Structure/activity relationships applied to the hydrogenation of α,β-unsaturated carbonyls: The hydrogenation of 3-butyne-2-one over alumina-supported palladium catalysts

The gas phase hydrogenation of 3-butyne-2-one, an alkynic ketone, over two alumina-supported palladium catalysts is investigated using infrared spectroscopy in a batch reactor at 373 K. The mean particle size of the palladium crystallites of the two catalysts are comparable (2.4 ± 0.1 nm). One catalyst (Pd(NO3)2/Al2O3) is prepared from a palladium(II) nitrate precursor, whereas the other catalyst (PdCl2/Al2O3) is prepared using palladium(II) chloride as the Pd precursor compound. A three-stage sequential process is observed with the Pd(NO3)2/Al2O3 catalyst facilitating complete reduction all the way through to 2-butanol. However, hydrogenation stops at 2-butanone with the PdCl2/Al2O3 catalyst. The inability of the PdCl2/Al2O3 catalyst to reduce 2-butanone is attributed to the inaccessibility of edge sites on this catalyst, which are blocked by chlorine retention originating from the catalyst’s preparative process. The reaction profiles observed for the hydrogenation of this alkynic ketone are consistent with the site-selective chemistry recently reported for the hydrogenation of crotonaldehyde, an alkenic aldehyde, over the same two catalysts. Thus, it is suggested that a previously postulated structure/activity relationship may be generic for the hydrogenation of α,β-unsaturated carbonyl compounds over supported Pd catalysts

Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer

Purpose: The PI3K/Akt signaling axis contributes to the dysregulation of many dominant features in breast cancer including cell proliferation, survival, metabolism, motility, and genomic instability. While multiple studies have demonstrated that basal-like or triple-negative breast tumors have uniformly high PI3K/Akt activity, genomic alterations that mediate dysregulation of this pathway in this subset of highly aggressive breast tumors remain to be determined. Methods: In this study, we present an integrated genomic analysis based on the use of a PI3K gene expression signature as a framework to analyze orthogonal genomic data from human breast tumors, including RNA expression, DNA copy number alterations, and protein expression. In combination with data from a genome-wide RNA-mediated interference screen in human breast cancer cell lines, we identified essential genetic drivers of PI3K/Akt signaling. Results: Our in silico analyses identified SOX4 amplification as a novel modulator of PI3K/Akt signaling in breast cancers and in vitro studies confirmed its role in regulating Akt phosphorylation. Conclusions: Taken together, these data establish a role for SOX4-mediated PI3K/Akt signaling in breast cancer and suggest that SOX4 may represent a novel therapeutic target and/or biomarker for current PI3K family therapies

Investigating the structure of star-forming regions using INDICATE

The ability to make meaningful comparisons between theoretical and observational data of star-forming regions is key to understanding the star formation process. In this paper, we test the performance of INDICATE, a new method to quantify the clustering tendencies of individual stars in a region, on synthetic star-forming regions with substructured, and smooth, centrally concentrated distributions. INDICATE quantifies the amount of stellar affiliation of each individual star, and also determines whether this affiliation is above random expectation for the star-forming region in question. We show that INDICATE cannot be used to quantify the overall structure of a region due to a degeneracy when applied to regions with different geometries. We test the ability of INDICATE to detect differences in the local stellar surface density and its ability to detect and quantify mass segregation. We then compare it to other methods such as the mass segregation ratio ΛMSR, the local stellar surface density ratio ΣLDR, and the cumulative distribution of stellar positions. INDICATE detects significant differences in the clustering tendencies of the most massive stars when they are at the centre of a smooth, centrally concentrated distribution, corresponding to areas of greater stellar surface density. When applied to a subset of the 50 most massive stars, we show INDICATE can detect signals of mass segregation. We apply INDICATE to the following nearby star-forming regions: Taurus, ONC, NGC 1333, IC 348, and ρ Ophiuchi and find a diverse range of clustering tendencies in these regions

The Heumann-Hotzel model for aging revisited

Since its proposition in 1995, the Heumann-Hotzel model has remained as an obscure model of biological aging. The main arguments used against it were its apparent inability to describe populations with many age intervals and its failure to prevent a population extinction when only deleterious mutations are present. We find that with a simple and minor change in the model these difficulties can be surmounted. Our numerical simulations show a plethora of interesting features: the catastrophic senescence, the Gompertz law and that postponing the reproduction increases the survival probability, as has already been experimentally confirmed for the Drosophila fly.Comment: 11 pages, 5 figures, to be published in Phys. Rev.

Comment on "Resolving the 180-deg Ambiguity in Solar Vector Magnetic Field Data: Evaluating the Effects of Noise, Spatial Resolution, and Method Assumptions"

In a recent paper, Leka at al. (Solar Phys. 260, 83, 2009)constructed a synthetic vector magnetogram representing a three-dimensional magnetic structure defined only within a fraction of an arcsec in height. They rebinned the magnetogram to simulate conditions of limited spatial resolution and then compared the results of various azimuth disambiguation methods on the resampled data. Methods relying on the physical calculation of potential and/or non-potential magnetic fields failed in nearly the same, extended parts of the field of view and Leka et al. (2009) attributed these failures to the limited spatial resolution. This study shows that the failure of these methods is not due to the limited spatial resolution but due to the narrowly defined test data. Such narrow magnetic structures are not realistic in the real Sun. Physics-based disambiguation methods, adapted for solar magnetic fields extending to infinity, are not designed to handle such data; hence, they could only fail this test. I demonstrate how an appropriate limited-resolution disambiguation test can be performed by constructing a synthetic vector magnetogram very similar to that of Leka et al. (2009) but representing a structure defined in the semi-infinite space above the solar photosphere. For this magnetogram I find that even a simple potential-field disambiguation method manages to resolve the ambiguity very successfully, regardless of limited spatial resolution. Therefore, despite the conclusions of Leka et al. (2009), a proper limited-spatial-resolution test of azimuth disambiguation methods is yet to be performed in order to identify the best ideas and algorithms.Comment: Solar Physics, in press (19 pp., 5 figures, 2 tables

DCE-MRI biomarkers of tumour heterogeneity predict CRC liver metastasis shrinkage following bevacizumab and FOLFOX-6

Background: There is limited evidence that imaging biomarkers can predict subsequent response to therapy. Such prognostic and/or predictive biomarkers would facilitate development of personalised medicine. We hypothesised that pre-treatment measurement of the heterogeneity of tumour vascular enhancement could predict clinical outcome following combination anti-angiogenic and cytotoxic chemotherapy in colorectal cancer (CRC) liver metastases. Methods: Ten patients with 26 CRC liver metastases had two dynamic contrast-enhanced MRI (DCE-MRI) examinations before starting first-line bevacizumab and FOLFOX-6. Pre-treatment biomarkers of tumour microvasculature were computed and a regression analysis was performed against the post-treatment change in tumour volume after five cycles of therapy. The ability of the resulting linear model to predict tumour shrinkage was evaluated using leave-one-out validation. Robustness to inter-visit variation was investigated using data from a second baseline scan. Results: In all, 86% of the variance in post-treatment tumour shrinkage was explained by the median extravascular extracellular volume (ve), tumour enhancing fraction (EF), and microvascular uniformity (assessed with the fractal measure box dimension, d0) (R2=0.86, P<0.00005). Other variables, including baseline volume were not statistically significant. Median prediction error was 12%. Equivalent results were obtained from the second scan. Conclusion: Traditional image analyses may over-simplify tumour biology. Measuring microvascular heterogeneity may yield important prognostic and/or predictive biomarkers

The use of a smartphone app and an activity tracker to promote physical activity in the management of chronic obstructive pulmonary disease : randomized controlled feasibility study

Background: Chronic obstructive pulmonary disease (COPD) is highly prevalent and significantly affects the daily functioning of patients. Self-management strategies, including increasing physical activity, can help people with COPD have better health and a better quality of life. Digital mobile health (mHealth) techniques have the potential to aid the delivery of self-management interventions for COPD. We developed an mHealth intervention (Self-Management supported by Assistive, Rehabilitative, and Telehealth technologies-COPD [SMART-COPD]), delivered via a smartphone app and an activity tracker, to help people with COPD maintain (or increase) physical activity after undertaking pulmonary rehabilitation (PR). Objective: This study aimed to determine the feasibility and acceptability of using the SMART-COPD intervention for the self-management of physical activity and to explore the feasibility of conducting a future randomized controlled trial (RCT) to investigate its effectiveness. Methods: We conducted a randomized feasibility study. A total of 30 participants with COPD were randomly allocated to receive the SMART-COPD intervention (n=19) or control (n=11). Participants used SMART-COPD throughout PR and for 8 weeks afterward (ie, maintenance) to set physical activity goals and monitor their progress. Questionnaire-based and physical activity–based outcome measures were taken at baseline, the end of PR, and the end of maintenance. Participants, and health care professionals involved in PR delivery, were interviewed about their experiences with the technology. Results: Overall, 47% (14/30) of participants withdrew from the study. Difficulty in using the technology was a common reason for withdrawal. Participants who completed the study had better baseline health and more prior experience with digital technology, compared with participants who withdrew. Participants who completed the study were generally positive about the technology and found it easy to use. Some participants felt their health had benefitted from using the technology and that it assisted them in achieving physical activity goals. Activity tracking and self-reporting were both found to be problematic as outcome measures of physical activity for this study. There was dissatisfaction among some control group members regarding their allocation. Conclusions: mHealth shows promise in helping people with COPD self-manage their physical activity levels. mHealth interventions for COPD self-management may be more acceptable to people with prior experience of using digital technology and may be more beneficial if used at an earlier stage of COPD. Simplicity and usability were more important for engagement with the SMART-COPD intervention than personalization; therefore, the intervention should be simplified for future use. Future evaluation will require consideration of individual factors and their effect on mHealth efficacy and use; within-subject comparison of step count values; and an opportunity for control group participants to use the intervention if an RCT were to be carried out. Sample size calculations for a future evaluation would need to consider the high dropout rates

Probing the Environment with Galaxy Dynamics

I present various projects to study the halo dynamics of elliptical galaxies. This allows one to study the outer mass and orbital distributions of ellipticals in different environments, and the inner distributions of groups and clusters themselves.Comment: 5 pages, 2 figs, to appear in Proc. ESO Workshop, Groups of Galaxies in the Nearby Universe (5-9 Dec 2005), eds. I. Saviane, V. Ivanov & J. Borissova (Springer-Verlag

Off-Diagonal Elements of the DeWitt Expansion from the Quantum Mechanical Path Integral

The DeWitt expansion of the matrix element M_{xy} = \left\langle x \right| \exp -[\case{1}{2} (p-A)^2 + V]t \left| y \right\rangle, $(p=-i\partial)$ in powers of $t$ can be made in a number of ways. For $x=y$ (the case of interest when doing one-loop calculations) numerous approaches have been employed to determine this expansion to very high order; when $x \neq y$ (relevant for doing calculations beyond one-loop) there appear to be but two examples of performing the DeWitt expansion. In this paper we compute the off-diagonal elements of the DeWitt expansion coefficients using the Fock-Schwinger gauge. Our technique is based on representing $M_{xy}$ by a quantum mechanical path integral. We also generalize our method to the case of curved space, allowing us to determine the DeWitt expansion of \tilde M_{xy} = \langle x| \exp \case{1}{2} [\case{1}{\sqrt {g}} (\partial_\mu - i A_\mu)g^{\mu\nu}{\sqrt{g}}(\partial_\nu - i A_\nu) ] t| y \rangle by use of normal coordinates. By comparison with results for the DeWitt expansion of this matrix element obtained by the iterative solution of the diffusion equation, the relative merit of different approaches to the representation of $\tilde M_{xy}$ as a quantum mechanical path integral can be assessed. Furthermore, the exact dependence of $\tilde M_{xy}$ on some geometric scalars can be determined. In two appendices, we discuss boundary effects in the one-dimensional quantum mechanical path integral, and the curved space generalization of the Fock-Schwinger gauge.Comment: 16pp, REVTeX. One additional appendix concerning end-point effects for finite proper-time intervals; inclusion of these effects seem to make our results consistent with those from explicit heat-kernel method