Gene transfer vectors targeted to human prostate cancer : do we need better preclinical testing systems?

Destruction of cancer cells by genetically modified viral and nonviral vectors has been the aim of many research programs. The ability to target cytotoxic gene therapies to the cells of interest is an essential prerequisite, and the treatment has always had the potential to provide better and more long-lasting therapy than existing chemotherapies. However, the potency of these infectious agents requires effective testing systems, in which hypotheses can be explored both in vitro and in vivo before the establishment of clinical trials in humans. The real prospect of off-target effects should be eliminated in the preclinical stage, if current prejudices against such therapies are to be overcome. In this review we have set out, using adenoviral vectors as a commonly used example, to discuss some of the key parameters required to develop more effective testing, and to critically assess the current cellular models for the development and testing of prostate cancer biotherapy. Only by developing models that more closely mirror human tissues will we be able to translate literature publications into clinical trials and hence into acceptable alternative treatments for the most commonly diagnosed cancer in humans.

Solving tri-diagonal linear systems using field programmable gate arrays

In this paper, we present the outcomes of a project on the exploration of the use of Field Programmable Gate Arrays (FPGAs) as co-processors for scientific computation. We designed a custom circuit for the pipelined solving of multiple tri-diagonal linear systems. The design is well suited for applications that require many independent tri-diagonal system solves, such as finite difference methods for solving PDEs or applications utilising cubic spline interpolation. The selected solver algorithm was the Tri-Diagonal Matrix Algorithm (TDMA or Thomas Algorithm). Our solver supports user specified precision thought the use of a custom floating point VHDL library supporting addition, subtraction, multiplication and division. The variable precision TDMA solver was tested for correctness in simulation mode. The TDMA pipeline was tested successfully in hardware using a simplified solver model. The details of implementation, the limitations, and future work are also discussed.

Suitable stiffening systems for LiteSteel beams with web openings subjected to shear

Abstract: LiteSteel beam (LSB) is a new cold-formed steel hollow flange channel section produced using a simultaneous cold-forming and dual electric resistance welding process. It is commonly used as floor joists and bearers with web openings in residential, industrial and commercial buildings. Their shear strengths are considerably reduced when web openings are included for the purpose of locating building services. A cost effective method of eliminating the detrimental effects of a large web opening is to attach suitable stiffeners around the web openings of LSBs. Experimental and numerical studies were undertaken to investigate the shear behaviour and strength of LSBs with circular web openings reinforced using plate, stud, transverse and sleeve stiffeners with varying sizes and thicknesses. Both welding and varying screw-fastening arrangements were used to attach these stiffeners to the web of LSBs. Finite element models of LSBs with stiffened web openings in shear were developed to simulate their shear behaviour and strength of LSBs. They were then validated by comparing the results with experimental test results and used in a detailed parametric study. These studies have shown that plate stiffeners were the most suitable, however, their use based on the current American standards was found to be inadequate. Suitable screw-fastened plate stiffener arrangements with optimum thicknesses have been proposed for LSBs with web openings to restore their original shear capacity. This paper presents the details of the numerical study and the results.

High temperatures-related elderly mortality varied greatly from year to year : important information for heat-warning systems

We examined the variation in association between high temperatures and elderly mortality (age ≥ 75 years) from year to year in 83 US cities between 1987 and 2000. We used a Poisson regression model and decomposed the mortality risk for high temperatures into: a “main effect” due to high temperatures using lagged non-linear function, and an “added effect” due to consecutive high temperature days. We pooled yearly effects across both regional and national levels. The high temperature effects (both main and added effects) on elderly mortality varied greatly from year to year. In every city there was at least one year where higher temperatures were associated with lower mortality. Years with relatively high heat-related mortality were often followed by years with relatively low mortality. These year to year changes have important consequences for heat-warning systems and for predictions of heat-related mortality due to climate change.

Application of Resilience concept for enhanced management of water supply systems

This paper presents an approach to developing indicators for expressing resilience of a generic water supply system. The system is contextualised as a meta-system consisting of three subsystems to represent the water catchment and reservoir, treatment plant and the distribution system supplying the end-users. The level of final service delivery to end-users is considered as a surrogate measure of systemic resilience. A set of modelled relationships are used to explore relationships between system components when placed under simulated stress. Conceptual system behaviour of specific types of simulated pressure is created for illustration of parameters for indicator development. The approach is based on the hypothesis that an in-depth knowledge of resilience would enable development of decision support system capability which in turn will contribute towards enhanced management of a water supply system. In contrast to conventional water supply system management approaches, a resilience approach facilitates improvement in system efficiency by emphasising awareness of points-of-intervention where system managers can adjust operational control measures across the meta-system (and within subsystems) rather than expansion of the system in entirety in the form of new infrastructure development.

Candidate radial-inflow turbines and high-density working fluids for geothermal power systems

Optimisation of Organic Rankine Cycle (ORCs) for binary-cycle geothermal applications could play a major role in determining the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration: the selection of working fluid and appropriate operating conditions as well as optimisation of the turbine design for those conditions will determine the amount of power that can be extracted from a resource. In this paper, we present the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow machines based on a number of promising ORC systems that use five different working fluids: R134a, R143a, R236fa, R245fa and n-Pentane. Preliminary meanline analysis lead to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139–289 mm rotor diameter). The highest performing cycle, based on R134a, was found to produce 33% more net power from a 150 °C resource flowing at 10 kg/s than the lowest performing cycle, based on n-Pentane.

Candidate radial-inflow turbines and high-density working fluids for geothermal power systems

Optimisation of Organic Rankine Cycles (ORCs) for binary-cycle geothermal applications could play a major role in the competitiveness of low to moderate temperature geothermal resources. Part of this optimisation process is matching cycles to a given resource such that power output can be maximised. Two major and largely interrelated components of the cycle are the working fluid and the turbine. Both components need careful consideration. Due to the temperature differences in geothermal resources a one-size-fits-all approach to surface power infrastructure is not appropriate. Furthermore, the traditional use of steam as a working fluid does not seem practical due to the low temperatures of many resources. A variety of organic fluids with low boiling points may be utilised as ORC working fluids in binary power cycle loops. Due to differences in thermodynamic properties, certain fluids are able to extract more heat from a given resource than others over certain temperature and pressure ranges. This enables the tailoring of power cycle infrastructure to best match the geothermal resource through careful selection of the working fluid and turbine design optimisation to yield the optimum overall cycle performance. This paper presents the rationale for the use of radial-inflow turbines for ORC applications and the preliminary design of several radial-inflow turbines based on a selection of promising ORC cycles using five different high-density working fluids: R134a, R143a, R236fa, R245fa and n-Pentane at sub- or trans-critical conditions. Numerous studies published compare a variety of working fluids for various ORC configurations. However, there is little information specifically pertaining to the design and implementation of ORCs using realistic radial turbine designs in terms of pressure ratios, inlet pressure, rotor size and rotational speed. Preliminary 1D analysis leads to the generation of turbine designs for the various cycles with similar efficiencies (77%) but large differences in dimensions (139289 mm rotor diameter). The highest performing cycle (R134a) was found to produce 33% more net power from a 150°C resource flowing at 10 kg/s than the lowest performing cycle (n-Pentane).

Cross-entropy optimization for scaling factors of a fuzzy controller : a see-and-avoid approach for unmanned aerial systems

The Cross-Entropy (CE) is an efficient method for the estimation of rare-event probabilities and combinatorial optimization. This work presents a novel approach of the CE for optimization of a Soft-Computing controller. A Fuzzy controller was designed to command an unmanned aerial system (UAS) for avoiding collision task. The only sensor used to accomplish this task was a forward camera. The CE is used to reach a near-optimal controller by modifying the scaling factors of the controller inputs. The optimization was realized using the ROS-Gazebo simulation system. In order to evaluate the optimization a big amount of tests were carried out with a real quadcopter.

Untanglings: A novel approach to analyzing concurrent systems

Substantial research efforts have been expended to deal with the complexity of concurrent systems that is inherent to their analysis, e.g., works that tackle the well-known state space explosion problem. Approaches differ in the classes of properties that they are able to suitably check and this is largely a result of the way they balance the trade-off between analysis time and space employed to describe a concurrent system. One interesting class of properties is concerned with behavioral characteristics. These properties are conveniently expressed in terms of computations, or runs, in concurrent systems. This article introduces the theory of untanglings that exploits a particular representation of a collection of runs in a concurrent system. It is shown that a representative untangling of a bounded concurrent system can be constructed that captures all and only the behavior of the system. Representative untanglings strike a unique balance between time and space, yet provide a single model for the convenient extraction of various behavioral properties. Performance measurements in terms of construction time and size of representative untanglings with respect to the original specifications of concurrent systems, conducted on a collection of models from practice, confirm the scalability of the approach. Finally, this article demonstrates practical benefits of using representative untanglings when checking various behavioral properties of concurrent systems.

Parental bonding, family systems, and environmental predictors of adolescent homelessness

A multicausal model of adolescent homelessness is proposed, based upon the notion that homeless youth suffer from emotional, social, and cultural deprivation. The model was tested in a sample of homeless adolescents (n = 54) and a similar, but not homeless, control group (n = 58). Emotional deprivation was assessed on the Parental Bonding Inventory (Parker, Tupling,&Brown, 1979), whereas social and cultural deprivation were assessed on the Family Environment Scale (Moos&Moos, 1981). The homeless adolescents were found to be significantly more deprived emotionally, socially, and culturally than the controls. The results indicate support for a deprivation model of adolescent homelessness with implications for public policy and intervention planning.

Linear adaptive channel equalization for multiuser MIMO-OFDM systems

Linear adaptive channel equalization using the least mean square (LMS) algorithm and the recursive least-squares(RLS) algorithm for an innovative multi-user (MU) MIMOOFDM wireless broadband communications system is proposed. The proposed equalization method adaptively compensates the channel impairments caused by frequency selectivity in the propagation environment. Simulations for the proposed adaptive equalizer are conducted using a training sequence method to determine optimal performance through a comparative analysis. Results show an improvement of 0.15 in BER (at a SNR of 16 dB) when using Adaptive Equalization and RLS algorithm compared to the case in which no equalization is employed. In general, adaptive equalization using LMS and RLS algorithms showed to be significantly beneficial for MU-MIMO-OFDM systems.

Cellular model systems to study the tumor biological role of kallikrein-related peptidases in ovarian and prostate cancer

Since the identification of the gene family of kallikrein related peptidases (KLKs), their function has been robustly studied at the biochemical level. In vitro biochemical studies have shown that KLK proteases are involved in a number of extracellular processes that initiate intracellular signaling pathways by hydrolysis, as reviewed in Chapters 8, 9, and 15, Volume 1. These events have been associated with more invasive phenotypes of ovarian, prostate, and other cancers. Concomitantly, aberrant expression of KLKs has been associated with poor prognosis of patients with ovarian and prostate cancer (Borgoño and Diamandis, 2004; Clements et al., 2004; Yousef and Diamandis, 2009), with prostate-specific antigen (PSA, KLK3) being a long standing, clinically employed biomarker for prostate cancer (Lilja et al., 2008). Data generated from patient samples in clinical studies, alongwith biochemical activity, suggests that KLKs function in the development and progression of these diseases. To bridge the gap between their function at the molecular level and the clinical need for efficacious treatment and prognostic biomarkers, functional assessment at the in vitro cellular level, using various culture models, is increasing, particularly in a three-dimensional (3D) context (Abbott, 2003; Bissell and Radisky, 2001; Pampaloni et al., 2007; Yamada and Cukierman, 2007).

Multi-area reliability assessment of interconnected generating systems using hybrid approach

This paper present an efficient method using system state sampling technique in Monte Carlo simulation for reliability evaluation of multi-area power systems, at Hierarchical Level One (HLI). System state sampling is one of the common methods used in Monte Carlo simulation. The cpu time and memory requirement can be a problem, using this method. Combination of analytical and Monte Carlo method known as Hybrid method, as presented in this paper, can enhance the efficiency of the solution. Incorporation of load model in this study can be utilised either by sampling or enumeration. Both cases are examined in this paper, by application of the methods on Roy Billinton Test System(RBTS).

Learning hierarchical prototypes of motion time series for interactive systems

Abstract. For interactive systems, recognition, reproduction, and generalization of observed motion data are crucial for successful interaction. In this paper, we present a novel method for analysis of motion data that we refer to as K-OMM-trees. K-OMM-trees combine Ordered Means Models (OMMs) a model-based machine learning approach for time series with an hierarchical analysis technique for very large data sets, the K-tree algorithm. The proposed K-OMM-trees enable unsupervised prototype extraction of motion time series data with hierarchical data representation. After introducing the algorithmic details, we apply the proposed method to a gesture data set that includes substantial inter-class variations. Results from our studies show that K-OMM-trees are able to substantially increase the recognition performance and to learn an inherent data hierarchy with meaningful gesture abstractions.