A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu-Gli protein complexes.

Science.gov (United States)

Tukachinsky, Hanna; Lopez, Lyle V; Salic, Adrian

2010-10-18

In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu-Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu-Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu-Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu-Gli complexes, a process inhibited by PKA.

A mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes

Science.gov (United States)

Tukachinsky, Hanna; Lopez, Lyle V.

2010-01-01

In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find that Hh stimulation quickly recruits endogenous SuFu–Gli complexes to cilia, suggesting a model in which Smo activates Gli by relieving inhibition by SuFu. In support of this model, we find that Hh causes rapid dissociation of the SuFu–Gli complex, thus allowing Gli to enter the nucleus and activate transcription. Activation of protein kinase A (PKA), an inhibitor of Hh signaling, blocks ciliary localization of SuFu–Gli complexes, which in turn prevents their dissociation by signaling. Our results support a simple mechanism in which Hh signals at vertebrate cilia cause dissociation of inactive SuFu–Gli complexes, a process inhibited by PKA. PMID:20956384

Stromal cells expressing hedgehog-interacting protein regulate the proliferation of myeloid neoplasms

International Nuclear Information System (INIS)

Kobune, M; Iyama, S; Kikuchi, S; Horiguchi, H; Sato, T; Murase, K; Kawano, Y; Takada, K; Ono, K; Kamihara, Y; Hayashi, T; Miyanishi, K; Sato, Y; Takimoto, R; Kato, J

2012-01-01

Aberrant reactivation of hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer stem cells. However, involvement of the Hh-signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasms is unknown. In this study, we assessed the expression of Hh-related genes in primary human CD34 + cells, CD34 + blastic cells and BM stromal cells. Both Indian Hh (Ihh) and its signal transducer, smoothened (SMO), were expressed in CD34 + acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)-derived cells. However, Ihh expression was relatively low in BM stromal cells. Remarkably, expression of the intrinsic Hh-signaling inhibitor, human Hh-interacting protein (HHIP) in AML/MDS-derived stromal cells was markedly lower than in healthy donor-derived stromal cells. Moreover, HHIP expression levels in BM stromal cells highly correlated with their supporting activity for SMO + leukemic cells. Knockdown of HHIP gene in stromal cells increased their supporting activity although control cells marginally supported SMO + leukemic cell proliferation. The demethylating agent, 5-aza-2′-deoxycytidine rescued HHIP expression via demethylation of HHIP gene and reduced the leukemic cell-supporting activity of AML/MDS-derived stromal cells. This indicates that suppression of stromal HHIP could be associated with the proliferation of AML/MDS cells

Pascal y el Deísmo

OpenAIRE

Garrido Zaragozá, Juan José

2008-01-01

Este estudio contrapone la visión de Blaise Pascal (1623-1662) acerca del cristianismo al deísmo como religión natural. Después de un breve sumario acerca de los conceptos clave del deísmo, se analizan los textos en los que Pascal cuestiona la absoluta primacía de la razón y propone los límites que separan el orden natural del sobrenatural (revelación positiva). Por último en contraste con el deísmo se abordan, por una parte, los criterios establecidos por Pascal para distinguir lo verdadero ...

Antony Flew Del ateísmo al teísmo por la razón científica

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Javier Monserrat

2015-01-01

Full Text Available Nos hemos referido principalmente en los últimos números de Pensamiento a lo que se ha venido en llamar en la última década el Nuevo Ateísmo, representado por Richard Dawkins, Daniel Dennett, Sam Harris y Christopher Hitchens. Stephen Hawking no pertenece a este grupo, pero sus ideas han sido comentadas con frecuencia en relación a la cuestión de Dios. Por ello, hemos abordado también una discusión de su idea del universo y su referencia a Dios. El Nuevo Ateísmo da por supuesto que la ciencia moderna excluye taxativamente la existencia de Dios. Sin embargo, estos no son los únicos ateos. Tanto desde el campo de la ciencia (vg. Steven Weinberg, Carl Sagan, el mismo Roger Penrose, como igualmente desde el campo de la filosofía en los últimos siglos y en la actualidad, numerosos pensadores han llenado las filas del ateísmo. La filosofía clásica de la modernidad dogmática fue atea en gran parte; de ahí la dificultad, mantenida durante siglos, de que se entablase un diálogo entre el teísmo cristiano antiguo y aquel ateísmo dogmático de la modernidad.

Application of battery-based storage systems in household-demand smoothening in electricity-distribution grids

International Nuclear Information System (INIS)

Purvins, Arturs; Papaioannou, Ioulia T.; Debarberis, Luigi

2013-01-01

Highlights: ► Battery system application in demand smoothening in distribution grids is analysed. ► Five European countries are studied with and without high photovoltaic deployment. ► A sensitivity analysis for different battery system parameters is performed. ► A simple battery system management is sufficient for low demand smoothening. ► More elaborate management is required for high demand smoothening. - Abstract: This article analyses in technical terms the application of battery-based storage systems for household-demand smoothening in electricity-distribution grids. The analysis includes case studies of Denmark, Portugal, Greece, France and Italy. A high penetration of photovoltaic systems in distribution grids is considered as an additional scenario. A sensitivity analysis is performed in order to examine the smoothening effect of daily demand profiles for different configurations of the battery system. In general, battery-storage systems with low rated power and low battery capacity can smooth the demand sufficiently with the aid of a simple management process. For example, with 1 kW of peak demand, a 30–45% decrease in the variability of the daily demand profile can be achieved with a battery system of 0.1 kW rated power and up to 0.6 kW h battery capacity. However, further smoothening requires higher battery-system capacity and power. In this case, more elaborate management is also needed to use the battery system efficiently.

Smoothened-antagonists reverse homogentisic acid-induced alterations of Hedgehog signaling and primary cilium length in alkaptonuria.

Science.gov (United States)

Gambassi, Silvia; Geminiani, Michela; Thorpe, Stephen D; Bernardini, Giulia; Millucci, Lia; Braconi, Daniela; Orlandini, Maurizio; Thompson, Clare L; Petricci, Elena; Manetti, Fabrizio; Taddei, Maurizio; Knight, Martin M; Santucci, Annalisa

2017-11-01

Alkaptonuria (AKU) is an ultra-rare genetic disease, in which the accumulation of a toxic metabolite, homogentisic acid (HGA) leads to the systemic development of ochronotic aggregates. These aggregates cause severe complications mainly at the level of joints with extensive degradation of the articular cartilage. Primary cilia have been demonstrated to play an essential role in development and the maintenance of articular cartilage homeostasis, through their involvement in mechanosignaling and Hedgehog signaling pathways. Hedgehog signaling has been demonstrated to be activated in osteoarthritis (OA) and to drive cartilage degeneration in vivo. The numerous similarities between OA and AKU suggest that primary cilia Hedgehog signaling may also be altered in AKU. Thus, we characterized an AKU cellular model in which healthy chondrocytes were treated with HGA (66 µM) to replicate AKU cartilage pathology. We investigated the degree of activation of the Hedgehog signaling pathway and how treatment with inhibitors of the receptor Smoothened (Smo) influenced Hedgehog activation and primary cilia structure. The results obtained in this work provide a further step in the comprehension of the pathophysiological features of AKU, suggesting a potential therapeutic approach to modulate AKU cartilage degradation processes through manipulation of the Hedgehog pathway. © 2016 Wiley Periodicals, Inc.

The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts.

Science.gov (United States)

Vered, M; Peleg, O; Taicher, S; Buchner, A

2009-08-01

The aggressive biological behavior of odontogenic keratocysts (OKCs), unlike that of other odontogenic cysts, has argued for its recent re-classification as a neoplasm, 'keratocystic odontogenic tumor'. Identification of mutations in the PTCH gene in some of the OKCs that were expected to produce truncated proteins, resulting in loss of control of the cell cycle, provided additional support for OKCs having a neoplastic nature. We investigated the immunohistochemical expression of the sonic hedgehog (SHH) signaling pathway-related proteins, PTCH, smoothened (SMO) and GLI-1, and of the SHH-induced bcl-2 oncoprotein in a series of primary OKC (pOKC), recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome-associated OKCs (NBCCS-OKCs), and compared them to solid ameloblastomas (SAMs), unicystic ameloblastomas (UAMs), 'orthokeratinized' OKCs (oOKCs), dentigerous cysts (DCs) and radicular cysts (RCs). All studied lesions expressed the SHH pathway-related proteins in a similar pattern. The expression of bcl-2 in OKCs (pOKCs and NBCCS-OKCs) and SAMs was significantly higher than in oOKCs, DCs and RCs (P < 0.001). The present results of the immunoprofile of OKCs (that includes the expression of the SHH-related proteins and the SHH-induced bcl-2 oncoprotein) further support the notion of OKC having a neoplastic nature. As OKCs vary considerably in their biologic behavior, it is suggested that the quality and quantity of interactions between the SHH and other cell cycle regulatory pathways are likely to work synergistically to define the individual phenotype and corresponding biological behavior of this lesion.

Combined Kernel-Based BDT-SMO Classification of Hyperspectral Fused Images

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Fenghua Huang

2014-01-01

Full Text Available To solve the poor generalization and flexibility problems that single kernel SVM classifiers have while classifying combined spectral and spatial features, this paper proposed a solution to improve the classification accuracy and efficiency of hyperspectral fused images: (1 different radial basis kernel functions (RBFs are employed for spectral and textural features, and a new combined radial basis kernel function (CRBF is proposed by combining them in a weighted manner; (2 the binary decision tree-based multiclass SMO (BDT-SMO is used in the classification of hyperspectral fused images; (3 experiments are carried out, where the single radial basis function- (SRBF- based BDT-SMO classifier and the CRBF-based BDT-SMO classifier are used, respectively, to classify the land usages of hyperspectral fused images, and genetic algorithms (GA are used to optimize the kernel parameters of the classifiers. The results show that, compared with SRBF, CRBF-based BDT-SMO classifiers display greater classification accuracy and efficiency.

Metabolites in vertebrate Hedgehog signaling.

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Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Transduction of the Hedgehog signal through the dimerization of Fused and the nuclear translocation of Cubitus interruptus

Institute of Scientific and Technical Information of China (English)

Yanyan Zhang; Feifei Mao; Yi Lu; Wenqing Wu; Lei Zhang; Yun Zhao

2011-01-01

The Hedgehog (Hh) family of secreted proteins is essential for development in both vertebrates and invertebrates.As one of main morphogens during metazoan development,the graded Hh signal is transduced across the plasma membrane by Smoothened (Smo) through the differential phosphorylation of its cytoplasmic tail,leading to pathway activation and the differential expression of target genes.However,how Smo transduces the graded Hh signal via the Costal2 (Cos2)/Fused (Fu) complex remains poorly understood.Here we present a model of the cell response to a Hh gradient by translating Smo phosphorylation information to Fu dimerization and Cubitus interruptus (Ci)nuclear localization information.Our findings suggest that the phosphorylated C-terminus of Smo recruits the Cos2/Fu complex to the membrane through the interaction between Smo and Cos2,which further induces Fu dimerization.Dimerized Fu is phosphorylated and transduces the Hh signal by phosphorylating Cos2 and Suppressor of Fu (Su(fu)).We further show that this process promotes the dissociation of the full-length Ci (Ci155) and Cos2 or Su(fu),and results in the translocation of Ci155 into the nucleus,activating the expression of target genes.

Discovery of a Novel Inhibitor of the Hedgehog Signaling Pathway through Cell-based Compound Discovery and Target Prediction.

Science.gov (United States)

Kremer, Lea; Schultz-Fademrecht, Carsten; Baumann, Matthias; Habenberger, Peter; Choidas, Axel; Klebl, Bert; Kordes, Susanne; Schöler, Hans R; Sterneckert, Jared; Ziegler, Slava; Schneider, Gisbert; Waldmann, Herbert

2017-10-09

Cell-based assays enable monitoring of small-molecule bioactivity in a target-agnostic manner and help uncover new biological mechanisms. Subsequent identification and validation of the small-molecule targets, typically employing proteomics techniques, is very challenging and limited, in particular if the targets are membrane proteins. Herein, we demonstrate that the combination of cell-based bioactive-compound discovery with cheminformatic target prediction may provide an efficient approach to accelerate the process and render target identification and validation more efficient. Using a cell-based assay, we identified the pyrazolo-imidazole smoothib as a new inhibitor of hedgehog (Hh) signaling and an antagonist of the protein smoothened (SMO) with a novel chemotype. Smoothib targets the heptahelical bundle of SMO, prevents its ciliary localization, reduces the expression of Hh target genes, and suppresses the growth of Ptch +/- medulloblastoma cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Susceptibility to Stress Corrosion Cracking of 254SMO SS

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De Micheli Lorenzo

2002-01-01

Full Text Available The susceptibility to stress corrosion cracking (SCC of solubilized and sensitized 254SMO SS was studied in sodium chloride, and sodium fluoride solutions at 80 °C and sulfuric acid solutions in presence of sodium chloride at 25 °C. The influence of salt concentration, pH values and the addition of thiosulfate was examined. The susceptibility to SCC was evaluated by Slow Strain Rate Tests (SSRT, at 1.5 x 10-6 s-1 strain rate. The behavior of 254SMO was compared to those of AISI 316L SS and Hastelloy C276. 254SMO showed an excellent resistance to SCC in all conditions, except in the more acidic solutions (pH <= 1 where, in the sensitized conditions, intergranular stress corrosion cracking occurred.

Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

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Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

2015-01-01

The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

Resveratrol Enhances Neurite Outgrowth and Synaptogenesis Via Sonic Hedgehog Signaling Following Oxygen-Glucose Deprivation/Reoxygenation Injury

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Fanren Tang

2017-09-01

Full Text Available Background/Aims: Neurite outgrowth and synaptogenesis are critical steps for functional recovery after stroke. Resveratrol promotes neurite outgrowth and synaptogenesis, but the underlying mechanism is not well understood, although the Sonic hedgehog (Shh signaling pathway may be involved. Given that resveratrol activates sirtuin (Sirt1, the present study examined whether this is mediated by Shh signaling. Methods: Primary cortical neuron cultures were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R. Cell viability and apoptosis were evaluated with Cell Counting Kit 8 and by terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Neurite outgrowth and synaptogenesis were assessed by immunocytochemistry and western blotting, which was also used to examine the expression of Sirt1 and Shh signaling proteins. Results: Resveratrol and the Smoothened (Smo agonist purmophamine, which activates Shh signaling, increased viability, reduced apoptosis, and stimulated neurite outgrowth after OGD/R injury. Moreover, the expression of growth-associated protein(GAP-43, synaptophysin, Shh, Patched (Ptc-1, Smo, glioma-associated oncogene homolog (Gli-1, and Sirt1 were upregulated under these conditions. These effects were reversed by treatment with the Smo inhibitor cyclopamine, whereas the Sirt1 inhibitor sirtinol reduced the levels of Shh, Ptc-1, Smo, and Gli-1. Conclusions: Resveratrol reduces neuronal injury following OGD/R injury and enhances neurite outgrowth and synaptogenesis by activating Shh signaling, which in turn induces Sirt1.

El nuevo ateísmo

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Camino Cañón Loyes

2015-01-01

Full Text Available ¿Hay hoy razones filosóficas fuertes y plausibles para ser ateo o, en todo caso, para rechazar la religión? «El Nuevo Ateísmo» ofrece argumentos propios de una razón científica neopositivista, para criticar las creencias religiosas. Sus autores lo hacen aduciendo logros actuales de las ciencias, sin tener nunca en cuenta sus límites intrínsecos y mostrando gran desconocimiento de la interpretación de las creencias religiosas por parte de las comunidades que las profesan. Se muestran especialmente críticos con lo que consideran el potencial de violencia de dichas creencias. Su difusión no hay que buscarla en sus aportaciones teóricas, sino en haber generado un movimiento cultural en la web, con una influencia inimaginable por los ateos clásicos. Dialogar críticamente con el Nuevo Ateísmo requiere poner a punto los argumentos filosóficos en el contexto de la cultura científica actual. En particular, la cuestión del naturalismo, difundida como naturalización de la espiritualidad, «el problema realmente duro» de las neurociencias.

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

International Nuclear Information System (INIS)

Cervelli, Manuela; Grillo, Rosalba; Woster, Patrick M; Casero, Robert A Jr; Mariottini, Paolo; Bellavia, Gabriella; Fratini, Emiliano; Amendola, Roberto; Polticelli, Fabio; Barba, Marco; Federico, Rodolfo; Signore, Fabrizio; Gucciardo, Giacomo

2010-01-01

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials

Spermine oxidase (SMO activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

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Gucciardo Giacomo

2010-10-01

Full Text Available Abstract Background Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC. This study investigates the expression of spermine oxidase (SMO and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. Methods BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Results Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. Conclusions This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

Evaluation of the exothermicity of the chemi-ionization reaction Sm + O → SmO+ + e−

International Nuclear Information System (INIS)

Cox, Richard M; Kim, JungSoo; Armentrout, P. B.; Bartlett, Joshua; VanGundy, Robert A.; Heaven, Michael C.; Ard, Shaun G.; Shuman, Nicholas S.; Viggiano, Albert A.; Melko, Joshua J.

2015-01-01

The exothermicity of the chemi-ionization reaction Sm + O → SmO + + e − has been re-evaluated through the combination of several experimental methods. The thermal reactivity (300–650 K) of Sm + and SmO + with a range of species measured using a selected ion flow tube-mass spectrometer apparatus is reported and provides limits for the bond strength of SmO + , 5.661 eV ≤ D 0 (Sm + -O) ≤ 6.500 eV. A more precise value is measured to be 5.72 5 ± 0.07 eV, bracketed by the observed reactivity of Sm + and SmO + with several species using a guided ion beam tandem mass spectrometer (GIBMS). Combined with the established Sm ionization energy (IE), this value indicates an exothermicity of the title reaction of 0.08 ± 0.07 eV, ∼0.2 eV smaller than previous determinations. In addition, the ionization energy of SmO has been measured by resonantly enhanced two-photon ionization and pulsed-field ionization zero kinetic energy photoelectron spectroscopy to be 5.7427 ± 0.0006 eV, significantly higher than the literature value. Combined with literature bond energies of SmO, this value indicates an exothermicity of the title reaction of 0.14 ± 0.17 eV, independent from and in agreement with the GIBMS result presented here. The evaluated thermochemistry also suggests that D 0 (SmO) = 5.83 ± 0.07 eV, consistent with but more precise than the literature values. Implications of these results for interpretation of chemical release experiments in the thermosphere are discussed

Synthesis, characterization and thermal expansion studies on ThO2-SmO1.5 solid solutions

International Nuclear Information System (INIS)

Panneerselvam, G.; Antony, M.P.

2008-01-01

Full text: A highly homogeneous Th 1-x Sm x O 2 ; 0 ≤ x ≤ 0.8 solid solutions were synthesized by co-precipitation technique and the co-precipitated samples were sintered at 1473 K. Compositions of the solid solutions were characterized by standard wet-chemical analysis. X-ray diffraction measurements were performed in the sintered pellets for structural analysis, lattice parameter calculation and determination of solid solubility of SmO 1.5 in ThO 2 matrix. Bulk and theoretical densities of solid solutions were also determined. A fluorite structure was observed for ThO 2 -SmO 1.5 solid solutions with 0-55.2 mol % SmO 1.5 . Their thermal expansion coefficients were measured using high temperature X-ray diffraction technique. The mean linear thermal expansivity, αm for ThO 2 -SmO 1.5 solid solutions containing 17.9, 41.7 and 52.0 mole percent of SmO 1.5 were determined in the temperature range 298 to 2000 K for the first time. The mean linear thermal expansion coefficients for ThO 2 -SmO 1.5 solid solutions are 10.47x10 -6 K -1 , 11.16x10 -6 K -1 and 11.45x10 -6 K -1 , respectively. The percentage linear thermal expansion in this temperature range, for ThO 2 -SmO 1.5 solid solutions containing 17.9, 41.7 and 52.0 mol % SmO 1.5 are 1.82,1.94 and 1.99 respectively. It is suggested that the solid solutions are stable up to 2000 K. It is also suggested that the effect and nature of the dopant are the important parameters influenced in the thermal expansion of the ThO 2

CoSMoMVPA: Multi-Modal Multivariate Pattern Analysis of Neuroimaging Data in Matlab/GNU Octave.

Science.gov (United States)

Oosterhof, Nikolaas N; Connolly, Andrew C; Haxby, James V

2016-01-01

Recent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species. It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques. CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality. CoSMo

Evaluation of WO2014207069 A1: Multitarget Hedgehog pathway inhibitors and uses thereof.

Science.gov (United States)

Manetti, Fabrizio; Petricci, Elena

2016-01-01

In recent years, the involvement of the Hedgehog (Hh) signaling pathway in various human diseases and dysfunctions has been clearly demonstrated. Smoothened (Smo), one of the upstream signal transducers, has been the most druggable target of the Hh pathway. However, the emergence of resistance to Smo inhibitors and the identification of Smo-independent activation of the Hh pathway led to the need to find new chemical entities able to interfere with downstream components, such as Gli. For this purpose, two different computational approaches have been applied to a small-sized library of natural compounds. As a result, an isoflavone derivative that showed ability to inhibit both Smo and Gli1 has been identified; namely, Glabrescione B. A new synthetic approach has been planned for this compound and its derivatives. Biological evaluation demonstrated the mechanism of action and showed a promising preclinical profile.

NOTAS SOBRE JUDAÍSMO Y BIOÉTICA NOTAS SOBRE JUDAÍSMO E BIOÉTICA NOTES ABOUT JUDAISM AND BIOETHICS

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Ana María Tapia-Adler

2010-06-01

Full Text Available El presente artículo revisa algunos temas tradicionales de bioética desde la perspectiva del Judaísmo, refiere respuestas desde las fuentes originales, sus sucesivas exégesis y la legislación judía (Halajá, y revela la relación entre ciencia, fe y defensa de la vida en esta visión religiosa.O presente artigo revisa alguns temas tradicionais de bioética a partir da perspectiva do Judaísmo, em busca de respostas, com base nas fontes originais, nas sucessivas exegeses e na legislação judaica (Halajá, e revela a relação entre ciência, fé e defesa da vida nessa visão religiosa.The present article reviews some traditional bioethical topics from Jewish perspective, it gives answers derived from original sources, their subsequent exegesis and from Jewish legislation (Halajá, and it unveils relations among science, faith and defense of life according to this religious view.

On Deísmo. Another Case of Variation in Spanish Complementation

OpenAIRE

Camus Bergareche, Bruno

2013-01-01

El propòsit d’aquest treball és oferir una descripció suficient d’una construcció no normativa de l’espanyol actual coneguda amb el nom de deísmo. El deísmo es pot definir com l’ús de la preposició de davant d’una oració subordinada d’infinitiu, com ara No permito a mis hijos de llegar tarde ‘No permeto als meus fills arribar tard’. Aquesta estructura no és gens desconeguda en les variants cultes d’altres idiomes romànics, però en espanyol ha quedat confinada sobretot als dialectes meridional...

CoSMoMVPA: multi-modal multivariate pattern analysis of neuroimaging datain Matlab / GNU Octave

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Nikolaas N Oosterhof

2016-07-01

Full Text Available Recent years have seen an increase in the popularity of multivariate pattern (MVP analysis of functional magnetic resonance (fMRI data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens.CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species.It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques.CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality.CoSMo

Sonidegib, a novel smoothened inhibitor for the treatment of advanced basal cell carcinoma

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Doan HQ

2016-09-01

Full Text Available Hung Q Doan,1 Sirunya Silapunt,1 Michael R Migden2,3 1Department of Dermatology, University of Texas, McGovern Medical School, 2Mohs Surgery Unit, Department of Dermatology, 3Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Basal cell carcinoma (BCC is the most common nonmelanoma skin cancer. If left untreated, BCCs can become locally aggressive or even metastasize. Currently available treatments include local destruction, surgery, and radiation. Systemic options for advanced disease are limited. The Hedgehog (Hh pathway is aberrantly activated in a majority of BCCs and in other cancers. Hh pathway inhibitors are targeted agents that inhibit the aberrant activation of the Hh pathway, with smoothened being a targeted component. Sonidegib is a novel smoothened inhibitor that was recently approved by the US Food and Drug Administration. This review focuses on BCC pathogenesis and the clinical efficacy of sonidegib for the treatment of advanced BCC. Keywords: nonmelanoma skin cancer, Hedgehog pathway, clinical trials

ASC deficiency suppresses proliferation and prevents medulloblastoma incidence.

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Knight, E R W; Patel, E Y; Flowers, C A; Crowther, A J; Ting, J P; Miller, C R; Gershon, T R; Deshmukh, M

2015-01-15

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is silenced by promoter methylation in many types of tumors, yet ASC's role in most cancers remains unknown. Here, we show that ASC is highly expressed in a model of medulloblastoma, the most common malignant pediatric brain cancer; ASC is also expressed in human medulloblastomas. Importantly, while ASC deficiency did not affect normal cerebellar development, ASC knockout mice on the Smoothened (ND2:SmoA1) transgenic model of medulloblastoma exhibited a profound reduction in medulloblastoma incidence and a delayed tumor onset. A similar decrease in tumorigenesis with ASC deficiency was also seen in the hGFAP-Cre:SmoM2 mouse model of medulloblastoma. Interestingly, hyperproliferation of the external granule layer (EGL) was comparable at P20 in both wild-type and ASC-deficient SmoA1 mice. However, while the apoptosis and differentiation markers remained unchanged at this age, proliferation makers were decreased, and the EGL was reduced in thickness and area by P60. This reduction in proliferation with ASC deficiency was also seen in isolated SmoA1 cerebellar granule precursor cells in vitro, indicating that the effect of ASC deletion on proliferation was cell autonomous. Interestingly, ASC-deficient SmoA1 cerebella exhibited disrupted expression of genes in the transforming growth factor-β pathway and increased level of nuclear Smad3. Taken together, these results demonstrate an unexpected role for ASC in Sonic hedgehog-driven medulloblastoma tumorigenesis, thus identifying ASC as a promising novel target for antitumor therapy.

Generalized SMO algorithm for SVM-based multitask learning.

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Cai, Feng; Cherkassky, Vladimir

2012-06-01

Exploiting additional information to improve traditional inductive learning is an active research area in machine learning. In many supervised-learning applications, training data can be naturally separated into several groups, and incorporating this group information into learning may improve generalization. Recently, Vapnik proposed a general approach to formalizing such problems, known as "learning with structured data" and its support vector machine (SVM) based optimization formulation called SVM+. Liang and Cherkassky showed the connection between SVM+ and multitask learning (MTL) approaches in machine learning, and proposed an SVM-based formulation for MTL called SVM+MTL for classification. Training the SVM+MTL classifier requires the solution of a large quadratic programming optimization problem which scales as O(n(3)) with sample size n. So there is a need to develop computationally efficient algorithms for implementing SVM+MTL. This brief generalizes Platt's sequential minimal optimization (SMO) algorithm to the SVM+MTL setting. Empirical results show that, for typical SVM+MTL problems, the proposed generalized SMO achieves over 100 times speed-up, in comparison with general-purpose optimization routines.

Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

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Braun, Joerg E; Serebrov, Victor

2017-01-01

Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

Surface smoothening effects on growth of diamond films

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Reshi, Bilal Ahmad; Kumar, Shyam; Kartha, Moses J.; Varma, Raghava

2018-04-01

We have carried out a detailed study of the growth dynamics of the diamond film during initial time on diamond substrates. The diamond films are deposited using Microwave Plasma Chemical Vapor Deposition (MPCVD) method for different times. Surface morphology and its correlation with the number of hours of growth of thin films was invested using atomic force microscopy (AFM). Diamond films have smooth interface with average roughness of 48.6873nm. The initial growth dynamics of the thin film is investigated. Interestingly, it is found that there is a decrease in the surface roughness of the film. Thus a smoothening effect is observed in the grown films. The film enters into the growth regime in the later times. Our results also find application in building diamond detector.

Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation.

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Sasaki, Nobunari; Kurisu, Junko; Kengaku, Mineko

2010-12-01

The sonic hedgehog (Shh) pathway has essential roles in several processes during development of the vertebrate central nervous system (CNS). Here, we report that Shh regulates dendritic spine formation in hippocampal pyramidal neurons via a novel pathway that directly regulates the actin cytoskeleton. Shh signaling molecules Patched (Ptc) and Smoothened (Smo) are expressed in several types of postmitotic neurons, including cerebellar Purkinje cells and hippocampal pyramidal neurons. Knockdown of Smo induces dendritic spine formation in cultured hippocampal neurons independently of Gli-mediated transcriptional activity. Smo interacts with Tiam1, a guanine nucleotide exchange factor for Rac1, via its cytoplasmic C-terminal region. Inhibition of Tiam1 or Rac1 activity suppresses spine induction by Smo knockdown. Shh induces remodeling of the actin cytoskeleton independently of transcriptional activation in mouse embryonic fibroblasts. These findings demonstrate a novel Shh pathway that regulates the actin cytoskeleton via Tiam1-Rac1 activation. Copyright © 2010 Elsevier Inc. All rights reserved.

Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton.

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Long, Fanxin; Chung, Ung-il; Ohba, Shinsuke; McMahon, Jill; Kronenberg, Henry M; McMahon, Andrew P

2004-03-01

Indian hedgehog (Ihh) is indispensable for development of the osteoblast lineage in the endochondral skeleton. In order to determine whether Ihh is directly required for osteoblast differentiation, we have genetically manipulated smoothened (Smo), which encodes a transmembrane protein that is essential for transducing all Hedgehog (Hh) signals. Removal of Smo from perichondrial cells by the Cre-LoxP approach prevents formation of a normal bone collar and also abolishes development of the primary spongiosa. Analysis of chimeric embryos composed of wild-type and Smo(n/n) cells indicates that Smo(n/n) cells fail to contribute to osteoblasts in either the bone collar or the primary spongiosa but generate ectopic chondrocytes. In order to assess whether Ihh is sufficient to induce bone formation in vivo, we have analyzed the bone collar in the long bones of embryos in which Ihh was artificially expressed in all chondrocytes by the UAS-GAL4 bigenic system. Although ectopic Ihh does not induce overt ossification along the entire cartilage anlage, it promotes progression of the bone collar toward the epiphysis, suggesting a synergistic effect between ectopic Ihh and endogenous factors such as the bone morphogenetic proteins (BMPs). In keeping with this model, Hh signaling is further found to be required in BMP-induced osteogenesis in cultures of a limb-bud cell line. Taken together, these results demonstrate that Ihh signaling is directly required for the osteoblast lineage in the developing long bones and that Ihh functions in conjunction with other factors such as BMPs to induce osteoblast differentiation. We suggest that Ihh acts in vivo on a potential progenitor cell to promote osteoblast and prevent chondrocyte differentiation.

Adoção tardia: altruísmo, maturidade e estabilidade emocional

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Ebrahim Surama Gusmão

2001-01-01

Full Text Available A pesquisa teve por objetivo executar um estudo acerca das adoções tardias, comparando pais que realizaram adoções de crianças maiores de dois anos com pais que efetuaram adoções de bebês. Os principais elementos abordados foram: estado civil; idade; escolaridade; renda; presença de filhos biológicos; e motivações para a adoção. Investigaram-se também o altruísmo, a maturidade e a estabilidade emocional dos adotantes. A amostra consistiu de 27 adotantes tardios e 55 adotantes convencionais, participantes ou não de Grupos de Apoio à Adoção. O instrumento utilizado constou de um questionário sobre adoção; de questões sobre maturidade e estabilidade emocional; e de uma escala de altruísmo. Os resultados indicaram distinções referentes aos aspectos destacados. Os adotantes tardios apresentaram um nível sócio-econômico superior, um estado civil mais diferenciado, uma maior presença de filhos biológicos, e uma maturidade e estabilidade mais elevada. Quanto às motivações e ao altruísmo, apareceram diferenças significativas entre os dois grupos.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.

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Bakshi, Anshika; Chaudhary, Sandeep C; Rana, Mehtab; Elmets, Craig A; Athar, Mohammad

2017-12-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. © 2017 Wiley Periodicals, Inc.

Stenotrophomonas maltophilia responds to exogenous AHL signals through the LuxR solo SmoR (Smlt1839).

Science.gov (United States)

Martínez, Paula; Huedo, Pol; Martinez-Servat, Sònia; Planell, Raquel; Ferrer-Navarro, Mario; Daura, Xavier; Yero, Daniel; Gibert, Isidre

2015-01-01

Quorum Sensing (QS) mediated by Acyl Homoserine Lactone (AHL) molecules are probably the most widespread and studied among Gram-negative bacteria. Canonical AHL systems are composed by a synthase (LuxI family) and a regulator element (LuxR family), whose genes are usually adjacent in the genome. However, incomplete AHL-QS machinery lacking the synthase LuxI is frequently observed in Proteobacteria, and the regulator element is then referred as LuxR solo. It has been shown that certain LuxR solos participate in interspecific communication by detecting signals produced by different organisms. In the case of Stenotrophomonas maltophilia, a preliminary genome sequence analysis revealed numerous putative luxR genes, none of them associated to a luxI gene. From these, the hypothetical LuxR solo Smlt1839, here designated SmoR, presents a conserved AHL binding domain and a helix-turn-helix DNA binding motif. Its genomic organization-adjacent to hchA gene-indicate that SmoR belongs to the new family "LuxR regulator chaperone HchA-associated." AHL-binding assays revealed that SmoR binds to AHLs in-vitro, at least to oxo-C8-homoserine lactone, and it regulates operon transcription, likely by recognizing a conserved palindromic regulatory box in the hchA upstream region. Supplementation with concentrated supernatants from Pseudomonas aeruginosa, which contain significant amounts of AHLs, promoted swarming motility in S. maltophilia. Contrarily, no swarming stimulation was observed when the P. aeruginosa supernatant was treated with the lactonase AiiA from Bacillus subtilis, confirming that AHL contributes to enhance the swarming ability of S. maltophilia. Finally, mutation of smoR resulted in a swarming alteration and an apparent insensitivity to the exogenous AHLs provided by P. aeruginosa. In conclusion, our results demonstrate that S. maltophilia senses AHLs produced by neighboring bacteria through the LuxR solo SmoR, regulating population behaviors such as swarming

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

OpenAIRE

Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha; Vaidya, Vidita A.

2011-01-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and...

ABSENTEÍSMO: análise através do custo-efetividade

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Roberto Rodney Ferreira Junior

2017-06-01

Full Text Available Este artigo objetivou identificar por meio de indicadores, o custo-efetividade entre um absenteísmo organizacional existente e a medida adotada para superá-lo. Para a realização deste estudo, optou-se pela técnica metodológica da pesquisa bibliográfica, fundada na revisão de literatura. Com base nos textos selecionados e estudados. O resultado da pesquisa permitiu observar que tanto o atraso e a falta do trabalhador, por motivos intervenientes quanto às alternativas de superação adotadas, incorrem em custos para a empresa, necessitando, portanto, que o setor de finanças, analise e calcule o custo efetividade entre o absenteísmo existente e a medida de superação utilizada, para então identificar o custo-benefício e decidir pela alternativa mais adequada. Nesse aspecto, pôde-se concluir que a diferença entre o custo do absenteísmo e do custo da alternativa adotada, representará o custo-efetividade dos indicadores. Resta, portanto, analisar o custo-benefício de cada alternativa adotada em relação ao custo do absenteísmo, verificando a medida mais adequada a ser tomada.   This article aimed to identify, through indicators, the cost-effectiveness between an existing organizational absenteeism and the measure adopted to overcome it. For the accomplishment of this study, we opted for the methodological technique of bibliographical research, based on literature review, based on selected and studied texts. The result of the research allowed to observe that both the delay and the absences of the worker to work, due to intervening reasons and the adopted alternatives of overcoming, incur costs for the company, thus requiring that the finance sector analyzes and calculates the cost Effectiveness between existing absenteeism and the overcoming measure used, to identify the cost-benefit and decide on the most appropriate alternative. Thus, in this respect, it can be concluded that the difference between the cost of absenteeism and

CB-SMoT+: UNA EXTENSIÓN AL ALGORITMO CB-SMoT

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FRANCISCO MORENO

2012-12-01

Full Text Available Una trayectoria es un registro de la evoluciónde la posición de un objeto móvil. Por ejemplo,un vehículo que se mueve en el espacio durante unintervalo de tiempo. Una trayectoria se representamediante una secuencia de observaciones que indicanla posición y el tiempo en el que fue tomada cadaobservación. CB-SMoT es un algoritmo que identificalas partes de una trayectoria durante las cuales elobjeto mantuvo una velocidad promedio por debajode un límite dado. En este artículo se propone unaextensión para dicho algoritmo que permite identificarlas partes de una trayectoria durante las cualesel objeto mantuvo una velocidad promedio entre observacionespor debajo de un límite dado. Esto posibilitala identificación, por ejemplo, de violacionesa un límite de velocidad que no son advertidas porel algoritmo original. Para el estudio se usó el sistemade gestión de bases de datos PostgreSQL y losalgoritmos se implementaron en su lenguaje de programación,llamado PL/pgSQL. Además, se hicieronexperimentos con 100 trayectorias de vehículos conel propósito de mostrar la utilidad y la viabilidad de lapropuesta.

Overactivation of Hedgehog Signaling Alters Development of the Ovarian Vasculature in Mice1

Science.gov (United States)

Ren, Yi; Cowan, Robert G.; Migone, Fernando F.; Quirk, Susan M.

2012-01-01

ABSTRACT The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2cre/+SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2cre/+SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2cre/+SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately. PMID:22402963

PLURALISMO NA MODERNIDADE – E NO JUDAÍSMO DO SEGUNDO TEMPLO

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Edgard Leite

2012-09-01

Full Text Available O presente artigo foi apresentado na Mesa Redonda “Cristianismo, Judaísmo e Islamismo: fontes e aportes teóricos”, integrando o III Encontro do GT Nacional de História das Religiões e Religiosidades – ANPUH, na Universidade Federal de Santa Catarina (UFSC de 20 a 22 de Outubro de 2010.

Tamoxifen-inducible gene deletion reveals a distinct cell type associated with trabecular bone, and direct regulation of PTHrP expression and chondrocyte morphology by Ihh in growth region cartilage.

Science.gov (United States)

Hilton, Matthew J; Tu, Xiaolin; Long, Fanxin

2007-08-01

Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development by signaling to both chondrocytes and perichondrial cells. Previous efforts to delineate direct effects of Ihh on chondrocytes by Col2-Cre-mediated ablation of Smoothened (Smo, encoding a transmembrane protein indispensable for Ihh signaling) has been only partially successful, due to the inability to discriminate between chondrocytes and perichondrial cells. Here we report a transgenic line (Col2-Cre) expressing under the control of the Colalpha1(II) promoter an inert form of Cre that is activatable by exogenous tamoxifen (TM); TM administration at proper times during embryogenesis induced Cre activity in chondrocytes but not in the perichondrium. By using this mouse line, we deleted Smo within subsets of chondrocytes without affecting the perichondrium and found that Smo removal led to localized disruption of the expression of parathyroid hormone-related protein (PTHrP) and the morphology of chondrocytes. Unexpectedly, TM invariably induced Cre activity in a subset of cells associated with the trabecular bone surface of long bones. These cells, when genetically marked and cultured in vitro, were capable of producing bone nodules. Expression of the Col2-Cre transgene in these cells likely reflected the endogenous Colalpha1(II) promoter activity as similar cells were found to express the IIA isoform of Colalpha1(II) mRNA endogenously. In summary, the present study has not only provided evidence that Ihh signaling directly controls PTHrP expression and chondrocyte morphology in the growth region cartilage, but has also uncovered a distinct cell type associated with the trabecular bone that appears to possess osteogenic potential.

Os mentores intelectuais do confucionismo, do taoísmo e do hinduísmo na perspectiva weberiana

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Arilson Silva de Oliveira

2009-05-01

Full Text Available Resumo Analisaremos os literati confucionistas e taoístas (intelectuais chineses e os mestres brahmanas (intelectuais indianos, apresentados por Max Weber, no intuito de apreendermos as imagens de mundo religiosas nos "jardins intelectuais e encantados" da China e da Índia. Para tanto, temos como base as duas primeiras monografias que fazem parte da obra Gesammelte Aufsätse zur Religionssoziologie (Ensaios sobre sociologia da religião a propósito das religiões chinesas e indianas, as quais foram as primeiras a serem lançadas na série de sociologia comparativa das religiões mundiais de Weber. Verificamos que os intelectuais chineses contribuem para a preservação e continuidade de sua civilização, fortalecendo suas alianças com o Estado, enquanto os intelectuais indianos, na condição de agentes puramente religiosos, participam significativamente da integração cultural de seu país, preservando sua própria autonomia social. Palavras-chave: Confucionismo; Taoísmo; Hinduísmo; Intelectuais; Max Weber.Abstract This article analyzes the Confucian and Taoist literati (Chinese intellectuals and Brahmin masters (Indian intellectuals presented by Max Weber, in order to apprehend religious world images in the “enchanted intellectual gardens” of China and India. For such, the first two monographs which are part of the work entitled Gesammelte Aufsätse zur Religionssoziologie (Essays on the sociology of religion are considered in what concerns the Chinese and Indian religions, which were the first to be published in Weber’s world religions comparative sociology series. It was verified that Chinese intellectuals contribute to the preservation and continuity of their civilization, strengthening their alliances with the State, whereas Indian intellectuals, as purely religious agents, significantly take part in the process of the country’s cultural integration, preserving their own social autonomy. Key words: Confucianism; Taoism

Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

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Jain S

2017-03-01

Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

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Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

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Hyunjung Choi

Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Energy Technology Data Exchange (ETDEWEB)

Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-06-15

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

International Nuclear Information System (INIS)

Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

2017-01-01

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Removing Ocular Movement Artefacts by a Joint Smoothened Subspace Estimator

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Ronald Phlypo

2007-01-01

Full Text Available To cope with the severe masking of background cerebral activity in the electroencephalogram (EEG by ocular movement artefacts, we present a method which combines lower-order, short-term and higher-order, long-term statistics. The joint smoothened subspace estimator (JSSE calculates the joint information in both statistical models, subject to the constraint that the resulting estimated source should be sufficiently smooth in the time domain (i.e., has a large autocorrelation or self predictive power. It is shown that the JSSE is able to estimate a component from simulated data that is superior with respect to methodological artefact suppression to those of FastICA, SOBI, pSVD, or JADE/COM1 algorithms used for blind source separation (BSS. Interference and distortion suppression are of comparable order when compared with the above-mentioned methods. Results on patient data demonstrate that the method is able to suppress blinking and saccade artefacts in a fully automated way.

Monoteísmo e Intolerância Religiosa e Política

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Antonio Ozaí da Silva

2010-10-01

Full Text Available Este trabalho é uma reflexão sobre a relação entre monoteísmo e a intolerância religiosa e política presente na história. A premissa adotada afirma que os monoteísmos – judaico, cristão e islâmico – tendem a favorecer a intolerância entre os povos e em relação às opções religiosas e políticas dos indivíduos em suas respectivas nações. A dificuldade de aceitar o “outro” é, nessa perspectiva, inerente ao caráter monoteísta, isto é, à imposição de um Deus. A análise do politeísmo grego e da experiência monoteísta egípcia, resgatada por Freud, fornece elementos para pensarmos os monoteísmos que conhecemos.

Absenteísmo-doença segundo autorrelato de servidores públicos municipais em Belo Horizonte

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Celeste de Souza Rodrigues

2013-01-01

Full Text Available O objetivo do estudo é analisar o perfil de um conjunto de servidores públicos municipais que relataram, por ocasião de um inquérito, absenteísmo-doença nos últimos 12 meses. Em 2009 obteve-se uma amostra de 5.646 (14% do universo de 38.304 servidores municipais de Belo Horizonte. Um questionário foi disponibilizado em sítio da Internet, cuja entrada dependia do consentimento do respondente. Regressão de Poisson foi utilizada para determinar os fatores associados. A prevalência do absenteísmo-doença foi maior entre os servidores do sexo feminino (RP 1,12 e diminuiu com o aumento das faixas etárias: 30-39 anos (RP 0,79; 40-49 anos (RP 0,72; e 50 anos ou mais (RP 0,68. Absenteísmo-doença mostrou-se associado às atividades ligadas aos grupos de fiscalização e vigilância (RP 1,46, serviços gerais (RP 1,22, informação, educação e cultura (RP 1,50 e saúde (RP 1,50. As comorbidades mais presentes foram LER/Dort (RP 1,19, lombalgia (RP 1,16, depressão/ ansiedade (RP 1,20 e percepção de cansaço mental (RP 1,12. O relato de uso de medicação para depressão/ansiedade se mostrou fator protetor (RP 0,82. Maior probabilidade de transtorno mental (RP 1,23 segundo o SRQ20, insatisfação com a capacidade de trabalho (RP 1,08, condições razoáveis (RP 1,21 e condições precárias de trabalho (RP 1,19 foram associadas ao desfecho. Programas de promoção da saúde no trabalho visando a prevenção de comorbidades musculoesqueléticas e queixas psicossociais atenuariam as situações que provavelmente estão na origem do absenteísmo-doença.

GenBank blastx search result: AK241729 [KOME

Lifescience Database Archive (English)

Full Text Available AK241729 J065199L10 AF018073.1 AF018073 Rhodobacter sphaeroides operon regulator (smoC), periplasmic sorbito...l-binding protein (smoE), sorbitol/mannitol transport inner membrane protein (smoF), sorbitol.../mannitol transport inner membrane protein (smoG), sorbitol/mannitol transport ATP-binding transport protein (smoK), sorbit...ol dehydrogenase (smoS), mannitol dehydrogenase (mtlK),

GenBank blastx search result: AK240874 [KOME

Lifescience Database Archive (English)

Full Text Available AK240874 J065025K09 AF018073.1 AF018073 Rhodobacter sphaeroides operon regulator (smoC), periplasmic sorbito...l-binding protein (smoE), sorbitol/mannitol transport inner membrane protein (smoF), sorbitol.../mannitol transport inner membrane protein (smoG), sorbitol/mannitol transport ATP-binding transport protein (smoK), sorbit...ol dehydrogenase (smoS), mannitol dehydrogenase (mtlK),

GenBank blastx search result: AK243680 [KOME

Lifescience Database Archive (English)

Full Text Available AK243680 J100090I20 AF018073.1 AF018073 Rhodobacter sphaeroides operon regulator (smoC), periplasmic sorbito...l-binding protein (smoE), sorbitol/mannitol transport inner membrane protein (smoF), sorbitol.../mannitol transport inner membrane protein (smoG), sorbitol/mannitol transport ATP-binding transport protein (smoK), sorbit...ol dehydrogenase (smoS), mannitol dehydrogenase (mtlK),

GenBank blastx search result: AK061856 [KOME

Lifescience Database Archive (English)

Full Text Available AK061856 001-040-G03 AF018073.1 Rhodobacter sphaeroides operon regulator (smoC), periplasmic sorbitol...-binding protein (smoE), sorbitol/mannitol transport inner membrane protein (smoF), sorbitol.../mannitol transport inner membrane protein (smoG), sorbitol/mannitol transport ATP-binding transport protein (smoK), sorbitol

Single Directional SMO Algorithm for Least Squares Support Vector Machines

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Xigao Shao

2013-01-01

Full Text Available Working set selection is a major step in decomposition methods for training least squares support vector machines (LS-SVMs. In this paper, a new technique for the selection of working set in sequential minimal optimization- (SMO- type decomposition methods is proposed. By the new method, we can select a single direction to achieve the convergence of the optimality condition. A simple asymptotic convergence proof for the new algorithm is given. Experimental comparisons demonstrate that the classification accuracy of the new method is not largely different from the existing methods, but the training speed is faster than existing ones.

On Deísmo. Another Case of Variation in Spanish Complementation

OpenAIRE

Camus, Bruno

2013-01-01

The present paper is dedicated to study the non-standard Spanish construction known as deísmo. The construction can be defined as the use of the preposition de in front of subordinate infinite clauses like in the sentence No permito a mis hijos de llegar tarde ‘I do not allow my children to be late’. The phenomenon appears in other standard variants of Romance languages but in contemporary Spanish this construction seems confined to some southern peninsular dialects. In this study we analyse ...

Concepción de la Muerte en el Judaísmo

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Ana María Tapia-Adler

2008-06-01

Full Text Available El presente escrito, intentará presentar la concepción de la muerte en el judaísmo emanada de distintos textos fundamentales de la tradición judía. De allí que aparezcan en el mismo una serie de citas bíblicas, talmúdicas y una revisión de los ritos mortuorios que, en su mayor porcentaje están destinados a confortar a quienes continúan viviendo después de sufrir una pérdida.

Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

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Fecher LA

2015-11-01

Full Text Available Leslie A Fecher,1,3 William H Sharfman2 1Department of Internal Medicine and Dermatology, Indiana University Health Simon Cancer Center, Indianapolis, IN, USA; 2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3Department of Internal Medicine and Dermatology, University of Michigan, MI, USA Abstract: Cutaneous basal cell carcinoma (BCC is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449, a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. Keywords: basal cell carcinoma, hedgehog, smoothened, vismodegib, Gorlin, basal cell nevus syndrome

N-docosahexaenoylethanolamine regulates Hedgehog signaling and promotes growth of cortical axons

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Giorgi Kharebava

2015-12-01

Full Text Available Axonogenesis, a process for the establishment of neuron connectivity, is central to brain function. The role of metabolites derived from docosahexaenoic acid (DHA, 22:6n-3 that is specifically enriched in the brain, has not been addressed in axon development. In this study, we tested if synaptamide (N-docosahexaenoylethanolamine, an endogenous metabolite of DHA, affects axon growth in cultured cortical neurons. We found that synaptamide increased the average axon length, inhibited GLI family zinc finger 1 (GLI1 transcription and sonic hedgehog (Shh target gene expression while inducing cAMP elevation. Similar effects were produced by cyclopamine, a regulator of the Shh pathway. Conversely, Shh antagonized elevation of cAMP and blocked synaptamide-mediated increase in axon length. Activation of Shh pathway by a smoothened (SMO agonist (SAG or overexpression of SMO did not inhibit axon growth mediated by synaptamide or cyclopamine. Instead, adenylate cyclase inhibitor SQ22536 abolished synaptamide-mediated axon growth indicating requirement of cAMP elevation for this process. Our findings establish that synaptamide promotes axon growth while Shh antagonizes synaptamide-mediated cAMP elevation and axon growth by a SMO-independent, non-canonical pathway.

Evaluation of Semi-supervised Learning for Classification of Protein Crystallization Imagery.

Science.gov (United States)

Sigdel, Madhav; Dinç, İmren; Dinç, Semih; Sigdel, Madhu S; Pusey, Marc L; Aygün, Ramazan S

2014-03-01

In this paper, we investigate the performance of two wrapper methods for semi-supervised learning algorithms for classification of protein crystallization images with limited labeled images. Firstly, we evaluate the performance of semi-supervised approach using self-training with naïve Bayesian (NB) and sequential minimum optimization (SMO) as the base classifiers. The confidence values returned by these classifiers are used to select high confident predictions to be used for self-training. Secondly, we analyze the performance of Yet Another Two Stage Idea (YATSI) semi-supervised learning using NB, SMO, multilayer perceptron (MLP), J48 and random forest (RF) classifiers. These results are compared with the basic supervised learning using the same training sets. We perform our experiments on a dataset consisting of 2250 protein crystallization images for different proportions of training and test data. Our results indicate that NB and SMO using both self-training and YATSI semi-supervised approaches improve accuracies with respect to supervised learning. On the other hand, MLP, J48 and RF perform better using basic supervised learning. Overall, random forest classifier yields the best accuracy with supervised learning for our dataset.

Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis.

Science.gov (United States)

Lung, Shiu-Cheung; Liao, Pan; Yeung, Edward C; Hsiao, An-Shan; Xue, Yan; Chye, Mee-Len

2017-07-01

Fatty acids (FAs) and sterols are primary metabolites that exert interrelated functions as structural and signaling lipids. Despite their common syntheses from acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis ( Arabidopsis thaliana ) acyl-coenzyme A-binding proteins (ACBPs) are involved in FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dα1 and regulates phospholipid composition. Here, its specific role in the negative modulation of sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their strong promoter activities in developing ovules. Gas chromatography-mass spectrometry revealed quantitative and compositional changes in FAs and sterols upon overexpression or mutation of ACBP1 and/or SMO1-1 Aberrant levels of these metabolites may account for the downstream defect in lipid signaling. GLABRA2 ( GL2 ), encoding a phospholipid/sterol-binding homeodomain transcription factor, was up-regulated in developing seeds of acbp1 , smo1-1 , and ACBP1 +/- smo1-1 in comparison with the wild type. Consistent with the corresponding transcriptional alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were phenocopied in ACBP1 +/- smo1-1 Thus, ACBP1 appears to modulate the metabolism of two important lipid classes (FAs and sterols) influencing cellular signaling. © 2017 American Society of Plant Biologists. All Rights Reserved.

Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis1[OPEN

Science.gov (United States)

Hsiao, An-Shan; Xue, Yan

2017-01-01

Fatty acids (FAs) and sterols are primary metabolites that exert interrelated functions as structural and signaling lipids. Despite their common syntheses from acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis (Arabidopsis thaliana) acyl-coenzyme A-binding proteins (ACBPs) are involved in FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dα1 and regulates phospholipid composition. Here, its specific role in the negative modulation of sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their strong promoter activities in developing ovules. Gas chromatography-mass spectrometry revealed quantitative and compositional changes in FAs and sterols upon overexpression or mutation of ACBP1 and/or SMO1-1. Aberrant levels of these metabolites may account for the downstream defect in lipid signaling. GLABRA2 (GL2), encoding a phospholipid/sterol-binding homeodomain transcription factor, was up-regulated in developing seeds of acbp1, smo1-1, and ACBP1+/−smo1-1 in comparison with the wild type. Consistent with the corresponding transcriptional alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were phenocopied in ACBP1+/−smo1-1. Thus, ACBP1 appears to modulate the metabolism of two important lipid classes (FAs and sterols) influencing cellular signaling. PMID:28500265

Europeísmo y catolicismo en el discurso cultural y político catalán de la posguerra

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Carles Santacana i Torres

2016-09-01

Full Text Available Entre los elementos que configuran la reelaboración del discurso democrático en la posguerra, tienen un papel relevante la redefinición del catolicismo y un nuevo concepto de europeísmo. En el primer caso se trata de la adecuación del cristianismo a una concepción de sociedad democrática, que arranca de la introducción de pensadores católicos europeos a través de publicaciones y grupos que rompen con el nacionalcatolicismo. Por otra parte, el europeísmo define un discurso de identificación con la democracia y la libertad que adquiere todo su contenido en el contexto de la Guerra Fría, y que será un punto de encuentro para las diferentes corrientes democráticas.

Hazardous Traffic Event Detection Using Markov Blanket and Sequential Minimal Optimization (MB-SMO

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Lixin Yan

2016-07-01

Full Text Available The ability to identify hazardous traffic events is already considered as one of the most effective solutions for reducing the occurrence of crashes. Only certain particular hazardous traffic events have been studied in previous studies, which were mainly based on dedicated video stream data and GPS data. The objective of this study is twofold: (1 the Markov blanket (MB algorithm is employed to extract the main factors associated with hazardous traffic events; (2 a model is developed to identify hazardous traffic event using driving characteristics, vehicle trajectory, and vehicle position data. Twenty-two licensed drivers were recruited to carry out a natural driving experiment in Wuhan, China, and multi-sensor information data were collected for different types of traffic events. The results indicated that a vehicle’s speed, the standard deviation of speed, the standard deviation of skin conductance, the standard deviation of brake pressure, turn signal, the acceleration of steering, the standard deviation of acceleration, and the acceleration in Z (G have significant influences on hazardous traffic events. The sequential minimal optimization (SMO algorithm was adopted to build the identification model, and the accuracy of prediction was higher than 86%. Moreover, compared with other detection algorithms, the MB-SMO algorithm was ranked best in terms of the prediction accuracy. The conclusions can provide reference evidence for the development of dangerous situation warning products and the design of intelligent vehicles.

O IMPACTO DA ROTATIVIDADE E DO ABSENTEÍSMO DE PESSOAL SOBRE O CUSTO DO PRODUTO: UM ESTUDO EM UMA INDÚSTRIA GAÚCHA.

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Mauricio Farias Cardoso

2013-04-01

Full Text Available O objetivo deste estudo é analisar o impacto da rotatividade e absenteísmo de pessoal sobre o custo do produto em uma indústria gaúcha.  Para tanto, realizou-se um estudo de caso, que envolveu a participação de uma empresa multinacional, com unidade produtiva no estado do Rio Grande do Sul. Os dados foram coletados no período de 2011, por meio de entrevista semiestruturada com a responsável pelo setor de recursos humanos e também com supervisora de controladoria da empresa. Além das entrevistas foram analisados documentos contábeis e relatórios gerenciais de custos e de recursos humanos. O estudo limitou-se a analisar o produto de maior giro e o setor com maior índice de rotatividade e absenteísmo na empresa. Neste estudo foi possível demonstrar que a rotatividade e o absenteísmo apresentados pelo setor tiveram impacto relevante sobre o custo do produto analisado, diminuindo os resultados proporcionados pela venda deste produto nos períodos em que o custo apresentou maior elevação. 

Chemical Denaturants Smoothen Ruggedness on the Free Energy Landscape of Protein Folding.

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Malhotra, Pooja; Jethva, Prashant N; Udgaonkar, Jayant B

2017-08-08

To characterize experimentally the ruggedness of the free energy landscape of protein folding is challenging, because the distributed small free energy barriers are usually dominated by one, or a few, large activation free energy barriers. This study delineates changes in the roughness of the free energy landscape by making use of the observation that a decrease in ruggedness is accompanied invariably by an increase in folding cooperativity. Hydrogen exchange (HX) coupled to mass spectrometry was used to detect transient sampling of local energy minima and the global unfolded state on the free energy landscape of the small protein single-chain monellin. Under native conditions, local noncooperative openings result in interconversions between Boltzmann-distributed intermediate states, populated on an extremely rugged "uphill" energy landscape. The cooperativity of these interconversions was increased by selectively destabilizing the native state via mutations, and further by the addition of a chemical denaturant. The perturbation of stability alone resulted in seven backbone amide sites exchanging cooperatively. The size of the cooperatively exchanging and/or unfolding unit did not depend on the extent of protein destabilization. Only upon the addition of a denaturant to a destabilized mutant variant did seven additional backbone amide sites exchange cooperatively. Segmentwise analysis of the HX kinetics of the mutant variants further confirmed that the observed increase in cooperativity was due to the smoothing of the ruggedness of the free energy landscape of folding of the protein by the chemical denaturant.

Más allá del dequeísmo en cláusulas sustantivas: el caso de por más de que

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María Soledad Funes

2011-11-01

Full Text Available Las principales teorías sobre dequeísmo comparten el supuesto de que la preposición de carece de significado delante del conector que. A su vez, en el análisis de las conexiones concesivas propuesto por diversas gramáticas no se realizan diferenciaciones sintáctico-semánticas entre conectores como aunque; si bien y por más que. Desde la Gramática Cognitiva, se sostiene que toda elección del hablante es significativa y que hay motivación tanto para la presencia de la preposición en contextos del tipo “yo creía de que no era posible”, como respecto de la elección de un conector concesivo u otro en usos interclausales. En el presente trabajo, se propone ampliar el estudio del dequeísmo a partir del análisis de la locución concesiva por más de que. La presencia de la preposición de en esta locución está motivada por los mismos factores de distancia y defocalización que motivan el dequeísmo en contextos de subordinación sustantiva. 

INTERCONEXIÓN HOMBRE-MENTE-NATURALEZA DESDE EL TAOÍSMO UNA MIRADA DESDE EL YIN-YANG

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José Arlés Gómez Arévalo

2006-01-01

Full Text Available El presente artículo, corresponde al proyecto investigativo “Ciencia-espiritualidad”, que indaga, entre otros aspectos, por las conexiones que se establecen entre el mundo de la ciencia occidental y las antiguas tradiciones del Lejano Oriente, más concretamente por el aporte del hinduismo, del budismo y del taoísmo en la comprensión de las problemáticas del hombre contemporáneo. En esta investigación, se hace un análisis del taoísmo, tradición de la antigua civilización China y sus conexiones con la reflexión occidental sobre la energía, la mente humana y la naturaleza. En el pensamiento taoísta, hay una visión de unidad indisoluble entre hombre y naturaleza. El hombre mismo hace parte de la unidad del cosmos: él mismo es naturaleza. Desde esta perspectiva, se analizan algunos de los aportes que esta milenaria tradición hace a la investigación actual sobre ciencia y espiritualidad y a la comprensión de nuevos discursos que se constituyen en temas fronterizos entre la fe y la ciencia contemporánea.

Freud e o judaísmo: luto, trauma e transmissão

OpenAIRE

Indursky, Alexei Conte; Kveller, Daniel Boianovsky

2017-01-01

Resumo Este artigo almeja discutir a relação entre o conceito de transmissão na psicanálise e a posição do judaísmo no desejo de Freud. Interessa-nos compreender a operação subjetiva pela qual é possível tornar-se herdeiro, partindo do pressuposto de que a própria obra freudiana testemunha o modo como seu autor pôde apropriar-se da herança, tanto da cultura judaica quanto de sua genealogia familiar. Para isso, examinaremos a escritura de três de seus textos em contraponto a suas experiências ...

Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

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Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

2011-05-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

Absenteísmo por transtornos mentais em trabalhadores de saúde em um hospital no sul do Brasil

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Leni de Lima Santana

Full Text Available RESUMO Objetivo Descrever o perfil de adoecimento por transtornos mentais e comportamentais em trabalhadores de saúde de um hospital de ensino no sul do Brasil. Métodos pesquisa quantitativa, epidemiológica transversal retrospectiva cuja coleta de dados ocorreu por meio de documentos institucionais utilizados para alimentar o Sistema de Monitoramento da Saúde do Trabalhador de Enfermagem e envolveu todos os afastamentos ocorridos em 2011. Resultados Foram contabilizados 55 registros de afastamentos por Transtornos Mentais e Comportamentais que totalizaram 317 dias de absenteísmo. Os Técnicos de Enfermagem foram os profissionais mais afastados com o equivalente a 29,09% dos registros. As Unidades de Terapia Intensiva representaram os setores com o maior número de dias de absenteísmo, totalizando 81% e os Episódios depressivos obtiveram a frequência mais significativa, 52,72% dos transtornos mentais. Conclusão Os resultados evidenciaram que os transtornos mentais em trabalhadores de saúde constituem uma realidade preocupante que necessitam urgentemente de intervenções.

Underwater acoustic positioning system for the SMO and KM3NeT - Italia projects

Energy Technology Data Exchange (ETDEWEB)

Viola, S.; Barbagallo, G.; Cacopardo, G.; Calí, C.; Cocimano, R.; Coniglione, R.; Costa, M.; Cuttone, G.; D' Amato, C.; D' Amato, V.; D' Amico, A.; De Luca, V.; Del Tevere, F.; Distefano, C.; Ferrera, F.; Gmerk, A.; Grasso, R.; Imbesi, M.; Larosa, G.; Lattuada, D. [INFN - Laboratori Nazionali del Sud, via Santa Sofia 62, 95125 Catania (Italy); and others

2014-11-18

In the underwater neutrino telescopes, the positions of the Cherenkov light sensors and their movements must be known with an accuracy of few tens of centimetres. In this work, the activities of the SMO and KM3NeT-Italia teams for the development of an acoustic positioning system for KM3NeT-Italia project are presented. The KM3NeT-Italia project foresees the construction, within two years, of 8 towers in the view of the several km{sup 3}-scale neutrino telescope KM3NeT.

Underwater acoustic positioning system for the SMO and KM3NeT - Italia projects

International Nuclear Information System (INIS)

Viola, S.; Barbagallo, G.; Cacopardo, G.; Calí, C.; Cocimano, R.; Coniglione, R.; Costa, M.; Cuttone, G.; D'Amato, C.; D'Amato, V.; D'Amico, A.; De Luca, V.; Del Tevere, F.; Distefano, C.; Ferrera, F.; Gmerk, A.; Grasso, R.; Imbesi, M.; Larosa, G.; Lattuada, D.

2014-01-01

In the underwater neutrino telescopes, the positions of the Cherenkov light sensors and their movements must be known with an accuracy of few tens of centimetres. In this work, the activities of the SMO and KM3NeT-Italia teams for the development of an acoustic positioning system for KM3NeT-Italia project are presented. The KM3NeT-Italia project foresees the construction, within two years, of 8 towers in the view of the several km 3 -scale neutrino telescope KM3NeT

Validation of the "SmoCess-GP" instrument - a short patient questionnaire for assessing the smoking cessation activities of general practitioners: a cross-sectional study

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Wolf Jürgen

2010-02-01

Full Text Available Abstract Background We developed an instrument assessing the extent of smoking cessation activities by general practitioners (GPs within the Cologne Smoking Study (CoSmoS. The objective of the present study was to examine further psychometric quality of the "SmoCess-GP" instrument (Smoking Cessation by General Practitioners. Methods 127 current smokers who had participated in the Cologne Smoking Study (CoSmoS were included in our analyses. Confirmatory factor analysis (CFA was conducted to examine the model fit and to retest the single-factor structure of the instrument using the Mplus software. Further construct validity was tested with bivariate analysis using an instrument which measures patients' trust in physicians. Results CFA supported the unidimensional structure of the instrument. The factor loadings exceed the threshold of ≥ 0.50. All indicator reliabilities were higher than 0.30. The composite reliability was 0.86 and the average variance extracted (AVE resulted in a value of 0.50. The calculation of global fit indices identified a CFI value of 1.00 and for TLI a value of 1.02. The root mean square error of approximation (RMSEA indicates that 0% of the information is not accounted for by the model. The chi-square value was χ2df = 6 = 4.63 (p = 0.59. Analysis of discriminant validity resulted in a non-significiant correlation of r = 0.092 (p = 0.350. Conclusions Results indicate preliminary evidence for the construct validity of the "SmoCess-GP" instrument which therefore appears to be a promising tool for analyzing the extent of smoking cessation advice offered by GPs from the patients' perspective. Future research should examine the psychometric properties in a population based sample, further improvements of the instrument and should apply other methods of validation.

O monoteísmo islâmico

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Antonio Ozaí da Silva

2010-12-01

Full Text Available A proposta deste artigo é analisar a as origens e fundamentos da fé monoteísta islâmica, sua singularidade e o significado do Profeta Maomé enquanto modelo religioso, moral e político para a conduta dos muçulmanos. O objetivo é contribuir para a reflexão crítica sobre o Islamismo, para além dos preconceitos lingüísticos, políticos e culturais alimentados por setores da mídia ocidental, a qual tende a restringir o islamismo à vertente fundamentalista. As religiões monoteístas têm os seus fundamentalismos e suas “guerras justas”. E, no que diz respeito ao monoteísmo, as religiões não diferem em sua essência, já que se fundamentam na crença no Deus Único. Objetiva-se, ainda, instigar a análise sobre as relações entre religião e política, um tema polêmico em todas as crenças monoteístas.

Especulación, sentimiento y escisión en el joven Fichte: Análisis de sus Aforismos sobre religión y deísmo

OpenAIRE

Solé, María Jimena

2016-01-01

Este artículo propone un análisis de los Aforismos sobre religión y deísmo escritos por J. G. Fichte en 1790, poco antes de su conversión a la filosofía kantiana. Sostenemos que este texto no expresa la adhesión de Fichte al determinismo, ni al punto de vista del corazón, ni tampoco se limita a presentar la religión y el deísmo como dos sistemas opuestos. Según nuestra interpretación, Fichte defiende dos tesis. En primer lugar, que la mezcla de ambos sistemas es inaceptable y hay que respetar...

Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice.

Science.gov (United States)

Patel, Sita Sharan; Mahindroo, Neeraj; Udayabanu, Malairaman

2016-10-01

The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25-30g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350mg/kg, p.o.) (CUS+HYP), group IV received Hypericum perforatum extract (350mg/kg, p.o.) (CTRL+HYP); group V was subjected to CUS and received UD extract (50mg/kg, p.o.) (CUS+UD), group VI received UD extract (50mg/kg, p.o.) (CTRL+UD). CUS significantly induced body weight loss (p<0.05) and associative memory impairment in step down task (p<0.05) as compared to control mice. CUS significantly downregulated Smo (p<0.05), Gli1 (p<0.01), cyclin D1 (p<0.05), BDNF (p<0.01), TrKB (p<0.01) and MAPK1 (p<0.01) mRNA expression in hippocampus as compared to control mice. CUS significantly increased the levels of TBARS (p<0.01) and nitric oxide (p<0.001), and decreased catalase (p<0.001) and total thiol (p<0.01) in plasma resulting in oxidative stress and inflammation. Chronic UD administration significantly reverted CUS mediated body weight loss (p<0.05) and cognitive impairment (p<0.05). UD administration significantly decreased the levels of TBARS (p<0.01) and nitric oxide (p<0.05), and increased the levels of catalase (p<0.01) and total thiol (p<0.05) in plasma. Chronic UD administration significantly upregulated hippocampal Smo (p<0.05), Gli1 (p<0.001), cyclin D1 (p<0.05), BDNF (p<0.05), TrKB (p<0.05) and MAPK1 (p<0.05) in stressed mice. Further, UD extract did not reverse cyclopamine induced downregulation of Gli1 and Ptch1 mRNA in hippocampal slices. UD modulated Smo-Gli1 pathway in the hippocampus as well as exerted anti-inflammatory and antioxidant effects. UD extract might prove

Development of the Coastal Storm Modeling System (CoSMoS) for predicting the impact of storms on high-energy, active-margin coasts

Science.gov (United States)

Barnard, Patrick; Maarten van Ormondt,; Erikson, Li H.; Jodi Eshleman,; Hapke, Cheryl J.; Peter Ruggiero,; Peter Adams,; Foxgrover, Amy C.

2014-01-01

The Coastal Storm Modeling System (CoSMoS) applies a predominantly deterministic framework to make detailed predictions (meter scale) of storm-induced coastal flooding, erosion, and cliff failures over large geographic scales (100s of kilometers). CoSMoS was developed for hindcast studies, operational applications (i.e., nowcasts and multiday forecasts), and future climate scenarios (i.e., sea-level rise + storms) to provide emergency responders and coastal planners with critical storm hazards information that may be used to increase public safety, mitigate physical damages, and more effectively manage and allocate resources within complex coastal settings. The prototype system, developed for the California coast, uses the global WAVEWATCH III wave model, the TOPEX/Poseidon satellite altimetry-based global tide model, and atmospheric-forcing data from either the US National Weather Service (operational mode) or Global Climate Models (future climate mode), to determine regional wave and water-level boundary conditions. These physical processes are dynamically downscaled using a series of nested Delft3D-WAVE (SWAN) and Delft3D-FLOW (FLOW) models and linked at the coast to tightly spaced XBeach (eXtreme Beach) cross-shore profile models and a Bayesian probabilistic cliff failure model. Hindcast testing demonstrates that, despite uncertainties in preexisting beach morphology over the ~500 km alongshore extent of the pilot study area, CoSMoS effectively identifies discrete sections of the coast (100s of meters) that are vulnerable to coastal hazards under a range of current and future oceanographic forcing conditions, and is therefore an effective tool for operational and future climate scenario planning.

Angle Integrated Photoemission Study of SmO0.85F0.15FeAs

International Nuclear Information System (INIS)

Hong-Wei, Ou; Jia-Feng, Zhao; Yan, Zhang; Da-Wei, Shen; Bo, Zhou; Le-Xian, Yang; Cheng, He; Fei, Chen; Min, Xu; Yan, Chen; Dong-Lai, Feng; Tao, Wu; Xian-Hui, Chen

2008-01-01

The electronic structure of the new superconductor SmO 1-x F x FeAs (x = 0.15) is studied by angle-integrated photoemission spectroscopy. Our data show a sharp feature very close to the Fermi energy, and a relative flat distribution of the density of states between 0.5eV and 3eV binding energy, which agrees well with the band structure calculations considering an antiferromagnetic ground state. No noticeable gap opening is observed at 12K below the superconducting transition temperature, indicating the existence of large ungapped regions in the Brillouin zone. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma.

Directory of Open Access Journals (Sweden)

Robert C Castellino

Full Text Available BACKGROUND: Recent publications have described an important role for cross talk between PI-3 kinase and sonic hedgehog signaling pathways in the pathogenesis of medulloblastoma. METHODOLOGY/PRINCIPAL FINDINGS: We crossed mice with constitutive activation of Smoothened, SmoA1, with Pten deficient mice. Both constitutive and conditional Pten deficiency doubled the incidence of mice with symptoms of medulloblastoma and resulted in decreased survival. Analysis revealed a clear separation of gene signatures, with up-regulation of genes in the PI-3 kinase signaling pathway, including downstream activation of angiogenesis in SmoA1+/-; Pten +/- medulloblastomas. Western blotting and immunohistochemistry confirmed reduced or absent Pten, Akt activation, and increased angiogenesis in Pten deficient tumors. Down-regulated genes included genes in the sonic hedgehog pathway and tumor suppressor genes. SmoA1+/-; Pten +/+ medulloblastomas appeared classic in histology with increased proliferation and diffuse staining for apoptosis. In contrast, Pten deficient tumors exhibited extensive nodularity with neuronal differentiation separated by focal areas of intense staining for proliferation and virtually absent apoptosis. Examination of human medulloblastomas revealed low to absent PTEN expression in over half of the tumors. Kaplan-Meier analysis confirmed worse overall survival in patients whose tumor exhibited low to absent PTEN expression. CONCLUSIONS/SIGNIFICANCE: This suggests that PTEN expression is a marker of favorable prognosis and mouse models with activation of PI-3 kinase pathways may be important tools for preclinical evaluation of promising agents for the treatment of medulloblastoma.

Absenteísmo na enfermagem: uma revisão integrativa Absentismo en enfermería: una revisión integrativa Absenteeism in nursing: an integrative review

Directory of Open Access Journals (Sweden)

Michele Cristiene Nachtigall Barboza Martinato

2010-03-01

Full Text Available O absenteísmo na enfermagem é um problema de extrema preocupação, o qual interfere no cuidado ao cliente, sobrecarrega os demais integrantes da equipe e pode levar ao adoecimento. Objetiva-se neste estudo conhecer as produções científicas nacionais, resumos de artigos, publicados no período de 2003 a 2008, abrangendo o tema absenteísmo dos profissionais de enfermagem. Realizou-se uma busca on-line, nas bases de dados: LILACS, SciELO, BDENF e Portal CAPES. Da análise emergiram dois temas: Doenças que geram o absenteísmo nos profissionais de enfermagem; e Estratégias criadas para minimizar o absenteísmo. Concluiu-se que os profissionais de enfermagem são acometidos por inúmeros problemas de saúde, sendo uma das causas do absenteísmo. Destacaram-se as estratégias do dimensionamento de pessoal e as ações preventivas como modos de estabelecerem melhores condições de trabalho, minimizando o absenteísmo.El absentismo en la enfermería es un asunto de extrema preocupación, interferir con el cuidado del cliente, abruma a los otros miembros del equipo y puede conducir a la enfermedad. El objetivo de este estudio fue conocer la producción científica nacional, los resúmenes de artículos publicados desde 2003 hasta 2008, que abarca el tema de ausentismo de los profesionales de enfermería. Llevó a cabo una búsqueda en línea, en bases de datos: LILACS, SciELO, BDENF y el Portal de la CAPES. El análisis surgieron dos temas: Las enfermedades que generan en el ausentismo de los profesionales de enfermería, y las estrategias destinadas a reducir el absentismo. Llegó a la conclusión de que las enfermeras se ven afectados por numerosos problemas de salud, una de las causas de ausentismo. Destacó las estrategias para el diseño de las acciones personales y de prevención como la manera de establecer mejores condiciones de trabajo, reduciendo al mínimo el absentismo.Absenteeism in nursing staff is a matter of great concern. It

A 7-mer knowledge-based potential for detecting native protein structures from decoys

DEFF Research Database (Denmark)

Røgen, Peter

for faster sampling methods. Background: The C-alpha atoms define a polygonal curve in 3-space which is smoothened by the method presented in [1] and is illustrated below. The geometry of a 7-mer is described by two numbers that describe how stretched and curved the smoothening of the 7-mer is. These two...... numbers are called length and distance excess, c.f. [2], and give one point in the length - distance excess - plane, LDE-plane. Method: Given a sequence of amino acids, we break it down to all its 7-mers and search a database of known 3d-structures for similar 7-mer sequences. For the query 7-mer we...... define an energy function in the LDE-plane. This energy is given by the 7-mer found and depends linearly on some design parameters. The energy function of the full query sequence, F, is then a sum over all 7-mers. For a protein P and a decoy D we ideally want F(D)-F(P)=constant.RMSD( D , P ), where 0...

Projected 21st century coastal flooding in the Southern California Bight. Part 1: Development of the third generation CoSMoS model

Science.gov (United States)

O'Neill, Andrea; Erikson, Li; Barnard, Patrick; Limber, Patrick; Vitousek, Sean; Warrick, Jonathan; Foxgrover, Amy C.; Lovering, Jessica

2018-01-01

Due to the effects of climate change over the course of the next century, the combination of rising sea levels, severe storms, and coastal change will threaten the sustainability of coastal communities, development, and ecosystems as we know them today. To clearly identify coastal vulnerabilities and develop appropriate adaptation strategies due to projected increased levels of coastal flooding and erosion, coastal managers need local-scale hazards projections using the best available climate and coastal science. In collaboration with leading scientists world-wide, the USGS designed the Coastal Storm Modeling System (CoSMoS) to assess the coastal impacts of climate change for the California coast, including the combination of sea-level rise, storms, and coastal change. In this project, we directly address the needs of coastal resource managers in Southern California by integrating a vast range of global climate change projections in a thorough and comprehensive numerical modeling framework. In Part 1 of a two-part submission on CoSMoS, methods and the latest improvements are discussed, and an example of hazard projections is presented.

Da compaixão à inocência: Nietzsche e Schopenhauer em torno da questão do egoísmo = From compassion to innocence: Nietzsche and Schopenhauer around the issue of selfishness

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Oliveira, Jelson Roberto de

2015-01-01

Full Text Available Pretende-se demonstrar nesse trabalho como Nietzsche formula, nos escritos que formam o segundo período de sua produção filosófica, uma crítica à moral da compaixão proposta por Schopenhauer. Para isso, far-se-á uma revisão das teses schopenhaurianas segundo as quais o egoísmo é o motivo antimoral por excelência e, contrariamente, o altruísmo é a base legítima da moralidade. Analisar-se-á, também, o procedimento usado por Nietzsche para, de um lado, criticar esse ideal e, de outro, chegar à inocência como principal resultado de seu programa filosófico

Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

Science.gov (United States)

Fecher, Leslie A; Sharfman, William H

2015-01-01

Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

Una aproximación al tema de “judaísmo y política” desde las fuentes

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Ana María Tapia-Adler

2007-03-01

Full Text Available En esta presentación el análisis está centrado en el Judaísmo y las relaciones de poder que se dieron en su interior en la antigüedad. Se enfatiza la relación entre el poder político y el religioso considerando el papel de reyes, sacerdotes y profetas, en los primeros tiempos y cómo fue variando en el transcurso de la historia, después de la desaparición de la profecía en Israel y la destrucción del Segundo Templo.

Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures

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Dong Hongmei

2010-12-01

Full Text Available Abstract Background Hedgehog (HH signaling is critical for the expansion of granule neuron precursors (GNPs within the external granular layer (EGL during cerebellar development. Aberrant HH signaling within GNPs is thought to give rise to medulloblastoma (MB - the most commonly-observed form of malignant pediatric brain tumor. Evidence in both invertebrates and vertebrates indicates that cyclic AMP-dependent protein kinase A (PKA antagonizes HH signalling. Receptors specific for the neuropeptide pituitary adenylyl cyclase activating polypeptide (PACAP, gene name ADCYAP1 are expressed in GNPs. PACAP has been shown to protect GNPs from apoptosis in vitro, and to interact with HH signaling to regulate GNP proliferation. PACAP/ptch1 double mutant mice exhibit an increased incidence of MB compared to ptch1 mice, indicating that PACAP may regulate HH pathway-mediated MB pathogenesis. Methods Primary MB tumorsphere cultures were prepared from thirteen ptch1+/-/p53+/- double mutant mice and treated with the smoothened (SMO agonist purmorphamine, the SMO antagonist SANT-1, the neuropeptide PACAP, the PKA activator forskolin, and the PKA inhibitor H89. Gene expression of gli1 and [3H]-thymidine incorporation were assessed to determine drug effects on HH pathway activity and proliferation, respectively. PKA activity was determined in cell extracts by Western blotting using a phospho-PKA substrate antibody. Results Primary tumor cells cultured for 1-week under serum-free conditions grew as tumorspheres and were found to express PAC1 receptor transcripts. Gli1 gene expression was significantly reduced by SANT-1, PACAP and forskolin, but was unaffected by purmorphamine. The attenuation of gli1 gene expression by PACAP was reversed by the PKA inhibitor H89, which also blocked PKA activation. Treatment of tumorsphere cultures with PACAP, forskolin, and SANT-1 for 24 or 48 hours reduced proliferation. Conclusions Primary tumorspheres derived from ptch1+/-/p53

Pituitary adenylyl cyclase activating polypeptide inhibits gli1 gene expression and proliferation in primary medulloblastoma derived tumorsphere cultures

International Nuclear Information System (INIS)

Cohen, Joseph R; Resnick, Daniel Z; Niewiadomski, Pawel; Dong, Hongmei; Liau, Linda M; Waschek, James A

2010-01-01

Hedgehog (HH) signaling is critical for the expansion of granule neuron precursors (GNPs) within the external granular layer (EGL) during cerebellar development. Aberrant HH signaling within GNPs is thought to give rise to medulloblastoma (MB) - the most commonly-observed form of malignant pediatric brain tumor. Evidence in both invertebrates and vertebrates indicates that cyclic AMP-dependent protein kinase A (PKA) antagonizes HH signalling. Receptors specific for the neuropeptide pituitary adenylyl cyclase activating polypeptide (PACAP, gene name ADCYAP1) are expressed in GNPs. PACAP has been shown to protect GNPs from apoptosis in vitro, and to interact with HH signaling to regulate GNP proliferation. PACAP/ptch1 double mutant mice exhibit an increased incidence of MB compared to ptch1 mice, indicating that PACAP may regulate HH pathway-mediated MB pathogenesis. Primary MB tumorsphere cultures were prepared from thirteen ptch1 +/- /p53 +/- double mutant mice and treated with the smoothened (SMO) agonist purmorphamine, the SMO antagonist SANT-1, the neuropeptide PACAP, the PKA activator forskolin, and the PKA inhibitor H89. Gene expression of gli1 and [ 3 H]-thymidine incorporation were assessed to determine drug effects on HH pathway activity and proliferation, respectively. PKA activity was determined in cell extracts by Western blotting using a phospho-PKA substrate antibody. Primary tumor cells cultured for 1-week under serum-free conditions grew as tumorspheres and were found to express PAC1 receptor transcripts. Gli1 gene expression was significantly reduced by SANT-1, PACAP and forskolin, but was unaffected by purmorphamine. The attenuation of gli1 gene expression by PACAP was reversed by the PKA inhibitor H89, which also blocked PKA activation. Treatment of tumorsphere cultures with PACAP, forskolin, and SANT-1 for 24 or 48 hours reduced proliferation. Primary tumorspheres derived from ptch1 +/- /p53 +/- mice exhibit constitutive HH pathway activity

Nutritional Status Assessment (SMO 016E)

Science.gov (United States)

Smith, S. M.; Zwart, S. R.; Heer, M.; Ericson, K.; Coburn, S. P.; Booth, S. A.; Jones, J. A.; Lupton, J.

2009-01-01

Until 2006, it was not been possible to assess nutritional status of crewmembers on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in status of several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. Collecting samples during flight is one of the objectives of SMO 016E, and it is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment variables will be expanded to include ones that will allow us to better understand changes in folate, vitamin K, and vitamin B6 status, as well as risk factors for cardiovascular and oxidative damage during and after flight. Stress hormones and hormones that affect bone and muscle metabolism will also be measured. Measuring these additional variables will allow us to better monitor the health of crewmembers and make more accurate recommendations for their rehabilitation. Several nutritional assessment variables are altered at landing, but it is not known how long these changes persist. We extended the original protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how

Absenteísmo de consultas especializadas nos sistema de saúde público: relação entre causas e o processo de trabalho de equipes de saúde da família, João Pessoa – PB, Brasil.

Directory of Open Access Journals (Sweden)

Ronald Pereira CAVALCANTI

2013-09-01

Full Text Available O absenteísmo dos usuários nos serviços de saúde pública é um tema de constante abordagem na gestão do Sistema Único de Saúde. O município João Pessoa adotou ações de acompanhamento do absenteísmo de consultas especializadas o que despertou a necessidade de avaliar suas causas, relacionando ao processo de trabalho de Equipes de Saúde da Família. Foram realizadas visitas de observação e entrevistas a usuários em áreas de três equipes de saúde da família, complementadas com dados secundários e revisão bibliográfica. Os dados foram analisados através de estatística descritiva e análise de conteúdo de narrativa. Verificou-se um aumento de 7% do absenteísmo no período 2009/2010; discrepância nesse aumento entre as três equipes estudadas; relação do absenteísmo inversamente proporcional ao número de visitas domiciliares realizadas pelos agentes comunitários de saúde; não houve relação direta do absenteísmo com excesso de encaminhamentos para consultas especializadas. Nesse estudo foi possível observar que se trata de um fenômeno multi - causal, onde as relações de causa / efeito perpassam todos os atores envolvidos (trabalhadores, gestão e usuários, sendo as causas relacionadas com o serviço e gestão neste artigo entendidas como passíveis de correções mediante readequação do processo de trabalho das equipes.

A reinvenção do heroísmo na contemporaneidade: a busca de uma estética relacional ativista

OpenAIRE

Tania Alice Caplain Feix

2013-01-01

O artigo aborda as performances realizadas pelo Coletivo de performance carioca Heróis do Cotidiano, que investiga a possibilidade e as condições de surgimento e expansão do hero¬ísmo na Contemporaneidade. Pela criação de micro-utopias temporárias e locais, o Coletivo realiza uma apropriação do espaço público, dialogando com o conceito de Estética Relacional de Nicolas Bourriaud, estabelecendo novas formas de sociabilidade e estabelecendo proces¬sos de subjetivação diferentes daqueles propost...

Joel e a esperança em um Deus universal e libertador frente à ambiguidade do monoteísmo

OpenAIRE

S. Rossi, Luiz Alexandre; Neves, Natalino das

2017-01-01

O artigo tem por objetivo comparar os resultados entre as principais reformas políticoreligiosas em nome do monoteísmo em Israel com a mensagem de Joel. Descrever-se-á as reformas de Ezequias e Josias, e a reforma étnica de Esdras e Neemias. Na sequência, é apresentada a mensagem universalista e libertadora de Joel, com destaque para as perícopes de Joel 3,1-5 e 4,4-8, visando a comparação entre esta e aquelas. Trata-se de uma pesquisa essencialmente bibliográfica. O resultado evidencia que a...

A role for hedgehog signaling in the differentiation of the insertion site of the patellar tendon in the mouse.

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Chia-Feng Liu

Full Text Available Tendons are typically composed of two histologically different regions: the midsubstance and insertion site. We previously showed that Gli1, a downstream effector of the hedgehog (Hh signaling pathway, is expressed only in the insertion site of the mouse patellar tendon during its differentiation. To test for a functional role of Hh signaling, we targeted the Smoothened (Smo gene in vivo using a Cre/Lox system. Constitutive activation of the Hh pathway in the mid-substance caused molecular markers of the insertion site, e.g. type II collagen, to be ectopically expressed or up-regulated in the midsubstance. This was confirmed using a novel organ culture method in vitro. Conversely, when Smo was excised in the scleraxis-positive cell population, the development of the fibrocartilaginous insertion site was affected. Whole transcriptome analysis revealed that the expression of genes involved in chondrogenesis and mineralization was down-regulated in the insertion site, and expression of insertion site markers was decreased. Biomechanical testing of murine adult patellar tendon, which developed in the absence of Hh signaling, showed impairment of tendon structural properties (lower linear stiffness and greater displacement and material properties (greater strain, although the linear modulus of the mutant group was not significantly lower than controls. These studies provide new insights into the role of Hh signaling during tendon development.

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

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Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

2012-09-01

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

Critical pitting temperature for Type 254 SMO stainless steel in chloride solutions

International Nuclear Information System (INIS)

Abd El Meguid, E.A.; Abd El Latif, A.A.

2007-01-01

The variation with time of the open circuit potential of high molybdenum containing stainless steel (Type 254 SMO) was measured in 4% sodium chloride solution in the temperatures range 30-100 deg. C. The plot of steady state potentials as function of temperature showed an inflection at 50 deg. C, attributed to the decrease of oxygen solubility in test solution above 50 deg. C. Potentiodynamic cycling anodic polarization technique was used to determine the critical pitting potential (E pit ) and the critical protection potential (E prot ) of the steel in 4-30% NaCl solutions at temperatures between 30 and 100 deg. C. By plotting the two values versus solution temperature, the corresponding critical pitting (CPT) and the critical protection (CPrT) temperatures were determined. Both parameters decreased with increasing chloride content. Above the CPT, E pit and E prot decreased linearly with log[Cl - ]. The addition of bromide ions to the solution shifted both E pit and E prot towards positive values. In 4% NaCl, E pit increased linearly with pH in the range 1-10. The combined effect of chloride ion concentration and pH on the morphology of the pits was examined by scanning electron microscopy (SEM) following potentiodynamic cycling anodic polarization

Life on earth: to reduce egotism and increase cooperaation La vida en la tierra: mermarl al egoísmo y aumentar la cooperación

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Jorge Eliécer Ossa Londoño

2002-04-01

Full Text Available This short essay collects the thoughts of the author stimulated by some preliminary readings on the sujet of environmental ethics. The concept of life on earth is proposed as the fundamental basis for an ethics of the inviromental. Egotism as an ontogenetc principle for the construction of the individuality of the living being: and cooperation, as a necessary organizing axis, are recognized in this context and it is proposed that a rule of thumb to manage the very complex relatinships with the environment could lay on the capacity of the human being to increase cooperation and reduce his egotism. Este corto ensayo recoge las reflexiones del autor, estimuladas por algunas lecturas preliminares sobre el tema de ética ambiental. Se propone el concepto de la vida en la tierra como base fundamental de una ética planetaria y se rescata el egoísmo ontogénico como una función necesaria para la construcción del individuo vivo y la cooperación como principio organizador necesario. Se sugiere que la capacidad del ser humano para incrementar su sentido de cooperación y para reducir su egoísmo, podrá ser la regla de oro para manejar las complejas relaciones con el entorno.

Fatores de risco para absenteísmo com licença médica em trabalhadores da indústria de petróleo

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Nágila Soares Xavier Oenning

2014-02-01

Full Text Available OBJETIVO : Identificar fatores de risco para o absenteísmo com licença médica em trabalhadores de empresa de petróleo. MÉTODOS : Estudo caso-controle (120 casos e 656 controles aninhado a um estudo de coorte retrospectivo com todos os trabalhadores de uma empresa de petróleo na Região Norte-Nordeste do Brasil entre 2007 e 2009. A variável resposta utilizada para representar o absenteísmo com licença médica foi a incidência média de faltas com licenças médicas no período, definida pela razão entre o total de dias de licenças médicas e os dias potencialmente trabalháveis no período. Análise de regressão logística foi utilizada para investigar a associação entre incidência média de faltas > 5,0% no período e as variáveis sexo, cargo, idade, tempo de atuação, regime de trabalho, tabagismo, hipertensão arterial, índice de massa corporal, atividade física, risco coronariano, sono, glicemia, diabetes não controlado, doença do aparelho cardiovascular, digestivo, aparelho locomotor, neurológica, neoplasia, posturas forçadas no trabalho, satisfação com o trabalho, relacionamento com a chefia e atenção concentrada no trabalho. RESULTADOS : A incidência média de faltas com licenças médicas > 5,0% no período da coorte foi 15,5%. O modelo logístico revelou que trabalhadores com incidência média de faltas > 5,0% tiveram 2,6 vezes mais chance de ser do sexo feminino; 2,0 vezes mais chance de ser fumante; 1,8 vez mais chance de ser ex-fumante, 2,2 vezes mais chance de relatar sono anormal e 10,5 vezes mais chance de estarem insatisfeitos com o trabalho do que trabalhadores com incidência média de faltas ≤ 5,0% no período. CONCLUSÕES : Sexo feminino, ser fumante ou ex-fumante, estar insatisfeito com o trabalho e relatar sono anormal são bons preditores de absenteísmo ao trabalho por doença.

[Smoļenskas-Rīgas aktis 13. gs.-14. gs. pirmā puse : kompleksa "Moscowitica-Ruthenica" dokumenti par Smoļenskas un Rīgas attiecībām = Смоленско-рижские акты XIII в.-первая половина XIV в. : документ�

Index Scriptorium Estoniae

Levans, Andris, 1968-

2011-01-01

Arvustus: Smoļenskas-Rīgas aktis 13. gs.-14. gs. pirmā puse : kompleksa "Moscowitica-Ruthenica" dokumenti par Smoļenskas un Rīgas attiecībām = Смоленско-рижские акты XIII в.-первая половина XIV в. : документы комплекса Moscowitica-Ruthenica об отношениях Смоленска и Риги /koostajad Leksanders Ivanovs, Anatolijs Kuzņcovs. Vēstures avoti ; 6 (Riga: Latvijas Valsts vēstures arcīva izdevniecība, 2009)

A novel osteogenic oxysterol compound for therapeutic development to promote bone growth: activation of hedgehog signaling and osteogenesis through smoothened binding.

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Montgomery, Scott R; Nargizyan, Taya; Meliton, Vicente; Nachtergaele, Sigrid; Rohatgi, Rajat; Stappenbeck, Frank; Jung, Michael E; Johnson, Jared S; Aghdasi, Bayan; Tian, Haijun; Weintraub, Gil; Inoue, Hirokazu; Atti, Elisa; Tetradis, Sotirios; Pereira, Renata C; Hokugo, Akishige; Alobaidaan, Raed; Tan, Yanlin; Hahn, Theodor J; Wang, Jeffrey C; Parhami, Farhad

2014-08-01

Osteogenic factors are often used in orthopedics to promote bone growth, improve fracture healing, and induce spine fusion. Osteogenic oxysterols are naturally occurring molecules that were shown to induce osteogenic differentiation in vitro and promote spine fusion in vivo. The purpose of this study was to identify an osteogenic oxysterol more suitable for clinical development than those previously reported, and evaluate its ability to promote osteogenesis in vitro and spine fusion in rats in vivo. Among more than 100 oxysterol analogues synthesized, Oxy133 induced significant expression of osteogenic markers Runx2, osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) in C3H10T1/2 mouse embryonic fibroblasts and in M2-10B4 mouse marrow stromal cells. Oxy133-induced activation of an 8X-Gli luciferase reporter, its direct binding to Smoothened, and the inhibition of Oxy133-induced osteogenic effects by the Hedgehog (Hh) pathway inhibitor, cyclopamine, demonstrated the role of Hh pathway in mediating osteogenic responses to Oxy133. Oxy133 did not stimulate osteogenesis via BMP or Wnt signaling. Oxy133 induced the expression of OSX, BSP, and OCN, and stimulated robust mineralization in primary human mesenchymal stem cells. In vivo, bilateral spine fusion occurred through endochondral ossification and was observed in animals treated with Oxy133 at the fusion site on X-ray after 4 weeks and confirmed with manual assessment, micro-CT (µCT), and histology after 8 weeks, with equal efficiency to recombinant human bone morphogenetic protein-2 (rhBMP-2). Unlike rhBMP-2, Oxy133 did not induce adipogenesis in the fusion mass and resulted in denser bone evidenced by greater bone volume/tissue volume (BV/TV) ratio and smaller trabecular separation. Findings here suggest that Oxy133 has significant potential as an osteogenic molecule with greater ease of synthesis and improved time to fusion compared to previously studied oxysterols. Small

Absenteeism at a Medium Size Philanthropic Hospital Absenteísmo em Hospital Filantrópico de Médio Porte

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Ilidia Terezinha Martelli Takahashi

2011-06-01

Full Text Available The absenteeism is a complex administrative problem for organizations. In hospitals, it becomes even more complicated as the patient care can not be interrupted. The term absenteeism - disease, refers to the time off work due to health problems. It is intended to analyze the absence of workers due to health problems is related to age, sex, length of employment at the institution, part work shift and functional category. This is a retrospective, descriptive and documentary study. Data was collected from medical certificates submitted in the period from 01 July 2007 to 30 June 2008 to the sector of human resources of a medium-sized philanthropic hospital. The analysis results show that the number of certificates is greater in females (90.80% and staff that work less time in the institution (61.19%. It was found that the number of certificates is higher in workers who make the rotation between morning and afternoon shifts. It was also noted that workers aged over 48 years, had lower number of certificates than the younger ones. The nursing technicians assistant were the professional categories that had presented more certificates (46.05%. The results identify several factors related to absenteeism and provide subsidies to strengthen actions to monitor the health of workers and also the implementation of actions aimed at improving the quality of life at work. O absenteísmo é um complexo problema administrativo para as organizações. Nos hospitais, torna-se ainda mais complicado, pois o cuidado ao cliente não pode ser interrompido. Entende-se por absenteísmo-doença, as faltas ao trabalho por problemas de saúde. Tem-se como objetivo analisar as faltas dos trabalhadores por causas de saúde relacionando-as com idade, sexo, tempo de trabalho na instituição, turno de trabalho e categoria funcional. Trata-se de um estudo retrospectivo, descritivo edocumental. Os dados foram coletados dos atestados de saúde apresentados no período de 01 julho de

Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

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Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

2016-02-01

Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

KANTIAN'S ETHICS AND THE POSSIBILITY OF ALTRUISM (THOMAS NAGEL A ÉTICA KANTIANA E A POSSIBILIDADE DO ALTRUÍSMO (THOMAS NAGEL

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Jürgen Stolzenberg

2010-12-01

Full Text Available The present article discusses the relation of Th. Nagel’s ethics of altruism with kantian ethics. According to Nagel himself, his position resembles that of Kant in two respects: it defends the thesis of the autonomy of moral motivation, and it bases moral on a determinate self-conception of persons. However, differently from Kant, the principle of Nagel’s ethics is just the modest presupposition that persons essentially understand themselves as being one among a plurality of other persons. Starting from the nagelian argument in The Possibility of Altruism (1970, but contemplating also Nagel’s more recent position in The Last Word (1999, it is argued that in order to defend his conception of a rational ethics in a convincing way, Nagel has to approximate himself more to the kantian foundation of ethics than he wants to admit.O presente artigo discute a relação da ética do altruísmo, defendida por Thomas Nagel, com a ética kantiana. Segundo o próprio Nagel, sua posição é semelhante à de Kant sob dois aspectos: ela defende a tese da autonomia da motivação moral, e ela funda a moral numa determinada autoconcepção da pessoa. No entanto, diferentemente de Kant, o princípio da ética nageliana é apenas o pressuposto modesto de que uma pessoa essencialmente considera a si mesma como sendo uma numa pluralidade de pessoas. Partindo do argumento nageliano em The Possibility of Altruísmo (1970, mas contemplando também a posição mais recente de Nagel em The Last Word (1999, argumenta-se que Nagel só pode defender sua concepção de uma ética racional de modo convincente, se ele se aproximar mais da fundamentação kantiana da ética do que ele pretende.

The role of the Hedgehog signaling pathway in cancer: A comprehensive review

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Ana Marija Skoda

2018-02-01

Full Text Available The Hedgehog (Hh signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh], Patched receptor (Ptch1, Ptch2, Smoothened receptor (Smo, Suppressor of fused homolog (Sufu, kinesin protein Kif7, protein kinase A (PKA, and cyclic adenosine monophosphate (cAMP. The activator form of Gli travels to the nucleus and stimulates the transcription of the target genes by binding to their promoters. The main target genes of the Hh signaling pathway are PTCH1, PTCH2, and GLI1. Deregulation of the Hh signaling pathway is associated with developmental anomalies and cancer, including Gorlin syndrome, and sporadic cancers, such as basal cell carcinoma, medulloblastoma, pancreatic, breast, colon, ovarian, and small-cell lung carcinomas. The aberrant activation of the Hh signaling pathway is caused by mutations in the related genes (ligand-independent signaling or by the excessive expression of the Hh signaling molecules (ligand-dependent signaling – autocrine or paracrine. Several Hh signaling pathway inhibitors, such as vismodegib and sonidegib, have been developed for cancer treatment. These drugs are regarded as promising cancer therapies, especially for patients with refractory/advanced cancers.

Identification of Cleavage Sites Recognized by the 3C-Like Cysteine Protease within the Two Polyproteins of Strawberry Mottle Virus

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Hélène Sanfaçon

2017-04-01

Full Text Available Strawberry mottle virus (SMoV, family Secoviridae, order Picornavirales is one of several viruses found in association with strawberry decline disease in Eastern Canada. The SMoV genome consists of two positive-sense single-stranded RNAs, each encoding one large polyprotein. The RNA1 polyprotein (P1 includes the domains for a putative helicase, a VPg, a 3C-like cysteine protease and an RNA-dependent RNA polymerase at its C-terminus, and one or two protein domains at its N-terminus. The RNA2 polyprotein (P2 is predicted to contain the domains for a movement protein (MP and one or several coat proteins at its N-terminus, and one or more additional domains for proteins of unknown function at its C-terminus. The RNA1-encoded 3C-like protease is presumed to cleave the two polyproteins in cis (P1 and in trans (P2. Using in vitro processing assays, we systematically scanned the two polyproteins for cleavage sites recognized by this protease. We identified five cis-cleavage sites in P1, with cleavage between the putative helicase and VPg domains being the most efficient. The presence of six protein domains in the SMoV P1, including two upstream of the putative helicase domain, is a feature shared with nepoviruses but not with comoviruses. Results from trans-cleavage assays indicate that the RNA1-encoded 3C-like protease recognized a single cleavage site, which was between the predicted MP and coat protein domains in the P2 polyprotein. The cleavage site consensus sequence for the SMoV 3C-like protease is AxE (E or Q/(G or S.

Macroepizoísmo em Libinia ferreirae (Crustacea, Brachyura, Majidae Macroepizoites on Libinia ferreirae (Crustacea, Brachyura, Majidae

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Vanessa C. Winter

2006-06-01

Full Text Available Um estudo de distribuição dos macroepizóicos foi realizado numa população do caranguejo-aranha Libinia ferreirae Brito Capello, 1871 proveniente do litoral dos estados do Paraná e de Santa Catarina. O material biológico foi obtido junto aos pescadores, e faz parte do rejeito de pesca. Os caranguejos foram mensurados e os macroepizóicos identificados e contados. Os seguintes macroepizóicos sésseis foram registrados: Calliactis tricolor (Lesueur, 1817 (Cnidaria; Actiniaria (Cnidaria; Arca sp. (Mollusca; Ostreidae (Mollusca; Acanthodesia tenuis (Desor, 1848 (Bryozoa; Cirripedia e duas espécies tubícolas de Gammaridea (Crustacea. Além destes organismos ocorreram dois tubos desabitados e quatro animais vágeis. A anêmona C. tricolor foi a espécie mais abundante e freqüente, sendo, provavelmente, utilizada como mecanismo de camuflagem pelo caranguejo. O macroepizoísmo em L. ferreirae está relacionado com a idade ou tamanho do caranguejo, tendo maior incidência naqueles mais velhos ou de maior porte. Entretanto, a densidade dos macroepizóicos por caranguejo se mantém em torno de três. Não há relação entre o macroepizoísmo e o sexo do hospedeiro; somente fêmeas ovígeras utilizam desse recurso mais freqüentemente do que as não-ovígeras. Devido à maior área de fixação, os macroepizóicos colonizam principalmente a carapaça do caranguejo, enquanto nos pereiópodos há predominância de Bryozoa.A study of the distribution of the macroepizoites was carried out on a population of the spider crab Libinia ferreirae Brito Capello, 1871 from the Southern Brazilian coast. Crabs were obtained from shrimps and fishes by-catch. They were measured, and their macroepizoites were identified and counted. The following sessile macroepizoites were registered: Calliactis tricolor (Lesueur, 1817 (Cnidaria; Actiniaria (Cnidaria; Arca sp. (Mollusca; Ostreidae (Mollusca; Acanthodesia tenuis (Desor, 1848 (Bryozoa; Cirripedia and two species

Ectopic Overexpression of Sonic Hedgehog (Shh Induces Stromal Expansion and Metaplasia in the Adult Murine Pancreas

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Volker Fendrich

2011-10-01

Full Text Available Ligand-dependent activation of the Hedgehog (Hh signaling pathway has been implicated in both tumor initiation and metastasis of pancreatic ductal adenocarcinoma (PDAC. Prior studies in genetically engineered mouse models (GEMMs have assessed the role of Hh signaling by cell autonomous expression of a constitutively active Gli2 within epithelial cells. On the contrary, aberrant pathway reactivation in the human exocrine pancreas occurs principally as a consequence of Sonic Hh ligand (Shh overexpression from epithelial cells. To recapitulate the cognate pathophysiology of Hh signaling observed in the human pancreas, we examined GEMM where Hh ligand is conditionally overexpressed within the mature exocrine pancreas using a tamoxifen-inducible Elastase-Cre promoter (Ela-CreERT2;LSL-mShh. We also facilitated potential cell autonomous epithelial responsiveness to secreted Hh ligand by generating compound transgenic mice with concomitant expression of the Hh receptor Smoothened (Ela-CreERT2;LSL-mShh;LSL-mSmo. Of interest, none of these mice developed intraductal precursor lesions or PDAC during the follow-up period of up to 12 months after tamoxifen induction. Instead, all animals demonstrated marked expansion of stromal cells, consistent with the previously described epithelial-to-stromal paracrine Hh signaling. Hh responsiveness was mirrored by the expression of primary cilia within the expanded mesenchymal compartment and the absence within mature acinar cells. In the absence of cooperating mutations, Hh ligand overexpression in the mature exocrine pancreas is insufficient to induce neoplasia, even when epithelial cells coexpress the Smo receptor. This autochthonous model serves as a platform for studying epithelial stromal interactions in pancreatic carcinogenesis.

Gli as a novel therapeutic target in malignant pleural mesothelioma.

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Hui Li

Full Text Available Malignant pleural mesothelioma (MPM is a highly aggressive tumor with poor prognosis. Current treatment is rarely curative, thus novel meaningful therapies are urgently needed. Inhibition of Hedgehog (Hh signaling at the cell membrane level in several cancers has shown anti-cancer activity in recent clinical studies. Evidence of Hh-independent Gli activation suggests Gli as a more potent therapeutic target. The current study is aimed to evaluate the potential of Gli as a therapeutic target to treat MPM. The expression profiles of Gli factors and other Hh signaling components were characterized in 46 MPM patient tissue samples by RT-PCR and immunohistochemistry. Cultured cell lines were employed to investigate the requirement of Gli activation in tumor cell growth by inhibiting Gli through siRNA or a novel small molecule Gli inhibitor (Gli-I. A xenograft model was used to evaluate Gli-I in vivo. In addition, a side by side comparison between Gli and Smoothened (Smo inhibition was conducted in vitro using siRNA and small molecule inhibitors. Our study reported aberrant Gli1 and Gli2 activation in a large majority of tissues. Inhibition of Gli by siRNAs or Gli-I suppressed cell growth dramatically both in vitro and in vivo. Inhibition of Gli exhibited better cytotoxicity than that of Smo by siRNA and small molecule inhibitors vismodegib and cyclopamine. Combination of Gli-I and pemetrexed, as well as Gli-I and vismodegib demonstrated synergistic effects in suppression of MPM proliferation in vitro. In summary, Gli activation plays a critical role in MPM. Inhibition of Gli function holds strong potential to become a novel, clinically effective approach to treat MPM.

[Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients].

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Zenner, H P; Pfister, M; Friese, N; Zrenner, E; Röcken, M

2014-07-01

To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

The hedgehog receptor patched is involved in cholesterol transport.

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Michel Bidet

Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase.

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Juan M Alonso-Dominguez

Full Text Available Patched homolog 1 gene (PTCH1 expression and the ratio of PTCH1 to Smoothened (SMO expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0.71 vs. 0.72. In order to reduce the number of genes to be analyzed, PTCH1 was the selected measurement. High and low PTCH1 expression groups had significantly different cumulative incidences of imatinib failure (IF, which was defined as discontinuation of imatinib due to lack of efficacy (5% vs. 25% at 4 years, P = 0.013, probabilities of achieving a major molecular response (81% vs. 53% at first year, P = 0.02, and proportions of early molecular failure (14% vs. 43%, P = 0.015. Every progression to an advanced phase (n = 3 and CML-related death (n = 2 occurred in the low PTCH1 group (P<0.001 for both comparisons. PTCH1 was an independent prognostic factor for the prediction of IF. We also validated previously published thresholds for PTCH1 expression. Therefore, we confirmed that PTCH1 expression can predict the imatinib response in CML patients in CP by applying a more rigorous statistical analysis. Thus, PTCH1 expression is a promising molecular marker for predicting the imatinib response in CML patients in CP.

Dor orofacial e absenteísmo em trabalhadores da indústria metalúrgica e mecânica Orofacial pain and absenteeism in workers of the metallurgic and mechanics industry

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Josimari Telino de Lacerda

2008-12-01

Full Text Available O objetivo do estudo foi verificar a prevalência de dor orofacial e sua relação com absenteísmo em trabalhadores do setor metalúrgico e mecânico do município de Xanxerê, Santa Catarina. Realizou-se um estudo transversal envolvendo todos os trabalhadores do sexo masculino (n = 480 das 13 indústrias do setor no município. As informações foram coletadas por meio de entrevistas estruturadas. Informações sócio-demográficas, prevalência, severidade e localização de dor orofacial no último semestre, bem como sobre falta ao trabalho devido à dor orofacial, compuseram o questionário. Dados de identificação, setor e turno de trabalho foram coletados nos departamentos de recursos humanos das empresas. Os dados foram analisados por meio de estatística descritiva e testes de associação de qui-quadrado de Pearson entre absenteísmo e dor orofacial. A prevalência de dor orofacial foi de 66,1%, sendo dor de dente provocada ou dor de dente espontânea os tipos mais frequentes. O absenteísmo devido a dor orofacial no último semestre foi relatado por 9,3% dos trabalhadores, mostrando-se associado à dor de dente espontânea (p The objective of this study was to assess the prevalence of orofacial pain and its association with absenteeism in worke rs of the metallurgic and mechanics industry of the city of Xanxerê, Brazil. A cross sectional study was performed involving all male workers(n=480 of the 13 industries of the sector in the city. The information was collected by means of structured interviews. Socio-demographic information, prevalence, severity and localization of orofacial pain in the last semester as well as on absenteeism due to orofacial pain formed the questionnaire. Identification data, work sector and shift were collected in the departments of human resources of the companies. The data were assessed using descriptive statistics and Pearson chi-squared tests between absenteeism and pain in the orofacial region. The

Bmi1 Is Required for Hedgehog Pathway-Driven Medulloblastoma Expansion

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Lowell Evan Michael

2008-12-01

Full Text Available Inappropriate Hedgehog (Hh signaling underlies development of a subset of medulloblastomas, and tumors with elevated HH signaling activity express the stem cell self-renewal gene BMI1. To test whether Bmi1 is required for Hh-driven medulloblastoma development, we varied Bmi1 gene dosage in transgenic mice expressing an oncogenic Hh effector, SmoA1, driven by a glial fibrillary acidic protein (GFAP promoter. Whereas 100% of SmoA1; Bmi1+/+ or SmoA1;Bmi1+/- mice examined between postnatal (P days 14 and 26 had typical medulloblastomas (N = 29, tumors were not detected in any of the SmoA1;Bmi1-/- animals examined (N = 6. Instead, small ectopic collections of cells were present in the region of greatest tumor load in SmoA1 animals, suggesting that medulloblastomas were initiated but failed to undergo expansion into frank tumors. Cells within these Bmi1-/- lesions expressed SmoA1 but were largely nonproliferative, in contrast to cells in Bmi1+/+ tumors (6.2% vs 81.9% PCNA-positive, respectively. Ectopic cells were negative for the progenitor marker nestin, strongly GFAP-positive, and highly apoptotic, relative to Bmi1+/+ tumor cells (29.6% vs 6.3% TUNEL-positive. The alterations in proliferation and apoptosis in SmoA1;Bmi1-/- ectopic cells are associated with reduced levels of Cyclin D1 and elevated expression of cyclin-dependent kinase inhibitor p19Arf, two inversely regulated downstream targets of Bmi1. These data provide the first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain, suggest a crucial role for Bmi1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion, and implicate Bmi1 as a key factor required for Hh pathway-driven tumorigenesis.

Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms1

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Zhang, Xia; Sun, Shuangli; Nie, Xiang; Boutté, Yohann; Grison, Magali; Li, Panpan; Kuang, Susu

2016-01-01

Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4α-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin-defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4α-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development. PMID:27006488

O absenteísmo da equipe de enfermagem em unidade de pronto socorro de um hospital universitário

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Elisângela Cristina de Campos

2009-06-01

Full Text Available O absenteísmo ou ausentismo é o termo utilizado para caracterizar as ausências dos funcionários ao trabalho.Essas ausências são definidas em previstas e não previstas. Para este estudo especificamos as ausênciasprevistas como folgas, feriados e férias e para as não previstas ficam as faltas, licenças medicas, nojo e outraslicenças. O objetivo foi investigar o real numero de ausências dos técnicos e auxiliares de enfermagem de umPronto Socorro de um Hospital Universitário do interior do estado de São Paulo para definir o Índice deSegurança Técnica-IST. Foi utilizada metodologia quantitativa descritiva, e a coleta de dados feita de janeiro de2006 a junho de 2007, a partir de arquivos administrativos após autorização do serviço. Entre os principaisachados encontramos um IST cuja média gira em torno de 51%. Concluímos que, embora próximo, estáligeiramente superior ao encontrado em outra realidade de Hospital Universitário. Entre as ausências nãoprevistas, destacam-se as licenças médicas, que podem estar relacionadas à sobrecarga da equipe.

The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

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Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

2015-12-04

The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

G-Protein Gαs controls medulloblastoma initiation by suppressing sonic hedgehog signaling.

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He, Xuelian; Lu, Q Richard

2015-01-01

We identify Gαs as a novel tumor suppressor in medulloblastoma that functions principally by inhibition of sonic hedgehog signaling. Gαs not only stimulates cyclic adenosine monophosphate (cAMP)-dependent signaling but also inhibits ciliary trafficking of hedgehog components. Elevation of cAMP inhibits medulloblastoma growth and augments inhibition of smoothened to decrease tumor cell proliferation, thus highlighting Gαs as a potential therapeutic target.

Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms.

Science.gov (United States)

Zhang, Xia; Sun, Shuangli; Nie, Xiang; Boutté, Yohann; Grison, Magali; Li, Panpan; Kuang, Susu; Men, Shuzhen

2016-05-01

Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4α-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin-defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4α-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development. © 2016 American Society of Plant Biologists. All Rights Reserved.

Problemas de saúde responsáveis pelo absenteísmo de trabalhadores de enfermagem de um hospital universitário - DOI: 10.4025/actascihealthsci.v25i2.2232 Health problems responsible for the nursing staff disease-absenteeism in a university hospital - DOI: 10.4025/actascihealthsci.v25i2.2232

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Doris Marli Petry Paulo da Silva

2003-04-01

Full Text Available Entende-se por absenteísmo-doença as faltas do trabalhador devidas a problemas de saúde diagnosticados para efeito de licença-saúde. Com o objetivo de identificar os problemas de saúde responsáveis pelo absenteísmo-doença em trabalhadores de enfermagem de um hospital universitário, foi realizado um levantamento retrospectivo das faltas (494 justificadas por licenças-saúde, equivalentes a 1.491 dias de trabalho perdidos em um ano, calculados os índices de absenteísmo-doença e identificadas suas causas. A Unidade de Pediatria apresentou o maior índice de freqüência (If=0,35; a maior porcentagem de tempo perdido (Tp=4,19% ocorreu no Pronto Atendimento, entre auxiliares de Enfermagem, enquanto os enfermeiros apresentaram maiores índices nas UTIs, If=0,17 e Tp=3,93%. Os problemas de saúde foram relacionados aos sistemas respiratório, geniturinário, digestivo e osteomuscular, aos órgãos dos sentidos e ao aparelho reprodutor feminino. Concluímos que os índices de absenteísmo-doença apresentam-se elevados. As causas do adoecimento dos trabalhadores apresentam interface com inadequadas condições de trabalho e fatores de risco presentes no cotidiano da enfermagem.Disease-absenteeism is the frequent absence from work due to some illness. A retrospective survey of the sick-leave (494 absences during a year was performed. Aiming to identify health problems responsible for the nursing staff disease-absenteeism of a university hospital. Both frequency index and percentage of lost time were calculated, and the health problems were identified. The results showed that the highest frequency index occurred in the Pediatric Unit (Fi=0.35 and the highest percentage of lost time due to absence occurred in the Emergency Unit (Lt=4.19% among the Nursing Auxiliaries; the nurses showed the highest frequency in the Intensive Care Unit, Fi=0.17 and Lt=3.93%. Health problems of nursing staff were related to the respiratory and genito

Insuficiencia de los constructos psicológicos en la educación del altruismo Insuficiência dos construtos psicológicos no ensino do altruísmo Insufficiency of psychological constructs in education in altruism

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Alfonso Osorio

2010-04-01

Full Text Available Con frecuencia los estudios relacionados con el altruismo lo abordan desde constructos psicológicos como la memoria, la afectividad, la motivación o el aprendizaje. Son escasas, en cambio, las aproximaciones desde la voluntad y la virtud. El presente artículo pretende vincular estos conceptos con ese campo de investigación, para aportar nuevas claves de interpretación sobre la educación del altruismo y para el diseño de estrategias pedagógicas en este campo. Algunas evidencias empíricas muestran que los constructos psicológicos resultan insuficientes para explicar la conducta altruista y suformación, mientras que recurriendo también a la visión aristotélica de la voluntad y de la virtud se alcanza una comprensión más íntegra y pedagógica del altruismo como objeto educativo.Freqüentemente, estudos associados com altruísmo o abordam desde construtos psicológicos como memória, emoção, motivação ou aprendizagem. São poucas, entretanto, as abordagens a partir da vontade e da virtude. Este artigo tenta vincular esses conceitos com esse campo da investigação, para fornecer novas pistas na interpretação acerca do ensino do altruísmo e na concepção de estratégias de ensino nesta área. Algumas evidências empíricas indicam que os constructos psicológicos são insuficientes para explicar o comportamento altruísta e sua formação, enquanto se recorrer à visão aristotélica da vontade e da virtude chega-se a uma compreensão mais plena e pedagógica do altruísmo como objeto de ensinoStudies dealing with altruism often approach the subject from psychological constructs such as memory, feelings, motivation or learning. Very few deal with it from the standpoint of volition and virtue. This article attempts to link these concepts to that field of research in an effort to provide new keys for interpretation regarding education in altruism and for the design of teaching strategies in this field. Some empirical evidence

Protein-RNA interface residue prediction using machine learning: an assessment of the state of the art.

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Walia, Rasna R; Caragea, Cornelia; Lewis, Benjamin A; Towfic, Fadi; Terribilini, Michael; El-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2012-05-10

)-based representation (PSSMSeq) outperform those that use an amino acid identity based representation (IDSeq) or a smoothed PSSM (SmoPSSMSeq); (ii) Structure-based classifiers that use smoothed PSSM representation (SmoPSSMStr) outperform those that use PSSM (PSSMStr) as well as sequence identity based representation (IDStr). PSSMSeq classifiers, when tested on an independent test set of 44 proteins, achieve performance that is comparable to that of three state-of-the-art structure-based predictors (including those that exploit geometric features) in terms of Matthews Correlation Coefficient (MCC), although the structure-based methods achieve substantially higher Specificity (albeit at the expense of Sensitivity) compared to sequence-based methods. We also find that the expected performance of the classifiers on a residue level can be markedly different from that on a protein level. Our experiments show that the classifiers trained on three different non-redundant protein-RNA interface datasets achieve comparable cross-validation performance. However, we find that the results are significantly affected by differences in the distance threshold used to define interface residues. Our results demonstrate that protein-RNA interface residue predictors that use a PSSM-based encoding of sequence windows outperform classifiers that use other encodings of sequence windows. While structure-based methods that exploit geometric features can yield significant increases in the Specificity of protein-RNA interface residue predictions, such increases are offset by decreases in Sensitivity. These results underscore the importance of comparing alternative methods using rigorous statistical procedures, multiple performance measures, and datasets that are constructed based on several alternative definitions of interface residues and redundancy cutoffs as well as including evaluations on independent test sets into the comparisons.

KRMILJENJE MIKROKRMILNIŠKEGA MODULA ARDUINO IN NJEGOVA UPORABA PRI KOMUNIKACIJI Z OSTALIMI NAPRAVAMI

OpenAIRE

Ekart, Matej

2012-01-01

V diplomskem delu smo obravnavali mikrokrmilniški modul Arduino. Opisali smo strojno opremo modela Uno, ki ga uporabljamo v praktičnem delu, ter predstavili osnovne karakteristike ostalih modelov. V nadaljevanju smo spoznali odprtokodno razvojno okolje Arduino in Arduino programski jezik. V praktičnem delu smo preverili, kako se odprtokodna platforma Arduino izkaže v praksi. Razvili smo avtomatski sistem za samodejno zalivanje, pri čemer smo uporabili številne dodatne komponente, ki smo ji...

A QUESTÃO DE DEUS PARA O SER HUMANO E PARA O CRISTÃO: AS FORMAS CONTEMPORÂNEAS DE ATEÍSMO PRÁTICO E O TESTEMUNHO CRISTÃO

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Juvenal Savian Filho

2005-01-01

Full Text Available O tema do ateísmo e o testemunho cristão – também designado, aqui, como “a questão de Deus” para o ser humano e para o cristão –, aparece, na Gaudium et Spes1, nos números 19-22, concluindo o primeiro capítulo da Constituição Pastoral, dedicado à reflexão sobre a dignidade humana. O capítulo I se abre com a afirmação da dignidade humana, dado o fato de homem e mulher terem sido criados à imagem e semelhança de Deus, capazes de conhecer e amar o seu criador (n. 12, para, em seguida, referir-se ao pecado, fruto do abuso de liberdade e da procura do bem fora de Deus.

NANOG Expression as a Responsive Biomarker during Treatment with Hedgehog Signal Inhibitor in Acute Myeloid Leukemia

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Seiji Kakiuchi

2017-02-01

Full Text Available Aberrant activation of the Hedgehog (Hh signaling pathway is involved in the maintenance of leukemic stem cell (LSCs populations. PF-0444913 (PF-913 is a novel inhibitor that selectively targets Smoothened (SMO, which regulates the Hh pathway. Treatment with PF-913 has shown promising results in an early phase study of acute myeloid leukemia (AML. However, a detailed mode of action for PF-913 and relevant biomarkers remain to be elucidated. In this study, we examined bone marrow samples derived from AML patients under PF-913 monotherapy. Gene set enrichment analysis (GSEA revealed that PF-913 treatment affected the self-renewal signature and cell-cycle regulation associated with LSC-like properties. We then focused on the expression of a pluripotency factor, NANOG, because previous reports showed that a downstream effector in the Hh pathway, GLI, directly binds to the NANOG promoter and that the GLI-NANOG axis promotes stemness and growth in several cancers. In this study, we found that a change in NANOG transcripts was closely associated with GLI-target genes and NANOG transcripts can be a responsive biomarker during PF-913 therapy. Additionally, the treatment of AML with PF-913 holds promise, possibly through inducing quiescent leukemia stem cells toward cell cycling.

Sonic Hedgehog Signaling Drives Proliferation of Synoviocytes in Rheumatoid Arthritis: A Possible Novel Therapeutic Target

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Mingxia Wang

2014-01-01

Full Text Available Sonic hedgehog (Shh signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS. We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1 in RA synovial tissues was examined by immunohistochemistry (IHC and in FLS by IHC, immunofluorescence (IF, quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P<0.05. Cyclopamine (a specific inhibitor of Shh signaling decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.

Sequence Based Prediction of Antioxidant Proteins Using a Classifier Selection Strategy.

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Lina Zhang

Full Text Available Antioxidant proteins perform significant functions in maintaining oxidation/antioxidation balance and have potential therapies for some diseases. Accurate identification of antioxidant proteins could contribute to revealing physiological processes of oxidation/antioxidation balance and developing novel antioxidation-based drugs. In this study, an ensemble method is presented to predict antioxidant proteins with hybrid features, incorporating SSI (Secondary Structure Information, PSSM (Position Specific Scoring Matrix, RSA (Relative Solvent Accessibility, and CTD (Composition, Transition, Distribution. The prediction results of the ensemble predictor are determined by an average of prediction results of multiple base classifiers. Based on a classifier selection strategy, we obtain an optimal ensemble classifier composed of RF (Random Forest, SMO (Sequential Minimal Optimization, NNA (Nearest Neighbor Algorithm, and J48 with an accuracy of 0.925. A Relief combined with IFS (Incremental Feature Selection method is adopted to obtain optimal features from hybrid features. With the optimal features, the ensemble method achieves improved performance with a sensitivity of 0.95, a specificity of 0.93, an accuracy of 0.94, and an MCC (Matthew's Correlation Coefficient of 0.880, far better than the existing method. To evaluate the prediction performance objectively, the proposed method is compared with existing methods on the same independent testing dataset. Encouragingly, our method performs better than previous studies. In addition, our method achieves more balanced performance with a sensitivity of 0.878 and a specificity of 0.860. These results suggest that the proposed ensemble method can be a potential candidate for antioxidant protein prediction. For public access, we develop a user-friendly web server for antioxidant protein identification that is freely accessible at http://antioxidant.weka.cc.

A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.

Science.gov (United States)

Bohnenpoll, Tobias; Wittern, Anna B; Mamo, Tamrat M; Weiss, Anna-Carina; Rudat, Carsten; Kleppa, Marc-Jens; Schuster-Gossler, Karin; Wojahn, Irina; Lüdtke, Timo H-W; Trowe, Mark-Oliver; Kispert, Andreas

2017-08-01

The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH) family of secreted proteins, Sonic hedgehog (SHH) as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO) to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development. We showed that HH signaling is not only required for proliferation and SMC differentiation of cells of the inner mesenchymal region but also for survival of cells of the outer mesenchymal region, and for epithelial proliferation and differentiation. We identified the Forkhead transcription factor gene Foxf1 as a target of HH signaling in the ureteric mesenchyme. Expression of a repressor version of FOXF1 in this tissue completely recapitulated the mesenchymal and epithelial proliferation and differentiation defects associated with loss of HH signaling while re-expression of a wildtype version of FOXF1 in the inner mesenchymal layer restored these cellular programs when HH signaling was inhibited. We further showed that expression of Bmp4 in the ureteric mesenchyme depends on HH signaling and Foxf1, and that exogenous BMP4 rescued cell proliferation and epithelial differentiation in ureters with abrogated HH signaling or FOXF1 function. We conclude that SHH uses a FOXF1-BMP4 module to coordinate the cellular programs for ureter elongation and differentiation, and suggest that deregulation of this signaling axis occurs in human congenital anomalies of the kidney and urinary tract (CAKUT).

A SHH-FOXF1-BMP4 signaling axis regulating growth and differentiation of epithelial and mesenchymal tissues in ureter development.

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Tobias Bohnenpoll

2017-08-01

Full Text Available The differentiated cell types of the epithelial and mesenchymal tissue compartments of the mature ureter of the mouse arise in a precise temporal and spatial sequence from uncommitted precursor cells of the distal ureteric bud epithelium and its surrounding mesenchyme. Previous genetic efforts identified a member of the Hedgehog (HH family of secreted proteins, Sonic hedgehog (SHH as a crucial epithelial signal for growth and differentiation of the ureteric mesenchyme. Here, we used conditional loss- and gain-of-function experiments of the unique HH signal transducer Smoothened (SMO to further characterize the cellular functions and unravel the effector genes of HH signaling in ureter development. We showed that HH signaling is not only required for proliferation and SMC differentiation of cells of the inner mesenchymal region but also for survival of cells of the outer mesenchymal region, and for epithelial proliferation and differentiation. We identified the Forkhead transcription factor gene Foxf1 as a target of HH signaling in the ureteric mesenchyme. Expression of a repressor version of FOXF1 in this tissue completely recapitulated the mesenchymal and epithelial proliferation and differentiation defects associated with loss of HH signaling while re-expression of a wildtype version of FOXF1 in the inner mesenchymal layer restored these cellular programs when HH signaling was inhibited. We further showed that expression of Bmp4 in the ureteric mesenchyme depends on HH signaling and Foxf1, and that exogenous BMP4 rescued cell proliferation and epithelial differentiation in ureters with abrogated HH signaling or FOXF1 function. We conclude that SHH uses a FOXF1-BMP4 module to coordinate the cellular programs for ureter elongation and differentiation, and suggest that deregulation of this signaling axis occurs in human congenital anomalies of the kidney and urinary tract (CAKUT.

O Ateísmo Francês Contemporâneo: uma comparação crítica entre Michel Onfray e André Compte-Sponville (Contemporary French Atheism: a Critical Comparison between Michel Onfray and André Comte-Sponville - DOI: 10.5752/P.2175-5841.2010v8n18p127

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Agnaldo Cuoco Portugal

2011-04-01

Full Text Available Michel Onfray e André Comte-Sponville são os dois mais famosos representantes do ateísmo filosófico francês contemporâneo, que continua uma tradição iniciada no século XVIII de negação irreligiosa da noção monoteísta de Deus. Embora compartilhando várias ideias, como o naturalismo e, obviamente, a rejeição do monoteísmo, suas propostas têm diferenças importantes. Onfray imputa à religião a maioria dos males enfrentados pela humanidade, recusando-se a fazer qualquer concessão à tradição religiosa monoteísta, e propondo uma filosofia libertária de tipo hedonista e materialista. Comte-Sponville vê aspectos positivos na religião no tocante à manutenção da unidade social e propõe uma espiritualidade mística ateia. O artigo faz uma breve apresentação de suas teses e formula críticas a ambas as propostas. Onfray está muito mais preocupado em convencer de uma proposta política do que em argumentar filosoficamente em favor de uma tese e Comte-Sponville não parece perceber as consequências auto-refutadoras do naturalismo, que também torna muito problemática a própria noção de moralidade. Palavras-chave: Michel Onfray; Comte-Sponville; ateísmo; neoateísmo; naturalismo.  Abstract Michel Onfray and André Comte-Sponville are the most famous representatives of philosophical contemporary French atheism, which is a continuation of a tradition begun in the 18th Century of irreligious denying of the monotheistic notion of God. Although sharing many ideas, like naturalism and, obviously, the rejection of the monotheistic conception of God, their proposals show important distinctions. Onfray blames on religion most of evils faced by humanity, refusing to make any concession to monotheism, and proposing a libertarian, hedonistic, materialistic philosophy. Comte-Sponville sees positive aspects in religion regarding the keeping of social unity, and puts forward an atheistic spirituality. The article makes a brief

STRATEGIJA NAČRTOVANJA IN IZVEDBE PREDSTAVITVE PODJETJA STILLES D.O.O. NA MEDNARODNEM SEJMU POHIŠTVA V MILANU

OpenAIRE

Murenc, Matej Matic

2012-01-01

V delu diplomskega seminarja smo predstavili strategijo sejemskih predstavitev. Opisali smo značilnosti te strategije in aktivnosti, ki se odvijajo med njenim izvajanjem. V prvem delu naloge smo povzeli teoretično znanje različnih avtorjev. Strategijo predstavitve smo opredelili kot instrument pospeševanja prodaje. Nato pa smo spoznali različne vrste sejmov in njihove značilnosti. Spoznali smo, zakaj so sejemske predstavitve uspešne, in razloge, zakaj lahko predstavitve spodletijo. Raziskali ...

Perfil do absenteísmo em um banco estatal em Minas Gerais: análise no período de 1998 a 2003 Absenteeism profile in a state bank in Minas Gerais between 1998 a 2003

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Luiz Sérgio Silva

2008-12-01

Full Text Available O objetivo dessa pesquisa foi estudar o perfil do absenteísmo em uma empresa bancária estatal e estimar a prevalência de afastamentos pelas doenças que mais acometeram seus trabalhadores. Foi realizado um estudo transversal, descritivo e quantitativo abordando absenteísmo e prevalência de causas de afastamento em um banco estatal no estado de Minas Gerais, no período de 1998 a 2003. Os índices de absenteísmo apresentaram distribuição heterogênea, estando em queda no período estudado, exceto a taxa de freqüência, devido a modificações nos números que compõem seus numeradores e denominadores. As prevalências das doenças osteomusculares e dos distúrbios mentais e comportamentais foram 33,25 e 22,21 afastamentos por 1.000 trabalhadores, respectivamente. Houve predomínio de afastamentos de trabalhadores do sexo feminino, com idade entre 40 e 49 anos de idade, com tempo de empresa superior a 21 anos e com funções com menores valores de remuneração. O estudo indicou que as doenças osteomusculares e do tecido conjuntivo que antes predominavam na empresa estão em queda. Houve também ascensão dos distúrbios mentais e comportamentais, indicando possível mudança no perfil de adoecimento. Mais estudos são necessários para a explicação dos resultados observados.The purpose of this paper was to study the profile of absenteeism in a state bank and to establish the more frequent causes for sick leaves among the members of the staff. A cross-cut, descriptive and quantitative study was developed for approaching absenteeism and its most frequent causes in a state bank in the state of Minas Gerais between 1998 and 2003. The absenteeism rates were homogenous, with a decrease during the period of the study, except for the frequency rates, as a result of alterations in their numerators and denominators. The prevalence of musculoskeletal diseases and mental disorders was of 33,25 and 22,21 leaves per 1,000 workers respectively

Egoísmo de tres cuartillos: el sabotaje de los hacendados al tajón público de carnes en Santafé, 1798-1817

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Sergio Mejía

2015-01-01

Full Text Available Se estudia una serie de anomalías en el abasto de carnes de Santafé de Bogotá entre 1798 y 1817, causadas por la reticencia de los hacendados a acatar la orden del virrey Mendinueta de expender sus productos en una nueva carnicería o tajón en el centro de la ciudad. Decididos a no pagar el acarreo correspondiente, y valiéndose del cabildo (del que eran dueños, estos hacendados terminaron por imponer su voluntad sobre el virrey, quien transigió con un aumento del 50 % en el precio de la carne, a cambio de establecer el tajón. El caso muestra la debilidad del Estado colonial en sus postrimerías y pone en evidencia el egoísmo ante lo público de los potentados santafereños, que, al cabo de dos años, se convirtieron en beneméritos republicanos. Se usan papeles de los fondos: Abastos, Milicias y Marina, Miscelánea de la Colonia y Gobierno del Archivo General de la Nación de Bogotá.

SPLETNE UČILNICE IN E-LISTOVNIK "MAHARA"

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Tivadar, Petra

2011-01-01

V diplomskem delu smo opredelili, kaj je IKT, e-učenje, e-izobraževanje, izobraževanje na daljavo in hitro e-učenje. Nato smo opredelili, kaj so spletne učilnice in jih nekaj navedli. Opredelili smo, kaj je e-listovnik, kaj nam omogoča ter proučili prednosti in slabosti njegove uporabe. Osredotočili smo se na e-listovnik Mahara. Pregledali in preverili smo možnosti, ki jih Mahara ponuja, ter ugotavljali, zakaj jo uporabljati. Proučili smo tudi, kako jo uporabljati v izobraževanju in kakšne so...

KULTURNE RAZLIKE PRI TRGOVANJU MED SLOVENIJO IN KITAJSKO

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Potrpin, Tea

2012-01-01

V diplomski nalogi smo predstavili pojme kulture, medkulturnih razlik ter osnove poslovnega bontona. Na kratko smo predstavili splošne znamenitosti Slovenije in Kitajske, in njune gospodarske ter zgodovinske značilnosti, največ poudarka pa smo namenili poslovnemu bontonu oziroma medkulturnim razlikam. Analizirali smo dosedanje skupno poslovanje teh dveh držav ter ugotovili, da sta Slovenija in Kitajska povezani še iz časov Jugoslavije. Očitno smo uspeli dobro preučiti njihovo kulturo (in Kit...

GRADNJA INDUSTRIJSKEGA OBJEKTA Z VOTLIMI ARMIRANOBETONSKIMI MONTAŽNIMI PANELNIMI ELEMENTI

OpenAIRE

Skrbinek, Aleksander

2015-01-01

V diplomskem delu smo obravnavali gradnjo industrijske hale z uporabo armiranobetonskih montažnih panelnih elementov. Celotno diplomsko nalogo smo razdelili na več delov. V prvem delu smo opisali razvoj armiranega betona, saj je bil le ta ključnega pomena pri razvoju montažne gradnje. Potem smo predstavili sistem montažne gradnje z uporabo votlih AB montažnih panelnih elementov. Prav tako smo prikazali proizvodnjo elementov in primerjali med klasično armiranobetonsko gradnjo ter gradnjo s...

VPLIV VIRUSNEGA MARKETINGA NA VEDENJE POTROŠNIKOV

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Perčič, Luka

2016-01-01

V diplomski nalogi smo se posvetili virusnemu marketingu. Opredelili smo prednosti in slabosti virusnega marketinga ter vzroke za njegovo uspešnost. V teoretičnem delu smo opisali spletno tržno komuniciranje ter virusni marketing. Opisali smo, katera orodja se uporabljajo, njihove prednosti in slabosti. V raziskovalnem delu smo z anketnim vprašalnikom preverili, kako pogosto se anketiranci srečujejo z virusnimi oglasi in kako pogosto tovrstne oglase širijo. Zanimalo nas je tudi, kakšen odn...

Dielektrične lastnosti vodnih raztopin nekaterih mono- in polisaharidov

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Gubenšek, Špela

2017-01-01

V magistrskem delu smo raztopinam različnih saharidov določali dielektrične lastnosti. Analizirali smo vodne raztopine glukoze, fruktoze, inulina, dekstrina, maltodekstrina, oligofruktoze in glukozno-fruktoznega sirupa. Saharide smo okarakterizirali tako, da smo določili njihove reducirajoče lastnosti in v glukozno-fruktoznem sirupu delež fruktoze. Za določanje dielektrične konstante v območju frekvenc izmenične napetosti med 20 kHz in 2 MHz smo uporabili kapacitivno metodo in LCR merilnik. ...

ZAZNAVA IN VPLIV BARV NA PRIMERU TISKANIH OGLASOV

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Spes, Katja

2015-01-01

V diplomski nalogi smo s pomočjo literature opisali simboliko osnovnih barv, vpliv, ki ga imajo na ljudi, ter njihov pomen v oglasnih sporočilih. Omejili smo se na tiskane oglase (plakate, časopise, revije, neposredno pošto in embalažo) in opisali njihove prednosti in slabosti. Z anketnim vprašalnikom smo ugotavljali, na katere barve smo najbolj pozorni in katerim lastnostim se posamezne barve bolj približajo. Osredotočili smo se na sedem barv

ANALIZA UPORABNIŠKIH VMESNIKOV NA MOBILNIH NAPRAVAH

OpenAIRE

Bohak, Gregor

2012-01-01

V diplomskem delu smo predstavili pravila in smernice oblikovanja uporabniških vmesnikov na mobilnih napravah. Omejili smo se na platforme Google Android, Nokia Symbian, Nokia MeeGo, Apple iOS ter Microsoft Windows Phone 7. Za vsako izmed platform smo predstavili splošen model uporabniškega vmesnika, splošen model uporabniškega vmesnika aplikacije, navigacijske vzorce ter gradnike. Vse skupaj tudi smo obogatili z veliko grafičnega materiala. V drugem delu smo na podlagi pridobljenega znanja p...

Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.

Science.gov (United States)

Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan

2018-06-01

Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.

The CoxD protein, a novel AAA+ ATPase involved in metal cluster assembly: hydrolysis of nucleotide-triphosphates and oligomerization.

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Tobias Maisel

Full Text Available CoxD of the α-proteobacterium Oligotropha carboxidovorans is a membrane protein which is involved in the posttranslational biosynthesis of the [CuSMoO₂] cluster in the active site of the enzyme CO dehydrogenase. The bacteria synthesize CoxD only in the presence of CO. Recombinant CoxD produced in E. coli K38 pGP1-2/pETMW2 appeared in inclusion bodies from where it was solubilized by urea and refolded by stepwise dilution. Circular dichroism spectroscopy revealed the presence of secondary structural elements in refolded CoxD. CoxD is a P-loop ATPase of the AAA-protein family. Refolded CoxD catalyzed the hydrolysis of MgATP yielding MgADP and inorganic phosphate at a 1∶1∶1 molar ratio. The reaction was inhibited by the slow hydrolysable MgATP-γ-S. GTPase activity of CoxD did not exceed 2% of the ATPase activity. Employing different methods (non linear regression, Hanes and Woolf, Lineweaver-Burk, preparations of CoxD revealed a mean K(M value of 0.69±0.14 mM ATP and an apparent V(max value of 19.3±2.3 nmol ATP hydrolyzed min⁻¹ mg⁻¹. Sucrose density gradient centrifugation and gel filtration showed that refolded CoxD can exist in various multimeric states (2-mer, 4-mer or 6-mer, preferentially as hexamer or dimer. Within weeks the hexamer dissociates into the dimer, a process which can be reversed by MgATP or MgATP-γ-S within hours. Only the hexamers and the dimers exhibited MgATPase activity. Transmission electron microscopy of negatively stained CoxD preparations revealed distinct particles within a size range of 10-16 nm, which further corroborates the oligomeric organization. The 3D structure of CoxD was modeled with the 3D structure of BchI from Rhodobacter capsulatus as template. It has the key elements of an AAA+ domain in the same arrangement and at same positions as in BchI and displays the characteristic inserts of the PS-II-insert clade. Possible functions of CoxD in [CuSMoO₂] cluster assembly are discussed.

ANALIZA IN PRIMERJAVA MOBILNIH PLATFORM IZ VIDIKA RAZVIJALCA

OpenAIRE

Kokol, Nejc

2014-01-01

V diplomski nalogi se ukvarjamo s platformami Android, iOS in Windows Phone. Predstavili smo sam začetek pametnih telefonov in prelomnico, ki so jo povzročili na globalnem trgu. Predvsem pa smo se osredotočili na vodilne mobilne platforme Android, Windows Phone in iOS. Opisali smo njihovo zgodovino razvoja in strukturo. Izpostavili smo tudi njihove prednosti in slabosti, ki so še danes prisotne. Velik poudarek smo namenili vidiku razvijalca, kateremu so danes ponujene različne priložnosti za ...

Molecular evolution of the polyamine oxidase gene family in Metazoa

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Polticelli Fabio

2012-06-01

Full Text Available Abstract Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO and acetylpolyamine oxidase (APAO, specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO, it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported

FINANČNO NAČRTOVANJE

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Jurjevčič, Bor

2009-01-01

V diplomskem delu smo opisali problem finančnega načrtovanja v slovenskih podjetjih, pri tem pa smo se omejili na mikropodjetja in mala podjetja ter samostojne podjetnike, še posebej pa smo se posvetili finančnemu načrtu diverzifikacije lastnega podjetja, FI BOR, d. o. o. V prvem delu diplomske naloge smo opisali teoretičen vidik in pomen finančnega načrtovanja za podjetja, izvedeli anketo med podjetji o njihovem finančnem načrtovanju, pri čemer smo ugotovili, da se anketirana podjetja p...

Pomen ustrezne podjetniške ekipe in njene motivacije za uspeh start-up podjetja

OpenAIRE

Kumer, Špela

2015-01-01

V diplomskem projektu smo podrobneje preučevali vpliv podjetniške ekipe in njene motivacije na uspeh start-up podjetja. V teoretičnem delu smo najprej razložili osnovne pojme, povezane s start-up podjetji ter opisali načine dela, ki se v takih podjetjih uporabljajo. Na kratko smo opisali tudi podjetniški proces, katerega sestavni del je med drugim podjetniška ekipa. Podjetniško ekipo smo raziskovali podrobneje – navedli smo njeno optimalno sestavo, potrebne lastnosti ekipe in izkušnje...

ABSENTIZEM IN FLUKTUACIJA V OBČINI ŠKOFJA LOKA

OpenAIRE

Hafner, Urban

2014-01-01

V diplomskem delu smo raziskali absentizem in fluktuacijo v občini Škofja Loka. Diplomsko delo je sestavljeno iz teoretičnega in empiričnega dela. V teoretičnem delu smo s pomočjo literature razložili strokovne pojme s poudarkom na absentizmu in fluktuaciji. Predstavili smo organizacijo in s formulami za izračun stopnje absentizma in fluktuacije izračunali vrednosti teh dveh pojmov za leta 2011, 2012 in 2013. V empiričnem delu smo kot orodje uporabili anketni vprašalnik, ki smo ga raz...

INEL Sample Management Office

International Nuclear Information System (INIS)

Watkins, C.

1994-01-01

The Idaho National Engineering Laboratory (INEL) Sample Management Office (SMO) was formed as part of the EG ampersand G Idaho Environmental Restoration Program (ERP) in June, 1990. Since then, the SMO has been recognized and sought out by other prime contractors and programs at the INEL. Since December 1991, the DOE-ID Division Directors for the Environmental Restoration Division and Waste Management Division supported the expansion of the INEL ERP SMO into the INEL site wide SMO. The INEL SMO serves as a point of contact for multiple environmental analytical chemistry and laboratory issues (e.g., capacity, capability). The SMO chemists work with project managers during planning to help develop data quality objectives, select appropriate analytical methods, identify special analytical services needs, identify a source for the services, and ensure that requirements for sampling and analysis (e.g., preservations, sample volumes) are clear and technically accurate. The SMO chemists also prepare work scope statements for the laboratories performing the analyses

PRIMERJAVA POROČIL ZA VODENJE INFORMATIKE COBIT 4.1 IN COBIT 5

OpenAIRE

Štagar, Darja

2012-01-01

V diplomskem delu smo predstavili področja upravljanja informatike, ki jih je za uspešno poslovanje potrebno upravljati organizirano. Priporočljiva je uporaba različnih standardov in priporočil, zato smo v delu predstavili nekatere standarde in priporočila, ki to omogočajo. Glavna tema te naloge so priporočila za vodenje informatike CobIT, ki smo jih tudi podrobneje predstavili. Obravnavali smo zadnji dve različici, CobIT 4.1 in CobIT 5. Ker sta si med seboj bistveno različni, smo ju primerja...

UPORABA PISARNE V OBLAKU ZA POTREBE DRUŽINSKEGA IN MLADINSKEGA CENTRA

OpenAIRE

Repnik, Tina

2013-01-01

V diplomski nalogi smo v prvem delu teoretično obravnavali teledelo in računalništvo v oblaku. Preučili smo poznane rešitve računalništva v oblaku na trgu in se odločili za uporabo storitev enega izmed vodilnih podjetij s tega področja Google. Opredelili smo začetke in razvoj Googlea v svetu. Za potrebe Družinskega in mladinskega centra v Cerkljah smo z uporabo storitve Google Drive in Google Koledar ustvarili pisarno v oblaku. Za vse, ki niso vešči uporabe naštetih storitev, smo pripravi...

Victimización y heroísmo. Disputas de las memorias emblemáticas de la izquierda chilena en dos fechas conmemorativas: aniversario del golpe de Estado y día del joven combatiente

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Tamara vidaurrazaga aránguiz

2015-01-01

Full Text Available En el presente trabajo proponemos reflexionar en torno a dos memorias emblemáticas y dicotómicas que tienen lugar dentro de la izquierda chilena a la hora de recordar a quienes resistieron a la dictadura de Pinochet, reelaboraciones que hemos denominado memoria de la victimización y memoria del heroísmo, y que ejemplificaremos en dos fechas icónicas para la izquierda chilena: la conmemoración del Golpe de Estado cada 11 de septiembre, y el Día del Joven Combatiente rememorado cada 29 de marzo. Lo que nos interesa es reflexionar en torno a la marmolización que implican estas dos reconstrucciones, y la dificultad para imaginar un futuro para el proyecto político heredado por la izquierda chilena al sumirnos en esta dicotomía estanca.

On-chip growth of semiconductor metal oxide nanowires for gas sensors: A review

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Chu Manh Hung

2017-09-01

Full Text Available Semiconductor metal oxide nanowires (SMO-NWs show great potential for novel gas sensor applications because of their distinct properties, such as a high surface area to volume aspect ratio, high crystallinity and perfect pathway for electron transfer (length of NW. SMO-NW sensors can be configured as resistors or field-effect transistors for gas detection and different configurations, such as a single NW, multiple NWs, and networked NW films, have been established. Surface-functionalizing NWs with catalyst elements and self-heating NWs provide additional advantages for highly selective and low-power consumption gas sensors. However, an appropriate design of SMO-NWs is of practical importance in enhancing the gas-sensing performance of SMO-NW sensors. The on-chip growth of SMO-NWs possesses many advantages which can thus be effectively used for the large-scale fabrication of SMO-NW sensors with improved gas response and stability. This review aims to provide up-to-date information on the on-chip fabrication of SnO2, ZnO, WO3, CuO, and other SMO-NW sensors. It also discusses a variety of promising approaches that help advance the on-chip fabrication of SMO-NW-based gas sensors and other NW-based devices.

IZBOLJŠAVA STATISTIČNEGA NADZORA PROCESA V PODJETJU VIP - VIRANT D.O.O.

OpenAIRE

Dolžan, Tomaž

2014-01-01

Tema diplomske naloge so kabelski snopi oziroma povezave, ki se uporabljajo v namen avtomobilske industrije. Pri obravnavanih kabelskih snopih gre za problematiko statističnega nadzora proizvodnega procesa. V nalogi smo se ukvarjali z izboljšavo dosedanjega statističnega nadzora proizvodnega procesa in pri tem dobili tudi konkretne podatke za dva parametra, katera smo merili. Meritve smo opravljali na podlagi jemanja vzorcev iz proizvodnega procesa. Opisali smo preteklo stanje statističnega n...

Abordagem multifatorial do absenteísmo por doença em trabalhadores de enfermagem Abordaje multifactorial del ausentismo por enfermedad en trabajadores de enfermería A multifactorial approach to sickness absenteeism among nursing staff

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Roberta Carolina Ferreira

2012-04-01

Full Text Available OBJETIVO: Analisar fatores associados ao absenteísmo por doença autorreferido em trabalhadores de enfermagem. MÉTODOS: Estudo transversal com 1.509 trabalhadores de três hospitais públicos no município do Rio de Janeiro, RJ, em 2006. O absenteísmo foi classificado em três níveis: nenhum dia, poucos dias (um a nove dias e muitos dias (> 10 dias, a partir da resposta a uma pergunta do questionário de avaliação do índice de capacidade para o trabalho. As análises de regressão logística levaram em conta um modelo conceitual com base em determinantes distais (condições socioeconômicas, de níveis intermediários I (características ocupacionais e II (características do estilo de vida, e proximais (doenças e condições de saúde. RESULTADOS: As frequências de absenteísmo por doença foram de 20,3% e 16,6% para poucos e muitos dias, respectivamente. Aqueles que referiram mais de um emprego, doenças osteomusculares e avaliaram sua saúde como ruim ou regular apresentaram chances mais elevadas de absenteísmo. Comparados aos enfermeiros, os auxiliares tiveram menor chance de referir poucos dias e os técnicos, maiores chances de apresentar muitos dias de ausência. Chances mais elevadas de referir muitos dias de ausência foram observadas entre os servidores públicos em relação aos contratados (OR = 3,12; IC95% 1,86;5,22 e entre os casados (OR = 1,73; IC95% 1,14;2,63 e separados, divorciados e viúvos (OR = 2,06; IC95% 1,27;3,35, comparados aos solteiros. CONCLUSÕES: Diferentes variáveis foram associadas às duas modalidades de absenteísmo, o que sugere sua determinação múltipla e complexa, relacionada a fatores de diversos níveis que não podem ser explicados apenas por problemas de saúde.OBJETIVO: Analizar factores asociados al ausentismo por enfermedad auto referida en trabajadores de enfermería. MÉTODOS: Estudio transversal con 1.509 trabajadores de tres hospitales públicos en Rio de Janeiro, Sureste de Brasil

Indian hedgehog signaling triggers Nkx3.2 protein degradation during chondrocyte maturation

Science.gov (United States)

Choi, Seung-Won; Jeong, Da-Un; Kim, Jeong-Ah; Lee, Boyoung; Joeng, Kyu Sang; Long, Fanxin; Kim, Dae-Won

2015-01-01

The Indian hedgehog (Ihh) pathway plays an essential role in facilitating chondrocyte hypertrophy and bone formation during skeletal development. Nkx3.2 is initially induced in chondrocyte precursor cells, maintained in early-stage chondrocytes, and down-regulated in terminal-stage chondrocytes. Consistent with these expression patterns, Nkx3.2 has been shown to enhance chondrocyte differentiation and cell survival, while inhibiting chondrocyte hypertrophy and apoptosis. Thus, in this work, we investigate whether Nkx3.2, an early stage chondrogenic factor, can be regulated by Ihh, a key regulator for chondrocyte hypertrophy. Here, we show that Ihh signaling can induce proteasomal degradation of Nkx3.2. In addition, we found that Ihh can suppress levels of Lrp (Wnt co-receptor) and Sfrp (Wnt antagonist) expression, which, in turn, may selectively enhance Lrp-independent non-canonical Wnt pathways in chondrocyte. In agreement with these findings, Ihh-induced Nkx3.2 degradation requires Wnt5a, which is capable of triggering Nkx3.2 degradation. Finally, we found that Nkx3.2 protein levels in chondrocytes are remarkably elevated in mice defective in Ihh signaling by deletion of either Ihh or Smoothened. Thus, these results suggest that Ihh/Wnt5a signaling may play a role in negative regulation of Nkx3.2 for appropriate progression of chondrocyte hypertrophy during chondrogenesis. PMID:22507129

Talent management kot metoda razvoja človeških virov

OpenAIRE

Pavić, Lazar

2016-01-01

V magistrskem delu smo predstavili talent management kot eno izmed sodobnih metod razvoja človeških virov. Magistrsko delo obsega naslednja poglavja: uvod, teoretični del, empirični del, perspektivni del in sklep. V uvodnem delu magistrskega dela smo podrobnejše opisali področje in opredelili raziskovalni problem, predstavili smo namen, cilje in raziskovalne hipoteze, predpostavke in omejitve raziskave kot tudi predvidene metode raziskovanja. V teoretičnem delu magistrskega dela smo p...

PRIPRAVA STROKOVNIH PODLAG ZA UVEDBO SISTEMA ZA UPRAVLJANJE INFORMACIJSKE VARNOSTI

OpenAIRE

Tršelič, Tugomir

2014-01-01

V diplomskem delu smo raziskali področje informacijske varnosti. Namen raziskave je bil priprava strokovnih podlag, na osnovi katerih smo pridobili podporo vodstva za vpeljavo sistema upravljanja z informacijsko varnostjo v podjetju. V raziskavo smo vključili ključne koncepte informacijske varnosti, pregled novih tehnologij, opravljene lokalne in globalne raziskave s področja varnostnih incidentov in pregled pomembne področne zakonodaje. Ugotovitve smo nadgradili s pregledom ključnih področni...

Anthony Collins revisitado : deísmo, panteísmo y ateísmo en los tiempos modernos

OpenAIRE

Benítez, Miguel

2007-01-01

Con ocasión de la refutación de una interpretación reciente del pensamiento de Anthony Collins, fundada en presupuestos metodológicos erráticos y tributarios, en definitiva, de la concepción propia de los apologistas en tiempos de las Luces, este trabajo denuncia los abusos en la historiografía de los tiempos modernos de una mal llamada lectura entre líneas, que implica no el examen detenido del texto en su complejidad, sino el menosprecio de la letra, y pr...

Pozitivni in negativni vplivi risank na otroke

OpenAIRE

Povše, Nika

2017-01-01

V tej diplomski nalogi smo raziskovali pozitivne in negativne vplive risank na otroke. Začeli smo z zgodovino televizije, tako svetovno zgodovino kot zgodovino televizije na Slovenskem. Na isti način smo pregledali tudi zgodovino risank. Raziskovali smo otrokov razvoj, predvsem tiste vidike, ki so izpostavljeni vplivom risank, kot so morala, jezik, domišljija in učenje. Sledilo je raziskovanje negativnih in pozitivnih vplivov, ki jih imajo risanke na otroke, kar je tudi naš glavni problem te ...

Analiza koristnosti in stroškov

OpenAIRE

Škrjanec, Blaž

2017-01-01

V zaključni nalogi smo iskali rešitev za izkop jarka za polaganje optičnega kabla. V prvem delu smo predstavili analizo koristnosti, analizo stroškov, analizo koristnosti in stroškov ter metode odločanja. Na podlagi omenjenih metod za podporo odločanja smo v nadaljevanju prišli do končne odločitve. Na podlagi vseh zbranih rezultatov smo dokazali da je rovokopač najprimernejša rešitev za dani problem.

DEJAVNIKI STRESA V RAČUNOVODSKI DEJAVNOSTI ORGANIZACIJ X IN Y

OpenAIRE

Kotolenko, Maša

2009-01-01

V diplomskem delu smo se lotili raziskave o stresorjih na delovnem mestu, natančneje v računovodski dejavnosti. Najprej smo definirali pojem stresor. Sledila je predstavitev mikro in makro stresorjev, prisotnih v delovnem okolju. Pri tej predstavitvi smo se osredotočili na mikro in makro stresorje v računovodski dejavnosti. Predstavili smo po mnenju različnih avtorjev najpogostejše stresorje v računovodski dejavnosti, definicijo posameznega stresorja ter njihove značilnosti. V nadaljevanju je...

ABSENTIZEM IN FLUKTUACIJA V POSLOVALNICAH PODJETJA X d. o. o.

OpenAIRE

Janc, Mojca

2011-01-01

V diplomskem delu smo predstavili problem absentizma in fluktuacije v poslovalnicah podjetja X d. o. o.. Diplomsko nalogo smo razdelili na teoretični in empirični del. V teoretičnem delu smo opredelili absentizem, opisali vrste absentizma, našteli vzroke, ki vplivajo nanj, podrobneje opisali zdravstveni absentizem, našteli njegove vzroke, prikazali gibanje zdravstvenega absentizma v Sloveniji in ga primerjali z drugimi državami Evropske unije. Našteli smo tudi ključne elemente, za obvladovanj...

Aberrant Hedgehog ligands induce progressive pancreatic fibrosis by paracrine activation of myofibroblasts and ductular cells in transgenic zebrafish.

Directory of Open Access Journals (Sweden)

In Hye Jung

Full Text Available Hedgehog (Hh signaling is frequently up-regulated in fibrogenic pancreatic diseases including chronic pancreatitis and pancreatic cancer. Although recent series suggest exclusive paracrine activation of stromal cells by Hh ligands from epithelial components, debates still exist on how Hh signaling works in pathologic conditions. To explore how Hh signaling affects the pancreas, we investigated transgenic phenotypes in zebrafish that over-express either Indian Hh or Sonic Hh along with green fluorescence protein (GFP to enable real-time observation, or GFP alone as control, at the ptf1a domain. Transgenic embryos and zebrafish were serially followed for transgenic phenotypes, and investigated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR, in situ hybridization, and immunohistochemistry. Over-expression of Ihh or Shh reveals virtually identical phenotypes. Hh induces morphologic changes in a developing pancreas without derangement in acinar differentiation. In older zebrafish, Hh induces progressive pancreatic fibrosis intermingled with proliferating ductular structures, which is accompanied by the destruction of the acinar structures. Both myofibroblasts and ductular are activated and proliferated by paracrine Hh signaling, showing restricted expression of Hh downstream components including Patched1 (Ptc1, Smoothened (Smo, and Gli1/2 in those Hh-responsive cells. Hh ligands induce matrix metalloproteinases (MMPs, especially MMP9 in all Hh-responsive cells, and transform growth factor-ß1 (TGFß1 only in ductular cells. Aberrant Hh over-expression, however, does not induce pancreatic tumors. On treatment with inhibitors, embryonic phenotypes are reversed by either cyclopamine or Hedgehog Primary Inhibitor-4 (HPI-4. Pancreatic fibrosis is only prevented by HPI-4. Our study provides strong evidence of Hh signaling which induces pancreatic fibrosis through paracrine activation of Hh-responsive cells in vivo. Induction of

Systematic study of source mask optimization and verification flows

Science.gov (United States)

Ben, Yu; Latypov, Azat; Chua, Gek Soon; Zou, Yi

2012-06-01

Source mask optimization (SMO) emerged as powerful resolution enhancement technique (RET) for advanced technology nodes. However, there is a plethora of flow and verification metrics in the field, confounding the end user of the technique. Systemic study of different flows and the possible unification thereof is missing. This contribution is intended to reveal the pros and cons of different SMO approaches and verification metrics, understand the commonality and difference, and provide a generic guideline for RET selection via SMO. The paper discusses 3 different type of variations commonly arise in SMO, namely pattern preparation & selection, availability of relevant OPC recipe for freeform source and finally the metrics used in source verification. Several pattern selection algorithms are compared and advantages of systematic pattern selection algorithms are discussed. In the absence of a full resist model for SMO, alternative SMO flow without full resist model is reviewed. Preferred verification flow with quality metrics of DOF and MEEF is examined.

A semantic web ontology for small molecules and their biological targets.

Science.gov (United States)

Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

2010-05-24

A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

Optimizacija razvoza po lastnih prodajalnah izbranega podjetja

OpenAIRE

Bagari, Jasmina

2015-01-01

V diplomskem delu obravnavamo problematiko optimizacije razvoza pekovskih izdelkov v lastne prodajalne. Reševanja problematike smo se lotili s pomočjo sledilnega sistema Trak 8. Najprej smo naredili posnetek stanja in nato analizirali pridobljene podatke. Prišli smo do zaključka, da lahko proge razvoza bolj racionalno in točno načrtujemo. S tem odpravimo podvojene kilometre, prazne kilometre in zmanjšamo stroške razvoza. Po prestrukturiranju vseh prog smo prišli do spoznanja, da lahko lastne ...

Analiza pokritosti področij ISACA v dodiplomskih in magistrskih študijah v Sloveniji

OpenAIRE

Gjeorgievski, Emil

2017-01-01

V diplomski nalogi smo raziskali in analizirali pokritost ISACA področij v dodiplomskih in podipolomskih študijih v Sloveniji. Opisali smo in definirali ISACA področij (CRISC/CISA/CISM/CGEIT) in ocenili kakšen vpliv imajo na dodiplomske in podiplomske študije. S pomočjo spletne strani 1ka.si smo pripravili spletno anketo in skupaj s spremljajočim dopisom posredovali na izbrane kontaktne e-naslove slovenskih fakultet.. Pridobljene rezultate smo statistično analizirali in grafično predstavili. ...

Školjčni diagram aksialne turbine

OpenAIRE

Močnik, Jan

2017-01-01

V zaključni nalogi smo obravnavali karakteristike in postopek določanja karakteristik aksialne vodne turbine. Opazovali smo, kako se izhodna moč in izkoristek turbine spreminjata pri različnih obratovalnih pogojih. Meritve smo izvedli na modelnem preizkuševališču FM3SU, na katerem je bila nameščena modelna različica aksialne vodne turbine. Med preizkusom smo merili volumenski tok in tlak vode pred vstopom v turbino, vrtilno frekvenco gonilnika turbine ter zaviralno silo. Na podlagi meritev s...

VLOGA IZVEDENCA ZA RAČUNOVODSTVO V KAZENSKIH POSTOPKIH

OpenAIRE

Golnar, Brigita

2015-01-01

V našem diplomskem seminarju smo spoznali forenzično računovodstvo. Ker je ta veja računovodstva močno povezana s pravno stroko, smo bolje predstavili pravni vidik, ki se navezuje na našo temo. V okviru tega smo se dotaknili kazenskega procesnega prava in opisali kazenski in dokazni postopek. Poudarek celotnega diplomskega seminarja temelji na tem, kakšna je vloga izvedenca v kazenskih postopkih. Spoznali smo, da je vloga izvedenca v kazenskih postopkih lahko zelo pomembna, zato mora izvedene...

A Synthesis Model of Sustainable Market Orientation: Conceptualization, Measurement, and Influence on Academic Accreditation--A Case Study of Egyptian-Accredited Faculties

Science.gov (United States)

Abou-Warda, Sherein H.

2014-01-01

Higher education institutions are increasingly concerned about accreditation. Although sustainable market orientation (SMO) bears on academic accreditation, to date, no study has developed a valid scale of SMO or assessed its influence on accreditation. The purpose of this paper is to construct and validate an SMO scale that was developed in…

OGLAŠEVANJE TRGOVSKEGA CENTRA X

OpenAIRE

Dautović, Sabrina

2013-01-01

V diplomskem delu smo se ukvarjali s problematiko uspešnega oglaševanja trgovskega centra X. V teoretičnem delu smo opisali cilje oglaševanja, predstavili pet odločitev o oglaševanju, podali temeljne strategije trženja, opisali, na podlagi česa se kupci odločijo za izbiro prodajalne in kakšni so njihovi motivi za nakup. Opredelili smo pojem trgovski center in analizirali konkurente. V praktičnem delu smo opisali izvedbo ankete, analizirali odgovore in s pomočjo dobljenih odgovorov ovr...

Premagovanje izzivov življenja z disleksijo od otroštva do odraslosti

OpenAIRE

Javornik, Pia

2017-01-01

V magistrskem delu smo raziskali izzive, s katerimi se srečujejo osebe z disleksijo skozi celoten razvojni potek od otroštva do odraslosti. V teoretičnem delu smo povzeli nekatere definicije ter teoretične razlage disleksije in njeno izražanje skozi različna razvojna obdobja, vezana na potek znotraj izobraževalnega sistema. Predstavili smo zakonodajne možnosti prilagajanja vzgojno izobraževalnega procesa osebam z disleksijo v slovenskem prostoru. V nadaljevanju smo se osredotočili na značilno...

VPLIV LIKOVNE TEHNIKE NA IZBIRO BARV PRI PREDŠOLSKEM OTROKU

OpenAIRE

Marčec, Tamara

2013-01-01

Diplomsko delo z naslovom Vpliv likovne tehnike na izbiro barv pri predšolskem otroku je sestavljeno iz teoretičnega in praktičnega dela. V teoretičnem delu smo na kratko predstavili ustvarjalnost, njene faze in faktorje ter kako spodbujamo ali zaviramo ustvarjalnost pri predšolskem otroku. Nato smo nadaljevali in opisali vlogo in pomen barve za predšolskega otroka. Predstavili smo likovna področja in vsako na kratko opisali. Kasneje smo podrobneje opisali področje slikanja, kajti naše de...

Data base formation for important components of reactor TRIGA MARK II

Energy Technology Data Exchange (ETDEWEB)

Jordan, R; Mavko, B; Kozuh, M [Inst. Jozef Stefan, Ljubljana (Slovenia)

1992-07-01

The paper represents specific data base formation for reactor TRIGA MARK II in Podgorica. Reactor operation data from year 1985 to 1990 were collected. Two groups of collected data were formed. The first group includes components data and the second group covers data of reactor scrams. Time related and demand related models were used for data evaluation. Parameters were estimated by classical method. Similar data bases are useful everywhere where components unavailabilities may have severe drawback. (author) [Slovenian] V referatu smo prikazali raziskavo, v okviru katere smo za raziskovalni reaktor TRIGA MARK II v Podgorici izoblikovali specificno bazo podatkov. Zbrali smo podatke obratovanja reaktorja od leta 1985 do 1990. Rezultate raziskave dogodkov smo razdelili v dve glavni skupini. V prvo spadajo obratovalni podatki o komponentah, v drugo skupino pa spadajo zagoni oz. zaustavitve reaktorja. Podatke smo ovrednotili z modelom v casovnem prostoru in z modelom na zahtevo. Parametre modelov smo dolocili s klasicno metodo. Opisane baze podatkov so uporabne povsod, kjer so lahko posledice nezanesljivega delovanja sistemov velike. [author].

STRATEGIJE VARNOSTNEGA KOPIRANJA PODATKOV IN REŠITVE ZA MALA PODJETJA

OpenAIRE

Kočevar, Dušan

2012-01-01

V diplomskem delu bomo definirali in predstavili strategije varnostnega kopiranja podatkov in pomen podatkov za podjetja. V teoretičnem delu smo opisali zgodovino varnostnega kopiranja in arhiviranja, medije za shranjevanje in podatkovne repozitorne modele. Opisali in primerjali smo strategije in pristope varnostnega kopiranja ter predstavili statistiko izgube podatkov. Zraven tradicionalnih pristopov smo predstavili tudi varnostno shranjeva...

PROBLEM RAZVAJENOSTI OTROK IN POUK KNJIŽEVNOSTI V TRETJEM TRILETJU OSNOVNE ŠOLE

OpenAIRE

Videtič, Mojca

2013-01-01

V diplomskem delu smo skušali prikazati, kolikšna je vključenost elementov razvajenosti v berilih za tretje triletje osnovnih šol. Pri analizi smo se omejili na berila iz Kataloga učbenikov. Skušali smo predstaviti problematiko razvajenosti v okviru pouka književnosti. V prvem delu diplomskega dela smo predstavili pojme, ki so ključni pri analizi tega problema (načini razvajanja, posledice razvajenosti, čustvena inteligenca), in skušali podati nekaj predlogov za lažje in uspešnejše delo z raz...

RAZVOJ OBLAČIL V HIP HOP KULTURI

OpenAIRE

Marić, Sanja

2010-01-01

V diplomskem delu smo raziskovali, kako so se hip hop oblačila razvijala skozi obdobja v hip hop kulturi. V teoretičnem deli smo ugotavljali ozadje in dejavnike, ki so vplivali na razvoj hip hop kulture, v empiričnem delu diplomske naloge pa smo izvedli anketni vprašalnik z glavnimi akterji hip hop kulture na slovenski hip hop sceni. Rezultati, ki smo jih dobili, kažejo da so imela oblačila velik vpliv na prepoznavnost in razvoj hip hop kulture po celem svetu. K temu so največ pripomogli ustv...

Changes in ankle joint motion after Supramalleolar osteotomy: a cadaveric model.

Science.gov (United States)

Kim, Hak Jun; Yeo, Eui Dong; Rhyu, Im Joo; Lee, Soon-Hyuck; Lee, Yeon Soo; Lee, Young Koo

2017-09-09

Malalignment of the ankle joint has been found after trauma, by neurological disorders, genetic predisposition and other unidentified factors, and results in asymmetrical joint loading. For a medial open wedge supramalleolar osteotomy(SMO), there are some debates as to whether concurrent fibular osteotomy should be performed. We assessed the changes in motion of ankle joint and plantar pressure after supramalleolar osteotomy without fibular osteotomy. Ten lower leg specimens below the knee were prepared from fresh-frozen human cadavers. They were harvested from five males (10 ankles)whose average age was 70 years. We assessed the motion of ankle joint as well as plantar pressure for SS(supra-syndesmotic) SMO and IS(intra-syndesmotic) SMO. After the osteotomy, each specimen was subjected to axial compression from 20 N preload to 350 N representing half-body weight. For the measurement of the motion of ankle joint, the changes in gap and point, angles in ankle joint were measured. The plantar pressure were also recorded using TekScan sensors. The changes in the various gap, point, and angles movements on SS-SMO and IS-SMO showed no statistically significant differences between the two groups. Regarding the shift of plantar center of force (COF) were noted in the anterolateral direction, but not statistically significant. SS-SMO and IS-SMO with intact fibula showed similar biomechanical effect on the ankle joint. We propose that IS-SMO should be considered carefully for the treatment of osteoarthrosis when fibular osteotomy is not performed because lateral cortex fracture was less likely using the intrasyndesmosis plane because of soft tissue support.

OBLIKOVANJE EKOLOŠKE EMBALAŽE

OpenAIRE

Vehovar, Barbara

2012-01-01

V diplomskem delu smo predstavili ekološko oblikovanje embalaže, ki je vidno skozi grafično podobo in pomen le-tega za okolje. Najprej smo se posvetili embalaži in njenim značilnostim ter nadaljevali z ekološkim vidikom embalaže. Nato smo se osredotočili na ekološko oblikovanje ter elemente, ki asociirajo na ekološkost. Za konec smo analizirali nekaj embalaž kozmetičnih izdelkov ter oblikovali ekološko embalažo za enega od analiziranih, ki je po našem mnenju imel najmanj ekološko embalažo....

Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.

Science.gov (United States)

Gurgel, Clarissa Araújo Silva; Buim, Marcilei Eliza Cavichiolli; Carvalho, Kátia Cândido; Sales, Caroline Brandi Schlaepfer; Reis, Mitermayer Galvão; de Souza, Renata Oliveira; de Faro Valverde, Ludmila; de Azevedo, Roberto Almeida; Dos Santos, Jean Nunes; Soares, Fernando Augusto; Ramos, Eduardo Antônio Gonçalves

2014-09-01

Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB). We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry. We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521). Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sinteza bakrovih, kobaltovih in nikljevih koordinacijskih spojin z izoniazidom

OpenAIRE

Hrastar, Sabina

2016-01-01

V diplomskem delu sem se ukvarjala s sintezo in karakterizacijo novih bakrovih, kobaltovih in nikljevih koordinacijskih spojin. Za sintezo smo uporabili bakrov acetat monohidrat, kobaltov acetat tetrahidrat in nikljev acetata tetrahidrat ter ligand izoniazid. Izvedli smo sedemdeset sinteznih reakcij, pri čemer smo spreminjali različne parametre: čas sinteze, temperaturo, topilo (destilirana voda, metanol, etanol, aceton, acetonitril, tetrahidrofuran, diklorometan, N,N-dimetilformamid) in post...

Algoritmi stiskanja sekvenc DNK

OpenAIRE

Dobnik, Matej

2017-01-01

V diplomskem delu smo na kratko opisali lastnosti in značilnosti zaporedij deoksiribonukleinske kisline (v nadaljevanju DNK) ter algoritmov stiskanja podatkov. Implementirali smo algoritem LZW in Huffmanov algoritem, ki sta prilagojena stiskanju zaporedij DNK, ter izboljšan algoritem DNABIT Compress, ki se ga enostavno razširja z novimi možnostmi. Vse algoritme smo med seboj primerjali glede na učinkovitost stiskanja.

PRISTOPI K MONETIZACIJI MOBILNIH APLIKACIJ

OpenAIRE

Plavčak, Gregor

2016-01-01

Diplomsko delo zajema pregled prihodkovnih modelov in različnih pristopov monetizacije mobilnih aplikacij. Predstavili smo ponudnike mobilnih operacijskih sistemov, proizvajalce pametnih naprav, distribucijske platforme, mobilne operaterje, ponudnike mobilnih aplikacij in končne uporabnike. Raziskali in predstavili smo brezplačni prihodkovni model, plačljivi prihodkovni model, prihodkovni model mikro transakcij, naročnin, oglaševanja, partnerstva in podpornih aplikacij. Na kratko smo analizi...

Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose

Science.gov (United States)

Zhu, Shu Yun; Dong, Ying; Tu, Jie; Zhou, Yue; Zhou, Xing Hua; Xu, Bin

2014-01-01

Background: Silybum marianum has been used as herbal medicine for the treatment of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia since ancient times. Silybum marianum oil (SMO), a by-product of silymarin production, is rich in essential fatty acids, phospholipids, sterols, and vitamin E. However, it has not been very good development and use. Objective: In the present study, we used olive oil as a control to investigate the antioxidant and anti-aging effect of SMO in D-galactose (D-gal)-induced aging mice. Materials and Methods: D-gal was injected intraperitoneally (500 mg/kg body weight daily) for 7 weeks while SMO was simultaneously administered orally. The triglycerides (TRIG) and cholesterol (CHOL) levels were estimated in the serum. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), monoamine oxidase (MAO), malondialdehyde (MDA), caspase-3, and Bcl-2 were determined in the liver and brain. The activities of Na+-K+-adenosine triphosphatase (ATPase), Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity of the liver mitochondrial were estimated. Results: SMO decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels of MAO and MDA in the liver and brain were reduced by SMO administration in aging mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased the concentration of caspase-3 and improved the activity of Bcl-2 in the liver and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity. Conclusion: These results indicate that SMO effectively attenuated oxidative damage and improved apoptosis related factors as well as liver mitochondrial dysfunction in aging mice. PMID:24914315

Comparison of wind turbines based on power curve analysis

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-02-01

In the study measured power curves for 46 wind turbines were analyzed with the purpose to establish the basis for a consistent comparison of the efficiency of the wind turbines. Emphasis is on wind turbines above 500 kW rated power, with power curves measured after 1994 according to international recommendations. The available power curves fulfilling these requirements were smoothened according to a procedure developed for the purpose in such a way that the smoothened power curves are equally representative as the measured curves. The resulting smoothened power curves are presented in a standardized format for the subsequent processing. Using wind turbine data from the power curve documentation the analysis results in curves for specific energy production (kWh/M{sup 2}/yr) versus specific rotor load (kW/M{sup 2}) for a range of mean wind speeds. On this basis generalized curves for specific annual energy production versus specific rotor load are established for a number of generalized wind turbine concepts. The 46 smoothened standardized power curves presented in the report, the procedure developed to establish them, and the results of the analysis based on them aim at providers of measured power curves as well as users of them including manufacturers, advisors and decision makers. (au)

Accurate torque-sensorless control approach for interior permanent-magnet synchronous machine based on cascaded sliding mode observer

Directory of Open Access Journals (Sweden)

Kai-Hui Zhao

2017-06-01

Full Text Available To improve the accuracy of torque control for vector control of interior permanent-magnet synchronous machine (IPMSM, this study proposes a torque-sensorless control method based on cascaded sliding mode observer (SMO. First, the active flux model is discussed, which converts the model of IPMSM into the equivalent model of surface-mounted permanent-magnet synchronous machine. Second, to reduce chattering caused by system parameters variations and external disturbances, the cascaded observer is designed, which is composed of a variable gain adaptive SMO and an active flux SMO. The variable gain adaptive SMO is designed to estimate the speed, rotor position and stator resistance in the d–q reference frame. The active flux SMO is designed to estimate the active flux and torque in the α–β reference frame. Global asymptotic stability of the observers is guaranteed by the Lyapunov stability analysis. Finally, simulations and experiments are carried out to verify the effectiveness of the proposed control scheme.

Fuzzy Sliding Mode Observer with Grey Prediction for the Estimation of the State-of-Charge of a Lithium-Ion Battery

Directory of Open Access Journals (Sweden)

Daehyun Kim

2015-11-01

Full Text Available We propose a state-of-charge (SOC estimation method for Li-ion batteries that combines a fuzzy sliding mode observer (FSMO with grey prediction. Unlike the existing methods based on a conventional first-order sliding mode observer (SMO and an adaptive gain SMO, the proposed method eliminates chattering in SOC estimation. In this method, which uses a fuzzy inference system, the gains of the SMO are adjusted according to the predicted future error and present estimation error of the terminal voltage. To forecast the future error value, a one-step-ahead terminal voltage prediction is obtained using a grey predictor. The proposed estimation method is validated through two types of discharge tests (a pulse discharge test and a random discharge test. The SOC estimation results are compared to the results of the conventional first-order SMO-based and the adaptive gain SMO-based methods. The experimental results show that the proposed method not only reduces chattering, but also improves estimation accuracy.

A bioinformatics approach for precision medicine off-label drug drug selection among triple negative breast cancer patients.

Science.gov (United States)

Cheng, Lijun; Schneider, Bryan P; Li, Lang

2016-07-01

Cancer has been extensively characterized on the basis of genomics. The integration of genetic information about cancers with data on how the cancers respond to target based therapy to help to optimum cancer treatment. The increasing usage of sequencing technology in cancer research and clinical practice has enormously advanced our understanding of cancer mechanisms. The cancer precision medicine is becoming a reality. Although off-label drug usage is a common practice in treating cancer, it suffers from the lack of knowledge base for proper cancer drug selections. This eminent need has become even more apparent considering the upcoming genomics data. In this paper, a personalized medicine knowledge base is constructed by integrating various cancer drugs, drug-target database, and knowledge sources for the proper cancer drugs and their target selections. Based on the knowledge base, a bioinformatics approach for cancer drugs selection in precision medicine is developed. It integrates personal molecular profile data, including copy number variation, mutation, and gene expression. By analyzing the 85 triple negative breast cancer (TNBC) patient data in the Cancer Genome Altar, we have shown that 71.7% of the TNBC patients have FDA approved drug targets, and 51.7% of the patients have more than one drug target. Sixty-five drug targets are identified as TNBC treatment targets and 85 candidate drugs are recommended. Many existing TNBC candidate targets, such as Poly (ADP-Ribose) Polymerase 1 (PARP1), Cell division protein kinase 6 (CDK6), epidermal growth factor receptor, etc., were identified. On the other hand, we found some additional targets that are not yet fully investigated in the TNBC, such as Gamma-Glutamyl Hydrolase (GGH), Thymidylate Synthetase (TYMS), Protein Tyrosine Kinase 6 (PTK6), Topoisomerase (DNA) I, Mitochondrial (TOP1MT), Smoothened, Frizzled Class Receptor (SMO), etc. Our additional analysis of target and drug selection strategy is also fully

Tumor suppressor protein SMAR1 modulates the roughness of cell surface: combined AFM and SEM study

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Mamgain Hitesh

2009-10-01

Full Text Available Abstract Background Imaging tools such as scanning electron microscope (SEM and atomic force microscope (AFM can be used to produce high-resolution topographic images of biomedical specimens and hence are well suited for imaging alterations in cell morphology. We have studied the correlation of SMAR1 expression with cell surface smoothness in cell lines as well as in different grades of human breast cancer and mouse tumor sections. Methods We validated knockdown and overexpression of SMAR1 using RT-PCR as well as Western blotting in human embryonic kidney (HEK 293, human breast cancer (MCF-7 and mouse melanoma (B16F1 cell lines. The samples were then processed for cell surface roughness studies using atomic force microscopy (AFM and scanning electron microscopy (SEM. The same samples were used for microarray analysis as well. Tumors sections from control and SMAR1 treated mice as well as tissues sections from different grades of human breast cancer on poly L-lysine coated slides were used for AFM and SEM studies. Results Tumor sections from mice injected with melanoma cells showed pronounced surface roughness. In contrast, tumor sections obtained from nude mice that were first injected with melanoma cells followed by repeated injections of SMAR1-P44 peptide, exhibited relatively smoother surface profile. Interestingly, human breast cancer tissue sections that showed reduced SMAR1 expression exhibited increased surface roughness compared to the adjacent normal breast tissue. Our AFM data establishes that treatment of cells with SMAR1-P44 results into increase in cytoskeletal volume that is supported by comparative gene expression data showing an increase in the expression of specific cytoskeletal proteins compared to the control cells. Altogether, these findings indicate that tumor suppressor function of SMAR1 might be exhibited through smoothening of cell surface by regulating expression of cell surface proteins. Conclusion Tumor suppressor

Optimizacija procesnih parametrov za stabilizacijo in izboljšanje sposobnosti struženja

OpenAIRE

Mlinar, Andrej

2017-01-01

Magistrska naloga obravnava proizvodni proces izdelka z ozkim tolerančnim območjem. V procesu izdelave se je pojavil problem nestabilnosti obdelovalnega procesa. Pred analizo obdelovalnega procesa smo najprej z metodo analize merilnega sistema preverili merilni proces. Po preverjanju ustreznosti merilnega procesa smo v nadaljevanju preverili obstoječi obdelovalni proces. Iz analize statistične kontrole procesa obstoječega stanja smo ugotovili, da je proces potrebno stabilizirati. Za stabiliza...

SINTEZA BAKROVIH, NIKLJEVIH IN KOBALTOVIH KOORDINACIJSKIH SPOJIN Z NIKOTINSKO, IZONIKOTINSKO IN PIKOLINSKO KISLINO

OpenAIRE

Goljat, Leja

2013-01-01

Koordinacijske spojine so dandanes pogosto sintetizirane in imajo širok spekter uporabnosti. Namen raziskave je bil sintetizirati nove in že znane koordinacijske spojine z bakrom, kobaltom in nikljem. V sklopu diplomskega dela smo izvedli 27 reakcij sinteze koordinacijskih spojin z bakrom, kobaltom in nikljem ter ligandi nikotinsko, izonikotinsko in pikolinsko kislino. Kot topila smo uporabili vodo, N,N-dimetilformamid in mešanico metanola in acetonitrila. Produkte sintez smo nato analizirali...

SU-F-T-333: Deliverability Considerations in Modulated Photon Radiotherapy (XMRT)

Energy Technology Data Exchange (ETDEWEB)

McGeachy, P [Department of Medical Physics, CancerCare Manitoba, Winnipeg, MB (Canada); Weppler, S; Villarreal-Barajas, J [Department of Physics and Astronomy, University of Calgary, Calgary, Alberta (Canada); Department of Medical Physics, Tom Baker Cancer Center, Calgary, AB (Canada); Zinchenko, Y [Department of Mathematics and Statistics, University of Calgary, Calgary, Alberta (Canada); Khan, R [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO (United States)

2016-06-15

Purpose: Modulated Photon Radiotherapy (XMRT), which simultaneously optimizes photon beamlet energy (6 and 18 MV) and fluence, has shown dosimetric improvements for fluence map optimization (FMO) when compared to conventional single-energy intensity modulated radiotherapy. However, generating deliverable multi-leaf collimator (MLC) sequences for XMRT needs to be explored. Therefore, two problems were investigated: 1) The ability to generate MLC-sequenced fluence maps from FMO XMRT solutions for a prostate case 2) The impact of fluence smoothening constraints imposed in the FMO on the deliverability and dose distribution. Methods: XMRT FMO solutions for a clinical prostate case employing standard dosimetric constraints, prescriptions, and a seven coplanar beam arrangement were generated. Smoothening constraints in the FMO utilized a sum of positive gradients approach. Sequenced maps were generated using an in-house optimization algorithm (MLCSO). The maximum leaf speed, minimum leaf separation, and transmission through MLC leaves were set to 2.5 mm/s, 1 mm, and 1%, respectively. The resulting sequenced maps for each field were compared with the original FMO solutions through gamma analysis (0.5%/0.5 mm) and root mean square error (RMSE). This comparison was done for both the smoothed and unsmoothed XMRT solutions. Results: Average RMSE and gamma agreement of 0.44, 93%and 0.36, 95% were obtained for unsmoothed 6 and 18 MV contributions from XMRT sequenced maps. The sequenced maps with smoothening constraints had better agreement with their respective optimal fluences, with RMSEs of 0 and gamma pass rates of 100% for all comparisons. This improved smoothening led to increased dose to critical structures (rectum, bladder, and femoral heads); however solutions were still clinically acceptable. Conclusion: For a clinical prostate case, XMRT FMO fluence maps were suitable for conversion into deliverable MLC sequences. Imposing smoothening constraints during FMO resulted

CARACTERÍSTICAS DEMOGRÁFICAS, HÁBITOS DE VIDA E HISTORIA DEL CONSUMO DE TABACO DE LOS FUMADORES OCASIONALES EN ESPAÑA

Directory of Open Access Journals (Sweden)

Lucía Díez Gañán

2002-01-01

Full Text Available Back ground. This study des cribes the so cio de mo grap hic cha rac te ris tics, health-re lated li fest yle, and his tory of to bac co con sump tion of the oc casional smo kers in Spain, and exa mines whet her they show dif fe ren ces against daily smo kers. Met hods. Data were ob tai ned from the Na tional Health Sur vey of Spain, ca rried out in 1993 through hou sehold in ter - views on a sam ple re pre sen ta ti ve of the non-ins ti tu tio na li sed po pu la tion aged 16 year and ol der. Analy ses were per for med with lo gis tic re gres sion and ad justed for so cio de mo grap hic, health-sta te and life-style va ria bles. Results. Out of the 6,668 smo kers in the sur vey, oc casional smokers were 9.2%, whi le daily smo kers of £5 ci garettes and >5 cigarettes were 9.9% and 80.9%, res pectively. As com pared with daily smo kers of >5 ci garettes, oc casional smo kers were more fre - quently wo men (odds ra tio (0R:2.12; CI95%:1.72-2.61, youn ger (OR aged 25-44 ver sus 16-24 years: 0.75; 0.58-0.96, with lo wer alcohol con sumption (p for li near trend: 0.0349, and hig her lei su - re-time physi cal ac tivity (p for li near trend: 5 ci garettes. Con clu sions: Occa sio nal smo kers show so cio de mo grap hic cha rac te ris tics, health-re lated li fest yle, and his tory of to bac co con sump tion dif fe rent from daily smo kers. Such dif fe ren ces sug gest that re search and in ter ven tion pro grams spe cifically tai lo red to oc ca sio nal smo kers should be de veloped.

Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

Science.gov (United States)

Ruiz-Perez, Victor L; Blair, Helen J; Rodriguez-Andres, M Elena; Blanco, Maria Jose; Wilson, Amy; Liu, Yu-Ning; Miles, Colin; Peters, Heiko; Goodship, Judith A

2007-08-01

EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.

Study on the absenteeism of nursing professionals in a psychiatric center in Manaus, Brazil Estudio sobre ausentismo en profesionales de enfermería del centro psiquiátrico de Manaus, Brasil Estudo do absenteísmo dos profissionais de enfermagem de um centro psiquiátrico em Manaus, Brasil

Directory of Open Access Journals (Sweden)

Sandra Greice Becker

2008-02-01

Full Text Available This quantitative study was performed to research the rate of absenteeism of nursing professionals in a psychiatric center in Manaus, from January/2004 to January/2005, in the Human Resources sector of the institution. In this period, the records of workers who were absent from their professional activities for at least one day were checked. Results showed that there were 415 absence reports in the nursing team during the studied period, by 74.29% of nursing professionals. The average rate of absenteeism is 2.79. The main reason reported for absenteeism was illness. These data suggest further studies are needed in order to improve professionals' health, allowing for better quality of life, and, consequently, for providing better health care to Single Health System users.Con el objetivo de investigar sobre el índice de ausentismo en trabajadores de enfermería del Centro Psiquiátrico de Manaus, se realizó una investigación cuantitativa durante el periodo de enero de 2004 a enero del 2005 en el sector de recursos humanos de la institución en mención. Durante este periodo se buscó a través de consulta documental, registros de los trabajadores que tuvieron faltas de por lo menos 1 día en sus actividades laborales. Los resultados mostraron que durante el periodo de la investigación, hubo 415 registros de faltas por parte del equipo de enfermería, totalizando 74,29%. El índice del ausentismo profesional fue en promedio 2.79. Se observó que el principal motivo del ausentismo fue por enfermedad. Este hecho resalta la necesidad de mejorar la salud del trabajador, favoreciendo a una mejor calidad de vida en el trabajo y en consecuencia una mejor atención a la salud del usuario a través del SUS.Com o objetivo de investigar o índice de absenteísmo dos trabalhadores de enfermagem de um Centro Psiquiátrico em Manaus, realizou-se esta pesquisa quantitativa, no período de janeiro de 2004 a janeiro de 2005, no setor de recursos humanos da

ZADOVOLJSTVO UPORABNIKOV TURISTIČNIH STORITEV

OpenAIRE

Stanonik, Tana

2015-01-01

Zadovoljstvo uporabnikov turističnih storitev je eden ključnih dejavnikov za uspešno poslovanje ponudnikov turističnih storitev. V teoretičnem delu diplomske naloge smo na kratko razjasnili glavna pojma turizem ter zadovoljstvo. Opisali smo nekaj dejavnikov, ki vplivajo na zadovoljstvo uporabnikov turističnih storitev. Govorimo o kakovosti storitev v turizmu, nakupnem vedenju turistov ter o lojalnosti turistov. Opisali smo tudi samo merjenje zadovoljstva turistov ter razjasnili kako se v ...

Prenova razsvetljave na Fakulteti za elektrotehniko

OpenAIRE

ŠTAJDOHAR, JAN

2015-01-01

Pri energetskem pregledu stavbe Fakultete za elektrotehniko v Ljubljani je bilo ugotovljeno, da je razsvetljava prostorov na fakulteti v veliko primerih stara, neprimerna in energetsko potratna. V diplomski nalogi smo se posvetili energetski analizi prenove razsvetljave predavalnice P7 in kabineta AZ101. Pri načrtovanju in izbiri svetil smo upoštevali vse tehnične in energetske smernice za učinkovito razsvetljavo prostorov za izobraževanje. V uvodu smo opisali fizikalne osnove svetlobe, k...

Uveljavljanje trendov digitalizacije v podjetjih - Industrija 4.0

OpenAIRE

Belej, Klemen

2016-01-01

V diplomskem delu smo predstavili digitalizacijo v podjetjih in opredelili manj znan pojem Industrijo 4.0. Opisali smo koncept Industrije 4.0, prikazali razvoj industrijskih revolucij in predstavili novejše tehnologije, ki se pojavljajo v podjetjih kot so: big data, internet stvari, aditivna tehnologija, razširjena resničnost... Podrobneje so predstavljeni kolaborativni roboti, ki lahko sodelujejo s človekom. Pojasnili smo tudi vlogo vitke proizvodnje v Industriji 4.0. Ker je v podjetjih kon...

RAZVOJ APLIKACIJE ZA UPRAVLJANJE SLIK IN ALBUMOV NA MOBILNI PLATFORMI ANDROID

OpenAIRE

Kupnik, Domen

2012-01-01

V okviru diplomske naloge smo izdelali mobilno aplikacijo na operacijskem sistemu Android OS za upravljanje slik in albumov. V teoretičnem delu smo najprej predstavili že obstoječe podobne aplikacije. Nato smo se seznanili z arhitekturo operacijskega sistema Android OS in s kompletom za razvijanje aplikacij Android SDK. V nadaljevanju sledi še predstavitev lokacijskega podsistema Google Map ter podrobnejši opis uporabljenih funkcionalnosti. V praktičnem delu prikažemo implementacijo aplikacij...

On the radiological consequences near and far away from the catastrophically damaged Chernobyl Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Susnik, J [Reactor Engineering Div., Inst. Jozef Stefan, Ljubljana (Slovenia)

1992-07-01

The influence of the radioactive cloud rise at the site on the potential expected post accidental doses, using the WASH-1400 PWR-1A scenario and the CRAC 2 model, was studied. The UNSCEAR 1988 was used to estimate the activity of the cloud that contaminated Slovenia and neighbouring areas. The contamination levels at the J.Stefan Institute were used for comparison (the match was surprisingly good). Some of the expected doses due to early irradiation from the cloud, ground, inhalation and ingestion are also shown. Dose reduction possibilities were estimated. (author) [Slovenian] Preucili smo vpliv dviga radioaktivnega oblaka na lokaciji JE na potencialne ponezgodne doze, pri cemer smo izhajali iz WASH-1400 PWR-1A scenarija in uporabili program CRAC2. UNSCEAR 1988 smo uporabili za oceno aktivnosti oblaka, ki je onesnazil Slovenijo in sosednja podrocja. Nivoje kontaminacije izmerjene na lokaciji Instituta J. Stefan smo uporabili za primerjavo (ujemanje je bilo presenetljivo dobro). Podajamo tudi nekatere pricakovane doze zgodnjega obsevanja iz oblaka, s tal, vdihovanja in vnosa hrane. Ocenili smo mozna znizanja doz. [author].

Dissipation of sulfamethoxazole in pasture soils as affected by soil and environmental factors.

Science.gov (United States)

Srinivasan, Prakash; Sarmah, Ajit K

2014-05-01

The dissipation of sulfamethoxazole (SMO) antibiotic in three different soils was investigated through laboratory incubation studies. The experiments were conducted under different incubation conditions such as initial chemical concentration, soil depth, temperature, and with sterilisation. The results indicate that SMO dissipated rapidly in New Zealand pasture soils, and the 50% dissipation times (DT50) in Hamilton, Te Kowhai and Horotiu soils under non-sterile conditions were 9.24, 4.3 and 13.33 days respectively. During the incubation period for each sampling event the soil dehydrogenase activity (DHA) and the variation in microbial community were monitored thorough phospholipid fatty acid extraction analysis (PLFA). The DHA data correlated well with the dissipation rate constants of SMO antibiotic, an increase in the DHA activity resulted in faster antibiotic dissipation. The PLFA analysis was indicative of higher bacterial presence as compared to fungal community, highlighting the type of microbial community responsible for dissipation. The results indicate that with increasing soil depth, SMO dissipation in soil was slower (except for Horotiu) while with increase in temperature the antibiotic loss was faster, and was noticeable in all the soils. Both the degree of biological activity and the temperature of the soil influenced overall SMO dissipation. SMO is not likely to persist more than 5-6 months in all three soils suggesting that natural biodegradation may be sufficient for the removal of these contaminants from the soil. Its dissipation in sterile soils indicated abiotic factors such as strong sorption onto soil components to play a role in the dissipation of SMO. Copyright © 2014 Elsevier B.V. All rights reserved.

OBRAVNAVA PACIENTA S PSIHOZO

OpenAIRE

Majcen, Sabrina

2011-01-01

V diplomskem delu smo predstavili pacienta s psihozo, pri katerem se kažejo problemi pri vsakodnevnem funkcioniranju zaradi številnih dejavnikov, ki so povezani s samo boleznijo. V teoretičnem delu je zajeta opredelitev psihoze, vrste psihotičnih motenj, znaki in simptomi ter načini zdravljenja. Posebno poglavje smo namenili zdravstveni negi pacienta s to boleznijo ter kakovosti življenja. V empiričnem delu diplomskega dela so predstavljeni rezultati kvalitativne raziskave, ki smo jo izve...

VARNOSTNA POLITIKA NA PODROČJU INFORMATIKE

OpenAIRE

Šavor, Gašper

2011-01-01

Informacijska tehnologija postaja vse bolj pomemben del poslovanja vsakega podjetja ter ţivljenja vsakega posameznika. Zato je v interesu vseh, da so ključne informacije dobro zaščitene. V prvem delu diplomske naloge smo predstavili informacijske sisteme, njihovo delitev ter vrste. Prav tako smo podrobneje predstavili ţivljenjski cikel ter 4-stopenjski model razvoja informacijskega sistema. V osrednjem delu naloge smo se osredotočili na nevarnosti na področju informatike ter vrste zašči...

VPLIV ODNOSA S STARŠI NA SAMOPOŠKODOVALNO VEDENJE MLADOSTNIKOV

OpenAIRE

Majhen, Maša

2016-01-01

Samopoškodovalno vedenje se najpogosteje pojavlja med mladostniki. Ker pa je družina eden izmed najpomembnejših socialnih sistemov v mladostnikovem življenju, smo želeli ugotoviti ali obstaja kakšna povezanost med mladostnikovim odnosom s starši in omenjenim pojavom. Ugotoviti smo želeli ali obstajajo znotraj družinskih odnosov in procesov dejavniki, ki vplivajo na verjetnost pojava samopoškodovalnega vedenja pri mladostnikih. Na podlagi preučene literature smo predvidevali, da zanemarjanje ...

POSLOVNO KOMUNICIRANJE V KITAJSKI KULTURI

OpenAIRE

Koprivnik, David

2016-01-01

Določena oblika komuniciranja je prisotna povsod, torej tudi v poslovnem svetu, kjer s pomočjo poslovnega komuniciranja, poslovnih običajev ter pogajanj poteka poslovanje med različnimi podjetji. Poslovno komuniciranje pa poteka tako med podjetji kot tudi znotraj podjetja. V diplomskem projektu smo obravnavali poslovno komuniciranje v kitajski kulturi, ki smo jo primerjali z ostalimi azijskimi državami. Ugotoviti smo, kako se kulture azijskih držav razlikujejo med seboj, kje so si pod...

Aplikacija za avtomatizirano prepoznavanje listov dreves in grmov kritosemenk za operacijski sistem Android

OpenAIRE

Puhmeister, Sandro

2016-01-01

V tem diplomskem delu smo implementirali aplikacijo za avtomatizirano prepoznavanje listov dreves in grmov kritosemenk za operacijski sistem Android, pri čemer smo postopek prepoznavanja vrste razdelili na štiri ključne faze: zajem slik, obdelavo slik, luščenje značilnic in določitev vrste. Pri zajetju slik smo uporabili privzeto aplikacijo operacijskega sistema Android, kjer uporabnik zajame dve fotografiji (fotografira spodnjo in vrhnjo površino lista) za obdelavo slik. Pri obdelavi slik sm...

SPOLNO NADLEGOVANJE NA DELOVNEM MESTU

OpenAIRE

Rubič, Gašper

2016-01-01

V diplomskem delu smo v uvodu predstavili problem spolnega nadlegovanja na delovnem mestu in predstavili podjetje TEKSTIL d.d. V nadaljevanju smo z anketo raziskali, ali problem spolnega nadlegovanja na delovnem mestu v obravnavanem podjetju obstaja in če, kako se nanj odziva okolje. V teoretičnem delu smo nadaljevali in predstavili definicijo spolnega nadlegovanja, ki je kakršna koli oblika nezaželenega verbalnega in neverbalnega ali fizičnega ravnanja spolne narave z učinkom ali nameno...

FLEXICMS - ODPRTOKODNI SISTEM UPRAVLJANJE Z VSEBINO

OpenAIRE

Pirnat, Miha

2012-01-01

V diplomski nalogi smo implementirali spletni sistem upravljanja vsebine, ki smo ga poimenovali FlexiCMS. Glavni cilj je bil zgraditi majhen in pregleden sistem, a z dovolj funkcionalnosti, da je primeren za realne spletne strani. FlexiCMS je implementiran v programskem jeziku PHP za spletne strežnike Apache. Za shranjevanje podatkov strani se uporablja podatkovna baza MySQL. Načrtovali smo ga kot minimalističen sistem in pri tem imeli v mislih najpogostejše funkcije spletnih strani. Vgr...

Absenteísmo de trabalhadores de enfermagem em um hospital universitário Ausentismo en los trabajadores de enfermería de un hospital universitario Absenteeism of nursing workers from a university hospital

Directory of Open Access Journals (Sweden)

Dóris Marli Petry Paulo da Silva

2000-10-01

Full Text Available Objetivando identificar os índice de absenteísmo-doença entre os trabalhadores de enfermagem do hospital universitário, foi realizado um levantamento das faltas por licença-saúde registradas durante doze meses e calculado o índice de freqüência e a porcentagem de tempo perdido. Os dados foram coletados através de consulta documental aos registros do departamento pessoal da instituição estudada e transcritos em um protocolo. Diante dos resultados obtidos, constatou-se que o maior índice de freqüência ocorreu na Pediatria (If=0,35 e a porcentagem de tempo perdido de trabalho ocorreu no Pronto Atendimento (Tp=4,19. Concluiu-se que os índices de absenteísmo-doença entre os trabalhadores apresentam-se elevados, indicando a necessidade de criação de um banco de dados para otimizar o registro das faltas, facilitar seu controle e possibilitar futuras pesquisas.Con el objetivo de identificar el índice de ausentismo/enfermedad entre los trabajadores de enfermería de un hospital universitario fue realizado un examen de las ausencias por incapacidad médica registrada durante doce meses, fue calculado el índice de frecuencia y el porcentaje de tiempo perdido. Los datos fueron recolectados a través de consulta documental en los registros del departamento de personal de la institución estudiada y copiados en un protocolo. De los resultados obtenidos, se constató que el mayor índice de frecuencia ocurrió en Pediatría (If =0,35 y el porcentaje de tiempo perdido de trabajo ocurrió en el servicio de Urgencias(Tp = 4,19. Se concluye que los índices de ausentismo/enfermedad entre los trabajadores se presentan elevados, indicando la necesidad de crear un banco de datos para optimizar el registro de faltas, facilitar el control y posibilitar futuras investigaciones.The purpose of this study was to identify the rates of absenteeism of nursing workers from a University Hospital due to diseases. Therefore, the author verified the number of

Near-Infrared Spectroscopic Measurement of the Effect of Leg Dominance on Muscle Oxygen Saturation During Cycling

Science.gov (United States)

Ellerby, Gwenn E. C.; Lee, Stuart M. C.; Paunescu, Lelia Adelina; Pereira, Chelsea; Smith, Charles P.; Soller, Babs R.

2011-01-01

The effect of leg dominance on the symmetry of the biomechanics during cycling remains uncertain -- asymmetries have been observed in kinematics and kinetics, while symmetries were found in muscle activation. No studies have yet investigated the symmetry of muscle metabolism during cycling. Near-infrared spectroscopy (NIRS) provides a non-invasive method to investigate the metabolic responses of specific muscles during cycling. PURPOSE: To determine whether there was an effect of leg dominance on thigh muscle oxygen saturation (SmO2) during incrementally loaded submaximal cycling using NIRS. METHODS: Eight right leg dominant, untrained subjects (5 men, 3 women; 31+/-2 yrs; 168.6+/-1.0 cm; 67.2+/-1.8 kg, mean +/- SE) volunteered to participate. Spectra were collected bilaterally from the vastus lateralis (VL) during supine rest and cycling. SmO2 was calculated using previously published methods. Subjects pedaled at 65 rpm while resistance to pedaling was increased in 0.5 kp increments from 0.5 kp every 3 min until the subject reached 80% of age-predicted maximal heart rate. SmO2 was averaged over 3 min for each completed stage. A two-way ANOVA was performed to test for leg differences. A priori contrasts were used to compare work levels to rest. RESULTS: VL SmO2 was not different between the dominant and non-dominant legs at rest and during exercise (p=0.57). How SmO2 changed with workload was also not different between legs (p=0.32). SmO2 at 0.5 kp (60.3+/-4.0, p=0.12) and 1.0 kp (59.5+/-4.0, p=0.10) was not different from rest (69.1+/-4.0). SmO2 at 1.5 kp (55.4 4.0, p=0.02), 2.0 kp (55.7+/-5.0, p=0.04), and 2.5 kp (43.4+/-7.9, p=0.01) was significantly lower than rest. CONCLUSION: VL SmO2 during cycling is not different between dominant and non-dominant legs and decreases with moderate workload in untrained cyclists. Assuming blood flow is directed equally to both legs, similar levels of oxygen extraction (as indicated by SmO2) suggests the metabolic load of

Magnetic and electronic properties of SrMnO3 thin films

Science.gov (United States)

Mandal, Arup Kumar; Panchal, Gyanendra; Choudhary, R. J.; Phase, D. M.

2018-05-01

Single phase hexagonal bulk SrMnO3 (SMO) was prepared by solid state route and it was used for depositing thin films by pulsed laser deposition (PLD) technique on single crystalline (100) oriented SrTiO3 (STO) substrate. X-ray diffraction shows that the thin film is deposited in cubic SrMnO3 phase. From X-ray absorption at the Mn L edge we observed the mixed valency of Mn (Mn3+& Mn4+) due to strain induced by the lattice mismatching between SMO and STO. Due to this mixed valency of Mn ion in SMO film, the ferromagnetic nature is observed at lower temperature because of double exchange. After post annealing with very low oxygen partial pressure, magnetic and electronic property of SMO films are effectively modified.

Sensorless control of ship propulsion interior permanent magnet synchronous motor based on a new sliding mode observer.

Science.gov (United States)

Ren, Jun-Jie; Liu, Yan-Cheng; Wang, Ning; Liu, Si-Yuan

2015-01-01

This paper proposes a sensorless speed control strategy for ship propulsion interior permanent magnet synchronous motor (IPMSM) based on a new sliding-mode observer (SMO). In the SMO the low-pass filter and the method of arc-tangent calculation of extended electromotive force (EMF) or phase-locked loop (PLL) technique are not used. The calculation of the rotor speed is deduced from the Lyapunov function stability analysis. In order to reduce system chattering, sigmoid functions with switching gains being adaptively updated by fuzzy logic systems are innovatively incorporated into the SMO. Finally, simulation results for a 4.088 MW ship propulsion IPMSM and experimental results from a 7.5 kW IPMSM drive are provided to verify the effectiveness of the proposed SMO method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Gender differences in child/adolescent personality traits

OpenAIRE

Zupančič, Maja; Slobodskaya, Helena R.; Knyazev, Gennady G.

2015-01-01

V raziskavi smo primerjali razlike med spoloma, kot se odražajo skozi starševo zaznavo izraznosti osebnostnih potez pri različno starih skupinah slovenskih in ruskih otrok/mladostnikov. Vzorce razlik med spoloma v zgodnjem mladostništvu smo preučevali tudi z dvema metodama, s starševo oceno osebnosti njihovih otrok in s samooceno mladostnikov. Z Vprašalnikom medosebnih razlik med otroki (Halverson idr., 2003) smo zbrali podatke o velikih vzorcih ciljnih posameznikov (starih od 2 do 15 let) v ...

BINAURALNO SNEMANJE ZVOKA

OpenAIRE

Rupnik, Luka

2015-01-01

V diplomskem delu smo preučili in opisali binauralno snemanje zvoka. Izdelali smo tri različne stopnje snemalne glave z vstavljenimi mikrofoni Primo EM172-Z1 in te medsebojno primerjali. Meritve usmerjenosti zajemanja avdio signala glede na vsako stopnjo izdelave so bile opravljene s programom ARTA, ki je namenjen za opravljanje različnih akustičnih meritev. Za snemanje avdio signala je bil uporabljen snemalnik zvoka ZOOM Handy Recorder H4n. Z mikrofoni, vgrajenimi v snemalnik, smo v stereo t...

POSLOVNI BONTON V BRAZILSKI, FRANCOSKI IN ARGENTINSKI KULTURI

OpenAIRE

Flisar, Tajda

2016-01-01

V diplomskem projektu smo opisali poslovno komuniciranje, poslovni bonton ter komuniciranje s tujimi poslovnimi partnerji. Zelo pomembno pri poslovanju s tujimi partnerji je, da se vsak posameznik pred odhodom v tujino pozanima o kulturi države. To zelo vpliva na uspešnost posla. Osredotočili smo se na poslovni bonton brazilske, francoske in argentinske kulture. Skozi diplomski projekt smo ugotovili, da so si države po kulturi in navadah med seboj različne. Poleg tega sta Argentina in Bra...

BARVA IN BARVANJE BOMBAŽA Z NARAVNIMI BARVILI

OpenAIRE

Munda, Tamara

2011-01-01

V diplomskem delu smo raziskali možnosti barvanja bombažne tkanine z naravnimi rastlinskimi barvili, pridobljenimi iz kurkume, koprive in hrastovega lubja. Barvanje je potekalo po izčrpalnem postopku, ob dodatku različnih kovinskih soli (Fe, Al, Cu) ali brez njih, pri različnih pH vrednostih. Kovinske soli vplivajo na barvni ton in boljše vezanje barvila z vlaknom. Po barvanju smo vzorce oprali. Izvedli smo tudi spektrofotometrično vrednotenje barve na opranih in neopranih vzorcih. Pri barvan...

PLANINSKE VSEBINE V PROGRAMU GIBALNIH DEJAVNOSTI VRTCA

OpenAIRE

Pavletič, Zvezdana

2016-01-01

V diplomskem delu Planinske vsebine v programu gibalnih dejavnosti vrtca, smo raziskali planinske vsebine, s katerimi v vrtcu spodbujamo gibalni razvoj predšolskih otrok. V teoretičnem delu naloge smo pregledali razvojne značilnosti predšolskih otrok, področja otrokovega razvoja in proučili dejavnike, ki pomembno vplivajo na otrokov razvoj. Proučili smo hojo kot sestavni del razvoja motorike otroka, njen pomen za ohranjanje zdravja, krepitev srčno-žilnega in dihalnega sistema. Predstavili sm...

Uporaba algoritmov inteligence rojev za rešitev problema dostavnih vozil

OpenAIRE

Hlastec, Urban

2018-01-01

V magistrski nalogi smo obravnavali in implementirali algoritem umetne kolonije čebel za reševanje problema dostavnih vozil z več skladišči. Zanimalo nas je, kako so algoritmi s področja inteligence rojev ustrezni in uporabni za reševanje optimizacijskih problemov. V nalogi smo združili algoritem umetne kolonije čebel ter algoritem za reševanje problema dostavnih vozil. Primerjali smo tudi rezultate pred optimizacijo različnih spremenljivk in po in tako ugotovili, kaj najbolj vpliva na hitros...

Combining selection valve and mixing chamber for nanoflow gradient generation: Toward developing a liquid chromatography cartridge coupled with mass spectrometer for protein and peptide analysis.

Science.gov (United States)

Chen, Apeng; Lu, Joann J; Gu, Congying; Zhang, Min; Lynch, Kyle B; Liu, Shaorong

2015-08-05

Toward developing a micro HPLC cartridge, we have recently built a high-pressure electroosmotic pump (EOP). However, we do not recommend people to use this pump to deliver an organic solvent directly, because it often makes the pump rate unstable. We have experimented several approaches to address this issue, but none of them are satisfactory. Here, we develop an innovative approach to address this issue. We first create an abruption (a dead-volume) within a fluid conduit. We then utilize an EOP to withdraw, via a selection valve, a train of eluent solutions having decreasing eluting power into the fluid conduit. When these solutions are further aspirated through the dead-volume, these solutions are partially mixed, smoothening concentration transitions between two adjacent eluent solutions. As these solutions are pushed back, through the dead-volume again, a smooth gradient profile is formed. In this work, we characterize this scheme for gradient formation, and we incorporate this approach with a high-pressure EOP, a nanoliter injection valve, and a capillary column, yielding a micro HPLC system. We then couple this micro HPLC with an electrospray ionization - mass spectrometer for peptide and protein separations and identifications. Copyright © 2015 Elsevier B.V. All rights reserved.

Dynamics of a bistable Miura-origami structure

Science.gov (United States)

Fang, Hongbin; Li, Suyi; Ji, Huimin; Wang, K. W.

2017-05-01

Origami-inspired structures and materials have shown extraordinary properties and performances originating from the intricate geometries of folding. However, current state of the art studies have mostly focused on static and quasistatic characteristics. This research performs a comprehensive experimental and analytical study on the dynamics of origami folding through investigating a stacked Miura-Ori (SMO) structure with intrinsic bistability. We fabricate and experimentally investigated a bistable SMO prototype with rigid facets and flexible crease lines. Under harmonic base excitation, the SMO exhibits both intrawell and interwell oscillations. Spectrum analyses reveal that the dominant nonlinearities of SMO are quadratic and cubic, which generate rich dynamics including subharmonic and chaotic oscillations. The identified nonlinearities indicate that a third-order polynomial can be employed to approximate the measured force-displacement relationship. Such an approximation is validated via numerical study by qualitatively reproducing the phenomena observed in the experiments. The dynamic characteristics of the bistable SMO resemble those of a Helmholtz-Duffing oscillator (HDO); this suggests the possibility of applying the established tools and insights of HDO to predict origami dynamics. We also show that the bistability of SMO can be programmed within a large design space via tailoring the crease stiffness and initial stress-free configurations. The results of this research offer a wealth of fundamental insights into the dynamics of origami folding, and provide a solid foundation for developing foldable and deployable structures and materials with embedded dynamic functionalities.

One-pot synthesis of magnetic hybrid materials based on ovoid-like carboxymethyl-cellulose/cetyltrimethylammonium-bromide templates

Energy Technology Data Exchange (ETDEWEB)

Torres-Martínez, Nubia E. [Universidad Autónoma de Nuevo León, Facultad de Ingeniería Mecánica y Eléctrica, San Nicolás de los Garza, 66450 Nuevo León (Mexico); Garza-Navarro, M.A., E-mail: marco.garzanr@uanl.edu.mx [Universidad Autónoma de Nuevo León, Facultad de Ingeniería Mecánica y Eléctrica, San Nicolás de los Garza, 66450 Nuevo León (Mexico); Universidad Autónoma de Nuevo León, Centro de Innovación, Investigación y Desarrollo en Ingeniería y Tecnología, Apodaca, 66600 Nuevo León (Mexico); Lucio-Porto, Raúl [Université de Nantes, CNRS, Institut des Matériaux Jean Rouxel (IMN), 2 rue de la Houssinière, BP32229, 44322 Nantes Cedex 3 (France); and others

2013-09-16

A novel one-pot synthetic procedure to obtain magnetic hybrid nanostructured materials (HNM), based on magnetic spinel-metal-oxide (SMO) nanoparticles stabilized in ovoid-like carboxymethyl-cellulose (CMC)/cetyltrimethylammonium-bromide (CTAB) templates, is reported. The HNM were synthesized from the controlled hydrolysis of inorganic salts of Fe (II) and Fe (III) into aqueous dissolutions of CMC and CTAB. The synthesized HNM were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and static magnetic measurements. The experimental evidence suggests that, due to the competition between CTAB molecules and SMO nanoparticles to occupy CMC intermolecular sites nearby to its carboxylate functional groups, the size of both, SMO nanoparticles and ovoid-like CMC/CTAB templates can be tuned, varying the CTAB:SMO weight ratio. Moreover, it was found that the magnetic response of the HNM depends on the confinement degree of the SMO nanoparticles into the CMC/CTAB template. Hence, their magnetic characteristics can be adjusted controlling the size of the template, the quantity and distribution of the SMO nanoparticles within the template and their size. - Graphical abstract: Display Omitted - Highlights: • The synthesis of magnetic hybrid materials is reported. • The hybrid materials were synthesized following a novel one-pot procedure. • The magnetic nanoparticles were stabilized in ovoid-like templates. • The size of the templates was tuned adjusting nanoparticles weight content. • The magnetic properties of hybrid materials depend on the size of the template.

Co-contaminants and factors affecting the sorption behaviour of two sulfonamides in pasture soils

International Nuclear Information System (INIS)

Srinivasan, Prakash; Sarmah, Ajit K.; Manley-Harris, Merilyn

2013-01-01

We investigated the effect of soil pH, organic carbon, ionic strength and steroid hormones on the sorption of sulfamethoxazole (SMO) and sulfachloropyridazine (SCP) in three pastoral soils of New Zealand. A model linking sorbate speciation with species-specific sorption coefficients describing the pH dependence of the apparent sorption coefficients was used to derive the fraction of each species of SMO. All soils displayed a decrease in sorption when pH was increased, with SMO exhibiting the highest sorption at pH 2. The cationic form of SMO appeared to sorb more close to pH ≥ pK a1 and, when pH ≥ pK a2 (6.5, 7.5 and 8.5) the anionic species seems to dominate, however, its sorption affinity to all soils was low. SMO sorption was affected by ionic strengths and organic carbon content, while the presence of hormones showed only a subtle decrease in SCP sorption in a selected model pasture soil. -- Highlights: •The effect of OC content on sulfamethoxazole sorption is nullified by the pH effect. •Steroid hormone has a subtle influence on the sulfachloropyridazine sorption in pastoral soil. •Increased hormone concentrations decrease sulfachloropyridazine sorption in soils. -- Sorption affinity of SMO and SCP are strongly governed by multitude of factors, and variations in these factors can be significant when manure and fertilisers are added to soil

Dynamics of a bistable Miura-origami structure.

Science.gov (United States)

Fang, Hongbin; Li, Suyi; Ji, Huimin; Wang, K W

2017-05-01

Origami-inspired structures and materials have shown extraordinary properties and performances originating from the intricate geometries of folding. However, current state of the art studies have mostly focused on static and quasistatic characteristics. This research performs a comprehensive experimental and analytical study on the dynamics of origami folding through investigating a stacked Miura-Ori (SMO) structure with intrinsic bistability. We fabricate and experimentally investigated a bistable SMO prototype with rigid facets and flexible crease lines. Under harmonic base excitation, the SMO exhibits both intrawell and interwell oscillations. Spectrum analyses reveal that the dominant nonlinearities of SMO are quadratic and cubic, which generate rich dynamics including subharmonic and chaotic oscillations. The identified nonlinearities indicate that a third-order polynomial can be employed to approximate the measured force-displacement relationship. Such an approximation is validated via numerical study by qualitatively reproducing the phenomena observed in the experiments. The dynamic characteristics of the bistable SMO resemble those of a Helmholtz-Duffing oscillator (HDO); this suggests the possibility of applying the established tools and insights of HDO to predict origami dynamics. We also show that the bistability of SMO can be programmed within a large design space via tailoring the crease stiffness and initial stress-free configurations. The results of this research offer a wealth of fundamental insights into the dynamics of origami folding, and provide a solid foundation for developing foldable and deployable structures and materials with embedded dynamic functionalities.

INTERES PREDŠOLSKIH OTROK DO POSLUŠANJA GLASBE

OpenAIRE

Zajc, Martina

2015-01-01

Poslušanje glasbe vpliva na otrokov glasbeni, estetski, moralni, telesni in duševni razvoj. V diplomski nalogi z naslovom Interes predšolskih otrok do poslušanja glasbe smo v empiričnem delu opravili raziskavo, s katero smo želeli izvedeti, kakšen interes imajo predšolski otroci do različnih zvrsti glasbe. Poleg tega nas je zanimalo, kakšno glasbo ponujajo vzgojitelji otrokom v vrtcu in koliko časa posvetijo poslušanju glasbe. Ugotovili smo, da imajo otroci velik interes do poslušanja ...

VREDNOST ZNAMKE "HELLO KITTY"

OpenAIRE

Pompe, Polona

2013-01-01

Raziskovalno delo temelji na vrednosti znamke ter predšolskih otrocih. Ta dva sklopa smo najprej podkrepili s teorijo, v empiričnem delu pa med seboj povezali. Predšolski otroci in njihovi starši se prepletajo. Zato smo v empiričnem delu naloge izvedli kvantitativno raziskavo. Z njo smo ugotavljali, kakšna je vrednost znamke Hello Kitty v očeh predšolskih otrok. To vrednost pa je predstavljalo zavedanje o znamki, čustvena navezanost na samo znamko, podoba o znamki ter zaznana kakovost znamke....

ANALIZA PRIMEROV UPORABE VELIKE KOLIČINE PODATKOV

OpenAIRE

Koželj, Marko

2013-01-01

Diplomski seminar predstavlja računalništvo v oblaku in velike količine podatkov. Ta dva pojma sta novi poslovni priložnosti za podjetja. Vsekakor bodo brez teh dveh inovacij podjetja težko preživela na mednarodnih trgih. V diplomskem seminarju smo obravnavali računalništvo v oblaku. Na kratko smo povedali osnovne značilnosti, razvoj skozi leta, arhitekturo, tipe in SWOT analizo računalništva v oblaku. Kasneje smo se osredotočili na velike količine podatkov, jih definirali, pojasnili zgod...

Vsakodnevni predatorji

OpenAIRE

Čermelj, Katarina

2015-01-01

V diplomskem delu bomo govorili o spolnem nadlegovanju. V teoretičnem delu smo naredili pregled različnih zakonskih določil spolnega nadlegovanja in kako ga le ta definirajo. Odkrili smo, da v večini razvitih držav ni inkriminirano ter da se kazensko preganja le nadlegovanje na delovnem mestu. Predstavili smo tudi poglede družbe na spolno nadlegovanje ter kako se obnašajo prisotni, ko se zgodi. Na spolno nadlegovanje imajo velik vpliv mediji, še posebno, če spolno nadlegovanje in seks...

VPLIV DIREKTNEGA IN DIFUZNEGA SONČNEGA SEVANJA NA SILICIJEVE SONČNE CELICE

OpenAIRE

Veberič, Tomi

2011-01-01

Cilj diplomske naloge je ovrednotenje električnih lastnosti in vpliva sončnega sevanja na silicijeve sončne celice s pomočjo opravljenih raziskav in meritev. Rezultate meritev sončnega sevanja smo analizirali s programskim paketom Matlab. Pri sami analizi smo na podlagi večletnih meritev sončnega sevanja izračunali izkoristek posamezne silicijeve sončne celice glede na direktno in difuzno komponento sončnega sevanja in tako ovrednotili električne lastnosti sončnih celic. V okviru tega smo v d...

A Comparison of the Bariatric Procedures that Are Performed in the Treatment of Super Morbid Obesity.

Science.gov (United States)

Uno, Kohei; Seki, Yosuke; Kasama, Kazunori; Wakamatsu, Kotaro; Umezawa, Akiko; Yanaga, Katsuhiko; Kurokawa, Yoshimochi

2017-10-01

We have experienced numerous cases of super morbid obesity (SMO), defined by a BMI of ≥50 kg/m 2 , in which laparoscopic sleeve gastrectomy (LSG) was not able to achieve a sufficient weight loss effect. However, the most appropriate procedure for the treatment of SMO has not yet been established. The subjects included 248 successive patients who underwent surgery at our hospital from June 2006 to December 2012. We divided the subjects into an SMO group (BMI, 50 to <70 kg/m 2 ) and a morbid obesity (MO) group (BMI, 35 to <50 kg/m 2 ). The subjects underwent LSG, LSG with duodenojejunal bypass (LSG/DJB), or laparoscopic Roux-en-Y gastric bypass (LRYGB). The weight loss effects, safety of surgery, and metabolic profile changes were compared. Sixty-two subjects were classified into the SMO group (25%). The percent excess weight loss (%EWL) after LSG among the patients in the SMO group was not significantly different from that of patients who underwent other procedures. LSG was associated with a significantly lower success rate in terms of weight loss (%EWL ≥ 50%), in comparison to the weight loss at 1 year after LRYGB and at 2 years after LSG/DJB and LRYGB. Among the patients in the MO group, the %EWL and the rate of successful weight loss did not differ to a statistically significant extent. This study demonstrated that in patients with SMO, LSG/DJB and LRYGB can achieve superior weight loss effects in comparison to LSG.

SEGMENTACIJA TRGA V PODJETJU SI.MOBIL

OpenAIRE

Mihelič, Urša

2014-01-01

Problem, ki smo ga obravnavali, je bila manjša prodaja od pričakovane, s posebnim poudarkom na segmentaciji trga. Je namreč eden od močnejših dejavnikov pri izplenu podjetja Si.mobil. V teoretičnem delu diplomskega dela smo se osredotočili na segmentacijo trga na splošno. S pomočjo literature smo ugotavljali, kaj sploh pomeni pojem segmentacija trga, kakšne so ravni segmentiranja, kakšni so postopki in faze segmentiranja trga ter tudi kakšne so osnove za segmentiranje porabniškega trga. O...

RAZLIKE MED PODJETNIKI IN PODJETNICAMI V SLOVENIJI: ŠTUDIJA PRIMERA

OpenAIRE

Sekavčnik, Marjeta

2013-01-01

Namen diplomskega seminarja je bil ugotoviti kakšne so razlike med podjetniki in podjetnicami v Sloveniji in zakaj do njih prihaja. Tega smo se lotili tako, da smo diplomski seminar razdelili na dva večja dela in sicer na teoretični in empirični del oz. študijo primera. Pri teoretičnem delu smo se najprej seznanili z osnovnimi pojmi podjetništva, spoznali kakšni so razlogi (motivi) podjetnikov in podjetnic, da se odločijo za podjetniško kariero, ugotovili kakšne so njihove osebnostne znači...

OGLAŠEVANJE NA DRUŽBENIH OMREŽJIH NA PRIMERU FACEBOOKA

OpenAIRE

Novak, Martina

2012-01-01

V diplomskem delu obravnavamo družbene medije kot novo priložnost za promocijo in oglaševanje podjetij. Spoznali smo družbena omrežja na splošno in nekaj teh, ki jih uporabljamo tudi v Sloveniji na kratko predstavili. Podrobneje smo se osredotočili na družbeno omrežje Facebook, predvsem na samo spletno stran, njen izgled in storitve, ki jih ponuja uporabnikom. V nalogi je podrobneje opisan Facebook kot orodje za uporabo oglaševanja. Spoznali smo brezplačne in plačljive načine promocije in ogl...

NAČRT TRŽENJA ROMANTIČNEGA HOTELA RENESANSE KOT DEL POSLOVNEGA NAČRTA

OpenAIRE

Božič, Tanja

2010-01-01

V diplomskem delu smo oblikovali marketinški načrt romantičnega hotela Renesanse. V prvem delu diplomskega dela proučujemo teoretična izhodišča v povezavi z marketinškim načrtom. Pojasnili smo integralno vlogo marketinškega načrta v poslovnem načrtu podjetja. Opredelili smo ga kot pot, načine, možnosti za doseganje načrtovane prodaje podjetniških učinkov (izdelkov in/ali storitev). V drugem, praktičnem delu diplomskega dela predstavljamo celostno marketinško strategijo hotela Renesan...

PREPOZNAVNOST PLESNEGA LJUDSKEGA IZROČILA PRI OSNOVNOŠOLCIH

OpenAIRE

Žižek, Tamara

2016-01-01

Diplomsko delo z naslovom Prepoznavnost plesnega ljudskega izročila pri osnovnošolcih sestavljata teoretični in empirični del. V teoretičnem delu smo predstavili ples na splošno ter ljudski ples, osredotočili smo se bolj podrobno na en slovenski ljudski ples, ki se imenuje štajeriš. Predstavili smo tudi poučevanje ljudskih plesov, kaj je pomembno za vodenje folklorne skupine, opisali oblačila, ki se imenujejo narodne noše, ter na kratko predstavili nekaj izbranih šeg in navad naših prednikov...

Options for sustaining solar-powered mosquito trapping systems on Rusinga Island, Western Kenya

NARCIS (Netherlands)

Oria, Prisca A.; Wijnands, Michiel; Alaii, Jane; Leeuwis, Cees

2018-01-01

Background: In 2012, a donor-supported proof of principle study was launched to eliminate malaria from Rusinga Island, western Kenya, using solar-powered mosquito trapping systems (SMoTS). SMoTS, which also provided power for room lighting and charging mobile telephones, were installed in houses. In

Os sertões: atualidade e arcaísmo na representação cultural de um conflito brasileiro Os sertões: present time and archaism in the cultural representation of a Brazilian conflict

Directory of Open Access Journals (Sweden)

Paulo Venancio Filho

1998-07-01

Full Text Available Este texto busca contrapor os aspectos antagônicos da revolta de Canudos tal como percebido por Euclides da Cunha em Os sertões. A revolta revelava tragicamente a permanência de um arcaísmo irresolvido. O horror da guerra, o confronto entre a ‘civilização’ e a ‘barbárie’ ainda se manifestam cem anos depois do conflito. O mesmo confronto que a literatura já pressentia e descrevia. Aquele que, no plano não menos verdadeiro da ficção, também se revela no romance O coração das trevas, de Joseph Conrad, publicado em 1902, o mesmo ano da publicação de Os sertões.The article examines antagonistic aspects of the battle of Canudos as portrayed by Euclides da Cunha in Os sertões. In tragic fashion, the rebellion made it apparent that an archaism had not been resolved. The horror of war, the conflict between civilization and barbarism, is still with us one hundred years later - the same conflict that literature foresaw and described. In the realm of fiction (yet no less truthful, this conflict was also portrayed in Joseph Conrad’s Heart of Darkness, published in 1902, the same year as Os sertões.

O ensino religioso em Franz Rosenzwieg

OpenAIRE

Guarnieri, Maria Cristina Mariante

2007-01-01

Frente a discussão que se apresenta sobre “Ensino de Religião”, essa comunicação pretende propor uma reflexão a partir do pensador Franz Rosenzweig (1886-1929). Partindo do pressuposto que a religião se dá na experiência concreta, Rosenzweig terá como preocupação principal o ensino religioso, o que transforma uma possível teoria da religião em uma pedagogia da religião, pois, para ele, compreender judaísmo é praticar judaísmo. O objetivo de Rosenzweig não é validar o judaísmo – a religião. É ...

OGLAŠEVANJE NA FACEBOOKU

OpenAIRE

Renko, Katica

2013-01-01

V magistrskem delu smo se seznanili z oglaševanjem na Facebooku. S pregledom gradiva, ki nam je ponujeno, smo preverili pogoje, načine, oblike … oglaševanja, ki pa smo jih s pregledom situacije v praksi preverili in dopolnili. Ob zaključku dela lahko rečemo, da je oglaševanje preko FB enostavnejše, cenejše, dostopnejše, omogoča nam ažurnost in samo komunikacijo z naslovniki, ki so potencialni kupci naših ponudb. Množični mediji nam omogočajo mnogotero obliko oglaševanja. Izbrana oblika ponuja...

The role of surface preparation in corrosion protection of copper with nanometer-thick ALD alumina coatings

Energy Technology Data Exchange (ETDEWEB)

Mirhashemihaghighi, Shadi; Światowska, Jolanta [PSL Research University, CNRS – Chimie ParisTech, Institut de Recherche de Chimie Paris (IRCP), 11 rue Pierre et Marie Curie, 75005 Paris (France); Maurice, Vincent, E-mail: vincent.maurice@chimie-paristech.fr [PSL Research University, CNRS – Chimie ParisTech, Institut de Recherche de Chimie Paris (IRCP), 11 rue Pierre et Marie Curie, 75005 Paris (France); Seyeux, Antoine; Klein, Lorena H. [PSL Research University, CNRS – Chimie ParisTech, Institut de Recherche de Chimie Paris (IRCP), 11 rue Pierre et Marie Curie, 75005 Paris (France); Salmi, Emma; Ritala, Mikko [Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55, FIN-00014 Helsinki (Finland); Marcus, Philippe [PSL Research University, CNRS – Chimie ParisTech, Institut de Recherche de Chimie Paris (IRCP), 11 rue Pierre et Marie Curie, 75005 Paris (France)

2016-11-30

Highlights: • 10–50 nm thick alumina coatings were grown on copper by atomic layer deposition. • Surface smoothening by substrate annealing was studied as pre-deposition treatment. • Corrosion protection is promoted by pre-treatment for 10 nm but not for thicker films. • Local adhesion failure is assigned to the stresses accumulated in the thicker films. • Surface smoothening decreases the interfacial strength bearing the film stresses. - Abstract: Surface smoothening by substrate annealing was studied as a pre-treatment for improving the corrosion protection provided to copper by 10, 20 and 50 nm thick alumina coatings deposited by atomic layer deposition. The interplay between substrate surface state and deposited film thickness for controlling the corrosion protection provided by ultrathin barrier films is demonstrated. Pre-annealing at 750 °C heals out the dispersed surface heterogeneities left by electropolishing and reduces the surface roughness to less than 2 nm independently of the deposited film thickness. For 10 nm coatings, substrate surface smoothening promotes the corrosion resistance. However, for 20 and 50 nm coatings, it is detrimental to the corrosion protection due to local detachment of the deposited films. The weaker adherence of the thicker coatings is assigned to the stresses accumulated in the films with increasing deposited thickness. Healing out the local heterogeneities on the substrate surface diminishes the interfacial strength that is bearing the stresses of the deposited films, thereby increasing adhesion failure for the thicker films. Pitting corrosion occurs at the local sites of adhesion failure. Intergranular corrosion occurs at the initially well coated substrate grain boundaries because of the growth of a more defective and permeable coating at grain boundaries.

Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

Energy Technology Data Exchange (ETDEWEB)

Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Fu, Chao [Department of Ultrasonography, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China); Cao, Zhang, E-mail: zzzhangcao@126.com [Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan (China)

2015-08-28

Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2.

Sonic hedgehog stimulates glycolysis and proliferation of breast cancer cells: Modulation of PFKFB3 activation

International Nuclear Information System (INIS)

Ge, Xin; Lyu, Pengwei; Gu, Yuanting; Li, Lin; Li, Jingruo; Wang, Yan; Zhang, Linfeng; Fu, Chao; Cao, Zhang

2015-01-01

Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did not alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser 461 , along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

International Nuclear Information System (INIS)

Lee, Seung Joon; Krauthauser, Candice; Maduskuie, Victoria; Fawcett, Paul T; Olson, James M; Rajasekaran, Sigrid A

2011-01-01

Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models. Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo. Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model. The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma

O ecologismo dos pobres

Directory of Open Access Journals (Sweden)

Juan Martinez ALIER

1997-12-01

Full Text Available O ecologísmo tem colocado em cheque as leis capitalistas de mercado, principalmente na sua fase globalizada, devido à apropriação e exploração inconsequente dos recursos naturais. Ao mesmo tempo tem apontado que o meio ambiente não se reduz ao tratamento somente cientifico da natureza. O presente artigo ressalta aspectos importantes do ecologísmo como a participação das mulheres, o marxismo, o neo-narodnismo, etc. e é rico em exemplos de problemas ambientais decorrentes das relações de produção. O ecologísmo dos pobres é apontado como uma perspectiva necessária às lutas ambientais no Terceiro Mundo.

Non-stoichiometry of MoS2 phase prepared by sputtering

International Nuclear Information System (INIS)

Ito, T.; Nakajima, K.

1978-01-01

The lattice parameters and S/Mo atomic ratio in sputtered MoS 2 films have been examined as a function of sputtering conditions, especially the vacuum pressure in the chamber. It was found that the deposited films had a defect MoS 2 structure ranging from 1.6 to 2 in S/Mo ratio, depending on the pressure. (author)

Forearm muscle oxygenation during sustained isometric contractions in rock climbers

Directory of Open Access Journals (Sweden)

Jan Kodejška

2016-02-01

Full Text Available Background. Bouldering and lead climbing are divergent disciplines of the sport of rock climbing. Bouldering moves are short and powerful, whilst sport climbing is longer and require a greater degree of endurance. Aim. The aim of this study was to compare forearm muscle oxygenation during sustained isometric contraction between lead climbers (LC and boulderers (BO. Methods. Eight BO and twelve LC completed maximal finger flexor strength test and sustained contractions to exhaustion at 60% of maximum voluntary contraction (MVC. Differences between BO and LC in maximal strength, time to exhaustion, force time integral (FTI, and tissue oxygenation (SmO2 were assessed by t-test for independent samples. Results. LC showed significantly lower level of average tissue oxygenation (BO 38.9% SmO2, s = 7.4; LC 28.7% SmO2, s = 7.1 and maximal tissue deoxygenation (BO 25.6% SmO2, s = 8.2; LC 13.5% SmO2, s = 8.5. LC demonstrated significantly lower finger flexor strength (519 N, s = 72 than BO (621 N, s = 142. LC sustained a longer time of contraction (not significantly (BO 52.2 s, s = 11.5; LC 60.6 s, s = 13 and achieved a similar value of FTI (BO 17421 Ns, s = 4291; LO 17476 Ns, s = 5036 in the endurance test. Conclusions. The results showed lower deoxygenation during sustained contraction in BO than LC despite similar FTI, indicating different local metabolic pathways in both groups.

Hieroglyfické písmo

Czech Academy of Sciences Publication Activity Database

Dvořák, Tomáš

2017-01-01

Roč. 39, č. 1 (2017), s. 83-107 ISSN 1210-0250 Institutional support: RVO:67985955 Keywords : Carlo Ginzburg * indexical paradigm * script * self-registering instruments Subject RIV: AB - History OBOR OECD: Philosophy, History and Philosophy of science and technology

PROGRAMSKE REŠITVE ZA LASTNIKE PSOV

OpenAIRE

Kisovec, Ksenja

2016-01-01

Lastniki in ljubitelji psov se vsakodnevno srečujejo z izgubljenimi živalmi. Hitro iskanje lahko pomeni razliko med življenjem in smrtjo male živali. V diplomskem delu smo predstavili implementacijo mobilne rešitve, ki deluje na platformi Windows Mobile. Raziskali in implementirali smo sledenje psom, opominjanje na pomembne datume, izboljšan pregled nad veterinami ter pasjimi šolami.

Optimization of laser accelerated proton beams for possible applications

Energy Technology Data Exchange (ETDEWEB)

Al-Omari, Husam [GSI Helmholtzzentrum fuer Schwerionenforschung GmbH, Planckstrasse 1, 64291 Darmstadt (Germany); Collaboration: LIGHT-Collaboration

2013-07-01

Optimization of transported proton beams through a pulsed solenoid in the laser proton experiment LIGHT at GSI has been studied numerically. TraceWin, SRIM and ATIMA codes were employed for this study with an initial distribution generated by MATLAB program fitted to Phelix measured data. Two individual tools have been used to produce protons beam as a later beam source: an aperture located at the solenoid focal spot as energy selection tool; and a scattering foil at a suitable position in the beam path that smoothens the simulated radial energy imprint on the beam profile. The simulation results show that the proton energy spectrum is filtered by the aperture and the radial energy correlation is smoothened.

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

Directory of Open Access Journals (Sweden)

Olson James M

2011-04-01

Full Text Available Abstract Background Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models. Methods Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo. Results Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model. Conclusions The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.

Valores, altruísmo e comportamentos de ajuda: comparando doadores e não doadores de sangue = Values, altruism and helping behaviors: comparing donors and non-donors of blood = Valores, altruismo y comportamientos de ayuda: comparando donantes y no-donantes de sangrep

Directory of Open Access Journals (Sweden)

Gouveia, Valdiney Velôso

2014-01-01

Full Text Available Os comportamentos de ajuda e altruísmo consistem em ações em prol do bem-estar do outro, variando quanto ao grau de entrega e sendo fundamentais para as relações interpessoais. Portanto, saber o que motiva tais comportamentos pode contribuir para compreender a natureza humana e desenvolver intervenções fomentando condutas pró-sociais. Este estudo objetivou conhecer em que medida os valores humanos se correlacionam com estes construtos em grupos de doadores e não doadores de sangue. Participaram 142 pessoas da população geral (idade: M=27, DP=19,93; 60,6% mulheres, compondo, equitativamente, os dois grupos (doadores e não doadores. Por meio de ANOVA avaliou-se em que medida as pontuações destes diferiam acerca dos construtos avaliados. Observou-se que os doadores são mais altruístas e apresentam mais comportamentos de ajuda, além destes construtos terem apresentado correlações com valores que caracterizam uma orientação universalista. Discutem-se estes achados à luz da teoria funcionalista dos valores humanos

ℓ0 -based sparse hyperspectral unmixing using spectral information and a multi-objectives formulation

Science.gov (United States)

Xu, Xia; Shi, Zhenwei; Pan, Bin

2018-07-01

Sparse unmixing aims at recovering pure materials from hyperpspectral images and estimating their abundance fractions. Sparse unmixing is actually ℓ0 problem which is NP-h ard, and a relaxation is often used. In this paper, we attempt to deal with ℓ0 problem directly via a multi-objective based method, which is a non-convex manner. The characteristics of hyperspectral images are integrated into the proposed method, which leads to a new spectra and multi-objective based sparse unmixing method (SMoSU). In order to solve the ℓ0 norm optimization problem, the spectral library is encoded in a binary vector, and a bit-wise flipping strategy is used to generate new individuals in the evolution process. However, a multi-objective method usually produces a number of non-dominated solutions, while sparse unmixing requires a single solution. How to make the final decision for sparse unmixing is challenging. To handle this problem, we integrate the spectral characteristic of hyperspectral images into SMoSU. By considering the spectral correlation in hyperspectral data, we improve the Tchebycheff decomposition function in SMoSU via a new regularization item. This regularization item is able to enforce the individual divergence in the evolution process of SMoSU. In this way, the diversity and convergence of population is further balanced, which is beneficial to the concentration of individuals. In the experiments part, three synthetic datasets and one real-world data are used to analyse the effectiveness of SMoSU, and several state-of-art sparse unmixing algorithms are compared.

Severe maternal morbidity in Zanzibar's referral hospital: Measuring the impact of in-hospital care.

Directory of Open Access Journals (Sweden)

Tanneke Herklots

Full Text Available to analyse the impact of in-hospital care on severe maternal morbidity using WHO's near-miss approach in the low-resource, high mortality setting of Zanzibar's referral hospital.Mnazi Mmoja Hospital, a tertiary care facility, in Zanzibar, Tanzania.We identified all cases of morbidity and mortality in women admitted within 42 days after the end of pregnancy at Mnazi Mmoja Hospital in the period from April to October 2016. The severity of complications was classified using WHO's near-miss approach definitions: potentially life-threatening condition (PLTC, maternal near-miss (MNM or maternal death (MD. Quality of in-hospital care was assessed using the mortality index (MI defined as ratio between mortality and severe maternal outcome (SMO where SMO = MD + MNM, cause-specific case facility rates and comparison with predicted mortality based on the Maternal Severity Index model.5551 women were included. 569 (10.3% had a potentially life-threatening condition and 65 (1.2% a severe maternal outcome (SMO: 37 maternal near-miss cases and 28 maternal deaths. The mortality index was high at 0.43 and similar for women who developed a SMO within 12 hours of admission and women who developed a SMO after 12 hours. A standardized mortality ratio of 6.03 was found; six times higher than that expected in moderate maternal mortality settings given the same severity of cases. Obstetric haemorrhage was found to be the main cause of SMO. Ruptured uterus and admission to ICU had the highest case-fatality rates. Maternal death cases seemed to have received essential interventions less often.WHO's near-miss approach can be used in this setting. The high mortality index observed shows that in-hospital care is not preventing progression of disease adequately once a severe complication occurs. Almost one in two women experiencing life-threatening complications will die. This is six times higher than in moderate mortality settings.

Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

Science.gov (United States)

Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

2018-02-06

Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

PRIMERJAVA SUHIH TRAVIŠČ IZ DVEH RAZLIČNIH GEOLOŠKIH PODLAG GLEDE NA C-S-R EKOLOŠKE STRATEGIJE RASTLIN

OpenAIRE

Hartman, Klavdija

2009-01-01

V diplomski nalogi smo opravili floristično in funkcionalno primerjavo dveh tipov suhih travišč v hribovitem celinskem predelu Slovenije (asociacija Scabioso hladnikianae-Caricetum humilis, razred Festuco-Brometea in asociacija Homogyno alpinae-Nardetum, razred Calluno-Ulicetea), ki sta razvita na različni geološki podlagi (karbonatna oz. nekarbonatna silikatna). Analizirali smo 30 še neobjavljenih popisov asociacije Scabioso hladnikianae-Caricetum humilis in 32 objavljenih popisov asociaci...

Zaznana povezanost med komponentami zavarovalne storitve pri uporabnikih dopolnilnega zdravstvenega zavarovanja

OpenAIRE

Šebjan, Urban

2015-01-01

V prispevku proučujemo odnose med komponentami storitve dopolnilno prostovoljno zdravstveno zavarovanje (DPZZ), ki jim uporabniki pripisujejo različno vlogo. Raziskovalni model s štirimi konstrukti (pomembnost kakovosti, dodatnih kritij, cenovnih popustov storitve dpzz in ugleda zavarovalnice) in indikatorjem pomembnost zavarovalne premije dpzz smo preverili z modeliranjem strukturnih enačb (SEM) na vzorcu 300 slovenskih uporabnikov storitve DPZZ. Ugotovili smo, da se pomen komponente storitv...

Zaznana povezanost med komponentami zavarovalne storitve pri uporabnikih dopolnilnega zdravstvenega zavarovanja:

OpenAIRE

Šebjan, Urban

2013-01-01

V prispevku proučujemo odnose med komponentami storitve dopolnilno prostovoljno zdravstveno zavarovanje (DPZZ), ki jim uporabniki pripisujejo različno vlogo. Raziskovalni model s štirimi konstrukti (pomembnost kakovosti, dodatnih kritij, cenovnih popustov storitve dpzz in ugleda zavarovalnice) in indikatorjem pomembnost zavarovalne premije dpzz smo preverili z modeliranjem strukturnih enačb (SEM) na vzorcu 300 slovenskih uporabnikov storitve DPZZ. Ugotovili smo, da se pomen komponente storitv...

Crevice Corrosion Behavior of 45 Molybdenum-Containing Stainless Steels in Seawater.

Science.gov (United States)

1981-12-01

Armco, Avesta Jernverks, Cabot, Carpenter Technology, Crucible, Eastern, Firth-Brown, Huntington, Jessup, Langley Alloys, and Uddeholm. 16...Department of Energy, Report ANL/OTEC-BCM-022. 7. Wallen, B., and M. Liljas, " Avesta 254 SMO - A New, High Molybdenum Stainless Steel," presented at NKM8...1977).; 11. Wallen, B., " Avesta 254 SMO - A Stainless Steel for Seawater Service," presented at the Advanced Stainless Steels for Turbine Condensors

Power law-based local search in spider monkey optimisation for lower order system modelling

Science.gov (United States)

Sharma, Ajay; Sharma, Harish; Bhargava, Annapurna; Sharma, Nirmala

2017-01-01

The nature-inspired algorithms (NIAs) have shown efficiency to solve many complex real-world optimisation problems. The efficiency of NIAs is measured by their ability to find adequate results within a reasonable amount of time, rather than an ability to guarantee the optimal solution. This paper presents a solution for lower order system modelling using spider monkey optimisation (SMO) algorithm to obtain a better approximation for lower order systems and reflects almost original higher order system's characteristics. Further, a local search strategy, namely, power law-based local search is incorporated with SMO. The proposed strategy is named as power law-based local search in SMO (PLSMO). The efficiency, accuracy and reliability of the proposed algorithm is tested over 20 well-known benchmark functions. Then, the PLSMO algorithm is applied to solve the lower order system modelling problem.

Informacijska podpora Kolesarski zvezi Slovenije

OpenAIRE

Mahkovec, Tine

2015-01-01

V diplomskem delu je predstavljen razvoj informacijskega sistema za podporo delovanju Kolesarski zvezi Slovenije (v nadaljevanju KZS). V prvem delu diplomske naloge smo predstavili delovanje KZS, njene ključne delovne procese in sodelujoče osebe ter predstavili glavna uporabljena orodja in metode. V osrednjem delu smo izvedli glavne aktivnosti objektnega razvoja informacijskih sistemov (v nadaljevanju IS) ki vključuje zajem zahtev, analizo in arhitekturno načrtovanje. Aktivnosti implement...

PRODUKCIJA DOKUMENTARNIH FILMOV O ŽIVALIH

OpenAIRE

Vrabec, Petra

2016-01-01

Diplomsko delo opisuje produkcijo dokumentarnega filma o živalih in bralca vodi skozi potek produkcijskega procesa. Z diplomskim delom želimo ugotoviti standarde za doseganje visokokakovostnih dokumentarnih filmih o živalih. Lotili smo se pregleda predprodukcijskega procesa, elementov, vključenih v fazo planiranja, in kaj je pri tem potrebno upoštevati. Pogledali smo produkcijske pristope in opremo ter situacije, v katerih se uporablja. Prikazujemo, kaj je pomembno v zaključni fazi postproduk...

PRIMERJAVA GEODETSKIH METOD NA ZAHTEVNEM GRADBENEM OBJEKTU

OpenAIRE

Reberčnik, Matic

2017-01-01

V projektni nalogi smo v uvodnih poglavjih predstavili različne načine izvajanja geodetskih meritev, ki jih v gradbeništvu uporabljamo pri analizi pomikov in deformacij gradbenih konstrukcij ter terena, na katerem so le-te postavljene. V nadaljevanju opisujemo terestične in GNSS (globalni navigacijski satelitski sistem) metode, ki smo jih uporabljali pri izvajanju meritev na izbranem premostitvenem objektu avtocestnega odseka v Sloveniji (zaradi varovanja podatkov ga imenujemo Objekt 1). Pod...

ANALIZA OKOLJSKIH VPLIVOV PROIZVODNJE PIVA IZ VIDIKA CELOTNEGA ŽIVLJENJSKEGA CIKLA

OpenAIRE

Balajc, Renata

2010-01-01

V okviru diplomskega dela smo z analizo življenjskega cikla (LCA) ocenili vplive na okolje (abiotsko izkoriščanje surovinskih virov, potencial acidifikacije, evtrofikacije, globalnega segrevanja, tanjšanja ozonske plasti, tvorbe fotokemičnega potenciala), ki nastajajo v celotnem življenjskem ciklu proizvodnje piva, ki obsega: pridobivanje surovin, dobavo in transport materialov in embalaže, proizvodnjo in ravnanje po uporabi. Analizirali smo okoljske vplive posameznih faz proizvodnje piva s p...

Storitve REST in APIji s tehnologijo verige blokov

OpenAIRE

BALANTIČ, DOMEN

2017-01-01

V diplomski nalogi smo opisali osnovne koncepte in principe tehnologije verige blokov, ki omogoča decentraliziran način shranjevanja podatkov. Prednost decentraliziranega hranjenja podatkov je v visoki stopnji integritete shranjenih podatkov, saj jih po shranitvi v verigo blokov praktično nemogoče spreminjati. Opisali smo lastnosti treh najbolj priljubljenih in razširjenih platform verige blokov - platforme Bitcoin, platforme Ethereum in platforme Hyperledger Fabric - in jih med seboj podrobn...

CD200-expressing human basal cell carcinoma cells initiate tumor growth.

Science.gov (United States)

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Programski jezik MicroPython na mikrokrmilnikih ARM Cortex-M4

OpenAIRE

Brajnik, Mark

2017-01-01

V sklopu diplomske naloge je narejen pregled programskega jezika MicroPython in primerjava z najpogosteje uporabljenima programskima jezikoma za mikrokrmilnike. MicroPython smo uporabili za programiranje razvojne plošče Nucleo L476RG. Opravili smo namestitev MicroPython strojno-programske opreme na razvojno ploščo Nucleo L476RG, primerjali hitrost izvajanja programske kode z Arduinom Uno ter prikazali uporabo MicroPythona in Arduina na primerih sledilnega robota in PID krmiljenja elektromotor...

PODATKOVNE STORITVE ADO.NET IN ADO.NET ENTITY FRAMEWORK

OpenAIRE

Volavc, Franc

2012-01-01

V diplomskem delu smo predstavili Microsoftovi ogrodji ADO.NET in ADO.NET Entity Framework. Preučili in analizirali smo metode za dostop do podatkovnih virov, ki jih ponujata ogrodji, ter nato te ugotovitve preslikati v odločitveno drevo, katero bo programerjem in razvijalcem informacijskih sistemov pomagalo pri odločanju glede pristopa za dostop do podatkovnih virov. Ker bomo v diplomskem delu predstavili Microsoftovi ogrodji, bomo posledično omejeni zgolj na Microsoftovo tehnologijo, se pra...

Tratado Sobre os gigantes, de Fílon de Alexandria: apresentação, tradução, notas

Directory of Open Access Journals (Sweden)

César Motta Rios

2008-03-01

Full Text Available A importância da obra de Fílon de Alexandria ainda hoje é múltipla e real inclusive para o judaísmo. Conforme observado por David Runia (RUNIA, 1990, p. 185-186, seu estudo é válido para qualquer um que se interesse por literatura judaico-­helenística, judaísmo do segundo templo, Novo Testamento, patrística e gnosticismo, cultura helenística e filosofia grega.

VPLIV VAN DER WAALSOVIH SIL NA TVORBO ASOCIIRANIH MOLEKUL

OpenAIRE

Kuster, Bernarda

2014-01-01

Namen diplomske naloge je preučiti vpliv van der Waalsovih sil na tvorbo asociiranih molekul. V ta namen smo izbrali površinsko aktivne snovi, ki imajo amfifilne lastnosti in vplivajo na povšinske in medfazne napetosti ter pri določeni koncentraciji, imenovani kritična micelna koncentracija (CMC), tvorijo molekulske skupke, ki jim pravimo micele. Kritično micelno koncentracijo smo določili trem površinsko aktivnim snovem: heksadeciltrimetilamonijevemu bromidu, tetradeciltrimetilamonijevemu b...

Tržna analiza in razvoj aluminijastih ohišij LED svetil

OpenAIRE

Gorišek, Krešimir

2014-01-01

V magistrskem delu je predstavljena tržna analiza oziroma natančneje analiza zunanjega okolja organizacije. Privlačnost panoge smo ocenjevali s Porterjevim modelom konkurence v panogi in ugotovitve predstavili. Analizo širšega zunanjega okolja oziroma analizo političnih, ekonomskih, socialnih, tehnoloških, okoljskih in pravnih elementov smo izvedli s PESTEL analizo in ugotovitve predstavili. Magistrsko delo obsega tudi razvoj aluminijastih ohišij LED (Light Emitting Diode) svetil. Podrobneje ...

ORGANIZACIJSKO VZDUŠJE V JAVNEM ZAVODU

OpenAIRE

Čeh, Tanja

2011-01-01

Organizacijsko vzdušje je za vsako organizacijo zelo pomembno. Vzdušje v organizaciji je odvisno od zadovoljstva zaposlenih na delovnem mestu, organiziranosti dela, načinu vodenja, medosebnih odnosov, nagradah in željah glede njihovega dela, kariere in izobraževanja. V teoretičnem delu smo bolj podrobno spoznali organizacijsko vzdušje, zgodovino ter dimenzije organizacijskega vzdušja, prav tako smo predstavili organizacijsko kulturo ter razlike med organizacijskim vzdušjem in kulturo ter...

Analiza in primerjava oblačnih storitev za razvoj mobilnih zalednih storitev

OpenAIRE

Damiš, Aleksander

2018-01-01

Magistrsko delo posega na področje uporabe zalednih oblačnih storitev na mobilnih napravah, ki postajajo vedno bolj priljubljene, saj razvijalcem omogočajo hitro vzpostavitev, povezljivost in enostavno upravljanje med mobilnimi aplikacijami in zaledjem, kjer se hranijo podatki. V raziskovalnem delu smo predstavili koncept storitev računalništva v oblaku, opazovali njen razvoj in prehod uporabe storitev na mobilne platforme ter možnosti njihove uporabe. Podrobno smo analizirali in predstavili ...

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

Science.gov (United States)

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Characterisation of agricultural waste-derived biochars and their sorption potential for sulfamethoxazole in pasture soil: A spectroscopic investigation

International Nuclear Information System (INIS)

Srinivasan, Prakash; Sarmah, Ajit K.

2015-01-01

We investigated the effects of feedstock type and pyrolysis temperatures on the sorptive potential of a model pastoral soil amended with biochars for sulfamethoxazole (SMO), using laboratory batch sorption studies. The results indicated that high temperature chars exhibited enhanced adsorptive potential, compared to low temperature chars. Pine sawdust (PSD) biochar produced at 700 °C using the steam gasification process exhibited the highest sorptive capacity (2-fold greater than the control treatment) for SMO among the three biochars used. Soils amended with green waste (GW) biochars produced at three different pyrolysis temperatures showed a small increase in SMO sorption with the increases in temperature. The NMR spectra, the elemental molar ratios (H/C, O/C) and polarity index (O + N)/C of the biochars revealed that PSD biochar possessed the highest degree of aromatic condensation compared to CC and GW chars. These results correlated well with the sorption affinity of each biochar, with effective distribution coefficient (K d eff ) being highest for PSD and lowest for GW biochars. X-ray photoelectron spectroscopy results for the biochars showed a relatively large difference in oxygen containing surface functional groups amongst the GW biochars. However, they exhibited nearly identical sorption affinity to SMO, indicating negligible role of oxygen containing surface functional groups on SMO sorption. These observations provide important information on the use of biochars as engineered sorbents for environmental applications, such as reducing the bioavailability of antibiotics and/or predicting the fate of sulfonamides in biochar-amended soils. - Highlights: • High temperature chars showed enhanced adsorptive potential, compared to low temperature chars. • Oxygen containing acidic functional groups of biochar play negligible role in sorption. • Biochar properties like specific surface area and aromaticity enhanced its sorption capacity. • Amendment of

Fotointerpretation and geological integration of San Diego-El Naranjo thermal zone in the Nayarit State, Mexico; Fotointerpretacion e integracion geologica de la zona termal de San Diego-El Naranjo, Nayarit, Mexico

Energy Technology Data Exchange (ETDEWEB)

Castillo H, Daniel [Gerencia de Proyectos Geotermoelectricos de la Comision Federal de Electricidad, Morelia (Mexico)

1996-01-01

The lithological, structural and thermal characteristics of a zone located in the State of Nayarit, Mexico between the Sierra Madre Occidental (SMO) and the Llanura Costera del Pacifico (PCP) are presented. The SMO is constituted by both extrusive and intrusive rocks of Oligo-Miocene age whereas the PCP is formed by conglomerates and erosional products derived from the disintegration of these rocks. Nine thermal superficial manifestations were observed at the site, with temperatures ranging from 35 degrees celsius to 80 degrees celsius. The chemical nature of these geothermal fluids is sodium-sulfate with estimated deep temperatures of 185 degrees celsius. From the structural view point, the zone is affected by faults and fractures aligned NE-SW and NW-SE; these structural trends control the thermalism. On the other hand, a 20 x 20 km ring-shaped geologic feature was identified within the area, which may be associated with the SMO. [Espanol] Se presentan las caracteristicas litologicas, estructurales y termales de una zona del Estado de Nayarit, comprendida entre las Provincias de la Sierra Madre Occidental (SMO) y la Llanura Costera del Pacifico (PCP). La primera comprende rocas igneas, intrusivas y extrusivas, de edad oligomiocenica. La segunda agrupa productos erosivos y conglomeraticos producidos por la desintegracion de las rocas; su edad se considera del Cuaternario. En la zona existen nueve localidades termales con un intervalo de temperatura de 35 grados celsius a 80 grados celsius, y un caracter quimico sulfatado-sodico. Por geotermometria se obtuvo una temperatura de 185 grados celsius. Estructuralmente dominan las fallas y fracturas NE-SW y NW-SE, que afectan a todas las rocas expuestas y controlan tambien al termalismo. Dentro del area se identifico una geoforma circular de 20 x 20 km, que se considera asociada y controlada geneticamente por la SMO.

Characterisation of agricultural waste-derived biochars and their sorption potential for sulfamethoxazole in pasture soil: A spectroscopic investigation

Energy Technology Data Exchange (ETDEWEB)

Srinivasan, Prakash; Sarmah, Ajit K., E-mail: a.sarmah@auckland.ac.nz

2015-01-01

We investigated the effects of feedstock type and pyrolysis temperatures on the sorptive potential of a model pastoral soil amended with biochars for sulfamethoxazole (SMO), using laboratory batch sorption studies. The results indicated that high temperature chars exhibited enhanced adsorptive potential, compared to low temperature chars. Pine sawdust (PSD) biochar produced at 700 °C using the steam gasification process exhibited the highest sorptive capacity (2-fold greater than the control treatment) for SMO among the three biochars used. Soils amended with green waste (GW) biochars produced at three different pyrolysis temperatures showed a small increase in SMO sorption with the increases in temperature. The NMR spectra, the elemental molar ratios (H/C, O/C) and polarity index (O + N)/C of the biochars revealed that PSD biochar possessed the highest degree of aromatic condensation compared to CC and GW chars. These results correlated well with the sorption affinity of each biochar, with effective distribution coefficient (K{sub d}{sup eff}) being highest for PSD and lowest for GW biochars. X-ray photoelectron spectroscopy results for the biochars showed a relatively large difference in oxygen containing surface functional groups amongst the GW biochars. However, they exhibited nearly identical sorption affinity to SMO, indicating negligible role of oxygen containing surface functional groups on SMO sorption. These observations provide important information on the use of biochars as engineered sorbents for environmental applications, such as reducing the bioavailability of antibiotics and/or predicting the fate of sulfonamides in biochar-amended soils. - Highlights: • High temperature chars showed enhanced adsorptive potential, compared to low temperature chars. • Oxygen containing acidic functional groups of biochar play negligible role in sorption. • Biochar properties like specific surface area and aromaticity enhanced its sorption capacity. �

Accurate kinematic measurement at interfaces between dissimilar materials using conforming finite-element-based digital image correlation

KAUST Repository

Tao, Ran; Moussawi, Ali; Lubineau, Gilles; Pan, Bing

2016-01-01

Digital image correlation (DIC) is now an extensively applied full-field measurement technique with subpixel accuracy. A systematic drawback of this technique, however, is the smoothening of the kinematic field (e.g., displacement and strains

Inquisição, religiosidade e transformações culturais: a sinagoga das mulheres e a sobrevivência do judaísmo feminino no Brasil colonial - Nordeste, séculos XVI-XVII

Directory of Open Access Journals (Sweden)

Angelo Adriano Faria de Assis

2002-01-01

Full Text Available A visitação do Santo Ofício ao Nordeste açucareiro entre 1591e 1595 traria à tona os conflitos sociais e a disputa de interesses entre cristãos velhos e novos. Principais delatados, os neoconversos tornam-se figuras centrais das acusações feitas à mesa e vítimas em potencial das generalizações sobre seu suposto comportamento criptojudaico, acusados das mais diversas heresias. Dentre os delatados, chama a atenção o significativo número de mulheres, baluartes da resistência judaica, difusoras de sua cultura e tradições para as novas gerações. Responsáveis pelo ambiente doméstico, seriam as grandes propagadoras do judaísmo secreto e diminuto que se tornara possível após as proibições de livre crença no mundo português a partir de 1497, e a instauração da Inquisição, em 1536, quando os lares passaram a representar papel preponderante para a divulgação e sobrevivência das tradições dos filhos de Israel.The visit of the Holly Inquisition to the northeast of Brazil between 1591 and 1595 would expose social conflicts and disputes of interests among old and new Christians. The last were the potential victims and the main accused of maintaining a crypto-judaic behavior, performing several heresies. Among the accused, there was an impressive number of women, center of Jewish resistence, transmitting the culture and the tradition to the new generations. After the prohibition of any other faith than Catholicism in the Portuguese world in 1497 and the stablishment of the Inquisition in 1536, women would become responsible for the diffusion of secret Judaism. Homes became a central place to the survival of Jewish traditions.

Exploring Life Forms for Linking Orthopteran Assemblage and Grassland Plant Community

Directory of Open Access Journals (Sweden)

Labadessa Rocco

2015-06-01

Full Text Available Kobilice predstavljajo večino biomase žuželk v številnih travniških ekosistemih. Vendar povezava med tradicionalnimi opisi združb kobilic in rastlinskimi združbami ni enostavna. Raziskali smo uporabnost koncepta življenjskih oblik za proučevanje teh ekosistemskih odnosov. Za ta namen smo klasificirali trideset vzorčenih pol-naravnih karbonatnih travišč na podlagi deleža dominantnih življenjskih oblik zelišč. Vrste kobilic smo združili v štiri kategorije na podlagi kategorizacije življenjskih oblik po Bei-Bienko. Povezavo rastlinskih združb, vrstne sestave kobilic in okoljskih dejavnikov smo testirali z kanonično korespondenčno analizo. Skupine Orthoptera so se pojavljale v rastlinskih združbah in nakazovale tudi vpliv vegetacijskih sprememb na vrstno sestavo kobilic. Vrste giobiontov so se pojavljale v najbolj motenih rastlinskih združbah, medtem ko so hortobionti in tamnobionti bolj navezani na bolj ohranjene traviščne tipe. Zaključimo lahko, da nam življenjske oblike lahko pomagajo povezati vrstno sestavo kobilic s naravovarstvenim statusom travišča. Informacija o teh odnosih v združbi na lokalni ravni lahko pomaga upravljavcem pri tolmačenju kart, ki prikazujejo spremembe v habitatnih tipih kot spremembe v biodiverziteti.

Evaluación de absentismo dos enfermeria profesional en una unidad de cuidados intensivos neonatal

Directory of Open Access Journals (Sweden)

Carolina Sampaio OLIVEIRA

2011-04-01

Full Text Available O absenteísmo é um problema que para os trabalhadores de enfermagem da área hospitalar gera graves conseqüências, como a queda na qualidade da assistência prestada ao cliente e o aumento do estresse e ansiedade nos membros da equipe de trabalho. Este artigo busca identificar os fatores geradores de absenteísmo apresentados por funcionários de enfermagem alocados em uma UTIN de um hospital escola do município de Cuiabá- MT, no período de janeiro de 2009 a janeiro de 2011. Trata-se de pesquisa quantitativa com abordagem descritiva, exploratória e documental. Foi realizado um levantamento do absenteísmo, e registros de 35 profissionais de enfermagem. Pode-se concluir que houve a predominância do sexo feminino (90,33% e (45,16% dos profissionais possuíam mais de um vínculo empregatício. Em relação às ausências (54, 84% confirmam já ter se ausentado do trabalho por motivo doença sendo as mais prevalentes relacionadas ao aparelho respiratório totalizando 17,32% seguido pelas doenças osteomusculares em 12,59%%. O absenteísmo-doença na unidade de escolha foi considerável, elevado, indicando, ações que favoreçam o controle da saúde do trabalhador

Raziskava stališč o leseni gradnji v Sloveniji v letu 2006

OpenAIRE

Kitek Kuzman, Manja; Hrovatin, Jasna

2007-01-01

Lesena gradnja predstavlja na področju stanovanjskih stavb v Sloveniji le majhen delež celotne gradnje. Želeli smo ugotoviti, kaj je vzrok tako majhnegadeleža lesene gradnje v Sloveniji. Z javnomnenjsko raziskavo "Slovensko javno mnenje o leseni gradnji" smo anketirance spraševali o poznavanju lesene gradnje in njenih prednostih. Zbiranje podatkov je bilo opravljeno z metodo CATI. Ugotovljeno je bilo, da javnost ni dovolj seznanjenas prednostmi lesene gradnje.Večina vprašanih, ki živi v indiv...

UČINEK OSEMTEDENSKE AEROBNE VADBE PLAVALCEV V STAROSTI OD PETNAJSTEGA DO OSEMNAJSTEGA LETA

OpenAIRE

Majhen, Domen

2011-01-01

Plavanje je predvsem aerobni šport. Vadba vzdržljivosti ima v plavanju velik pomen, saj so tekmovalne discipline, (z izjemo 50 metrskih disciplin) in s tem napori, daljši od 30 sekund. Z daljšanjem tekmovalnih razdalj so vedno bolj prisotni aerobni energijski procesi. Proces treninga je sestavljen iz treh faz: planiranje, izvajanje in vodenje procesa treninga ter nadzor. Testirani plavalci so opravili 15-tedenski makrocikel, ki smo ga razdelili na 5 mezociklov. Merjenja in napredek smo spreml...

Uniform flow around a circular cylinder in the subcritical range - using the Self-induced angular Moment Method turbulence model

DEFF Research Database (Denmark)

Johansson, Jens; Nielsen, Mogens Peter

The uniform flow around a circular cylinder at Reynolds number 1e5 is simulated in a three dimensional domain by means of the newly developed Self-induced angular Moment Method, SMoM, turbulence model. The global force coefficients, Strouhal number, pressure distributions and wall shear stress...... distributions are compared to experimental findings reported in literature. The SMoM turbulence model is found to provide maximum, minimum and time-mean pressure coefficient distributions in very good agreement with experimental findings....

Uvajanje funkcionalnega živila na slovenski trg: primer Pomurskih mlekarn

OpenAIRE

Hari, Sebjan

2009-01-01

V letu 2009 smo s pomočjo terenske in spletne ankete ugotavljali potencialni interes potrošnikov za novo funkcionalno živilo Pomurskih mlekarn — mleko z dodatki fitosterolov. Iz rezultatov obeh anket smo ugotovili, da je prepoznavnost pojma »funkcionalno živilo« zelo slaba, pozna ga le 20% anketirancev, kjer je poznavanje pojma odvisno od starosti in izobrazbe. Približno 50% anketirancev je pripravljenih kupiti izdelek (pripravljenost ni odvisna od starosti in izobrazbe), le približno 30% pa ...

SIMULACIJE DELOVANJA LEDVIC S PROGRAMSKIM ORODJEM PHYSIOEX

OpenAIRE

Kovačevič, Tadej

2016-01-01

V diplomskem delu smo predstavili uporabnost simulacij na področju fiziologije ledvic. Namen diplomskega dela je predstaviti simulacije na različnih področjih fiziologije ledvic. Simulacije so temeljile na vodenih primerih, ki nam jih omogoča simulacijski program. Za študente in že izobraženo zdravstveno osebje so izrednega pomena. Opisali smo anatomijo in fiziologijo ledvic, predstavili simulacije na področju fiziologije ledvic in pomen simulacij v procesu izobraževanja. Rezultati kažejo, da...

Revitalizacija religije u sjeni naslijeđa liberalne zakonske regulative: stavovi o pobačaju

OpenAIRE

Goldberger, Goran

2009-01-01

U ovom tekstu se analiziraju stavovi ispitanika o zakonskom reguliranju pobačaja u Hrvatskoj, koje smo ukrštali s religijskom samoidentifikacijom i praksom te sociodemografskim obilježjima ispitanika. Na taj način smo željeli ukazati na eventualnu prisutnost razlika u stavovima o pobačaju i zagovaranju opcije života ili opcije izbora, s obzirom na navedene karakteristike ispitanika. Polazeći od pretpostavke utjecaja konteksta društvenih promjena s početka 90-ih na stavove ...

Robust source and mask optimization compensating for mask topography effects in computational lithography.

Science.gov (United States)

Li, Jia; Lam, Edmund Y

2014-04-21

Mask topography effects need to be taken into consideration for a more accurate solution of source mask optimization (SMO) in advanced optical lithography. However, rigorous 3D mask models generally involve intensive computation and conventional SMO fails to manipulate the mask-induced undesired phase errors that degrade the usable depth of focus (uDOF) and process yield. In this work, an optimization approach incorporating pupil wavefront aberrations into SMO procedure is developed as an alternative to maximize the uDOF. We first design the pupil wavefront function by adding primary and secondary spherical aberrations through the coefficients of the Zernike polynomials, and then apply the conjugate gradient method to achieve an optimal source-mask pair under the condition of aberrated pupil. We also use a statistical model to determine the Zernike coefficients for the phase control and adjustment. Rigorous simulations of thick masks show that this approach provides compensation for mask topography effects by improving the pattern fidelity and increasing uDOF.

Acute asthma severity identification of expert system flow in emergency department

Science.gov (United States)

Sharif, Nurul Atikah Mohd; Ahmad, Norazura; Ahmad, Nazihah; Desa, Wan Laailatul Hanim Mat

2017-11-01

Integration of computerized system in healthcare management help in smoothening the documentation of patient records, highly accesses of knowledge and clinical practices guideline, and advice on decision making. Exploit the advancement of artificial intelligent such as fuzzy logic and rule-based reasoning may improve the management of emergency department in terms of uncertainty condition and medical practices adherence towards clinical guideline. This paper presenting details of the emergency department flow for acute asthma severity identification with the embedding of acute asthma severity identification expert system (AASIES). Currently, AASIES is still in preliminary stage of system validation. However, the implementation of AASIES in asthma bay management is hope can reduce the usage of paper for manual documentation and be a pioneer for the development of a more complex decision support system to smoothen the ED management and more systematic.

Fast and cheap prototyping of non-standard optical components for sensing speckle dynamics

DEFF Research Database (Denmark)

Jakobsen, Michael Linde; Olesen, Anders Sig; Stubager, Jørgen

2016-01-01

As a part of the work carried out a project supported by the Danish council for technology and innovation, we have investigated the option of smoothening standard CNC machined surfaces. In the process of constructing optical prototypes, involving custom-designed optics, the development price...... and time can become a prohibitively large part of a research budget. Machining the optical surfaces of a molding tool may be done directly using diamond turning, but it is expensive and time consuming. Alternatively, a more standardized and cheaper machining method can be used, however, calling for manual...... surfaces of various shapes succeeding a standard CNC machining process. Different coatings have been tested for their abilities to fill and smoothen out structures of larger scales, while removing the small-scale roughness, which is critical for optical uses. In this work we will present an optical element...

UČINKOVITO UPRAVLJANJE VAROVANJA PODATKOV V KARTIČNEM PLAČILNEM PROMETU

OpenAIRE

Šauperl, Blanka

2012-01-01

Uvedba zahtev standarda PCI DSS je za banko, ki nudi storitve vezane na kartično poslovanje, obvezna. V minulih letih so banke investirale v kompleksne rešitve, s katerimi zagotavljajo visok nivo informacijske varnosti. Kljub temu standard PCI DSS v določenih zahtevah predstavlja dodatne varnostne ukrepe, ki jih morajo uvesti banke. V raziskovalnem delu smo izvedli analizo standarda PCI DSS, s katero smo ugotovili vidike, v katerih je standard šibek a so za učinkovito uvedbo varnostnih za...

SAMOOSKRBA GOSPODINJSKEGA ODJEMA S SONČNO ELEKTRARNO IN BATERIJSKIM SISTEMOM

OpenAIRE

VIDMAJER, DAVID

2016-01-01

Diplomsko delo opiše in analizira otočno delovanje stanovanjskega objekta za štiričlansko družino z izbiro primerne sončne elektrarne, litij-ionskih baterij in dizelskega agregata (off-grid system). V diplomski nalogi smo na kratko predstavili problematiko delovanja sončne elektrarne, delovanje otočnega sistema in elemente, ki so nujni za njegovo obratovanje, ter opis in delovanje baterij. Sledi opis enačb za modeliranje komponent otočnega sistema, po kateremu principu smo naredili tudi nadal...

PROJEKT VPELJAVE SUIV V PODJETJE ALPINA, D.O.O.

OpenAIRE

Vehar, Klemen

2013-01-01

Namen magistrskega dela je prikazati, kako lahko s pomočjo napotkov standarda ISO/IEC 27003 in z uporabo računalniških orodij za projektno vodenje izdelamo plan vpeljave SUIV za določeno organizacijo. V teoretičnemu delu smo prikazali osnove s področja varnosti informacijskega sistema. Predstavili smo družino standardov ISO 27000 in druge standarde, ki služijo kot osnova pri vpeljavi sistema za upravljanje informacijske varnosti (SUIV) v organizacijo in so v praksi največkrat uporabljeni....

Okolju prijazno delovanje hotela

OpenAIRE

Miljanović, Biljana

2018-01-01

Magistrsko delo obravnava problematiko trajnostnega poslovanja hotelov. Tako v hotelski dejavnosti, kot tudi v turističnem sektorju postajajo načela trajnostnega razvoja vse pomembnejša. Ob vplivih na okolje velja poudariti tudi ekonomski in socialni vidik. V raziskavo smo vključili izbrani hotel iz hotelske verige xy. Namen je bilo raziskati, katere možnosti so nam na dosegu za bolj trajnostno poslovanje hotela. Pri tem smo vključili različne vplive na okolje, od odpadkov, porabe električne ...

Spolno nadlegovanje v slovenski policiji

OpenAIRE

Kmetič, Andreja

2017-01-01

V magistrski nalogi, ki je pred nami, obravnavamo spolno nadlegovanje v slovenski policiji. Ker se tematika magistrske naloge osredotoča predvsem na delovanje policije, smo velik del posvetili teoretični razlagi. Pomembno vprašanje nam je predstavljal zgodovinski začetek samega spolnega nadlegovanja, saj nas je zanimalo, kdaj se je o tem sploh začelo govoriti oziroma pisati. S pomočjo različnih avtorjev smo definirali pomen spolnega nadlegovanja in ugotovili, da gre v večini primerov za o...

Analiza vpliva barve na učinkovitost grafično oblikovanega logotipa

OpenAIRE

Piko, Maja

2017-01-01

V magistrskem delu smo obravnavali vpliv barv na učinkovitost logotipa, pri čemer smo želeli ugotoviti, ali je barva najučinkovitejša za predstavljanje izbrane dejavnosti. Učinkovitost barve pomeni, da jo anketiranci prepoznajo kot najbolj preferenčno. Osrednji motiv naloge je bil dokazati vpliv barve na učinkovitost logotipa in njegovo boljšo povezanost, prepoznavnost ter pozitivno asociacijo na dejavnost, ki jo predstavlja. Logotip je sestavljen iz različnih elementov, eden izmed njih pa je...

The Festuco-Brometea Grasslands on Sandstone and Marl-Clay-Sandstone Substrata in Tuscany (Northern-Central Italy

Directory of Open Access Journals (Sweden)

Foggi Bruno

2014-06-01

Full Text Available Travišča v katerih prevladujeta vrsti Bromus erectus in/ali Brachypodium rupestre pokrivajo velike površine na podlagi iz peščenjaka in laporasto-glinastega peščenjaka (apnenec je izključen na Apeninih in območju pred njimi med provincama Pistoia in Arezzo (Toskana, srednja Italija. Naša raziskava je bila osredotočena na 71 neobjavljenih in 45 objavljenih vegetacijskih popisov iz Toskane in sosednjih območij. Originalni popisi opisujejo asociacije Astragalo monspessulani-Brometum erecti, Centaureo bracteatae-Brometum erecti in Ononido masquillerii-Brometum erecti. Popise smo obdelali z multivariatno analizo s katero smo zaznali 9 skupin. Konsistenstnost skupin smo preverili s povprečjem NMDS proti Ellenberg/Pignatti indikatorskim vrednostim in CCA proti horotipom in rastnim oblikam. Diagnostične vrste posameznih skupin smo določili z navezanostjo vrst, ki temelji na φ koeficientu asociacije. Z analizo smo podatkovni niz razdelili na dva klastra; prvi (A vključuje nekaj popisov termofilne cenoze z nižje nadmorske višine, ki jih opišemo kot prehod med submediteranskim aspektom razreda Festuco-Brometea in drugih mediteranskih zeliščnih in grmiščnih razredov; drugi klaster (B pa vključuje večino podatkovnega niza in ga lahko členimo na pionirske, mezokserofilne (skupini B1 in B2a in mezofilne združbe (skupina B2b. Popise klastrov B1 in B2a uvrščamo v asociacijo Coronillo minimae-Astragaletum monspessulanii in tri druge skupine: združba Plantago argentea-Carex caryophyllea, združba Tragopogon samaritani-Bromus erectus in Festuco trachyphyllae-Brometum erecti ass. nova. Mezofilna skupina (B2b vključuje popise asociacij Centaureo bracteatae-Brometum erecti in Ononido masquillerii- Brometum erecti, skupaj z delno spremenjeno združbo. Zaradi majhnih razlik v florističnem, ekološkem in horološkem pogledu med temi traviščnimi tipi predlagamo, da jih obravnavamo kot tri subasociacije Centaureo bracteatae

JWST-MIRI spectrometer main optics design and main results

Science.gov (United States)

Navarro, Ramón; Schoenmaker, Ton; Kroes, Gabby; Oudenhuysen, Ad; Jager, Rieks; Venema, Lars

2017-11-01

MIRI ('Mid InfraRed Instrument') is the combined imager and integral field spectrometer for the 5-29 micron wavelength range under development for the James Webb Space Telescope JWST. The flight acceptance tests of the Spectrometer Main Optics flight models (SMO), part of the MIRI spectrometer, are completed in the summer of 2008 and the system is delivered to the MIRI-JWST consortium. The two SMO arms contain 14 mirrors and form the MIRI optical system together with 12 selectable gratings on grating wheels. The entire system operates at a temperature of 7 Kelvin and is designed on the basis of a 'no adjustments' philosophy. This means that the optical alignment precision depends strongly on the design, tolerance analysis and detailed knowledge of the manufacturing process. Because in principle no corrections are needed after assembly, continuous tracking of the alignment performance during the design and manufacturing phases is important. The flight hardware is inspected with respect to performance parameters like alignment and image quality. The stability of these parameters is investigated after exposure to various vibration levels and successive cryogenic cool downs. This paper describes the philosophy behind the acceptance tests, the chosen test strategy and reports the results of these tests. In addition the paper covers the design of the optical test setup, focusing on the simulation of the optical interfaces of the SMO. Also the relation to the SMO qualification and verification program is addressed.

Second medical opinions: the views of oncology patients and their physicians.

Science.gov (United States)

Philip, Jennifer; Gold, Michelle; Schwarz, Max; Komesaroff, Paul

2010-09-01

Second medical opinions (SMOs) are common in oncology practice, but the nature of these consultations has received relatively little attention. This study examines the views of patients with advanced cancer and their physicians of SMOs. Parallel, concurrent surveys were developed for patients and physicians. The first was distributed to outpatients with advanced cancer-attending specialist clinics in an Australian quaternary hospital. The second survey, developed on the basis of results of exploratory interviews with medical oncologists, was distributed to medical oncologists in Australia. Seventeen of fifty two (33%) patients had sought a SMO, most commonly prompted by concerns around communication with their first doctor, the extreme and desperate nature of their medical condition and the need for reassurance. Most (94%) patients found the SMO helpful, with satisfaction related to improved communication and reassurance. Patients were concerned that seeking a second medical opinion may affect their relationship with their primary doctor. Most physicians (82%) reported seeing between one and five SMO per month, with patients being motivated by the need for additional information and reassurance. Physicians regarded SMO patients as having greater information needs (84%), greater psychosocial needs (58%) and requiring more of the physician's time and energy (77%) than other patients. SMOs are common in cancer care with most patients motivated by the need for improved communication, additional information and reassurance. Physicians identify patients who seek SMOs as having additional psychosocial needs compared with other oncology patients.

Primerjava učinkovitosti različnih kombinacij herbicidov in njihov vpliv na plevelno združbo v vinogradu

OpenAIRE

Arnečič, Suzana

2011-01-01

V letih 2008 in 2009 smo na Univerzitetnem centru Meranovo Fakultete za kmetijstvo in biosistemske vede v vinogradu sorte 'Renski rizling' ugotavljali učinkovitost enajstih herbicidov oziroma njihovih kombinacij za zatiranje plevelne združbe pod trtami. Poskus je bil zastavljen po metodi naključnih blokov v treh ponovitvah. Ocenjevali smo učinkovitost herbicidov in pokrovnost tal s plevelno združbo. V letu 2008 je bila statistično značilna najmanjša pokrovnost tal s plevelno združbo pri obrav...

Ocena potresne odpornosti družinske hiše v Grosuplju

OpenAIRE

Žitnik, Luka

2017-01-01

V diplomski nalogi je predstavljena ocena potresne odpornosti zidane hiše v Grosuplju. Potresno analizo smo izvedli z metodo horizontalnih sil na podlagi zahtev, ki jih podajata standarda Evrokod 6 in Evrokod 8. Diploma je razdeljena na teoretični in praktični del. V teoretičnem delu so predstavljeni postopki za določitev potresne obtežbe, račun nosilnosti posameznih zidov ter oceno odpornosti celotne konstrukcije. Povečanje obremenitve zaradi vpliva slučajne ekscentričnosti smo upoštevali na...

PLESNA VZGOJA IN RAZLIČNE GLASBENE ZVRSTI

OpenAIRE

Trstenjak, Simona

2016-01-01

Namen diplomskega dela Plesna vzgoja in različne glasbene zvrsti je s pomočjo teoretičnih izhodišč, ob opazovanju plesnega izražanja otrok, ugotoviti vpliv posamezne glasbene zvrsti na otroka pri plesni vzgoji. Diplomsko delo je sestavljeno iz dveh delov, teoretičnega in empiričnega. V teoretičnem delu smo predstavili teorijo plesne vzgoje v predšolskem obdobju, kjer smo podrobneje opisali sam pomen in vpliv plesne vzgoje na predšolskega otroka, vsebine, cilje in načela ter metode plesne vzgo...

O ecologismo dos pobres

OpenAIRE

ALIER, Juan Martinez

1997-01-01

O ecologísmo tem colocado em cheque as leis capitalistas de mercado, principalmente na sua fase globalizada, devido à apropriação e exploração inconsequente dos recursos naturais. Ao mesmo tempo tem apontado que o meio ambiente não se reduz ao tratamento somente cientifico da natureza. O presente artigo ressalta aspectos importantes do ecologísmo como a participação das mulheres, o marxismo, o neo-narodnismo, etc. e é rico em exemplos de problemas ambientais decorrentes das relações de produç...

IZBOLJŠANJE PROCESA VZDRŽEVANJA V PODJETJU ELEKTRODE JESENICE D.O.O.

OpenAIRE

Filipov, Slobodan

2016-01-01

V podjetju Elektrode Jesenice, d. o. o., se soočajo s pomanjkljivim in neučinkovitim vzdrževanjem. Glavni namen diplomskega dela je izboljšanje procesa vzdrževanja v podjetju, saj je trenutno stanje precej neurejeno, učinkovito vzdrževanje pa je eden od pomembnih dejavnikov uspešnosti podjetja. V prvem delu diplomskega dela smo predstavili nekaj načinov vzdrževanja, ki jih podjetja dandanes najpogosteje uporabljajo. Osredotočili smo se na preventivno vzdrževanje in za vlečno-rezalno lini...

MOTIVACIJA PRI LIKOVNI VZGOJI

OpenAIRE

Kerin, Tjaša

2011-01-01

V teoretičnem delu diplomskega dela predstavljamo splošen pojem motivacije, pomen motivacije ter teoretična izhodišča. Povezujemo splošna teoretična izhodišča s poučevanjem likovne vzgoje ter artikulacijske značilnosti pri njenem pouku. Ob tem smo tudi izpostavili pomembnost motivacije pri likovni vzgoji ter navedli nekaj možnosti za uspešno realizacijo le-te. Dotaknili smo se tudi individualizacije pri likovni vzgoji ter sredstev za spodbujanje motivacije. V empiričnem delu dela predsta...

INTERNET STVARI IN ANALIZA DODANE VREDNOSTI PAMETNE NAPRAVE ZA KONČNEGA UPORABNIKA

OpenAIRE

Čander, Tamara

2016-01-01

Če smo še pred nekaj leti govorili o svetovnem spletu kot o revoluciji, danes vemo, da to še nikakor ni vse. Priča smo novemu valu tehnološkega napredka, ki transformira naše okolje in vsakodnevne predmete v ekosistem informacij. Internet stvari je skupek tehnologij, ki povezujejo stvarnost z digitalnimi svetom preko senzorjev in značk, vgrajenih v naprave za vsakodnevno rabo. Čeprav si strokovnjaki o potencialni velikosti trga, ki ga ta fenomen odpira, niso povsem enotni, pa so vsi prepričan...

FRANŠIZING - PRILOŽNOST ZA RAST PODJETIJ

OpenAIRE

Prosenc, Iztok

2010-01-01

Diplomsko delo najprej prikazuje teoretična izhodišča franšiznega načina poslovanja, katera smo zasledili v strokovni literaturi. V nadaljevanju teoretična dognanja primerjamo z razvojem in položajem franšizinga v Poslovnem sistemu Mercator d.d.. Ugotavljamo, da ima Mercatorjev franšizni sistem pomembno vlogo na področju franšiznih sistemov v Sloveniji. V raziskovalnem delu diplomske naloge smo potrdili vse tri zastavljene hipoteze, ki so: - Franšizing prinaša dobiček Mercatorju - U...

Bazalna i stimulirana insulinemija, lipoproteinske frakcije i subfrakcije u pretilih bolesnika s insulin neovisnom šećernom bolešću

OpenAIRE

Grbeša, Dubravka; Ivandić, Ante; Jovanovac, Marija; Prpić, Ivana; Kuveždić, Marija

1989-01-01

Ispitivali smo dinamiku sekrecije insulina i C-peptida, te lipoproteinski status u 43 bolesnika (27 pretilih i 16 normalne tjelesne mase) sa insulin neovisnom šećernom bolešću. Našli smo signifikantno više vrijednosti kolesterola i triglicerida, dok je HDL2 bio signifikantno niži u pretilih bolesnika. Nije bilo statistički značajnijih razlika u koncentracijama LDL a, HDL-a i HDL3. Koncentracije insulina, i bazalnog i stimuliranog, bile su nesignifikantno, a C-peptida signifikantno povišene u ...

KRITIČNI DEJAVNIKI UPORABE INFORMACIJSKIH REŠITEV ANALITIČNEGA UPRAVLJANJA ODNOSOV S STRANKAMI

OpenAIRE

Šebjan, Urban

2016-01-01

V doktorski disertaciji smo proučevali uporabo informacijskih rešitev analitičnega upravljanja odnosov (IR aCRM) s strankami, pri čemer smo poglobljeno proučevali analitična orodja in tehnike za analiziranje podatkov o strankah in poslovnih partnerjih IR aCRM. IR aCRM predstavlja perspektivno področje, ki je danes za organizacije izjemno zanimivo, a hkrati tudi strateško zahtevno področje, saj zahteva kompetenten kader in ustrezno tehnološko podporo. Čeprav je področje izjemno perspektivno, j...

KOMUNIKACIJA IN VIZUALNA KOMUNIKACIJA

OpenAIRE

Petrena, Polona

2013-01-01

Področja komunikacije, vizualne komunikacije in psihologije komunikacije so med seboj tesno povezana in so neizbežni dejavniki našega vsakdanjega življenja. Diplomsko delo zajema opis dejstev ter ugotovitev za našteta področja in razjasnjuje razlike med besedno in nebesedno komunikacijo ter predelavo kognitivnih sporočil. Ugotovili smo, da ljudje že od nekdaj upodabljamo svoje ideje, sporočila in da smo močno dovzetni za vse oblike komunikacije. Na naše razumevanje in dojemanje sporočil pa im...

ETIČNOST POSLOVANJA MANAGERJEV

OpenAIRE

Možir, Nina

2012-01-01

V diplomskem seminarju smo obravnavali temo etičnost poslovanja managerjev. Ta tema je trenutno v gospodarstvu zelo aktualna saj je vedno več primerov neetičnosti poslovanja v podjetjih. Pomembno je da se management v podjetju zaveda, da je etika v poslovanju zelo pomembna. Managerji ne smejo obravnavati etike, kot le še en dodatni strošek v podjetju, saj mu lahko doprinese razne koristi in uspešnost podjetja. Ugotoviti smo hoteli ali se etičnost managerjev izplača ali je pomembno, ...

Izboljšanje organiziranosti logistike v podjetju Stilles d.o.o.

OpenAIRE

Kostevc, Žiga

2015-01-01

V diplomski nalogi je predstavljena analiza izboljšanja organiziranosti logistike v podjetju Stilles d.o.o. Namen diplomske naloge je podati predloge za izboljšanje organiziranosti logistike v oddelku odpreme in izhodne logistike. Osredotočili smo se tudi na izboljšanje sodelovanja med obratom končne montaže in skladiščenjem blaga, kjer gre za prejem izdelkov iz proizvodnje v skladišče. V okviru diplomske naloge smo predstavili teoretične osnove za razumevanje logistike in skladiščnega po...

Uporaba službenih psov za različne namene delovnih procesov

OpenAIRE

Rejc, Sara

2017-01-01

Pred vami se nahaja diplomsko delo z naslovom Uporaba službenih psov za različne namene delovnih procesov. Glavni namen in cilj diplomskega dela je proučiti in opisati uporabo službenega psa, predvsem v policiji, vojski in zaporih, kar predstavlja jedro tega diplomskega dela. Želeli smo prikazati vsestransko uporabnost psov v svetu ljudi. Ugotovili smo, da je enota reševalnih psov pomemben del ekipe pri iskanju pogrešanih in poškodovanih oseb. Na tem mestu je podrobneje opisano šolanje psa in...

Matere z motnjami v duševnem razvoju

OpenAIRE

Kolarič, Sandra

2015-01-01

S pregledom tuje literature in že opravljenih raziskav v tujini smo v teoretičnem delu magistrske naloge zajeli značilnosti mater z motnjami v duševnem razvoju, dejavnike, ki vplivajo na uspešnost opravljanja materinske vloge, ter pravice oseb z motnjami v duševnem razvoju do starševstva, v povezavi z zakonodajo na slovenskem. Navedli smo vzroke za omejevanje reprodukcije pri ženskah z motnjami v duševnem razvoju in problematiko odvzema skrbništva materam z motnjami v duševnem razvoju nad otr...

DOLOČITEV POVRŠINSKE NAPETOSTI Z METODO KAPILARNEGA DVIGA DVOFAZNIH SISTEMOV

OpenAIRE

Kravanja, Gregor

2014-01-01

Namen magistrske naloge je bil postavitev merilne naprave in razvoj nove metode merjenja površinske napetosti s kapilarnim dvigom dvofaznih sistemov v okolici kritične točke. Za pridobitev natančnih in primerljivih meritev je bilo potrebno poznati natančni notranji premer tankih kapilar. Določili smo ga z metodo laserskega tipanja na nemški koordinatni merilni napravi ZEISS tipa UMC-850 s pomočjo merilne programske opreme CALYPSO 5.1.4. Za merjenje ravnotežne višine smo uporabili računalniški...

Antiavtoritarnost in šola

OpenAIRE

Lah, Irena

2017-01-01

V iskanju odgovora na vprašanje, zakaj se človeštvo, kljub vsesplošni demokratizaciji in dostopnosti javnega šolanja v razvitih družbah in kljub dosedanjemu skokovitemu znanstvenemu in tehnološkemu razvoju, še vedno srečuje z najosnovnejšimi človeškimi problemi, smo želeli raziskati vlogo avtoritete in antiavtoritarnosti v razmerju do šole pri neuspešnem soočenju in reševanju problemov človeštva. V ta namen smo najprej raziskali zgodovinske temelje nosilcev avtoritete v obliki tradici...

VODENJE PROJEKTOV VIRTUALNIH SKUPIN V VIRTUALNIH SKUPNOSTIH ZA ODPRTOKODNI RAZVOJ PROGRAMSKIH REŠITEV

OpenAIRE

Harej Pulko, Katja

2009-01-01

S prihodom interneta, se je spremenil način povezovanja in komunikacije med ljudmi. Pred tem smo lahko s sogovornikom komunicirali le preko stacionarnega telefona, pisem ali, če smo se z osebo srečali »v živo«. Nato so postale aktualne video konference, mobilni telefoni in internet. Danes se zdi, da gre čas hitreje. A vendarle hitrost časa ostaja enaka. Le komunikacija je lahko bolj dinamična, več možnosti imamo za sodelovanje in povezovanje, tudi z ljudmi na drugi strani sveta. Za komunikaci...

UPORABA SODOBNIH TEHNOLOGIJ SPLETNEGA OGLAŠEVANJA

OpenAIRE

Kostanjevec, Mateja

2016-01-01

Splet je postal za večino že skoraj nepogrešljiv del vsakdana. Na spletu iščemo informacije, delimo informacije, se družimo. Ker ogromno časa preživimo na spletu, je postalo zelo pomembno za podjetja, da so prisotna na spletu. Svoje potencialne kupce lahko na spletu dosežejo s postavitvijo spletnega mesta in spletnim oglaševanjem. V diplomskem delu smo najprej opredelili marketinško komuniciranje, katera so orodja in kako le ta vplivajo na potencialne kupce. Opredelili smo tudi oglaševan...

ZASNOVA KAVARNE V MESTNEM SREDIŠČU

OpenAIRE

Raškovič, Nataša

2013-01-01

Kavarne že več stoletij oblikujejo navade in kulture mest po svetu. Žal je pri nas vedno manj pravih, mestnih kavarn, ki bi ob dobri kavi in sladici znale ponuditi tudi ambient in vzdušje. V diplomskem delu smo se ukvarjali s tem, kako v starem mestnem jedru postaviti sodobno pravo kavarno, ki bi s svojim izgledom zaključila vogal Slovenske in Gledališke ulice. Na podlagi analize lokacije smo postavili večnamenski objekt, v njegovo pritličje pa umestili funkcionalen tloris kavarne s pravim...

Ecosystem service trade-offs and their influencing factors: A case study in the Loess Plateau of China.

Science.gov (United States)

Feng, Qiang; Zhao, Wenwu; Fu, Bojie; Ding, Jingyi; Wang, Shuai

2017-12-31

Soil erosion control (SEC), carbon sequestration (CAS), and soil moisture (SMO) strongly interact in the semi-arid Loess Plateau. Since SMO has supportive effects on SEC and CAS, it can be considered as ecosystem service (ES), and there is an immediate need to coordinate the relationships among these ecosystem services (ESs) to promote the sustainability of vegetation recovery. In this study, we quantified the ESs, ES trade-offs, and the environmental factors in 151 sample plots in the Ansai watershed, and we used a redundancy analysis (RDA) to clarify the effects of environmental factors on these ESs and their trade-offs. The results were as follows: (1) the general trend in the SEC of vegetation types was Robinia pseudoacacia (CH)>native grass (NG)>small arbor (ST)>Hippophae rhamnoides (SJ)>artificial grass (AG)>Caragana korshinskii (NT)>apple orchard (GY)>crop (CP); the CAS trend was CH>SJ>NT>AG>CP>ST>GY>NG; and the SMO trend was CP>NG>GY>AG>SJ>ST>CH>NT. (2) For SEC-SMO trade-offs, the influence of vegetation type, altitude, silt and sand composition was dominant. The arrangement of NG, AG, and SJ could decrease the extent of the trade-offs. (3) For CAS-SMO trade-offs, vegetation coverage and types were the dominant factors, but the effects were not complex. The extent of these trade-offs was lowest for NT, and that for SJ was the second lowest. (4) Considering the relationships among the three ESs, SJ was the most appropriate afforestation plant. Combing the vegetation types, slope position, slope gradient, and soil properties could regulate these ES relationships. The dominant factors influencing ES trade-offs varied among the different soil layers, so we must consider the corresponding influencing factors to regulate ESs. Moreover, manual management measures were also important for coordinating the ES relationships. Our research provides a better understanding of the mechanisms influencing the relationships among ESs. Copyright © 2017 Elsevier B.V. All

Supporting the low-voltage distribution network with supercapacitors; Untersuchungen zur Stuetzung des Versorgungsnetzes mit Doppelschichtkondensatoren

Energy Technology Data Exchange (ETDEWEB)

Guetif, Abdelkader [VDE Pruef- und Zertifizierungsinstitut GmbH, Offenbach am Main (Germany); Kurrat, Michael [Technische Univ. Braunschweig (Germany). Inst. fuer Hochspannungstechnik und Elektrische Energieanlagen; Meins, Juergen [Technische Univ. Braunschweig (Germany). Inst. fuer Elektrische Maschinen; Turki, Faical [Paul Vahle GmbH und Co. KG, Kamen (Germany)

2012-07-01

Supercapacitors have the ability to support the electricity grid by balancing voltage drops, net flicker and harmonics due to their high power density low reaction time. The task in order to have improved power quality relates in large extend by interchanging the electricity grid with real and imaginary power in short interval (milliseconds to seconds) of time. Because of quadratic relationship between voltage and stored energy a bidirectional buck-boost converter is required between energy storage and inverter. In the next step a dedicated controller has been built to couple an inverter with available three phase system 400 V - 50 Hz and it was put into operation. Another key point of this work is to determine the power and the energy content in the energy storage system to smoothen the grid. As an example here a load curve for a residential area has been considered. This load curve has to be smoothened for few minutes interval of time. With the help of cascade controller the energy content in the energy storage system, power for optimal utilization of energy content from storage can be controlled thus a reasonable grid smoothening can be realized. The described strategy tries to keep the energy content in the energy storage system constant for longer duration. Thus the required capacity of the energy storage system can be reduced and investment cost can also be reduced. The energy controller that functions as superimposed control loop gives reference input to control the complete system (Energy storage system, DC-DC converter and inverter). Different types of control methods are considered and their characteristics are simulated. In addition, the performance of total system (Energy storage system, DC-DC converter and inverter) for grid support during operation of Asynchronous machine using an example has been shown. Simulations have been made to support critical parallel operation of grid in period of milliseconds. A test bench has been made to verify the

Comparing side chain packing in soluble proteins, protein-protein interfaces, and transmembrane proteins.

Science.gov (United States)

Gaines, J C; Acebes, S; Virrueta, A; Butler, M; Regan, L; O'Hern, C S

2018-05-01

We compare side chain prediction and packing of core and non-core regions of soluble proteins, protein-protein interfaces, and transmembrane proteins. We first identified or created comparable databases of high-resolution crystal structures of these 3 protein classes. We show that the solvent-inaccessible cores of the 3 classes of proteins are equally densely packed. As a result, the side chains of core residues at protein-protein interfaces and in the membrane-exposed regions of transmembrane proteins can be predicted by the hard-sphere plus stereochemical constraint model with the same high prediction accuracies (>90%) as core residues in soluble proteins. We also find that for all 3 classes of proteins, as one moves away from the solvent-inaccessible core, the packing fraction decreases as the solvent accessibility increases. However, the side chain predictability remains high (80% within 30°) up to a relative solvent accessibility, rSASA≲0.3, for all 3 protein classes. Our results show that ≈40% of the interface regions in protein complexes are "core", that is, densely packed with side chain conformations that can be accurately predicted using the hard-sphere model. We propose packing fraction as a metric that can be used to distinguish real protein-protein interactions from designed, non-binding, decoys. Our results also show that cores of membrane proteins are the same as cores of soluble proteins. Thus, the computational methods we are developing for the analysis of the effect of hydrophobic core mutations in soluble proteins will be equally applicable to analyses of mutations in membrane proteins. © 2018 Wiley Periodicals, Inc.

Fuel and combustion stratification study of Partially Premixed Combustion

NARCIS (Netherlands)

Izadi Najafabadi, M.; Dam, N.; Somers, B.; Johansson, B.

2016-01-01

Relatively high levels of stratification is one of the main advantages of Partially Premixed Combustion (PPC) over the Homogeneous Charge Compression Ignition (HCCI) concept. Fuel stratification smoothens heat release and improves controllability of this kind of combustion. However, the lack of a

APLIKASI METODE KHUN-TUCKER DALAM PENJUALAN OLI MOBIL (Studi Kasus : PT. Anugrah Mitra Dewata

Directory of Open Access Journals (Sweden)

Ni Made Asih

2012-11-01

Full Text Available Aplikasikan Metode Khun-Tucker dalam kasus penjualan oli mobil padaPT. Anugrah Mitra Dewata merupakan salah satu kasus optimasi bersyarat, untukmengetahui oli apa yang harus diproduksi oleh perusahaan, agar mencapai keuntunganmaksimal dan nilai-nilai ekstrim yang akan diperoleh, yang nantinya berperandalam menentukan tingkat keuntungan yang diperoleh perusahaan. Metode Khun-Tucker ini dapat dipergunakan untuk mencari solusi optimal dari suatu fungsi tanpamemandang sifat apakah linier atau nonlinier. Dalam proses pengerjaannya MetodeKhun-Tucker secara esensial melibatkan langkah-langkah yang sama seperti halnyaMerode Lagrange, yaitu: Membentuk Lagrangian untuk dapat menghitungtitik-titik kritisnya, mencari semua solusi (x; , dan menghitung nilai f(x. Dalamproses pencarian semua solusi x dan nya dibantu dengan menggunakan programMATLAB. Hasil penelitian menunjukkan pada caturwulan I dengan memproduksioli SMO HP sebanyak 587 liter diperoleh keuntungan maksimal perusahaansebesar Rp 19.837.000 . Untuk caturwulan II dengan memproduksi oli SMO HPPLUS sebanyak 776 liter diperoleh keuntungan maksimal perusahaan sebesar Rp20.112.000. Untuk caturwulan III dengan memproduksi oli SMO HP sebanyak 470liter diperoleh keuntungan maksimal perusahaan sebesar Rp 20.029.000.

Condicionamientos internos en la variación de los pronombres personales átonos en Los hechos de Don Miguel Lucas de Iranzo

Directory of Open Access Journals (Sweden)

Francisco Díaz Montesinos

2004-06-01

Full Text Available The aim of this paper is to analyse the linguistic factors constraining the use of personal clitics lo(s, la(s, le(s in XVth Century Middle-Age Castilian, as revealed in the Relación de los Hechos de Don Miguel Lucas de Iranzo (1458. A multivariate analysis of data from this text shows that internal (morphological, syntactic, lexical and textual factors interact and allows us to imagine the simplest and original context where leísmo could start. A nearly categorical tendency to employ le for male referents as direct objects is developed with human antecedents and where Latin used dative case or alternated between dative and accusative case. If Latin used accusative case, occurrence of le (leísmo depends on a set of linguistic constraints whose effect is systematic and predictable, as shows a logistic regression analysis carried out in this paper. Use of le (leísmo for human antecedents is constrained by the following internal factors: etymology, the number and the clitic's position within the sentence, type of syntactic structure and the verb's tense.

Pre-conceptual core design of a small modular fast reactor cooled by supercritical CO{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Liu, Baolin; Cao, Liangzhi; Wu, Hongchun [School of Nuclear Science and Technology, Xi’an Jiaotong University, No 28, Xianning West Road, Xi’an 710049, Shaanxi (China); Yuan, Xianbao, E-mail: ztsbaby@163.com [School of Nuclear Science and Technology, Xi’an Jiaotong University, No 28, Xianning West Road, Xi’an 710049, Shaanxi (China); College of Mechanical & Power Engineering, China Three Gorges University, No 8, Daxue Road, Yichang 443002, Hubei (China); Wang, Kunpeng [Nuclear and Radiation Safety Center, PO Box 8088, Beijing 100082 (China)

2016-04-15

Abstracts: A Small Modular fast reactor cooled by Supercritical CO{sub 2} (SMoSC) is pre-conceptually designed through three-dimensional coupled neutronics/thermal-hydraulics analysis. The power rating of the SMoSC is designed to be 300 MW{sub th} to meet the energy demand of small electrical grids. The excellent thermal properties of supercritical CO{sub 2} (S-CO{sub 2}) are employed to obtain a high thermal efficiency of about 40% with an electric output of 120 MWe. MOX fuel is utilized in the core design to improve fuel efficiency. The tube-in-duct (TID) assembly is applied to get lower coolant volume fraction and reduce the positive coolant void reactivity. According to the coupled neutronics/thermal-hydraulics calculations, the coolant void reactivity is kept negative throughout the whole core life. With a specific power density of 9.6 kW/kg and an average discharge burnup of 70.1 GWd/tHM, the SmoSC can be operated for 20 Effective Full Power Years (EFPYs) without refueling.

Revealing the Molecular Structure and the Transport Mechanism at the Base of Primary Cilia Using Superresolution STED Microscopy

Science.gov (United States)

Yang, Tung-Lin

the width of the basal body, distant from the potential Y-links region of the TZ. Moreover, IFT88 was intriguingly distributed in two distinct patterns, forming three puncta or a Y shape at the ciliary base found in human retinal pigment epithelial cells (RPE), human fibroblasts (HFF), mouse inner medullary collecting duct (IMCD) cells and mouse embryonic fibroblasts (MEFs). We hypothesize that the two distribution states of IFT88 correspond to the open and closed gating states of the TZ, where IFT particles aggregate to form three puncta when the gate is closed, and move to form the branches of the Y-shape pattern when the gate is open. Two reservoirs of IFT particles, correlating with phases of ciliary growth, were localized relative to the internal structure of the TZ. These subdiffraction images reveal unprecedented architectural details of the TZ, providing a basic structural framework for future functional studies. To visualize the dynamic movement of IFT particles within primary cilia, we further conducted superresolution live-cell imaging of IFT88 fused to EYFP in IMCD cells. Our findings, in particular, show IFT88 particles pass through the TZ at a reduced speed by approximately 50%, implying the gating mechanism is involved at this region to slow down IFT trafficking. Finally, we report the distinct transport pathways of IFT88 and Smo (Smoothened), an essential player to hedgehog signaling, to support our hypothesis that two proteins are transported in different mechanisms at the ciliary base, based on dual-color superresolution imaging.

Development of a restricted state space stochastic differential equation model for bacterial growth in rich media

DEFF Research Database (Denmark)

Møller, Jan Kloppenborg; Philipsen, Kirsten Riber; Christiansen, Lasse Engbo

2012-01-01

In the present study, bacterial growth in a rich media is analysed in a Stochastic Differential Equation (SDE) framework. It is demonstrated that the SDE formulation and smoothened state estimates provide a systematic framework for data driven model improvements, using random walk hidden states...

Plant gum exudates (Karau) and mucilages, their biological sources ...

African Journals Online (AJOL)

In recent years those polymers derived from plants have evoke tremendous interest because of their industrial applications as diluent binders, thickening agents, smoothening, emulsifiers, gelling agents and stabilizers. This increasing research in this group of these plant materials are clear indications of their increasing ...

Strange effects of strong high-frequency excitation

DEFF Research Database (Denmark)

Thomsen, Jon Juel

2003-01-01

Three general effects of mechanical high-frequency excitation (HFE) are described: Stiffening - an apparent change in the stiffness associated with an equilibrium; Biasing - a tendency for a system to move towards a particular state which does not exist or is unstable without HFE; and Smoothening...

Protein docking prediction using predicted protein-protein interface

Directory of Open Access Journals (Sweden)

Li Bin

2012-01-01

Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

Protein docking prediction using predicted protein-protein interface.

Science.gov (United States)

Li, Bin; Kihara, Daisuke

2012-01-10

Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm), is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

Prediction of Protein-Protein Interactions Related to Protein Complexes Based on Protein Interaction Networks

Directory of Open Access Journals (Sweden)

Peng Liu

2015-01-01

Full Text Available A method for predicting protein-protein interactions based on detected protein complexes is proposed to repair deficient interactions derived from high-throughput biological experiments. Protein complexes are pruned and decomposed into small parts based on the adaptive k-cores method to predict protein-protein interactions associated with the complexes. The proposed method is adaptive to protein complexes with different structure, number, and size of nodes in a protein-protein interaction network. Based on different complex sets detected by various algorithms, we can obtain different prediction sets of protein-protein interactions. The reliability of the predicted interaction sets is proved by using estimations with statistical tests and direct confirmation of the biological data. In comparison with the approaches which predict the interactions based on the cliques, the overlap of the predictions is small. Similarly, the overlaps among the predicted sets of interactions derived from various complex sets are also small. Thus, every predicted set of interactions may complement and improve the quality of the original network data. Meanwhile, the predictions from the proposed method replenish protein-protein interactions associated with protein complexes using only the network topology.

Extension of optical lithography by mask-litho integration with computational lithography

Science.gov (United States)

Takigawa, T.; Gronlund, K.; Wiley, J.

2010-05-01

Wafer lithography process windows can be enlarged by using source mask co-optimization (SMO). Recently, SMO including freeform wafer scanner illumination sources has been developed. Freeform sources are generated by a programmable illumination system using a micro-mirror array or by custom Diffractive Optical Elements (DOE). The combination of freeform sources and complex masks generated by SMO show increased wafer lithography process window and reduced MEEF. Full-chip mask optimization using source optimized by SMO can generate complex masks with small variable feature size sub-resolution assist features (SRAF). These complex masks create challenges for accurate mask pattern writing and low false-defect inspection. The accuracy of the small variable-sized mask SRAF patterns is degraded by short range mask process proximity effects. To address the accuracy needed for these complex masks, we developed a highly accurate mask process correction (MPC) capability. It is also difficult to achieve low false-defect inspections of complex masks with conventional mask defect inspection systems. A printability check system, Mask Lithography Manufacturability Check (M-LMC), is developed and integrated with 199-nm high NA inspection system, NPI. M-LMC successfully identifies printable defects from all of the masses of raw defect images collected during the inspection of a complex mask. Long range mask CD uniformity errors are compensated by scanner dose control. A mask CD uniformity error map obtained by mask metrology system is used as input data to the scanner. Using this method, wafer CD uniformity is improved. As reviewed above, mask-litho integration technology with computational lithography is becoming increasingly important.

»Nočem biti odvisna«: Ali javne prevajalske in tolmaške storitve res negativno vplivajo na aktivno vključenost migrantov v državo gostiteljico?

Directory of Open Access Journals (Sweden)

Nike Kocijančič Pokorn

2016-12-01

Full Text Available Prispevek se sprašuje o upravičenosti določenih političnih ukrepov, ki odrekajo zagotavljanje prevajanja in tolmačenja migrantom, ter zagovarja nove pristope k jezikovni in prevodni politiki, in sicer prek raziskave, ki je bila zasnovana kot odziv na trditve, da prevajalske in tolmaške storitve ovirajo integracijo nedavnih priseljencev. Raziskava je bila izvedena na skupini prosilcev za mednarodno zaščito v azilnem domu v Ljubljani. Najprej smo zbrali podatke o jezikovnem ozadju vseh stanovalcev azilnega doma v avgustu 2014 (56 stanovalcev iz 19 različnih držav, nato pa sestavili reprezentativno skupino 18 prosilcev za mednarodno zaščito na podlagi njihovega maternega jezika in jih razdelili na dve skupini glede na čas bivanja v Sloveniji v času intervjuja (krajše ali daljše obdobje. Kvantitativne podatke o jezikovnih profilih smo zbrali z vprašalnikom, kvalitativne pa s pomočjo polstrukturiranih intervjujev, izvedenih v letu 2014, in dveh ponovitvenih intervjujev v letu 2015. Nato smo kvalitativno analizirali transkripcije vseh posnetih intervjujev, pri čemer smo se osredotočali na jezikovne in komunikacijske rešitve na različnih stopnjah migrantovega življenja v državi gostiteljici. Rezultati kažejo, da je osnovne kompromise mogoče doseči, saj so prevajalske in tolmaške storitve komplementarni koraki do neodvisnosti in kot take ne ovirajo učenja dominantnega oz. nacionalnega jezika države gostiteljice, temveč ga podpirajo.

OBNAŠANJE ŽVIŽGAČEV V RAČUNOVODSTVU - PRIMER SLOVENIJE

OpenAIRE

Koprivnik, Tamara

2016-01-01

Še vedno živimo v času slabega gospodarskega stanja, katerega posledice se kažejo tudi v porastu gospodarskega kriminala. Glede na to, da je gospodarski kriminal vedno težje odkrivati, so lahko žvižgači ključnega pomena pri odkrivanju in preprečevanju le-tega. V podjetjih so pogosto priča gospodarskemu kriminalu ravno računovodje, zato smo se v magistrskem delu osredotočili na njih. Problem, ki smo si ga zastavili v magistrskem delu je, da ni znano, kateri demografski dejavniki vplivajo na ob...

VPLIV STRESA NA DELO IN ZDRAVJE REŠEVALCEV V NUJNI MEDICINSKI POMOČI

OpenAIRE

Javernik, Tanja

2012-01-01

Izhodišča: V diplomskem delu smo izpostavili stres, ki je neizogiben del življenja v nujni medicinski pomoči. Reševalci v nujni medicinski pomoči se dnevno srečujejo z različnimi obremenjujočimi situacijami, ki lahko vplivajo na počutje, delovanje organizma, psihično ravnovesje, imunost in zdravje posameznika. Z raziskavo smo ugotavljali, v kolikšni meri so reševalci v službi nujne medicinske pomoči pri svojem delu izpostavljeni stresnim situacijam in obremenitvam kot so: neučakani pacient...

Okoljski vplivi planinskih koč v visokogorju Kamniško-Savinjskih Alp

Directory of Open Access Journals (Sweden)

Nejc Bobovnik

2014-12-01

Full Text Available Planinske koče so v neposeljenem gorskem svetu skoraj edini lokalni vir onesnaževanja. V raziskavi smo opredelili štiri okoljske vplive planinskih koč: oskrbovanje in ravnanje z odpadki, ogrevanje in pridobivanje električne energije, oskrba z vodo in ravnanje z odpadnimi vodami ter število in obnašanje obiskovalcev. S pomočjo ankete smo ocenili okoljske vplive izbranih planinskih koč. Najbolj problematična sta velika količina odpadkov in porabljene vode, kot dobro lahko označimo oskrbovanje, kot zelo dobro ogrevanje koč in pridobivanje električne energije.

Stres pri delu v nujni medicinski pomoči - prehospitalna enota

OpenAIRE

Ploder, Matej

2013-01-01

Izhodišča: V diplomskem delu smo se lotili vprašanja, kako stres vpliva na delo reševalcev v prehospitalni enoti nujne medicinske pomoči. Reševalci in zdravniki nujne medicinske pomoči se vsakodnevno srečujejo s situacijami, ki vplivajo na njihovo nadaljnjo delo, počutje in psihično stabilnost, predvsem pa na njihovo zdravje, od tragičnih nesreč, katerim so priča, do trenutkov, ko svojega poslanstva ne bi zamenjali za nič na svetu. Pri raziskavi smo ugotavljali, kaj reševalcem sploh predstavl...

Oblikovanje in izdelava embalaže za nakit Katja Koselj Jewellery

OpenAIRE

Gregorka, Nika

2017-01-01

Dandanes je vloga videza embalaže vedno pomembnejša in je zato eden izmed bistvenih elementov pri darilni embalaži. Ker embalaža s svojo podobo izraža tudi kakovost izdelka, je le-ta včasih še pomembnejša kot izdelek, ki ga predstavlja. Potemtakem je pomembno, da je kakovostna, preprosta, koristna in okolju prijazna. V diplomskem delu smo predstavili izdelavo in načrtovanje embalaže za slovenski ročno izdelani nakit oblikovalke Katje Koselj. V pregledu literature smo opisali pojem embalaže, n...

DOPRINOS DRUŽBENO ODGOVORNEGA PODJETJA K USKLAJEVANJU DELA IN DRUŽINSKEGA ŽIVLJENJA

OpenAIRE

Povhe, Ksenija

2010-01-01

Za temo diplomskega dela smo izbrali problematiko usklajevanja družinskega in poklicnega življenja, ker menimo, da se ženske — matere pri usklajevanju obeh prioritet soočamo z večjimi težavami kot moški. Naš namen je bil preučiti pojem družbene odgovornosti in zakonodajo na področju družinske politike ter spoznati, ali lahko tudi podjetja s svojim prostovoljnim razumevanjem družine, omogočijo staršem lažje usklajevanje delovnega in družinskega življenja. Spoznali smo, da je družbena odgovorno...

UPORABA SUPERKRITIČNEGA OGLIKOVEGA DIOKSIDA (SC CO 2 ) ZA IZOLACIJO ENCIMOV IN PROTEINOV IZ CELIC ČRNE KVASOVKE TRIMMATOSTROMA SALINUM

OpenAIRE

Bosilj, Monika

2012-01-01

Namen diplomske naloge je določiti vpliv superkritičnega ogljikovega dioksida (SC CO2) na preživetje črnih kvasovk Trimmatostroma salinum in izločanje proteinov in nukleinskih kislin iz celične suspenzije T. salinum. Suspenzijo s kulturo T. salinum smo v visokotlačnem šaržnem reaktorju izpostavili SC CO2 pri tlaku 100 bar in 35 °C. Rezultati so pokazali, da se je s podaljševanjem časa inkubacije v SC CO2 preživelost celic T. salinum zmanjševala. Merili smo tudi aktivnost encimov celulaze, α-a...

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

Science.gov (United States)

Todorovic Balint, Milena; Jelicic, Jelena; Mihaljevic, Biljana; Kostic, Jelena; Stanic, Bojana; Balint, Bela; Pejanovic, Nadja; Lucic, Bojana; Tosic, Natasa; Marjanovic, Irena; Stojiljkovic, Maja; Karan-Djurasevic, Teodora; Perisic, Ognjen; Rakocevic, Goran; Popovic, Milos; Raicevic, Sava; Bila, Jelena; Antic, Darko; Andjelic, Bosko; Pavlovic, Sonja

2016-01-01

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach. PMID:27164089

Generalized modular multilevel converter and modulation

DEFF Research Database (Denmark)

Liu, Hui; Loh, Poh Chiang; Blaabjerg, Frede

2014-01-01

converters regulating a power grid. The generalized topology derived and notated as GMMC can then be altered to create various types of MMC, including the traditional topology that is presently well-known. This effort has not been previously discussed, and may smoothen the understanding of MMC operation...

Sadhana | Indian Academy of Sciences

Indian Academy of Sciences (India)

Keywords. Single phase; double-frequency ripple; active power decoupling; reduced stress; reliability. Abstract. Single-phase DC–AC power electronic converters suffer from pulsating power at double the line frequency. The commonest practice to handle the issue is to provide a huge electrolytic capacitor for smoothening ...

Celibato en el Judaísmo Antiguo

Directory of Open Access Journals (Sweden)

van der Horst, Pieter W.

2002-06-01

Full Text Available Even though the first commandment in the Bible, «Be fruitful and multiply» (Gen. 1:28, countered the development of sexual asceticism in early Judaism, yet there is clear evidence of persons and groups choosing voluntary celibacy as a Jewish way of life. The evidence concerning the Essenes, the Therapeutae, Banus, Shim'on ben Azzai, John the Baptist and Jesus of Nazareth is discussed in this article as are the consequences for the rise of celibacy in early Christianity.

Aunque el primer mandamiento de la Biblia, «Creced y multiplicaos» (Gen. 1:28, no propiciara el desarrollo del ascetismo sexual en el judaismo antiguo, hay claros testimonios de personas y grupos que eligen el celibato voluntario como una forma de vida judía. En este artículo se examinan las pruebas relativas a los esenios, los Therapeutae, Banus, Shim'on ben Azzai, Juan el Bautista y Jesús de Nazaret, así como sus consecuencias en el desarrollo del celibato en el cristianismo primitivo.

3D-Printed external light traps for solar cells

NARCIS (Netherlands)

van Dijk, L.; Paetzold, U.W.; Blab, Gerhard; Marcus, E.A.P.; Oostra, A.J.; van de Groep, J.; Polman, A.; Schropp, R.E.I.; Di Vece, M.

2015-01-01

We demonstrate a universally applicable 3D-printed external light trap for solar cells. We placed a macroscopic external light trap made of smoothened, silver coated plastic at the sun-facing surface of different types of solar cells. The trap consists of a reflective parabolic concentrator on top

Oligomeric protein structure networks: insights into protein-protein interactions

Directory of Open Access Journals (Sweden)

Brinda KV

2005-12-01

Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

Hedgehog signaling and therapeutics in pancreatic cancer.

LENUS (Irish Health Repository)

Kelleher, Fergal C

2012-02-01

OBJECTIVE: To conduct a systematic review of the role that the hedgehog signaling pathway has in pancreatic cancer tumorigenesis. METHOD: PubMed search (2000-2010) and literature based references. RESULTS: Firstly, in 2009 a genetic analysis of pancreatic cancers found that a core set of 12 cellular signaling pathways including hedgehog were genetically altered in 67-100% of cases. Secondly, in vitro and in vivo studies of treatment with cyclopamine (a naturally occurring antagonist of the hedgehog signaling pathway component; Smoothened) has shown that inhibition of hedgehog can abrogate pancreatic cancer metastasis. Thirdly, experimental evidence has demonstrated that sonic hedgehog (Shh) is correlated with desmoplasia in pancreatic cancer. This is important because targeting the Shh pathway potentially may facilitate chemotherapeutic drug delivery as pancreatic cancers tend to have a dense fibrotic stroma that extrinsically compresses the tumor vasculature leading to a hypoperfusing intratumoral circulation. It is probable that patients with locally advanced pancreatic cancer will derive the greatest benefit from treatment with Smoothened antagonists. Fourthly, it has been found that ligand dependent activation by hedgehog occurs in the tumor stromal microenvironment in pancreatic cancer, a paracrine effect on tumorigenesis. Finally, in pancreatic cancer, cells with the CD44+CD24+ESA+ immunophenotype select a population enriched for cancer initiating stem cells. Shh is increased 46-fold in CD44+CD24+ESA+ cells compared with normal pancreatic epithelial cells. Medications that destruct pancreatic cancer initiating stem cells are a potentially novel strategy in cancer treatment. CONCLUSIONS: Aberrant hedgehog signaling occurs in pancreatic cancer tumorigenesis and therapeutics that target the transmembrane receptor Smoothened abrogate hedgehog signaling and may improve the outcomes of patients with pancreatic cancer.

Several organic parameters on underlying hazardous constituents list can not be measured at the universal treatment standards

International Nuclear Information System (INIS)

Johnson, H.C.

1998-01-01

The Idaho National Engineering and Environmental Laboratory (INEEL) has several permitted treatment, storage and disposal facilities. The INEEL Sample Management Office (SMO) conducts all analysis subcontracting activities for Department of Energy Environmental Management programs at the INEEL. In this role, the INEEL SMO has had the opportunity to subcontract the analyses of various wastes (including ash from an interim status incinerator) requesting a target analyte list equivalent to the constituents listed in 40 Code of Federal Regulations. These analyses are required to ensure that treated wastes do not contain underlying hazardous constituents (UHC) at concentrations greater than the universal treatment standards (UTS) prior to land disposal. The INEEL SMO has conducted a good-faith effort by negotiating with several commercial laboratories to identify the lowest possible quantitation and detection limits that can be achieved for the organic UHC analytes. The results of this negotiating effort has been the discovery that no single laboratory (currently under subcontract with the INEEL SMO) can achieve a detection level that is within an order of magnitude of the UTS for all organic parameters on a clean sample matrix (e.g., sand). This does not mean that there is no laboratory that can achieve the order of magnitude requirements for all organic UHCs on a clean sample matrix. The negotiations held to date indicate that it is likely that no laboratory can achieve the order of magnitude requirements for a difficult sample matrix (e.g., an incinerator ash). The authors suggest that the regulation needs to be revised to address the disparity between what is achievable in the laboratory and the regulatory levels required by the UTS

O2 supplementation to secure the near-infrared spectroscopy determined brain and muscle oxygenation in vascular surgical patients: a presentation of 100 cases

Directory of Open Access Journals (Sweden)

Kim Zillo Rokamp

2014-02-01

Full Text Available This study addresses three questions for securing tissue oxygenation in brain (rScO2 and muscle (SmO2 for 100 patients (age 71 ± 6 yrs; mean ± SD undergoing vascular surgery: i Does preoxygenation (inhaling 100% oxygen before anesthesia increase tissue oxygenation, ii Does inhalation of 70% oxygen during surgery prevent a critical reduction in rScO2 (< 50%, and iii is a decrease in rScO2 and/or SmO2 related to reduced blood pressure and/or cardiac output? Intravenous anesthesia was provided to all patients and the intraoperative inspired oxygen fraction was set to 0.70 while tissue oxygenation was determined by INVOS 5100C. Preoxygenation increased rScO2 (from 65 ± 8% to 72 ± 9%; P < 0.05 and SmO2 (from 75 ± 9% to 78 ± 9%; P < 0.05 and during surgery rScO2 and SmO2 were maintained at the baseline level in most patients. Following anesthesia and tracheal intubation an eventual change in rScO2 correlated to cardiac output and cardiac stroke volume (coefficient of contingence=0.36; P=0.0003 rather to a change in mean arterial pressure and for five patients rScO2 was reduced to below 50%. We conclude that i increased oxygen delivery enhances tissue oxygenation, ii oxygen supports tissue oxygenation but does not prevent a critical reduction in cerebral oxygenation sufficiently, and iii an eventual decrease in tissue oxygenation seems related to a reduction in cardiac output rather than to hypotension.

Social Media Optimization. Su implementación en las webs de las pymes del Parque Tecnológico de Andalucía (PTA

Directory of Open Access Journals (Sweden)

Ana María Belmonte Jiménez

2011-10-01

Full Text Available Por su importancia en el tejido empresarial andaluz, se ha realizado un análisis web de 35 pymes de diversos sectores del PTA Málaga  y la implantación del SMO (Social Media Optimization en dichas empresas pequeñas y medianas para conocer cuál es el estado de la cuestión. La técnica utilizada para analizar las páginas webs de las pymes de distintos sectores del PTA ha sido el método del análisis de contenido. Para realizar el análisis de las webs del PTA, en cuanto a la implementación del SMO, se han identificado la presencia o ausencia (presencia=1, ausencia=0 de ocho unidades de análisis establecidas para medir el SMO: marcadores sociales, web feed, enlaces, contenido difundible, mashups, widgets, medios sociales, botones. A tenor de los resultados obtenidos según las empresas analizadas, concretamente las pymes del PTA de Málaga, se observa tienen una baja implementación del social media optimization en sus páginas web.

Mapping of calf muscle oxygenation and haemoglobin content during dynamic plantar flexion exercise by multi-channel time-resolved near-infrared spectroscopy

International Nuclear Information System (INIS)

Torricelli, Alessandro; Quaresima, Valentina; Pifferi, Antonio; Biscotti, Giovanni; Spinelli, Lorenzo; Taroni, Paola; Ferrari, Marco; Cubeddu, Rinaldo

2004-01-01

A compact and fast multi-channel time-resolved near-infrared spectroscopy system for tissue oximetry was developed. It employs semiconductor laser and fibre optics for delivery of optical signals. Photons are collected by eight 1 mm fibres and detected by a multianode photomultiplier. A time-correlated single photon counting board is used for the parallel acquisition of time-resolved reflectance curves. Estimate of the reduced scattering coefficient is achieved by fitting with a standard model of diffusion theory, while the modified Lambert-Beer law is used to assess the absorption coefficient. In vivo measurements were performed on five healthy volunteers to monitor spatial changes in calf muscle (medial and lateral gastrocnemius; MG, LG) oxygen saturation (SmO 2 ) and total haemoglobin concentration (tHb) during dynamic plantar flexion exercise performed at 50% of the maximal voluntary contraction. At rest SmO 2 was 73.0 ± 0.9 and 70.5 ± 1.7% in MG and LG, respectively (P = 0.045). At the end of the exercise, SmO 2 decreased (69.1 ± 1.8 and 63.8 ± 2.1% in MG and LG, respectively; P 2 and tHb

System design and improvement of an emergency department using Simulation-Based Multi-Objective Optimization

International Nuclear Information System (INIS)

Uriarte, A Goienetxea; Zúñiga, E Ruiz; Moris, M Urenda; Ng, A H C

2015-01-01

Discrete Event Simulation (DES) is nowadays widely used to support decision makers in system analysis and improvement. However, the use of simulation for improving stochastic logistic processes is not common among healthcare providers. The process of improving healthcare systems involves the necessity to deal with trade-off optimal solutions that take into consideration a multiple number of variables and objectives. Complementing DES with Multi-Objective Optimization (SMO) creates a superior base for finding these solutions and in consequence, facilitates the decision-making process. This paper presents how SMO has been applied for system improvement analysis in a Swedish Emergency Department (ED). A significant number of input variables, constraints and objectives were considered when defining the optimization problem. As a result of the project, the decision makers were provided with a range of optimal solutions which reduces considerably the length of stay and waiting times for the ED patients. SMO has proved to be an appropriate technique to support healthcare system design and improvement processes. A key factor for the success of this project has been the involvement and engagement of the stakeholders during the whole process. (paper)

Protein nanoparticles for therapeutic protein delivery.

Science.gov (United States)

Herrera Estrada, L P; Champion, J A

2015-06-01

Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

IDEJNA ZASNOVA GORSKE KOČE S SAMOZADOSTNO OSKRBO ENERGIJE

OpenAIRE

Stopar, Ana

2012-01-01

V današnjem času, ko smo priča številnim podnebnim spremembam, moramo posvetiti večjo pozornost varstvu okolja. Desetletja smo z okoljem delali samo z ozirom na našo korist in »ugodje« ter s tem povzročili številne negativne vplive na našo okolico. Ekološko zavedanje se je v zadnjem času močno povečalo in tako prišlo v vse stroke, tudi v arhitekturo in v gradbeništvo. Trajnostna arhitektura je postala osnovna komponentna sonaravnega razoja. Posegi v prostor se omejujejo na najmanjšo možno mer...

ŽENSKO PODJETNIŠTVO V SLOVENIJI

OpenAIRE

Zver, Doroteja

2015-01-01

Namen diplomskega seminarja je bil preučiti, kakšne so značilnosti podjetništva v Sloveniji, ter ugotoviti, s kakšnimi ovirami se srečujejo ženske pri vključevanju v podjetništvo. Prav tako nas je zanimala vloga žensk na vodilnih položajih. V teoretičnem delu smo se najprej seznanili s tem, kaj sploh je podjetništvo in navedli nekaj definicij različnih avtorjev, prav tako smo opredelili tudi pojem žensko podjetništvo in raziskali, kakšne so značilnosti ženskega podjetništva v Sloveniji, pr...

OBDAVČITEV ŠTUDENTSKEGA DELA IN NJEGOVA PRAVNA UREDITEV

OpenAIRE

Grobelnik, Andreja

2011-01-01

V diplomskem delu smo obravnavali pravno ureditev in obdavčitev študentskega dela v Sloveniji ter v Nemčiji. Proučili smo glavne razlike in podobnosti pri nas in v Nemčiji. Glavna razlika je ta, da so nemški študentje izenačeni z ostalimi državljani ter da jim teče delovna doba za opravljeno delo. Naravnani so k študiju, pri nas pa postavljajo na prvo mesto delo in delovne izkušnje. Razlika je tudi v tem, da si morajo študenti v Nemčiji sami plačevati posamezne prispevke in zavarovanja te...

Grade III Coronary Artery Perforation Following PCI and Unusual Stent Graft Delivery System

Directory of Open Access Journals (Sweden)

Sreckovic Miodrag

2014-06-01

Full Text Available Koronarne perforacije su retke ali izuzetno neugodne komlikacije perkutanih intervencija. Perforacije koronarnh arterija trećeg stepena po Elisu predstvaljaju najozbiljniju formu perforacija i zahtevaju hitno zbrinjavanje. Često je neophodno uraditi perikardiocentezu i primeniti brojne interventne tehnike kako bismo rešili perforaciju. Stentovi prekriveni politetrafluoroetilenom(PTFE postali su jedno od najčešće korišćenih perkutanih rešenja, ali su njihove mane visoki profil i slaba fleksibilnost. U našem slučaju, pokušali smo da poboljšamo plasiranje PTFE stenta montiranjem na metalni stent, koji smo iskoristili kao nosač.

Phase changes in superaustenitic steels after long-term annealing

Energy Technology Data Exchange (ETDEWEB)

Svoboda, M.; Kroupa, A. [Inst. of Physics of Materials, Academy of Sciences of Czech Republic, Brno (Czech Republic); Sopousek, J.; Vrest' al, J. [Inst. of Theoretical and Physical Chemistry, Masaryk Univ., Brno (Czech Republic); Miodownik, P. [Thermotech Ltd, The Surrey Research Park, Guildford (United Kingdom)

2004-11-01

A structural study was performed on the austenitic steels Avesta 254 SMO and Avesta 654 SMO after annealing at 700 C for 500, 3188, and 6170 h. Both Avesta steels initially show an unexpectedly large amount of the Laves phase, followed by a relatively slow development of the Sigma phase with equilibrium apparently not yet reached after 3188 h. Thermodynamic calculations confirm that the driving forces for alternative precipitates are very similar thus making it easy to form metastable precipitates that only change very slowly to the equilibrium state. TTT calculations also confirm that the Laves phase precipitates earlier than the Sigma phase as the temperature is lowered. (orig.)

Auto-avaliação de escolas e produção de conhecimento científico com o projecto QUALIS

OpenAIRE

Arroz, Ana Margarida Moura

2010-01-01

2º Colóquio Avaliação de Escolas. Angra do Heroísmo Universidade dos Açores, Campus do Pico da Urze, Angra do Heroísmo, Açores, Portugal, 2 de Outubro de 2010. Dado que a estrutura do modelo permite uma considerável margem de manobra das equipas de auto-avaliação na selecção e ênfase atribuída aos diferentes aspectos do funcionamento da escola no relatório que elaboram… "interessa-nos estudar até que ponto a informação que as equipas de auto-avaliação mobilizam no processo avaliativo e os ...

Evolution of classical projected phase space density in billiards

Indian Academy of Sciences (India)

A knowledge of the spectral decomposition of Lt allows one to evaluate corre- lations, averages and other ... from anti-normal ordering. Ω{e−ιξ∗ â†e−ιξâ} ..... zero k (k ≃ 0.70) in the power spectrum of the (smoothened) kernel KP (q, q,t) for.

'Equivalent' potential to SVZ moments to order 4>

International Nuclear Information System (INIS)

Bertlmann, R.A.

1984-01-01

We extend the 'equivalent' potential of Bell and Bertlmann on the basis of field theory by accounting for operators of dimension 6 and 8. There is no sign of flavour smoothening. The discrepancy between Schroedinger result and moment result improves but is still present. The moment result remains remarkably stable. (Author)

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African Journals Online (AJOL)

USER

2014-11-17

Nov 17, 2014 ... forecasting and smoothening technique that projects the future values of a series based entirely on its own inertia. ARIMA modeling takes into account trends, seasonality, cycles, errors and non-stationary aspects of a data set when making forecasts. It reduces ... robust, can cope with missing values, and.

Protein-protein interactions: an application of Tus-Ter mediated protein microarray system.

Science.gov (United States)

Sitaraman, Kalavathy; Chatterjee, Deb K

2011-01-01

In this chapter, we present a novel, cost-effective microarray strategy that utilizes expression-ready plasmid DNAs to generate protein arrays on-demand and its use to validate protein-protein interactions. These expression plasmids were constructed in such a way so as to serve a dual purpose of synthesizing the protein of interest as well as capturing the synthesized protein. The microarray system is based on the high affinity binding of Escherichia coli "Tus" protein to "Ter," a 20 bp DNA sequence involved in the regulation of DNA replication. The protein expression is carried out in a cell-free protein synthesis system, with rabbit reticulocyte lysates, and the target proteins are detected either by labeled incorporated tag specific or by gene-specific antibodies. This microarray system has been successfully used for the detection of protein-protein interaction because both the target protein and the query protein can be transcribed and translated simultaneously in the microarray slides. The utility of this system for detecting protein-protein interaction is demonstrated by a few well-known examples: Jun/Fos, FRB/FKBP12, p53/MDM2, and CDK4/p16. In all these cases, the presence of protein complexes resulted in the localization of fluorophores at the specific sites of the immobilized target plasmids. Interestingly, during our interactions studies we also detected a previously unknown interaction between CDK2 and p16. Thus, this Tus-Ter based system of protein microarray can be used for the validation of known protein interactions as well as for identifying new protein-protein interactions. In addition, it can be used to examine and identify targets of nucleic acid-protein, ligand-receptor, enzyme-substrate, and drug-protein interactions.

Truly Absorbed Microbial Protein Synthesis, Rumen Bypass Protein, Endogenous Protein, and Total Metabolizable Protein from Starchy and Protein-Rich Raw Materials

NARCIS (Netherlands)

Parand, Ehsan; Vakili, Alireza; Mesgaran, Mohsen Danesh; Duinkerken, Van Gert; Yu, Peiqiang

2015-01-01

This study was carried out to measure truly absorbed microbial protein synthesis, rumen bypass protein, and endogenous protein loss, as well as total metabolizable protein, from starchy and protein-rich raw feed materials with model comparisons. Predictions by the DVE2010 system as a more

Entre o sentido da colonização e o arcaísmo como projeto: a superação de um dilema através do conceito de capital escravista-mercantil

Directory of Open Access Journals (Sweden)

João Paulo A. de Souza

2008-03-01

Full Text Available Neste artigo, discute-se a proposta de Pires e Costa (1995, 2000 segundo a qual a economia brasileira no período escravista teria estado sujeita a uma forma específica do capital: o capital escravista-mercantil. Ela permite a superação da dicotomia entre o modelo interpretativo do Sentido da Colonização, proposto originalmente por Caio Prado Júnior, e o modelo do Arcaísmo como Projeto, proposto por Fragoso e Florentino (2001. O primeiro, por retratar a sociedade colonial como uma projeção imediata da expansão comercial européia, tem enfrentado dificuldades em acomodar as recentes evidências empíricas de que a economia colonial podia apresentar uma relativa autonomia, realizando acumulação endógena. O segundo, ao tentar de forma explícita acomodar essas evidências, acaba recusando a existência de um sentido da colonização tal como originalmente formulado. Para explicitar como o modelo do capital escravista-mercantil supera esse dilema, apresentamos uma analogia com o desenvolvimento da teoria do valor de Marx em O Capital.This paper discusses Pires and Costa's (1995, 2000 claim that the Brazilian economy during the slavery period functioned under the direction of a specific form of capital, called mercantile slavery capital. Their proposal allows us to overcome a dichotomy between the traditional interpretive model of the Meaning of Colonization, originally proposed by Caio Prado Júnior in the 1940's, and the new model of Archaism as a Project, proposed by Fragoso and Florentino (2001. The former, by depicting the Brazilian colonial society as an immediate result of the European commercial expansion, has had difficulties in explaining recent empirical evidence that the colonial economy was relatively autonomous, being able to carry out endogenous capital accumulation. The latter, however, in trying to explicitly accommodate this evidence turns out to reject the original formulation of the Meaning of Colonization as a

Composition of Overlapping Protein-Protein and Protein-Ligand Interfaces.

Directory of Open Access Journals (Sweden)

Ruzianisra Mohamed

Full Text Available Protein-protein interactions (PPIs play a major role in many biological processes and they represent an important class of targets for therapeutic intervention. However, targeting PPIs is challenging because often no convenient natural substrates are available as starting point for small-molecule design. Here, we explored the characteristics of protein interfaces in five non-redundant datasets of 174 protein-protein (PP complexes, and 161 protein-ligand (PL complexes from the ABC database, 436 PP complexes, and 196 PL complexes from the PIBASE database and a dataset of 89 PL complexes from the Timbal database. In all cases, the small molecule ligands must bind at the respective PP interface. We observed similar amino acid frequencies in all three datasets. Remarkably, also the characteristics of PP contacts and overlapping PL contacts are highly similar.

Protein- protein interaction detection system using fluorescent protein microdomains

Science.gov (United States)

Waldo, Geoffrey S.; Cabantous, Stephanie

2010-02-23

The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

Design specific joint optimization of masks and sources on a very large scale

Science.gov (United States)

Lai, K.; Gabrani, M.; Demaris, D.; Casati, N.; Torres, A.; Sarkar, S.; Strenski, P.; Bagheri, S.; Scarpazza, D.; Rosenbluth, A. E.; Melville, D. O.; Wächter, A.; Lee, J.; Austel, V.; Szeto-Millstone, M.; Tian, K.; Barahona, F.; Inoue, T.; Sakamoto, M.

2011-04-01

Joint optimization (JO) of source and mask together is known to produce better SMO solutions than sequential optimization of the source and the mask. However, large scale JO problems are very difficult to solve because the global impact of the source variables causes an enormous number of mask variables to be coupled together. This work presents innovation that minimize this runtime bottleneck. The proposed SMO parallelization algorithm allows separate mask regions to be processed efficiently across multiple CPUs in a high performance computing (HPC) environment, despite the fact that a truly joint optimization is being carried out with source variables that interact across the entire mask. Building on this engine a progressive deletion (PD) method was developed that can directly compute "binding constructs" for the optimization, i.e. our method can essentially determine the particular feature content which limits the process window attainable by the optimum source. This method allows us to minimize the uncertainty inherent to different clustering/ranking methods in seeking an overall optimum source that results from the use of heuristic metrics. An objective benchmarking of the effectiveness of different pattern sampling methods was performed during postoptimization analysis. The PD serves as a golden standard for us to develop optimum pattern clustering/ranking algorithms. With this work, it is shown that it is not necessary to exhaustively optimize the entire mask together with the source in order to identify these binding clips. If the number of clips to be optimized exceeds the practical limit of the parallel SMO engine one can starts with a pattern selection step to achieve high clip count compression before SMO. With this LSSO capability one can address the challenging problem of layout-specific design, or improve the technology source as cell layouts and sample layouts replace lithography test structures in the development cycle.

Uživanje alkohola med starostniki v domačem okolju: rezultati presejalnega testa SMAST-G

Directory of Open Access Journals (Sweden)

Radojka Kobentar

2017-06-01

Full Text Available Uvod: Dosedanje raziskave kažejo, da je tvegano ali škodljivo uživanje alkohola med starostniki prisotno v obsegu med 5 % in 23 % te populacije. Z raziskavo smo želeli preučiti pojavnost uživanja alkohola v starosti v povezavi z demografskimi dejavniki, socialno vključenostjo in samooceno zdravja. Metode: Uporabljen je bil standardizirani vprašalnik Short Michigan Alcoholism Screening Test – Geriatric version (SMAST-G. Nenaključno so bili vključeni starostniki nad 65 let, živeči v domačem okolju, ki so razumeli besedilo. Podatke smo obdelali z opisno statistiko in testom hi-kvadrat. Rezultati: Ugotovili smo, da je med starostniki 30,0 % takšnih, ki imajo možne težave z alkoholom. Statistična značilnost večjega uživanja alkohola se je pokazala pri nižji izobrazbi (x2 = 12,255, p = 0,007 ter pri moškem spolu (x2 = 14,641, p < 0,001. Ugotovili smo statistično povezanost uživanja alkohola s samooceno zdravja (x2 = 12,085, p = 0,017 ter s posameznimi spremenljivkami socialne vključenosti, in sicer z oceno socialnih odnosov (x2 = 14,124, p< 0,001 in z (neobstojem osebnih ciljev za prihodnost (x2 = 12,156, p = 0,016. Diskusija in zaključek: Uživanje alkohola se pri starostnikih povezuje s slabšo kakovostjo socialnih odnosov in nižjo samooceno zdravja. Raziskava kaže na potrebo po zvišanju znanja starostnikov o vplivih uživanja alkohola na zdravje, na potrebo po njihovi integraciji v socialno okolje ter po nadaljnjem raziskovanju problema uživanja alkohola v starosti.

The oxidation of alkylaryl sulfides and benzo[b]thiophenes by Escherichia coli cells expressing wild-type and engineered styrene monooxygenase from Pseudomonas putida CA-3.

Science.gov (United States)

Nikodinovic-Runic, Jasmina; Coulombel, Lydie; Francuski, Djordje; Sharma, Narain D; Boyd, Derek R; Ferrall, Rory Moore O; O'Connor, Kevin E

2013-06-01

Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by Escherichia coli Bl21(DE3) cells expressing styrene monooxygenase (SMO) from Pseudomonas putida CA-3. Thioanisole was consumed at 83.3 μmoles min(-1) g cell dry weight(-1) resulting mainly in the formation of R-thioanisole sulfoxide with an enantiomeric excess (ee) value of 45 %. The rate of 2-methyl-, 2-chloro- and 2-bromo-thioanisole consumption was 2-fold lower than that of thioanisole. Surprisingly, the 2-methylthioanisole sulfoxide product had the opposite (S) configuration to that of the other 2-substituted thioanisole derivatives and had a higher ee value (84 %). The rate of oxidation of 4-substituted thioanisoles was higher than the corresponding 2-substituted substrates but the ee values of the products were consistently lower (10-23 %). The rate of benzo[b]thiophene and 2-methylbenzo[b]thiophene sulfoxidation was approximately 10-fold lower than that of thioanisole. The ee value of the benzo[b]thiophene sulfoxide could not be determined as the product racemized rapidly. E. coli cells expressing an engineered SMO (SMOeng R3-11) oxidised 2-substituted thioanisoles between 1.8- and 2.8-fold faster compared to cells expressing the wild-type enzyme. SMOeng R3-11 oxidised benzo[b]thiophene and 2-methylbenzo[b]thiophene 10.1 and 5.6 times faster that the wild-type enzyme. The stereospecificity of the reaction catalysed by SMOeng was unchanged from that of the wild type. Using the X-ray crystal structure of the P. putida S12 SMO, it was evident that the entrance of substrates into the SMO active site is limited by the binding pocket bottleneck formed by the side chains of Val-211 and Asn-46 carboxyamide group.

Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

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Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

2007-08-01

INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

The influence of negative training set size on machine learning-based virtual screening.

Science.gov (United States)

Kurczab, Rafał; Smusz, Sabina; Bojarski, Andrzej J

2014-01-01

The paper presents a thorough analysis of the influence of the number of negative training examples on the performance of machine learning methods. The impact of this rather neglected aspect of machine learning methods application was examined for sets containing a fixed number of positive and a varying number of negative examples randomly selected from the ZINC database. An increase in the ratio of positive to negative training instances was found to greatly influence most of the investigated evaluating parameters of ML methods in simulated virtual screening experiments. In a majority of cases, substantial increases in precision and MCC were observed in conjunction with some decreases in hit recall. The analysis of dynamics of those variations let us recommend an optimal composition of training data. The study was performed on several protein targets, 5 machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest) and 2 types of molecular fingerprints (MACCS and CDK FP). The most effective classification was provided by the combination of CDK FP with SMO or Random Forest algorithms. The Naïve Bayes models appeared to be hardly sensitive to changes in the number of negative instances in the training set. In conclusion, the ratio of positive to negative training instances should be taken into account during the preparation of machine learning experiments, as it might significantly influence the performance of particular classifier. What is more, the optimization of negative training set size can be applied as a boosting-like approach in machine learning-based virtual screening.

Protein-protein interaction network-based detection of functionally similar proteins within species.

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Song, Baoxing; Wang, Fen; Guo, Yang; Sang, Qing; Liu, Min; Li, Dengyun; Fang, Wei; Zhang, Deli

2012-07-01

Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent. Copyright © 2012 Wiley Periodicals, Inc.

Protein-Protein Docking in Drug Design and Discovery.

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Kaczor, Agnieszka A; Bartuzi, Damian; Stępniewski, Tomasz Maciej; Matosiuk, Dariusz; Selent, Jana

2018-01-01

Protein-protein interactions (PPIs) are responsible for a number of key physiological processes in the living cells and underlie the pathomechanism of many diseases. Nowadays, along with the concept of so-called "hot spots" in protein-protein interactions, which are well-defined interface regions responsible for most of the binding energy, these interfaces can be targeted with modulators. In order to apply structure-based design techniques to design PPIs modulators, a three-dimensional structure of protein complex has to be available. In this context in silico approaches, in particular protein-protein docking, are a valuable complement to experimental methods for elucidating 3D structure of protein complexes. Protein-protein docking is easy to use and does not require significant computer resources and time (in contrast to molecular dynamics) and it results in 3D structure of a protein complex (in contrast to sequence-based methods of predicting binding interfaces). However, protein-protein docking cannot address all the aspects of protein dynamics, in particular the global conformational changes during protein complex formation. In spite of this fact, protein-protein docking is widely used to model complexes of water-soluble proteins and less commonly to predict structures of transmembrane protein assemblies, including dimers and oligomers of G protein-coupled receptors (GPCRs). In this chapter we review the principles of protein-protein docking, available algorithms and software and discuss the recent examples, benefits, and drawbacks of protein-protein docking application to water-soluble proteins, membrane anchoring and transmembrane proteins, including GPCRs.

Evolution of protein-protein interactions

Indian Academy of Sciences (India)

Evolution of protein-protein interactions · Our interests in protein-protein interactions · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20.

Protein function prediction using neighbor relativity in protein-protein interaction network.

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Moosavi, Sobhan; Rahgozar, Masoud; Rahimi, Amir

2013-04-01

There is a large gap between the number of discovered proteins and the number of functionally annotated ones. Due to the high cost of determining protein function by wet-lab research, function prediction has become a major task for computational biology and bioinformatics. Some researches utilize the proteins interaction information to predict function for un-annotated proteins. In this paper, we propose a novel approach called "Neighbor Relativity Coefficient" (NRC) based on interaction network topology which estimates the functional similarity between two proteins. NRC is calculated for each pair of proteins based on their graph-based features including distance, common neighbors and the number of paths between them. In order to ascribe function to an un-annotated protein, NRC estimates a weight for each neighbor to transfer its annotation to the unknown protein. Finally, the unknown protein will be annotated by the top score transferred functions. We also investigate the effect of using different coefficients for various types of functions. The proposed method has been evaluated on Saccharomyces cerevisiae and Homo sapiens interaction networks. The performance analysis demonstrates that NRC yields better results in comparison with previous protein function prediction approaches that utilize interaction network. Copyright © 2012 Elsevier Ltd. All rights reserved.

Protein Structure Prediction by Protein Threading

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Xu, Ying; Liu, Zhijie; Cai, Liming; Xu, Dong

The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on "the inverse protein folding problem" laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term "protein threading." These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now.

Specificity and affinity quantification of protein-protein interactions.

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Yan, Zhiqiang; Guo, Liyong; Hu, Liang; Wang, Jin

2013-05-01

Most biological processes are mediated by the protein-protein interactions. Determination of the protein-protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein-protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein-protein complexes. The scoring function of protein-protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein-protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein-protein complex against competitive ones. We developed a scoring function (named as SPA-PP, specificity and affinity of the protein-protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein-protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein-protein structure and affinity. The algorithm is implemented in C language, and the code can be downloaded from http://dl.dropbox.com/u/1865642/Optimization.cpp.

Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration

International Nuclear Information System (INIS)

Osawa, Hiroyuki; Ohnishi, Hirohide; Takano, Koji; Noguti, Takasi; Mashima, Hirosato; Hoshino, Hiroko; Kita, Hiroto; Sato, Kiichi; Matsui, Hirofumi; Sugano, Kentaro

2006-01-01

Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca 2+ ] i ). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca 2+ ] i , activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system

Health Parameter Estimation with Second-Order Sliding Mode Observer for a Turbofan Engine

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Xiaodong Chang

2017-07-01

Full Text Available In this paper the problem of health parameter estimation in an aero-engine is investigated by using an unknown input observer-based methodology, implemented by a second-order sliding mode observer (SOSMO. Unlike the conventional state estimator-based schemes, such as Kalman filters (KF and sliding mode observers (SMO, the proposed scheme uses a “reconstruction signal” to estimate health parameters modeled as artificial inputs, and is not only applicable to long-time health degradation, but reacts much quicker in handling abrupt fault cases. In view of the inevitable uncertainties in engine dynamics and modeling, a weighting matrix is created to minimize such effect on estimation by using the linear matrix inequalities (LMI. A big step toward uncertainty modeling is taken compared with our previous SMO-based work, in that uncertainties are considered in a more practical form. Moreover, to avoid chattering in sliding modes, the super-twisting algorithm (STA is employed in observer design. Various simulations are carried out, based on the comparisons between the KF-based scheme, the SMO-based scheme in our earlier research, and the proposed method. The results consistently demonstrate the capabilities and advantages of the proposed approach in health parameter estimation.

Ground-based FTIR retrievals of SF6 on Reunion Island

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M. Zhou

2018-02-01

Full Text Available SF6 total columns were successfully retrieved from FTIR (Fourier transform infrared measurements (Saint Denis and Maïdo on Reunion Island (21° S, 55° E between 2004 and 2016 using the SFIT4 algorithm: the retrieval strategy and the error budget were presented. The FTIR SF6 retrieval has independent information in only one individual layer, covering the whole of the troposphere and the lower stratosphere. The trend in SF6 was analysed based on the FTIR-retrieved dry-air column-averaged mole fractions (XSF6 on Reunion Island, the in situ measurements at America Samoa (SMO and the collocated satellite measurements (Michelson Interferometer for Passive Atmospheric Sounding, MIPAS, and Atmospheric Chemistry Experiment Fourier Transform Spectrometer, ACE-FTS in the southern tropics. The SF6 annual growth rate from FTIR retrievals is 0.265 ± 0.013 pptv year−1 for 2004–2016, which is slightly weaker than that from the SMO in situ measurements (0.285 ± 0.002 pptv year−1 for the same time period. The SF6 trend in the troposphere from MIPAS and ACE-FTS observations is also close to the ones from the FTIR retrievals and the SMO in situ measurements.

Ground-based FTIR retrievals of SF6 on Reunion Island

Science.gov (United States)

Zhou, Minqiang; Langerock, Bavo; Vigouroux, Corinne; Wang, Pucai; Hermans, Christian; Stiller, Gabriele; Walker, Kaley A.; Dutton, Geoff; Mahieu, Emmanuel; De Mazière, Martine

2018-02-01

SF6 total columns were successfully retrieved from FTIR (Fourier transform infrared) measurements (Saint Denis and Maïdo) on Reunion Island (21° S, 55° E) between 2004 and 2016 using the SFIT4 algorithm: the retrieval strategy and the error budget were presented. The FTIR SF6 retrieval has independent information in only one individual layer, covering the whole of the troposphere and the lower stratosphere. The trend in SF6 was analysed based on the FTIR-retrieved dry-air column-averaged mole fractions (XSF6) on Reunion Island, the in situ measurements at America Samoa (SMO) and the collocated satellite measurements (Michelson Interferometer for Passive Atmospheric Sounding, MIPAS, and Atmospheric Chemistry Experiment Fourier Transform Spectrometer, ACE-FTS) in the southern tropics. The SF6 annual growth rate from FTIR retrievals is 0.265 ± 0.013 pptv year-1 for 2004-2016, which is slightly weaker than that from the SMO in situ measurements (0.285 ± 0.002 pptv year-1) for the same time period. The SF6 trend in the troposphere from MIPAS and ACE-FTS observations is also close to the ones from the FTIR retrievals and the SMO in situ measurements.

Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores: lessons after 2 yr of monitoring in the Archipelago.

Science.gov (United States)

Borges, Paulo A V; Guerreiro, Orlando; Ferreira, Maria T; Borges, Annabella; Ferreira, Filomena; Bicudo, Nuno; Nunes, Lina; Marcos, Rita S; Arroz, Ana M; Scheffrahn, Rudolf H; Myles, Timothy G

2014-01-01

The dispersal flights of West Indian drywood termite, Cryptotermes brevis (Walker) (Isoptera: Kalotermitidae) were surveyed in the major cities of Azores. The sampling device used to estimate termite density consisted of a yellow adhesive trap (size 45 by 24 cm), placed with an artificial or natural light source in a dark attic environment. In addition, data from two other projects were used to improve the knowledge about the geographical distribution of the species. The level of infestation in the two main Azorean towns differed, with high levels in the houses of Angra do Heroísmo, whereas in Ponta Delgada, there are fewer houses with high levels of infestation. The infestation in Ponta Delgada shows a pattern of spreading from the center outward to the city's periphery, whereas in Angra do Heroísmo, there was a pattern of spreading outward from several foci. The heavy infestation observed in Angra do Heroísmo and the clear increase of infestation levels observed from 2010 to 2011 is a reason for concern and calls for an urgent application of an Integrated Pest Management (IPM) control strategy. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Organizacijska kultura v slovenskih tujih podjetjih

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Denis Benjamin Kmetec

2017-12-01

Full Text Available Raziskovalno vprašanje (RV: Kakšna je prevladujoča organizacijska kultura v tujih podjetjih v Sloveniji in kakšna usmerjenost k posameznim kulturam se kaže na različnih ravneh organiziranosti? Namen: Namen raziskave je bil raziskati prevladujoči tip organizacijske kulture v izbranih mikro, malih, srednjih in velikih podjetjih s tujim lastništvom v Republiki Sloveniji. Metoda: Za pridobivanje podatkov in informacij smo uporabili vprašalnik po tipologiji Camerona in Quina, ki smo ga poslali v 437 podjetij. Rezultati: Anketirani, ki so zaposleni v slovenskih podjetjih s tujim kapitalom, si želijo kulture klana, kot prevladujoči kulturi v podjetju pa dojemajo kulturo trga in kulturo hierarhije. Organizacija: Dobljeni izidi iz empiričnega dela raziskave pripomorejo k boljšemu razumevanju organizacijske kulture v uspešnih tujih podjetij. Družba: V slovenskem gospodarskem okolju je organizacijska kultura v tujih podjetjih osnova za njeno nadaljnje raziskovanje. Originalnost: Kot prvi smo ugotavljali ali glede na identificirani tip organizacijske kulture obstaja večja uspešnost podjetij s tujim lastništvom. Omejitve/nadaljnje raziskovanje: obstaja priložnost za nadaljnje raziskovanje na področju povezave uspešnosti podjetij in njihove stabilnosti.

Detection of protein complex from protein-protein interaction network using Markov clustering

International Nuclear Information System (INIS)

Ochieng, P J; Kusuma, W A; Haryanto, T

2017-01-01

Detection of complexes, or groups of functionally related proteins, is an important challenge while analysing biological networks. However, existing algorithms to identify protein complexes are insufficient when applied to dense networks of experimentally derived interaction data. Therefore, we introduced a graph clustering method based on Markov clustering algorithm to identify protein complex within highly interconnected protein-protein interaction networks. Protein-protein interaction network was first constructed to develop geometrical network, the network was then partitioned using Markov clustering to detect protein complexes. The interest of the proposed method was illustrated by its application to Human Proteins associated to type II diabetes mellitus. Flow simulation of MCL algorithm was initially performed and topological properties of the resultant network were analysed for detection of the protein complex. The results indicated the proposed method successfully detect an overall of 34 complexes with 11 complexes consisting of overlapping modules and 20 non-overlapping modules. The major complex consisted of 102 proteins and 521 interactions with cluster modularity and density of 0.745 and 0.101 respectively. The comparison analysis revealed MCL out perform AP, MCODE and SCPS algorithms with high clustering coefficient (0.751) network density and modularity index (0.630). This demonstrated MCL was the most reliable and efficient graph clustering algorithm for detection of protein complexes from PPI networks. (paper)

Coarse-grain modelling of protein-protein interactions

NARCIS (Netherlands)

Baaden, Marc; Marrink, Siewert J.

2013-01-01

Here, we review recent advances towards the modelling of protein-protein interactions (PPI) at the coarse-grained (CG) level, a technique that is now widely used to understand protein affinity, aggregation and self-assembly behaviour. PPI models of soluble proteins and membrane proteins are

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African Journals Online (AJOL)

transistor TRI (2N3773), which controls the electronic switch unit. The capacitor C3. (470pF) is placed at the output of the rectifier to smoothen the rectified signal and maintain an effective trigger voltage for the transistor. TR1. Electronic Switch. The electronic switch is basically controlled by the transistor TR1 and the electro-.

Detection of protein-protein interactions by ribosome display and protein in situ immobilisation.

Science.gov (United States)

He, Mingyue; Liu, Hong; Turner, Martin; Taussig, Michael J

2009-12-31

We describe a method for identification of protein-protein interactions by combining two cell-free protein technologies, namely ribosome display and protein in situ immobilisation. The method requires only PCR fragments as the starting material, the target proteins being made through cell-free protein synthesis, either associated with their encoding mRNA as ribosome complexes or immobilised on a solid surface. The use of ribosome complexes allows identification of interacting protein partners from their attached coding mRNA. To demonstrate the procedures, we have employed the lymphocyte signalling proteins Vav1 and Grb2 and confirmed the interaction between Grb2 and the N-terminal SH3 domain of Vav1. The method has promise for library screening of pairwise protein interactions, down to the analytical level of individual domain or motif mapping.

Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

Science.gov (United States)

Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

2011-05-20

Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.

A Novel Approach for Protein-Named Entity Recognition and Protein-Protein Interaction Extraction

Directory of Open Access Journals (Sweden)

Meijing Li

2015-01-01

Full Text Available Many researchers focus on developing protein-named entity recognition (Protein-NER or PPI extraction systems. However, the studies about these two topics cannot be merged well; then existing PPI extraction systems’ Protein-NER still needs to improve. In this paper, we developed the protein-protein interaction extraction system named PPIMiner based on Support Vector Machine (SVM and parsing tree. PPIMiner consists of three main models: natural language processing (NLP model, Protein-NER model, and PPI discovery model. The Protein-NER model, which is named ProNER, identifies the protein names based on two methods: dictionary-based method and machine learning-based method. ProNER is capable of identifying more proteins than dictionary-based Protein-NER model in other existing systems. The final discovered PPIs extracted via PPI discovery model are represented in detail because we showed the protein interaction types and the occurrence frequency through two different methods. In the experiments, the result shows that the performances achieved by our ProNER and PPI discovery model are better than other existing tools. PPIMiner applied this protein-named entity recognition approach and parsing tree based PPI extraction method to improve the performance of PPI extraction. We also provide an easy-to-use interface to access PPIs database and an online system for PPIs extraction and Protein-NER.

Protein complex prediction in large ontology attributed protein-protein interaction networks.

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Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Li, Yanpeng; Xu, Bo

2013-01-01

Protein complexes are important for unraveling the secrets of cellular organization and function. Many computational approaches have been developed to predict protein complexes in protein-protein interaction (PPI) networks. However, most existing approaches focus mainly on the topological structure of PPI networks, and largely ignore the gene ontology (GO) annotation information. In this paper, we constructed ontology attributed PPI networks with PPI data and GO resource. After constructing ontology attributed networks, we proposed a novel approach called CSO (clustering based on network structure and ontology attribute similarity). Structural information and GO attribute information are complementary in ontology attributed networks. CSO can effectively take advantage of the correlation between frequent GO annotation sets and the dense subgraph for protein complex prediction. Our proposed CSO approach was applied to four different yeast PPI data sets and predicted many well-known protein complexes. The experimental results showed that CSO was valuable in predicting protein complexes and achieved state-of-the-art performance.

Protein surface shielding agents in protein crystallization

International Nuclear Information System (INIS)

Hašek, J.

2011-01-01

The crystallization process can be controlled by protein surface shielding agents blocking undesirable competitive adhesion modes during non-equilibrium processes of deposition of protein molecules on the surface of growing crystalline blocks. The hypothesis is based on a number of experimental proofs from diffraction experiments and also retrieved from the Protein Data Bank. The molecules adhering temporarily on the surface of protein molecules change the propensity of protein molecules to deposit on the crystal surface in a definite position and orientation. The concepts of competitive adhesion modes and protein surface shielding agents acting on the surface of molecules in a non-equilibrium process of protein crystallization provide a useful platform for the control of crystallization. The desirable goal, i.e. a transient preference of a single dominating adhesion mode between protein molecules during crystallization, leads to uniform deposition of proteins in a crystal. This condition is the most important factor for diffraction quality and thus also for the accuracy of protein structure determination. The presented hypothesis is a generalization of the experimentally well proven behaviour of hydrophilic polymers on the surface of protein molecules of other compounds

The Development of Protein Microarrays and Their Applications in DNA-Protein and Protein-Protein Interaction Analyses of Arabidopsis Transcription Factors

Science.gov (United States)

Gong, Wei; He, Kun; Covington, Mike; Dinesh-Kumar, S. P.; Snyder, Michael; Harmer, Stacey L.; Zhu, Yu-Xian; Deng, Xing Wang

2009-01-01

We used our collection of Arabidopsis transcription factor (TF) ORFeome clones to construct protein microarrays containing as many as 802 TF proteins. These protein microarrays were used for both protein-DNA and protein-protein interaction analyses. For protein-DNA interaction studies, we examined AP2/ERF family TFs and their cognate cis-elements. By careful comparison of the DNA-binding specificity of 13 TFs on the protein microarray with previous non-microarray data, we showed that protein microarrays provide an efficient and high throughput tool for genome-wide analysis of TF-DNA interactions. This microarray protein-DNA interaction analysis allowed us to derive a comprehensive view of DNA-binding profiles of AP2/ERF family proteins in Arabidopsis. It also revealed four TFs that bound the EE (evening element) and had the expected phased gene expression under clock-regulation, thus providing a basis for further functional analysis of their roles in clock regulation of gene expression. We also developed procedures for detecting protein interactions using this TF protein microarray and discovered four novel partners that interact with HY5, which can be validated by yeast two-hybrid assays. Thus, plant TF protein microarrays offer an attractive high-throughput alternative to traditional techniques for TF functional characterization on a global scale. PMID:19802365

Protein sequence comparison and protein evolution

Energy Technology Data Exchange (ETDEWEB)

Pearson, W.R. [Univ. of Virginia, Charlottesville, VA (United States). Dept. of Biochemistry

1995-12-31

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. This tutorial examines how the information conserved during the evolution of a protein molecule can be used to infer reliably homology, and thus a shared proteinfold and possibly a shared active site or function. The authors start by reviewing a geological/evolutionary time scale. Next they look at the evolution of several protein families. During the tutorial, these families will be used to demonstrate that homologous protein ancestry can be inferred with confidence. They also examine different modes of protein evolution and consider some hypotheses that have been presented to explain the very earliest events in protein evolution. The next part of the tutorial will examine the technical aspects of protein sequence comparison. Both optimal and heuristic algorithms and their associated parameters that are used to characterize protein sequence similarities are discussed. Perhaps more importantly, they survey the statistics of local similarity scores, and how these statistics can both be used to improve the selectivity of a search and to evaluate the significance of a match. They them examine distantly related members of three protein families, the serine proteases, the glutathione transferases, and the G-protein-coupled receptors (GCRs). Finally, the discuss how sequence similarity can be used to examine internal repeated or mosaic structures in proteins.

On the analysis of protein-protein interactions via knowledge-based potentials for the prediction of protein-protein docking

DEFF Research Database (Denmark)

Feliu, Elisenda; Aloy, Patrick; Oliva, Baldo

2011-01-01

Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions for s...... and with independence of the partner. This information is encoded at the residue level and could be easily incorporated in the initial grid scoring for Fast Fourier Transform rigid-body docking methods.......Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions...... for selecting rigid-body docking poses. These potentials include the energetic component that provides the residues with a particular secondary structure and surface accessibility. These scoring functions have been tested on a state-of-art benchmark dataset and on a decoy dataset of permanent interactions. Our...

Proteins interacting with cloning scars: a source of false positive protein-protein interactions.

Science.gov (United States)

Banks, Charles A S; Boanca, Gina; Lee, Zachary T; Florens, Laurence; Washburn, Michael P

2015-02-23

A common approach for exploring the interactome, the network of protein-protein interactions in cells, uses a commercially available ORF library to express affinity tagged bait proteins; these can be expressed in cells and endogenous cellular proteins that copurify with the bait can be identified as putative interacting proteins using mass spectrometry. Control experiments can be used to limit false-positive results, but in many cases, there are still a surprising number of prey proteins that appear to copurify specifically with the bait. Here, we have identified one source of false-positive interactions in such studies. We have found that a combination of: 1) the variable sequence of the C-terminus of the bait with 2) a C-terminal valine "cloning scar" present in a commercially available ORF library, can in some cases create a peptide motif that results in the aberrant co-purification of endogenous cellular proteins. Control experiments may not identify false positives resulting from such artificial motifs, as aberrant binding depends on sequences that vary from one bait to another. It is possible that such cryptic protein binding might occur in other systems using affinity tagged proteins; this study highlights the importance of conducting careful follow-up studies where novel protein-protein interactions are suspected.

The effect of protein-protein and protein-membrane interactions on membrane fouling in ultrafiltration

NARCIS (Netherlands)

Huisman, I.H.; Prádanos, P.; Hernández, A.

2000-01-01

It was studied how protein-protein and protein-membrane interactions influence the filtration performance during the ultrafiltration of protein solutions over polymeric membranes. This was done by measuring flux, streaming potential, and protein transmission during filtration of bovine serum albumin

Fluorogen-activating proteins: beyond classical fluorescent proteins

Directory of Open Access Journals (Sweden)

Shengnan Xu

2018-05-01

Full Text Available Fluorescence imaging is a powerful technique for the real-time noninvasive monitoring of protein dynamics. Recently, fluorogen activating proteins (FAPs/fluorogen probes for protein imaging were developed. Unlike the traditional fluorescent proteins (FPs, FAPs do not fluoresce unless bound to their specific small-molecule fluorogens. When using FAPs/fluorogen probes, a washing step is not required for the removal of free probes from the cells, thus allowing rapid and specific detection of proteins in living cells with high signal-to-noise ratio. Furthermore, with different fluorogens, living cell multi-color proteins labeling system was developed. In this review, we describe about the discovery of FAPs, the design strategy of FAP fluorogens, the application of the FAP technology and the advances of FAP technology in protein labeling systems. KEY WORDS: Fluorogen activating proteins, Fluorogens, Genetically encoded sensors, Fluorescence imaging, Molecular imaging

リコーにおけるバランストスコアカード（Balanced Scorecard BSC)の活用について-BSCから戦略的目標管理制度（Strategic Management　by　Objectives:SMO)へ-

OpenAIRE

中嶋,教夫

2005-01-01

BSC は Kaplan と Norton が 1992年に発表した概念であるが、その特徴は企業の戦略やビジョンを可視化し、それらを実行に移す為の戦略マネジメント・システムとして説明されることが多い。 しかしながら、 BSC は企業の実態に合わせて様々に活用されている。 特に、わが国で最も早い時期に BSC を導入したリコー社は、BSC の活用形態に工夫を加え、戦略的目標管理制度（SMO）を活用している。 そこで、本稿では、リコー社の業績評価システムがどのような変遷をたどって、BSC からさらに SMO を活用するにいたったのかを概観し、リコー社の業績評価システムに対して考察を加えることを目的としている。...

Protein immobilization strategies for protein biochips

NARCIS (Netherlands)

Rusmini, F.; Rusmini, Federica; Zhong, Zhiyuan; Feijen, Jan

2007-01-01

In the past few years, protein biochips have emerged as promising proteomic and diagnostic tools for obtaining information about protein functions and interactions. Important technological innovations have been made. However, considerable development is still required, especially regarding protein

Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

International Nuclear Information System (INIS)

Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

2016-01-01

Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration

Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

International Nuclear Information System (INIS)

Yu, P.

2007-01-01

The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

Prihodnja osvetlitev in nočna podoba mest: študija primera

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Simon Rankel

2014-06-01

Full Text Available Prihodnja osvetlitev na podlagi polprevodniških virov svetlobe bo spremenila nočno podobo mest. Možnosti njihove umestitve in uporabe v urbanem prostoru so številne. V članku zato proučujemo, ali bi njihova prihodnja uporaba v splošni zunanji razsvetljavi pozitivno vplivala na človekovo sprejemanje tako osvetljenega urbanega prostora. Na podlagi inovativne uporabe omenjenih virov svetlobe smo izoblikovali dva različna koncepta osvetlitve. Prvi koncept temelji na ploskovni osvetlitvi, drugi pa na detajlnem prikazu arhitekturno–urbanih elementov. Predlogi za osvetlitev so bili narejeni na petih različnih lokacijah mesta. Poleg izpolnjevanja funkcionalnih potreb upoštevajo tudi urbanistični in arhitekturni vidik osvetljevanja. Z ocenami afektivne kakovosti slikovnih prikazov smo predstavili in proučevali temeljna afektivna stanja anketiranih. Ugotovitve kažejo, da so se anketiranci pri večini predlogov strinjali pri ocenah spremenljivk »prijetnost« in »pozornost. Statistika pokaže med konceptoma značilne razlike pri ocenah obeh spremenljivk. Pri neposredni primerjavi obeh konceptov smo ugotovili, da je naklonjenost anketirancev do določenega osvetlitvenega koncepta odvisna tudi od mestne lokacije. S člankom želimo poudariti pomen nočne podobe mesta pri razvoju prihodnjih strategij osvetlitve, ki temeljijo na polprevodniških virih svetlobe.

A tool for urban soundscape evaluation applying Support Vector Machines for developing a soundscape classification model.

Science.gov (United States)

Torija, Antonio J; Ruiz, Diego P; Ramos-Ridao, Angel F

2014-06-01

To ensure appropriate soundscape management in urban environments, the urban-planning authorities need a range of tools that enable such a task to be performed. An essential step during the management of urban areas from a sound standpoint should be the evaluation of the soundscape in such an area. In this sense, it has been widely acknowledged that a subjective and acoustical categorization of a soundscape is the first step to evaluate it, providing a basis for designing or adapting it to match people's expectations as well. In this sense, this work proposes a model for automatic classification of urban soundscapes. This model is intended for the automatic classification of urban soundscapes based on underlying acoustical and perceptual criteria. Thus, this classification model is proposed to be used as a tool for a comprehensive urban soundscape evaluation. Because of the great complexity associated with the problem, two machine learning techniques, Support Vector Machines (SVM) and Support Vector Machines trained with Sequential Minimal Optimization (SMO), are implemented in developing model classification. The results indicate that the SMO model outperforms the SVM model in the specific task of soundscape classification. With the implementation of the SMO algorithm, the classification model achieves an outstanding performance (91.3% of instances correctly classified). © 2013 Elsevier B.V. All rights reserved.

Short-Circuit Fault Tolerant Control of a Wind Turbine Driven Induction Generator Based on Sliding Mode Observers

Directory of Open Access Journals (Sweden)

Takwa Sellami

2017-10-01

Full Text Available The installed energy production capacity of wind turbines is growing intensely on a global scale, making the reliability of wind turbine subsystems of greater significance. However, many faults like Inter-Turn Short-Circuit (ITSC may affect the turbine generator and quickly lead to a decline in supplied power quality. In this framework, this paper proposes a Sliding Mode Observer (SMO-based Fault Tolerant Control (FTC scheme for Induction Generator (IG-based variable-speed grid-connected wind turbines. First, the dynamic models of the wind turbine subsystems were developed. The control schemes were elaborated based on the Maximum Power Point Tracking (MPPT method and Indirect Rotor Flux Oriented Control (IRFOC method. The grid control was also established by regulating the active and reactive powers. The performance of the wind turbine system and the stability of injected power to the grid were hence analyzed under both healthy and faulty conditions. The robust developed SMO-based Fault Detection and Isolation (FDI scheme was proved to be fast and efficient for ITSC detection and localization.Afterwards, SMO were involved in scheming the FTC technique. Accordingly, simulation results assert the efficacy of the proposed ITSC FTC method for variable-speed wind turbines with faulty IG in protecting the subsystems from damage and ensuring continuous connection of the wind turbine to the grid during ITSC faults, hence maintaining power quality.

Support Vector Machine and Application in Seizure Prediction

KAUST Repository

Qiu, Simeng

2018-04-01

Nowadays, Machine learning (ML) has been utilized in various kinds of area which across the range from engineering field to business area. In this paper, we first present several kernel machine learning methods of solving classification, regression and clustering problems. These have good performance but also have some limitations. We present examples to each method and analyze the advantages and disadvantages for solving different scenarios. Then we focus on one of the most popular classification methods, Support Vectors Machine (SVM). In addition, we introduce the basic theory, advantages and scenarios of using Support Vector Machine (SVM) deal with classification problems. We also explain a convenient approach of tacking SVM problems which are called Sequential Minimal Optimization (SMO). Moreover, one class SVM can be understood in a different way which is called Support Vector Data Description (SVDD). This is a famous non-linear model problem compared with SVM problems, SVDD can be solved by utilizing Gaussian RBF kernel function combined with SMO. At last, we compared the difference and performance of SVM-SMO implementation and SVM-SVDD implementation. About the application part, we utilized SVM method to handle seizure forecasting in canine epilepsy, after comparing the results from different methods such as random forest, extremely randomized tree, and SVM to classify preictal (pre-seizure) and interictal (interval-seizure) binary data. We draw the conclusion that SVM has the best performance.

Information assessment on predicting protein-protein interactions

Directory of Open Access Journals (Sweden)

Gerstein Mark

2004-10-01

Full Text Available Abstract Background Identifying protein-protein interactions is fundamental for understanding the molecular machinery of the cell. Proteome-wide studies of protein-protein interactions are of significant value, but the high-throughput experimental technologies suffer from high rates of both false positive and false negative predictions. In addition to high-throughput experimental data, many diverse types of genomic data can help predict protein-protein interactions, such as mRNA expression, localization, essentiality, and functional annotation. Evaluations of the information contributions from different evidences help to establish more parsimonious models with comparable or better prediction accuracy, and to obtain biological insights of the relationships between protein-protein interactions and other genomic information. Results Our assessment is based on the genomic features used in a Bayesian network approach to predict protein-protein interactions genome-wide in yeast. In the special case, when one does not have any missing information about any of the features, our analysis shows that there is a larger information contribution from the functional-classification than from expression correlations or essentiality. We also show that in this case alternative models, such as logistic regression and random forest, may be more effective than Bayesian networks for predicting interactions. Conclusions In the restricted problem posed by the complete-information subset, we identified that the MIPS and Gene Ontology (GO functional similarity datasets as the dominating information contributors for predicting the protein-protein interactions under the framework proposed by Jansen et al. Random forests based on the MIPS and GO information alone can give highly accurate classifications. In this particular subset of complete information, adding other genomic data does little for improving predictions. We also found that the data discretizations used in the

Changes and significance of oxygen-metabolism and SHH signal pathway in soldiers trained in high altitude after returning to plains

Directory of Open Access Journals (Sweden)

Li LIU

2012-11-01

Full Text Available Objective 　To observe the changes in oxygen metabolism and sonic hedgehog (SHH signaling pathway in soldiers returning to plains after being stationed and trained for 6 months in a plateau. Methods 　Eighty male officers and soldiers, aged 20-30 (22.3±2.9 years, after being stationed and trained on plateau (altitude 3960m for 6 months and returned to plain region (altitude 200m, were selected as subjects. Before their returning to plateau, 6 months after their station and training in plateau, and 2 days after their returning to plain, fasting venous blood samples were collected, the serum levels of superoxide dismutase (SOD, malondialdehyde (MDA and Sonic Hedgehog (SHH were determined by ELISA, the transcription of SHH mRNA was assayed by RT-PCR, and the expressions of SMO and nucleoprotein GLI2 were detected by Western blotting. All the data mentioned above were collected for statistical analysis. Results 　As the subjects entered and garrisoned in plateau for 6 months, the activity of SOD decreased and the content of MDA increased significantly (P < 0.05. Both the protein expression and mRNA transcription of SHH were significantly higher after staying in plateau than in plain. When they returned to plain, both parameters decreased significantly, but were still higher than that when they lived in plain (P < 0.01. The expressions of SMO and nucleoprotein GLI2 showed a same tendency of changes. Conclusion 　High altitude environment may have a great influence on oxygen metabolism of organism and SHH signal pathway, and the hypoxic environment of high altitude region is one of the conditions in activating the SHH signal pathway.

Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

Science.gov (United States)

Chen, Yan; Lu, Xiaoling; Guo, Luo; Ni, Wenli; Zhang, Yanping; Zhao, Liping; Wu, Lingjie; Sun, Shan; Zhang, Shasha; Tang, Mingliang; Li, Wenyan; Chai, Renjie; Li, Huawei

2017-01-01

Hair cell (HC) loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh) protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway. PMID:29311816

Hedgehog Signaling Promotes the Proliferation and Subsequent Hair Cell Formation of Progenitor Cells in the Neonatal Mouse Cochlea

Directory of Open Access Journals (Sweden)

Yan Chen

2017-12-01

Full Text Available Hair cell (HC loss is the major cause of permanent sensorineural hearing loss in mammals. Unlike lower vertebrates, mammalian cochlear HCs cannot regenerate spontaneously after damage, although the vestibular system does maintain limited HC regeneration capacity. Thus HC regeneration from the damaged sensory epithelium has been one of the main areas of research in the field of hearing restoration. Hedgehog signaling plays important roles during the embryonic development of the inner ear, and it is involved in progenitor cell proliferation and differentiation as well as the cell fate decision. In this study, we show that recombinant Sonic Hedgehog (Shh protein effectively promotes sphere formation, proliferation, and differentiation of Lgr5+ progenitor cells isolated from the neonatal mouse cochlea. To further explore this, we determined the effect of Hedgehog signaling on cell proliferation and HC regeneration in cultured cochlear explant from transgenic R26-SmoM2 mice that constitutively activate Hedgehog signaling in the supporting cells of the cochlea. Without neomycin treatment, up-regulation of Hedgehog signaling did not significantly promote cell proliferation or new HC formation. However, after injury to the sensory epithelium by neomycin treatment, the over-activation of Hedgehog signaling led to significant supporting cell proliferation and HC regeneration in the cochlear epithelium explants. RNA sequencing and real-time PCR were used to compare the transcripts of the cochleae from control mice and R26-SmoM2 mice, and multiple genes involved in the proliferation and differentiation processes were identified. This study has important implications for the treatment of sensorineural hearing loss by manipulating the Hedgehog signaling pathway.

Mapping Protein-Protein Interactions by Quantitative Proteomics

DEFF Research Database (Denmark)

Dengjel, Joern; Kratchmarova, Irina; Blagoev, Blagoy

2010-01-01

spectrometry (MS)-based proteomics in combination with affinity purification protocols has become the method of choice to map and track the dynamic changes in protein-protein interactions, including the ones occurring during cellular signaling events. Different quantitative MS strategies have been used...... to characterize protein interaction networks. In this chapter we describe in detail the use of stable isotope labeling by amino acids in cell culture (SILAC) for the quantitative analysis of stimulus-dependent dynamic protein interactions.......Proteins exert their function inside a cell generally in multiprotein complexes. These complexes are highly dynamic structures changing their composition over time and cell state. The same protein may thereby fulfill different functions depending on its binding partners. Quantitative mass...

ProDis-ContSHC: learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval.

Science.gov (United States)

Wang, Jingyan; Gao, Xin; Wang, Quanquan; Li, Yongping

2012-05-08

The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database. In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N(i) and N(j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N(i) and N(j).Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update the Protein Hierarchial

Biophysics of protein evolution and evolutionary protein biophysics

Science.gov (United States)

Sikosek, Tobias; Chan, Hue Sun

2014-01-01

The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

High quality protein microarray using in situ protein purification

Directory of Open Access Journals (Sweden)

Fleischmann Robert D

2009-08-01

Full Text Available Abstract Background In the postgenomic era, high throughput protein expression and protein microarray technologies have progressed markedly permitting screening of therapeutic reagents and discovery of novel protein functions. Hexa-histidine is one of the most commonly used fusion tags for protein expression due to its small size and convenient purification via immobilized metal ion affinity chromatography (IMAC. This purification process has been adapted to the protein microarray format, but the quality of in situ His-tagged protein purification on slides has not been systematically evaluated. We established methods to determine the level of purification of such proteins on metal chelate-modified slide surfaces. Optimized in situ purification of His-tagged recombinant proteins has the potential to become the new gold standard for cost-effective generation of high-quality and high-density protein microarrays. Results Two slide surfaces were examined, chelated Cu2+ slides suspended on a polyethylene glycol (PEG coating and chelated Ni2+ slides immobilized on a support without PEG coating. Using PEG-coated chelated Cu2+ slides, consistently higher purities of recombinant proteins were measured. An optimized wash buffer (PBST composed of 10 mM phosphate buffer, 2.7 mM KCl, 140 mM NaCl and 0.05% Tween 20, pH 7.4, further improved protein purity levels. Using Escherichia coli cell lysates expressing 90 recombinant Streptococcus pneumoniae proteins, 73 proteins were successfully immobilized, and 66 proteins were in situ purified with greater than 90% purity. We identified several antigens among the in situ-purified proteins via assays with anti-S. pneumoniae rabbit antibodies and a human patient antiserum, as a demonstration project of large scale microarray-based immunoproteomics profiling. The methodology is compatible with higher throughput formats of in vivo protein expression, eliminates the need for resin-based purification and circumvents

Can infrared spectroscopy provide information on protein-protein interactions?

Science.gov (United States)

Haris, Parvez I

2010-08-01

For most biophysical techniques, characterization of protein-protein interactions is challenging; this is especially true with methods that rely on a physical phenomenon that is common to both of the interacting proteins. Thus, for example, in IR spectroscopy, the carbonyl vibration (1600-1700 cm(-1)) associated with the amide bonds from both of the interacting proteins will overlap extensively, making the interpretation of spectral changes very complicated. Isotope-edited infrared spectroscopy, where one of the interacting proteins is uniformly labelled with (13)C or (13)C,(15)N has been introduced as a solution to this problem, enabling the study of protein-protein interactions using IR spectroscopy. The large shift of the amide I band (approx. 45 cm(-1) towards lower frequency) upon (13)C labelling of one of the proteins reveals the amide I band of the unlabelled protein, enabling it to be used as a probe for monitoring conformational changes. With site-specific isotopic labelling, structural resolution at the level of individual amino acid residues can be achieved. Furthermore, the ability to record IR spectra of proteins in diverse environments means that isotope-edited IR spectroscopy can be used to structurally characterize difficult systems such as protein-protein complexes bound to membranes or large insoluble peptide/protein aggregates. In the present article, examples of application of isotope-edited IR spectroscopy for studying protein-protein interactions are provided.

Protein and protein hydrolysates in sports nutrition.

Science.gov (United States)

van Loon, Luc J C; Kies, Arie K; Saris, Wim H M

2007-08-01

With the increasing knowledge about the role of nutrition in increasing exercise performance, it has become clear over the last 2 decades that amino acids, protein, and protein hydrolysates can play an important role. Most of the attention has been focused on their effects at a muscular level. As these nutrients are ingested, however, it also means that gastrointestinal digestibility and absorption can modulate their efficacy significantly. Therefore, discussing the role of amino acids, protein, and protein hydrolysates in sports nutrition entails holding a discussion on all levels of the metabolic route. On May 28-29, 2007, a small group of researchers active in the field of exercise science and protein metabolism presented an overview of the different aspects of the application of protein and protein hydrolysates in sports nutrition. In addition, they were asked to share their opinions on the future progress in their fields of research. In this overview, an introduction to the workshop and a short summary of its outcome is provided.

ProDis-ContSHC: Learning protein dissimilarity measures and hierarchical context coherently for protein-protein comparison in protein database retrieval

KAUST Repository

Wang, Jim Jing-Yan

2012-05-08

Background: The need to retrieve or classify protein molecules using structure or sequence-based similarity measures underlies a wide range of biomedical applications. Traditional protein search methods rely on a pairwise dissimilarity/similarity measure for comparing a pair of proteins. This kind of pairwise measures suffer from the limitation of neglecting the distribution of other proteins and thus cannot satisfy the need for high accuracy of the retrieval systems. Recent work in the machine learning community has shown that exploiting the global structure of the database and learning the contextual dissimilarity/similarity measures can improve the retrieval performance significantly. However, most existing contextual dissimilarity/similarity learning algorithms work in an unsupervised manner, which does not utilize the information of the known class labels of proteins in the database.Results: In this paper, we propose a novel protein-protein dissimilarity learning algorithm, ProDis-ContSHC. ProDis-ContSHC regularizes an existing dissimilarity measure dij by considering the contextual information of the proteins. The context of a protein is defined by its neighboring proteins. The basic idea is, for a pair of proteins (i, j), if their context N (i) and N (j) is similar to each other, the two proteins should also have a high similarity. We implement this idea by regularizing dij by a factor learned from the context N (i) and N (j). Moreover, we divide the context to hierarchial sub-context and get the contextual dissimilarity vector for each protein pair. Using the class label information of the proteins, we select the relevant (a pair of proteins that has the same class labels) and irrelevant (with different labels) protein pairs, and train an SVM model to distinguish between their contextual dissimilarity vectors. The SVM model is further used to learn a supervised regularizing factor. Finally, with the new Supervised learned Dissimilarity measure, we update

Targeting protein-protein interaction between MLL1 and reciprocal proteins for leukemia therapy.

Science.gov (United States)

Wang, Zhi-Hui; Li, Dong-Dong; Chen, Wei-Lin; You, Qi-Dong; Guo, Xiao-Ke

2018-01-15

The mixed lineage leukemia protein-1 (MLL1), as a lysine methyltransferase, predominantly regulates the methylation of histone H3 lysine 4 (H3K4) and functions in hematopoietic stem cell (HSC) self-renewal. MLL1 gene fuses with partner genes that results in the generation of MLL1 fusion proteins (MLL1-FPs), which are frequently detected in acute leukemia. In the progress of leukemogenesis, a great deal of proteins cooperate with MLL1 to form multiprotein complexes serving for the dysregulation of H3K4 methylation, the overexpression of homeobox (HOX) cluster genes, and the consequent generation of leukemia. Hence, disrupting the interactions between MLL1 and the reciprocal proteins has been considered to be a new treatment strategy for leukemia. Here, we reviewed potential protein-protein interactions (PPIs) between MLL1 and its reciprocal proteins, and summarized the inhibitors to target MLL1 PPIs. The druggability of MLL1 PPIs for leukemia were also discussed. Copyright © 2017. Published by Elsevier Ltd.

Mobile geographic information system solution for pavement condition surveys [summary].

Science.gov (United States)

2012-01-01

The State Materials Office (SMO) of the Florida : Department of Transportation (FDOT) performs : annual Pavement Condition Surveys (PCS) of : the Departments extensive pavement network. : This work is performed by single-person crews in : inertial...

Protein kinase substrate identification on functional protein arrays

Directory of Open Access Journals (Sweden)

Zhou Fang

2008-02-01

Full Text Available Abstract Background Over the last decade, kinases have emerged as attractive therapeutic targets for a number of different diseases, and numerous high throughput screening efforts in the pharmaceutical community are directed towards discovery of compounds that regulate kinase function. The emerging utility of systems biology approaches has necessitated the development of multiplex tools suitable for proteomic-scale experiments to replace lower throughput technologies such as mass spectroscopy for the study of protein phosphorylation. Recently, a new approach for identifying substrates of protein kinases has applied the miniaturized format of functional protein arrays to characterize phosphorylation for thousands of candidate protein substrates in a single experiment. This method involves the addition of protein kinases in solution to arrays of immobilized proteins to identify substrates using highly sensitive radioactive detection and hit identification algorithms. Results To date, the factors required for optimal performance of protein array-based kinase substrate identification have not been described. In the current study, we have carried out a detailed characterization of the protein array-based method for kinase substrate identification, including an examination of the effects of time, buffer compositions, and protein concentration on the results. The protein array approach was compared to standard solution-based assays for assessing substrate phosphorylation, and a correlation of greater than 80% was observed. The results presented here demonstrate how novel substrates for protein kinases can be quickly identified from arrays containing thousands of human proteins to provide new clues to protein kinase function. In addition, a pooling-deconvolution strategy was developed and applied that enhances characterization of specific kinase-substrate relationships and decreases reagent consumption. Conclusion Functional protein microarrays are an

Protein kinesis: The dynamics of protein trafficking and stability

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-31

The purpose of this conference is to provide a multidisciplinary forum for exchange of state-of-the-art information on protein kinesis. This volume contains abstracts of papers in the following areas: protein folding and modification in the endoplasmic reticulum; protein trafficking; protein translocation and folding; protein degradation; polarity; nuclear trafficking; membrane dynamics; and protein import into organelles.

Sealing of thermally-sprayed stainless steel coatings against corrosion using nickel electroplating technique

Directory of Open Access Journals (Sweden)

Hathaipat Koiprasert

2007-07-01

Full Text Available Electric arc spraying (EAS is one of the thermal spray techniques used for restoration and to providecorrosion resistance. It can be utilized to build up coatings to thicknesses of several millimeters, It is easy to use on-site. Most importantly, the cost of this technique is lower than other thermal spraying techniques thatmay be suitable for part restoration. A major disadvantage associated with the electric arc sprayed coating is its high porosity, which can be as high as 3-8% making it not appropriate for use in immersion condition. This work was carried out around the idea of using electroplating to seal off the pore of the EAS coating, with an aim to improve the corrosion resistance of the coating in immersion condition. This research compared the corrosion behavior of a stainless steel 316 electric arc sprayed coating in 2M NaOH solution at 25oC. It was found that the Ni plating used as sealant can improve the corrosion resistance of the EAS coating. Furthermore, the smoothened and plated stainless steel 316 coating has a better corrosion resistance than the plated EAS coating that was not ground to smoothen the surface before plating.

PENERAPAN METODE SELEKSI FITUR UNTUK MENINGKATKAN HASIL DIAGNOSIS KANKER PAYUDARA

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Elvira Sukma Wahyuni

2016-04-01

Full Text Available Tujuan utama penelitian ini adalah untuk meningkatkan peforma klasifikasi pada diagnosis kanker payudara dengan menerapkan seleksi fitur pada beberapa algoritme klasifikasi. Penelitian ini menggunakan database kanker payudara Wisconsin Breast Cancer Database (WBCD. Metode seleksi fitur F-score dan Rough Set akan dipasangkan dengan beberapa algoritme klasifikasi yaitu SMO (Sequential Minimal Optimization, Naive Bayes, Multi layer Perceptron, dan C4.5. Penelitian ini menggunakan 10 fold cross validation sebagai metode evaluasi. Hasil penelitian menunjukkan algoritme klasifikasi MLP dan C4.5 mengalami peningkatan peforma klasifikasi secara signifikan setelah dipasangkan dengan seleksi fitur rough set dan F-score, Naive Bayes menunjukan peforma terbaik ketika dipasangkan dengan metode seleksi fitur F-score saja, sedangkan SMO tidak menunjukkan peningkatan peforma klasifikas ketika dipasangkan pada kedua seleksi fitur. Kata kunci: kanker payudara, seleksi fitur, klasifikasi.

Agua y experiencia espiritual. Los jardines de letrados en China

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Caroline Alder

2007-10-01

Es importante precisar que todas estas formas de shanshui están íntimamente relacionadas con las principales corrientes filosófico-religiosas chinas que son el confucianismo, el taoísmo y el budismo. En efecto, si el taoísmo postula que el orden cósmico está regido por dos fuerzas opuestas y complementarias, el yin y el yang, el paisaje, al ser considerado como una visión cultural del mundo y por ende de la naturaleza, considera como elementos fundamentales la montaña y el agua. La montaña, elemento yang, masculino, estático y luminoso y el agua, elemento yin, femenino, dinámico y obscuro. Estos dos elementos aparecen siempre juntos en las distintas formas de expresión del paisaje chino.

El placer secreto

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Günter Jursch

2004-04-01

Full Text Available Muchas enfermedades crónicas tienen un componente psicosomático. En estos casos considero más apropiado aplicar la concepción del Lejano Oriente (p. e. Taoísmo y Budismo, por ser más cercana a la realidad que la concepción occidental (influida por el cristianismo, el judaísmo y el Islam. Aplicando el punto de vista de Oriente, busco el elemento positivo en la región en la que predomina lo malo, el punto blanco en el campo negro de la enfermedad. Este elemento positivo en el campo de la enfermedad muchas veces es un placer secreto, una alegría secreta o una ventaja que se obtiene o se espera obtener mediante la enfermedad.

Characterization of primary cilia and Hedgehog signaling during development of the human pancreas and in human pancreatic duct cancer cell lines

DEFF Research Database (Denmark)

Nielsen, Sonja K; Møllgård, Kjeld; Clement, Christian A

2008-01-01

Hedgehog (Hh) signaling controls pancreatic development and homeostasis; aberrant Hh signaling is associated with several pancreatic diseases. Here we investigated the link between Hh signaling and primary cilia in the human developing pancreatic ducts and in cultures of human pancreatic duct...... adenocarcinoma cell lines, PANC-1 and CFPAC-1. We show that the onset of Hh signaling from human embryogenesis to fetal development is associated with accumulation of Hh signaling components Smo and Gli2 in duct primary cilia and a reduction of Gli3 in the duct epithelium. Smo, Ptc, and Gli2 localized to primary...... cilia of PANC-1 and CFPAC-1 cells, which may maintain high levels of nonstimulated Hh pathway activity. These findings indicate that primary cilia are involved in pancreatic development and postnatal tissue homeostasis....

HKC: An Algorithm to Predict Protein Complexes in Protein-Protein Interaction Networks

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Xiaomin Wang

2011-01-01

Full Text Available With the availability of more and more genome-scale protein-protein interaction (PPI networks, research interests gradually shift to Systematic Analysis on these large data sets. A key topic is to predict protein complexes in PPI networks by identifying clusters that are densely connected within themselves but sparsely connected with the rest of the network. In this paper, we present a new topology-based algorithm, HKC, to detect protein complexes in genome-scale PPI networks. HKC mainly uses the concepts of highest k-core and cohesion to predict protein complexes by identifying overlapping clusters. The experiments on two data sets and two benchmarks show that our algorithm has relatively high F-measure and exhibits better performance compared with some other methods.

Molecular tweezers modulate 14-3-3 protein-protein interactions

Science.gov (United States)

Bier, David; Rose, Rolf; Bravo-Rodriguez, Kenny; Bartel, Maria; Ramirez-Anguita, Juan Manuel; Dutt, Som; Wilch, Constanze; Klärner, Frank-Gerrit; Sanchez-Garcia, Elsa; Schrader, Thomas; Ottmann, Christian

2013-03-01

Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions.

Changes in protein composition and protein phosphorylation during ...

African Journals Online (AJOL)

Changes in protein profiles and protein phosphorylation were studied in various stages of germinating somatic and zygotic embryos. Many proteins, which were expressed in cotyledonary stage somatic embryos, were also present in the zygotic embryos obtained from mature dry seed. The intensity of 22 kDa protein was ...

An ontology-based search engine for protein-protein interactions.

Science.gov (United States)

Park, Byungkyu; Han, Kyungsook

2010-01-18

Keyword matching or ID matching is the most common searching method in a large database of protein-protein interactions. They are purely syntactic methods, and retrieve the records in the database that contain a keyword or ID specified in a query. Such syntactic search methods often retrieve too few search results or no results despite many potential matches present in the database. We have developed a new method for representing protein-protein interactions and the Gene Ontology (GO) using modified Gödel numbers. This representation is hidden from users but enables a search engine using the representation to efficiently search protein-protein interactions in a biologically meaningful way. Given a query protein with optional search conditions expressed in one or more GO terms, the search engine finds all the interaction partners of the query protein by unique prime factorization of the modified Gödel numbers representing the query protein and the search conditions. Representing the biological relations of proteins and their GO annotations by modified Gödel numbers makes a search engine efficiently find all protein-protein interactions by prime factorization of the numbers. Keyword matching or ID matching search methods often miss the interactions involving a protein that has no explicit annotations matching the search condition, but our search engine retrieves such interactions as well if they satisfy the search condition with a more specific term in the ontology.

Water-Protein Interactions: The Secret of Protein Dynamics

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Silvia Martini

2013-01-01

Full Text Available Water-protein interactions help to maintain flexible conformation conditions which are required for multifunctional protein recognition processes. The intimate relationship between the protein surface and hydration water can be analyzed by studying experimental water properties measured in protein systems in solution. In particular, proteins in solution modify the structure and the dynamics of the bulk water at the solute-solvent interface. The ordering effects of proteins on hydration water are extended for several angstroms. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on the analysis of the effects of protein-solvent interactions on water protons NMR relaxation parameters. NMR relaxation parameters, especially the nonselective (R1NS and selective (R1SE spin-lattice relaxation rates of water protons, are useful for investigating the solvent dynamics at the macromolecule-solvent interfaces as well as the perturbation effects caused by the water-macromolecule interactions on the solvent dynamical properties. In this paper we demonstrate that Nuclear Magnetic Resonance Spectroscopy can be used to determine the dynamical contributions of proteins to the water molecules belonging to their hydration shells.

Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle*

Science.gov (United States)

Roy Choudhury, Swarup; Westfall, Corey S.; Laborde, John P.; Bisht, Naveen C.; Jez, Joseph M.; Pandey, Sona

2012-01-01

Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS) proteins, which accelerate the inherent GTPase activity of Gα proteins, are common in animals and encoded by large gene families; however, in plants G-protein signaling is thought to be more limited in scope. For example, Arabidopsis thaliana contains one Gα, one Gβ, three Gγ, and one RGS protein. Recent examination of the Glycine max (soybean) genome reveals a larger set of G-protein-related genes and raises the possibility of more intricate G-protein networks than previously observed in plants. Stopped-flow analysis of GTP-binding and GDP/GTP exchange for the four soybean Gα proteins (GmGα1–4) reveals differences in their kinetic properties. The soybean genome encodes two chimeric RGS proteins with an N-terminal seven transmembrane domain and a C-terminal RGS box. Both GmRGS interact with each of the four GmGα and regulate their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ for each GmGα, suggesting more than one possible rate of the G-protein cycle initiated by each of the Gα proteins. The differential effects of GmRGS1 and GmRGS2 on GmGα1–4 result from a single valine versus alanine difference. The emerging picture suggests complex regulation of the G-protein cycle in soybean and in other plants with expanded G-protein networks. PMID:22474294

Alignment of non-covalent interactions at protein-protein interfaces.

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Hongbo Zhu

Full Text Available BACKGROUND: The study and comparison of protein-protein interfaces is essential for the understanding of the mechanisms of interaction between proteins. While there are many methods for comparing protein structures and protein binding sites, so far no methods have been reported for comparing the geometry of non-covalent interactions occurring at protein-protein interfaces. METHODOLOGY/PRINCIPAL FINDINGS: Here we present a method for aligning non-covalent interactions between different protein-protein interfaces. The method aligns the vector representations of van der Waals interactions and hydrogen bonds based on their geometry. The method has been applied to a dataset which comprises a variety of protein-protein interfaces. The alignments are consistent to a large extent with the results obtained using two other complementary approaches. In addition, we apply the method to three examples of protein mimicry. The method successfully aligns respective interfaces and allows for recognizing conserved interface regions. CONCLUSIONS/SIGNIFICANCE: The Galinter method has been validated in the comparison of interfaces in which homologous subunits are involved, including cases of mimicry. The method is also applicable to comparing interfaces involving non-peptidic compounds. Galinter assists users in identifying local interface regions with similar patterns of non-covalent interactions. This is particularly relevant to the investigation of the molecular basis of interaction mimicry.

The Ser/Thr Protein Kinase Protein-Protein Interaction Map of M. tuberculosis.

Science.gov (United States)

Wu, Fan-Lin; Liu, Yin; Jiang, He-Wei; Luan, Yi-Zhao; Zhang, Hai-Nan; He, Xiang; Xu, Zhao-Wei; Hou, Jing-Li; Ji, Li-Yun; Xie, Zhi; Czajkowsky, Daniel M; Yan, Wei; Deng, Jiao-Yu; Bi, Li-Jun; Zhang, Xian-En; Tao, Sheng-Ce

2017-08-01

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, the leading cause of death among all infectious diseases. There are 11 eukaryotic-like serine/threonine protein kinases (STPKs) in Mtb, which are thought to play pivotal roles in cell growth, signal transduction and pathogenesis. However, their underlying mechanisms of action remain largely uncharacterized. In this study, using a Mtb proteome microarray, we have globally identified the binding proteins in Mtb for all of the STPKs, and constructed the first STPK protein interaction (KPI) map that includes 492 binding proteins and 1,027 interactions. Bioinformatics analysis showed that the interacting proteins reflect diverse functions, including roles in two-component system, transcription, protein degradation, and cell wall integrity. Functional investigations confirmed that PknG regulates cell wall integrity through key components of peptidoglycan (PG) biosynthesis, e.g. MurC. The global STPK-KPIs network constructed here is expected to serve as a rich resource for understanding the key signaling pathways in Mtb, thus facilitating drug development and effective control of Mtb. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Protein-protein interaction site predictions with three-dimensional probability distributions of interacting atoms on protein surfaces.

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Ching-Tai Chen

Full Text Available Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins and were tested on an independent dataset (consisting of 142 proteins. The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted

Protein-Protein Interaction Site Predictions with Three-Dimensional Probability Distributions of Interacting Atoms on Protein Surfaces

Science.gov (United States)

Chen, Ching-Tai; Peng, Hung-Pin; Jian, Jhih-Wei; Tsai, Keng-Chang; Chang, Jeng-Yih; Yang, Ei-Wen; Chen, Jun-Bo; Ho, Shinn-Ying; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with

Bioinformatic Prediction of WSSV-Host Protein-Protein Interaction

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Zheng Sun

2014-01-01

Full Text Available WSSV is one of the most dangerous pathogens in shrimp aquaculture. However, the molecular mechanism of how WSSV interacts with shrimp is still not very clear. In the present study, bioinformatic approaches were used to predict interactions between proteins from WSSV and shrimp. The genome data of WSSV (NC_003225.1 and the constructed transcriptome data of F. chinensis were used to screen potentially interacting proteins by searching in protein interaction databases, including STRING, Reactome, and DIP. Forty-four pairs of proteins were suggested to have interactions between WSSV and the shrimp. Gene ontology analysis revealed that 6 pairs of these interacting proteins were classified into “extracellular region” or “receptor complex” GO-terms. KEGG pathway analysis showed that they were involved in the “ECM-receptor interaction pathway.” In the 6 pairs of interacting proteins, an envelope protein called “collagen-like protein” (WSSV-CLP encoded by an early virus gene “wsv001” in WSSV interacted with 6 deduced proteins from the shrimp, including three integrin alpha (ITGA, two integrin beta (ITGB, and one syndecan (SDC. Sequence analysis on WSSV-CLP, ITGA, ITGB, and SDC revealed that they possessed the sequence features for protein-protein interactions. This study might provide new insights into the interaction mechanisms between WSSV and shrimp.

Research Article Special Issue

African Journals Online (AJOL)

pc

2018-05-01

May 1, 2018 ... Author Correspondence, e-mail: dr.abosaad@gmail.com ... The theory and practice of CF algorithms designed decisions regarding rating .... PART [20], Naïve Bayes (NB) [20] and Sequential Minimal Optimization (SMO) [20].

Protein subcellular localization assays using split fluorescent proteins

Science.gov (United States)

Waldo, Geoffrey S [Santa Fe, NM; Cabantous, Stephanie [Los Alamos, NM

2009-09-08

The invention provides protein subcellular localization assays using split fluorescent protein systems. The assays are conducted in living cells, do not require fixation and washing steps inherent in existing immunostaining and related techniques, and permit rapid, non-invasive, direct visualization of protein localization in living cells. The split fluorescent protein systems used in the practice of the invention generally comprise two or more self-complementing fragments of a fluorescent protein, such as GFP, wherein one or more of the fragments correspond to one or more beta-strand microdomains and are used to "tag" proteins of interest, and a complementary "assay" fragment of the fluorescent protein. Either or both of the fragments may be functionalized with a subcellular targeting sequence enabling it to be expressed in or directed to a particular subcellular compartment (i.e., the nucleus).

Human cancer protein-protein interaction network: a structural perspective.

Directory of Open Access Journals (Sweden)

Gozde Kar

2009-12-01

Full Text Available Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network. The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%. We illustrate the interface related affinity properties of two cancer-related hub

Hot-spot analysis for drug discovery targeting protein-protein interactions.

Science.gov (United States)

Rosell, Mireia; Fernández-Recio, Juan

2018-04-01

Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.

Interaction between plate make and protein in protein crystallisation screening.

Directory of Open Access Journals (Sweden)

Gordon J King

Full Text Available BACKGROUND: Protein crystallisation screening involves the parallel testing of large numbers of candidate conditions with the aim of identifying conditions suitable as a starting point for the production of diffraction quality crystals. Generally, condition screening is performed in 96-well plates. While previous studies have examined the effects of protein construct, protein purity, or crystallisation condition ingredients on protein crystallisation, few have examined the effect of the crystallisation plate. METHODOLOGY/PRINCIPAL FINDINGS: We performed a statistically rigorous examination of protein crystallisation, and evaluated interactions between crystallisation success and plate row/column, different plates of same make, different plate makes and different proteins. From our analysis of protein crystallisation, we found a significant interaction between plate make and the specific protein being crystallised. CONCLUSIONS/SIGNIFICANCE: Protein crystal structure determination is the principal method for determining protein structure but is limited by the need to produce crystals of the protein under study. Many important proteins are difficult to crystallize, so that identification of factors that assist crystallisation could open up the structure determination of these more challenging targets. Our findings suggest that protein crystallisation success may be improved by matching a protein with its optimal plate make.

Protein Charge and Mass Contribute to the Spatio-temporal Dynamics of Protein-Protein Interactions in a Minimal Proteome

Science.gov (United States)

Xu, Yu; Wang, Hong; Nussinov, Ruth; Ma, Buyong

2013-01-01

We constructed and simulated a ‘minimal proteome’ model using Langevin dynamics. It contains 206 essential protein types which were compiled from the literature. For comparison, we generated six proteomes with randomized concentrations. We found that the net charges and molecular weights of the proteins in the minimal genome are not random. The net charge of a protein decreases linearly with molecular weight, with small proteins being mostly positively charged and large proteins negatively charged. The protein copy numbers in the minimal genome have the tendency to maximize the number of protein-protein interactions in the network. Negatively charged proteins which tend to have larger sizes can provide large collision cross-section allowing them to interact with other proteins; on the other hand, the smaller positively charged proteins could have higher diffusion speed and are more likely to collide with other proteins. Proteomes with random charge/mass populations form less stable clusters than those with experimental protein copy numbers. Our study suggests that ‘proper’ populations of negatively and positively charged proteins are important for maintaining a protein-protein interaction network in a proteome. It is interesting to note that the minimal genome model based on the charge and mass of E. Coli may have a larger protein-protein interaction network than that based on the lower organism M. pneumoniae. PMID:23420643

Prediction of heterodimeric protein complexes from weighted protein-protein interaction networks using novel features and kernel functions.

Directory of Open Access Journals (Sweden)

Peiying Ruan

Full Text Available Since many proteins express their functional activity by interacting with other proteins and forming protein complexes, it is very useful to identify sets of proteins that form complexes. For that purpose, many prediction methods for protein complexes from protein-protein interactions have been developed such as MCL, MCODE, RNSC, PCP, RRW, and NWE. These methods have dealt with only complexes with size of more than three because the methods often are based on some density of subgraphs. However, heterodimeric protein complexes that consist of two distinct proteins occupy a large part according to several comprehensive databases of known complexes. In this paper, we propose several feature space mappings from protein-protein interaction data, in which each interaction is weighted based on reliability. Furthermore, we make use of prior knowledge on protein domains to develop feature space mappings, domain composition kernel and its combination kernel with our proposed features. We perform ten-fold cross-validation computational experiments. These results suggest that our proposed kernel considerably outperforms the naive Bayes-based method, which is the best existing method for predicting heterodimeric protein complexes.

NMR Studies of Protein Hydration and Protein-Ligand Interactions

Science.gov (United States)

Chong, Yuan

Water on the surface of a protein is called hydration water. Hydration water is known to play a crucial role in a variety of biological processes including protein folding, enzymatic activation, and drug binding. Although the significance of hydration water has been recognized, the underlying mechanism remains far from being understood. This dissertation employs a unique in-situ nuclear magnetic resonance (NMR) technique to study the mechanism of protein hydration and the role of hydration in alcohol-protein interactions. Water isotherms in proteins are measured at different temperatures via the in-situ NMR technique. Water is found to interact differently with hydrophilic and hydrophobic groups on the protein. Water adsorption on hydrophilic groups is hardly affected by the temperature, while water adsorption on hydrophobic groups strongly depends on the temperature around 10 C, below which the adsorption is substantially reduced. This effect is induced by the dramatic decrease in the protein flexibility below 10 C. Furthermore, nanosecond to microsecond protein dynamics and the free energy, enthalpy, and entropy of protein hydration are studied as a function of hydration level and temperature. A crossover at 10 C in protein dynamics and thermodynamics is revealed. The effect of water at hydrophilic groups on protein dynamics and thermodynamics shows little temperature dependence, whereas water at hydrophobic groups has stronger effect above 10 C. In addition, I investigate the role of water in alcohol binding to the protein using the in-situ NMR detection. The isotherms of alcohols are first measured on dry proteins, then on proteins with a series of controlled hydration levels. The free energy, enthalpy, and entropy of alcohol binding are also determined. Two distinct types of alcohol binding are identified. On the one hand, alcohols can directly bind to a few specific sites on the protein. This type of binding is independent of temperature and can be

Mapping monomeric threading to protein-protein structure prediction.

Science.gov (United States)

Guerler, Aysam; Govindarajoo, Brandon; Zhang, Yang

2013-03-25

The key step of template-based protein-protein structure prediction is the recognition of complexes from experimental structure libraries that have similar quaternary fold. Maintaining two monomer and dimer structure libraries is however laborious, and inappropriate library construction can degrade template recognition coverage. We propose a novel strategy SPRING to identify complexes by mapping monomeric threading alignments to protein-protein interactions based on the original oligomer entries in the PDB, which does not rely on library construction and increases the efficiency and quality of complex template recognitions. SPRING is tested on 1838 nonhomologous protein complexes which can recognize correct quaternary template structures with a TM score >0.5 in 1115 cases after excluding homologous proteins. The average TM score of the first model is 60% and 17% higher than that by HHsearch and COTH, respectively, while the number of targets with an interface RMSD benchmark proteins. Although the relative performance of SPRING and ZDOCK depends on the level of homology filters, a combination of the two methods can result in a significantly higher model quality than ZDOCK at all homology thresholds. These data demonstrate a new efficient approach to quaternary structure recognition that is ready to use for genome-scale modeling of protein-protein interactions due to the high speed and accuracy.

DiffSLC: A graph centrality method to detect essential proteins of a protein-protein interaction network.

Science.gov (United States)

Mistry, Divya; Wise, Roger P; Dickerson, Julie A

2017-01-01

Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be

A credit-card library approach for disrupting protein-protein interactions.

Science.gov (United States)

Xu, Yang; Shi, Jin; Yamamoto, Noboru; Moss, Jason A; Vogt, Peter K; Janda, Kim D

2006-04-15

Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in human cancers. Myc belongs to the family of basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factors. It is biologically active only as heterodimer with the bHLH-ZIP protein Max. Herein, we report a new strategy for the disruption of protein-protein interactions that has been corroborated through the design and synthesis of a small parallel library composed of 'credit-card' compounds. These compounds are derived from a planar, aromatic scaffold and functionalized with four points of diversity. From a 285 membered library, several hits were obtained that disrupted the c-Myc-Max interaction and cellular functions of c-Myc. The IC50 values determined for this small focused library for the disruption of Myc-Max dimerization are quite potent, especially since small molecule antagonists of protein-protein interactions are notoriously difficult to find. Furthermore, several of the compounds were active at the cellular level as shown by their biological effects on Myc action in chicken embryo fibroblast assays. In light of our findings, this approach is considered a valuable addition to the armamentarium of new molecules being developed to interact with protein-protein interfaces. Finally, this strategy for disrupting protein-protein interactions should prove applicable to other families of proteins.

Protein Correlation Profiles Identify Lipid Droplet Proteins with High Confidence*

Science.gov (United States)

Krahmer, Natalie; Hilger, Maximiliane; Kory, Nora; Wilfling, Florian; Stoehr, Gabriele; Mann, Matthias; Farese, Robert V.; Walther, Tobias C.

2013-01-01

Lipid droplets (LDs) are important organelles in energy metabolism and lipid storage. Their cores are composed of neutral lipids that form a hydrophobic phase and are surrounded by a phospholipid monolayer that harbors specific proteins. Most well-established LD proteins perform important functions, particularly in cellular lipid metabolism. Morphological studies show LDs in close proximity to and interacting with membrane-bound cellular organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and endosomes. Because of these close associations, it is difficult to purify LDs to homogeneity. Consequently, the confident identification of bona fide LD proteins via proteomics has been challenging. Here, we report a methodology for LD protein identification based on mass spectrometry and protein correlation profiles. Using LD purification and quantitative, high-resolution mass spectrometry, we identified LD proteins by correlating their purification profiles to those of known LD proteins. Application of the protein correlation profile strategy to LDs isolated from Drosophila S2 cells led to the identification of 111 LD proteins in a cellular LD fraction in which 1481 proteins were detected. LD localization was confirmed in a subset of identified proteins via microscopy of the expressed proteins, thereby validating the approach. Among the identified LD proteins were both well-characterized LD proteins and proteins not previously known to be localized to LDs. Our method provides a high-confidence LD proteome of Drosophila cells and a novel approach that can be applied to identify LD proteins of other cell types and tissues. PMID:23319140

2018-05-18T00:45:00Z https://www.ajol.info/index.php/all/oai oai:ojs ...

African Journals Online (AJOL)

There is a dearth of knowledge about the smoking habit among adolescents and ... Across-sectional study involving 400 randomly selected subjects from the ... to a modified version of the standard WHO questionnaire (WHO/SMO, 1984) for ...

Welding of austenitic stainless steel with a high molybdenum content

International Nuclear Information System (INIS)

Liljas, A.; Holmberg, B.

1984-01-01

Welding of austenitic steel is discussed. Welding tests of AVESTA 250 SMO (six percent Mo) are reported. Welding without special additives can make the joints susceptible for corrosion in aggressive environments, e.g. sea water. (L.E.)

ProteinShop: A tool for interactive protein manipulation and steering

Energy Technology Data Exchange (ETDEWEB)

Crivelli, Silvia; Kreylos, Oliver; Max, Nelson; Hamann, Bernd; Bethel, Wes

2004-05-25

We describe ProteinShop, a new visualization tool that streamlines and simplifies the process of determining optimal protein folds. ProteinShop may be used at different stages of a protein structure prediction process. First, it can create protein configurations containing secondary structures specified by the user. Second, it can interactively manipulate protein fragments to achieve desired folds by adjusting the dihedral angles of selected coil regions using an Inverse Kinematics method. Last, it serves as a visual framework to monitor and steer a protein structure prediction process that may be running on a remote machine. ProteinShop was used to create initial configurations for a protein structure prediction method developed by a team that competed in CASP5. ProteinShop's use accelerated the process of generating initial configurations, reducing the time required from days to hours. This paper describes the structure of ProteinShop and discusses its main features.

Prioritizing disease candidate proteins in cardiomyopathy-specific protein-protein interaction networks based on "guilt by association" analysis.

Directory of Open Access Journals (Sweden)

Wan Li

Full Text Available The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial. Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on "guilt by association" analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on "guilt by association" analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.

Modular protein switches derived from antibody mimetic proteins.

Science.gov (United States)

Nicholes, N; Date, A; Beaujean, P; Hauk, P; Kanwar, M; Ostermeier, M

2016-02-01

Protein switches have potential applications as biosensors and selective protein therapeutics. Protein switches built by fusion of proteins with the prerequisite input and output functions are currently developed using an ad hoc process. A modular switch platform in which existing switches could be readily adapted to respond to any ligand would be advantageous. We investigated the feasibility of a modular protein switch platform based on fusions of the enzyme TEM-1 β-lactamase (BLA) with two different antibody mimetic proteins: designed ankyrin repeat proteins (DARPins) and monobodies. We created libraries of random insertions of the gene encoding BLA into genes encoding a DARPin or a monobody designed to bind maltose-binding protein (MBP). From these libraries, we used a genetic selection system for β-lactamase activity to identify genes that conferred MBP-dependent ampicillin resistance to Escherichia coli. Some of these selected genes encoded switch proteins whose enzymatic activity increased up to 14-fold in the presence of MBP. We next introduced mutations into the antibody mimetic domain of these switches that were known to cause binding to different ligands. To different degrees, introduction of the mutations resulted in switches with the desired specificity, illustrating the potential modularity of these platforms. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protein-protein interactions and cancer: targeting the central dogma.

Science.gov (United States)

Garner, Amanda L; Janda, Kim D

2011-01-01

Between 40,000 and 200,000 protein-protein interactions have been predicted to exist within the human interactome. As these interactions are of a critical nature in many important cellular functions and their dysregulation is causal of disease, the modulation of these binding events has emerged as a leading, yet difficult therapeutic arena. In particular, the targeting of protein-protein interactions relevant to cancer is of fundamental importance as the tumor-promoting function of several aberrantly expressed proteins in the cancerous state is directly resultant of its ability to interact with a protein-binding partner. Of significance, these protein complexes play a crucial role in each of the steps of the central dogma of molecular biology, the fundamental processes of genetic transmission. With the many important discoveries being made regarding the mechanisms of these genetic process, the identification of new chemical probes are needed to better understand and validate the druggability of protein-protein interactions related to the central dogma. In this review, we provide an overview of current small molecule-based protein-protein interaction inhibitors for each stage of the central dogma: transcription, mRNA splicing and translation. Importantly, through our analysis we have uncovered a lack of necessary probes targeting mRNA splicing and translation, thus, opening up the possibility for expansion of these fields.

Prognostic value of hedgehog signaling pathway in digestive system cancers: A systematic review and meta-analysis.

Science.gov (United States)

Wang, Yihan; Peng, Qian; Jia, Hongyuan; Du, Xiao

2016-01-01

The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent. This study aimed to investigate the association between Hh pathway components and survival outcomes in patients with digestive system cancers. We conducted a comprehensive retrieval in PubMed, EMBASE and Cochrane library for relevant literatures until May 1st, 2015. The pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) with 95% confidence intervals (CIs) were calculated to clarify the prognostic value of Hh pathway components, including Shh, Gli1, Gli2, Smo and Ptch1. A total of 16 eligible articles with 3222 patients were included in the meta-analysis. Pooled HR suggested that over-expression of Shh and Gli1 were both associated with poor OS (HR = 1.87, 95% CI: 1.14-3.07 and HR = 1.96, 95% CI: 1.66-2.32, respectively) and DFS (HR = 2.37, 95% CI: 1.19-4.72 and HR = 2.18, 95% CI: 1.61-2.96, respectively). In addition, over-expression of Smo was associated with poor DFS (HR = 1.38, 95% CI: 1.08-1.75). This study reveals that over-expressed Hh pathway components, including Shh, Gli1 and Smo, are associated with poor prognosis in digestive system cancer patients. Hh signaling pathway may become a potential therapeutic target in digestive system cancers.

Čisti život

Directory of Open Access Journals (Sweden)

Sanja Cimer

2016-06-01

Full Text Available Ne, kažem.Znam, kad kažem „ne“, to je to s nama, čist račun, rekli smo, karte na stolu, vino, keksi, humor – presuhi; klima, poljupci, zemlja za cvijeće – prevlažni. Dogovori umjesto sapunica kao kod drugih. Ne gubimo vrijeme na stvari koje nikoga ne zanimaju, čak ih ni na televiziji ne gledamo, nemamo televizor, imamo pametnijeg posla, i zabavljamo se jer znamo da se svijet ne može spasiti, mi smo spašeni samo privremeno, vremena je malo i nikada ne bismo skočili, ali osjećali smo se tako živima dok su nam se noge klatile preko ograde na terasi zgrade. Gledala sam vrhove svojih tenisica, stražnja svjetla automobila koji su se tamo dolje redali jedan za drugim poput crvenih mrava, gurali se u kolonama kroz uske ulice, noge mi još nikada nisu djelovale toliko kratko.Kao na moru na madracu na napuhavanje, rekla sam i ugrizla se za jezik, koji je viski razvezao jer nisi izgledao kao da imaš madrac na napuhavanje.Samo te voda nosi kad padneš, objasnio si, zrak te ne nosi, a ipak si bio tako siguran u sebe, nikad nisi pogledao dolje, nikad se osvrnuo da pogledaš zabavu koju ostavljaš za sobom, nisi ništa propustio niti se ičega bojao, pa ni neoprezna tapšanja po leđima.

Targeting protein-protein interactions for parasite control.

Directory of Open Access Journals (Sweden)

Christina M Taylor

2011-04-01

Full Text Available Finding new drug targets for pathogenic infections would be of great utility for humanity, as there is a large need to develop new drugs to fight infections due to the developing resistance and side effects of current treatments. Current drug targets for pathogen infections involve only a single protein. However, proteins rarely act in isolation, and the majority of biological processes occur via interactions with other proteins, so protein-protein interactions (PPIs offer a realm of unexplored potential drug targets and are thought to be the next-generation of drug targets. Parasitic worms were chosen for this study because they have deleterious effects on human health, livestock, and plants, costing society billions of dollars annually and many sequenced genomes are available. In this study, we present a computational approach that utilizes whole genomes of 6 parasitic and 1 free-living worm species and 2 hosts. The species were placed in orthologous groups, then binned in species-specific orthologous groups. Proteins that are essential and conserved among species that span a phyla are of greatest value, as they provide foundations for developing broad-control strategies. Two PPI databases were used to find PPIs within the species specific bins. PPIs with unique helminth proteins and helminth proteins with unique features relative to the host, such as indels, were prioritized as drug targets. The PPIs were scored based on RNAi phenotype and homology to the PDB (Protein DataBank. EST data for the various life stages, GO annotation, and druggability were also taken into consideration. Several PPIs emerged from this study as potential drug targets. A few interactions were supported by co-localization of expression in M. incognita (plant parasite and B. malayi (H. sapiens parasite, which have extremely different modes of parasitism. As more genomes of pathogens are sequenced and PPI databases expanded, this methodology will become increasingly

ProteinHistorian: tools for the comparative analysis of eukaryote protein origin.

Directory of Open Access Journals (Sweden)

John A Capra

Full Text Available The evolutionary history of a protein reflects the functional history of its ancestors. Recent phylogenetic studies identified distinct evolutionary signatures that characterize proteins involved in cancer, Mendelian disease, and different ontogenic stages. Despite the potential to yield insight into the cellular functions and interactions of proteins, such comparative phylogenetic analyses are rarely performed, because they require custom algorithms. We developed ProteinHistorian to make tools for performing analyses of protein origins widely available. Given a list of proteins of interest, ProteinHistorian estimates the phylogenetic age of each protein, quantifies enrichment for proteins of specific ages, and compares variation in protein age with other protein attributes. ProteinHistorian allows flexibility in the definition of protein age by including several algorithms for estimating ages from different databases of evolutionary relationships. We illustrate the use of ProteinHistorian with three example analyses. First, we demonstrate that proteins with high expression in human, compared to chimpanzee and rhesus macaque, are significantly younger than those with human-specific low expression. Next, we show that human proteins with annotated regulatory functions are significantly younger than proteins with catalytic functions. Finally, we compare protein length and age in many eukaryotic species and, as expected from previous studies, find a positive, though often weak, correlation between protein age and length. ProteinHistorian is available through a web server with an intuitive interface and as a set of command line tools; this allows biologists and bioinformaticians alike to integrate these approaches into their analysis pipelines. ProteinHistorian's modular, extensible design facilitates the integration of new datasets and algorithms. The ProteinHistorian web server, source code, and pre-computed ages for 32 eukaryotic genomes are

Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis.

Science.gov (United States)

He, J; Cooper, H M; Reyes, A; Di Re, M; Sembongi, H; Litwin, T R; Gao, J; Neuman, K C; Fearnley, I M; Spinazzola, A; Walker, J E; Holt, I J

2012-07-01

Mitochondrial ribosomes and translation factors co-purify with mitochondrial nucleoids of human cells, based on affinity protein purification of tagged mitochondrial DNA binding proteins. Among the most frequently identified proteins were ATAD3 and prohibitin, which have been identified previously as nucleoid components, using a variety of methods. Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. Altered ATAD3 expression also perturbs mtDNA maintenance and replication. These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they support nucleic acid complexes at the inner membrane of the mitochondrion.

Mobile geographic information system (GIS) solution for pavement condition surveys.

Science.gov (United States)

2012-06-28

This report discusses the design and implementation of a software-based solution that will improve the data collection processes during the Pavement Condition Surveys (PCS) conducted by the State Materials Office (SMO) of the Florida Department of Tr...

Annotating the protein-RNA interaction sites in proteins using evolutionary information and protein backbone structure.

Science.gov (United States)

Li, Tao; Li, Qian-Zhong

2012-11-07

RNA-protein interactions play important roles in various biological processes. The precise detection of RNA-protein interaction sites is very important for understanding essential biological processes and annotating the function of the proteins. In this study, based on various features from amino acid sequence and structure, including evolutionary information, solvent accessible surface area and torsion angles (φ, ψ) in the backbone structure of the polypeptide chain, a computational method for predicting RNA-binding sites in proteins is proposed. When the method is applied to predict RNA-binding sites in three datasets: RBP86 containing 86 protein chains, RBP107 containing 107 proteins chains and RBP109 containing 109 proteins chains, better sensitivities and specificities are obtained compared to previously published methods in five-fold cross-validation tests. In order to make further examination for the efficiency of our method, the RBP107 dataset is used as training set, RBP86 and RBP109 datasets are used as the independent test sets. In addition, as examples of our prediction, RNA-binding sites in a few proteins are presented. The annotated results are consistent with the PDB annotation. These results show that our method is useful for annotating RNA binding sites of novel proteins.

Evolutionary diversification of protein-protein interactions by interface add-ons.

Science.gov (United States)

Plach, Maximilian G; Semmelmann, Florian; Busch, Florian; Busch, Markus; Heizinger, Leonhard; Wysocki, Vicki H; Merkl, Rainer; Sterner, Reinhard

2017-10-03

Cells contain a multitude of protein complexes whose subunits interact with high specificity. However, the number of different protein folds and interface geometries found in nature is limited. This raises the question of how protein-protein interaction specificity is achieved on the structural level and how the formation of nonphysiological complexes is avoided. Here, we describe structural elements called interface add-ons that fulfill this function and elucidate their role for the diversification of protein-protein interactions during evolution. We identified interface add-ons in 10% of a representative set of bacterial, heteromeric protein complexes. The importance of interface add-ons for protein-protein interaction specificity is demonstrated by an exemplary experimental characterization of over 30 cognate and hybrid glutamine amidotransferase complexes in combination with comprehensive genetic profiling and protein design. Moreover, growth experiments showed that the lack of interface add-ons can lead to physiologically harmful cross-talk between essential biosynthetic pathways. In sum, our complementary in silico, in vitro, and in vivo analysis argues that interface add-ons are a practical and widespread evolutionary strategy to prevent the formation of nonphysiological complexes by specializing protein-protein interactions.

The interface of protein structure, protein biophysics, and molecular evolution

Science.gov (United States)

Liberles, David A; Teichmann, Sarah A; Bahar, Ivet; Bastolla, Ugo; Bloom, Jesse; Bornberg-Bauer, Erich; Colwell, Lucy J; de Koning, A P Jason; Dokholyan, Nikolay V; Echave, Julian; Elofsson, Arne; Gerloff, Dietlind L; Goldstein, Richard A; Grahnen, Johan A; Holder, Mark T; Lakner, Clemens; Lartillot, Nicholas; Lovell, Simon C; Naylor, Gavin; Perica, Tina; Pollock, David D; Pupko, Tal; Regan, Lynne; Roger, Andrew; Rubinstein, Nimrod; Shakhnovich, Eugene; Sjölander, Kimmen; Sunyaev, Shamil; Teufel, Ashley I; Thorne, Jeffrey L; Thornton, Joseph W; Weinreich, Daniel M; Whelan, Simon

2012-01-01

Abstract The interface of protein structural biology, protein biophysics, molecular evolution, and molecular population genetics forms the foundations for a mechanistic understanding of many aspects of protein biochemistry. Current efforts in interdisciplinary protein modeling are in their infancy and the state-of-the art of such models is described. Beyond the relationship between amino acid substitution and static protein structure, protein function, and corresponding organismal fitness, other considerations are also discussed. More complex mutational processes such as insertion and deletion and domain rearrangements and even circular permutations should be evaluated. The role of intrinsically disordered proteins is still controversial, but may be increasingly important to consider. Protein geometry and protein dynamics as a deviation from static considerations of protein structure are also important. Protein expression level is known to be a major determinant of evolutionary rate and several considerations including selection at the mRNA level and the role of interaction specificity are discussed. Lastly, the relationship between modeling and needed high-throughput experimental data as well as experimental examination of protein evolution using ancestral sequence resurrection and in vitro biochemistry are presented, towards an aim of ultimately generating better models for biological inference and prediction. PMID:22528593

Racemic & quasi-racemic protein crystallography enabled by chemical protein synthesis.

Science.gov (United States)

Kent, Stephen Bh

2018-04-04

A racemic protein mixture can be used to form centrosymmetric crystals for structure determination by X-ray diffraction. Both the unnatural d-protein and the corresponding natural l-protein are made by total chemical synthesis based on native chemical ligation-chemoselective condensation of unprotected synthetic peptide segments. Racemic protein crystallography is important for structure determination of the many natural protein molecules that are refractory to crystallization. Racemic mixtures facilitate the crystallization of recalcitrant proteins, and give diffraction-quality crystals. Quasi-racemic crystallization, using a single d-protein molecule, can facilitate the determination of the structures of a series of l-protein analog molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Družbena segregacija avtohtonih migrantov v Mehiki: primer mesta Monterrey

Directory of Open Access Journals (Sweden)

Arun Kumar Acharya

2012-01-01

Full Text Available Značilen pojav, ki ga lahko opazimo v Mehiki, je ruralno urbana migracija oziroma preseljevanje ljudi s podeželja v mesta. Zadnjih nekaj let se stopnja preseljevanja avtohtonih prebivalcev v mesta na severu Mehike, še zlasti v Monterrey, kjer iščejo zaposlitev, nenadzorovano veča. Ko migranti prispejo v to velemesto, imajo zaradi prikrite diskriminacije težave s prilagajanjem mestnemu okolju. Glavni argument in hipoteza tega članka je, da se ti ljudje sami družbeno izolirajo in segregirajo, ker se bojijo (kulturne in rasne diskriminacije in nasilja. Podatke za to študijo smo zbrali s pomočjo terenske raziskave, za katero smo leta 2009 in 2010 v Monterreyu intervjuvali 350 avtohtonih prebivalcev, ki so se tja priselili iz različnih krajev v Mehiki.

Frontal lobe oxygenation is maintained during hypotension following propofol-fentanyl anesthesia

DEFF Research Database (Denmark)

Nissen, P.; Lieshout, J.J. van; Nielsen, H.B.

2009-01-01

Near-infrared spectroscopy (NIRS) assesses cerebral oxygen saturation (Sco2) as a balance between cerebral oxygen delivery and consumption. In 71 patients, we evaluated whether marked reduction in mean arterial pressure (MAP) during propofol-fentanyl anesthesia induction affects frontal lobe Sco2....... The NIRS-determined arm muscle oxygenation (Smo2), heart rate (HR), and cardiac output (CO) were monitored, endtidal carbon dioxide tension was controlled at 3.5 to 4.5 kPa, and central blood volume was maintained. Before anesthesia, the median (range) MAP, HR, and CO were 93 mm Hg (61-126 mm Hg), 76 beats......, the median (range) NIRS-determined Smo2 also decreased (73% [54%-94%] to 71% [52%-87%]), whereas Sco2 increased from 67% (46%-93%) to 74% (48%-95%) (P anesthesia induction, variables recovered and remained at preanesthetic levels during surgery. The findings...

General protein-protein cross-linking.

Science.gov (United States)

Alegria-Schaffer, Alice

2014-01-01

This protocol describes a general protein-to-protein cross-linking procedure using the water-soluble amine-reactive homobifunctional BS(3) (bis[sulfosuccinimidyl] suberate); however, the protocol can be easily adapted using other cross-linkers of similar properties. BS(3) is composed of two sulfo-NHS ester groups and an 11.4 Å linker. Sulfo-NHS ester groups react with primary amines in slightly alkaline conditions (pH 7.2-8.5) and yield stable amide bonds. The reaction releases N-hydroxysuccinimide (see an application of NHS esters on Labeling a protein with fluorophores using NHS ester derivitization). © 2014 Elsevier Inc. All rights reserved.

Quality control methodology for high-throughput protein-protein interaction screening.

Science.gov (United States)

Vazquez, Alexei; Rual, Jean-François; Venkatesan, Kavitha

2011-01-01

Protein-protein interactions are key to many aspects of the cell, including its cytoskeletal structure, the signaling processes in which it is involved, or its metabolism. Failure to form protein complexes or signaling cascades may sometimes translate into pathologic conditions such as cancer or neurodegenerative diseases. The set of all protein interactions between the proteins encoded by an organism constitutes its protein interaction network, representing a scaffold for biological function. Knowing the protein interaction network of an organism, combined with other sources of biological information, can unravel fundamental biological circuits and may help better understand the molecular basics of human diseases. The protein interaction network of an organism can be mapped by combining data obtained from both low-throughput screens, i.e., "one gene at a time" experiments and high-throughput screens, i.e., screens designed to interrogate large sets of proteins at once. In either case, quality controls are required to deal with the inherent imperfect nature of experimental assays. In this chapter, we discuss experimental and statistical methodologies to quantify error rates in high-throughput protein-protein interactions screens.

Quantifying the molecular origins of opposite solvent effects on protein-protein interactions.

Directory of Open Access Journals (Sweden)

Vincent Vagenende

Full Text Available Although the nature of solvent-protein interactions is generally weak and non-specific, addition of cosolvents such as denaturants and osmolytes strengthens protein-protein interactions for some proteins, whereas it weakens protein-protein interactions for others. This is exemplified by the puzzling observation that addition of glycerol oppositely affects the association constants of two antibodies, D1.3 and D44.1, with lysozyme. To resolve this conundrum, we develop a methodology based on the thermodynamic principles of preferential interaction theory and the quantitative characterization of local protein solvation from molecular dynamics simulations. We find that changes of preferential solvent interactions at the protein-protein interface quantitatively account for the opposite effects of glycerol on the antibody-antigen association constants. Detailed characterization of local protein solvation in the free and associated protein states reveals how opposite solvent effects on protein-protein interactions depend on the extent of dewetting of the protein-protein contact region and on structural changes that alter cooperative solvent-protein interactions at the periphery of the protein-protein interface. These results demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions, and establish a general methodology for predicting and understanding solvent effects on protein-protein interactions in diverse biological environments.

Our interests in protein-protein interactions

Indian Academy of Sciences (India)

protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

Science.gov (United States)

Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Fairhurst, Rick M.; Rayner, Julian C.

2015-01-01

Background A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing full-length ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion. Methodology/Principal Findings We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naïve controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further

[Detection of protein-protein interactions by FRET and BRET methods].

Science.gov (United States)

Matoulková, E; Vojtěšek, B

2014-01-01

Nowadays, in vivo protein-protein interaction studies have become preferable detecting meth-ods that enable to show or specify (already known) protein interactions and discover their inhibitors. They also facilitate detection of protein conformational changes and discovery or specification of signaling pathways in living cells. One group of in vivo methods enabling these findings is based on fluorescent resonance energy transfer (FRET) and its bio-luminescent modification (BRET). They are based on visualization of protein-protein interactions via light or enzymatic excitation of fluorescent or bio-luminescent proteins. These methods allow not only protein localization within the cell or its organelles (or small animals) but they also allow us to quantify fluorescent signals and to discover weak or strong interaction partners. In this review, we explain the principles of FRET and BRET, their applications in the characterization of protein-protein interactions and we describe several findings using these two methods that clarify molecular and cellular mechanisms and signals related to cancer biology.

Protein degradation and protein synthesis in long-term memory formation

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Timothy J Jarome

2014-06-01

Full Text Available Long-term memory (LTM formation requires transient changes in the activity of intracellular signaling cascades that are thought to regulate new gene transcription and de novo protein synthesis in the brain. Consistent with this, protein synthesis inhibitors impair LTM for a variety of behavioral tasks when infused into the brain around the time of training or following memory retrieval, suggesting that protein synthesis is a critical step in LTM storage in the brain. However, evidence suggests that protein degradation mediated by the ubiquitin-proteasome system may also be a critical regulator of LTM formation and stability following retrieval. This requirement for increased protein degradation has been shown in the same brain regions in which protein synthesis is required for LTM storage. Additionally, increases in the phosphorylation of proteins involved in translational control parallel increases in protein polyubiquitination and the increased demand for protein degradation is regulated by intracellular signaling molecules thought to regulate protein synthesis during LTM formation. In some cases inhibiting proteasome activity can rescue memory impairments that result from pharmacological blockade of protein synthesis, suggesting that protein degradation may control the requirement for protein synthesis during the memory storage process. Results such as these suggest that protein degradation and synthesis are both critical for LTM formation and may interact to properly consolidate and store memories in the brain. Here, we review the evidence implicating protein synthesis and degradation in LTM storage and highlight the areas of overlap between these two opposing processes. We also discuss evidence suggesting these two processes may interact to properly form and store memories. LTM storage likely requires a coordinated regulation between protein degradation and synthesis at multiple sites in the mammalian brain.

Evolutionary reprograming of protein-protein interaction specificity.