Transverse Galaxy Velocities from Multiple Topological Images

The study of the kinematics of galaxies within clusters or groups has the limitation that only one of the three velocity components and only two of the three spatial components of a galaxy position in six-dimensional phase space can normally be measured. However, if multiple topological images of a cluster exist, then the radial positions and sky plane mean velocities of galaxies in the cluster may also be measurable from photometry of the two cluster images. The vector arithmetic and principles of the analysis are presented. These are demonstrated by assuming the suggested topological identification of the clusters RX J1347.5-1145 and CL 09104+4109 to be correct and deducing the sky-plane relative velocity component along the axis common to both images of this would-be single cluster. Three out of four of the inferred transverse velocities are consistent with those expected in a rich cluster. A control sample of random `common' sky-plane axes, independent of the topological hypothesis, implies that this is not surprising. This shows that while galaxy kinematics are deducible from knowledge of cosmological topology, it is not easy to use them to refute a specific candidate manifold.Comment: 13 pages, 7 figures, accepted for MNRA

Present state of knowledge of the upper atmosphere: An assessment report; processes that control ozone and other climatically important trace gases

The state of knowledge of the upper atmosphere was assessed as of January 1986. The physical, chemical, and radiative processes which control the spatial and temporal distribution of ozone in the atmosphere; the predicted magnitude of ozone perturbations and climate changes for a variety of trace gas scenarios; and the ozone and temperature data used to detect the presence or absence of a long term trend were discussed. This assessment report was written by a small group of NASA scientists, was peer reviewed, and is based primarily on the comprehensive international assessment document entitled Atmospheric Ozone 1985: Assessment of Our Understanding of the Processes Controlling Its Present Distribution and Change, to be published as the World Meteorological Organization Global Ozone Research and Monitoring Project Report No. 16

Introducing Mexican needlets for CMB analysis: Issues for practical applications and comparison with standard needlets

Over the last few years, needlets have a emerged as a useful tool for the analysis of Cosmic Microwave Background (CMB) data. Our aim in this paper is first to introduce in the CMB literature a different form of needlets, known as Mexican needlets, first discussed in the mathematical literature by Geller and Mayeli (2009a,b). We then proceed with an extensive study of the properties of both standard and Mexican needlets; these properties depend on some parameters which can be tuned in order to optimize the performance for a given application. Our second aim in this paper is then to give practical advice on how to adjust these parameters in order to achieve the best properties for a given problem in CMB data analysis. In particular we investigate localization properties in real and harmonic spaces and propose a recipe on how to quantify the influence of galactic and point source masks on the needlet coefficients. We also show that for certain parameter values, the Mexican needlets provide a close approximation to the Spherical Mexican Hat Wavelets (whence their name), with some advantages concerning their numerical implementation and the derivation of their statistical properties.Comment: 40 pages, 11 figures, published version, main modification: added section on more realistic galactic and point source mask

Earth matter density uncertainty in atmospheric neutrino oscillations

That muon neutrinos $\nu_{\mu}$ oscillating into the mixture of tau neutrinos $\nu_{\tau}$ and sterile neutrinos $\nu_{s}$ has been studied to explain the atmospheric $\nu_{\mu}$ disappearance. In this scenario, the effect of Earth matter is a key to determine the fraction of $\nu_{s}$. Considering that the Earth matter density has uncertainty and this uncertainty has significant effects in some neutrino oscillation cases, such as the CP violation in very long baseline neutrino oscillations and the day-night asymmetry for solar neutrinos, we study the effects caused by this uncertainty in the above atmospheric $\nu_{\mu}$ oscillation scenario. We find that this uncertainty seems to have no significant effects and that the previous fitting results need not to be modified fortunately.Comment: 7 pages, 1 figure, to appear in Phys. Rev.

Hepatic resection for metastatic colorectal adenocarcinoma: A proposal of a prognostic scoring system

Background: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. Study Design: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S(t) = [S(o)(t)](exp(R - R(o))), where S(o)(t) is the survival rate of patients with none of the identified risk factors and R(o) = 0. Results: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R = 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). Conclusions: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies

In vitro analysis of promoter activity in Müller cells

PurposeRational modification of promoter architecture is necessary for manipulation of transgene activity and requires accurate deciphering of regulatory control elements. Identification of minimally sized promoters is critical to the design of viral vectors for gene therapy. To this end, we evaluated computational methods for predicting short DNA sequences capable of driving gene expression in Müller cells.MethodsWe measured enhanced green fluorescent protein (eGFP) expression levels driven by "full-length" promoters, and compared these data with computationally identified shorter promoter elements from the same genes. We cloned and screened over 90 sequences from nine Müller cell-associated genes: CAR2, CD44, GFAP, GLUL, PDGFRA, RLBP1, S100B, SLC1A3, and vimentin (VIM). We PCR-amplified the "full-length" promoter (~1500 bp), the proximal promoter (~500 bp), and the most proximal evolutionarily conserved region (ECR; 95-871 bp) for each gene, both with and without their respective 5' untranslated regions (UTRs), from C57BL/6J mouse genomic DNA. We selected and cloned additional ECRs from more distal genomic regions (both 5' and 3') of the VIM and CD44 genes, using both mouse and rat (Sprague-Dawley) genomic DNA as templates. PCR products were cloned into the pFTMGW or pFTM3GW lentiviral transfer vectors. Plasmid constructs were transfected into rat (wMC) or human (MIO-M1) Müller cells, and eGFP expression levels were evaluated by fluorescence microscopy and flow cytometry. Selected constructs were also examined in NIH/3T3 and Neuro-2a cells.ResultsSeveral ECRs from the nine Müller cell-associated genes were able to drive reporter gene expression as well as their longer counterparts. Preliminary comparisons of ECRs from the VIM and CD44 genes suggested that inclusion of UTRs in promoter constructs resulted in increased transgene expression levels. Systematic comparison of promoter activity from nine Müller cell-expressed genes supported this finding, and characteristic regulation profiles were evident among the different genes tested. Importantly, individual cloned promoter sequences were capable of driving distinct levels of transgene expression, resulting in up to eightfold more cells expressing eGFP with up to 3.8-fold higher mean fluorescence intensity (MFI). Furthermore, combining constructs into single regulatory "units" modulated transgene expression, suggesting that secondary gene sequences provided in cis may be used to fine-tune gene expression levels.ConclusionsIn this study, we demonstrate that computational and empirical methods, when used in combination, can efficiently identify short promoters that are active in cultured Müller cells. In addition, the pFTM3GW vector can be used to study the effects of combined promoter elements. We anticipate that these methods will expedite the design and testing of synthetic/chimeric promoter constructs that should be useful for both in vitro and in vivo applications

Splines and Wavelets on Geophysically Relevant Manifolds

Analysis on the unit sphere $\mathbb{S}^{2}$ found many applications in seismology, weather prediction, astrophysics, signal analysis, crystallography, computer vision, computerized tomography, neuroscience, and statistics. In the last two decades, the importance of these and other applications triggered the development of various tools such as splines and wavelet bases suitable for the unit spheres $\mathbb{S}^{2}$, $\>\>\mathbb{S}^{3}$ and the rotation group $SO(3)$. Present paper is a summary of some of results of the author and his collaborators on generalized (average) variational splines and localized frames (wavelets) on compact Riemannian manifolds. The results are illustrated by applications to Radon-type transforms on $\mathbb{S}^{d}$ and $SO(3)$.Comment: The final publication is available at http://www.springerlink.co

Functional promoter testing using a modified lentiviral transfer vector

PurposeThe importance of retinal glial cells in the maintenance of retinal health and in retinal degenerations has not been fully explored. Several groups have suggested that secretion of neurotrophic proteins from the retina's primary glial cell type, the Müller cell, holds promise for treating retinal degenerations. Tight regulation of transgene expression in Müller cells is likely to be critical to the efficacy of long-term neuroprotective therapies, due to the genetic heterogeneity and progressive nature of retinal disease. To this end, we developed a modified lentiviral (LV) transfer vector (pFTMGW) to accelerate the testing and evaluation of novel transcriptional regulatory elements. This vector facilitates identification and characterization of regulatory elements in terms of size, cell specificity and ability to control transgene expression levels.MethodsA synthetic multiple cloning site (MCS) which can accept up to five directionally cloned DNA regulatory elements was inserted immediately upstream of an enhanced green fluorescent protein (eGFP) reporter. A cytomegalovirus (CMV) promoter, required for tat-independent viral packaging, is located around 2 kb upstream of the eGFP reporter and is capable of directing transgene expression. A synthetic transcription blocker (TB) was inserted to insulate the MCS/eGFP from the CMV promoter. We evaluated eGFP expression from pFTMGW and control constructs using flow cytometry and quantitative reverse transcriptase polymerase chain reaction (RT-PCR). We also tested and compared the activity and cell specificity of a computationally identified promoter fragment from the rat vimentin gene (Vim409) in transfection and lentiviral infection experiments using fluorescence microscopy.ResultsTransfection data, quantitative RT-PCR, and flow cytometry show that around 85% of expression from the CMV promoter was blocked by the TB element, allowing direct evaluation of expression from the Vim409 candidate promoter cloned into the MCS. Lentiviruses generated from this construct containing the Vim409 promoter (without the TB element) drove robust eGFP expression in Müller cells in vitro and in vivo.ConclusionsThe TB element efficiently prevented eGFP expression by the upstream CMV promoter and the novel MCS facilitated testing of an evolutionarily conserved regulatory element. Additional sites allow for combinatorial testing of additional promoter, enhancer, and/or repressor elements in various configurations. This modified LV transfer vector is an effective tool for expediting functional analysis of gene regulatory elements in Müller glia, and should prove useful for promoter analyses in other cell types and tissues

61 Tiotropium Respimat in cystic fibrosis: Efficacy and safety results of phase III randomized placebo-controlled trial

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