264.7 de una serie de moléculas obtenidas en su mayoría de esponjas marinas, así como del condroitín sulfato (CS), proteoglicano de amplio uso en la terapéutica de la osteoartritis. La siguiente fase de nuestro proceso de cribado se realizó en cultivos primarios de queratinocitos humanos, en los que se evaluó la capacidad para inhibir la liberación de las citocinas factor de necrosis tumoral α (TNFα) e interleucina (IL)8. Estos estudios preliminares nos llevaron a la selección del derivado semisintético 4-Benzo[b]tiofen-2-il-3-bromo-5-hidroxi-5H-furan-2-ona (BTH) y del CS para su estudio en profundidad. En la última fase de nuestro estudio, el pretratamiento de queratinocitos primarios humanos con el CS inhibió la activación del NF-κB y, en consecuencia, la liberación de citocinas proinflamatorias. Además, disminuyó la translocación al núcleo de STAT3 así como su actividad transcripcional, demostrando su potencial interés como nuevo fármaco antipsoriásico. Por otro lado, el derivado semisintético BTH también disminuyó la liberación de citocinas y quimiocinas proinflamatorias gracias a su efecto inhibidor de la activación del NF-κB. Además, disminuyó la activación de STAT3 a través del bloqueo de la fosforilación en el residuo de tirosina 705 (Tyr705). Estos resultados fueron confirmados in vivo mediante dos modelos de psoriasis en ratón: la hiperplasia epidérmica inducida por 12-O-tetradecanoilforbol-13-acetato (TPA) y la inflamación psoriásica inducida por imiquimod. En ambos modelos, la administración tópica del BTH previno el desarrollo de lesiones psoriásicas a través de la supresión de la fosforilación del NF-κB y el STAT3, confirmando el potencial de esta molécula como nuevo fármaco antipsoriásico. Globalmente, la presente tesis arroja nueva luz sobre el papel de la adenosina y las vías de señalización del NF-κB y el STAT3 en la patogénesis de la psoriasis y pone de manifiesto la eficacia de moléculas sencillas de origen natural en la paliación de su curso, sugiriendo el potencial interés de estas estrategias farmacológicas en el desarrollo de nuevos abordajes terapéuticos para el tratamiento de esta enfermedad. [less ▲]

Detailed reference viewed: 206 (15 UL)