A Frequentist Approach to Computer Model Calibration

This paper considers the computer model calibration problem and provides a general frequentist solution. Under the proposed framework, the data model is semi-parametric with a nonparametric discrepancy function which accounts for any discrepancy between the physical reality and the computer model. In an attempt to solve a fundamentally important (but often ignored) identifiability issue between the computer model parameters and the discrepancy function, this paper proposes a new and identifiable parametrization of the calibration problem. It also develops a two-step procedure for estimating all the relevant quantities under the new parameterization. This estimation procedure is shown to enjoy excellent rates of convergence and can be straightforwardly implemented with existing software. For uncertainty quantification, bootstrapping is adopted to construct confidence regions for the quantities of interest. The practical performance of the proposed methodology is illustrated through simulation examples and an application to a computational fluid dynamics model.Comment: 21 pages, 2 figure

Systems Biology: A Therapeutic Target for Tumor Therapy

Tumor-related activities that seem to be operationally induced by the division of function, such as inflammation, neoangiogenesis, Warburg effect, immune response, extracellular matrix remodeling, cell proliferation rate, apoptosis, coagulation effects, present itself from a systems perspective as an enhancement of complexity. We hypothesized, that tumor systems-directed therapies might have the capability to use aggregated action effects, as adjustable sizes to therapeutically modulate the tumor systems’ stability, homeostasis, and robustness. We performed a retrospective analysis of recently published data on 224 patients with advanced and heavily pre-treated (10% to 63%) vascular sarcoma, melanoma, renal clear cell, cholangiocellular, carcinoma, hormone-refractory prostate cancer, and multivisceral Langerhans’ cell histiocytosis enrolled in nine multi-center phase II trials (11 centers). Each patient received a multi-targeted systems-directed therapy that consisted of metronomic low-dose chemotherapy, a COX-2 inhibitor, combined with one or two transcription modulators, pioglitazone +/− dexamethasone or IFN-alpha. These treatment schedules may attenuate the metastatic potential, tumor-associated inflammation, may exert site-specific activities, and induce long-term disease stabilization followed by prolonged objective response (3% to 48%) despite poor monoactivity of the respective drugs. Progression-free survival data are comparable with those of reductionist-designed standard first-line therapies. The differential response patterns indicate the therapies’ systems biological activity. Understanding systems biology as adjustable size may break through the barrier of complex tumor-stroma-interactions in a therapeutically relevant way: Comparatively high efficacy at moderate toxicity. Structured systems-directed therapies in metastatic cancer may get a source for detecting the topology of tumor-associated complex aggregated action effects as adjustable sizes available for targeted biomodulatory therapies

Is there a role for chemotherapy in prostate cancer?

There is evidence from randomised-controlled trials that patients with symptomatic hormone-refractory prostate cancer may experience palliative benefit from chemotherapy with mitoxantrone and prednisone. This treatment is well tolerated, even by elderly patients, although the cumulative dose of mitoxantrone is limited by cardiotoxicity. Treatment with docetaxel or paclitaxel, with or without estramustine, appears to convey higher rates of prostate-specific antigen response in phase II trials, but is more toxic. Large phase III trials comparing docetaxel with mitoxantrone have completed accrual. There is no role for chemotherapy in earlier stages of disease except in the context of a well-designed clinical trial

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans

Identifying and tracking turbulence structures

We present a statistical approach to object tracking which allows for paths to merge together or split apart. Paths are also allowed to be born, die, and go undetected for several frames. The splitting and merging of paths is a novel addition for a statistically-based tracking algorithm. This addition is essential for storm tracking, which is the motivation for this work. The utility of this tracker extends well beyond the tracking of storms however. It can be valuable in other tracking applications that have splitting or merging, such as vortices, radar/sonar signals, or groups of people. The method assumes that the location of an object behaves like a Gaussian Process when it is observable. Objects are required to be born, die, split, or merge according to a Markov State Model. Path correspondence is achieved by an algorithm that finds the paths that maximize the likelihood of the assumed model

Effect of the puroindoline locus and environment on Chinese fresh noodle texture

Grain produced from doubled-haploid (DH)wheat lines, developed from a hard- and a soft-grained wheat cultivar, were bulked according to Pinb (puroindoline b) genotypes for an assessment of Chinese fresh noodle texture by a trained taste panel. Each DH line was designated as 'soft' or 'hard' grained, based on a PCR amplification of the wildtype, soft allele, or the mutant, hard allele. Theoretically, the soft and hard grain bulks represented respective Pinb alleles and an independent assortment of unlinked alleles from the parents, Sunco and Chuanyu 12. Grains from the parents and DH lines were grown at 2 locations in Queensland, Australia, and one in Sichuan, China. The grains were milled and processed for a taste panel evaluation in Chengdu, Sichuan. Results suggest the Pinb alleles had a significant effect on noodle softness and explained 30% of the variation; the 'soft' Pinb allele conferred a softer noodle texture. Location had a significant effect on noodle smoothness; wheat grain grown at Biloela, Queensland, produced a smoother noodle texture than grain grown in Sichuan. The effect of location confirms the importance of environment as a variable for this quality character. This investigation exemplifies the utility of Pinb markers for specifically altering Chinese Fresh Noodle texture

Distributions, life history specialisation, and phylogeny of the rainforest vertebrates in the Australian Wet Tropics

The purpose of this data set was to compile distributional, general life-history characteristics and phylogenies for Australian tropical rain forest vertebrates to inform a wide\ud range of comparative studies on the determinants of biodiversity patterns and to assess the impacts of global climate change. We provide three distinct data sets: (1) a table of species specific distributional and life-history traits for 242 vertebrate species found in the rain forests\ud of the Australian Wet Tropics; (2) species distribution maps (GIS raster files) for 202 of the species displaying both the realized and potential distributions; and (3) phylogenies for these species. These species represent 93 birds, 31 amphibians, 31 mammals (including one\ud monotreme), and 47 reptiles. Where information exists, the distributional and life-history data compiled here present information on: indices of environmental specialization (ENFA), habitat specialization, average body mass and size, sexual dimorphism, reproductive characteristics such as age at first reproduction, clutch/litter size, number of reproductive bouts per year and breeding seasonality, longevity, time of day when most active, and dispersal ability; distributional characteristics such as range size (potential and realized for both total and core ranges) and observed ranges in temperature, precipitation, and elevation; and niche attributes such as environmental marginality and specialization. The distribution\ud maps provided represent a combination of presence-only ecological niche modeling (using MaxEnt) to estimate the potential distribution of a species followed by biogeographic clipping by expert opinion based on extensive field data and a subregional classification relevant to the\ud topography and biogeographic history of the region to produce best-possible estimates of the realized distribution. Our assemblage contains many species with a shared evolutionary history, and thus many analyses of these data will need to account for phylogeny. Although a\ud comprehensive phylogeny with branch length information does not exist for this diverse group of species, we present a best-estimate composite phylogeny constructed primarily from\ud recently published molecular phylogenies of included groups

Estimated use of ground water for irrigation in Wisconsin, 1984 /

Chiefly tables.Shipping list no.: 87-322-P.Bibliography: p. 4.Mode of access: Internet