John Lee

Excited states in Si38,40,42 nuclei have been studied via in-beam γ-ray spectroscopy with multinucleon removal reactions. Intense radioactive beams of S40 and S44 provided at the new facility of the RIKEN Radioactive Isotope Beam Factory enabled γ-γ coincidence measurements. A prominent γ line observed with an energy of 742 keV in Si42 confirms the 2 + state reported in an earlier study. Among the γ lines observed in coincidence with the 2 +→0 + transition, the most probable candidate for the transition from the yrast 4 + state was identified, leading to a 41+ energy of 2173 keV. The energy ratio of 2.93 between the 21+ and 41+ states indicates well-developed deformation in Si42 at N=28 and Z=14. Also for Si38,40 energy ratios with values of 2.09 and 2.56 were obtained. Together with the ratio for Si42, the results show a rapid deformation development of Si isotopes from N=24 to N=28. © 2012 American Physical Society.

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy. Broadband DOS combines multifrequency frequency-domain photon migration with time-independent near infrared spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations of methemoglobin, deoxyhemoglobin, and oxyhemoglobin were determined from absorption spectra acquired in "real time" during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 μM, representing 2.2 to 14.9% of the total hemoglobin content. These values agreed well with on-site ex vivo cooximetry data. The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue. As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models. Copyright © 2006 the American Physiological Society.

The unique properties of lasers create an enormous potential for specific treatment of chronic ear disease. Despite the widespread acceptance and use of the laser, however, a complete understanding of the time- and space-dependent temperature distribution in otic capsule bone immediately after pulsed laser exposure has not been elucidated. Using a liquid nitrogen- cooled mercury-cadmium telluride infrared detector, the temperature distribution in human cadaveric otic capsule bone was determined immediately after pulsed carbon dioxide laser exposure. The time- and space-dependent temperature increases and thermal diffusion were determined as a function of the laser power density and were found to vary linearly.

© Hsiao et al.; licensee BioMed Central.Background: Identifying cellular signaling pathways that become corrupted in the presence of androgens that increase the metastatic potential of organ-confined tumor cells is critical to devising strategies capable of attenuating the metastatic progression of hormone-naïve, organ-confined tumors. In localized prostate cancers, gene fusions that place ETS-family transcription factors under the control of androgens drive gene expression programs that increase the invasiveness of organ-confined tumor cells. C-X-C chemokine receptor type 4 is a downstream target of ERG, whose upregulation in prostate-tumor cells contributes to their migration from the prostate gland. Recent evidence suggests that CXCR4-mediated proliferation and metastasis of tumor cells is regulated by CXCR7 through its scavenging of chemokine CXCL12. However, the role of androgens in regulating CXCR4-mediated motility with respect to CXCR7 function in prostate-cancer cells remains unclear. Methods: Immunocytochemistry, western blot, and affinity-purification analyses were used to study how androgens influenced the expression, subcellular localization, and function of CXCR7, CXCR4, and androgen receptor in LNCaP prostate-tumor cells. Moreover, luciferase assays and quantitative polymerase chain reaction were used to study how chemokines CXCL11 and CXCL12 regulate androgen-regulated genes in LNCaP prostate-tumor cells. Lastly, cell motility assays were carried out to determine how androgens influenced CXCR4-dependent motility through CXCL12. Results: Here we show that, in the LNCaP prostate-tumor cell line, androgens coordinate the expression of CXCR4 and CXCR7, thereby promoting CXCL12/CXCR4-mediated cell motility. RNA interference experiments revealed functional interactions between AR and CXCR7 in these cells. Co-localization and affinity-purification experiments support a physical interaction between AR and CXCR7 in LNCaP cells. Unexpectedly, CXCR7 resided in the nuclear compartment and modulated AR-mediated transcription. Moreover, androgen-mediated cell motility correlated positively with the co-localization of CXCR4 and CXCR7 receptors, suggesting that cell migration may be linked to functional CXCR4/CXCR7 heterodimers. Lastly, CXCL12-mediated cell motility was CXCR7-dependent, with CXCR7 expression required for optimal expression of CXCR4 protein. Conclusions: Overall, our results suggest that inhibition of CXCR7 function might decrease the metastatic potential of organ-confined prostate cancers.

© 2015 American Psychological Association.Objective: To determine if a treatment for interepisode bipolar disorder I patients with insomnia improves mood state, sleep, and functioning. Method: Alongside psychiatric care, interepisode bipolar disorder I participants with insomnia were randomly allocated to a bipolar disorder-specific modification of cognitive behavior therapy for insomnia or psychoeducation as a comparison condition. Outcomes were assessed at baseline, the end of 8 sessions of treatment, and 6 months later. This pilot was conducted to determine initial feasibility and generate effect size estimates. Results: During the 6-month follow-up, the CBTI-BP group had fewer days in a bipolar episode relative to the PE group. The CBTI-BP group also experienced a significantly lower hypomania/mania relapse rate and a marginally lower overall mood episode relapse rate compared with the PE group. Relative to PE, CBTI-BP reduced insomnia severity and led to higher rates of insomnia remission at posttreatment and marginally higher rates at 6 months. Both CBTI-BP and PE showed statistically significant improvement on selected sleep and functional impairment measures. The effects of treatment were well sustained through follow-up for most outcomes, although some decline on secondary sleep benefits was observed. Conclusions: CBTI-BP was associated with reduced risk of mood episode relapse and improved sleep and functioning on certain outcomes in bipolar disorder. Hence, sleep disturbance appears to be an important pathway contributing to bipolar disorder. The need to develop bipolar disorder-specific sleep diary scoring standards is highlighted.

© 2015 Elsevier Inc. β-adrenergic signaling pathways mediate key aspects of cardiac function. Its dysregulation is associated with a range of cardiac diseases, including dilated cardiomyopathy. Previously, we established an iPSC model of familial DCM from patients with a mutation in TNNT2, a sarcomeric protein. Here, we found that the β-adrenergic agonist isoproterenol induced mature β-adrenergic signaling in iPSC-derived cardiomyocytes but that this pathway was blunted in DCM iPSC-CMs. Although expression levels of several β-adrenergic signaling components were unaltered between control and DCM iPSC-CMs, we found that phosphodiesterases 2A and PDE3A were upregulated in DCM iPSC-CMs and that PDE2A was also upregulated in DCM patient tissue. We further discovered increased nuclear localization of mutant TNNT2 and epigenetic modifications of PDE genes in both DCM iPSC-CMs and patient tissue. Notably, pharmacologic inhibition of PDE2A and PDE3A restored cAMP levels and ameliorated the impaired β-adrenergic signaling of DCM iPSC-CMs, suggesting therapeutic potential. In this paper, Wu etal. profiled the β-adrenergic signaling properties in human iPSC-CMs and demonstrated novel epigenetic mechanisms that underlie the compromised β-adrenergic signaling in DCM, a common cause of heart failure and cardiac transplantation. These results enhance our understanding of DCM pathogenesis and may uncover new therapeutic targets.

© 2016, UNESCO IBE.Using comparative data, this article examines the level and distribution of participation in adult education opportunities among countries that participated in PIAAC. It considers observed cross-country patterns in relation to some mechanisms that drive unequal chances to participate and to some policy issues that surround the provision, governance, and financing of different types of adult learning. It also explores recent policy developments relevant to AE in three selected countries.

This book provides a sustained and penetrating critique of a wide range of views in modern cognitive science and philosophy of the mind, from Turing's famous test for intelligence in machines to recent work in computational linguistic theory. While discussing many of the key arguments and topics, the authors also develop a distinctive analytic approach. Drawing on the methods of conceptual analysis first elaborated by Wittgenstein and Ryle, the authors seek to show that these methods still have a great deal to offer in the field of the cognitive theory and the philosophy of mind, providing a powerful alternative to many of the positions put forward in the contemporary literature. Amoung the many issues discussed in the book are the following: the Cartesian roots of modern conceptions of mind; Searle's 'Chinese Room' thought experiment; Fodor's 'language of thought' hypothesis; the place of 'folk psychology' in cognitivist thought; and the question of whether any machine may be said to 'think' or 'understand' in the ordinary senses of these words. Wide ranging, up-to-date and forcefully argued, this book represents a major intervention in contemporary debates about the status of cognitive science an the nature of mind. It will be of particular interest to students and scholars in philosophy, psychology, linguistics and computing sciences.