ICONGETM v1.0 – flexible NUOPC-driven two-way coupling via ESMF exchange grids between the unstructured-grid atmosphere model ICON and the structured-grid coastal ocean model GETM

Two-way model coupling is important for representing the mutual interactions and feedbacks between atmosphere and ocean dynamics. This work presents the development of the two-way coupled model system ICONGETM, consisting of the atmosphere model ICON and the ocean model GETM. ICONGETM is built on the latest NUOPC coupling software with flexible data exchange and conservative interpolation via ESMF exchange grids. With ICON providing a state-of-the-art kernel for numerical weather prediction on an unstructured mesh and GETM being an established coastal ocean model, ICONGETM is especially suited for high-resolution studies. For demonstration purposes the newly developed model system has been applied to a coastal upwelling scenario in the central Baltic Sea

High-resolution classification of south patagonian peat bog microforms reveals potential gaps in up-scaled CH4 fluxes by use of Unmanned Aerial System (UAS) and CIR imagery

South Patagonian peat bogs are little studied sources of methane (CH4). Since CH4 fluxes can vary greatly on a small scale of meters, high-quality maps are needed to accurately quantify CH4 fluxes from bogs. We used high-resolution color infrared (CIR) images captured by an Unmanned Aerial System (UAS) to investigate potential uncertainties in total ecosystem CH4 fluxes introduced by the classification of the surface area. An object-based approach was used to classify vegetation both on species and microform level. We achieved an overall Kappa Index of Agreement (KIA) of 0.90 for the species- and 0.83 for the microform-level classification, respectively. CH4 fluxes were determined by closed chamber measurements on four predominant microforms of the studied bog. Both classification approaches were employed to up-scale CH4 closed chamber measurements in a total area of around 1.8 hectares. Including proportions of the surface area where no chamber measurements were conducted, we estimated a potential uncertainty in ecosystem CH4 fluxes introduced by the classification of the surface area. This potential uncertainty ranged from 14.2 mg·m-2· day-1 to 26.8 mg·m-2· day-1. Our results show that a simple classification with only few classes potentially leads to pronounced bias in total ecosystem CH4 fluxes when plot-scale fluxes are up-scaled.Fil: Lehmann, Jan R. K.. Westfalische Wilhelms Universitat; AlemaniaFil: Münchberger, Wiebke. Westfalische Wilhelms Universitat; AlemaniaFil: Knoth, Christian. Westfalische Wilhelms Universitat; AlemaniaFil: Blodau, Christian. Westfalische Wilhelms Universitat; AlemaniaFil: Nieberding, Felix. Westfalische Wilhelms Universitat; AlemaniaFil: Prinz, Torsten. Westfalische Wilhelms Universitat; AlemaniaFil: Pancotto, Veronica Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Kleinebecker, Till. Westfalische Wilhelms Universitat; Alemani

Expression of LIM kinase 1 is associated with reversible G1/S phase arrest, chromosomal instability and prostate cancer

<p>Abstract</p> <p>Background</p> <p>LIM kinase 1 (LIMK1), a LIM domain containing serine/threonine kinase, modulates actin dynamics through inactivation of the actin depolymerizing protein cofilin. Recent studies have indicated an important role of LIMK1 in growth and invasion of prostate and breast cancer cells; however, the molecular mechanism whereby LIMK1 induces tumor progression is unknown. In this study, we investigated the effects of ectopic expression of LIMK1 on cellular morphology, cell cycle progression and expression profile of LIMK1 in prostate tumors.</p> <p>Results</p> <p>Ectopic expression of LIMK1 in benign prostatic hyperplasia cells (BPH), which naturally express low levels of LIMK1, resulted in appearance of abnormal mitotic spindles, multiple centrosomes and smaller chromosomal masses. Furthermore, a transient G1/S phase arrest and delayed G2/M progression was observed in BPH cells expressing LIMK1. When treated with chemotherapeutic agent Taxol, no metaphase arrest was noted in these cells. We have also noted increased nuclear staining of LIMK1 in tumors with higher Gleason Scores and incidence of metastasis.</p> <p>Conclusion</p> <p>Our results show that increased expression of LIMK1 results in chromosomal abnormalities, aberrant cell cycle progression and alteration of normal cellular response to microtubule stabilizing agent Taxol; and that LIMK1 expression may be associated with cancerous phenotype of the prostate.</p

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

FEBUKO and MODMEP: Field measurements and modelling of aerosol and cloud multiphase processes

An overview of the two FEBUKO aerosol–cloud interaction field experiments in the Thüringer Wald (Germany) in October 2001 and 2002 and the corresponding modelling project MODMEP is given. Experimentally, a variety of measurement methods were deployed to probe the gas phase, particles and cloud droplets at three sites upwind, downwind and within an orographic cloud with special emphasis on the budgets and interconversions of organic gas and particle phase constituents. Out of a total of 14 sampling periods within 30 cloud events three events (EI, EII and EIII) are selected for detailed analysis. At various occasions an impact of the cloud process on particle chemical composition such as on the organic compounds content, sulphate and nitrate and also on particle size distributions and particle mass is observed. Moreover, direct phase transfer of polar organic compound from the gas phase is found to be very important for the understanding of cloudwater composition. For the modelling side, a main result of the MODMEP project is the development of a cloud model, which combines a complex multiphase chemistry with detailed microphysics. Both components are described in a fine-resolved particle/drop spectrum. New numerical methods are developed for an efficient solution of the entire complex model. A further development of the CAPRAM mechanism has lead to a more detailed description of tropospheric aqueous phase organic chemistry. In parallel, effective tools for the reduction of highly complex reaction schemes are provided. Techniques are provided and tested which allow the description of complex multiphase chemistry and of detailed microphysics in multidimensional chemistry-transport models

Hospital use of systemic antifungal drugs

BACKGROUND: Sales data indicate a major increase in the prescription of antifungal drugs in the last two decades. Many new agents for systemic use that only recently have become available are likely to be prescribed intensively in acute care hospitals. Sales data do not adequately describe the developments of drug use density. Given the concerns about the potential emergence of antifungal drug resistance, data on drug use density, however, may be valuable and are needed for analyses of the relationship between drug use and antifungal resistance. METHODS: Hospital pharmacy records for the years 2001 to 2003 were evaluated, and the number of prescribed daily doses (PDD, defined according to locally used doses) per 100 patient days were calculated to compare systemic antifungal drug use density in different medical and surgical service areas between five state university hospitals. RESULTS: The 3-year averages in recent antifungal drug use for the five hospitals ranged between 8.6 and 29.3 PDD/100 patient days in the medical services (including subspecialties and intensive care), and between 1.1 and 4.0 PDD/100 patient days in the surgical services, respectively. In all five hospitals, systemic antifungal drug use was higher in the hematology-oncology service areas (mean, 48.4, range, 24 to 101 PDD/100 patient days, data for the year 2003) than in the medical intensive care units (mean, 18.3, range, 10 to 33 PDD/100) or in the surgical intensive care units (mean, 10.7, range, 6 to 18 PDD/100). Fluconazole was the most prescribed antifungal drug in all areas. In 2003, amphotericin B consumption had declined to 3 PDD/100 in the hematology-oncology areas while voriconazole use had increased to 10 PDD/100 in 2003. CONCLUSION: Hematology-oncology services are intense antifungal drug prescribing areas. Fluconazole and other azol antifungal drugs are the most prescribed drugs in all patient care areas while amphotericin B use has considerably decreased. The data may be useful as a benchmark for focused interventions to improve prescribing quality

High body burdens of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) in California women.

Following our first report on elevated polybrominated diphenyl ether (PBDE) concentrations in California women, we expanded our investigation to include diverse groups of local women. We analyzed additional adipose and serum samples collected in the late 1990s from San Francisco Bay Area women participating in a breast cancer study and in a reproductive study, respectively. Adipose samples (n = 32) were analyzed by low-resolution mass spectrometry in negative-ion chemical ionization mode, whereas serum samples (n = 50) were analyzed by dual-column gas chromatography with electron capture detection. The results confirmed our earlier findings. Concentrations of 2,2,4,4 -tetrabromodiphenyl ether (BDE-47) in contemporary California women ranged between 5 and 510 ng/g lipid, with a median (16.5 ng/g lipid) 3-10 times higher than those reported from Europe. In contrast, PBDEs were not measurable in any of 420 archived serum samples collected in the 1960s from San Francisco Bay Area women participating in a study of child development. BDE-47 concentrations did not increase with age or with concentrations of a polychlorinated biphenyl (PCB-153), suggesting other routes of exposure in addition to diet. Rising body burdens of endocrine-disrupting chemicals such as PBDEs may pose a potential public health threat

Change Point Estimation in Monitoring Survival Time

Precise identification of the time when a change in a hospital outcome has occurred enables clinical experts to search for a potential special cause more effectively. In this paper, we develop change point estimation methods for survival time of a clinical procedure in the presence of patient mix in a Bayesian framework. We apply Bayesian hierarchical models to formulate the change point where there exists a step change in the mean survival time of patients who underwent cardiac surgery. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. Markov Chain Monte Carlo is used to obtain posterior distributions of the change point parameters including location and magnitude of changes and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time CUSUM control charts for different magnitude scenarios. The proposed estimator shows a better performance where a longer follow-up period, censoring time, is applied. In comparison with the alternative built-in CUSUM estimator, more accurate and precise estimates are obtained by the Bayesian estimator. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.Peer reviewe