On a new NBUE property in multivariate sense: an application

Since multivariate lifetime data frequently occur in applications, various properties of multivariate distributions have been previously considered to model and describe the main concepts of aging commonly considered in the univariate setting. The generalization of univariate aging notions to the multivariate case involves, among other factors, appropriate definitions of multivariate quantiles and related notions, which are able to correctly describe the intrinsic characteristics of the concepts of aging that should be generalized, and which provide useful tools in the applications. A new multivariate version of the well-known New Better than Used in Expectation univariate aging notion is provided, by means of the concepts of the upper corrected orthant and multivariate excess-wealth function. Some of its properties are described, with particular attention paid to those that can be useful in the analysis of real data sets. Finally, through an example it is illustrated how the new multivariate aging notion influences the final results in the analysis of data on tumor growth from the Comprehensive Cohort Study performed by the German Breast Cancer Study Grou

An Ecological Basis for Ecosystem Management

This report was prepared by the Southwestern Regional Ecosystem Management Study Team composed of management and research biologists. The USDA Forest Service Southwestern Regions Regional Forester, Larry Henson, and the Rocky Mountain Forest and Range Experiment Station Director, Denver Burns, chartered this team to recommend an ecological basis for ecosystem management. This report is not intended to provide details on all aspects of ecosystem management; it simply provides information and makes recommendations for an ecological basis for ecosystem management. The report is not a decision document. It does not allocate resources on public lands nor does it make recommendations to that effect. The report of this Study Team may be relied upon as input in processes initiated under the National Environmental Policy Act (NEPA), National Forest Management Act (NFMA), Endangered Species Act (ESA), Administrative Procedures Act (APA), and other applicable laws. The information contained in this report is general in nature, rather than site specific. Implementation of ecosystem management and allocation of resources on Forest Service administered lands is the responsibility of the National Forest System in partnership with Forest Service Research and State and Private Forestry. Implementation is done through Forest and project plans that are subject to the NEPA process of disclosing the effects of proposed actions and affording the opportunity for public comment. The Southwestern Region follows a planning process for projects called Integrated Resource Management (IRM). The opinions expressed by the authors do not necessarily represent the policy or position of the U.S. Department of Agriculture, the Forest Service, The Nature Conservancy, or the Arizona Game and Fish Department. The Study Team acknowledges the valuable input of more than 50 individuals from various agencies, universities, professional organizations, and other groups who provided thoughtful comments of an earlier draft of this document. Some of their comments are included in Appendix 3

β1 integrins mediate the BMP2 dependent transcriptional control of osteoblast differentiation and osteogenesis

Osteoblast differentiation is a highly regulated process that requires coordinated information from both soluble factors and the extracellular matrix. Among these extracellular stimuli, chemical and physical properties of the matrix are sensed through cell surface receptors such as integrins and transmitted into the nucleus to drive specific gene expression. Here, we showed that the conditional deletion of β1 integrins in the osteo-precursor population severely impacts bone formation and homeostasis both in vivo and in vitro. Mutant mice displayed a severe bone deficit characterized by bone fragility and reduced bone mass. We showed that β1 integrins are required for proper BMP2 dependent signaling at the pre-osteoblastic stage, by positively modulating Smad1/5-dependent transcriptional activity at the nuclear level. The lack of β1 integrins results in a transcription modulation that relies on a cooperative defect with other transcription factors rather than a plain blunted BMP2 response. Our results point to a nuclear modulation of Smad1/5 transcriptional activity by β1 integrins, allowing a tight control of osteoblast differentiation

TITAN's Digital RFQ Ion Beam Cooler and Buncher, Operation and Performance

We present a description of the Radio Frequency Quadrupole (RFQ) ion trap built as part of the TITAN facility. It consists of a gas-filled, segmented, linear Paul trap and is the first stage of the TITAN setup with the purpose of cooling and bunching radioactive ion beams delivered from ISAC-TRIUMF. This is the first such device to be driven digitally, i.e., using a high voltage ($V_{pp} = \rm{400 \, V}$), wide bandwidth ($0.2 < f < 1.2 \, \rm{MHz}$) square-wave as compared to the typical sinusoidal wave form. Results from the commissioning of the device as well as systematic studies with stable and radioactive ions are presented including efficiency measurements with stable $^{133}$Cs and radioactive $^{124, 126}$Cs. A novel and unique mode of operation of this device is also demonstrated where the cooled ion bunches are extracted in reverse mode, i.e., in the same direction as previously injected.Comment: 34 pages, 17 figure

Oestrogen metabolites in relation to isoprostanes as a measure of oxidative stress

Objective  Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16Α-hydroxyoestrone (16Α-OHE1) are thought to curtail the greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related oestrogen levels to F 2a -isoprostane levels, a biomarker of oxidative stress. Design and participants  Data were obtained from 1647 women, aged 47–57 years, participating in the fifth annual follow-up of the Study of Women's Health Across the Nation (SWAN), a study of the menopausal transition. Measurements  Serum E2 and urinary 2-OHE1 and 16Α-OHE1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and urinary F 2a -isoprostanes were measured by enzyme immunoassay (EIA). Results  F 2a -isoprostane concentrations were elevated in women who smoked, a behaviour associated with increased oxidative stress, but not in stages of the natural menopause. Mean F 2a -isoprostane concentrations among pre- and postmenopausal women who smoked were 1082 and 1064 pg/ml, respectively, values double those in pre- (343 pg/ml) and postmenopausal (379 pg/ml) nonsmoking women. 2-OHE1 and F 2a -isoprostane concentrations were positively and highly correlated (partial correlations Ρ Y|X  = 0·44 and Ρ Y|X  = 0·43 in pre- and postmenopausal women, respectively). Similarly, 16Α-OHE1 concentrations were positively and highly correlated with F 2a -isoprostane concentrations (Ρ Y|X  = 0·52 and Ρ Y|X  = 0·59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F 2a -isoprostanes only in postmenopausal women (Ρ Y|X  = 0·20). Associations were adjusted for age, body mass index (BMI), race/ethnicity, lipids, physical activity level and alcohol consumption. Conclusions  This study does not support the commonly held hypothesis that levels of endogenous E2 or its oestrone metabolites favourably modify oxidative stress by decreasing F2 a -isoprostane levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74943/1/j.1365-2265.2007.03108.x.pd

Ramond-Ramond Fields, Fractional Branes and Orbifold Differential K-Theory

We study D-branes and Ramond-Ramond fields on global orbifolds of Type II string theory with vanishing H-flux using methods of equivariant K-theory and K-homology. We illustrate how Bredon equivariant cohomology naturally realizes stringy orbifold cohomology. We emphasize its role as the correct cohomological tool which captures known features of the low-energy effective field theory, and which provides new consistency conditions for fractional D-branes and Ramond-Ramond fields on orbifolds. We use an equivariant Chern character from equivariant K-theory to Bredon cohomology to define new Ramond-Ramond couplings of D-branes which generalize previous examples. We propose a definition for groups of differential characters associated to equivariant K-theory. We derive a Dirac quantization rule for Ramond-Ramond fluxes, and study flat Ramond-Ramond potentials on orbifolds.Comment: 46 pages; v2: typos correcte

Contemporary percutaneous treatment of unprotected left main coronary stenoses: initial results from a multicenter registry analysis 1994-1996.

BACKGROUND: Coronary artery bypass surgery (CABG) has been considered the therapy of choice for patients with unprotected left main (ULMT) coronary stenoses. Selected single-center reports suggest that the results of percutaneous intervention may now approach those of CABG. METHODS AND RESULTS: To assess the results of percutaneous ULMT treatment from a wide variety of experienced interventional centers, we requested data on consecutive patients treated after January 1, 1994, from 25 centers. One hundred seven patients were identified who were treated either electively (n=91) or for acute myocardial infarction (n=16). Of patients treated electively, 25% were considered inoperable, and 27% were considered high risk for bypass surgery. Primary treatment included stents (50%), directional atherectomy (24%), and balloon angioplasty (20%). Follow-up was 98.8% complete at 15+/-8 months. Results varied considerably, depending on presentation and treatment. For patient

Exploring mechanisms of lipid nanoparticle-mucus interactions in healthy and cystic fibrosis conditions

Mucus forms the first defense line of human lungs, and as such hampers the efficient delivery of therapeutics to the underlying epithelium. This holds particularly true for genetic cargo such as CRISPR-based gene editing tools which cannot readily surmount the mucosal barrier. While lipid nanoparticles (LNPs) emerge as versatile non-viral gene delivery systems that can help overcome the delivery challenge, many knowledge gaps remain, especially for diseased states such as cystic fibrosis (CF). This study provides fundamental insights into Cas9 mRNA or ribonucleoprotein-loaded LNP-mucus interactions in healthy and diseased states by assessing the impact of the genetic cargo, mucin sialylation, mucin concentration, ionic strength, pH, and polyethylene glycol (PEG) concentration and nature on LNP diffusivity leveraging experimental approaches and Brownian dynamics (BD) simulations. Taken together, this study identifies key mucus and LNP characteristics that are critical to enabling a rational LNP design for transmucosal delivery

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.