Proceedings, Vol. 1, Pages 466: H2-Sensing Performance of 2D WO3 Nanostructure—Effect of Anodization Parameter

Proceedings, Vol. 1, Pages 466: H2-Sensing Performance of 2D WO3 Nanostructure—Effect of Anodization Parameter

<p>Proceedings <a href="http://ift.tt/2w3b0EJ">doi: 10.3390/proceedings1040466</a></p> 
<p>Authors: 
    Anurat Wisitsora-at 
    Ditsayut Phokaratkul 
    Kata Jaruwongrangsee 
    Thitima M. Daniels 
    Wojtek Wlodarski 
    </p> 
<p>In this work, we investigate the effect of HNO3 anodizing solution concentration ranging from 1.5 to 3 M on H2-sensing performance of 2D WO3 nanostructures prepared by anodizing sputtered tungsten films. The thickness of WO3 nanosheets was found to reduce while the crystallinity degraded with increasing HNO3 concentration. However, the nanosheets anodized in 2 M HNO3 exhibited the highest response of 43.4 to 1 vol % H2, which was one order of magnitude larger than those fabricated with other concentrations at the optimal operating temperature of 350 °C. In addition, the optimal nanostructures displayed good H2 selectivity against NO2, CH4, C2H2 and C2H5OH.</p><br /><br />

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IJFS, Vol. 5, Pages 18: Does Gold Act as a Hedge and a Safe Haven for China’s Stock Market?

IJFS, Vol. 5, Pages 18: Does Gold Act as a Hedge and a Safe Haven for China’s Stock Market?

<p>International Journal of Financial Studies <a href="http://ift.tt/2vKncYw">doi: 10.3390/ijfs5030018</a></p> 
<p>Authors: 
    Ke Chen 
    Meng Wang 
    </p> 
<p>This paper examines the dynamic relationships between gold and stock markets in China. Using daily gold and stock indexes data, we estimated the DCC-GARCH model for the five bear markets since 31 October 2002, and simultaneously used different segments of China’s stock markets for analysis. Our main objective was to examine the time-varying correlations between gold and stock and to check the effectiveness of gold as a hedge or a safe haven for stocks. Results showed that: (1) the dynamic conditional correlations switched between positive and negative values over the periods under study; (2) due to the increasing investment demand of gold, the hedging effect of gold on China’s stock market has strengthened remarkably. Gold acts as a safe haven for only the latest two of the five bear markets analyzed (12 June 2015–26 August 2015 and 22 December 2015–29 February 2016); and (3) for non-bear markets, gold does not offer good risk hedging.</p><br /><br />

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Proceedings, Vol. 1, Pages 304: Fabrication of Sharp Tip-Separable Microneedle Device for Trans-Dermal Drug Delivery Systems

Proceedings, Vol. 1, Pages 304: Fabrication of Sharp Tip-Separable Microneedle Device for Trans-Dermal Drug Delivery Systems

<p>Proceedings <a href="http://ift.tt/2w3pTXR">doi: 10.3390/proceedings1040304</a></p> 
<p>Authors: 
    Yuki Nabekura 
    Hitoshi Fukuyu 
    Yoshihiro Hasegawa 
    Mitsuhiro Shikida 
    </p> 
<p>An alignment mechanism for producing a sharp tip-separable microneedle device for trans-dermal drug delivery systems has been developed. The needle and base parts were placed on a mechanical precision motion stage to align their central axes. The overlapping region between them in the height direction was controlled by inserting a thickness gauge between them. A 400-μm-high sharp tip-separable microneedle device was successfully produced by using the developed alignment mechanism with an accuracy of less than 19 μm. We also demonstrated that it can be used to produce an arrayed tip-separable microneedle device.</p><br /><br />

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Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE

Glioblastoma (GBM) is a deadly disease with few effective therapies. While much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is comprised of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage in order to support registration. Therapeutic arms with biomarkers may be added to the trial over time while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice.

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Personalized Medicine Based Approach to Model Patterns of Chemoresistance and Tumor Recurrence Using Ovarian Cancer Stem Cell Spheroids

Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. In order to screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary ALDH+ CD133+ ovarian cancer stem cells (OvCSCs) from different patient samples, and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immune-deficient mice. Drug responses to cisplatin and ALDH targeting compound or JAK2 inhibitor determined if the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor re-emergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying, and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with one single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to Cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression while those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH+ cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro, and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.

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Combined CDK4/6 and mTOR inhibition is synergistic against glioblastoma via multiple mechanisms

Purpose: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents. We investigate the efficacy of the combination of CDK4/6 inhibition and mTOR inhibition against GBM. Experimental Design: Preclinical in vitro and in vivo assays using primary GBM cell lines were performed. Results: We show that the CDK4/6 inhibitor palbociclib suppresses the activity of downstream mediators of the mTOR pathway, leading to rebound mTOR activation that can be blocked by the mTOR inhibitor everolimus. We further show that mTOR inhibition with everolimus leads to activation of the Ras mediator Erk that is reversible with palbociclib. The combined treatment strongly disrupts GBM metabolism, resulting in significant apoptosis. Further increasing the utility of the combination for brain cancers, everolimus significantly increases the brain concentration of palbociclib. Conclusions: Our findings demonstrate that the combination of CDK4/6 and mTOR inhibition has therapeutic potential against GBM and suggest it should be evaluated in a clinical trial.

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Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE

Glioblastoma (GBM) is a deadly disease with few effective therapies. While much has been learned about the molecular characteristics of the disease, this knowledge has not been translated into clinical improvements for patients. At the same time, many new therapies are being developed. Many of these therapies have potential biomarkers to identify responders. The result is an enormous amount of testable clinical questions that must be answered efficiently. The GBM Adaptive Global Innovative Learning Environment (GBM AGILE) is a novel, multi-arm, platform trial designed to address these challenges. It is the result of the collective work of over 130 oncologists, statisticians, pathologists, neurosurgeons, imagers, and translational and basic scientists from around the world. GBM AGILE is comprised of two stages. The first stage is a Bayesian adaptively randomized screening stage to identify effective therapies based on impact on overall survival compared with a common control. This stage also finds the population in which the therapy shows the most promise based on clinical indication and biomarker status. Highly effective therapies transition in an inferentially seamless manner in the identified population to a second confirmatory stage. The second stage uses fixed randomization to confirm the findings from the first stage in order to support registration. Therapeutic arms with biomarkers may be added to the trial over time while others complete testing. The design of GBM AGILE enables rapid clinical testing of new therapies and biomarkers to speed highly effective therapies to clinical practice.

http://ift.tt/2wh0Joo

Personalized Medicine Based Approach to Model Patterns of Chemoresistance and Tumor Recurrence Using Ovarian Cancer Stem Cell Spheroids

Purpose: Chemoresistant ovarian cancers grow in suspension within the ascites fluid. In order to screen the effect of chemotherapeutics and biologics on resistant ovarian cancers with a personalized basis, we developed a 3D hanging drop spheroid platform. Experimental Design: We initiated spheroids with primary ALDH+ CD133+ ovarian cancer stem cells (OvCSCs) from different patient samples, and demonstrated that stem cell progeny from harvested spheroids was similar to the primary tumor. OvCSC spheroids were utilized to initiate tumors in immune-deficient mice. Drug responses to cisplatin and ALDH targeting compound or JAK2 inhibitor determined if the OvCSC population within the spheroids could be targeted. Cells that escaped therapy were isolated and used to initiate new spheroids and model tumor re-emergence in a personalized manner. Results: OvCSC spheroids from different patients exhibited varying, and personalized responses to chemotherapeutics. Xenografts were established from OvCSC spheroids, even with one single spheroid. Distinct responses to therapy were observed in distinct primary tumor xenografts similar to those observed in spheroids. Spheroids resistant to Cisplatin/ALDH inhibitor therapy had persistent, albeit lower ALDH expression and complete loss of CD133 expression while those resistant to cisplatin/JAK2 inhibitor therapy were enriched for ALDH+ cells. Conclusions: Our 3D hanging drop suspension platform can be used to propagate primary OvCSCs that represent individual patient tumors effectively by differentiating in vitro, and initiating tumors in mice. Therefore, our platform can be used to study cancer stem cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.

http://ift.tt/2uRtqVj

Combined CDK4/6 and mTOR inhibition is synergistic against glioblastoma via multiple mechanisms

Purpose: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis is dysregulated in about 80% of GBMs. Single-agent CDK4/6 inhibitors have failed to provide durable responses in GBM, suggesting a need to combine them with other agents. We investigate the efficacy of the combination of CDK4/6 inhibition and mTOR inhibition against GBM. Experimental Design: Preclinical in vitro and in vivo assays using primary GBM cell lines were performed. Results: We show that the CDK4/6 inhibitor palbociclib suppresses the activity of downstream mediators of the mTOR pathway, leading to rebound mTOR activation that can be blocked by the mTOR inhibitor everolimus. We further show that mTOR inhibition with everolimus leads to activation of the Ras mediator Erk that is reversible with palbociclib. The combined treatment strongly disrupts GBM metabolism, resulting in significant apoptosis. Further increasing the utility of the combination for brain cancers, everolimus significantly increases the brain concentration of palbociclib. Conclusions: Our findings demonstrate that the combination of CDK4/6 and mTOR inhibition has therapeutic potential against GBM and suggest it should be evaluated in a clinical trial.

http://ift.tt/2whe2oO