In this thesis I present the first gravitational lensing results from the Southern Cosmology Survey (SCS). I provide a preliminary study of an automated pipeline analysis of a large survey, in preparation for larger surveys. Future large-area sky surveys, such as Pan-STARRS-1 (PS1), have similar characteristics to the SCS data and will require full automation of the processing. Therefore, this data set provides an ideal test case to highlight the problems which will be faced by such surveys. To analyse the large SCS dataset, I develop an automated weak lensing pipeline based on the KSB. This pipeline has been rigorously verified using simulations and data which I detail here. Results are shown from a weak lensing analysis of 152 optically-selected clusters in 56 square degrees. I fit universal Navarro, Frenk and White (NFW) profiles to measure cluster masses, and use the relatively large area of the survey to test the universal shape of cluster profiles using stacking of the tangential shears. I present the first lensing mass measurements of Sunyaev-Zel'dovich (SZ) selected clusters. It has been long thought that SZ surveys would be a powerful way to detect galaxy clusters for cosmological studies. Simulations show that the SZ detection is independent of redshift and that the threshold corresponds very closely to a threshold in mass. It was, however, not guaranteed that the first blind SZ experiments would detect mass. Using optical imaging from the SCS, I present lensing masses for three clusters selected by their SZ emission in the South Pole Telescope survey (SPT). I confirm that the SZ selection procedure is successful in detecting mass concentrations and find that the SZ clusters have amongst the largest masses, as high as 15×1014M . Consequently I can confirm that the first installment of SZ detections has detected large mass concentrations. Using the best fit masses for all the clusters, I analytically calculate the expected SZ integrated Y parameter. Finally, the scaling relation of Reyes et al. (2008) of lensing Mlens 200 against optical L200 is tested over the redshift range z = 0.1 − 0.3 and extended to z = 0.3 − 0.8. While there is some discrepancy in the lower redshift-range, we agree with Reyes et al (2008) in the higherredshift sample if we assume no evolution of the scaling relation. To test the tangential shear profile of these clusters, 98 clusters are stacked. We find that by allowing the model to vary from an NFW, a very good fit can be found with a higher normalisation of the shears and a lower concentration. This study supports that of Mandelbaum et al. (2008) who show that that massive halos have a lower concentration than expected. Like the SCS, new large area surveys such as PS1 are not very deep, and it is crucial to understand not only how to analyse this size of dataset, but also the sort of results one could expect to achieve. I show in this thesis that 2D mass reconstructions can be done on data of this quality, and large galaxy clusters successfully reconstructed. With a number density of n ∼ 9 it is possible to detect the most massive clusters with lensing, but it is difficult. With the lower number density of n ∼ 6 or lower expected from PS1 it will prove very difficult to detect individual clusters. However, PS1 will survey a massive area, and so the stacking analysis should work extremely well, and it should be possible to further test the shape of the cluster profiles with stacking as I demonstrated here with the smaller SCS dataset.


This case has been a flashpoint for recent debates over investor-state dispute settlement (ISDS). For Australia, subjected to its first ISDS claim, the case triggered extensive public discussion over whether to continue including ISDS clauses in future bilateral investment treaties (BITs) and investment chapters of free trade agreements (FTAs). More broadly, the case has been seen as epitomising all that is wrong with treaty-based ISDS: an unlikeable, pseudo-American multinational invoking a little-known treaty and an opaque arbitral procedure to claim billion-dollar damages arising from legislation enacted to protect public health. This distasteful image is likely to remain, especially in the public consciousness, despite the claim eventually being dismissed for treaty-shopping, and even though the award deserves to be analysed in broader context. Notably, the case is a rare successful invocation of abuse of right under general international law and even lowers the threshold for such an argument. The case may also encourage states to enhance their screening processes specifically to assess and manage litigation risks flowing from admitting a particular foreign investment.


Although advance selling and probabilistic selling differ in both motivation and implementation, we argue that they share a common characteristic---both offer consumers a choice involving buyer uncertainty. We develop a formal model to examine the general economics of purchase options that involve buyer uncertainty, explore the differences in buyer uncertainty created via these two strategies, and derive conditions under which one dominates the other. We show that the seller can address unobservable buyer heterogeneity by inducing sales involving buyer uncertainty via two different mechanisms: (1) homogenizing heterogeneous consumers and (2) separating heterogeneous consumers. Offering advance sales encourages customers to purchase while they are uncertain about their consumption states (more homogeneous), but offering probabilistic goods encourages customers to reveal their heterogeneity via self-selecting whether or not to purchase the uncertain product. The relative attractiveness of these two selling strategies depends on the degree of two types of buyer heterogeneity: (1) Max_Value-Heterogeneity, which is the variation in consumers' valuations for their preferred good, and (2) Strength-Heterogeneity, which is the variation in the strength of consumers' preferences. Neither strategy is advantageous unless the market exhibits sufficient Max_Value-Heterogeneity. However, whereas Strength-Heterogeneity can destroy the profit advantage of advance selling, a mid-range of Strength-Heterogeneity is necessary for probabilistic selling to be advantageous.


This paper re-examines the determinants of mutual fund fees paid by mutual fund shareholders for management costs and other expenses. There are two novelties with respect to previous studies. First, each type of fee is explained separately. Second, the paper employs a new dataset consisting of Spanish mutual funds, making it the second paper to study mutual fund fees outside the US market. Furthermore, the Spanish market has three interesting characteristics: (i) both distribution and management are highly dominated by banks and savings banks, which points towards potential conflicts of interest; (ii) Spanish mutual fund law imposes caps on all types of fees; and (iii) Spain ranks first in terms of average mutual fund fees among similar countries. We find significant differences in mutual fund fees not explained by the fundٳ investment objective. For instance, management companies owned by banks and savings banks charge higher management fees and redemption fees to nonguaranteed funds. Also, investors in older non-guaranteed funds and non-guaranteed funds with a lower average investment are more likely to end up paying higher management fees. Moreover, there is clear evidence that some mutual funds enjoy better conditions from custodial institutions than others. In contrast to evidence from the US market, larger funds are not associated with lower fees, but with higher custody fees for guaranteed funds and higher redemption fees for both types of funds. Finally, fee-setting by mutual funds is not related to fund before-fee performance.


This paper reviews 74 journal papers that investigate ICT integration from the framework of technological pedagogical content knowledge (TPACK). The TPACK framework is an extension of the pedagogical content knowledge (Shulman, 1986). TPACK is the type of integrative and transformative knowledge teachers need for effective use of ICT in classrooms. As a framework for the design of teacher education programs, the TPACK framework addresses the problem arising from overemphasis on technological knowledge in many ICT courses that are conducted in isolation from teachers' subject matter learning and pedagogical training. The present review we have conducted indicates that TPACK is a burgeoning area of research with more application in the North American region. Studies conducted to date employed varied and sophisticated research methods and they have yielded positive results in enhancing teachers' capability to integrate ICT for instructional practice. However, there are still many potential gaps that the TPACK framework could be employed to facilitate deeper change in education. In particular, we suggest more development and research of technological environments base on TPACK; study of students' learning conception with technology; and cross fertilization of TPACK with other theoretical frameworks related to the study of technology integration.


Abstract Fluorine-rich prismatine, (⃞, Fe, Mg)(Mg, Al, Fe)5Al4(Si, B, Al)5O21(OH, F), with F/(OH+F) = 0.36-0.40 and hercynite are major constituents of a Fe-Al-B-rich lens in ultrahigh-temperature granulite-facies quartz-sillimanite-hypersthene-cordierite gneisses of the Eastern Ghats belt, Andhra Pradesh5 India. Hemo-ilmenite, sapphirine, magnetite, biotite and sillimanite are subordinate. Lithium5 Be and B are concentrated in prismatine (140 ppm Li, 170 ppm Be, and 2.8-3.0 wt. % B2O3). Another Fe-rich lens is dominantly magnetite, which encloses fine-grained zincian ferrohögbomite-2N2S, (Fe2+,Mg, Zn, Al)6 (Al,Fe3+,Ti)16O30(OH)2, containing minor Ga2O3 (0.30-0.92 wt.%). Fe-Al-B-rich lenses with prismatine (or kornerupine) constitute a distinctive type of B-enrichment in granulite-facies rocks and have been reported from four other localities worldwide. A scenario involving a tourmaline- enriched lateritic precursor affected by dehydration melting is our preferred explanation for the origin of the Fe-Al-B-rich lenses at the five localities. Whole-rock analyses and field relationships at another of these localities, Bok se Puts5 Namaqualand, South Africa, are consistent with this scenario. Under granulite-facies Conditions5 tourmaline would have broken down to give kornerupine-prismatine (±other borosilicates) plus a sodic melt containing H2O and B. Removal of this melt depleted the rock in Na and B5 but the formation of ferromagnesian borosilicate phases in the restite prevented total loss of B.


We showed earlier that Tritrichomonas foetus-specific bovine immunoglobulin (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with clearance of this sexually transmitted infection. Eosinophils have been noted in previous studies of bovine trichomoniasis but the role of mast cells and IgE responses have not been reported. The hypothesis that IgE and mast cell degranulation play a role in clearance was tested in 25 virgin heifers inseminated experimentally and infected intravaginally with T. foetus strain D1 at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks, when tissues were fixed and secretions were collected for culture and antibody analysis. Immunohistochemistry using a monoclonal antibody to a soluble lipophosphoglycan (LPG)-containing surface antigen (TF1.17) demonstrated antigen uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen-positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and IgE T. foetus-specific antibodies increased in uterine secretions at weeks 6 and 9 after infection. This was inversely proportional to subepithelial mast cells numbers and most animals cleared the infection by the sampling time after the lowest mast cell count. Furthermore, soluble antigen was found in uterine epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast cells by antigen and perhaps LPG triggering appears to have resulted in degranulation. Released cytokines may account for production of predominantly Th2 (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the infection.


Cultivation of lisianthus (Eustoma grandiflorum (Raf.) Shinn.) is a minor industry in South Africa, with only a few growers producing the crop commercially. Commercial production at a location in Gauteng Province is hampered by rotting of the crowns and roots of plants that result in mortality of as much as 22% of the plants. At advanced stages of infection, the crowns of affected plants characteristically are covered with masses of fusoid, curved hyalophragmospores. Crowns and roots of symptomatic plants that were submitted by the grower in January 2003 were surface disinfested by immersing for 2 min in a 3% solution of sodium hypochlorite, and segments excised from the plant tissue were plated on potato dextrose agar supplemented with 50 mg l-1 of rifampicin. Fusarium solani (Mart.) Appel & Wollenw. (1), was consistently and exclusively isolated from the segments. Teleomorph Nectria haematococca Berk. & Broome, commonly developed in culture after incubation for 4 to 6 weeks, although no sexual structures were observed on infected plants. A spore suspension containing 104 micro- and macroconidia ml-1 was prepared for each of two single-conidial isolates of F. solani. Using a 0.8-mm-diameter hypodermic needle, 100 μl of each suspension was injected subepi-dermally into the crown of each of three 1-month-old disease-free lisian-thus plantlets (cv. Texas Blue Bell) growing in 500-ml plastic pots filled with sterilized vermiculite. In addition, each suspension was incorporated at 2% (vol/vol) into three pots with sterile vermiculite, and a plantlet was planted in each pot. Control plantlets were treated similarly, but with sterile distilled water. All inoculated plantlets developed crown rot and wilted within 2 weeks while maintained at 28°C in a greenhouse, regardless of mode of inoculation, and F. solani was readily reisolated from their crowns and roots. Control plantlets remained symptomless and did not yield F. solani. Crown and root infection of lisianthus by F. solani has been described (2,3), but to our knowledge, this is the first report of the disease in South Africa. References: (1) P. E. Nelson et al. Fusarium species: An Illustrated Manual for Identification. Pennsylvania State University Press, University Park. 1983. (2) J. J. Taubenhaus and W. N. Ezekiel. Phytopathology 24:19, 1934. (3) S. Wolcan et al. Plant Dis. 85:443, 2001.


We determine the basic phase diagram of the fish school model derived from data by Gautrais et al (2012 PLoS Comput. Biol. 8 e1002678), exploring its parameter space beyond the parameter values determined experimentally on groups of barred flagtails (Kuhlia mugil) swimming in a shallow tank. A modified model is studied alongside the original one, in which an additional frontal preference is introduced in the stimulus/response function to account for the angular weighting of interactions. Our study, mostly limited to groups of moderate size (in the order of 100 individuals), focused not only on the transition to schooling induced by increasing the swimming speed, but also on the conditions under which a school can exhibit milling dynamics and the corresponding behavioural transitions. We show the existence of a transition region between milling and schooling, in which the school exhibits multistability and intermittence between schooling and milling for the same combination of individual parameters. We also show that milling does not occur for arbitrarily large groups, mainly due to a distance dependence interaction of the model and information propagation delays in the school, which cause conflicting reactions for large groups. We finally discuss the biological significance of our findings, especially the dependence of behavioural transitions on social interactions, which were reported by Gautrais et al to be adaptive in the experimental conditions.


Platinum-group elements (referred to as PGE, comprising Pt, Pd, Rh, Ru, Ir, and Os) are strategic metals with a wide variety of industrial applications. Most of the world's PGE production is mined from large mafic-ultramafic intrusions such as the Bushveld Complex in South Africa, which currently provides 75% of the world's Pt production. The PGE mineralization is found within distinctive layers, tens to hundred of centimeters thick but extending laterally for many tens of kilometers, where the PGE occur at low parts per million levels as platinum-group minerals (PGM) and in solid solution within disseminated base-metal sulfides. There is still heated debate at the most fundamental level about the mode of formation of this class of deposit; genetic models range from primary magmatic sulfide collection to concentration by migrating halogen-rich fluids. A crucial line of evidence is the spatial relationship between the PGM, which are the most important PGE-bearing phases, and the base-metal sulfide aggregates or blebs. So far, all observations have been carried out using two-dimensional mineralogical studies where textural relationships with other minerals are ambiguous, and with statistical limitations owing to sampling of trace phases intersecting random surfaces. We present the first detailed three-dimensional in situ analysis of the PGM at the sample scale using high-resolution X-ray computed tomography coupled with conventional microscopic and mineralogical study. We find a striking and highly consistent relationship of PGM grains with the edges of complex-shaped magmatic sulfide blebs, and the intersection of these blebs with chromite-silicate grain boundaries. These new three-dimensional observations strongly support an orthomagmatic model coupled with nucleation and growth of PGM at the margins of sulfide liquid droplets.


Although simulation practice with standard patients became popular in curriculums since years of various countries, it hasn't been used in the education of pharmacists and pharmacy technicians in Turkey yet. In this study, it is aimed to conduct a pilot study with standard patients on students in the simulation laboratory for the first time and get feedback of them. This study was conducted with 22 pharmacy technicians, four pharmacy students and four standard patients in 15-16 December 2015. Six scenarios were used. After the study, video recordings of the "student-standard patient interaction" were watched with the students to improve the simulation laboratory and the practices planned to be. The physical properties of the place, the use of body language, issues related to the needs and feelings during practice for the development of training programs has come to fore during the feedback of the students. It is useful to generalize this pilot study in terms of both student groups for starting their profession with communication skills and achieving the golden standards in education.


This publication is a list of books, chapters, journal articles, staff papers, The Center for International Food and Agricultural Policy publications, International Science & Technology Practice & Policy Center papers, miscellaneous monographs, Center for Farm Financial Management papers, miscellaneous Extension publications, popular press articles, op-ed articles, speeches and unpublished papers, computer software, web pages, abstracts and book reviews and theses authored by members of the University of Minnesota Department of Applied Economics in 2014.


Scientists at Los Alamos National Laboratory are developing a miniature, tissue-engineered artificial lung that mimics the response of the human lung to drugs, toxins and other agents. "We breathe in and out thousands of times every day. And while we have control over what we eat or drink, we don't always have control over what we breathe in," said Jennifer Harris of Biosecurity and Public Health at Los Alamos, "and so we're making this miniature lung to be able to test on actual human cells whether something in the environment, or a drug, is toxic or harmful to us." Nicknamed "PuLMo" for Pulmonary Lung Model (Pulmo is also the Latin word for "lung")the device consists of two major parts, the bronchiolar unit and the alveolar unit—just like the human lung. The units are primarily made from various polymers and are connected by a microfluidic "circuit board" that manages fluid and air flow. "When we build our lung, we not only take into account the aspects of different cell types, the tissues that are involved, we also take into account that a lung is supposed to breathe, so PuLMo actually breathes," said Pulak Nath of Applied Modern Physics, who leads engineeringmore » efforts for the project. The most exciting application of PuLMo is a potentially revolutionary improvement in the reliability of drug-toxicity assessments and the prediction of new pharmaceutical success in humans, according to Harris. The PuLMo may also be designed to mimic lung disease conditions, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma, and may be used to study lung air-flow dynamics to better understand the mechanisms of toxins and drug delivery and the effects of smoking, particularly the less-understood effects of e-cigarettes.« less


The physiological and psychological benefits associated with regular engagement in physical activity are well documented. Previous research has noted enhanced feelings of control, competency, self-esteem and positive social interactions alongside a wide range of health benefits. However, most research has been concerned with young adults or clinical populations, while gender differences are rarely reported. This study aimed to investigate the effect of physical activity on mood states of older adults (50-65 year olds) in relation to gender (males versus females). A purposive sample of one hundred and sixty participants (males, n=80; females, n=80) was recruited from leisure centres across the Buckinghamshire region. All participants engaged in physical activity on average twice per week. One physical activity session was selected for investigation. Participants provided informed consent and completed the 20-scale Positive and Negative Affect Scale (PANAS; Watson et al., 1988) prior to, and immediately after, the designated physical activity session. This scale investigated feelings and emotions. Participants' responses were rated using a 5-point Likert scale. One-way ANOVA revealed lower mean scores for positive affect following physical activity in males (36.6 versus 32.5; P=0.002) and females (31.75 versus 28.37; P=0.03). Male scores following physical activity were significantly lower compared to females (-4.3 and -3.37, respectively). These results suggest that physical activity brings about positive affect in both males and females of 50-65 years of age, with males experiencing greater improvements in mood states. It appears that the positive mood changes associated with physical activity previously noted in the young and clinical patients also exist in the 50-65 year old population group. These findings call for a more concerted effort to engage older adults in regular physical activity.


A multi-agent system architecture for coordination of just-in-time production and distribution is presented. The problem to solve is two-fold: first the right amount of resources at the right time should be produced, and then these resources should be distributed to the right consumers. In order to solve the first problem, which is hard when the production and/or distribution time is relatively long, each consumer is equipped with an agent that makes predictions of future needs that it sends to a production agent. The second part of the problem is approached by forming clusters of consumers within which it is possible to redistribute resources fast and at a low cost in order to cope with discrepancies between predicted and actual consumption. Reallocation agents are introduced (one for each cluster) to manage the redistribution of resources. The suggested architecture is evaluated in a case study concerning management of district heating systems. Results from a preliminary simulation study show that the suggested approach makes it possible to control the trade-off between quality-of-service and degree of surplus production. We also compare the suggested approach to a reference control scheme (approximately corresponding to the current approach to district heating management), and conclude that it is possible to reduce the amount of resources produced while maintaining the quality of service. Finally, we describe a simulation experiment where the relation between the size of the clusters and the quality of service was studied.


Listeria monocytogenes and Escherichia coli are food borne pathogens of concern to the Australian dairy industry. Recent consumer and producer requests to allow the manufacture and sale of raw milk cheeses in Australia have caused concern for the industry since raw milk has been identified as a vehicle for the transmission of these, and other, pathogens. Globally L. monocytogenes and E. coli have been associated with severe food-borne illness arising from the consumption of cheeses, demonstrating the ability of these organisms to survive despite the adverse environmental conditions imposed upon them in fermented milk products. An understanding of the ability of pathogens to survive the inimical conditions imposed by fermentation could contribute to the prevention of further outbreaks.
This thesis describes the influence of temperature on low pH- and low water activity-induced inactivation of L. monocyto genes and E. coli in cheese made from both raw and pasteurised mil and in an analogous broth system. In addition, proteomic responses of L. monocytogenes to progressive acidification such as occurs during fermentation, were undertaken.
The influence of temperature, that is not of itself lethal (i.e. in the range of 4 - 45°C), on the survival of L. monocytogenes under growth preventing pH and water activity conditions was investigated. Bacterial inactivation under these conditions is referred to, in this thesis, as non-thermal inactivation. Inactivation rates for three strains of L. monocytogenes were determined in rich broth adjusted to pH 3.5 and water activity 0.90, to prevent growth, and for temperatures in the range 5 to 45°C. Twenty eight inactivation rates were determined, plotted on Arrhenius coordinates (i.e. 1/[absolute temperature] vs. In [rate]), and lines of best fit determined by simple linear regression. The inactivation rate responses were comparable to those reported elsewhere, namely for i) E. coli inactivation in a model salami product and analogous broth system (McQuestin et al. 2006); ii) E. coli and L. monocytogenes inactivation in broth adjusted to pH 3.5 and water activity 0.90 (Zhang et al. 2010); and iii) E. coli inactivation in a variety of fermented meat products and analogous systems (McQuestin et al. 2009). The results showed that non-lethal temperature is also a strong determinant of the rate of inactivation of L. monocytogenes in environments in which growth is prevented by pH and water activity. To extend these studies, a meta-analysis of 45 independent studies was undertaken to investigate the relative influence of pH, water activity, and temperature on L. monocytogenes survival. Published data were re-evaluated to determine rates of inactivation, providing 1195 data over a pH range from 2.7 to 7.4, a\(_w\) range from 0.793 to 0.99, temperature range from 0-68°C, and in various food products, and for various processes and L. monocytogenes strains. When the data were presented as an Arrhenius model, temperature (0-42°C) accounted for 25% of the variance in /n(inactivation rate) data. The pH or water activity measured in broth or in food accounted for 21% and 6% respectively, of the variability in the data.
The inactivation kinetics of L. monocytogenes and E. coli in cheese, when introduced as either contaminants in raw milk, or as post- pasteurisation contaminants in pasteurised milk used for cheese making, were evaluated. Raw and pasteurised semihard Manchego style cow's milk cheeses were prepared with milk inoculated with either L. monocytogenes Scott A or E. coli M23 (an acid tolerant non-pathogenic strain) prepared in both stationary and exponential stages of growth. The final pH of the cheese was 4.5 to 4.7 and final aw 0.91 to 0.92, conditions which, in combination, prevent the growth of both L. monocytogenes and E. coll. Cheeses were prepared and stored at six temperatures in the range 4°C to 25°C. Rates of change of microbial population density were determined and modelled using simple linear regression, where appropriate, and rates of change for both species plotted as a function of temperature using Arrhenius plots. Differences due to the physiological state of the cells (i.e., stationary or exponential growth phase) at the time of cheese making were also analysed. Consistent with the results of broth studies, temperature was shown to have the greatest effect on the rate of inactivation of both species of bacteria however the response was not the same as in broth.
A second cheese challenge trial was undertaken to ascertain the robustness to accidental contamination with bacterial pathogens of a raw sheep's milk, Roquefort-style, cheese. Cheeses were prepared under laboratory conditions from raw ewe's milk inoculated with three strains each of both L. monocytogenes and E. coli. Triplicate inoculated cheeses were matured at each of six temperatures in the range 4°C to 20°C. Pathogen inactivation rate was modelled using simple linear regression and rates of changes for both species plotted as a function of temperature as an Arrhenius plot. All trials were followed for the equivalent of the normal commercial maturation time for the cheese so that the effect of pH changes in the cheese (specifically, pH returning to neutrality later in ripening as is typical in mould-ripened cheeses) could be assessed. Fat content, protein content, a\(_w\) and pH were measured to ascertain the potential influence of these factors on the fate of the introduced pathogens in the cheese. The results confirmed that raw ewe's milk Roquefort-style cheese does not support the growth and survival of L .monocytogenes or E. coli and that inactivation of these pathogens occurs when conditions of pH and water activity become inimical for growth. The results show that the inactivation kinetics of E. coil and L .monocytogenes in raw ewe's milk Roquefort-style cheese are consistent with those observed in broth (but not those observed in semi-hard cheese) and support the hypothesis that vegetative bacterial pathogens in foods that prevent their growth are inactivated at a rate that increases with increasing temperature as hypothesised by Ross et al (2008). The results are not consistent, however, with one of the findings of Zhang et al (2010) who concluded that there was no systematic differences between either the non-thermal inactivation rates of E. coli and L. monocytogenes at temperatures in the range 5 to 40°C in inimical environments.
To begin to elucidate the physiology of such 'non-thermal' inactivation processes, the proteome changes in L monocytogenes in response to progressive acidification were studied in a model cheese fermentation system. Proteins synthesised by cultures subjected to conditions of pH decreasing from pH 5.0 to 4.6 over time were compared with proteins synthesised by stationary phase cultures grown under neutral pH conditions. In the initial growth stages, when pH was mild (pH 5.0) proteins commonly associated with cell growth were up-regulated. Proteins associated with stress responses (significantly, cold shock proteins, heat shock proteins and the Sigma B operon) were down regulated. As the cell culture continued to grow and the pH continued to decrease proteins associated with the acid-tolerance response and virulence (Sigma B operon, listeriolysin 0, internalin B, FOF1 system, PrfA) were upregulated to varying degrees. The use of proteomic techniques provided an overview of the physiology of L. monocytogenes subjected to low, and eventually inimical, pH and was consistent with current knowledge of acid-tolerance responses.
In all, the work presented in this thesis develops the present understanding of the response of L. monocytogenes and E. coli to non-lethal storage temperature and inimical conditions relevant to the manufacture of cheeses from both raw and pasteurised, milk. The results from Chapters 2 and 4 support the hypothesis that nonlethal temperature is a key factor governing the rate of inactivation of vegetative bacteria in foods when other hurdles prevent their growth but indicate that the temperature effect may not be independent of the effect of food type, bacterial species and bacterial strain.


SUMMARY To contribute to an understanding of the evolutionary processes that shape variation in immune responses, we compared several components of the innate and acquired arms of the immune system in five related, but ecologically diverse, migratory shorebirds (ruff Philomachus pugnax L., ruddy turnstone Arenaria interpres L., bar-tailed godwit Limosa lapponica L., sanderling Calidris alba Pallas and red knot C. canutus L.). We used a hemolysis-hemagglutination assay in free-living shorebirds to assess two of the innate components (natural antibodies and complement-mediated lysis), and a modified quantitative enzyme-linked immunosorbent assay in birds held in captivity to assess the acquired component (humoral antibodies against tetanus and diphtheria toxoid) of immunity. Ruddy turnstones showed the highest levels of both innate and acquired immune responses. We suggest that turnstones could have evolved strong immune responses because they scavenge among rotting organic material on the seashore, where they might be exposed to a particularly broad range of pathogens. Although ruffs stand out among shorebirds in having a high prevalence of avian malaria, they do not exhibit higher immune response levels. Our results indicate that relationships between immune response and infection are not likely to follow a broad general pattern, but instead depend on type of parasite exposure, among other factors.


Vodafone is a British mobile network operator with its headquarters in Newbury, Berkshire, England, UK. It is the largest mobile telecommunications network company in the world by turnover and has a market value of about £75 billion (August 2008). Vodafone currently has operations in 25 countries and partner networks in a further 42 countries.


Over the last four decades, academic and wider public interest in inequality and poverty has grown substantially. In this paper we address the question: what have been the major new directions in the analysis of inequality and poverty over the last thirty to forty years? We draw attention to developments under seven headings: changes in the extent of inequality and poverty, changes in the policy environment, increased scrutiny of the concepts of 'poverty' and inequality' and the rise of multidimensional approaches, the use of longitudinal perspectives, an increase in availability of and access to data, developments in analytical methods of measurement, and developments in modelling.


Herein, we report on the studies of GaN nanowires (GaNNWs) prepared via ametal-assisted photochemical electroless etchingmethod with Pt as the catalyst. It has been found that etching time greatly influences the growth of GaN NWs. The density and the length of nanowires increased with longer etching time, and excellent substrate coverage was observed. The average nanowire width and length are around 35 nm and 10 mm, respectively. Transmission electron microscopy (TEM) shows a single-crystalline wurtzite structure and is confirmed by X-ray measurements. The synthesis mechanism of GaN NWs using the metal-assisted photochemical electroless etching method was presented. Photoluminescence (PL) measurements of GaN NWs show red-shift PL peaks compared to the as-grown sample associated with the relaxation of compressive stress. Furthermore, a shift of the E2 peak to the lower frequency in the Raman spectra for the samples etched for a longer time confirms such a stress relaxation. Based on Raman measurements, the compressive stress sxx and the residual strain 3xx were evaluated to be 0.23 GPa and 2.6 10 , respectively. GaN NW synthesis using a low cost method might be used for the fabrication of power optoelectronic devices and gas sensors.


Objective: to study the causes and clinical manifestations of disease in children referred for hospitalization in children infectious diseases hospital in Saratov with a diagnosis of «acute flaccid paralysis». Material and methods: 157 children with the diagnosis on admission of the guide «acute flaccid paralysis». Conducted clinical examination and laboratory tests included a general analysis of cerebrospinal fluid, urine, virological examination of nasal swabs and faeces, with the definition of a serological ELISA method and RPHA immunoglobulins to influenza, rubella, and enterovirus, immunological study of blood, cerebrospinal fluid PCR, electromyography of the affected limbs. Results. 77 patients (49%) with the disease associated with the violation of the musculoskeletal system were registered. In the other cases revealed polyneuropathy was not of poliovirus etiology. Etiological nature of the disease could be explained by 54% of patients. In 37 (46%) patients the diagnosis was formulated in accordance with the severity of paralysis. One child was diagnosed with a vaccine-associated poliomyelitis. Conclusion. The diagnosis of «acute flaccid paralysis» used as administered requires a detailed interpretation in a hospital.


Background. Reductions in the size of the corpus callosum (CC) have been described for schizophrenia patients, but little is known about the possible regional differences in schizophrenia subtypes (paranoid, disorganised, undifferentiated, residual).  Methods. We recruited 58 chronically schizophrenic patients with different subtypes, and 31 age-and-gender matched healthy controls. The callosum was extracted from a midsagittal slice from T1 weighted magnetic resonance images, and areas of the total CC, its five subregions, CC length and total brain volume were compared between schizophrenia subtypes and controls. Five subregions were approximately matched to fibre pathways from cortical regions.  Results. Schizophrenia patients had reduced CC total area and length when compared with controls. Disorganised and undifferentiated schizophrenics had a smaller prefrontal area, while there was no significant difference for the paranoid and residual groups. The premotor/supplementary motor area was smaller in all schizophrenia subtypes. The motor area was smaller only in the disorganised group. A smaller sensory area was found in all subtypes except the residual group. Parietal, temporal and occipital areas were smaller in the paranoid and undifferentiated groups. Total brain volume was smaller in all schizophrenia subtypes compared with controls, but did not reach statistical significance.  Conclusion. These findings suggest that the heterogeneity of symptoms may lead to the different CC morphological characteristics in schizophrenia subtypes.


The recent rapid appreciation of house prices in many U.S. markets has prompted concern over the possible effects of a sharp decline in prices, especially for commercial banks and other real estate lenders. This article examines regional real estate booms and busts in the 1980s and 1990s: Only about half of state house price booms were followed by a severe decline in prices, but large declines occurred in several states that did not have a prior boom. Banks in states that had large house price declines experienced high loan default rates and, thus, low profit and high failure rates. Although U.S. banks may have become more exposed to residential real estate recently, they appear less vulnerable to a decline in house prices than banks in states with large price declines in the earlier period.


The world is constantly changing, and so does required and available knowledge, e.g. stored in Digital Libraries. Knowledge workers heavily rely on the availability and accessibility of knowledge contained in such libraries. The sheer mass of knowledge available today, however, requires sophisticated support for searching and, often considered as equally important, personalization.

In SEKT we address these challenges by using ontologies. Ontologies by nature make implicit knowledge explicit, they describe relevant parts of the world and make them machine understandable and processable. To be effective, ontologies need to change possibly as fast as the parts of the world they describe.

Change discovery aims at generating implicit requirements by inducing ontology changes from existing data. We here focus on {em usage-driven} change discovery. Usage data is a very valuable source of contextual information, based on which the ontology can be modified in order to reflect changes in the real world,

In a precedent deliverable we have presented a framework for usage-driven ontology evolution along with a set of methods for change discovery. In this deliverable we evaluate this framework by applying it to actual use cases from the BT DL case study. The use cases include (1) usage-based pruning of a generic ontology to obtain a personalized ontology, and (2) extending an existing ontology with personalized extensions obtained via Ontology Learning techniques. The evaluation results show the usefulness of applying usage data for the task of ontology evolution.


Computing has had a dramatic impact on the discipline of linguistics and is shaping the way we conceptualize both linguistics and language. Using Computers in Linguistics provides a non-technical introduction to recent developments in linguistic computing and offers specific guidance to the linguist or language professional who wishes to take advantage of them. Divided into eight chapters, each of the expert contributors focus on a different aspect of the interaction of computing and linguistics looking either at computational resources: the Internet, software for fieldwork and teaching linguistics, Unix utilities, or at computational developments: the availability of electronic texts, new methodologies in natural language processing, the development of the CELLAR computing environment for linguistic analysis.


Over the last few years, there has been a growing consensus that Canada has a "US problem." Something needs to be done to improve the overall tone of the bilateral relationship, and to try to increase Canada's influence over policy outcomes in the United States, in order to avoid calamities like restrictive border security policies or protectionist attacks on beef or lumber. There are apparently a few out there who think that the problem was solved by the Liberals' defeat in January, but most seem to agree that the problem is more deeply rooted than that, and requires some kind of larger rethinking of the way that Canada engages with the United States. That's where agreement ends, and the argument begins.Though it hasn't made much of an impact on the general public in Canada (and none at all in the US), there has been an impressively weighty debate on the question of how Canada can best influence US priorities and policies, featuring some brutally candid reflections on Canadian interests and values, some deep thinking about the underlying mechanics of the bilateral relationship, and even some surprising reversals by major players. There are, however, at least three reasons to be troubled by the way the debate has gone so far.First, the battle lines are still very "messy," and the debate has not yet been framed in a way that is accessible to the general public. The most common way of sorting things out-separating those who want to put together a "big deal" from those who want to take things one issue at a time-highlights one major cleavage but conceals many others. In fact, some of the more prominent proposals about how to advance the Canadian agenda actually involve several arguments folded together, and many of the participants in the debate seem unclear about exactly where they agree and disagree with their rivals. My main purpose here is therefore to try to recast the debate within a relatively simple typological framework, based on four different models of how the American political system works. Each of these four models points to a specific political "pathway" for influencing policy outcomes in the US, and may also entail answers to other pivotal strategic questions, such as whether to make diplomatic linkages between issues, and when and how Canada should pursue further economic or political integration.Second, the debate so far seems to lead us to a dead end. Each of the four types of "pathway" strategies I describe here has been severely undercut by its opponents, and at least some of the main proponents of each type have explicitly recognized that their favoured approach is inadequate by itself and/or cannot actually be pursued effectively at this time. What that means is until there are major changes in the US political environment, or someone comes up with an entirely new way of thinking about the bilateral relationship, we are left with trying to cobble together some kind of hybrid approach that would involve switching back and forth between different pathways, depending on the nature of the issue in play and the transnational political configuration of the moment. Just about everyone involved in the debate seems to agree that this is what Canada must do, either for a little while or for the foreseeable future. Unfortunately, there has so far been very little attention to the question of when and how this switching back and forth would actually work. I will therefore offer some preliminary thoughts on how to think about the larger arrangement of Canadian issues within the United States, and what that might tell us about how to make choices between different diplomatic pathways.That brings up the third reason to be unhappy with the debate as it has played out so far: each of the various iterations of the debate-including the current one, which is now nearly five years old-has been based almost entirely on hunches, impressions, and the occasional free-floating anecdote, with little or no hard evidence to support many of the most pivotal assessments and recommendations. …


Maritime Domain Awareness is important for both civilian and military applications. An important part of MDA is detection of unusual vessel activities such as piracy, smuggling, poaching, collisions, etc. Today's interconnected sensorsystems provide us with huge amounts of information over large geographical areas which can make the operators reach their cognitive capacity and start to miss important events. We propose and agent-based situation management system that automatically analyse sensor information to detect unusual activity and anomalies. The system combines knowledge-based detection with data-driven anomaly detection. The system is evaluated using information from both radar and AIS sensors.


OBJECTIVES
To investigate the clinical effectiveness, efficacy and cost effectiveness of splints (orthoses) in people with symptomatic basal thumb joint OA (BTOA).

METHODS
A pragmatic, multicentre parallel group randomized controlled trial at 17 National Health Service (NHS) hospital departments recruited adults with symptomatic BTOA and at least moderate hand pain and dysfunction. We randomized participants (1:1:1) using a computer-based minimization system to one of three treatment groups: a therapist supported self-management programme (SSM), a therapist supported self-management programme plus a verum thumb splint (SSM+S), or a therapist supported self-management programme plus a placebo thumb splint (SSM+PS). Participants were blinded to group allocation, received 90 min therapy over 8 weeks and were followed up for 12 weeks from baseline. Australian/Canadian (AUSCAN) hand pain at 8 weeks was the primary outcome, using intention to treat analysis. We calculated costs of treatment.

RESULTS
We randomized 349 participants to SSM (n = 116), SSM+S (n = 116) or SSM+PS (n = 117) and 292 (84%) provided AUSCAN Osteoarthritis Hand Index hand pain scores at the primary end point (8 weeks). All groups improved, with no mean treatment difference between groups: SSM+S vs SSM -0.5 (95% CI: -1.4, 0.4), P = 0.255; SSM+PS vs SSM -0.1 (95% CI: -1.0, 0.8), P = 0.829; and SSM+S vs SSM+PS -0.4 (95% CI: -1.4, 0.5), P = 0.378. The average 12-week costs were: SSM £586; SSM+S £738; and SSM+PS £685.

CONCLUSION
There was no additional benefit of adding a thumb splint to a high-quality evidence-based, supported self-management programme for thumb OA delivered by therapists.

TRIAL REGISTRATION
ISRCTN 54744256 (http://www.isrctn.com/ISRCTN54744256).


1. A general method for the development of a blood volume index was devised to allow inter-individual comparisons. 2. An accurate and acceptable blood volume index had to fulfil certain criteria; it had to be (1) not correlated with body size, (2) highly correlated with blood volume, (3) either dimension-less or expressible in units of length or of surface area and (4) simple to calculate. 3. Available data, from the Broussais Hospital, Paris, the Zuiderziekenhuis, Rotterdam and the Cleveland Clinic, Cleveland, Ohio, included six groups of normal subjects, male essential hypertensive patients and female essential hypertensive patients. 4. Extensive calculations, based on the available data, indicated that the equation BVI = BV/( a√H.W ) (BVI = blood volume index, BV = blood volume, H = body height, W = body weight and a = a constant depending on the chosen units) was the simplest index which satisfied the above requirements. 5. As the equation SA = 0.165 √( H.W ) (SA = body surface area, in m 2 , H in m and W in kg) is almost identical with the Dubois & Dubois formula predicting body surface area from height and weight, one may choose a = 0165 and the index BVI = BV/[0.165 √( H.W )] (/ H in m, W in kg, BV in ml and BVI in ml/m 2 ). Thus blood volume is referred to body surface area. 6. Blood volume referred to unit body surface area appears, at the present, to be the most appropriate 'blood volume index'. However, studies of data from larger groups and from more centres are needed to confirm this conclusion.


This paper explores the performance of rural governance institutions (Gram Panchayats) in Maharashtra, India. The results of a detailed set of household and village surveys we conducted point to a stunningly robust and participatory democratic process: Elections are freely contested, fairly tallied, highly participatory, non-coerced and lead to political representation believed by voters to strongly reflect their will. However, poverty alleviation schemes (one of the main tasks of rural Gram Panchayats) are patchy and poorly implemented. Beneath this veneer of representative democracy we find evidence of deeply ingrained clientilist structures. These allow land-owning elites of a leading caste (Marathas) to maintain political power which they use to undermine poverty alleviating policies that would redistribute income away from them. We explore theoretically the means by which this caste is able to use its dominance of land-ownership and its traditional position of caste ascendency to achieve political control. The data also allows us to test, both directly and indirectly, differing hypotheses regarding the means by which cultural power (caste) and land ownership yield political power for the elite even in a highly representative, fair and participatory democratic setting.


The incidence of type 1 diabetes (T1D) in young children is increasing markedly however young children have been overlooked in paediatric adherence research despite the unique challenges their care presents. We investigated the relation between maternal communication style and adherence to the dietary regimen in 40 children with T1D, aged 2-8 years, and their mothers. Mothers completed measures of children's sugar consumption, parent-child communication quality, and child psychological functioning. Mothers and children engaged in a videotaped problem-solving task related to the dietary regimen, with maternal utterances analysed for behavioural control style (e.g., commands versus suggestions) and cognitive complexity (e.g., provision of labels versus questions). Maternal communications which engaged children, behaviourally and cognitively, in the task were associated with better adherence, medical, communication quality, and child adjustment outcomes. We conclude that adherence and health (medical and psychological) are optimised when young children are given opportunities to participate in their care.


Sagopilone, an optimized fully synthetic epothilone, is a microtubule-stabilizing compound that has shown high in vitro and in vivo activity against a broad range of human tumor models. We analyzed the differential mechanism of action of sagopilone in non-small cell lung cancer cell lines in vitro. Sagopilone inhibited proliferation of non-small cell lung cancer cell lines at lower nanomolar concentration. The treatment with sagopilone caused strong disturbances of cellular cytoskeletal organization. Two concentration-dependent phenotypes were observed. At 2.5 nM sagopilone or 4 nM paclitaxel an aneuploid phenotype occur whereas a mitotic arrest phenotype was induced by 40 nM sagopilone or paclitaxel. Interestingly, treatment with 2.5 nM of sagopilone effectively inhibited cell proliferation, but - compared to high concentrations (40 nM) - only marginally induced apoptosis. Treatment with a high versus a low concentration of sagopilone or paclitaxel regulates a non-overlapping set of genes, indicating that both phenotypes substantially differ from each other. Genes involved in G2/M phase transition and the spindle assembly checkpoint, like Cyclin B1 and BUBR1 were upregulated by treatment with 40 nM sagopilone. Unexpectedly, also genes involved in DNA damage response were upregulated under that treatment. In contrast, treatment of A549 cells with a low concentration of sagopilone revealed an upregulation of direct transcriptional target genes of TP53, like CDKN1A, MDM2, GADD45A, FAS. Knockdown of TP53, which inhibited the transcriptional induction of TP53 target genes, led to a significant increase in apoptosis induction in A549 cells when treated with a low concentration of sagopilone. The results indicate that activation of TP53 and its downstream effectors like CDKN1A by low concentrations of sagopilone is responsible for the relative apoptosis resistance of A549 cells and might represent a mechanism of resistance to sagopilone.


Protecting the efficacy of temperature-sensitive drugs is a real challenge especially for the countries with hot climates. Over-the-counter medicines have recommended storage-temperature of around 20-30 °C, while ambient temperature in most metropolitan areas of Pakistan reach around 40-50 °C in summers, even under the shade. Other temperature-sensitive medicines require storage at around 4-8 °C. A reputation of spurious drugs due to mismanagement with regard to transport and storage also goes contrary to the interests of the pharmaceutical sector. This research investigates the preservation and storage of temperature-sensitive medicines in its specialized supply-chain (referred to as "cold chain†) and finds that while the import of active ingredients is rather well managed and controlled with storage at within the desired temperatures; the distribution-chain needs to be more adaptive of the standards in-order to better preserve efficacy of the medicines. Nevertheless, long hours of power black-outs (a common occurrence in Pakistan and other developing nations) further guarantee the deterioration of temperature-sensitive medicines stored at the chemist-shops. It is therefore, recommended that temperature-sensitive medicines should only be dispensed from stores that have standby-power.


The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies. Studies were conducted in cell culture and in rodent animal models to determine the efficacy of interferon-alpha (IFN-α), interferon (IFN) inducers and ribavirin, alone or in combination with IFN, in treating WNV. Intraperitoneal injection of IFN-α B/D (qd for 7 days), polyIpolyC(12)U [Ampligen (every other day for 7 days)] and topically applied imiquimod (qd for 7 days), administered from 1 day before viral challenge, were effective in protecting, respectively, 100%, 100% and 70% of BALB/c mice from mortality induced by subcutaneous injection of WNV. When IFN-α B/D or Ampligen treatments were delayed to 4–6 h before viral challenge in mice, efficacy was greatly diminished. Infected Syrian golden hamsters treated with interferon alphacon-1 (Infergen) and Ampligen 4–6 h before viral challenge gained more weight and had a greater survival than saline-treated animals. A combination study of subcutaneously administered Infergen (5 to 0.05 μg/kg/day) and ribavirin (75 to 7.5 mg/kg/day) in >7 week old hamsters demonstrated that Infergen was slightly efficacious in reducing mortality and disease signs; however, it was not synergistic in its antiviral effects when combined with ribavirin. Ribavirin treatment alone increased mortality of infected hamsters. The reduced mortality correlated with reduced plasma viraemia. Since WNV-infected patients have already been treated with IFN and ribavirin and future clinical trials have been suggested, this first report of IFN alone or in combination with ribavirin in WNV-infected animal models might provide useful information for subsequent treatment of patients.


If well managed, crises do not only pose a threat to political actors but also provide opportunities to show action, strengthening credibility and launching new policies. Within the field of crisis communication, research has primarily taken an interest in the rhetorical strategies of actors when explaining successes or failures. In this article, we examine key characteristics of what we refer to as crisis exploitation coverage in the news media. We do so based on a comparative quantitative study of 3 crisis cases (terror, floods, and financial crisis) selected due to their differences in journalistic routines and preparedness. The results of the study revealed that the similarities in the cases were more pronounced than their differences. All three cases showed high levels of descriptive journalism and issue framing in combination with unbalanced reporting—characteristics that were all favorable toward the governmental actors in charge of managing the crisis.


An important task in the analysis and reconstruction of curvilinear structures from unorganized 3-D point samples is the estimation of tangent information at each data point. Its main challenges are in (1) the selection of an appropriate scale of analysis to accommodate noise, density variation and sparsity in the data, and in (2) the formulation of a model and associated objective function that correctly expresses their effects. We pose this problem as one of estimating the neighborhood size for which the principal eigenvector of the data scatter matrix is best aligned with the true tangent of the curve, in a probabilistic sense. We analyze the perturbation on the direction of the eigenvector due to finite samples and noise using the expected statistics of the scatter matrix estimators, and employ a simple iterative procedure to choose the optimal neighborhood size. Experiments on synthetic and real data validate the behavior predicted by the model, and show competitive performance and improved stability over leading polynomial-fitting alternatives that require a preset scale.


Intensity-duration-frequency (IDF) curves usefully quantify extreme precipitation over various durations and return periods for engineering design. Unfortunately, sparse, infrequent, or short observations hinder the creation of robust IDF curves in many locations. This paper presents the first global, multi-temporal (1–360 h) dataset of generalized extreme value (GEV) parameters at 31 km resolution dubbed PXR-2 (Parametrized eXtreme Rain). Using these data we generalize site-specific studies to show that that GEV parameters typically scale robustly with event duration (r2 > 0.88). Thus, we propose a universal IDF formula that allows estimates of rainfall intensity for a continuous range of durations (PXR-4). This parameter scaling property opens the door to estimating sub-daily IDF from daily records. We evaluate this characteristic for selected global cities and a high-density rain gauge network in the United Kingdom. We find that intensities estimated with PXR-4 are within ±20% of PXR-2 for durations ranging between 2 and 360 h. PXR is immediately usable by earth scientists studying global precipitation extremes and a promising proof-of-concept for engineers designing infrastructure in data-scarce regions.


Alkylation has been successfully performed using propionaldehyde on four batches of T1 thermostable lipase (M1, M2, M3 and M4) with different degrees of modification (27% to 55%) to represent the different levels of hydrophobicity. Based on the crystal structure, T1 possessed 11 lysine residues, of which four of the lysine residues, Lys84, 102, 138 and 251 have scores between 53.7% and 95.8% exposure ratio, were totally exposed. Another four residues, Lys185, 329, 344 and 345 have a ratio between 20% and 50% (moderately exposed) and three of the lysine residues, Lys28, 207 and 229 are buried. The hydrolytic activity of the modified enzymes dropped drastically by 10 to 40-fold upon chemical modification, despite both the native and modified form showed distinctive α-helical bands at 208 and 222 nm by Far Ultra-Violet Circular Dichroism (CD) spectropolarimetry. As cooperative unfolding transitions were observed, the modified lipases were distinguished from the native state, which the former possessed a Tm in lower temperature range, 60-64 oC whilst the latter at 68 oC. Consequently, this has led us to the hypothesis of formation of a molten globule (MG)-like structure. Subsequent analysis of both native and modified lipases by Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) study was carried out to ascertain the modifications and the location of these modifications. Four lysine residues, Lys28, 84, 207 and 329 were clearly identified from the native spectrum. As expected, Lys84 and Lys102 were clearly modified. Surprisingly, Lys185 which has a very low exposure ratio (27.5%) was also identified to be one of the modified residues. To further support the hypothesis of the formation of a molten globule, intrinsic and extrinsic fluorescence were performed. A decrease of fluorescence intensity was observed for modified lipase M1, which was modified using 0.5% of propionaldehyde. However, subsequent addition of propionaldehyde enhanced the fluorescence intensity of M2, M3 and M4, which indicated an inversion of placement for tryptophans to a more hydrophobic environment. As for extrinsic fluorescence, the alkylated lipases showed a clear enhancement of fluorescence intensity as compared to the native lipase due to the exposure of the hydrophobic interior of the enzymes.


An increasingly complex and diverse collection of Machine Learning (ML) models as well as hardware/software stacks, collectively referred to as "ML artifacts", are being proposed - leading to a diverse landscape of ML. These ML innovations proposed have outpaced researchers' ability to analyze, study and adapt them. This is exacerbated by the complicated and sometimes non-reproducible procedures for ML evaluation. A common practice of sharing ML artifacts is through repositories where artifact authors post ad-hoc code and some documentation, but often fail to reveal critical information for others to reproduce their results. This results in users' inability to compare with artifact authors' claims or adapt the model to his/her own use. This paper discusses common challenges and pitfalls of ML evaluation and benchmarking, which can be used as a guideline for ML model authors when sharing ML artifacts, and for system developers when benchmarking or designing ML systems.


Gastrointestinal (GI) parasitic infection in cattle is a worldwide problem as a cause of reduced productivity and profitability. The present study deals with the prevalence of various GIparasitic infections in cattle in the Mahakaushal region of Madhya Pradesh. A total of 1243 faecal samples collected during a period of one year revealed, 249 (20.03%) were positive for one or more GIparasitism viz., Amphistomes (13.03%), Strongyle (5.47%), Moniezia (1.37%), Coccidia (1.21%), Fasciola (0.48%) and Toxocaravitulorum (0.16%) infection. Coproculture studies reveled thatHaemonchus was predominant nematode followed by Oesophagostomum, Trichostrongylus, Strongyloides and Bunostomum. Seasonal prevalence revealed significantly higher (p less than 0.01) prevalencein monsoon season (25.91%) than summer (21.40%) and winter (12.50%). Whereas, age wise prevalence was non-significantly higher in adult compared to young calves.


This paper summarizes our work on memory design and exploration for low power data-dominated embedded systems. The memory sub-system consists of an instruction cache and a data cache on-chip, and a large memory off-chip. Our procedure consists of: reducing the power consumption due to memory traffic by applying memory-optimizing loop transformations; and using a memory exploration procedure to choose a cache configuration (cache size and line size) that satisfies the system requirements of area, number of cycles and energy consumption. The memory exploration procedure is very efficient since it exploits the trends in the cycles and energy characteristics to reduce the search space significantly.


Background Patients in psychiatric wards typically have very limited access to individual psychological therapy. Inpatients often have significant time available, and an important transition back to everyday life to prepare for—but historically, there have been few trained therapists available on wards for the delivery of evidence-based therapy. Automated virtual reality (VR) therapy may be one route to increase the provision of powerful psychological treatments in psychiatric hospitals. The gameChange automated VR cognitive therapy is targeted at helping patients overcome anxious avoidance and re-engage in everyday situations (such as walking down the street, taking a bus, or going to a shop). This treatment target may fit well for many patients preparing for discharge. However, little is known about how VR therapy may be viewed in this setting. Objective The objectives of the study are to explore psychiatric hospital staff and patients' initial expectations of VR therapy, to gather patient and staff views of an automated VR cognitive therapy (gameChange) after briefly experiencing it, and to identify potential differences across National Health Service (NHS) mental health trusts for implementation. Guided by an implementation framework, the knowledge gained from this study will be used to assess the feasibility of VR treatment adoption into psychiatric hospitals. Methods Focus groups will be conducted with NHS staff and patients in acute psychiatric wards at 5 NHS mental health trusts across England. Staff and patients will be interviewed in separate groups. Individual interviews will also be conducted when preferred by a participant. Within each of the 5 trusts, 1 to 2 wards will be visited. A total of 8-15 staff and patients per ward will be recruited, with a minimum total of 50 staff and patients recruited across all sites. Focus group questions have been derived from the nonadoption, abandonment, and challenges to the scale-up, spread, and sustainability (NASSS) framework. Focus groups will discuss expectations of VR therapy before participants are given the opportunity to briefly try the gameChange VR therapy. Questions will then focus on opinions about the therapy and investigate feasibility of adoption, with particular consideration given to site specific issues. A thematic analysis will be conducted. Results As of May 15, 2020, 1 patient focus group has been conducted. Conclusions The study will provide unique insight from patients and staff into the potential for implementing automated VR therapy in psychiatric wards. Perspectives will be captured both on the use of immersive technology hardware and therapy-specific issues in such settings. International Registered Report Identifier (IRRID) DERR1-10.2196/20300


We present a new roadmap that can be used to guide a convex body to explore an unknown planar workspace, i.e., to map an unknown configuration space diffeomorphic to SE(2). This new roadmap is called the convex hierarchical generalized Voronoi graph (convex-HGVG). Since this roadmap is defined in terms of workspace distance information that is within line of sight of the convex body, we can use it to direct the robot to explore an unknown configuration space diffeomorphic to SE(2). The challenge in defining the roadmap is that SE(2), with holes removed from it, generally does not have a one-dimensional deformation retract. Therefore, we decompose the punctured SE (2) into contractible regions, in which we define convex generalized Voronoi graphs (convex-GVG), and then connect these graphs with additional structures called convex-R edges. We formally show that the convex-HGVG, which is the union of the convex-GVG edges and the convex-R edges, is indeed a roadmap.


BACKGROUND Polyalkylimide is a nonresorbable, biocompatible polymeric filler that has been used for several years to treat soft tissue deficits. The literature has shown a minor complication rate. We noticed that complications typically appear several years after injection. OBJECTIVE To evaluate the complications reported after treatment with polyalkylimide. METHODS AND MATERIALS We describe a retrospective evaluation, reported by members and candidate members of the Dutch Society of Cosmetic Medicine, of complications after use of polyalkylimide. RESULTS In total, 3,196 patients were treated, and 4,738 treatments were performed, from which 154 complications (patient complication rate 4.8%, treatment complication rate 3.3%) were reported. The most common complication was inflammation; other complications were hardening, migration, and accumulation of the product. In some patients, skin biopsy followed by histologic examination was performed. CONCLUSION Treatments with polyalkylimide have been reported to give rise to complications years after treatment. Even though the study described is a retrospective evaluation, we consider an overall complication rate of 4.8%, the severity of the complications, and the difficulty in treating them too high a risk for a cosmetic treatment. The Dutch Society of Cosmetic Medicine advises against the use of polyalkylimide.


This article argues that Samuelson's influential 1987 call for a 'Whig history of economic science' rests on a Whig historiography of the natural sciences. This contrasts with how science actually works: Samuelson neglects the critical role of controversy in the development of knowledge, leading to the misleading idea that scientists pursue discovery at the expense of reflection on the foundation and history of their subject. The consequence is institutional delegitimation: the exclusion of legitimate contrary hypotheses when economists test their theories, invalidating the test. Samuelson further confuses the history of ideas with the history of texts. This expands the scope of institutional delegitimation to a systematic misrepresentation of the actual ideas at stake in the economic controversies, erecting a permanent obstacle to the discovery of truth. I illustrate this with Samuelson's exclusion from consideration of two 'non-ignorable' contributions to macroeconomic theory: Schumpeter's Business Cycles, which he failed to recognise as a theory of endogenous capitalist self-restoration, and the concept of endogenous decline, excluded by his Whig reinterpretation of Marx's theory of value. Schumpeter and Marx offered opposed, but legitimate, alternatives to the post-war macroeconomic consensus of which Samuelson was a major architect. In particular, both recognised that deep and prolonged crises were a natural product of capitalism, not an inexplicable exception. To respond to the 2008 downturn, economics needs to reopen a wide discussion without excluding, a priori, any of these opposed theoretical explanations, instead seeking to understand clearly what each of them actually says and testing them against the empirical evidence of history.


Mountain regions provide essential ecosystem goods and services (EGS) for both mountain dwellers and people living outside these areas. Global change endangers the capacity of mountain ecosystems to provide key services. The Mountland project focused on three case study regions in the Swiss Alps and aimed to propose land-use practices and alternative policy solutions to ensure the provision of key EGS under climate and land-use changes. We summarized and synthesized the results of the project and provide insights into the ecological, socioeconomic, and political processes relevant for analyzing global change impacts on a European mountain region. In Mountland, an integrative approach was applied, combining methods from economics and the political and natural sciences to analyze ecosystem functioning from a holistic human-environment system perspective. In general, surveys, experiments, and model results revealed that climate and socioeconomic changes are likely to increase the vulnerability of the EGS analyzed. We regard the following key characteristics of coupled human-environment systems as central to our case study areas in mountain regions: thresholds, heterogeneity, trade-offs, and feedback. Our results suggest that the institutional framework should be strengthened in a way that better addresses these characteristics, allowing for (1) more integrative approaches, (2) a more network-oriented management and steering of political processes that integrate local stakeholders, and (3) enhanced capacity building to decrease the identified vulnerability as central elements in the policy process. Further, to maintain and support the future provision of EGS in mountain regions, policy making should also focus on project- oriented, cross-sectoral policies and spatial planning as a coordination instrument for land use in general.


Microvascular endothelial cell invasion into the fibrin provisional matrix is an integral component of angiogenesis during wound repair. Cell surface receptors which interact with extracellular matrix proteins participate in cell migration and invasion. Malignant cells use CD44-related chondroitin sulfate proteoglycan (CSPG) as a matrix receptor to mediate migration and invasion. In this study, we examine whether cell surface CSPG can mediate similar events in nonmalignant wound microvascular endothelial cells or whether use of CSPG for migration and invasion is a property largely restricted to malignant cells. After inhibiting CSPG synthesis with p-nitrophenyl beta-d xylopyranoside (beta-d xyloside), wound microvascular endothelial cells were capable of attaching and spreading on the surface of a fibrin gel; however, their ability to invade the fibrin matrix was virtually eliminated. To begin to examine the mechanism by which endothelial cells use CSPG to invade fibrin matrices, cell adhesion and migration on fibrinogen was examined. Endothelial cell adhesion and migration on fibrinogen were inhibited by both beta-d xyloside and after cleavage of chondroitin sulfate from the core protein by chondroitinase ABC. We have determined that wound microvascular endothelial cells express the majority of their proteoglycan as CSPG and that the CSPG core protein is immunologically related to CD44. PCR studies show that these cells express both the "standard" (CD44H) isoform and an isoform containing the variably spliced exon V3. In addition, anti-CD44 antibody blocks endothelial cell migration on fibrinogen. Affinity chromatography studies reveal that partially purified microvascular endothelial cell CSPG binds fibrinogen. These findings suggest that CD44-related CSPG, a molecule implicated in the invasive behavior of tumor cells, is capable of binding fibrinogen/fibrin, thereby mediating endothelial cell migration and invasion into the fibrin provisional matrix during wound repair.


Continuous cultures of a hybridoma cell line (Zac3) were performed in a stirred tank reactor with protein-free media. At steady state the medium was replaced by one contg. U-14C-labeled glucose. The fluxes leaving the reactor were analyzed with a scintillation counter to det. the specific activity of each. The gas and solid phases allowed detn. of the oxidn. and the assimilation ratio of the consumed glucose. The liq. phase was sepd. chromatog. to det. quant. the different species consumed or formed by the cells. Identical expts. were also performed with U-14C glutamine labeled. The major part of the glucose consumed (83.65%) was converted to lactate. By this method it was possible to complete the carbon balance. [on SciFinder (R)]


The problem of H∞ observer-based output feedback control for a class of switched systems with time-delay is addressed. By using a new state transformation, a delay-dependent sufficient condition for the problem to be solvable is given in terms of linear matrix inequalities. We show that when all subsystems have H∞ observer-based output feedback controllers satisfying the LMIs, the switched system has a switching H∞ observer-based output feedback controller. The key idea is to establish a new type of common Lyapunov function for all subsystems and the main feature is that a transformed subsystem is an equivalent descriptor subsystem to the observer-based feedback closed-loop subsystem. Furthermore, we extend these results to switched systems with multi-delay in the dynamics and in the objective function. A simulation example is presented to illustrate the validity of the results.


ABSTRACT Illinois is home to approximately 2,107 native plant species of which about 16% are listed as threatened or endangered (T & E). In addition to the common threats associated with the decline of these species, climate change is a rapidly emerging threat. Climate predictions for Illinois have estimated that summer temperatures will resemble present-day summers in Texas by mid- to late-century, while precipitation patterns are less predictable. Using NatureServe's Climate Change Vulnerability Index (CCVI) tool we evaluated the climate change vulnerability for all 331 of Illinois T & E plant species. Overall, we found that over 80% are vulnerable to climate change. Barriers to migration are a leading factor associated with vulnerability in Illinois, where 97% of listed species are affected by anthropogenic barriers and 24% are affected by natural barriers. The sensitivity of species to changes in temperature, precipitation, and hydrology are also associated with vulnerability. The CCVI score was associated with most of the dozen or so other factors incorporated in the tool, though to a lesser degree. This study provides insights into the most vulnerable plant species in Illinois and provides much needed information to land managers, policy makers, and researchers. By highlighting which T & E species are most vulnerable to climate change, and what factors are most responsible for their vulnerability, this work will aid in prioritizing limited resources and developing adaptation strategies for them.


ABSTRACT The paper analyses why Egypt's labour movement, while having played a significant role in the run-up to the 2011 revolution, has been increasingly marginalised politically ever since, failing to achieve either significant labour-specific gains and/or broader objectives related to the overall process of political transformation. It does so by investigating Egypt's movement of independent trade unions, the most dynamic element within the country's labour movement, from a comparative perspective. Specifically, the paper uses the experience of Brazil's New Unionism in the 1980s as a contrasting case, identifies the factors that have enabled and constrained what is arguably the most successful example of a New Unionist movement in the Global South, and applies this explanatory framework in an in-depth study on the trajectory of Egypt's New Unionism since 2011. The study identifies four key differences between the Brazilian and the Egyptian case that help explain the post-revolutionary trajectory of independent labour in the latter: the different sequencing of neoliberal reforms and political liberalisation; the revolutionary character of the Egyptian uprising; the different role of individual movement entrepreneurs; and the lack of significant socio-political allies in the Egyptian case.


The growing interest in e-Government raises the question of how governments can increase citizen adoption and usage of their online government services. e-Government becomes especially important given its potential to reduce costs and improve service compared with alternative traditional modes. Citizen trust is proposed to be an important catalyst of e-Government adoption. By investigating online tax services, already available and used extensively in the West, we propose several ways in which governments can increase citizen trust and thus encourage the adoption of this new and potentially significant mode of government service. The proposed e-Government adoption model also takes in account issues of cultural variables, risk, control and technology acceptance.Institution-based trust, such as an independent judicial system with appropriate legal powers, is proposed to be the major tactic to build trust in e-Government. In addition, among new users of online government services, characteristic-based and cognitive-based antecedents should be crucial; general psychological dispositions and knowledge of the process should also engender trust. Among experienced users, on the other hand, it is suggested that the nature of previous interactions with the e-Government system should be the major predictor of trust, and hence of continued use. These propositions are elucidated, as they apply to different cultures and to high-intrusive versus low-intrusive government services. This study has practical implications for the design of mechanisms for the adoption of e-Government.


The Madhyantavibhaga is classified by later Indian, Chinese, and Tibetan traditions as belonging to the Yogacara school, and is considered to be one the treatises of Maitreya. The text offers a treatment of some key doctrines of the Mahayana, including the three-nature theory and the doctrine of emptiness, which is addressed in a specifically Yogcra manner. This volume is divided into two parts. The first part contains a study of the text, including an introduction to Yogacara philosophy, an overview of the Madhyantavibhaga-corpus, and a detailed exegesis of the text, incorporating interpretations offered in recent scholarship. The second part contains a fully annotated translation of the text and its commentary, making significant use of Sthiramati's subcommentary in the notes. Published by American Institute of Buddhist Studies (AIBS)


Many efforts have been taken to generate realistic facial modeling and animation. This is inspired by the increasing appearance of virtual characters in film and video, inexpensive desktop processing power, and the potential for a new 3D immersive communication metaphor for human-computer interaction.

Wrinkles are important for realistic facial animation and modeling because they aid in recognizing human's expressions as well as person's age. Different techniques have been used to generate wrinkles, whether it is fine-scale or large-scale wrinkles.

This research focuses on introducing a new shape function for simulating a single wrinkle. However, it does not take into account the facial animation, and hence the modeling is only concerns with the wrinkling process triggered by user interaction.

To carry out this research, a simple method that allows the user to control the shape and location of the wrinkle is used. The process involves two major steps. The first step is to construct a face mesh, either by scanning through digital scanner or modeled by using a CG software and correctly upload it into the program.

The second step is to perform the wrinkling process. In this process, user will draw a stroke on top of the face mesh to represent the wrinkle by using the mouse. Points on the stroke are stored in a vector array and interpolated to obtain evenly closer distributed points.

Once this is done, the program is then required to find triangular meshes affected by the stroke drawn earlier and subdivide it into smaller triangular meshes. These triangular meshes need to be interpolated as well to produce evenly distributed points. Then, the wrinkle shape function is applied to the wrinkle points to see the effect of the wrinkle simulation.

In the end of this research, we will show that the research objective made is successfully achieved through the observation made by the third parties, and the wrinkle produced does meet the properties of real wrinkles.


"Starting in the mid-1990s, Africa embarked upon its longest period of sustained, positive per capita income growth since the 1960s. This growth recovery has made a dent in poverty and holds out hope that a number of African countries may reach the Millennium Development Goal targets for poverty and food security (MDG 1), if not by 2015, then within the following few years. Agricultural growth has been, and will remain, key to reducing poverty and hunger in Africa. To significantly reduce poverty, Africa needs to sustain, broaden, and accelerate its recent growth performance and boost its investments in agriculture. The recent spike in global food prices represents an opportunity that could support further agricultural sector growth in Africa. The unfolding financial crisis, on the other hand, could have the reverse effect, especially if it leads to lower investments in the sector." from author's abstract


Neutralising antibodies are an essential component in the immune response to virus infection and are often effective at preventing or attenuating viral diseases. The administration of cocktails of potently neutralising monoclonal antibodies (nAb) to abrogate viral infections has been demonstrated as an effective treatment to control disease progression caused by a diverse range of viruses. The mechanism of neutralisation is mediated predominantly by nAb binding to glycosylated envelope proteins displayed on the surface of virus particles, thereby preventing binding to host cell membrane bound receptor proteins and neutralising the entry process. Although a robust nAb response is elicited following infection with a number of viruses, many human viruses have evolved mechanisms to effectively evade the humoral immune response. The emergence or re-emergence of pathogenic human viruses poses a significant threat to the global population. The Ebolavirus epidemic of 2014-2015 arose from the emergence of a known virus in a new area, which rapidly spread through a naive population with devastating consequences, resulting in 11,323 fatalities from a total of 28,646 confirmed cases of infection. A rapid induction of potent, broadly nAbs was a possible pathway for infection control in the 17,323 survivors of the epidemic. The isolation of potent nAbs from seroconverted individuals following antigenic exposure provides the potential to develop novel therapeutics for administration within a region affected by an epidemic. To this end, the aim of this project was to develop a platform of methods to isolate human monoclonal antibodies directly from peripheral blood through the isolation of memory B-lymphocytes and subsequent stimulation to secrete antibodies using an in vitro culture system. Identification of DNA sequences encoding antibody heavy and light chain variable domains (VH and VL respectively), allowed for the production of recombinant antibody following the sub-cloning of VH and VL regions into plasmid expression vectors to provide a proof of principle of platform function. Secondly, the introduction of functional screens to the platform would provide a method to identify antibodies derived from memory B-cells with the ability to neutralise Ebolavirus pseudo-particles using in vitro entry inhibition assays.


: Background: One of the major causes of adverse Fetomaternal outcomes have been found to be the various Placenta mediated pregnancy Complications (PMCs). There are inconsistent studies that confirms or proves elevated Serum Homocysteine concentration to be one of the risk factors for Placenta Mediated Complications. Prospective and sufficiently powered studies that uses the pathophysiology of the disease as the basis of their study will help and encourage for a better management of women and fetuses at risk. Hence, this study focuses to determine whether elevated maternal plasma Homocysteine levels in early to mid-second trimester has any significant difference on the occurrence of Placenta-Mediated Complications (PMCs). Objectives: To study and compare the occurrence of Placenta mediated Complications and their Fetomaternal Outcome in women having normal and elevated Serum Homocysteine levels. Methodology: Females in their early second trimester (Gestational acid, presenting for prenatal care in the ANC clinic or planning to deliver at AVBRH Hospital will be selected. Fasting Blood samples will be taken in EDTA Vacutainer tubes and transported to the laboratory within 30min and then the maternal Serum Homocysteine levels will be estimated using the Enzyme-Linked Immunosorbent Assay. Women with raise Plasma Homocysteine Levels will be categorized into Group A and women with Normal Plasma Homocysteine Levels will be categorized into Group B. Pregnancy outcomes and complications will be extracted by studying the antenatal, perinatal, and postnatal medical records and comparison will be made between both the groups for the level of significance. Results: The Expected Outcome of this study will be a significant difference in the occurrence of Placenta Mediated Complications and related Adverse Fetomaternal Outcomes in women having elevated and normal Serum Homocysteine Levels. Conclusion: Our Study will prove the role of maternal homocysteine levels in occurrence of Placenta-mediated pregnancy Complications.


Despite the fact that most companies have embraced social media as part of the mar-keting mix, there still remains a significant lack of knowledge as to what drives com-munication effectiveness in this new kind of peer-to-peer environment where tradi-tional, well-settled marketing communication paradigms like domination and control do show their limits. Accordingly, corporate attempts to leverage marketing opportuni-ties in the social media ecosystem often prove to be a highly experimental trial-and-error process with uncertain outcomes.
Therefore, this book sets out to expand companies' understanding of how to success-fully manage corporate social media sites by providing a set of key drivers, which, when appropriately managed and controlled, can help to increase the audience base of a firm's social media presence. To this end, the author theoretically and quantitatively investigated within a corporate blog setting how specific characteristics of corporate postings affect future audience size. The selected characteristics are identified on three investigative levels that arise from the generic structure of social media postings, namely the source of information, the presentation of information, and the interaction with information. In this way, the author was able to map and to analyze a customer's integrated experience with a corporate social media message.
The research findings led to some applicable recommendations for companies running a social media presence. For instance, it is shown that selecting the right corporate spokespersons, presenting vivid content, or promoting conversational activity can be-come important tactical levers when it comes to the augmentation of corporate social media site attractiveness. Hence, this book helps to assist companies to effectively lev-erage the power of a wide set of pull factors.


INTRODUCTION
Chronic Kidney Disease (CKD) is becoming a major public health problem worldwide. The very diagnosis of CKD brings a plethora of psychological problems that adds to the agony of the debilitating illness. Financial difficulties apart from the excruciating physical burden of the disease, owing to series of psychosocial issues. Anxiety and depression are two major concerns that to be managed effectively to sustain the life of people undergoing Haemodialysis.

AIM
The study aimed at finding the effect of Cognitive Behaviour Therapy (CBT) on anxiety and depression among people undergoing haemodialysis.

MATERIALS AND METHODS
An experimental approach with Randomized controlled trial design was adopted for the study. The instruments used for data collection were Background Proforma and Hospital Anxiety and Depression Scale (HADS). A total of 150 subjects undergoing haemodialysis in a tertiary care hospital of South Karnataka were screened for inclusion and exclusion criteria and 80 participants were recruited for the study. Through computerized block randomization 40 each were allotted to experimental and control groups whereas 33 and 34 respectively in both the groups completed the study. CBT, a structured individual therapy of cognitive, behavioural and didactic techniques, with 10 weekly sessions each was administered to the experimental group. Non-directed counseling, a psychological intervention with ten weekly sessions of individual counseling was given to the control group.

RESULTS
The findings of the study revealed that there was a significant reduction of mean anxiety (F=76.739, p=0.001) and depression (F=57.326, p= 0.001) in the experimental group when compared with the control group.

CONCLUSION
Researchers concluded that CBT can be effectively utilized for people undergoing haemodialysis in order to obtain control over their negative thoughts thereby reducing anxiety and depression.


In this document, we identify several features that affect a
protocol's ability to operate in a multiprotocol environment and
propose the incorporation of these features into IPng. This memo
provides information for the Internet community. This memo does not
specify an Internet standard of any kind.


This paper reports a test of the theory of decision support systems design for user calibration that compares the efficiency of the visual computing paradigm with that of the conventional text paradigm over varied levels of problem novelty. Perfect user calibration exists when a user's confidence in a decision equals the quality of the decision. The laboratory study reported here compared the effects on user calibration of problems depicted either using a text paradigm or visual computing paradigm. The results support the theory. When problems are new and novel, visual depiction improves user calibration. As problems became more familiar and problem novelty decreases, no difference was found in user calibration between subjects exposed to visibility diagrams and those exposed to a traditional text paradigm.


This paper presents findings from an evaluation of the Computer Clubs for Girls, an initiative originally delivered in the South East of England, designed to encourage more girls to take up information technology (IT) courses and careers. By targeting girls aged 10–14, the club aimed to provide members with a 'gender relevant' experience of IT, tackling issues of access, confidence and negative attitudes about IT. The evaluation, conducted over four years, included the collection of quantitative and qualitative data from members and non-members of the clubs. It included a longitudinal component in order to assess the longer-term impacts of the club. The findings support the critical view that initiatives based on assumptions about the relationship between girls and IT misinterpret 'the problem' about female under-representation in IT, and are unlikely to have a significant or sustained impact on what remains an occupational and subject area divided by gender typing. The paper argues for an approach which challenges the social and cultural discourses that maintain this gender divide.


Cancers display heterogeneity in genetic profiles of the individual cancer cells and in the composition of different malignant and non-malignant cell populations. Such intra-tumor heterogeneity plays a role in treatment response and the emergence of resistance to cancer therapies. Approaches that address this complexity and improve stratification of patients for treatment are therefore highly warranted. Thus, the aims of this thesis were to further develop and apply in situ technologies for expression and mutation analyses of candidate cancer genes to gain a deeper understanding of cancer biology and to study intra-tumor heterogeneity.In paper I, we established and validated a procedure for scalable in situ hybridization of large gene sets in human formalin-fixed paraffin-embedded tissues for analysis of gene expression. This method was used in paper II for large-scale expression analysis of the tyrosine kinome and phosphatome, two gene families whose members are frequently mutated in many forms of cancers. Systematic, compartment-specific expression mapping at cell type resolution enabled us to identify several novel vascular markers that have gone unnoticed in bulk transcriptomic analyses. In papers III and IV, we used padlock probes for in situ mutation detection in single cells for studies of genetic intra-tumor heterogeneity. In paper III, multiplex detection and genotyping of oncogenic point mutations was demonstrated in routinely processed tissue materials, whereas in paper IV we further the application by demonstrating multiplex detection of fusion gene transcripts.Collectively, the work presented in this thesis employs in situ-based methods to obtain spatial resolution of gene expression and mutation patterns in normal and cancer tissues, thereby broadening our understanding of the cancer genome.