Evaluation of ice cloud representation in the ECMWF and UK Met Office models using CloudSat and CALIPSO data

Ice cloud representation in general circulation models remains a challenging task, due to the lack of accurate observations and the complexity of microphysical processes. In this article, we evaluate the ice water content (IWC) and ice cloud fraction statistical distributions from the numerical weather prediction models of the European Centre for Medium-Range Weather Forecasts (ECMWF) and the UK Met Office, exploiting the synergy between the CloudSat radar and CALIPSO lidar. Using the last three weeks of July 2006, we analyse the global ice cloud occurrence as a function of temperature and latitude and show that the models capture the main geographical and temperature-dependent distributions, but overestimate the ice cloud occurrence in the Tropics in the temperature range from −60 °C to −20 °C and in the Antarctic for temperatures higher than −20 °C, but underestimate ice cloud occurrence at very low temperatures. A global statistical comparison of the occurrence of grid-box mean IWC at different temperatures shows that both the mean and range of IWC increases with increasing temperature. Globally, the models capture most of the IWC variability in the temperature range between −60 °C and −5 °C, and also reproduce the observed latitudinal dependencies in the IWC distribution due to different meteorological regimes. Two versions of the ECMWF model are assessed. The recent operational version with a diagnostic representation of precipitating snow and mixed-phase ice cloud fails to represent the IWC distribution in the −20 °C to 0 °C range, but a new version with prognostic variables for liquid water, ice and snow is much closer to the observed distribution. The comparison of models and observations provides a much-needed analysis of the vertical distribution of IWC across the globe, highlighting the ability of the models to reproduce much of the observed variability as well as the deficiencies where further improvements are required.

Prediction of novel and analogous folds using fragment assembly and fold recognition

A number of new and newly improved methods for predicting protein structure developed by the Jones–University College London group were used to make predictions for the CASP6 experiment. Structures were predicted with a combination of fold recognition methods (mGenTHREADER, nFOLD, and THREADER) and a substantially enhanced version of FRAGFOLD, our fragment assembly method. Attempts at automatic domain parsing were made using DomPred and DomSSEA, which are based on a secondary structure parsing algorithm and additionally for DomPred, a simple local sequence alignment scoring function. Disorder prediction was carried out using a new SVM-based version of DISOPRED. Attempts were also made at domain docking and “microdomain” folding in order to build complete chain models for some targets.

Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures

Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazoleinduced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100 mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (�10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic–clonic seizures. These results extend the anticonvulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies.

Co-variation of temperature and precipitation in CMIP5 models and satellite observations

Current variability of precipitation (P) and its response to surface temperature (T) are analysed using coupled(CMIP5) and atmosphere-only (AMIP5) climate model simulations and compared with observational estimates. There is striking agreement between Global Precipitation Climatology Project (GPCP) observed and AMIP5 simulated P anomalies over land both globally and in the tropics suggesting that prescribed sea surface temperature and realistic radiative forcings are sufficient for simulating the interannual variability in continental P. Differences between the observed and simulated P variability over the ocean, originate primarily from the wet tropical regions, in particular the western Pacific, but are reduced slightly after 1995. All datasets show positive responses of P to T globally of around 2 %/K for simulations and 3-4 %/K in GPCP observations but model responses over the tropical oceans are around 3 times smaller than GPCP over the period 1988-2005. The observed anticorrelation between land and ocean P, linked with El Niño Southern Oscillation, is captured by the simulations. All data sets over the tropical ocean show a tendency for wet regions to become wetter and dry regions drier with warming. Over the wet region (75% precipitation percentile), the precipitation response is ~13-15%/K for GPCP and ~5%/K for models while trends in P are 2.4%/decade for GPCP, 0.6% /decade for CMIP5 and 0.9%/decade for AMIP5 suggesting that models are underestimating the precipitation responses or a deficiency exists in the satellite datasets.

Trends in Austral jet position in ensembles of high- and low-top CMIP5 models

Trends in the position of the DJF Austral jet have been analysed for multi-model ensemble simulations of a subset of high- and low-top models for the periods 1960-2000, 2000-2050, and 2050-2098 under the CMIP5 historical, RCP4.5, and RCP8.5 scenarios. Comparison with ERA-Interim, CFSR and the NCEP/NCAR reanalysis shows that the DJF and annual mean jet positions in CMIP5 models are equatorward of reanalyses for the 1979-2006 mean. Under the RCP8.5 scenario, the mean jet position in the high-top models moves 3 degrees poleward of its 1860-1900 position by 2098, compared to just over 2 degrees for the low-top models. Changes in jet position are linked to changes in the meridional temperature gradient. Compared to low-top models, the high-top models predict greater warming in the tropical upper troposphere due to increased greenhouse gases for all periods considered: up to 0.28 K/decade more in the period 2050-2098 under the RCP8.5 scenario. Larger polar lower-stratospheric cooling is seen in high-top models: -1.64 K/decade compared to -1.40 K/decade in the period 1960-2000, mainly in response to ozone depletion, and -0.41 K/decade compared to -0.12 K/decade in the period 2050-2098, mainly in response to increases in greenhouse gases. Analysis suggests that there may be a linear relationship between the trend in jet position and meridional temperature gradient, even under strong forcing. There were no clear indications of an approach to a geometric limit on the absolute magnitude of the poleward shift by 2100.

Evaluation of water and energy budgets in regional climate models applied over Europe

This study presents a model intercomparison of four regional climate models (RCMs) and one variable resolution atmospheric general circulation model (AGCM) applied over Europe with special focus on the hydrological cycle and the surface energy budget. The models simulated the 15 years from 1979 to 1993 by using quasi-observed boundary conditions derived from ECMWF re-analyses (ERA). The model intercomparison focuses on two large atchments representing two different climate conditions covering two areas of major research interest within Europe. The first is the Danube catchment which represents a continental climate dominated by advection from the surrounding land areas. It is used to analyse the common model error of a too dry and too warm simulation of the summertime climate of southeastern Europe. This summer warming and drying problem is seen in many RCMs, and to a less extent in GCMs. The second area is the Baltic Sea catchment which represents maritime climate dominated by advection from the ocean and from the Baltic Sea. This catchment is a research area of many studies within Europe and also covered by the BALTEX program. The observed data used are monthly mean surface air temperature, precipitation and river discharge. For all models, these are used to estimate mean monthly biases of all components of the hydrological cycle over land. In addition, the mean monthly deviations of the surface energy fluxes from ERA data are computed. Atmospheric moisture fluxes from ERA are compared with those of one model to provide an independent estimate of the convergence bias derived from the observed data. These help to add weight to some of the inferred estimates and explain some of the discrepancies between them. An evaluation of these biases and deviations suggests possible sources of error in each of the models. For the Danube catchment, systematic errors in the dynamics cause the prominent summer drying problem for three of the RCMs, while for the fourth RCM this is related to deficiencies in the land surface parametrization. The AGCM does not show this drying problem. For the Baltic Sea catchment, all models similarily overestimate the precipitation throughout the year except during the summer. This model deficit is probably caused by the internal model parametrizations, such as the large-scale condensation and the convection schemes.

Markov models of aging: theory and practice

We review and structure some of the mathematical and statistical models that have been developed over the past half century to grapple with theoretical and experimental questions about the stochastic development of aging over the life course. We suggest that the mathematical models are in large part addressing the problem of partitioning the randomness in aging: How does aging vary between individuals, and within an individual over the lifecourse? How much of the variation is inherently related to some qualities of the individual, and how much is entirely random? How much of the randomness is cumulative, and how much is merely short-term flutter? We propose that recent lines of statistical inquiry in survival analysis could usefully grapple with these questions, all the more so if they were more explicitly linked to the relevant mathematical and biological models of aging. To this end, we describe points of contact among the various lines of mathematical and statistical research. We suggest some directions for future work, including the exploration of information-theoretic measures for evaluating components of stochastic models as the basis for analyzing experiments and anchoring theoretical discussions of aging.

A comparison of Shiga-toxin negative Escherichia coli O157 aflagellate and intimin deficient mutants in porcine in vitro and in vivo models of infection

Isolation of Shiga-toxin (Stx) positive Escherichia coli O157:H7 from commercially grown pigs has been reported. Furthermore, experimental infection studies have demonstrated that Stx-positive E. coli O157:H7 can persist in 12-week-old experimentally orally inoculated conventional pigs for up to 2 months and that persistence was not dependent upon intimin. We have shown that the flagellum of Stx-negative E. coli O157:H7 does not have a role to play in pathogenesis in ruminant models whereas, in poultry, the flagellum of E. coli O157:H7 was important for long-term persistent infection. The contribution of the flagellum of Stx-negative E. coli O157 in the colonisation of pigs was investigated by adherence assays on a porcine (IPI-21) cell line, porcine in vitro organ culture (IVOC) and experimental oral inoculation of conventional 14-week-old pigs. E. coli O157:H7 NCTC12900nal(r) and isogenic aflagellate and intimin deficient mutants adhered equally well to IPI-21 cells. In porcine IVOC association assays, E. coli O157:H7 NCTC12900nal(r) was associated in significantly higher numbers to tissues from the caecum and the terminal rectum than other sites. The aflagellate and intimin deficient mutants significantly adhered in greater numbers to more IVOC gastrointestinal tissues than the parent. Groups of 14-week-old pigs were dosed orally with 10(10) CFU/10 ml of either E. coli O157:H7 NCTC12900nal(r) or isogenic aflagellate and intimin deficient mutants and recovery of each test strain was similar. Histological analysis of pig tissues at post mortem examination revealed that E. coli O157 specifically stained bacteria were associated with the mucosa of the ascending and spiral colon. These data suggest that colonisation and persistence of Stx-negative E. coli O157:H7 in pigs, involves mechanisms that do not require the flagellum or intimin.

Application of DIGE and mass spectrometry in the study of type 2 Diabetes Mellitus (T2DM) mouse models

Knowledge of the differences between the amounts and types of protein that are expressed in diseased compared to healthy subjects may give an understanding of the biological pathways that cause disease. This is the reasoning behind the presented protocol, which uses difference gel electrophoresis to discover up‐ or down‐regulated proteins between mice of different genotypes, or of those fed on different diets, that may thus be prone to develop diabetes‐like phenotypes. Subsequent analysis of these proteins by tandem mass spectrometry typically facilitates their identification with a high degree of confidence.

Fingerprints of changes in annual and seasonal precipitation from CMIP5 models over land and ocean

By comparing annual and seasonal changes in precipitation over land and ocean since 1950 simulated by the CMIP5 (Coupled Model Intercomparison Project, phase 5) climate models in which natural and anthropogenic forcings have been included, we find that clear global-scale and regional-scale changes due to human influence are expected to have occurred over both land and ocean. These include moistening over northern high latitude land and ocean throughout all seasons and over the northern subtropical oceans during boreal winter. However we show that this signal of human influence is less distinct when considered over the relatively small area of land for which there are adequate observations to make assessments of multi-decadal scale trends. These results imply that extensive and significant changes in precipitation over the land and ocean may have already happened, even though, inadequacies in observations in some parts of the world make it difficult to identify conclusively such a human fingerprint on the global water cycle. In some regions and seasons, due to aliasing of different kinds of variability as a result of sub sampling by the sparse and changing observational coverage, observed trends appear to have been increased, underscoring the difficulties of interpreting the apparent magnitude of observed changes in precipitation.

Oxidoalkoxidovanadium(V) complexes: synthesis, characterization and comparison of X-ray crystal structures

The reaction of VO(acac)(2) with the ONO-chelator obtained by the condensation of salicylaldehyde with 2-hydroxybenzoylhydrazine (H2L) in a monohydric alcohol. (ROH) medium produces VO(OR)L]-type oxidoalkoxido complexes (1-7) where R = Me, Pr-n, Pr-i, Bu-n, Bu-i, Bu-t and (n)Pen. All the complexes show the metal atom to have a five-coordinate square pyramidal environment, although in some complexes there is an additional weak V center dot center dot center dot O interaction in the sixth axial position. In acetonitrile medium and in the presence of a cis-diol (ethylene glycol), H2L reacts with VO(acac)(2) to form a six-coordinate complex, [VO(OCH2CH2OH)L] (8). When the reaction is carried out in acetonitrile medium in the presence of 2-amino ethanol, a completely different type of product containing the square pyramidal complex anion [VO2L](-) associated with the cation [NH3CH2CH2OH](+) is obtained. It was noted previously that on being reacted with monodentate nitrogen donor bases B (which are stronger than pyridine), the [VO(OR)L] complexes react to form the same complex anion [VO2L](-) associated with the corresponding cation [BH](+). The coordination environment around the V(V) acceptor center of the water soluble [BH](+)[VO2L](-)satisfies one of the several requirements for an efficient antidiabetic vanadium species such as water solubility, nature of donor atoms of the ligand and their disposition around the VO2+ acceptor center.

Synthesis and crystal structures of μ-oxido- and μ-hydroxido-bridged dinuclear iron(III) complexes with an N2O donor ligand - a theoretical study on the influence of weak forces on the Fe-O-Fe bridging angle

The synthesis and crystal structures of three nonheme di-iron(III) complexes with a tridentate N,N,O Schiff-base ligand, 2-({[2-(dimethylamino) ethyl] imino} methyl) phenol (HL), are reported. Complexes [Fe2OL2(NCO)(2)] (1a) and [Fe2OL2(SAL)(2)]center dot H2O [SAL = o-(CHO)C6H4O-] (1b) are unsupported mu-oxido-bridged dimers, and [Fe-2(OH)L-2(HCOO)(2)-(Cl)] (2) is a mu-hydroxido-bridged dimer supported by a formato bridging ligand. All complexes have been characterized by X-ray crystallography and spectroscopic analysis. Complex 1b has been reported previously; however, it has been reinvestigated to confirm the presence of a crucial water molecule in the solid state. Structural analyses show that in 1a the iron atoms are pentacoordinate with a bent Fe-O-Fe angle [142.7(2)degrees], whereas in 2 the metal centers are hexacoordinate with a normal Fe-OH-Fe bridging angle [137.9(2)degrees]. The Fe-O-Fe angles in complexes 1a and 1b differ significantly to those usually shown by (mu-oxido) Fe-III complexes. A theoretical study has been performed in order to rationalize this deviation. Moreover, the influence of the water molecule observed in the solid-state structure of 1b on the Fe-O-Fe angle is also analyzed theoretically.

A comparison of the anticancer properties of isoxanthohumol and 8-prenylnaringenin using in vitro models of colon cancer

The hops plant (Humulus lupulus L.) is an essential ingredient in beer and contains a number of potentially bioactive prenylflavonoids, the predominant being the weakly estrogenic isoxanthohumol (Ix), which can be converted to the more strongly estrogenic 8-PN by the colonic microbiota. The aim of this study was to investigate the biological activity of 8-PN and Ix using in vitro models representing key stages of colorectal carcinogenesis, namely cell growth and viability (MTT assay), cell-cycle progression (DNA content assay), DNA damage (Comet assay), and invasion (Matrigel assay). A significant decrease in Caco-2 cell viability was noted after both 8-PN and Ix treatments at the higher doses (40 and 50 μM, respectively) although the impact on cell cycle differed between the two compounds. The decreased cell viability observed after Ix treatment was associated with a concentration-dependent increase in G2/M and an increased sub-G1 cell-cycle fraction, whereas treatment with 8-PN was associated with an elevated G0/G1 and an increased sub-G1 cell-cycle fraction. Significant antigenotoxic activity was noted at all 8-PN concentrations tested (5-40 μM). Although significant antigenotoxic activity was also noted with Ix treatment at ≤25 μM, at a higher dose, Ix itself exerted genotoxic activity. In a dose-dependent manner, both compounds inhibited HT115 cell invasion with reductions up to 52 and 46% for Ix and 8-PN, respectively, in comparison to untreated cells. This study demonstrated that both Ix and its gut microbial metabolite 8-PN exert anticancer effects on models of key stages of colon tumourigenesis.