Performance-based building and innovation: Balancing client and industry needs

One reason for the interest in performance-based building is that it is commonly advocated as a powerful way of enhancing innovation performance by articulating building performance outcomes, and by offering relevant procurement actors the discretion to innovate to meet these performance requirements more effectively and/or efficiently. The paper argues that the current approach to performance-based building assumes that relevant actors have the capacity, ability and motivation to innovate from a business perspective. It is proposed that the prevailing conceptualization of PBB is too restrictive and should be broadened explicitly to accommodate the required business logic that must be in place before actors will innovate. The relevant performance-based building and innovation literature is synthesized to support the assertion. The paper concludes with an innovation-focused definition of performance-based building

β2-adrenergic signalling promotes cell migration by upregulating expression of the metastasis-associated molecule LYPD3

Metastasis is associated with poor prognosis in breast cancer. Although some studies suggest beta-blockers increase survival by delaying metastasis, others have been discordant. This study provides both insights into the anomalous findings and identifies potential biomarkers that may be treatment targets. Cell line models of basal-type and oestrogen receptor-positive breast cancer were profiled for basal levels of adrenoceptor gene/protein expression, and β2-adrenoceptor mediated cell behaviour including migration, invasion, adhesion, and survival in response to adrenoceptor agonist/antagonist treatment. Protein profiling and histology identified biomarkers and drug targets. Baseline levels of adrenoceptor gene expression are higher in basal-type rather than oestrogen receptor-positive cancer cells. Norepinephrine (NE) treatment increased invasive capacity in all cell lines but did not increase proliferation/survival. Protein profiling revealed the upregulation of the pro-metastatic gene Ly6/PLAUR Domain-Containing Protein 3 (LYPD3) in norepinephrine-treated MDA-MB-468 cells. Histology confirmed selective LYPD3 expression in primary and metastatic breast tumour samples. These findings demonstrate that basal-type cancer cells show a more aggressive adrenoceptor-β2-activated phenotype in the resting and stimulated state, which is attenuated by adrenoceptor-β2 inhibition. This study also highlights the first association between ADRβ2 signalling and LYPD3; its knockdown significantly reduced the basal and norepinephrine-induced activity of MCF-7 cells in vitro. The regulation of ADRβ2 signalling by LYPD3 and its metastasis promoting activities, reveal LYPD3 as a promising therapeutic target in the treatment of breast and other cancers

Constraints on energetic particles in the Fleischmann-Pons experiment

In recent Fleischmann–Pons experiments carried out by different groups, a thermal signal is seen indicative of excess energy production of a magnitude much greater than can be accounted for by chemistry. Correlated with the excess heat appears to be 4He, with the associated energy near 24 MeV per helium atom. In nuclear reactions, the energy produced is expressed through the kinetic energy of the products; hence, it would be natural to assume that some of the reaction energy ends up as kinetic energy of the 4He nucleus. Depending on the energy that the helium nucleus is born with, it will result in radiation (such as neutrons or x-rays) that can be seen outside of the cell. We have computed estimates of the expected neutron and x-ray emission as a function of helium energy and compared the results with upper limits taken from experiments. Experimental results with upper limits of neutron emission between 0.008 and 0.8 n/J are found to correspond to upper limits in alpha energy between 6.2 and 20.2 keV

Whither Capitalism? Financial externalities and crisis

As with global warming, so with financial crises – externalities have a lot to answer for. We look at three of them. First the financial accelerator due to ‘fire sales’ of collateral assets -- a form of pecuniary externality that leads to liquidity being undervalued. Second the ‘risk- shifting’ behaviour of highly-levered financial institutions who keep the upside of risky investment while passing the downside to others thanks to limited liability. Finally, the network externality where the structure of the financial industry helps propagate shocks around the system unless this is checked by some form of circuit breaker, or ‘ring-fence’. The contrast between crisis-induced Great Recession and its aftermath of slow growth in the West and the rapid - and (so far) sustained - growth in the East suggests that successful economic progress may depend on how well these externalities are managed

Latent HIV in primary T lymphocytes is unresponsive to histone deacetylase inhibitors

Recently, there is considerable interest in the field of anti-HIV therapy to identify and develop chromatin-modifying histone deacetylase (HDAC) inhibitors that can effectively reactivate latent HIV in patients. The hope is that this would help eliminate cells harboring latent HIV and achieve an eventual cure of the virus. However, how effectively these drugs can stimulate latent HIVs in quiescent primary CD4 T cells, despite their relevant potencies demonstrated in cell line models of HIV latency, is not clear. Here, we show that the HDAC inhibitors valproic acid (VPA) and trichostatin A (TSA) are unable to reactivate HIV in latently infected primary CD4 T cells generated in the H80 co-culture system. This raises a concern that the drugs inhibiting HDAC function alone might not be sufficient for stimulating latent HIV in resting CD4 T cells in patients and not achieve any anticipated reduction in the pool of latent reservoirs

Corporate Social Responsibility and Islamic Financial Institutions (IFIs): Management Perceptions from IFIs in Bahrain

Islamic finance is gaining greater attention in the finance industry, and this paper analyses how Islamic financial institutions (IFIs) are responding to the welfare needs of society. Using interview data with managers and content analysis of the disclosures, this study attempts to understand management perceptions of corporate social responsibility (CSR) in IFIs. A thorough understanding of CSR by managers, as evident in the interviews, has not been translated fully into practice. The partial use of IFIs’ potential role in social welfare would add further challenges in the era of financialisation

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag