Rate-Dependent Nucleation and Growth of NaO2 in Na-O2 Batteries

Understanding the oxygen reduction reaction kinetics in the presence of Na ions and the formation mechanism of discharge product(s) is key to enhancing Na–O2 battery performance. Here we show NaO2 as the only discharge product from Na–O2 cells with carbon nanotubes in 1,2-dimethoxyethane from X-ray diffraction and Raman spectroscopy. Sodium peroxide dihydrate was not detected in the discharged electrode with up to 6000 ppm of H2O added to the electrolyte, but it was detected with ambient air exposure. In addition, we show that the sizes and distributions of NaO2 can be highly dependent on the discharge rate, and we discuss the formation mechanisms responsible for this rate dependence. Micron-sized (∼500 nm) and nanometer-scale (∼50 nm) cubes were found on the top and bottom of a carbon nanotube (CNT) carpet electrode and along CNT sidewalls at 10 mA/g, while only micron-scale cubes (∼2 μm) were found on the top and bottom of the CNT carpet at 1000 mA/g, respectively.Seventh Framework Programme (European Commission) (Marie Curie International Outgoing Fellowship, 2007-2013))National Science Foundation (U.S.) (MRSEC Program, award number DMR-0819762)Robert Bosch GmbH (Bosch Energy Research Network (BERN) Grant)China Clean Energy Research Center-Clean Vehicles Consortium (CERC-CVC) (award number DE-PI0000012)Skolkovo Institute of Science and Technology (Skoltech-MIT Center for Electochemical Energy Storage

FGF8 isoform b expression in human prostate cancer.

Overexpression of fibroblast growth factor 8 (FGF8) mRNA has been previously described in prostate cancer. Of its four isoforms, FGF8b is thought to be the most important in carcinogenesis. We hypothesised that immunodetection of FGF8b in archival prostate cancer specimens is of potential prognostic value. Using a selected cohort of prostate tumours from transurethral (n=30) and radical prostatectomies (n=59), an optimised protocol for FGF8b immunoreactivity was used to corroborate expression with clinical parameters. No expression was observed in benign prostates (n=10). In prostate cancer, immunoreactivity was localised to the malignant epithelium with weak signals in the adjacent stroma. Expression of FGF8b in stage T1 and T2 cancers were 40 and 67%, respectively. In contrast, FGF8b expression was present in 94% of T3 and 100% of T4 cancers. By histological grade, FGF8b was found in 41% of low-grade cancers (Gleason score 4-6), 60% of intermediate-grade cancers (Gleason score 7 and 92% of high-grade cancers (Gleason score 8-10). The intensity of expression was significantly associated with stage (P=0.0004) and grade (P<0.0001) of disease. We further hypothesised that FGF8b overexpression resulted from enhanced transcription and translation rather than from abnormalities involving the FGF8 gene locus. This was tested by means of fluorescent in situ hybridisation in 20 cancer specimens to map the FGF8 gene locus. FGF8 gene copy number in benign and malignant nuclei was found to be similar (2.33+/-0.57 and 2.0+/-0.81, respectively P=0.51). Based on these findings, we propose a multicentre study on cohorts of patients to further evaluate FGF8b as a potential prognostic marker in prostate cancer

Pathway-based expression profiling of benign prostatic hyperplasia and prostate cancer delineates an immunophilin molecule associated with cancer progression

Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to ARreactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis. Expression of FKBP52 was positively correlated with that of c-Myc. The functional cross-talk between c-Myc and FKBP52 was established using c-Myc specific-siRNA to LNCaP cells that resulted in reduction of FKBP52. A non-canonical E-box sequence housing a putative c-Myc binding site was detected on the FKBP4 promoter using in silico search. LNCaP cells transfected with the FKBP52 promoter cloned in pGL3 basic showed increased luciferase activity which declined considerably when the promoter-construct was co-transfected with c-Myc specific-siRNA. ChIP-PCR confirmed the binding of c-Myc with the conserved E-box located in the FKBP52 promoter. c-Myc downregulation concomitantly affected expression of FGF8. Since expression of FGF8 is controlled by AR, our study unveiled a novel functional axis between c-Myc, AR and FGF8 operating through FKBP52

Pten (phosphatase and tensin homologue gene) haploinsufficiency promotes insulin hypersensitivity

AIMS/HYPOTHESIS: Insulin controls glucose metabolism via multiple signalling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway in muscle and adipose tissue. The protein/lipid phosphatase Pten (phosphatase and tensin homologue deleted on chromosome 10) attenuates PI3K signalling by dephosphorylating the phosphatidylinositol 3,4,5-trisphosphate generated by PI3K. The current study was aimed at investigating the effect of haploinsufficiency for Pten on insulin-stimulated glucose uptake. MATERIALS AND METHODS: Insulin sensitivity in Pten heterozygous (Pten(+/−)) mice was investigated in i.p. insulin challenge and glucose tolerance tests. Glucose uptake was monitored in vitro in primary cultures of myocytes from Pten(+/−) mice, and in vivo by positron emission tomography. The phosphorylation status of protein kinase B (PKB/Akt), a downstream signalling protein in the PI3K pathway, and glycogen synthase kinase 3β (GSK3β), a substrate of PKB/Akt, was determined by western immunoblotting. RESULTS: Following i.p. insulin challenge, blood glucose levels in Pten(+/−) mice remained depressed for up to 120 min, whereas glucose levels in wild-type mice began to recover after approximately 30 min. After glucose challenge, blood glucose returned to normal about twice as rapidly in Pten(+/−) mice. Enhanced glucose uptake was observed both in Pten(+/−) myocytes and in skeletal muscle of Pten(+/−) mice by PET. PKB and GSK3β phosphorylation was enhanced and prolonged in Pten(+/−) myocytes. CONCLUSIONS/INTERPRETATION: Pten is a key negative regulator of insulin-stimulated glucose uptake in vitro and in vivo. The partial reduction of Pten due to Pten haploinsufficiency is enough to elicit enhanced insulin sensitivity and glucose tolerance in Pten(+/−) mice

Foreign equity portfolio flow and corruption: a cross-country evidence

This study examines the impact of foreign equity portfolio investment on corruption. Employing a large dataset of 44 countries from 2001 to 2015 and three different measures of corruption, our results show that foreign investors from well-governed countries tend to foster public accountability, reduce asymmetry information and corruption. We find empirical evidence that foreign equity portfolio investment interacts with stock market development and central bank transparency to reduce corruption. Our results suggest that stock market development and central bank transparency are regarded as complementary by international portfolio investors. Further analysis indicates that corruption appears more prevalent in countries where domestic investors dominate the stock market. Our results are robust to endogeneity using dynamic generalized methods of moments (GMM). The findings suggest that attracting foreign equity investors reduces corruption, implying significant benefits for portfolio diversification

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.</p> <p>Methods</p> <p>A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.</p> <p>Results</p> <p>A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. <it>Pik3r1</it>, <it>E2f3, Akr1c3</it>, <it>Csf1</it>, <it>Jag2</it>, <it>Plcg1</it>, <it>Rpl37a</it>, <it>Sod2</it>, <it>Topors</it>, <it>Hras</it>, <it>Mdm2, Camk2g</it>, <it>Fstl1</it>, <it>Il13ra1</it>, <it>Mtap </it>and <it>Tp53 </it>were associated with multiple survival events.</p> <p>Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for <it>Syne1</it>, <it>Pdcd4</it>, <it>Ighg1</it>, <it>Tgfa</it>, <it>Pla2g7</it>, and <it>Paics</it>. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. <it>C2</it>, <it>Egfr</it>, <it>Prkcb</it>, <it>Igf2bp3</it>, and <it>Gdf10 </it>had gender-dependent associations; <it>Sox10</it>, <it>Rps20</it>, <it>Rab31</it>, and <it>Vav3 </it>had race-dependent associations; <it>Chi3l1</it>, <it>Prkcb</it>, <it>Polr2d</it>, and <it>Apool </it>had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.</p> <p>Conclusions</p> <p>Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.</p

No evidence for involvement of SDHD in neuroblastoma pathogenesis

BACKGROUND: Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma. METHODS: SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria. RESULTS: Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype. CONCLUSIONS: Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis

Fast growth associated with aberrant vasculature and hypoxia in fibroblast growth factor 8b (FGF8b) over-expressing PC-3 prostate tumour xenografts

Background: Prostate tumours are commonly poorly oxygenated which is associated with tumour progression and development of resistance to chemotherapeutic drugs and radiotherapy. Fibroblast growth factor 8b (FGF8b) is a mitogenic and angiogenic factor, which is expressed at an increased level in human prostate tumours and is associated with a poor prognosis. We studied the effect of FGF8b on tumour oxygenation and growth parameters in xenografts in comparison with vascular endothelial growth factor (VEGF)-expressing xenografts, representing another fast growing and angiogenic tumour model. Methods: Subcutaneous tumours of PC-3 cells transfected with FGF8b, VEGF or empty (mock) vectors were produced and studied for vascularity, cell proliferation, glucose metabolism and oxygenation. Tumours were evaluated by immunohistochemistry (IHC), flow cytometry, use of radiolabelled markers of energy metabolism ([F-18] FDG) and hypoxia ([F-18] EF5), and intratumoral polarographic measurements of pO(2). Results: Both FGF8b and VEGF tumours grew rapidly in nude mice and showed highly vascularised morphology. Perfusion studies, pO(2) measurements, [F-18] EF5 and [F-18] FDG uptake as well as IHC staining for glucose transport protein (GLUT1) and hypoxia inducible factor (HIF) 1 showed that VEGF xenografts were well-perfused and oxygenised, as expected, whereas FGF8b tumours were as hypoxic as mock tumours. These results suggest that FGF8b-induced tumour capillaries are defective. Nevertheless, the growth rate of hypoxic FGF8b tumours was highly increased, as that of well-oxygenised VEGF tumours, when compared with hypoxic mock tumour controls. Conclusion: FGF8b is able to induce fast growth in strongly hypoxic tumour microenvironment whereas VEGF-stimulated growth advantage is associated with improved perfusion and oxygenation of prostate tumour xenografts

Financial and corporate social performance in the UK listed firms: the relevance of non-linearity and lag effects

Using environmental, social and governance scores compiled by Reuters Datastream for each company’s corporate social performance (CSP), we examine the relationship between CSP and corporate financial performance (CFP) of 314 UK listed companies over the period 2002–2015. We further evaluate the relationship between prior and subsequent CFP and prior and subsequent CSP. Based on the system-GMM estimation method, we provide direct evidence that suggests that while CFP and CSP can be linked linearly; however, when we examine the impact of CSP on CFP, the association is more non-linear (cubic) than linear. Our results suggest that firms periodically adjust their level of commitment to society, in order to meet their target CSP. The primary contributions of this paper are testing (1) the non-monotonous relationship between CSP and CFP, (2) the lagged relationship between the two and the optimality of CSP levels, and (3) the presence of a virtuous circle. Our results further suggest that CSP contributes to CFP better during post-crisis years. Our findings are robust to year-on-year changes in CFP and CSP, financial versus non-financial firms, and the intensity of corporate social responsibility (CSR) engagement across industries