In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

Within-subject intra- and inter-method consistency of two experimental risk attitude elicitation methods

We compare the consistency of choices in two methods to used elicit risk preferences on an aggregate as well as on an individual level. We asked subjects to choose twice from a list of nine decision between two lotteries, as introduced by Holt and Laury (2002, 2005) alternating with nine decisions using the budget approach introduced by Andreoni and Harbaugh (2009). We find that while on an aggregate(subject pool) level the results are (roughly) consistent, on an individual(within-subject) level,behavior is far from consistent. Within each method as well as across methods we observe low correlations. This again questions the reliability of experimental risk elicitation measures and the ability to use results from such methods to control for the risk aversion of subjects when explaining e�ects in other experimental games.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Properties of hand-made clay balls used as a novel filter media

Filtration using granular media such as quarried sand, anthracite and granular activated carbon is a well-known technique used in both water and wastewater treatment. A relatively new prefiltration method called pebble matrix filtration (PMF) technology has been proved effective in treating high turbidity water during heavy rain periods that occur in many parts of the world. Sand and pebbles are the principal filter media used in PMF laboratory and pilot field trials conducted in the UK, Papua New Guinea and Serbia. However during first full-scale trials at a water treatment plant in Sri Lanka in 2008, problems were encountered in sourcing the required uniform size and shape of pebbles due to cost, scarcity and Government regulations on pebble dredging. As an alternative to pebbles, hand-made clay pebbles (balls) were fired in a kiln and their performance evaluated for the sustainability of the PMF system. These clay balls within a filter bed are subjected to stresses due to self-weight and overburden, therefore, it is important that clay balls should be able to withstand these stresses in water saturated conditions. In this paper, experimentally determined physical properties including compression failure load (Uniaxial Compressive Strength) and tensile strength at failure (theoretical) of hand-made clay balls are described. Hand-made clay balls fired between the kiln temperatures of 875oC to 960oC gave failure loads of between 3.0 kN and 7.1 kN. In another test when clay balls were fired to 1250oC the failure load was 35.0 kN compared to natural Scottish cobbles with an average failure load of 29.5 kN. The uniaxial compressive strength of clay balls obtained by experiment has been presented in terms of the tensile yield stress of clay balls. Based on the effective stress principle in soil mechanics, a method for the estimation of maximum theoretical load on clay balls used as filter media is proposed and compared with experimental failure loads.

Econometric fellows and Nobel Laureates in economics

An academic award is method by which peers offer recognition of intellectual efforts. In this paper we take a purely descriptive look at the relationship between becoming a Fellow of the Econometric Society and receiving the Nobel Prize in economics. We discover some interesting aspects: of all 69 Nobel Prize Laureates between 1969 and 2011, only 9 of them were not also Fellows. Moreover, the proportion of future novel winners among the Fellows has been quite high throughout time and a large share of researchers who became Fellows between the 1930s and 1950s became Nobel Laureates at a later stage. On average, researchers became Fellows relatively early in their career (14.9 years after their PhD) and those who were subsequently made Nobel Laureates became Fellows earlier than other researchers. Interestingly, Harvard and MIT have been the dominant PhD granting institutions to generate Fellows and Nobel Laureates in the past.

Curbing resource consumption using team-based feedback : paper printing in a longitudinal case study

This paper details a team-based feedback approach for reducing resource consumption. The approach uses paper printing within office environments as a case study. It communicates the print usage of each participant’s team rather than the participant’s individual print usage. Feedback is provided weekly via emails and contains normative information, along with eco-metrics and team-based comparative statistics. The approach was empirically evaluated to study the effectiveness of the feedback method. The experiment comprised of 16 people belonging to 4 teams with data on their print usage gathered over 58 weeks, using the first 30-35 weeks as a baseline. The study showed a significant reduction in individual printing with an average of 28%. The experiment confirms the underlying hypothesis that participants are persuaded to reduce their print usage in order to improve the overall printing behaviour of their teams. The research provides clear pathways for future research to qualitatively investigate our findings.

The effect of injury diagnosis on expected Postconcussion Syndrome (PCS) symptom reporting and illness perception

Objective: To determine if systematic variation of diagnostic terminology (i.e. concussion, minor head injury [MHI], mild traumatic brain injury [mTBI]) following a standardized injury description produced different expected symptoms and illness perceptions. We hypothesized that worse outcomes would be expected of mTBI, compared to other diagnoses, and that MHI would be perceived as worse than concussion. Method:108 volunteers were randomly allocated to conditions in which they read a vignette describing a motor vehicle accident-related mTBI followed by: a diagnosis of mTBI (n=27), MHI (n=24), concussion (n=31); or, no diagnosis (n=26). All groups rated: a) event ‘undesirability’; b) illness perception, and; c) expected Postconcussion Syndrome (PCS) and Posttraumatic Stress Disorder (PTSD) symptoms six months post injury. Results: On average, more PCS symptomatology was expected following mTBI compared to other diagnoses, but this difference was not statistically significant. There was a statistically significant group effect on undesirability (mTBI>concussion & MHI), PTSD symptomatology (mTBI & no diagnosis>concussion), and negative illness perception (mTBI & no diagnosis>concussion). Conclusion: In general, diagnostic terminology did not affect anticipated PCS symptoms six months post injury, but other outcomes were affected. Given that these diagnostic terms are used interchangeably, this study suggests that changing terminology can influence known contributors to poor mTBI outcome.

Numerical simulation of red blood cells' deformation using SPH method

A numerical simulation method for the Red Blood Cells’ (RBC) deformation is presented in this study. The two-dimensional RBC membrane is modeled by the spring network, where the elastic stretch/compression energy and the bending energy are considered with the constraint of constant RBC surface area. Smoothed Particle Hydrodynamics (SPH) method is used to solve the Navier-Stokes equation coupled with the Plasma-RBC membrane and Cytoplasm- RBC membrane interaction. To verify the method, the motion of a single RBC is simulated in Poiseuille flow and compared with the results reported earlier. Typical motion and deformation mechanism of the RBC is observed.

Stability and convergence of a finite volume method for the space fractional advection-dispersion equation

We consider the space fractional advection–dispersion equation, which is obtained from the classical advection–diffusion equation by replacing the spatial derivatives with a generalised derivative of fractional order. We derive a finite volume method that utilises fractionally-shifted Grünwald formulae for the discretisation of the fractional derivative, to numerically solve the equation on a finite domain with homogeneous Dirichlet boundary conditions. We prove that the method is stable and convergent when coupled with an implicit timestepping strategy. Results of numerical experiments are presented that support the theoretical analysis.

Mixed convection over a horizontal plate with streamwise non-uniform surface temperature distribution

Numerical investigation on mixed convection of a two-dimensional incompressible laminar flow over a horizontal flat plate with streamwise sinusoidal distribution of surface temperature has been performed for different values of Rayleigh number, Reynolds number and frequency of periodic temperature for constant Prandtl number and amplitude of periodic temperature. Finite element method adapted to rectangular non-uniform mesh elements by a non-linear parametric solution algorithm basis numerical scheme has been employed. The investigating parameters are the Rayleigh number, the Reynolds number and frequency of periodic temperature. The effect of variation of individual investigating parameters on mixed convection flow characteristics has been studied to observe the hydrodynamic and thermal behavior for while keeping the other parameters constant. The fluid considered in this study is air with Prandtl number 0.72. The results are obtained for the Rayleigh number range of 102 to 104, Reynolds number ranging from 1 to 100 and the frequency of periodic temperature from 1 to 5. Isotherms, streamlines, average and local Nusselt numbers are presented to show the effect of the different values of aforementioned investigating parameters on fluid flow and heat transfer.

Rule-based transit signal priority control method using a real-time transit travel time prediction model

An advanced rule-based Transit Signal Priority (TSP) control method is presented in this paper. An on-line transit travel time prediction model is the key component of the proposed method, which enables the selection of the most appropriate TSP plans for the prevailing traffic and transit condition. The new method also adopts a priority plan re-development feature that enables modifying or even switching the already implemented priority plan to accommodate changes in the traffic conditions. The proposed method utilizes conventional green extension and red truncation strategies and also two new strategies including green truncation and queue clearance. The new method is evaluated against a typical active TSP strategy and also the base case scenario assuming no TSP control in microsimulation. The evaluation results indicate that the proposed method can produce significant benefits in reducing the bus delay time and improving the service regularity with negligible adverse impacts on the non-transit street traffic.

Improved foreground detection via block-based classifier cascade with probabilistic decision integration

Background subtraction is a fundamental low-level processing task in numerous computer vision applications. The vast majority of algorithms process images on a pixel-by-pixel basis, where an independent decision is made for each pixel. A general limitation of such processing is that rich contextual information is not taken into account. We propose a block-based method capable of dealing with noise, illumination variations, and dynamic backgrounds, while still obtaining smooth contours of foreground objects. Specifically, image sequences are analyzed on an overlapping block-by-block basis. A low-dimensional texture descriptor obtained from each block is passed through an adaptive classifier cascade, where each stage handles a distinct problem. A probabilistic foreground mask generation approach then exploits block overlaps to integrate interim block-level decisions into final pixel-level foreground segmentation. Unlike many pixel-based methods, ad-hoc postprocessing of foreground masks is not required. Experiments on the difficult Wallflower and I2R datasets show that the proposed approach obtains on average better results (both qualitatively and quantitatively) than several prominent methods. We furthermore propose the use of tracking performance as an unbiased approach for assessing the practical usefulness of foreground segmentation methods, and show that the proposed approach leads to considerable improvements in tracking accuracy on the CAVIAR dataset.

Grouping people in social networks using a weighted multi-constraints clustering method

Grouping users in social networks is an important process that improves matching and recommendation activities in social networks. The data mining methods of clustering can be used in grouping the users in social networks. However, the existing general purpose clustering algorithms perform poorly on the social network data due to the special nature of users' data in social networks. One main reason is the constraints that need to be considered in grouping users in social networks. Another reason is the need of capturing large amount of information about users which imposes computational complexity to an algorithm. In this paper, we propose a scalable and effective constraint-based clustering algorithm based on a global similarity measure that takes into consideration the users' constraints and their importance in social networks. Each constraint's importance is calculated based on the occurrence of this constraint in the dataset. Performance of the algorithm is demonstrated on a dataset obtained from an online dating website using internal and external evaluation measures. Results show that the proposed algorithm is able to increases the accuracy of matching users in social networks by 10% in comparison to other algorithms.

Assessing the impacts of lifetime sun exposure on skin damage and skin aging using a non-invasive method

Background: Ultraviolet radiation exposure during an individuals' lifetime is a known risk factor for the development of skin cancer. However, less evidence is available on assessing the relationship between lifetime sun exposure and skin damage and skin aging. Objectives: This study aims to assess the relationship between lifetime sun exposure and skin damage and skin aging using a non-invasive measure of exposure. Methods: We recruited 180 participants (73 males, 107 females) aged 18-83 years. Digital imaging of skin hyper-pigmentation (skin damage) and skin wrinkling (skin aging) on the facial region was measured. Lifetime sun exposure (presented as hours) was calculated from the participants' age multiplied by the estimated annual time outdoors for each year of life. We analyzed the effects of lifetime sun exposure on skin damage and skin aging. We adjust for the influence of age, sex, occupation, history of skin cancer, eye color, hair color, and skin color. Results: There were non-linear relationships between lifetime sun exposure and skin damage and skin aging. Younger participant's skin is much more sensitive to sun exposure than those who were over 50 years of age. As such, there were negative interactions between lifetime sun exposure and age. Age had linear effects on skin damage and skin aging. Conclusion: The data presented showed that self reported lifetime sun exposure was positively associated with skin damage and skin aging, in particular, the younger people. Future health promotion for sun exposure needs to pay attention to this group for skin cancer prevention messaging. (C) 2012 Elsevier B.V. All rights reserved.

Service condition of railroad corridors around the insulated rail joints

Railroad corridors contain large number of Insulated Rail Joints (IRJs) that act as safety critical elements in the circuitries of the signaling and broken rail identification systems. IRJs are regarded as sources of excitation for the passage of loaded wheels leading to high impact forces; these forces in turn cause dips, cross levels and twists to the railroad geometry in close proximity to the sections containing the IRJs in addition to the local damages to the railhead of the IRJs. Therefore, a systematic monitoring of the IRJs in railroad is prudent to mitigate potential risk of their sudden failure (e.g., broken tie plates) under the traffic. This paper presents a simple method of periodic recording of images using time-lapse photography and total station surveying measurements to understand the ongoing deterioration of the IRJs and their surroundings. Over a 500 day period, data were collected to examine the trends in narrowing of the joint gap due to plastic deformation the railhead edges and the dips, cross levels and twists caused to the railroad geometry due to the settlement of ties (sleepers) around the IRJs. The results reflect that the average progressive settlement beneath the IRJs is larger than that under the continuously welded rail, which leads to excessive deviation of railroad profile, cross levels and twists.