The Max-Planck-Institute global ocean/sea ice model with orthogonal curvilinear coordinates

The Hamburg Ocean Primitive Equation model has undergone significant development in recent years. Most notable is the treatment of horizontal discretisation which has undergone transition from a staggered E-grid to an orthogonal curvilinear C-grid. The treatment of subgridscale mixing has been improved by the inclusion of a new formulation of bottom boundary layer (BBL) slope convection, an isopycnal diffusion scheme, and a Gent and McWilliams style eddy-induced mixing parameterisation. The model setup described here has a north pole over Greenland and a south pole on the coast of the Weddell Sea. This gives relatively high resolution in the sinking regions associated with the thermohaline circulation. Results are presented from a 450 year climatologically forced integration. The forcing is a product of the German Ocean Model Intercomparison Project and is derived from the European Centre for Medium Range Weather Forecasting reanalysis. The main emphasis is on the model's representation of key quantities that are easily associated with the ocean's role in the global climate system. The global and Atlantic northward poleward heat transports have peaks of 1.43 and 0.84 PW, at 18degrees and 21degrees N respectively. The Atlantic meridional overturning streamfunction has a peak of 15.7 Sv in the North Atlantic and an outflow of 11.9 Sv at 30degrees S. Comparison with a simulation excluding BBL shows that the scheme is responsible for up to a 25% increase in North Atlantic heat transport, with significant improvement of the depths of convection in the Greenland, Labrador and Irminger Seas. Despite the improvements, comparison with observations shows the heat transport still to be too weak. Other outstanding problems include an incorrect Gulf Stream pathway, a too strong Antarctic Circumpolar Current, and a too weak renewal of Antarctic Intermediate Water. Nevertheless, the model has been coupled to the atmospheric GCM ECHAM5 and run successfully for over 250 years without any surface flux corrections. (C) 2002 Elsevier Science Ltd. All rights reserved

Histone deacetylases 1, 2 and 3 are highly expressed in prostate cancer and HDAC2 expression is associated with shorter PSA relapse time after radical prostatectomy

High activity of histone deacetylases (HDACs) causes epigenetic alterations associated with malignant cell behaviour. Consequently, HDAC inhibitors have entered late-phase clinical trials as new antineoplastic drugs. However, little is known about expression and function of specific HDAC isoforms in human tumours including prostate cancer. We investigated the expression of class I HDACs in 192 prostate carcinomas by immunohistochemistry and correlated our findings to clinicopathological parameters including follow-up data. Class I HDAC isoforms were strongly expressed in the majority of the cases (HDAC1: 69.8%, HDAC2: 74%, HDAC3: 94.8%). High rates of HDAC1 and HDAC2 expression were significantly associated with tumour dedifferentiation. Strong expression of all HDACs was accompanied by enhanced tumour cell proliferation. In addition, HDAC2 was an independent prognostic marker in our prostate cancer cohort. In conclusion, we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. The class I HDAC isoforms 1, 2 and 3 are differentially expressed in prostate cancer, which might be important for upcoming studies on HDAC inhibitors in this tumour entity. Also, the highly significant prognostic value of HDAC2 clearly deserves further study

Novelty-Related fMRI Responses of Precuneus and Medial Temporal Regions in Individuals at Risk for Alzheimer Disease

BACKGROUND AND OBJECTIVES: We assessed whether novelty-related fMRI activity in medial temporal lobe regions and the precuneus follows an inverted U-shaped pattern across the clinical spectrum of increased Alzheimer disease (AD) risk as previously suggested. Specifically, we tested for potentially increased activity in individuals with a higher AD risk due to subjective cognitive decline (SCD) or mild cognitive impairment (MCI). We further tested whether activity differences related to diagnostic groups were accounted for by CSF markers of AD or brain atrophy. METHODS: We studied 499 participants aged 60-88 years from the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE) who underwent task-fMRI. Participants included 163 cognitively normal (healthy control, HC) individuals, 222 SCD, 82 MCI, and 32 patients with clinical diagnosis of mild AD. CSF levels of β-amyloid 42/40 ratio and phosphorylated-tau181 were available from 232 participants. We used region-based analyses to assess novelty-related activity (novel > highly familiar scenes) in entorhinal cortex, hippocampus, and precuneus as well as whole-brain voxel-wise analyses. First, general linear models tested differences in fMRI activity between participant groups. Complementary regression models tested quadratic relationships between memory impairment and activity. Second, relationships of activity with AD CSF biomarkers and brain volume were analyzed. Analyses were controlled for age, sex, study site, and education. RESULTS: In the precuneus, we observed an inverted U-shaped pattern of novelty-related activity across groups, with higher activity in SCD and MCI compared with HC, but not in patients with AD who showed relatively lower activity than MCI. This nonlinear pattern was confirmed by a quadratic relationship between memory impairment and precuneus activity. Precuneus activity was not related to AD biomarkers or brain volume. In contrast to the precuneus, hippocampal activity was reduced in AD dementia compared with all other groups and related to AD biomarkers. DISCUSSION: Novelty-related activity in the precuneus follows a nonlinear pattern across the clinical spectrum of increased AD risk. Although the underlying mechanism remains unclear, increased precuneus activity might represent an early signature of memory impairment. Our results highlight the nonlinearity of activity alterations that should be considered in clinical trials using functional outcome measures or targeting hyperactivity

Enhancing methane production from lignocellulosic biomass by combined steam‑explosion pretreatment and bioaugmentation with cellulolytic bacterium Caldicellulosiruptor bescii

Background: Biogas production from lignocellulosic biomass is generally considered to be challenging due to the recalcitrant nature of this biomass. In this study, the recalcitrance of birch was reduced by applying steam-explosion (SE) pretreatment (210 °C and 10 min). Moreover, bioaugmentation with the cellulolytic bacterium Caldicellulosiruptor bescii was applied to possibly enhance the methane production from steam-exploded birch in an anaerobic digestion (AD) process under thermophilic conditions (62 °C). Results: Overall, the combined SE and bioaugmentation enhanced the methane yield up to 140% compared to untreated birch, while SE alone contributed to the major share of methane enhancement by 118%. The best methane improvement of 140% on day 50 was observed in bottles fed with pretreated birch and bioaugmentation with lower dosages of C. bescii (2 and 5% of inoculum volume). The maximum methane production rate also increased from 4-mL CH4/ g VS (volatile solids)/day for untreated birch to 9-14-mL CH4/ g VS/day for steam-exploded birch with applied bioaugmentation. Bioaugmentation was particularly effective for increasing the initial methane production rate of the pretreated birch yielding 21-44% more methane than the pretreated birch without applied bioaugmentation. The extent of solubilization of the organic matter was increased by more than twofold when combined SE pretreatment and bioaugmentation was used in comparison with the methane production from untreated birch. The beneficial effects of SE and bioaugmentation on methane yield indicated that biomass recalcitrance and hydrolysis step are the limiting factors for efficient AD of lignocellulosic biomass. Microbial community analysis by 16S rRNA amplicon sequencing showed that the microbial community composition was altered by the pretreatment and bioaugmentation processes. Notably, the enhanced methane production by pretreatment and bioaugmentation was well correlated with the increase in abundance of key bacterial and archaeal communities, particularly the hydrolytic bacterium Caldicoprobacter, several members of syntrophic acetate oxidizing bacteria and the hydrogenotrophic Methanothermobacter. Conclusion: Our findings demonstrate the potential of combined SE and bioaugmentation for enhancing methane production from lignocellulosic biomass

Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer’s disease: results from the DELCODE study

Background Neuroinflammation constitutes a pathological hallmark of Alzheimer’s disease (AD). Still, it remains unresolved if peripheral inflammatory markers can be utilized for research purposes similar to blood-based beta-amyloid and neurodegeneration measures. We investigated experimental inflammation markers in serum and analyzed interrelations towards AD pathology features in a cohort with a focus on at-risk stages of AD. Methods Data of 74 healthy controls (HC), 99 subjective cognitive decline (SCD), 75 mild cognitive impairment (MCI), 23 AD relatives, and 38 AD subjects were obtained from the DELCODE cohort. A panel of 20 serum biomarkers was determined using immunoassays. Analyses were adjusted for age, sex, APOE status, and body mass index and included correlations between serum and CSF marker levels and AD biomarker levels. Group-wise comparisons were based on screening diagnosis and routine AD biomarker-based schematics. Structural imaging data were combined into composite scores representing Braak stage regions and related to serum biomarker levels. The Preclinical Alzheimer’s Cognitive Composite (PACC5) score was used to test for associations between the biomarkers and cognitive performance. Results Each experimental marker displayed an individual profile of interrelations to AD biomarkers, imaging, or cognition features. Serum-soluble AXL (sAXL), IL-6, and YKL-40 showed the most striking associations. Soluble AXL was significantly elevated in AD subjects with pathological CSF beta-amyloid/tau profile and negatively related to structural imaging and cognitive function. Serum IL-6 was negatively correlated to structural measures of Braak regions, without associations to corresponding IL-6 CSF levels or other AD features. Serum YKL-40 correlated most consistently to CSF AD biomarker profiles and showed the strongest negative relations to structure, but none to cognitive outcomes. Conclusions Serum sAXL, IL-6, and YKL-40 relate to different AD features, including the degree of neuropathology and cognitive functioning. This may suggest that peripheral blood signatures correspond to specific stages of the disease. As serum markers did not reflect the corresponding CSF protein levels, our data highlight the need to interpret serum inflammatory markers depending on the respective protein’s specific biology and cellular origin. These marker-specific differences will have to be considered to further define and interpret blood-based inflammatory profiles for AD research

Pressure Dependent Line Intensity and Continuum Absorption for Pure Co2: Predictions by Requantized Molecular Dynamics Simulations

We investigate the pressure dependence of the line intensities retrieved from fits, using accurate isolated line shapes, of pure CO2 spectra predicted using classical molecular dynamics simulations (rCMDS). For that, rCMDS have been carried out, at 296 K and 215 K, for pressure from 0.5 to 1 atm. An accurate ab initio intermolecular potential has been used to represent the CO2-CO2 interactions. The usual quadratic speed dependent hard collision model, taking into account the first-order line-mixing, is used to fit the simulated spectra. The results show that the retrieved line intensities linearly decrease with increasing pressure and that this decrease is larger at low temperature, consistently with the experimental results 1 . Quantitatively, at 1 atm and room temperature (resp. 215 K), our predictions show that the retrieved intensity can be up to 2% (resp. 4%) smaller than the intensity obtained at zero pressure. The effect decreases with increasing rotational quantum number. From the spectra fit baselines, a continuum absorption proportional with the square of pressure, is deduced. Our analysis shows that the observed pressure dependent intensity and the continuum are mostly due to incomplete or ongoing collisions, which govern the dipole auto-correlation function at very short times. These collisions transfer a fraction of the intensity from the core region of the line to a broad and weak continuum, and thus reduce its area