A global blended tropopause based on ERA data, Part II: trends and tropical broadening

A new tropopause definition involving a flow-dependent blending of the traditional thermal tropopause with one based on potential vorticity has been developed and applied to the European Centre for Medium-Range Weather Forecasts (ECMWF) reanalyses (ERA), ERA-40 and ERA-Interim. Global and regional trends in tropopause characteristics for annual and solsticial seasonal means are presented here, with emphasis on significant results for the newer ERA-Interim data for 1989-2007. The global-mean tropopause is rising at a rate of 47 m decade−1 , with pressure falling at 1.0 hPa decade−1 , and temperature falling at 0.18 K decade−1 . The Antarctic tropopause shows decreasing heights,warming,and increasing westerly winds. The Arctic tropopause also shows a warming, but with decreasing westerly winds. In the tropics the trends are small, but at the latitudes of the sub-tropical jets they are almost double the global values. It is found that these changes are mainly concentrated in the eastern hemisphere. Previous and new metrics for the rate of broadening of the tropics, based on both height and wind, give trends in the range 0.9◦ decade−1 to 2.2◦ decade−1 . For ERA-40 the global height and pressure trends for the period 1979-2001 are similar: 39 m decade−1 and -0.8 hPa decade−1. These values are smaller than those found from the thermal tropopause definition with this data set, as was used in most previous studies.

Synthesis, characterization, crystal structure, and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative

The reaction of cis-[RuCl2(dmso)(4)] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c] quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L-1)(2)] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL1). Treatment of RuCl3 center dot 3H(2)O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl2(L-2)(2)] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c] quinazoline (L-2). Complex 2 was also obtained from the reaction of RuCl3 center dot 3H(2)O with L-2 in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K-b and the linear Stern-Volmer quenching constant K-SV

Synthesis, crystal structures and magnetic properties of a phenoxo-bridged dinuclear Cu(II) complex and a dicyanamide bridged novel molecular rectangle based on it

The phenoxo-bridged dinuclear Cu-II complex [Cu2L2-(NCNCN)(2)] (1) and the dicyanamide-bridged molecular rectangle [Cu4L4{mu(1,5)-(NCNCN)(2)}]center dot(ClO4)(2)(H2O)(2) (2) were synthesized using the tridentate reduced Schiff-base ligand HL {2-[(2-dimethylamino-ethylamino) methyl] phenol}. The complexes were characterized by X-ray structural analyses and variable-temperature magnetic susceptibility measurements. Complex 2 was formed through the joining of the phenoxo-bridged dinuclear Cu2O2 cores of 1 via the mu(1,5)-bridging mode of dicyanamide. The structural properties of the Cu2O2 cores in two complexes are significantly different. The geometry of the copper ions is distorted trigonal bipyramid in 1 but is nearly square-pyramidal in 2. These differences have a marked effect on the magnetic properties of two compounds. Although both are antiferromagnetically coupled, the coupling constants (J = -185.2 and -500.9 cm(-1) for 1 and 2, respectively) differ considerably.

Understanding advances in the simulation of intraseasonal variability in the ECMWF model. Part II: the application of process-based diagnostics

In Part I of this study it was shown that moving from a moisture-convergent- to a relative-humidity-dependent organized entrainment rate in the formulation for deep convection was responsible for significant advances in the simulation of the Madden – Julian Oscillation (MJO) in the ECMWF model. However, the application of traditional MJO diagnostics were not adequate to understand why changing the control on convection had such a pronounced impact on the representation of the MJO. In this study a set of process-based diagnostics are applied to the hindcast experiments described in Part I to identify the physical mechanisms responsible for the advances in MJO simulation. Increasing the sensitivity of the deep convection scheme to environmental moisture is shown to modify the relationship between precipitation and moisture in the model. Through dry-air entrainment, convective plumes ascending in low-humidity environments terminate lower in the atmosphere. As a result, there is an increase in the occurrence of cumulus congestus, which acts to moisten the mid troposphere. Due to the modified precipitation – moisture relationship more moisture is able to build up, which effectively preconditions the tropical atmosphere for the t ransition t o d eep convection. R esults from this study suggest that a tropospheric moisture control on convection is key to simulating the interaction between the convective heating and the large-scale wave forcing associated with the MJO.

Filter for Car Tracking Based on Acceleration and Steering Angle

The motion of a car is described using a stochastic model in which the driving processes are the steering angle and the tangential acceleration. The model incorporates exactly the kinematic constraint that the wheels do not slip sideways. Two filters based on this model have been implemented, namely the standard EKF, and a new filter (the CUF) in which the expectation and the covariance of the system state are propagated accurately. Experiments show that i) the CUF is better than the EKF at predicting future positions of the car; and ii) the filter outputs can be used to control the measurement process, leading to improved ability to recover from errors in predictive tracking.

Advances in Model-Based Traffic Vision

Model based vision allows use of prior knowledge of the shape and appearance of specific objects to be used in the interpretation of a visual scene; it provides a powerful and natural way to enforce the view consistency constraint. A model based vision system has been developed within ESPRIT VIEWS: P2152 which is able to classify and track moving objects (cars and other vehicles) in complex, cluttered traffic scenes. The fundamental basis of the method has been previously reported. This paper presents recent developments which have extended the scope of the system to include (i) multiple cameras, (ii) variable camera geometry, and (iii) articulated objects. All three enhancements have easily been accommodated within the original model-based approach

Model-based vehicle detection and classification using orthographic approximations

This paper reports the current state of work to simplify our previous model-based methods for visual tracking of vehicles for use in a real-time system intended to provide continuous monitoring and classification of traffic from a fixed camera on a busy multi-lane motorway. The main constraints of the system design were: (i) all low level processing to be carried out by low-cost auxiliary hardware, (ii) all 3-D reasoning to be carried out automatically off-line, at set-up time. The system developed uses three main stages: (i) pose and model hypothesis using 1-D templates, (ii) hypothesis tracking, and (iii) hypothesis verification, using 2-D templates. Stages (i) & (iii) have radically different computing performance and computational costs, and need to be carefully balanced for efficiency. Together, they provide an effective way to locate, track and classify vehicles.

The effect of doubled CO2 and model basic state biases on the monsoon-ENSO system. II: Changing ENSO regimes

Integrations of a fully-coupled climate model with and without flux adjustments in the equatorial oceans are performed under 2×CO2 conditions to explore in more detail the impact of increased greenhouse gas forcing on the monsoon-ENSO system. When flux adjustments are used to correct some systematic model biases, ENSO behaviour in the modelled future climate features distinct irregular and periodic (biennial) regimes. Comparison with the observed record yields some consistency with ENSO modes primarily based on air-sea interaction and those dependent on basinwide ocean wave dynamics. Simple theory is also used to draw analogies between the regimes and irregular (stochastically forced) and self-excited oscillations respectively. Periodic behaviour is also found in the Asian-Australian monsoon system, part of an overall biennial tendency of the model under these conditions related to strong monsoon forcing and increased coupling between the Indian and Pacific Oceans. The tropospheric biennial oscillation (TBO) thus serves as a useful descriptor for the coupled monsoon-ENSO system in this case. The presence of obvious regime changes in the monsoon-ENSO system on interdecadal timescales, when using flux adjustments, suggests there may be greater uncertainty in projections of future climate, although further modelling studies are required to confirm the realism and cause of such changes.

Proliferative and anti-proliferative effects of titanium- and iron-based metallocene anti-cancer drugs

In previous work we have found that Cp2TiCl2 and its corresponding deriv. of tamoxifen, Titanocene tamoxifen, show an unexpected proliferative effect on hormone dependent breast cancer cells MCF-7. In order to check if this behavior is a general trend for titanocene derivs. we have tested two other titanocene derivs., Titanocene Y and Titanocene K, on this cell line. Interestingly, these two titanocene complexes behave in a totally different manner. Titanocene K is highly proliferative on MCF-7 cells even at low concns. (0.5 .mu.M), thus behave almost similarly to Cp2TiCl2. This proliferative effect is also obsd. in the presence of bovine serum albumin (BSA). In contrast, Titanocene Y alone has almost no effect on MCF-7 at a concn. of 10 .mu.M, but exhibits a significant dose dependent cytotoxic effect of up to 50% when incubated with BSA (20-50 .mu.g/mL). This confirms the crucial role played by the binding to serum proteins in the expression of the in vivo, cytotoxicity of the titanocene complexes. From the hydridolithiation reaction of 6-p-anisylfulvene with LiBEt3H followed by transmetallation with iron dichloride [bis-[(p-methoxy-benzyl)cyclopentadienyl]iron(II)] (Ferrocene Y) was synthesized. This complex, which was characterized by single crystal X-ray diffraction, contains the robust ferrocenyl unit instead of Ti assocd. with easily leaving groups such as chlorine and shows only a modest cytotoxicity against MCF-7 or MDA-MB-231 cells.

The cumulus-capped boundary layer. II: Interface fluxes

This paper considers the relationship between the mean temperature and humidity profiles and the fluxes of heat and moisture at cloud base and the base of the inversion in the cumulus-capped boundary layer. The relationships derived are based on an approximate form of the scalar-flux budget and the scaling properties of the turbulent kinetic energy (TKE) budget. The scalar-flux budget gives a relationship between the change in the virtual potential temperature across either the cloud base transition zone or the inversion and the flux at the base of the layer. The scaling properties of the TKE budget lead to a relationship between the heat and moisture fluxes and the mean subsaturation through the liquid-water flux. The 'jump relation' for the virtual potential temperature at cloud base shows the close connection between the cumulus mass flux in the cumulus-capped boundary layer and the entrainment velocity in the dry-convective boundary layer. Gravity waves are shown to be an important feature of the inversion.

Modelling the lava dome extruded at Soufrière Hills Volcano, Montserrat, August 2005–May 2006. Part II: Rockfall activity and talus deformation

During many lava dome-forming eruptions, persistent rockfalls and the concurrent development of a substantial talus apron around the foot of the dome are important aspects of the observed activity. An improved understanding of internal dome structure, including the shape and internal boundaries of the talus apron, is critical for determining when a lava dome is poised for a major collapse and how this collapse might ensue. We consider a period of lava dome growth at the Soufrière Hills Volcano, Montserrat, from August 2005 to May 2006, during which a 100 × 106 m3 lava dome developed that culminated in a major dome-collapse event on 20 May 2006. We use an axi-symmetrical Finite Element Method model to simulate the growth and evolution of the lava dome, including the development of the talus apron. We first test the generic behaviour of this continuum model, which has core lava and carapace/talus components. Our model describes the generation rate of talus, including its spatial and temporal variation, as well as its post-generation deformation, which is important for an improved understanding of the internal configuration and structure of the dome. We then use our model to simulate the 2005 to 2006 Soufrière Hills dome growth using measured dome volumes and extrusion rates to drive the model and generate the evolving configuration of the dome core and carapace/talus domains. The evolution of the model is compared with the observed rockfall seismicity using event counts and seismic energy parameters, which are used here as a measure of rockfall intensity and hence a first-order proxy for volumes. The range of model-derived volume increments of talus aggraded to the talus slope per recorded rockfall event, approximately 3 × 103–13 × 103 m3 per rockfall, is high with respect to estimates based on observed events. From this, it is inferred that some of the volumetric growth of the talus apron (perhaps up to 60–70%) might have occurred in the form of aseismic deformation of the talus, forced by an internal, laterally spreading core. Talus apron growth by this mechanism has not previously been identified, and this suggests that the core, hosting hot gas-rich lava, could have a greater lateral extent than previously considered.

Decision-making in a phase II clinical trial: a new approach combining Bayesian and frequentist concepts

The aim of a phase H clinical trial is to decide whether or not to develop an experimental therapy further through phase III clinical evaluation. In this paper, we present a Bayesian approach to the phase H trial, although we assume that subsequent phase III clinical trials will hat,e standard frequentist analyses. The decision whether to conduct the phase III trial is based on the posterior predictive probability of a significant result being obtained. This fusion of Bayesian and frequentist techniques accepts the current paradigm for expressing objective evidence of therapeutic value, while optimizing the form of the phase II investigation that leads to it. By using prior information, we can assess whether a phase II study is needed at all, and how much or what sort of evidence is required. The proposed approach is illustrated by the design of a phase II clinical trial of a multi-drug resistance modulator used in combination with standard chemotherapy in the treatment of metastatic breast cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.

An adaptive group sequential design for phase II/III clinical trials that select a single treatment from several

There is increasing interest in combining Phases II and III of clinical development into a single trial in which one of a small number of competing experimental treatments is ultimately selected and where a valid comparison is made between this treatment and the control treatment. Such a trial usually proceeds in stages, with the least promising experimental treatments dropped as soon as possible. In this paper we present a highly flexible design that uses adaptive group sequential methodology to monitor an order statistic. By using this approach, it is possible to design a trial which can have any number of stages, begins with any number of experimental treatments, and permits any number of these to continue at any stage. The test statistic used is based upon efficient scores, so the method can be easily applied to binary, ordinal, failure time, or normally distributed outcomes. The method is illustrated with an example, and simulations are conducted to investigate its type I error rate and power under a range of scenarios.

Immunogenetics of drug-induced skin blistering disorders. Part II: Synthesis

The overall immunopathogenesis relevant to a large series of disorders caused by a drug or its associated hyperimmune condition is discussed based upon examining the genetics of severe drug-induced bullous skin problems (sporadic idiosyncratic adverse events including Stevens-Johnson syndrome and Toxic epidermal necrolysis). New results from an exemplar study on shared precipitating and perpetuating inner causes with other related disease phenotypes including aphtous stomatitis, Behcets, erythema multiforme, Hashimoto's thyroiditis, pemphigus, periodic fevers, Sweet's syndrome and drug-induced multisystem hypersensitivity are presented. A call for a collaborative, wider demographic profiling and deeper immunotyping in suggested future work is made.

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

Background and Purpose-Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume. Methods-Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III. Results-The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms. Discussion-Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place. (Stroke. 2009;40:1347-1352.)