Multi-dimensional parameter estimation of heavy-tailed moving averages

In this paper we present a parametric estimation method for certain multi-parameter heavy-tailed L\'evy-driven moving averages. The theory relies on recent multivariate central limit theorems obtained in [3] via Malliavin calculus on Poisson spaces. Our minimal contrast approach is related to the papers [14, 15], which propose to use the marginal empirical characteristic function to estimate the one-dimensional parameter of the kernel function and the stability index of the driving L\'evy motion. We extend their work to allow for a multi-parametric framework that in particular includes the important examples of the linear fractional stable motion, the stable Ornstein-Uhlenbeck process, certain CARMA(2, 1) models and Ornstein-Uhlenbeck processes with a periodic component among other models. We present both the consistency and the associated central limit theorem of the minimal contrast estimator. Furthermore, we demonstrate numerical analysis to uncover the finite sample performance of our method

Wild-Type Drosophila melanogaster as a Model Host to Analyze Nitrogen Source Dependent Virulence of Candida albicans

The fungal pathogen Candida albicans is a common cause of opportunistic infections in humans. We report that wild-type Drosophila melanogaster (OrR) flies are susceptible to virulent C. albicans infections and have established experimental conditions that enable OrR flies to serve as model hosts for studying C. albicans virulence. After injection into the thorax, wild-type C. albicans cells disseminate and invade tissues throughout the fly, leading to lethality. Similar to results obtained monitoring systemic infections in mice, well-characterized cph1Δ efg1Δ and csh3Δ fungal mutants exhibit attenuated virulence in flies. Using the OrR fly host model, we assessed the virulence of C. albicans strains individually lacking functional components of the SPS sensing pathway. In response to extracellular amino acids, the plasma membrane localized SPS-sensor (Ssy1, Ptr3, and Ssy5) activates two transcription factors (Stp1 and Stp2) to differentially control two distinct modes of nitrogen acquisition (host protein catabolism and amino acid uptake, respectively). Our results indicate that a functional SPS-sensor and Stp1 controlled genes required for host protein catabolism and utilization, including the major secreted aspartyl protease SAP2, are required to establish virulent infections. By contrast, Stp2, which activates genes required for amino acid uptake, is dispensable for virulence. These results indicate that nutrient availability within infected hosts directly influences C. albicans virulence

The compositional and evolutionary logic of metabolism

Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure

The panorama of future sick-leave diagnoses among young adults initially long-term sickness absent due to neck, shoulder, or back diagnoses. An 11-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Little is known about future sick-leave diagnoses among individuals on long-term sickness absence. The aim of this study was to describe the panorama of sick-leave diagnoses over time among young adults initially sick-listed for ≥ 28 days due to back, neck, or shoulder diagnoses</p> <p>Methods</p> <p>An 11-year prospective population-based cohort study including all 213 individuals in a Swedish municipality who, in 1985, were aged 25–34 years and had a new sick-leave spell ≥ 28 days due to neck, shoulder, or back diagnoses.</p> <p>Results</p> <p>Over the 11-year period, the young adults in this cohort had 176,825 sick-leave days in 7,878 sick-leave periods (in 4,610 sick-leave spells) due to disorders in 17 of the 18 ICD-8 diagnostic categories (International Classification of Diseases, Revision 8). Musculoskeletal or mental diagnoses accounted for most of the sick-leave days, whereas most of the sick-leave periods were due to musculoskeletal, respiratory, or infectious disorders, or to unclassified symptoms. Most cohort members had had four to eight different sick-leave diagnoses over the 11 years, although some had had up to 11 diagnoses. Only two individuals (1%) had been sickness absent solely due to musculoskeletal diagnoses.</p> <p>Conclusion</p> <p>Although the young adults initially were sick listed with back, neck, or shoulder diagnoses, their sickness absence during the follow up were due to a wide variety of other medical diagnoses. It might be that the ill-health content of sickness absence due to back pain is greater than usually assumed. More research on prognoses of sick-leave diagnoses among long-term sick listed is warranted.</p

Systematic Mutational Analysis of the Intracellular Regions of Yeast Gap1 Permease

The yeast general amino acid permease Gap1 is a convenient model for studying the intracellular trafficking of membrane proteins. Present at the plasma membrane when the nitrogen source is poor, it undergoes ubiquitin-dependent endocytosis and degradation upon addition of a good nitrogen source, e.g. ammonium. It comprises 12 transmembrane domains (TM) flanked by cytosol-facing N- and C-terminal tails (NT, CT). The NT of Gap1 contains the acceptor lysines for ubiquitylation and its CT includes a sequence essential to exit from the endoplasmic reticulum (ER).Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Pathways of Carbon Assimilation and Ammonia Oxidation Suggested by Environmental Genomic Analyses of Marine Crenarchaeota

Marine Crenarchaeota represent an abundant component of oceanic microbiota with potential to significantly influence biogeochemical cycling in marine ecosystems. Prior studies using specific archaeal lipid biomarkers and isotopic analyses indicated that planktonic Crenarchaeota have the capacity for autotrophic growth, and more recent cultivation studies support an ammonia-based chemolithoautotrophic energy metabolism. We report here analysis of fosmid sequences derived from the uncultivated marine crenarchaeote, Cenarchaeum symbiosum, focused on the reconstruction of carbon and energy metabolism. Genes predicted to encode multiple components of a modified 3-hydroxypropionate cycle of autotrophic carbon assimilation were identified, consistent with utilization of carbon dioxide as a carbon source. Additionally, genes predicted to encode a near complete oxidative tricarboxylic acid cycle were also identified, consistent with the consumption of organic carbon and in the production of intermediates for amino acid and cofactor biosynthesis. Therefore, C. symbiosum has the potential to function either as a strict autotroph, or as a mixotroph utilizing both carbon dioxide and organic material as carbon sources. From the standpoint of energy metabolism, genes predicted to encode ammonia monooxygenase subunits, ammonia permease, urease, and urea transporters were identified, consistent with the use of reduced nitrogen compounds as energy sources fueling autotrophic metabolism. Homologues of these genes, recovered from ocean waters worldwide, demonstrate the conservation and ubiquity of crenarchaeal pathways for carbon assimilation and ammonia oxidation. These findings further substantiate the likely global metabolic importance of Crenarchaeota with respect to key steps in the biogeochemical transformation of carbon and nitrogen in marine ecosystems

The Vlochos Archaeological Project: Report on the 2016– 2018 seasons of Greek-Swedish archaeological work at Vlochos, Thessaly

The Vlochos Archaeological Project (2016–2018) was a Greek-Swedish archaeological investigation of the remains of the ancient urban site at Vlochos in western Thessaly, Greece. Employing a wide array of noninvasive methods, the project succeeded in completely mapping the visible remains, which had previously not been systematically investigated. The extensive remains of multi-period urban fortifications, a ClassicalHellenistic city, a Roman town, and a Late Antique fortress were identified, evidence of the long history of habitation on this site. Since comparatively little fieldwork has been conducted in the region, the results significantly increase our knowledge of the history and archaeology of Thessaly