A murine model in which to study multiple drug resistance in human hepatocellular carcinoma was developed. PRF/PLC/5 hepatoma cells (Alex 0) and an induced multidrug resistant clone (Alex 0.5) were injected intrasplenically into severe combined immunodeficiency mice. In 70% of injected mice, hepatoma cells engrafted in the liver and grew as intrahepatic metastasis. Since Alex cells contain an integrated hepatitis B virus genome and secrete hepatitis B surface antigen (HBsAg), the serum HBsAg concentration in tumor-bearing mice was used to quantitate tumor burden. Tumor wet weight determined at necropsy was directly proportional to the serum HBsAg concentration. In Alex 0 cells, IC50s for doxorubicin, vinblastine, and cis-platinum were 0.35 microM, 0.029 microM, and 3.70 microM, respectively. Alex 0.5 cells were 25-, 14-, and 1.4-fold more resistant to doxorubicin, vinblastine, and cis-platinum, respectively. Immunoblotting of Alex 0 cell membranes with an anti-P-glycoprotein antibody (C219) revealed small amounts of P-glycoprotein, whereas Alex 0.5 membranes overexpressed the protein. Concurrent exposure to verapamil (10 microM) sensitized both cell lines to the cytotoxic action of vinblastine and doxorubicin but had no effect on the cytotoxicity of cis-platinum. Mice bearing intrahepatic xenografts derived from Alex 0 and 0.5 cells had no response to treatment with i.v. vinblastine or doxorubicin, as was anticipated from in vitro drug testing. Addition of verapamil to vinblastine treatment did not improve the success of in vivo chemotherapy. Immunotherapy with a human anti-P-glycoprotein antibody (MRK16) suppressed the in vivo growth of tumors derived from both cell lines. The effect was most pronounced in mice bearing Alex 0.5 tumors. Immunoblotting of tumors which initially responded to MRK16 therapy, but subsequently relapsed, revealed a marked decrease in P-glycoprotein expression when compared to results in tumors that were untreated or treated with vinblastine or control antibody. In summary, we have developed an intrahepatic tumor xenograft model of human hepatocellular carcinoma in mice that permits noninvasive serial quantification of tumor burden by determination of serum HBsAg levels and demonstrated a positive response to immunotherapy with anti-P-glycoprotein antibodies.


During the epoch when the first collapsed structures formed (6<z<50) our Universe went through an extended period of changes. Some of the radiation from the first stars and accreting black holes in those structures escaped and changed the state of the Intergalactic Medium (IGM). The era of this global phase change in which the state of the IGM was transformed from cold and neutral to warm and ionized, is called the Epoch of Reionization.In this thesis we focus on numerical methods to calculate the effects of this escaping radiation. We start by considering the performance of the cosmological radiative transfer code C2-Ray. We find that although this code efficiently and accurately solves for the changes in the ionized fractions, it can yield inaccurate results for the temperature changes. We introduce two new elements to improve the code. The first element, an adaptive time step algorithm, quickly determines an optimal time step by only considering the computational cells relevant for this determination. The second element, asynchronous evolution, allows different cells to evolve with different time steps. An important constituent of methods to calculate the effects of ionizing radiation is the transport of photons through the computational domain or ``ray-tracing''. We devise a novel ray tracing method called PYRAMID which uses a new geometry - the pyramidal geometry. This geometry shares properties with both the standard Cartesian and spherical geometries. This makes it on the one hand easy to use in conjunction with a Cartesian grid and on the other hand ideally suited to trace radiation from a radially emitting source. A time-dependent photoionization calculation not only requires tracing the path of photons but also solving the coupled set of photoionization and thermal equations. Several different solvers for these equations are in use in cosmological radiative transfer codes. We conduct a detailed and quantitative comparison of four different standard solvers in which we evaluate how their accuracy depends on the choice of the time step. This comparison shows that their performance can be characterized by two simple parameters and that the C2-Ray generally performs best.


A simple, cheap, accurate, portable and easy to operate microwave reflected type
moisture meter has been developed to determine the moisture content and
consequently to assess the quality of the in service wooden cross-arms. The
investigation shows that the dielectric properties of the Chengal wood are dependent
on the moisture content (MC) at microwave frequencies. The moisture in wood
contributes in two different forms, one below fiber saturation point (FSP) and the
other above FSP. Both dielectric constant and dielectric loss factor for Chengal
wood increases slowly when the Me increases from zero up to FSP and increases
rapidly with MC above FSP.
Investigation was made to find the optimum conditions for the sensor design. The
optimum condition for best sensitivity of the sensor was determined through
experimental and theoretical methods. It was found out that the sensitivity can be
controlled by thickness of protective cover and the optimum thickness is about 1 mm.
The investigation to find out the minimum thickness of the cross-arms section to
avoid interference was discussed. It was found that the minimum thickness for the cross-anns to reach a semi-infinite length was about 50mrn. The operating principles
of the sensor are based on the plane wave propagation theory and the dielectric
mixture theory. The details of Weiner's mixture model were discussed and it was
used as the theoretical model to predict and convince the experimental results.
In the actual service condition, moisture content of Chengal wooden cross-arms
varied within certain range. For decayed wood, its MC varying between Equilibrium
moisture content (EMC) to about 45% of dry basis and the sound wood MC between
EMC to about 30% of dry basis. It was quite hard for the cross-arms to achieve
higher level ofM C. Once the cross-arms achieve a higher level ofMC, it may take
about 20 hours to return to EMC level. The densities of severely decayed, partly
decayed and sound wood were different from each other even from the same species
of wood. The densities were found to vary between 680kgm-3 to 820kgm-3. The
reflected power signal for severely decayed, partly decay and sound wood at EMC
were less than 0.05, 0.05 to 0.10 and 0.13 to 0.15 respectively. It was found that the
microwave reflected type sensor can determine the decay stage of the wooden cross
arms at EMC.
A HP-basic program was written to develop the meter scale for microwave moisture
meter. The meter scale contains two types of reading. They are MC reading and
stage of decay reading. The mean error were 2.3% and 1.1% for severely decayed
and sound wood respectively and the maximum error were found to be 5.4% and 3.9% respectively.


Background: Guidelines recommend inhaled corticosteroids (ICS) as maintenance treatment for patients with chronic obstructive pulmonary disease (COPD) with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <50% predicted and frequent exacerbations, although they have only a small preventive effect on the accelerated decline in lung function. Combined treatment with ICS and long acting β2 agonists (LABA) may provide benefit to the stability of COPD, but it is unknown if withdrawal of ICS will result in disease deterioration. Methods: The effects of 1 year withdrawal of the ICS fluticasone propionate (FP) after a 3 month run-in treatment period with FP combined with the LABA salmeterol (S) (500 μg FP + 50 μg S twice daily; SFC) were investigated in patients with COPD in a randomised, double blind study. 497 patients were enrolled from 39 centres throughout the Netherlands; 373 were randomised and 293 completed the study. Results: The drop out rate after randomisation was similar in the two groups. Withdrawal of FP resulted in a sustained decrease in FEV1: mean (SE) change from baseline −4.4 (0.9)% (S) v −0.1 (0.9)% (SFC); adjusted difference 4.1 (95% CI 1.6 to 6.6) percentage points (p<0.001). Corresponding figures for the FEV1/FVC ratio were −3.7 (0.8)% (S) v 0.0 (0.8)% (SFC) (p = 0.002). The annual moderate to severe exacerbation rate was 1.6 and 1.3 in the S and SFC groups, respectively (adjusted rate ratio 1.2; 95% CI 0.9 to 1.5; p = 0.15). The mean annual incidence rate of mild exacerbations was 1.3 (S) v 0.6 (SFC), p = 0.020. An immediate and sustained increase in dyspnoea score (scale 0–4; mean difference between groups 0.17 (0.04), p<0.001) and in the percentage of disturbed nights (6 (2) percentage points, p<0.001) occurred after withdrawal of fluticasone. Conclusions: Withdrawal of FP in COPD patients using SFC resulted in acute and persistent deterioration in lung function and dyspnoea and in an increase in mild exacerbations and percentage of disturbed nights. This study clearly indicates a key role for ICS in the management of COPD as their discontinuation leads to disease deterioration, even under treatment with a LABA.


Small-molecule inhibitors of cyclin-dependent kinases (CDKs) are known to induce cell cycle arrest and apoptosis in certain cancer cells. In order to evaluate the antitumor activity of one such inhibitor, GW8510, against human lung cancers, we analyzed the effects of GW8510 on six non-small cell lung cancer (NSCLC) cell lines (A549, H1299, H460, H226, H358, and H322) and normal human fibroblast (NHFB). We treated the cells with GW8510 at concentrations of 0-10 μM, and found that it suppressed cell growth in vitro in all the lung cancer cells but not in NHFB. Subsequent study showed that GW8510 induced apoptosis and cell cycle arrest in the A549, H1299 and H460 cells in a time- and dose-dependent manner. Western blot analysis showed that GW8510 downregulated the expression of X-linked inhibitor of apoptosis (XIAP) but had no detectable effect on the expression of Bax, Bak, or Bcl2. GW8510 also downregulated XIAP mRNA level, suggesting that downregulation of XIAP expression occurs at the transcriptional level. Moreover, ectopic XIAP expression diminished growth inhibition and apoptosis induction by GW8510. Importantly, GW8510 was not capable of inducing apoptosis of NHFB cells. These results suggest that GW8510 might provide a treatment strategy for human NSCLC and XIAP is an important target for GW8510-induced apoptosis of NSCLC cells that occurs through inhibition of XIAP mRNA transcription.


Codifications and standards of fundamental rights diverge in the EU member states as a result of differences in legal tradition, constitutional values and historical developments. Although such differences are difficult to reconcile with the notion of universality of human rights protection and an increasingly united Europe, they cannot be ignored. Moreover, many hold on to the idea of a national constitutional identity that is reflected in respect for national constitutional values. The European Court of Human Rights, entrusted with the task of developing and maintaining reasonable standards of fundamental rights protection for the entire Council of Europe, faces the challenge of having to balance respect for diversity with the need for uniform and effective rights protection. It is often thought that the famous margin of appreciation doctrine is the Court's main tool in finding this balance. This paper shows, however, that the Court's application of the doctrine has made it into a rather meaningless and empty rhetorical device without any real practical value. This is different for the Court's use of incrementalism, which increasingly seems to have replaced the use of the margin of appreciation doctrine as an instrument to deal with the need to reconcile European standard setting and national diversity. This paper demonstrates that the Court often combines case-based decision-making with the creation of sets of criteria and standards of a more general nature. It concludes that this approach is highly valuable, as it does not only help the Court to deal with diverging fundamental rights standards, but also allows it to combine its functions of being a 'constitutional' court for fundamental rights issues as well as court of last instance for individual victims of fundamental rights violations. Nevertheless, this paper argues that the Court could even further benefit from the potential of its strategic instruments if it would make better use of filtering mechanisms such as its 'priority policy' and if it would reconsider the use of its margin of appreciation doctrine.


Concurrent programming is becoming more important due to the growing dominance of multi-core processors and the prevalence of graphical user interfaces (GUIs). To prepare students for the concurrent future, instructors have begun to address concurrency earlier in their curricula. Unfortunately, test-driven development, which enables students and practitioners to quickly develop reliable single-threaded programs, is not as effective in the domain of concurrent programming. This paper describes how ConcJUnit can simplify the task of writing unit tests for multi-threaded programs, and provides examples that can be used to introduce students to concurrent programming.


BACKGROUND
The Medical Outcomes Study 36 Item Short-Form (SF-36) questionnaire is one of the most widely used measures of health related quality of life in medical research, including studies on pain-related conditions. Although scores in each of its eight domains rarely conform to a normal distribution, it is most widely analysed using simple parametric statistical techniques. Some have suggested a need for more complex or non-parametric analytical approaches, and this quandary faces researchers recurrently when using the SF-36. In this study of chronic pain, we compared results arising from the SF-36 between three study sub-samples, using conventional parametric, non-parametric, bootstrapping and log transforming methods.

METHODS
Respondents to a postal survey conducted in Aberdeen, Leeds and London (n = 3002, response rate 52%) were categorized in three groups according to previously validated questionnaires: those with chronic pain of predominantly neuropathic origin (POPNO, n = 241), those with chronic pain (non-POPNO, n = 1179), and those with no chronic pain (n = 1537). SF-36 scores were compared between these groups, using: ANOVA and t-tests; Kruskall-Wallis and Mann-Whitney U-tests; bootstrapping methods; and log transformation with ANOVA.

RESULTS
There were highly significant differences between the three groups, with lower scores in all SF-36 domains found those with chronic pain (P < 0.001). Those with chronic POPNO had lower scores in all domains than those with chronic pain (non-POPNO) (P < 0.001). These results were the same after applying each statistical method.

CONCLUSIONS
In this study, the choice of statistical approach had no influence on the results. We conclude that the conventional approach, using straightforward parametric tests, is both simplest and the best for allowing comparison with other studies. We are likely to adopt this in future studies.


The global increase in renewable energy initiatives has been followed by the need to include the social impact of any project as a core element. Significant challenges for renewable energy development include uncertainty in assessing social impacts at local scales, participation and social acceptance. Multi-criteria decision analysis (MCDA) approaches have been widely used in energy planning to address these challenges. This article reviews how social criteria and participation mechanisms have been incorporated into decision-making processes for renewable energy projects. A total of 184 articles were analyzed. A total of 490 indicators that estimated social impacts were identified and organized into nine criteria: employment, social acceptance, social development, health impact, governance, visual impact, knowledge and awareness, cultural value and social justice. Most research included analytical hierarchy process methodologies, and the articles were geographically concentrated in Asia and Europe. Most articles included a participative component (92.3%), and the majority of them were based on expert consultation (75.4%). Of the articles that exclusively considered experts, almost 40% did not provide any description of the expert elicitation process. Results revealed advances in the use of MCDA but highlighted important challenges—related to improving expert consultation methodologies and broadening the participation of stakeholders—when developing renewable energy initiatives and policies.


This paper presents the application of a complete digital calibration methodology to the improvement of a Hall sensor-based current measurement microsystem. It is a step-by-step illustration of how generic calibration techniques and circuits can be used on a practical example. At system-level, the microsystem is analyzed and its imperfections identified. The circuit is designed so that for each imperfection to be cancelled, detection and compensation nodes are identified. To these nodes, generic digital calibration circuits are connected to perform continuous background calibration. In the presented current measurement microsystem, the use of this methodology reduced the sensitivity drift down to 50 ppm/degC, which is 10 times less than the state of the art


This Article identifies, justifies, and explains the parameters of a largely ignored but important category of cases - what is here called "preventive adjudication.�? In this category of cases, courts offer opinions without any "command�? to the parties, and these opinions are meant to avoid future harm, not remedy past harm. Despite receiving little attention in the legal literature, preventive adjudication is pervasive throughout law. It happens in declaratory judgment actions about wills, patents, and unconstitutionally vague statutes; in paternity and maternity petitions; in petitions to have missing persons declared dead; in boundary disputes; in actions to quiet title. This Article explains what preventive adjudication is and how it should and should not be used. Preventive adjudication is intuitively appealing, because it helps people avoid harm and clarifies the law. But there are downsides to deciding cases in advance instead of waiting for remedial adjudication. The argument for preventive adjudication is therefore a qualified one. This Article identifies not only the merits of preventive adjudication but also the crucial limiting principles. One limiting principle is administrative and error costs; another is the adequacy of discounting, i.e., taking into account the uncertainty of future events. People discount for many kinds of uncertainty, and discounting is usually adequate for uncertainty caused by law. But discounting is inadequate when the law causes uncertainty about inescapable threshold questions for human behavior, such as legal parenthood, citizenship, marital status, or death. Discounting is also inadequate for uncertainty about property rights, because uncertainty undermines the policy reasons for having property rules in the first place. Where discounting is inadequate, preventive adjudication is especially valuable. This Article also shows how this normative understanding of preventive adjudication can be translated into the actual practice of courts in the United States. Legal systems in the United States have two ways of determining which cases should be decided by preventive adjudication: sometimes they rely on judicial discretion to decide if preventive adjudication is appropriate in each case ("retail sorting�?); and sometimes they specify categories of cases in which preventive adjudication is available ("wholesale sorting�?). An analysis of both approaches shows that wholesale sorting - which is common in state courts but almost unknown in federal courts - better aligns the actual practice of preventive adjudication with the cases in which it is justifiable.


The aim of this paper is to investigate the fi rms' incentives to engage in process R&D under vertical industrial setting, when the raising rivals' cost effect is present. We show that R&D investment of the downstream duopoly fi rm raises the rival's marginal costs of production. The downstream R&D behavior can give rise to the symmetric investment games, i.e., the prisoner's dilemma, the deadlock game and the harmony game, between downstream competitors. If the costs of the R&D investments made by the downstream fi rms are large enough, the downstream fi rms can participate in the harmony game, which results in the investment hold-up or the creation of the R&D-avoiding cartel. For more R&D-effi cient downstream fi rms, the downstream investment game can end up in the prisoner's dilemma or the deadlock game. In the prisoner's dilemma, both downstream fi rms invest in R&D, but such a behavior is not Pareto optimal. In the prisoner's dilemma, greed and fear make fi rms invest in R&D. In the deadlock game, both downstream fi rms invest in R&D, and such a behavior is Pareto optimal. The R&D investments are not induced by any social tension (greed or fear).


Submillimetre molecular line observations of molecular clouds in our galaxy are presented, and the data analysed using various alternative cloud models. A critical review is given of the methods commonly used to interpret molecular line data, including both theoretical considerations and issues relating to calibration and comparability of results obtained with different telescopes. A detailed comparison is made between results predicted from large velocity gradient (LVG) models, including the generalisation to non-monotonic velocity flows, and those given by "microturbulent" clouds. An LVG model is employed in an investigation of conditions in the molecular outflows frequently found in star formation regions, for which observations in the CO J=3-2 rotational transition at 345 GHz are presented. These are combined with lower frequency data from the literature to derive various properties of the outflows for a sample of 13 sources. The most important result is that local H2 densities exist in the outflows which are higher, typically by an order of magnitude, than previously derived average values obtained using only lower frequency data. Observations are presented of the S255 and DR21 clouds in the transitions CO J=2-1, CO J=3-2, CS J=7-6, HCN J=4-3, HCO+ J=4-3 and -3H13CO+ J=4-3 and are supplemented by continuum data at 350 s. n and (for DR21) at 20 pm. It is shown that, although some features of the data can be understood in terms of an LVG model, there is compelling evidence for fragmentation of the clouds on length scales much smaller than the cloud sizes. The data are used to constrain the local H2 densities and relative molecular abundances in the clumpy cloud cores, and compared with lower frequency results from the literature. The implications of these results for the star formation environment are discussed, and an assessment made of possible strategies for their further investigation.


The formation of regional production networks in East Asia has occurred mainly through market forces, without much help from regional institutions in promoting the creation of a single Asian market. While this approach has served the region well in the past, the drastic changes experienced since the 2008–2009 financial crisis and the challenges Asian countries are facing—growing inequalities and competition, on the one hand, and enhanced threats to the environment and people's health on the other—have rendered more urgent the need for intergovernmental cooperation at global and regional levels. Asia's institutions for regionalism need strengthening through reform and innovation such as better governance and resourcing, greater and more effective participation and delegation of powers, overall streamlining of regional architecture, including the phasing out of outdated or irrelevant institutions and, where needed, the creation of new ones. Ultimately, given its rootedness in regional order, institutional efficacy is a function of the ability and willingness of its members, especially influential stakeholders, to collaborate.


ABSTRACT Involvement of children with autism spectrum conditions (ASC) in the design of new educational technology is becoming more prevalent. Despite potential barriers due to communication and ideation difficulties for children with ASC, adapted participatory design methods can successfully facilitate their direct involvement. Nonetheless, methods requiring face-to-face communication can still be difficult for children with ASC and research suggests that technology mediation could facilitate their contribution. This study explores the use of collaborative virtual environments (CVEs) as a medium through which students evaluated existing computer games and offered suggestions for game development. CVEs in which the users were represented by (a) avatars and (b) video-pods were compared to a face-to-face condition. Twelve typically developing (aged 8–9 years), 12 higher ability ASC (12–14) and 4 lower ability ASC children (12–14) participated. All student groups preferred the video-pod CVE and students with ASC were generally better able to contribute effectively through this medium than face-to-face.


his work has a double purpose, on one hand, to know the dehydration of a futsal team during the competition, and on the other, to assess the effects of an intervention programme, which last fifteen days, in order to make players aware of the importance of hydration in sport performance and avoid processes of dehydration during the competition and training. Three official matches were evaluated, the first before the intervention programme and the second and the third in the following two weeks. The mean of the dehydration in the three marches were 1.7±1.0%, 0.8±0.8% and 0.9±0.7%, respectively. Comparing the dehydration values of the first match (before the intervention) with the following two matches (during and after the programme) we find significant differences during the half time (and the end of the match. Results give us the idea that the futsal players, despite having many opportunities to drink enough fluid, don´t drink all they need and reach a high dehydration that could affect players´ performance. The use of strategies to improve fluid replacement produces a significant decrease of the dehydration during the competition. KEY WORDS: Fluid replacement, dehydration, futsal and competition.


ABSTRACT Amdinocillin (mecillinam) is a β-lactam antibiotic that is used mainly for the treatment of uncomplicated urinary tract infections. The objectives of this study were to identify mutations that confer amdinocillin resistance on laboratory-isolated mutants and clinical isolates of Escherichia coli and to determine why amdinocillin resistance remains rare clinically even though resistance is easily selected in the laboratory. Under laboratory selection, frequencies of mutation to amdinocillin resistance varied from 8 × 10−8 to 2 × 10−5 per cell, depending on the concentration of amdinocillin used during selection. Several genes have been demonstrated to give amdinocillin resistance, but here eight novel genes previously unknown to be involved in amdinocillin resistance were identified. These genes encode functions involved in the respiratory chain, the ribosome, cysteine biosynthesis, tRNA synthesis, and pyrophosphate metabolism. The clinical isolates exhibited significantly greater fitness than the laboratory-isolated mutants and a different mutation spectrum. The cysB gene was mutated (inactivated) in all of the clinical isolates, in contrast to the laboratory-isolated mutants, where mainly other types of more costly mutations were found. Our results suggest that the frequency of mutation to amdinocillin resistance is high because of the large mutational target (at least 38 genes). However, the majority of these resistant mutants have a low growth rate, reducing the probability that they are stably maintained in the bladder. Inactivation of the cysB gene and a resulting loss of cysteine biosynthesis are the major mechanism of amdinocillin resistance in clinical isolates of E. coli.


The oversupply of ethane, a major component of natural gas liquids, has stimulated the wide applications of ethylene since the shale gas revolution. However, ethylene production is energy-intensive and represents the most energy-consuming single process in the chemical industry. In this communication, we report, for the first time, a novel low-thermal-budget process for the co-production of ethylene and pure hydrogen using a proton-conducting electrochemical deprotonation cell. At a constant current density of 1 A cm−2, corresponding to a hydrogen production rate of 0.448 mol cm−2 per day, and 400 °C, a close to 100% ethylene selectivity was achieved under an electrochemical overpotential of 140 mV. Compared to an industrial ethane steam cracker, the electrochemical deprotonation process can achieve a 65% saving in process energy and reduce the carbon footprint by as much as 72% or even more if renewable electricity and heat are used. If the heating value of produced hydrogen is taken into account, the electrochemical deprotonation process actually has a net gain in processing energy. The electrochemical deprotonation process at reduced temperatures in the present study provides a disruptive approach for petrochemical manufacturing, shifting the paradigm from thermal chemical practice to a clean energy regime.


In recent years, the study of norm-regulated multi-agent systems (MAS) has attracted a lot of attention. The Kanger-Lindahl theory of normative positions has great potential of serving as the logical foundation for normative systems for MAS, but its generality, which allows for great freedom when interpreting the theory, may also become a challenge for practical applications. As an important step towards a typology of interpretations of the theory, we study the application of normative positions in the context of a basic class of transition systems in which transitions are deterministic and associated with a single agent performing an act. By an interpretation of the types of normative positions in terms of permitting or prohibiting different types (with respect to some condition on a number of agents) of state transitions in this context, lexicons for two different systems of types of normative positions are suggested and discussed. It is demonstrated that both interpretations are natural and useful, depending on how the notion of agency is understood and whether a 'system norms' or an 'agent-specific norms' perspective is taken.


Cancer diagnosis requires better screening of early stages of pathology and monitoring patient responses to treatment. Current technologies in the clinical sector are expensive, sophisticated and time consuming. This paper develops a novel Raman based alternative for currently existing epigenetics research approaches. The proposed Raman approach can 'upgrade' cancer epigenetic tests and answer many questions by monitoring the biochemistry of cancer cells. We will show that Raman spectroscopy and Raman imaging can detect the relative amounts of acetylated and methylated lysine by monitoring the vibrations of the acetyl and methyl chemical functional groups. In comparison to existing tests and assays used to monitor molecular processes of acetylation and methylation of all proteins, Raman-based methods have the potential to be a powerful alternative for conventional methods of cell biology, because they allow non-invasive detection of cellular acetylation and methylation processes that are not limited to only those events that are sensitive to a specific antibody. Vibrational Raman signatures of acetylation and methylation processes in epithelial cells of human breast tissue (ductal and lobular carcinoma) have been used to identify and discriminate structures in normal and cancerous tissues. Our results demonstrate that the stretching vibration of the acetyl group observed at around 2938–2942 cm−1 and the methyl group at 2970 cm−1 by Raman spectroscopy is useful in monitoring these epigenetic molecular processes in cancer cells. The Raman vibrational marker is markedly blue-shifted from 2905 cm−1 (non-acetylated C–H vibrations) for normal cells to 2942 cm−1 (vibrations of the acetylated functional group) in cancer cells. The sensitivity and specificity obtained directly from PLSDA and cross-validation for a chosen model gives a sensitivity and specificity of 86.1% and 91.3% for calibration and 85.3% and 91.3% for cross-validation, respectively. The results presented in the paper provide strong evidence that the global acetylation level of histone and non-histone proteins increases in human breast cancer cells.


This paper considers the impact of exposure to road safety threat appeals on intention to take driving risks among young male drivers. In particular, attention is given to the potential for driving-related self-esteem and the personality variable of impulsiveness to moderate this impact. The paper describes an experiment in which participants were exposed to mortality salient or neutral facts. The dependent variable was self-reported intention to take driving risks. Participants (n=80) were male university students with a full driver's licence. Participants with high driving-related self-esteem, who were exposed to death related facts and images, reported greater intentions to take driving risks than those exposed to neutral information. Impulsiveness was identified as a significant contributor to risky driving intentions. Though limited in its ecological validity, the study presents an opportunity to reconsider our understanding of resilience to driving-related health promotion campaigns.


Background Shiga toxigenic Escherichia coli (STEC) is an emerging global pathogen and remains a major cause of food-borne illness with more severe symptoms including hemorrhagic colitis and hemolytic-uremic syndrome. Since the characterization of the archetypal STEC serotype, E. coli O157:H7, more than 250 STEC serotypes have been defined. Many of these non-O157 STEC are associated with clinical cases of equal severity as O157. In this study, we utilize whole genome sequencing of 44 STEC strains from eight serogroups associated with human infection to establish their evolutionary relationships and contrast this with their virulence gene profiles and established typing methods. Results Our phylogenomic analysis delineated these STEC strains into seven distinct lineages, each with a characteristic repertoire of virulence factors. Some lineages included commensal or other E. coli pathotypes. Multiple independent acquisitions of the Locus for Enterocyte Effacement were identified, each associated with a distinct repertoire of effector genes. Lineages were inconsistent with O-antigen typing in several instances, consistent with lateral gene transfer within the O-antigen locus. STEC lineages could be defined by the conservation of clustered regularly interspaced short palindromic repeats (CRISPRs), however, no CRISPR profile could differentiate STEC from other E. coli strains. Six genomic regions (ranging from 500 bp - 10 kbp) were found to be conserved across all STEC in this dataset and may dictate interactions with Stx phage lysogeny. Conclusions The genomic analyses reported here present non-O157 STEC as a diverse group of pathogenic E. coli emerging from multiple lineages that independently acquired mobile genetic elements that promote pathogenesis.


A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.


New methodologies have been developed to optimize EGR rate and injection timing in diesel engines, with the aim of minimizing fuel consumption (FC) and NOx engine-out emissions. The approach entails the application of a recently developed control-oriented engine model, which includes the simulation of the heat release rate, of the in-cylinder pressure and brake torque, as well as of the NOx emission levels. The engine model was coupled with a C-class vehicle model, in order to derive the engine speed and torque demand for several driving cycles, including the NEDC, FTP, AUDC, ARDC and AMDC. The optimization process was based on the minimization of a target function, which takes into account FC and NOx emission levels. The selected control variables of the problem are the injection timing of the main pulse and the position of the EGR valve, which have been considered as the most influential engine parameters on both fuel consumption and NOx emissions. The gear number has also been selected for optimization. One benchmark tool, which is based on the dynamic programming technique, and one real-time tool, which implements a static optimization method, have been developed for the optimization process. A new mathematical technique has been introduced and applied in order to decrease the computational time of the optimizers to a great extent. It was verified that the real-time method has the potential of being implemented in the engine control unit (ECU), in order to realize an onboard optimization of the selected engine and vehicle parameters


Twitter is a micro blogging and social media gains more attention rapidly with the number of users is increasing every year. Flexible service provided by Twitter has changed the way how people exchange and share information with each other. Users can share latest information through a short status or tweet with other users who are their online friends. It also changes how users document their lives, interaction and friendship. Twitter users can come from various backgrounds including politicians in conveying information. The use of Twitter can also affect the audience through messages in the form of status. This study focuses on the type of Twitter content categories and messages trends by the heads of the political parties which involve the government leader, namely Dato Sri Najib Tun Abdul Razak and The Opposition, Dato Sri Dr. Wan Azizah Wan Ismail in Malaysian politics. Content analysis was conducted on 216 statuses which had been updated during the 12-day Sarawak state election campaign. The selection on Dato Sri Najib Tun Razak and Dato Sri Dr. Wan Azizah Wan Ismail Twitter's accounts is because they are the heads of their respective parties. They also stayed in Sarawak during the campaign period. The study found that both leaders were focusing on information message category during the campaign period compared to other categories. However, the leaders' was not consistent in updating Twitter status during the period. The status update had increased in the first ten days of the campaign. For the last three days before the polling day, the status updates had decreased. The highest status updates is on the second day of the campaign period is because the head of government politicians updated status on his Twitter regarding to the National Transformation Annual Programme Report 2015. While the lowest status updates is on the first day of the campaign.


Key Points By October 2004, the United States will have begun initial deployment of a missile defense capability--albeit a modest, limited, and not completely proven one--to defend the homeland against a limited ballistic missile attack. The gradual phase-in of ballistic missile defense deployments will mark an important change in the policy context of the missile defense issue. Past debate focused on whether missile defenses should be deployed and whether they would work. These issues will now share the limelight with another pressing question: how would missile defenses actually be used? Operating a missile defense system presents seven challenges: * to whom weapons release authority should be delegated * how limited missile defense assets should be allocated * what roles the President and Secretary of Defense should play during intercept operations * how strike options should be coordinated with defenses * which U.S. command should be responsible for conducting missile defense operations * how testing and operational requirements should best be balanced * what arrangements are needed to notify Russia when the United States launches missile defense interceptors, to reduce possible miscalculation by Moscow. To manage the transition to defense, policy guidance to address these challenges will have to be somewhat flexible; it will likely evolve over time, based on the evolution of the system as well as operational experience and future testing using varied assumptions and scenarios. ********** If all goes according to plan, by the end of 2004, the United States will deploy eight ground-based midcourse defense (GMD) interceptors (1) in Alaska and California, along with land-, sea-, and space-based sensors and the command and control systems to support the interceptors. By the end of 2005, 12 more GMD interceptors will be added, along with additional sensors and interceptor missiles on Navy ships. The initial deployments of 2004-2005 are only the first step on the path to the Bush administration goal of an integrated, global missile defense (2) to protect the United States, its friends and allies, and deployed forces against limited attacks by ballistic missiles of all ranges (short-, medium-, intermediate-, and long-range) in all phases of flight (boost, midcourse, and terminal). (3) The main concern driving this goal is not the ballistic missiles of major powers such as Russia but the proliferation of weapons of mass destruction (WMD) and ballistic missiles--particularly for rogue states such as North Korea and Iran. The program, however, is not tied to country-specific threats; instead, it takes a capabilities-based approach that "focuses more on how an adversary might fight than who the adversary might be and where a war might occur." (4) This means, as the director of the Missile Defense Agency (MDA) observed: We have to consider a wide range of missile threats posed by a long list of potential adversaries. And those threats are constantly changing and unpredictable.... A capability-based approach relies on continuing and comprehensive assessments of the threat, available technology, and what can be built to do an acceptable job, and does not accommodate a hard requirement that may not be appropriate. (5) Thus, there is no final architecture. Under the current plan, the missile defense program will proceed in 2-year block increments of spiral development. (6) For the most part, the Bush administration has been careful not to oversell the initial defensive capabilities so that expectations do not exceed reality. Officials have characterized the first deployments as "very basic" and a "nascent defensive system." (7) Secretary of Defense Donald Rumsfeld called it a "capability with a small 'c'" (to distinguish it from a formal initial operational capability) that "will probably, one would hope, improve as you go along. …


One common aspect of all human beings, regardless of education level, income level, location and so on, is that they are all consumers. The key of success in marketing strategy both in terms of local and global aspects is understanding consumer behavior. So aim of this study was to investigate the role of socio-cultural factors on sports consumer behavior. This research was survey- descriptive. The study population were included all sports consumers in Tehran. The sampling method was random. Based on the PASS statistical software, research sample size was determined in the range of 321 to 384 people. Data collection instrument was two questionnaires. The validity was content validity and construct validity. In order to data analyzing was used Path analysis and analytic hierarchy process (AHP). The results showed that social factors (social class, idea leaders, family and references group) and cultural factors (culture and religion) have a significant positive effect on sports consumer behavior. Also sociocultural factors prioritize results showed that social class with the relative weight of 0.391 is the most important component. In this study found companies to gain competitive advantage should have be given to customers and meet their needs (better than competitors). In addition, customers buy products with different trends that should be considered in formulating marketing strategies.


OBJECTIVE
To develop and validate a prognostic model that estimates survival over a 180-day period for seriously ill hospitalized adults (phase I of SUPPORT [Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments]) and to compare this model's predictions with those of an existing prognostic system and with physicians' independent estimates (SUPPORT phase II).

DESIGN
Prospective cohort study.

SETTING
5 tertiary care academic centers in the United States.

PARTICIPANTS
4301 hospitalized adults were selected for phase I according to diagnosis and severity of illness; 4028 patients were evaluated from phase II.

MEASUREMENTS
A survival model was developed using the following predictor variables: diagnosis, age, number of days in the hospital before study entry, presence of cancer, neurologic function, and 11 physiologic measures recorded on day 3 after study entry. Physicians were interviewed on day 3. Patients were followed for survival for 180 days after study entry.

RESULTS
The area under the receiver-operating characteristics (ROC) curve for prediction of surviving 180 days was 0.79 in phase I, 0.78 in the phase II independent validation, and 0.78 when the acute physiology score from the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III prognostic scoring system was substituted for the SUPPORT physiology score. For phase II patients, the SUPPORT model had equal discrimination and slightly improved calibration compared with physician's estimates. Combining the SUPPORT model with physician's estimates improved both predictive accuracy (ROC curve area = 0.82) and the ability to identify patients with high probabilities of survival or death.

CONCLUSIONS
A limited amount of readily available clinical information can provide a foundation for long-term survival estimates that are as accurate as physicians' estimates. The best survival estimates combine an objective prognosis with a physician's clinical estimate.


Monopartite members of the family Potyviridae utilize three virus-encoded proteinases to cleave the viral polyprotein into mature proteins. The amino-terminal region of the viral polyprotein is autolytically cleaved by the P1 proteinase. A domain required for P1 proteinase activity of Wheat streak mosaic virus (WSMV) was mapped using a series of templates with nested 3 « -truncations or 5 « -deletions to program in vitro transcription–translation reactions. The WSMV P1 proteinase cleavage site was mapped to a position downstream of amino acid residue 348 and upstream of amino acid residue 353, with the peptide bond between amino acid residues Y 352 and G 353 the most probable site of hydrolysis. An alignment of potyvirus polyprotein sequences in the carboxy-terminal region of the P1 domain revealed WSMV P1 contained conserved H 257 , D 267 , S 303 and FIVXG 325–329 residues upstream of the cleavage site that are typical of serine proteinases and shown by others to be required for P1 proteolysis in Tobacco etch virus . Insertion of the GUS reporter gene immediately downstream of the P1 cleavage site in a full-length clone of WSMV resulted in systemic infection and GUS expression upon inoculation of plants with in vitro transcripts. When cleaved by P1 at the amino terminus and NIa proteinase at a site engineered in the carboxy-terminus, active GUS protein expressed by WSMV in infected wheat had electrophoretic mobility similar to wild-type GUS protein.


We consider opportunistic routing in wireless mesh networks. We exploit the inherent diversity of the broadcast nature of wireless by making use of multipath routing. We present a novel optimization framework for opportunistic routing based on network utility maximization (NUM) that enables us to derive optimal flow control, routing, scheduling, and rate adaptation schemes, where we use network coding to ease the routing problem. All previous work on NUM assumed unicast transmissions; however, the wireless medium is by its nature broadcast and a transmission will be received by multiple nodes. The structure of our design is fundamentally different; this is due to the fact that our link rate constraints are defined per broadcast region instead of links in isolation. We prove optimality and derive a primal-dual algorithm that lays the basis for a practical protocol. Optimal MAC scheduling is difficult to implement, and we use 802.11-like random scheduling rather than optimal in our comparisons. Under random scheduling, our protocol becomes fully decentralized (we assume ideal signaling). The use of network coding introduces additional constraints on scheduling, and we propose a novel scheme to avoid starvation. We simulate realistic topologies and show that we can achieve 20%-200% throughput improvement compared to single path routing, and several times compared to a recent related opportunistic protocol (MORE).


During a traumatic brain injury (TBI) sustained in combination with hemorrhagic shock the brain undergoes anoxic conditions resulting from swelling and blood loss. Traditional intravenous solutions are used to replace blood volume, but are unable to replace the blood's oxygen carrying capacity. A proposed treatment based on isotonic solutions containing hemoglobin-based oxygen carriers (HBOC's) which were intended to provide readily available oxygen was developed. However, cell-free hemoglobin was shown to have excessive oxidative potential. Polynitroxylated Pegylated Hemoglobin (PNPH) was developed to address this shortcoming. During PNPH synthesis a combination of polyethylene glycol (PEG) and (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO), is bound to the cysteine and lysine residues on the protein. The PEG serves as a physical buffer, slowing oxygen release, while the TEMPO converts released superoxide radicals and counteracts their adverse effects. This antioxidant capability allows PNPH's to successfully serve in their role, however, the synthesis of PNPH's remains labor and cost intensive. This research focuses on the development of a TEMPO and PEG containing copolymer which can be bound to cell-free hemoglobin to serve in the same antioxidant capacity with additional benefits. These benefits include: increased PEG and TEMPO loading capacity, optimizability in the ratio between PEG and TEMPO, and a potentially easier synthesis pathway. This document focuses on the development of TEMPO containing ring-opening metastasis polymerization compatible monomers as a component of the target polymer and TBI treatment. Thesis Mentor:_______________________ Dr. Hans-Joerg Schanz Honors Director:_______________________


Chemical analysis of a southern Australian marine sponge, an Ianthella sp., yielded dictyodendrins F–J (1–5) as new examples of a rare class of marine alkaloid. Structures were assigned on the basis of detailed spectroscopic analysis, while biosynthetic considerations suggested a relationship between the dictyodendrins and co-metabolites belonging to the lamellarin and ianthellidone structure classes. The dictyodendrins 1 and 3–5 exhibited significant BACE inhibitory activity (IC50 1–2 μM), with the differential cytotoxicity displayed by 1–4 towards two human colon cancer cell lines (IC50 2–16 μM) marking them as both cytotoxins and probable substrates for the multi-drug resistance efflux pump P-glycoprotein. The dictyodendrins 1–5 did not inhibit growth of Gram −ve bacteria or fungi, but 1, 3, and 4 were selective Gram +ve antibacterials (IC50 1–3 μM). Dictyodendrin J (5), with its unique seco-carbon skeleton and unusual 1,2-diketone functionality, exhibited a promising non-cytotoxic biological activity profile, inclusive of significant BACE inhibitory activity (IC50 2 μM), supportive of further investigation.


Objective: A variety of nasal skin reconstruction methods are available to meet the esthetic patient's needs. In this article, we review some of modifications of these procedures and share our experience in reconstruction of different parts of the nasal skin following skin tumor ablation. Patients and Methods : From January 2010 to January 2014, 171 patients underwent nasal skin reconstruction after excising cancerous lesions of the involved nasal skin. The patient's history, pre- and post-operation photographs, and the surgery data were collected and assessed. Demographic data related to the type of cancer, defect size and location, type of reconstruction were collected. Results: A variety of local flaps were used based on location and defect features. Nearly all flaps healed primarily without postsurgical significant complications. Conclusion: According to the results and the outcomes of the operations, we concluded that a certain flaps are more effective than others in nasal skin reconstruction. Local flap reconstruction of the nose has good esthetic result with low complication rate.


This paper focuses on emotion recognition and understanding in Contemporary Western music. The study seeks to investigate the relationship between perceived emotion and musical features in the fore-mentioned musical genre. A set of 27 Contemporary music excerpts is used as stimuli to gather responses from both musicians and non-musicians which are then mapped on an emotional plane in terms of arousal and valence dimensions. Audio signal analysis techniques are applied to the corpus and a base feature set is obtained. The feature set contains characteristics ranging from low-level spectral and temporal acoustic features to high-level contextual features. The feature extraction process is discussed with particular emphasis on the interaction between acoustical and struc-tural parameters. Statistical relations between audio features and emotional ratings from psychological experiments are systematically investigated. Finally, a linear model is created using the best features and the mean ratings and its prediction efficiency is evaluated and discussed.


Space-planted populations derived from 'Holt' and 'Oto'indiangrass, (L.) Nash, were used to obtain heritability estimates for forage yield, in vitro dry matter digestibility (IYDMD), crude protein, and heading date and to determine their genotypic correlations. Heritability estimates were determined by variance component analyses and by parent-progeny regression. Average narrow sense heritability estimates for the two populations were 0.43, 0.42, and 0.50, for forage yield, IVDMD, and protein, respectively. Narrow sense heritability estimates for heading date were 0.90 or larger. Genotypic correlations of yield and IVDMD were negative for the Holt population but were positive, although low, for the Oto population in 1976. Protein and IVDMD had positive genotypic correlations for both populations. Heading date was positively correlated with yield but was negatively correlated with IVDMD and protein.


Title of dissertation: DIAGNOSING CLOUDS AND HAZES IN EXOPLANET ATMOSPHERES Jonathan David Fraine, Doctor of Philosophy, 2015 Dissertation directed by: Professor L. Drake Deming Department of Astronomy Exoplanet atmospheres provide a probe into the conditions on alien worlds, from hot Jupiters to Super-Earths. We can now glimpse the behaviour of extreme solar systems that defy our understanding of planet formation and capture our imaginations about the possibilities for understanding planets and life in our universe. I combined multi-epoch, multi-instrument observations from both space and ground based facilities. I developed observational techniques and tools to constrain exoplanetary atmospheric compositions, temperature profiles, and scale heights over a span of planetary masses and wavelengths, that provided a probe into the properties of these diverse planetary atmospheres. I led a team that used the Spitzer Space Telescope, with the IR Array Camera (IRAC), to observe the well known transiting Super-Earth, GJ 1214b (∼ 2.7 R⊕). My precisely constrained infrared transit depth, error ∼ O(40 ppm), significantly constrained the lack of any molecular detections out to a wavelength of 5μm. The significance of this null detection challenges self-consistent models for the atmosphere of this super-Earth. Models must invoke thick, grey opacity clouds that uniformly cause the atmosphere to be opaque at all wavelengths. My team and I used the Hubble Space Telescope Wide Field Camera 3 (HSTWFC3) to spectroscopically probe the atmosphere of the transiting warm Neptune, HAT-P-11b (∼ 4.5 R⊕), and detected the first molecular signature from a small exoplanet (Rp < RSaturn), inferring the presence of a hydrogen rich atmosphere. The average densities of many transiting exoplanets are known, but the degree to which atmospheric composition – abundance of Hydrogen relative to other atoms and molecules – correlates with the bulk composition has not yet been established. In an effort to characterize the atmospheric metallicity in greater detail, my team observed HAT-P-11 using warm Spitzer IRAC at 3.6 and 4.5 μm. The nondetections of eclipses HAT-P-11b provided upper limits on the temperature profile at 3.6 and 4.5 μm. I am one of the founding members of the ACCESS collaboration (Arizona-CfACatólica Exoplanet Spectroscopy Survey), a ground based observational campaign to spectroscopically survey a catalogue of exoplanetary atmospheres using major optical telescopes. I observed several of our targets from the 6.5m Magellan-Baade telescope. The results of my first observation provided low signal-to-noise constraints on the cloud properties of the hot Jupiter WASP-4b, as well as the UV radiation environment produced by its host star, WASP-4. The combination of these observational constraints provided greater insight into the end-products of the planet formation process, and developed the knowledge base of our community for both cloudy and clear worlds. DIAGNOSING CLOUDS AND HAZES IN EXOPLANET ATMOSPHERES


The paper has a dual purpose. First, we suggest that entrepreneurs in their establishment of new businesses draw on a range of pre-existing socially embedded routines for creating acceptance by their environment. Also they draw upon external resources that are used in patterning specific practices. This ability is treated as entrepreneurial assets. Secondly, we argue that the existence and patterning of these socially embedded routines used in new business development are contingent on the institutional context. We see the institutional context as complex and fragmented, composed and shaped by different institutional domains: the normative, the cognitive and the regulatory domain.


Energy consumption and energy production remain at the top of the list of concerns for politicians and for consumers, especially when the bill comes due and when climate change impacts our lives. The City of Austin is among the pioneers of green building in the United States, and through visionary policies and practices Austin has changed not only where our energy comes from, but also how energy is both used and saved.

 Austin Energy, Austin's public owned utility, began going green in 1985 with public education and policy changes, and eventually became the first to use a green rating system for residential buildings. The Green Building Program's focus continues to expand, eventually including commercial construction, multifamily projects, municipal buildings, and consulting services. The program now rates new and retrofit construction in the areas of energy conservation, water conservation, sustainable materials, health and safety, and community.

Rich MacMath is currently the lead Green Building Program staff member working with the City of Austin's Neighborhood Housing and Community Development Department to create an affordable, solar powered, green built subdivision in Austin. He is happy to share with us all of they ways to make our homes energy efficient now, as well as Austin Energy's vision of the future.


This article studies the negative signals associated with non-promotion. I first show theoretically that, when workers' productivity rises little with additional years on the same job level, the negative signal associated with non-promotion leads to wage decreases. On the other hand, when additional job-level tenure leads to a sizable increase in productivity, workers' wages increase. I test my model's predictions using the personnel records from a large US firm from 1970-1988. I find a clear hump-shaped wage-job-tenure profile for workers who stay in the same job level, which supports my model's prediction.


Mobile technologies have facilitated a radical shift in work and private life. In this article, we seek to better understand how individual mobile technology users have made sense of these changes and adapted to them. We have used narrative enquiry and sensemaking to collect and analyze the data. The findings show that mobile technology use blurs the boundaries between work and private life, making traditional time and place distinctions less relevant. Furthermore, work and private life can be integrated in ways that may be either competitive or complementary. We also observed an effect rarely discussed in the literature—the way personal and professional aspirations affect how work and private life are integrated. Implications include the need for researchers and organizations to understand the wider consequences that arise from the integration of work and private life roles.


This paper will examine the implications of Brexit for social security rights as they affect Northern Ireland. The paper begins with a consideration of the UK-wide implications for social security arising from Brexit including the potential impact on rights derived from EU law and the legal challenges inherent in reconciling existing EU laws with new domestic UK legislation, with concerns over the potential for parliamentary or independent scrutiny of this process. The general constitutional and political uncertainties for Northern Ireland arising from Brexit are considered in order to contextualise the examination of the most prominent social security implications for Northern Ireland – and the Republic of Ireland – stemming from the issue of cross-border working and the aggregation and exportability of social security entitlements. The paper brings together the positions of the UK, Northern Ireland, Republic of Ireland and the EU, as of January 2018, to provide a robust assessment of the cumulative issues that that will impact on social security rights in Northern Ireland post-Brexit.


A new specimen of an earliest Hettangian (Jurassic) belemnite (Coeloidea, Cephalopoda) is described herein. It displays the complete, typically belemnitid proostracum, the ink sac with its duct, questionable remains of the nuchal cartilage, and half of the phragmocone. Since the apical part of the phragmocone is missing, it is unclear what kind of rostrum was present and a taxonomic assignment is thus impossible. This represents the earliest record of an undoubted belemnitid proostracum of clear stratigraphic affi nity.


Given a multivariate time series, possibly of high dimension, with unknown and time-varying joint distribution, it is of interest to be able to completely partition the time series into disjoint, contiguous subseries, each of which has different distributional or pattern attributes from the preceding and succeeding subseries. An additional feature of many time series is that they display self-affinity, so that subseries at one time scale are similar to subseries at another after application of an affine transformation. Such qualities are observed in time series from many disciplines, including biology, medicine, economics, finance, and computer science. This paper defines the relevant multiobjective combinatorial optimization problem with limited assumptions as a biobjective one, and a specialized evolutionary algorithm is presented which finds optimal self-affine time series partitionings with a minimum of choice parameters. The algorithm not only finds partitionings for all possible numbers of partitions given data constraints, but also for self-affinities between these partitionings and some fine-grained partitioning. The resulting set of Pareto-efficient solution sets provides a rich representation of the self-affine properties of a multivariate time series at different locations and time scales.


We exploit the randomness generated by a seat allocation mechanism utilized in Parliamentary elections that determines those politicians who get elected from a given district by a small margin, and those who lose. Using detailed information on personal attributes of more than 2,000 elected Members of the Parliament (MPs) and the votes received by each political party in every district and each of the five consecutive Parliamentary elections in Turkey between 1991 and 2011, we show that elected MPs are more likely to switch parties after an election if they faced electoral uncertainty and experienced a narrowly-won victory. The tendency to switch parties goes up as it becomes more lucrative to hold the post of MP. The impact of election uncertainty on party-switching is greater for younger MPs, and for those who are less educated. The propensity to switch due to uncertainty is higher if the MP is a member of the governing party, but only if the seat is valuable (if the majority of the party in the Parliament is slim). Politicians switch parties after an election to improve their ex-ante re-election probability in the following election. Although switching parties during a legislative session (between elections) for personal career concerns creates moral hazard, we find that party-switching MPs are more likely to get elected in the next election. These results point to forward-looking opportunistic behavior of politicians regarding their strategy to win future elections, and they indicate that politicians switch parties primarily for career concerns and for financial benefits that are associated with longer tenure in the Parliament. The results also signify that competition between political parties continues after the election, in the form of gaining seats in the Parliament post- election by transferring elected representatives of competing parties. This constitutes another dimension of the political agency problem.


We use the 1988 PSID to study the effects of income and wealth on transfers of money and time between individuals and their parents as well as the effects of incomes of other relatives on these flows. We relate the relative incomes of parents and parents in-law to transfer amounts given and received by married couples. We also study how the relative incomes of divorced parents influence transfers. We find that money transfers tend to reduce inequality in household incomes and that time transfers are only weakly related to income differences. Richer siblings give more to parents and receive less. Among parents and parents in-law the richer set of parents is more likely to give money and less likely to receive money. The same is true of divorced parents. In contrast to the implications of simple exchange models of transfers, there is little evidence in the cross section or in the analysis using siblings that parental income or wealth raises time transfers from children or that time transfers are exchanged for money transfers. In the cross section and among siblings, the strong negative relationship between time transfers and distance from parents is not associated with a strong negative relationship between distance and money transfers. We discuss the implications of our results for alternative models of transfers.


Plants are used to the treatment and prevention of many of metabolic, degenerative and cardiovascular diseases. Obesity is one of the most common metabolic diseases which is considered one of the global health problems. The present study aimed to screen anti-lipase effect of Portulaca oleracea, Urtica urens, Brassica napus and Lathyrus hierosolymitanus traditional Palestinian medicinal wild plants. Anti-lipase activity was measured by using porcine pancreatic lipase inhibitory test which was established by using the UV-visible spectrophotometer method, while orlistat (anti-obesity drug) was used as a positive control reference. The porcine pancreatic lipase inhibitory effect for organic and aqueous extracts of Urtica urens were 157 μg/ml and 157.1 μg/ml, respectively. While the anti-lipase IC50 value for the organic extract of P. oleracea was 262.03 μg/ml. In addition, the aqueous extracts of Brassica napus and Portulaca oleracea have anti-lipase activity with the IC50 values 296.87 μg/ml and 417.62 μg/ml, respectively. Meanwhile, Lathyrus hierosolymitanus both aqueous and organic extracts were almost inactive. The results showed that Urtica urens, Portulaca oleracea, and Brassica napus have anti-lipase activity, which provided evidence for their folkloric use as functional food and medicine. These three plants could be used as antilipase agents in the pharmaceutical and nutritional industries or may be used as fatty food additives in order to decrease the absorption and digestion of fats from food.


A number of optoelectronic threshold effects arising under intensive stimulated radiative recombination of hot dense electron-hole plasma (EHP) in a thin (~1um) epitaxial layer of GaAs has been revealed. These effects' build-up and decay time intervals are of ~10 ps or less at room temperature (which makes it possible to modulate the optical and electrical properties of semiconductor heterostructures and devices with a frequency of ~ 100 GHz). These effects are observed when the stimulated recombination emission appears in picoseconds. The emission intensity can be as high as ~108 W/cm2 and the EHP concentration can change several times by magnitude. The revealed class of optoelectronic effects has its origin in strong mutual influence between the stimulated emission and dynamical processes in dense EHP. The acquired knowledge of somewhat uncommon mechanism of changes of EHP concentration and temperature, of intensity and spectrum of stimulated emission, of the gain, transparency, band-gap width, etc. can be used for successful construction of semiconductor high-speed powerful optoelectronic devices (such as semiconductor lasers and superluminescence diodes, semiconductor light-wave converters, modulators of the optical transparency and photoconductivity7)


Mary Douglas, in Purity and Danger and Elizabeth Grosz, in Volatile Bodies concur that the human body whose boundaries are traversed or transgressed is troubling, threatening and risky. The threats to which Douglas and Grosz separately refer are largely ideological and cultural threats, but their identification of the problematic nature of ruptured or unusual bodily boundaries is nevertheless relevant to the analysis of the actual bodily disorder with which this thesis is concerned. Disease, cannibalism and monstrosity are forms of bodily behaviour or conditions in which boundaries are inherently, or are rendered, unclear, and in the sixteenth-century books of Ambroise Pare, Jean de Lery and Michel de Montaigne, the question of the disorderly nature of these three physical phenomena is addressed. A fundamental feature of the books produced by these three writers is the emphasis on the experience of the form of bodily disorder in question on which the written account is based. Pare, a surgeon, treated plague patients and dissected monstrous specimens before writing about his experiences in his Œuvres completes', Lery observed the practice of cannibalism in Brazil before returning to Europe and witnessing the consumption of human flesh during the siege of Sancerre; and Montaigne, whose final essay is significantly entitled 'De ľexperience', develops a method of writing, or essaying, which involves the writer attempting to evaluate critically all received experiences and information before arriving at his own conclusion. The depiction of cannibalism, monstrosity and disease in the books of these three writers will be examined using a methodology developed around the principles of Mikhail Bakhtin's theory of dialogism. The particular relevance of this literary theory to the theme of the disordered body in French sixteenth-century books is the emphasis that Bakhtm also places on the writer's experience of his subject matter. In addition, Bakhtm argues that writers experience an impulse to consummate, in other words to define, explain and contextualise, and present as complete the world they observe. This thesis argues that the question of bodily boundaries raised by Douglas and Grosz can be addressed by Bakhtinian theory, and seeks to illustrate the ways in which Pare, Lery and Montaigne exhibit an awareness of the problem of the disordered body, and develop narrative strategies to overcome it which correspond to the functions of a Bakhtinian Author.


OF DISSERTATION Deep Neural Networks for Multi-Label Text Classification: Application to Coding Electronic Medical Records Coding Electronic Medical Records (EMRs) with diagnosis and procedure codes is an essential task for billing, secondary data analyses, and monitoring health trends. Both speed and accuracy of coding are critical. While coding errors could lead to more patient-side financial burden and misinterpretation of a patients well-being, timely coding is also needed to avoid backlogs and additional costs for the healthcare facility. Therefore, it is necessary to develop automated diagnosis and procedure code recommendation methods that can be used by professional medical coders. The main difficulty with developing automated EMR coding methods is the nature of the label space. The standardized vocabularies used for medical coding contain over 10 thousand codes. The label space is large, and the label distribution is extremely unbalanced – most codes occur very infrequently, with a few codes occurring several orders of magnitude more than others. A few codes never occur in training dataset at all. In this work, we present three methods to handle the large unbalanced label space. First, we study how to augment EMR training data with biomedical data (research articles indexed on PubMed) to improve the performance of standard neural networks for text classification. PubMed indexes more than 23 million citations. Many of the indexed articles contain relevant information about diagnosis and procedure codes. Therefore, we present a novel method of incorporating this unstructured data in PubMed using transfer learning. Second, we combine ideas from metric learning with recent advances in neural networks to form a novel neural architecture that better handles infrequent codes. And third, we present new methods to predict codes that have never appeared in the training dataset. Overall, our contributions constitute advances in neural multi-label text classification with potential consequences for improving EMR coding.


This book takes a fresh look at corporate strategy, exploring it from a feminist perspective. Challenging male-dominated theory, Corporate Strategy looks at unquestioned assumptions held about strategy in practice and academia, including whether women approach strategy differently from men, and if so, how their approach differs?Reviewing the histories of strategy and feminism, the book explores the reasons why so few serious works on strategy have been written by women, and investigates the continued lack of women at senior levels within many organizations. Angelique du Toit draws on postmodern arguments to illustrate the claims made for the necessity of diversity within organizations, and challenges the fact that positions of power, both in society and organizations remain the exclusive right of men. Corporate Strategy argues that if an organization is to survive and succeed in the global economy, it has to pay more than lip service to issues surrounding diversity.


Nowadays, percutaneous pulmonary valve implantation is a successful alternative to surgery for patients requiring treatment of pulmonary valve dysfunction. However, owing to the wide variety of implantation site morphology, size and dynamics, only about 15 per cent of cases are suitable for current devices. In order to increase the number of patients who could benefit from minimally invasive procedures, a new valved stent graft for percutaneous implantation has been designed recently. In this study, patient-specific computational analyses have been applied to investigate the suitability of new device designs, using real data from 62 patients who had undergone surgical pulmonary valve replacement. Magnetic resonance images of these patients before surgery were elaborated using imaging post-processing software to reconstruct the three-dimensional volume of each patient's implantation site. Three stent designs were created and tested in these patient outflow tracts using finite-element simulations: stent graft SG1 resembles the first device tested in animals; stent graft SG2 is a custom device tailored for a specific patient morphology; and stent graft SG3 represents a hypothetical larger device. The three devices showed an implantation success rate of 37 per cent, 42 per cent and 63 per cent, respectively. Using patient-specific simulations, we have shown that a percutaneous approach with these new devices may be possible for many patients who are currently referred for surgery. Furthermore, when the new devices become available, the methodologies described may help clinicians in the decision-making process, by enabling virtual implantation prior to the actual procedure.


This study investigates tourist's motivations for visiting religious sites in Lesvos, a religious destination island in Greece. Data was collected in Lesvos during the Orthodox Easter period of 2013 implementing a sample of 210 tourists who had visited a monastery during their stay on the island. In order to measure tourists' motivation for religious site visitation in Lesvos, 15 motivation components were used. Data analysis included descriptive analysis and factor analysis. The findings based on descriptive statistics (Mean Scores) suggest that the main reasons for visitation to monasteries and churches in Lesvos Island were pilgrimage motives, i.e. "To worship", "I have made a vow" and "In order to get well (health reasons)". On the other hand, the reasons with the lowest Mean Scores regarding visitation to monasteries and churches in Lesvos Island were secular reasons: "It is in "fashion"- it is trendy", "To do shopping", and for "Research /educational reasons". Factor analysis of the motivations components identified 3 factors, interpreting 66.5% of the total variance, i.e. "Secular and cultural motives", "Pilgrimage motives", and "Spiritual motives". The findings of this research offer important practical implications for promoting Lesvos for religion tourism.


Over the last three decades, survival rate from malignancies has steadily increased, turning major focus on quality of life in remission. Unfortunately, a major side effect of medical interventions including chemotherapy, radiotherapy, and/or surgery is premature ovarian failure and infertility for many patients. Ovarian tissue cryopreservation is an experimental technique used to preserve reproductive potential in patients who are pre-pubertal, must urgently undergo gonadotoxic treatment or who have other medical conditions requiring treatment that may undermine ovarian reserve and will lead to sub or infertility. We will review the indications, available techniques of tissue harvesting, and methods for freezing and auto transplanting cortical ovarian tissue. We will discuss outcomes, the potential risk of reintroducing malignancy and lastly, cutting-edge research models being developed in the field.


Background: Postprandial hyperlipidemia is associated with impaired endothelial function. Peanut consumption favorably affects the lipid and lipoprotein profile; however, the effects on endothelial function remain unclear. Objective: The purpose of the study was to evaluate the effects of acute peanut consumption as part of a high-fat meal on postprandial endothelial function. Methods: We conducted a randomized, controlled, crossover postprandial study to evaluate the effect of acute peanut consumption on postprandial lipids and endothelial function as assessed by flow-mediated dilatation (FMD) of the brachial artery in 15 healthy overweight or obese men [mean age: 26.7 y; mean body mass index (in kg/m2): 31.4]. Participants consumed, in a randomized order, a peanut meal containing 3 ounces (85 g) ground peanuts (1198 kcal; 40.0% carbohydrate, 47.7% fat, 19.4% saturated fat, 13.2% protein) and a control meal matched for energy and macronutrient content. Meals were in the form of a shake, scheduled ≥1 wk apart. Lipids, lipoproteins, glucose, and insulin were measured at baseline (0 min) and at 30, 60, 120, and 240 min after shake consumption. FMD was measured at baseline and at 240 min. Results: Acute peanut consumption blunted the serum triglyceride (TG) response 120 and 240 min after consumption compared with the control meal (means ± SEMs—120 min: 188.9 ± 19.4 compared with 197.5 ± 20.7 mg/dL; 240 min: 189.9 ± 24.3 compared with 197.3 ± 18.4 mg/dL; P < 0.05 for both). Total, LDL, and HDL cholesterol and glucose and insulin responses were similar between the test meals. Compared with baseline, only the control meal significantly decreased FMD at 240 min (control: −1.2% ± 0.5%; P = 0.029; peanut: −0.6% ± 0.5%; P = 0.3). Participants with higher baseline total (>150 mg/dL) and LDL (>100 mg/dL)-cholesterol concentrations showed a significant decrease in FMD after the control meal (−1.8%, P = 0.017; −2.0%, P = 0.038), whereas the peanut meal maintained endothelial function in all participants irrespective of total- and LDL-cholesterol concentrations. Conclusion: The inclusion of 85 g peanuts (3 ounces) as part of a high-fat meal improved the postprandial TG response and preserved endothelial function in healthy overweight or obese men. This trial was registered at clinicaltrials.gov as NCT01405300.


Identification of novel targets for the development of more effective antimalarial drugs and vaccines is a primary goal of the Plasmodium genome project. However, deciding which gene products are ideal drug/vaccine targets remains a difficult task. Currently, a systematic disruption of every single gene in Plasmodium is technically challenging. Hence, we have developed a computational approach to prioritize potential targets. A pathway/genome database (PGDB) integrates pathway information with information about the complete genome of an organism. We have constructed PlasmoCyc, a PGDB for Plasmodium falciparum 3D7, using its annotated genomic sequence. In addition to the annotations provided in the genome database, we add 956 additional annotations to proteins annotated as "hypothetical" using the GeneQuiz annotation system. We apply a novel computational algorithm to PlasmoCyc to identify 216 "chokepoint enzymes." All three clinically validated drug targets are chokepoint enzymes. A total of 87.5% of proposed drug targets with biological evidence in the literature are chokepoint reactions. Therefore, identifying chokepoint enzymes represents one systematic way to identify potential metabolic drug targets.


: The (re)attribution of place names plays a significant yet subtle role in the production of spatial and national identity. Since 1948, the Israeli administration has endeavoured to Hebraize (and therefore Judaize) the space in the Israel/Palestine region. Yet, Arabic names of major neighbourhoods within Jerusalem have survived while their Palestinian residents have not been allowed to return since they fled or were expelled in 1948. This article explores this toponymic paradox. After delving into the Israeli efforts to create and maintain an (almost) exclusively Hebraized landscape and the variety of ensuing toponymic clashes, this paper examines different reasons that might explain the 'resistance' of Arabic names in areas of Israel's proclaimed capital city. Using concepts such as toponymic attachment and place identity, this paper reveals much about the strength of traditional naming practices versus imposed policies, including in contexts of disputed territories where the Other's toponyms tend to represent a threat to One's narrative of claimed land.


Abstract Systems biology is an emerging field that aims at obtaining a system-level understanding of biological processes. The modelling and simulation of networks of biochemical reactions have great and promising application potential but require reliable kinetic data. In order to support the systems biology community with such data we have developed SABIO-RK (System for the Analysis of Biochemical Pathways - Reaction Kinetics), a curated database with information about biochemical reactions and their kinetic properties, which allows researchers to obtain and compare kinetic data and to integrate them into models of biochemical networks. SABIO-RK is freely available for academic use at http://sabio.villa-bosch.de/SABIORK/.


In the high-associativity caches, the hardware overheads of the cache replacement policy become problem. To avoid this problem, the Adaptive Demotion Policy (ADP) is proposed. The ADP focuses on the priority value demotion at a cache miss, and it can achieve a higher performance compared with conventional cache replacement policies. The ADP can be implemented with small hardware resources, and the priority value update logic can be implemented with a small hardware cost. The ADP can suit for various applications by the appropriate selection of its insertion, promotion and selection policies. If the dynamic selection of the suitable policies for the running application is possible, the performance of the cache replacement policy will be increased. In order to achieve the dynamic selection of the suitable policies, this paper focuses on the global fluctuations of the priority values. At first, the cache is partitioned into several partitions. At every cache access, the total of priority values in each partition is calculated. At every set interval, the fluctuations of total priority values in all the partitions are checked, and the information is used to detect the behavior of the application. This paper adapts this mechanism to the ADP, and the adapted cache replacement policy is called the ADP-G. The performance evaluation shows that the ADP-G achieves the MPKI reductions and the IPC improvements, compared to the LRU policy, the RRIP policy and the ADP.


The  primary  aim  of  this  study  was  to  identify  the  motives  for  self‐ initiated mobility  of  highly  educated  New  Zealanders  across  national boundaries.  It  further  seeks  to  identify  the  relative  importance of  these motives  and  to  explore  relationships  between motivation  and mobility behaviour.    This  study  on  self‐initiated  mobility  is  opportune  as  an increasingly globalised market place and a demand  for  the  skills of  the highly educated result in competition for workers. Most literature concerning mobility focuses on expatriate assignment.  By comparison,  self‐initiated  movers  remain  an  under‐researched  group. Moreover,  of  the  limited  research  on  self‐initiated mobility, most  have used  interviewing  and  narrative  methods,  so  that  the  available information  is  detailed  but  restricted  to  individual  experiences.    This study  used  a  self‐report  survey  via  the  internet  to  collect  both quantitative  and  qualitative  data  and  yielded  2,608  useable  responses from New Zealanders living and working throughout the world.   It was highly exploratory, using  the analytical marketing  tool CHAID  to show linkages between subjective attitudinal motives and objective measures of mobility behaviours. The  desire  for  cultural  and  travel  opportunities  was  the  dominant subjective  motive,  being  the  best  predictor  for  the  objective  mobility behaviours of establishment, current spatiality and return propensity and being  a  secondary  predictor  for  restlessness.   Other  associations were evident  between  the  quality  of  life  motive  and  the  behaviour  of restlessness,  the  career  motive  and  cultural  globalism  and  the relationships motive and  the behaviour of  latent  transience.   Economics and  the political  environment motives were not  found  to be  significant predictors of any behaviour. The subjective data  reinforced  the  importance of  the cultural and  travel opportunities  and  career  motives,  ranking  these  the  most  important motives  in a decision to be mobile.   Within these motives, opportunities for  travel  and  adventure  and  for  career  development  were  central. Economics was  ranked as  the  third most  important motive,  contrary  to extant literature, followed by relationships, quality of life and the political environment.   The priority accorded  to each of  these six motives varies according  to gender,  location and  life stage, creating different equations of motivation.


We present an analysis of weakly convex discontinuity adaptive (WCDA) models for regularizing three-dimensional (3D) quantitative microwave imaging. In particular, we are concerned with complex permittivity reconstructions from sparse measurements such that the reconstruction process is significantly accelerated. When dealing with such a highly underdetermined problem, it is crucial to employ regularization, relying in this case on prior knowledge about the structural properties of the underlying permittivity profile: we consider piecewise homogeneous objects. We present a numerical study on the choice of the potential function parameter for the Huber function and for two selected WCDA functions, one of which (the Leclerc–Cauchy-Lorentzian function) is designed to be more edge-preserving than the other (the Leclerc–Huber function). We evaluate the effect of reducing the number of (simulated) scattered field data on the reconstruction quality. Furthermore, reconstructions from subsampled single-frequency experimental data from the 3D Fresnel database illustrate the effectiveness of WCDA regularization.


ABSTRACT This article traces the origins of legalized discrimination, religious hatred, and systematic marginalization of a community of Malaysian Muslims – the Shias – perpetuated in the name of Islam. It demonstrates how a central government-derived fatwa (religious legal opinion) banning Shi'ism and the propagation of Shia teachings in the country since 1996 has been used to justify a range of human rights violations, not limited to the religious freedom of this minority group. Apart from Syariah legislation, the state has utilized this fatwa alongside other tools, including the religious bureaucracy and the media, to persecute Shia in Malaysia. Anti-Shia efforts are also supported and propagated by non-state Islamists who often work hand-in-hand with state actors.


Empirical orthogonal functions (EOFs) are widely used in climate research to identify dominant patterns of variability and to reduce the dimensionality of climate data. EOFs, however, can be difficult to interpret. Rotated empirical orthogonal functions (REOFs) have been proposed as more physical entities with simpler patterns than EOFs. This study presents a new approach for finding climate patterns with simple structures that overcomes the problems encountered with rotation. The method achieves simplicity of the patterns by using the main properties of EOFs and REOFs simultaneously. Orthogonal patterns that maximise variance subject to a constraint that induces a form of simplicity are found. The simplified empirical orthogonal function (SEOF) patterns, being more 'local', are constrained to have zero loadings outside the main centre of action. The method is applied to winter Northern Hemisphere (NH) monthly mean sea level pressure (SLP) reanalyses over the period 1948–2000. The 'simplified' leading patterns of variability are identified and compared to the leading patterns obtained from EOFs and REOFs. Copyright © 2005 Royal Meteorological Society.


In recent years, parties and candidates challenging key democratic norms have won unprecedented popular support in liberal democracies across the globe. Drawing on public opinion data from the World Values Survey and various national polls, we show that the success of anti-establishment parties and candidates is not a temporal or geographic aberration, but rather a reflection of growing popular disaffection with liberal-democratic norms and institutions, and of increasing support for authoritarian interpretations of democracy. The record number of anti-system politicians in office raises uncertainty about the strength of supposedly "consolidated" liberal democracies and highlights the need for further analysis of the signs of democratic deconsolidation.


Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa). Large cationic molecules can also permeate the channel, albeit at a much lower rate. We further show that Panx1 channels provide a molecular pathway for flux of ATP and other anionic (glutamate) and cationic signaling metabolites (spermidine). These results verify large molecule permeation directly through caspase-activated Panx1 channels that can support their many physiological roles.