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

Acceleration Of Protons To Above 6 MeV Using H2O >Snow> Nanowire Targets

A scheme is presented for using H2O >snow> nanowire targets for the generation of fast protons. This novel method may relax the requirements for very high laser intensities, thus reducing the size and cost of laser based ion acceleration system.Physic

5.5-7.5 MeV Proton generation by a moderate intensity ultra-short laser interaction with H2O nano-wire targets

We report on the first generation of 5.5-7.5 MeV protons by a moderate intensity short-pulse laser (4.5 \times 1017 W/cm^2, 50 fsec) interacting with H2O nano-wires (snow) deposited on a Sapphire substrate. In this setup, the laser intensity is locally enhanced by the tip of the snow nano-wire, leading to high spatial gradients. Accordingly, the plasma near the tip is subject to enhanced ponderomotive potential, and confined charge separation is obtained. Electrostatic fields of extremely high intensities are produced over the short scale length, and protons are accelerated to MeV-level energies.Comment: submitted to PRL, under press embargo. 6 figure

Influence of slope of rise and event order of aircraft noise events on high resolution actimetry parameters

Zusammenfassung: Starts und Landungen in der Nacht sind bei den meisten Verkehrsflughäfen durch eine Nachtflugsperre eingeschränkt. Die Empfindlichkeit der Bevölkerung, durch Fluglärm im Schlaf gestört zu werden, ist daher zu Randzeiten, also abends und morgens, besonders gross. In einer experimentellen Feldstudie bei Anwohnern in der Umgebung des Flughafens Zürich untersuchten wir die Wirkung von Fluglärmereignissen auf Körperreaktionen vor dem Aufwachen am Morgen. Dabei wurden in den Schlafzimmern der Versuchspersonen zuvor aufgezeichnete Fluglärm-Geräusche abgespielt. Mit einem nichtinvasiven Aufzeichnungsverfahren für schlafphysiologische Parameter (Hochauflösende Aktimetrie-, Herz- und Atemparameter) wurden Körperbewegungen ereigniskorreliert registriert. Die Resultate ergaben, dass vor allem die ersten paar Lärmereignisse am frühen Morgen die stärksten Reaktionen evozierten und diese mit zunehmender Anzahl erlebter Lärmereignisse abnehmen, was vermuten lässt, dass die zuvor erlebte Anzahl Überflüge eine systematische Wirkung hat, insbesondere wenn die Ereignisse innerhalb kurzer Zeitintervalle auftreten. Es zeigte sich auch, dass die Motilität von der Anstiegsgeschwindigkeit des Schallpegels abhängt, steilere Anstiegsflanken - wie sie typischerweise direkt unterhalb von Landeanflugschneisen auftreten - erzeugen stärkere Bewegungsreaktionen. Dies ist im Einklang mit einer neueren Untersuchung über den Zusammenhang zwischen nächtlichem Flug- und Eisenbahnlärm und Aufwachwahrscheinlichkei

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

A Paradigmatic Analysis of Digital Application Marketplaces

This paper offers a paradigmatic analysis of digital application marketplaces for advancing information systems (IS) research on digital platforms and ecosystems. We refer to the notion of digital application marketplace, colloquially called “appstores,” as a platform component that offers a venue for exchanging applications between developers and end-users belonging to a single or multiple ecosystems. Such marketplaces exhibit diversity in features and assumptions, and we propose that examining this diversity, and its ideal types, will help us to further understand the relationship between application marketplaces, platforms, and platform ecosystems. To this end, we generate a typology that distinguishes four kinds of digital application marketplaces: closed, censored, focused, and open marketplaces. The paper also offers implications for actors wishing to make informed decisions about their relationship to a particular digital application marketplace

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

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

Inhibition of the glycaemic response by onion : a comparison between lactose-tolerant and lactose-intolerant adults

This document is the Accepted Manuscript of the following article: R Hoffman, G Ranjbar and A M Madden, ‘Inhibition of the glycaemic response by onion: a comparison between lactose-tolerant and lactose-intolerant adults’, European Journal of Clinical Nutritin, (2016), 70: 1089-1091. The Version of Record is available online at doi: 10.1038/ejcn.2016.44.This pilot study compared inhibition of the glycaemic response to glucose by a dietary source of quercetin glucosides (onion) in lactose-tolerant adults (n = 12) and lactose-intolerant adults (n = 12). We hypothesised that lactose-intolerant people (who do not express lactase) will retain intact quercetin glucosides that can inhibit glucose uptake via the glucose transporter SGLT1 whereas lactose-tolerant people (who do express lactase) will hydrolyse quercetin glucosides to free quercetin which does not inhibit glucose uptake. In a glucose tolerance test, reduction of peak glucose levels by an onion meal was higher in lactose-intolerant people than lactose-tolerant people (44.2% versus 19.3%, p = 0.04). Incremental area under the blood glucose curve was reduced more in lactose-intolerant people, but was not statistically significantly (54.5% versus 42.1%, p = 0.42). A diet containing quercetin glucosides may be of greater benefit for glycaemic control in lactose-intolerant people than in lactose-tolerant people.Peer reviewedFinal Accepted Versio

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/