Constructing and generalizing multivariate copulas: a generalizing approach

Recently, Liebscher (2006) introduced a general construction scheme of d-variate copulas which generalizes the Archimedean family. Similarly, Morillas (2005) proposed a method to obtain a variety of new copulas from a given d-copula. Both approaches coincide only for the particular subclass of Archimedean copulas. Within this work we present a unifying framework which includes both Liebscher and Morillas copulas as special cases. Above that, more general copulas may be constructed. First examples are given. --construction of d-variate copulas,Archimedean copulas

Chemical defenses of the Caribbean sponges Agelas wiedenmayeri and Agelas conifera

Previous studies have determined that Caribbean reef sponges of the genus Agelas are chemically defended from fish predation by brominated pyrrole alkaloids, and that the compounds responsible for this defense have been elucidated for one species, Agelas clathrodes. In this study, we expand our understanding of chemical defense in this common sponge genus to include the characterization of defensive metabolites in the tissues of Agelas wiedenmayeri and Agelas conifera. Bioassay-directed isolation of defensive metabolites was undertaken using fish feeding assays carried out in laboratory aquaria and in the field. Agelas wiedenmayeri contained the same two major metabolites as Agelas clathrodes, 4,5-dibromopyrrole-2-carboxylic acid (1), and oroidin (2), in addition to a small amount of bromoageliferin (7). The two major metabolites were present at higher concentrations in samples of Agelas wiedenmayeri than in Agelas clathrodes, and their relative concentrations were reversed, with Agelas wiedenmayeri on average containing more 4,5-dibromopyrrole-2-carboxylic acid (1) (2.0 mg/mL) than oroidin (2) (0.8 mg/mL). Agelas conifera contained a mixture of dimeric bromopyrrole alkaloids dominated by sceptrin (3), with <10% each of dibromosceptrin (5), bromoageliferin (7), dibromoageliferin (8), ageliferin (6), and bromosceptrin (4). Mean concentration of sceptrin (3) in sponge tissue was 5.3 mg/mL; this compound deterred feeding of reef fish in aquarium assays at 1.0 mg/mL, the lowest concentration assayed. Sceptrin (3) concentrations were higher in sponges collected in the southern Bahama Islands than those collected in the middle Bahamas, but reasons for this variation remain unclear. The structure-activity relationship of the pyrrole group was investigated by assaying derivatives of the active metabolites. Feeding deterrent activity of the molecule was enhanced by the addition of bromine to the pyrrole group, but not affected by exchange of the heteroatom from N to O or S. Combining an understanding of the structure-activity relationship of Agelas metabolites with an understanding of the variation in these metabolites across the genus may provide insight into the evolution of defensive chemistry in this highly successful taxa of pan-tropical sponges

Multivariate Copula Models at Work: Outperforming the desert island copula?

Since the pioneering work of Embrechts and co-authors in 1999, copula models enjoy steadily increasing popularity in finance. Whereas copulas are well-studied in the bivariate case, the higher-dimensional case still offers several open issues and it is by far not clear how to construct copulas which sufficiently capture the characteristics of financial returns. For this reason, elliptical copulas (i.e. Gaussian and Student-t copula) still dominate both empirical and practical applications. On the other hand, several attractive construction schemes appeared in the recent literature prom sing flexible but still manageable dependence models. The aim of this work is to empirically investigate whether these models are really capable to outperform its benchmark, i.e. the Student-t copula (which is termed by Paul Embrechts as "desert island copula" on account of its excellent fit to financial returns) and, in addition, to compare the fit of these different copula classes among themselves. --KS-copula,Hierarchical Archimedian,Product copulas,Pair-copula decomposition

Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer

Background: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue. Methods: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread. Results: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease. Conclusions: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease

Persistence of Methicillin-resistant Staphylococcus aureus (MRSA) in pig herds over a two year period

Aim of this study was to determine if a known MRSA contamination within a pig herd could persist for a period of two years. Material and Methods: 16 pig herds with a known MRSA contamination were asked to participate in this study. Per herd, five dust swabs (Sodibox®) were collected every two months for a period of two years. Samples were tested for presence of MRSA by culture and two PCR’s for confirmation of MRSA. Isolates were typed by spa- en MLVA-typing

The Fantastic Four: A plug 'n' play set of optimal control pulses for enhancing nmr spectroscopy

We present highly robust, optimal control-based shaped pulses designed to replace all 90{\deg} and 180{\deg} hard pulses in a given pulse sequence for improved performance. Special attention was devoted to ensuring that the pulses can be simply substituted in a one-to-one fashion for the original hard pulses without any additional modification of the existing sequence. The set of four pulses for each nucleus therefore consists of 90{\deg} and 180{\deg} point-to-point (PP) and universal rotation (UR) pulses of identical duration. These 1 ms pulses provide uniform performance over resonance offsets of 20 kHz (1H) and 35 kHz (13C) and tolerate reasonably large radio frequency (RF) inhomogeneity/miscalibration of (+/-)15% (1H) and (+/-)10% (13C), making them especially suitable for NMR of small-to-medium-sized molecules (for which relaxation effects during the pulse are negligible) at an accessible and widely utilized spectrometer field strength of 600 MHz. The experimental performance of conventional hard-pulse sequences is shown to be greatly improved by incorporating the new pulses, each set referred to as the Fantastic Four (Fanta4).Comment: 28 pages, 19 figure

Livestock density as risk factor for livestock-associated methicillin-resistant Staphylococcus aureus, the Netherlands

To determine whether persons living in areas of high animal density are at increased risk for carrying livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA), we used an existing dataset of persons in the Netherlands with LA-MRSA carriage and controls who carried other types of MRSA. Results of running univariate and multivariate logistic regression models indicated that living in livestock-dense areas increases the odds of nasal carriage of LA-MRSA. We found that doubling pig, cattle, and veal calf densities per municipality increased the odds of LA-MRSA carriage over carriage of other types of MRSA by 24.7% (95% CI 0.9%–54.2%), 76.9% (95% CI 11.3%–81.3%), and 24.1% (95% CI 5.5%–45.9%), respectively, after adjusting for direct animal contact, living in a rural area, and the probable source of MRSA carriage. Controlling the spread of LA-MRSA thus requires giving attention to community members in animal-dense regions who are unaffiliated with livestock farming

Generation of Covalently Closed Circular DNA of Hepatitis B Viruses via Intracellular Recycling Is Regulated in a Virus Specific Manner

Persistence of hepatitis B virus (HBV) infection requires covalently closed circular (ccc)DNA formation and amplification, which can occur via intracellular recycling of the viral polymerase-linked relaxed circular (rc) DNA genomes present in virions. Here we reveal a fundamental difference between HBV and the related duck hepatitis B virus (DHBV) in the recycling mechanism. Direct comparison of HBV and DHBV cccDNA amplification in cross-species transfection experiments showed that, in the same human cell background, DHBV but not HBV rcDNA converts efficiently into cccDNA. By characterizing the distinct forms of HBV and DHBV rcDNA accumulating in the cells we find that nuclear import, complete versus partial release from the capsid and complete versus partial removal of the covalently bound polymerase contribute to limiting HBV cccDNA formation; particularly, we identify genome region-selectively opened nuclear capsids as a putative novel HBV uncoating intermediate. However, the presence in the nucleus of around 40% of completely uncoated rcDNA that lacks most if not all of the covalently bound protein strongly suggests a major block further downstream that operates in the HBV but not DHBV recycling pathway. In summary, our results uncover an unexpected contribution of the virus to cccDNA formation that might help to better understand the persistence of HBV infection. Moreover, efficient DHBV cccDNA formation in human hepatoma cells should greatly facilitate experimental identification, and possibly inhibition, of the human cell factors involved in the process

"Safe" Coulomb Excitation of 30Mg

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin nat-Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative de-excitation gamma ray yields the B(E2; 0+ -> 2+) value of 30Mg was determined to be 241(31) e2fm4. Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope 30Mg lies still outside the ``island of inversion''