Bad expression influences time to androgen escape in prostate cancer

<b>OBJECTIVE</b>: To assess the role of selected downstream Bcl-2 family members (Bad, Bax, Bcl-2 and Bcl-xL) in the development of androgen-independent prostate cancer (AIPC), as androgen-deprivation therapy is the treatment of choice in advanced prostate cancer, yet patients generally relapse and progress to an AI state within 18–24 months. <b>PATIENTS, MATERIALS AND METHODS</b>: The patient cohort was established by retrospectively selecting patients with prostate cancer who had an initial response to androgen-deprivation therapy, but subsequently relapsed with AIPC. In all, 58 patients with prostate cancer were included with matched androgen-dependent (AD) and AI prostate tumours available for immunohistochemical analysis; two independent observers using a weighted-histoscore method scored the staining. Changes in Bad, Bax, Bcl-2 and Bcl-xL expression during transition to AIPC were evaluated and then correlated to known clinical variables. <b>RESULTS</b>: High Bad expression in AD tumours was associated with an increased time to biochemical relapse (<i>P</i> = 0.007) and a trend towards improved overall survival (<i>P</i> = 0.053). There were also trends towards a decrease in Bad (<i>P</i> = 0.068) and Bax (<i>P</i> = 0.055) expression with progression to AIPC. There were no significant results for Bcl-2 or Bcl-xL. <b>CONCLUSION</b>: There is evidence to suggest that Bad expression levels at diagnosis influence time to biochemical relapse and overall survival, and that levels of pro-apoptotic proteins Bad and Bax fall during AIPC development. Bad might therefore represent a possible positive prognostic marker and potential therapeutic target for AIPC in the future

Componential coding in the condition monitoring of electrical machines Part 2: application to a conventional machine and a novel machine

This paper (Part 2) presents the practical application of componential coding, the principles of which were described in the accompanying Part 1 paper. Four major issues are addressed, including optimization of the neural network, assessment of the anomaly detection results, development of diagnostic approaches (based on the reconstruction error) and also benchmarking of componential coding with other techniques (including waveform measures, Fourier-based signal reconstruction and principal component analysis). This is achieved by applying componential coding to the data monitored from both a conventional induction motor and from a novel transverse flux motor. The results reveal that machine condition monitoring using componential coding is not only capable of detecting and then diagnosing anomalies but it also outperforms other conventional techniques in that it is able to separate very small and localized anomalies

Surrogate-based optimization of tidal turbine arrays: a case study for the Faro-Olhão inlet

This paper presents a study for estimating the size of a tidal turbine array for the Faro-Olhão Inlet (Potugal) using a surrogate optimization approach. The method compromises problem formulation, hydro-morphodynamic modelling, surrogate construction and validation, and constraint optimization. A total of 26 surrogates were built using linear RBFs as a function of two design variables: number of rows in the array and Tidal Energy Converters (TECs) per row. Surrogates describe array performance and environmental effects associated with hydrodynamic and morphological aspects of the multi inlet lagoon. After validation, surrogate models were used to formulate a constraint optimization model. Results evidence that the largest array size that satisfies performance and environmental constraints is made of 3 rows and 10 TECs per row.Eduardo González-Gorbeña has received funding for the OpTiCA project (http://msca-optica.eu/) from the Marie Skłodowska-Curie Actions of the European Union's H2020-MSCA-IF-EF-RI-2016 / GA#: 748747. The paper is a contribution to the SCORE pro-ject, funded by the Portuguese Foundation for Science and Technology (FCT–PTDC/AAG-TEC/1710/2014). André Pacheco was supported by the Portuguese Foun-dation for Science and Technology under the Portuguese Researchers’ Programme 2014 entitled “Exploring new concepts for extracting energy from tides” (IF/00286/2014/CP1234).info:eu-repo/semantics/publishedVersio

In Situ Hybridization and Monoclonal Antibody Analysis of Plasma Membrane Ca-Pump mRNA and Protein in Submandibular Glands of Rabbit, Rat and Man

The degree of supersaturation of saliva with calcium (Ca) is related to the mineral phase of enamel in erupted teeth, the incidence of caries, and the formation of calculus. The mechanisms for regulating salivary Ca concentration are therefore of relevance to dentistry. Sections of rabbit, rat and human submandibular gland (SMG) were processed for immuno-histochemistry with a specific anti-plasma membrane Ca-pump antibody, 5F10. Western blots confirm that the molecular weight of the proteins identified by our antibody (135 kDa) is consistent with an appropriate molecular weight for PMCA antigen (135-150 kDa). Tissue sections were also processed for in situ hybridization to study the distribution of the PMCA mRNA isoforms. In mammals, the PMCAl gene is reported to code for a PMCA protein with a role in maintaining the intracellular Ca levels in both epithelial and non-epithelial cells. Other genes including the PMCA2 and PMCA4 genes may code for PMCA proteins specific to Ca transporting tissues. Our studies demonstrate cytoplasmic labeling of PMCA mRNA with hPMCA-1 and hPMCA-4 specific cDNA probes in humans, and rPMCA-1 and rPMCA-2 specific oligonucleotide probes in rats. Labeling of PMCA protein and all mRNA isoforms was found in the cytoplasm of the interlobular and intralobular ducts (except for intercalated ducts). The demonstrated presence of PMCA in SMGs of rabbit, rat, and man, may suggest a role for PMCA in the regulation of intracellular Ca and in a mechanism for regulating and maintaining the high concentration of Ca in saliva

Safety assessment of underground vehicles passing over highly resilient curved tracks in the presence of a broken rail

Vehicle–track interaction for a new resilient slab track designed to reduce noise and vibration levels was analysed, in order to assess the derailment risk on a curved track when encountering a broken rail. Sensitivity of the rail support spacing of the relative position of the rail breakage between two adjacent rail supports and of running speed were analysed for two different elasticities of the rail fastening system. In none of the cases analysed was observed an appreciable difference between either of the elastic systems. As was expected, the most unfavourable situations were those with greater rail support spacing and those with greater distance from the breakage to the nearest rail support, although in none of the simulations performed did a derailment occur when running over the broken rail. When varying the running speed, the most favourable condition was obtained for an intermediate speed, due to the superposition of two antagonistic effects

Understanding signaling cascades in melanoma

Understanding regulatory pathways involved in melanoma development and progression has advanced significantly in recent years. It is now appreciated that melanoma is the result of complex changes in multiple signaling pathways that affect growth control, metabolism, motility and the ability to escape cell death programs. Here we review the major signaling pathways currently known to be deregulated in melanoma with an implication to its development and progression. Among these pathways are Ras, B-Raf, MEK, PTEN, phosphatidylinositol-3 kinase (PI3Ks) and Akt which are constitutively activated in a significant number of melanoma tumors, in most cases due to genomic change. Other pathways discussed in this review include the [Janus kinase/signal transducer and activator of transcription (JAK/STAT), transforming growth factor-beta pathways which are also activated in melanoma, although the underlying mechanism is not yet clear. As a paradigm for remodeled signaling pathways, melanoma also offers a unique opportunity for targeted drug development.Fil: Lopez Bergami, Pablo Roberto. Sanford-burnham Medical Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fitchmann, B. Sanford-burnham Medical Research Institute; Estados UnidosFil: Ronai, Ze´ev. Sanford-burnham Medical Research Institute; Estados Unido

Synergistic Effect of Co and Mn Co-Doping on SnO2 Lithium-Ion Anodes

The incorporation of transition metals (TMs) such as Co, Fe, and Mn into SnO2 substantially improves the reversibility of the conversion and the alloying reaction when used as a negative electrode active material in lithium-ion batteries. Moreover, it was shown that the specific benefits of different TM dopants can be combined when introducing more than one dopant into the SnO2 lattice. Herein, a careful characterization of Co and Mn co-doped SnO2 via transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy and X-ray diffraction including Rietveld refinement is reported. Based on this in-depth investigation of the crystal structure and the distribution of the two TM dopants within the lattice, an ex situ X-ray photoelectron spectroscopy and ex situ X-ray absorption spectroscopy were performed to better understand the de-/lithiation mechanism and the synergistic impact of the Co and Mn co-doping. The results specifically suggest that the antithetical redox behaviour of the two dopants might play a decisive role for the enhanced reversibility of the de-/lithiation reaction

Respecting the deal: how to manage co-opetitive actors in open innovation

Platforms like E-bay allow product seekers and providers to meet and exchange goods. On the same way in open innovation, as defined by Chesbrough, an enterprise can collect ideas from outside the company. But on E-bay, the seeker can return the product if it does not correspond to the expectations, since E-bay is the third-party actor in charge of assuring that the agreement between seekers and providers will be respected. So who does provide the same service for what concerns open innovation, where specifications might not fully defined? In this paper we shall describe the business model of an organizational structure to support the elicitation and respect of agreements between actors, who have conflicting interests but that gain from cooperating together. The concepts of the model will be illustrated to derive a set of propositions and a simple example will illustrate one of its possible instantiations. The description of our first evaluation phase shall find place at the end

A Cognitive Mapping Approach to Business Models: Representing Causal Structures and Mechanisms

Research has highlighted the cognitive nature of the business model intended as a cognitive representation describing a business’ value creation and value capture activities. Whereas the content of the business model has been extensively investigated from this perspective, less attention has been paid to the business model’s causal structure – i.e. the pattern of causeeffect relations that, in top managers’ or entrepreneurs’ understandings, link value creation and value capture activities. Building on the strategic cognition literature, this paper argues that conceptualizing and analyzing business models as cognitive maps can shed light on four important properties of a business model’s causal structure: the levels of complexity, focus, and clustering that characterize the causal structure; and the mechanisms underlying the causal links featured in that structure. I use examples of business models drawn from the literature as illustrations to describe these four properties. Finally, I discuss the value of a cognitive mapping approach for augmenting extant theories and practices of business model design