Interplay between topological insulators and superconductors

Topological insulators are insulating in the bulk but possess metallic surface states protected by time-reversal symmetry. Here, we report on a detailed electronic transport study in high-quality Bi 2Se 3 topological insulator thin films contacted by superconducting (In, Al, and W) electrodes. The resistance of the film shows an abrupt and significant upturn when the electrodes become superconducting. In turn, the Bi 2Se 3 film greatly weakens the superconductivity of the electrodes, significantly reducing both their transition temperatures and their critical fields. A possible interpretation of these results is that the superconducting electrodes are accessing the surface states and the experimental results are consequences of the interplay between the Cooper pairs of the electrodes and the spin-polarized current of the surface states in Bi 2Se 3. © 2012 American Physical Society.published_or_final_versio

Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

Background: Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. Methods: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin alpha and beta subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. Results: All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin alpha and beta subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Conclusions: Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Transaction costs (TCs) in green building (GB) incentive schemes: Gross Floor Area (GFA) Concession Scheme in Hong Kong

It is claimed that transaction costs (TCs) affect the effectiveness of any green building (GB) policy. However, few studies have empirically applied TC analysis to GB incentives, which normally should have analyzed the TCs borne by different stakeholders. These include TC typology and determinants during the implementation process, especially the extra administration process where TCs possibly may be incurred. The lack of such in-depth analysis tends to make incentive-design ignore efficiency and fairness amongst the stakeholders. This study aims to improve the efficiency of GB incentives through analyzing TCs borne by the private sector stakeholders. It would identify TC typologies and determinants, and TCs measurement and allocation to different stakeholders. As TCs are policy context-specific, this paper takes a popular GB incentive scheme, Gross Floor Area (GFA) Concession Scheme, as an example. Interviews were conducted with 20 industry experts to validate TCs types and determinants, and to gauge the magnitude of TCs borne by different stakeholders. These empirical evidences are helpful for policy-makers and practitioners to better understand the impacts of TCs, so as to improve the effectiveness of future incentive schemes. In addition, GB policy recommendations for Hong Kong are proposed and many of which are relevant to other countries.</p

Applicability of ‘Aging in Place’ in redeveloped public rental housing estates in Hong Kong

Rapidly aging society is a global phenomenon with serious societal impact. With the rapid growth in the aging population in Hong Kong, it is foreseeable that every flat unit will accommodate one senior citizen. To address this looming problem, the Hong Kong Government has introduced several aged friendly home design elements and care facilities to redeveloped public rental housing estates. This study aimed to investigate the implementation of the “aging in place” philosophy, through evaluating the applicability and effectiveness of those facilities. A redevelopment project, the Un Chau Estate in Hong Kong was selected as a case study. Ecological theory is applied to evaluate the case study at micro, meso and macro scales. The methodological approaches include (a) a questionnaire survey, (b) face-to-face group discussions and (c) in-depth interviews. Results reveal that senior satisfaction levels with the new elements investigated were below the levels of perceived importance. In particular, the seniors emphasized the lack of a sense of home and privacy in their residences. They were, however, moderately satisfied with the independence and dignity and comfort and health elements. The results also reveal that the provision of common facilities is not up to standard in meeting the needs of the elderly. The majority of the elderly consistently opined that aging in place is their priority. To some extent, the extreme case of Hong Kong as a showcase of a dense populated aged Asian city, sheds light on how public housing (re)development can be designed to facilitate aging in place. A more comprehensive and refined approach at micro, meso, and macro scales is necessary to guarantee the satisfactory implementation of aging in place.</p

Achieving sustainable urban development with an ageing population : an “age-friendly city and community” approach

202202 bcvcVersion of RecordOthersThe first author acknowledges the PhD studentship offered by the Ng Wing Hong Laboratoryfor the Sustainable City, Department of Building and Real Estate, the Hong Kong PolytechnicUniversity.Publishe