Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease

HD (Huntington's disease) is a late onset heritable neurodegenerative disorder that is characterized by neuronal dysfunction and death, particularly in the cerebral cortex and medium spiny neurons of the striatum. This is followed by progressive chorea, dementia and emotional dysfunction, eventually resulting in death. HD is caused by an expanded CAG repeat in the first exon of the HD gene that results in an abnormally elongated polyQ (polyglutamine) tract in its protein product, Htt (Huntingtin). Wild-type Htt is largely cytoplasmic; however, in HD, proteolytic N-terminal fragments of Htt form insoluble deposits in both the cytoplasm and nucleus, provoking the idea that mutHtt (mutant Htt) causes transcriptional dysfunction. While a number of specific transcription factors and co-factors have been proposed as mediators of mutHtt toxicity, the causal relationship between these Htt/transcription factor interactions and HD pathology remains unknown. Previous work has highlighted REST [RE1 (repressor element 1)-silencing transcription factor] as one such transcription factor. REST is a master regulator of neuronal genes, repressing their expression. Many of its direct target genes are known or suspected to have a role in HD pathogenesis, including BDNF (brain-derived neurotrophic factor). Recent evidence has also shown that REST regulates transcription of regulatory miRNAs (microRNAs), many of which are known to regulate neuronal gene expression and are dysregulated in HD. Thus repression of miRNAs constitutes a second, indirect mechanism by which REST can alter the neuronal transcriptome in HD. We will describe the evidence that disruption to the REST regulon brought about by a loss of interaction between REST and mutHtt may be a key contributory factor in the widespread dysregulation of gene expression in HD.

Linear and non-linear transmission of equity return volatility: evidence from the US, Japan and Australia

This paper models the transmission of shocks between the US, Japanese and Australian equity markets. Tests for the existence of linear and non-linear transmission of volatility across the markets are performed using parametric and non-parametric techniques. In particular the size and sign of return innovations are important factors in determining the degree of spillovers in volatility. It is found that a multivariate asymmetric GARCH formulation can explain almost all of the non-linear causality between markets. These results have important implications for the construction of models and forecasts of international equity returns.

Linear and non-linear (non-)forecastability of high-frequency exchange rates

This paper forecasts Daily Sterling exchange rate returns using various naive, linear and non-linear univariate time-series models. The accuracy of the forecasts is evaluated using mean squared error and sign prediction criteria. These show only a very modest improvement over forecasts generated by a random walk model. The Pesaran–Timmerman test and a comparison with forecasts generated artificially shows that even the best models have no evidence of market timing ability.

Use of virulence determinants and seropathotypes to distinguish high- and low-risk Escherichia coli O157 and non-O157 isolates from Europe

The presence of 10 virulence genes was examined using polymerase chain reaction (PCR) in 365 European O157 and non-O157 Escherichia coli isolates associated with verotoxin production. Strain-specific PCR data were analysed using hierarchical clustering. The resulting dendrogram clearly separated O157 from non-O157 strains. The former clustered typical high-risk seropathotype (SPT) A strains from all regions, including Sweden and Spain, which were homogenous by Cramer's V statistic, and strains with less typical O157 features mostly from Hungary. The non-O157 strains divided into a high-risk SPTB harbouring O26, O111 and O103 strains, a group pathogenic to pigs, and a group with few virulence genes other than for verotoxin. The data demonstrate SPT designation and selected PCR separated verotoxigenic E. coli of high and low risk to humans; although more virulence genes or pulsed-field gel electrophoresis will need to be included to separate high-risk strains further for epidemiological tracing.

LTE and LTE-A interworking and interoperability with 3GPP and non-3GPP wireless networks

This paper provides a high-level overview of E-UTRAN interworking and interoperability with existing Third Generation Partnership Project (3GPP) and non-3GPP wireless networks. E-UTRAN access networks (LTE and LTE-A) are currently the latest technologies for 3GPP evolution specified in Release 8, 9 and beyond. These technologies promise higher throughputs and lower latency while also reducing the cost of delivering the services to fit with subscriber demands. 3GPP offers a direct transition path from the current 3GPP UTRAN/GERAN networks to LTE including seamless handover. E-UTRAN and other wireless networks interworking is an option that allows operators to maximize the life of their existing network components before a complete transition to truly 4G networks. Network convergence, backward compatibility and interpretability are regarded as the next major challenge in the evolution and the integration of mobile wireless communications. In this paper, interworking and interoperability between the E-UTRAN Evolved Packet Core (EPC) architecture and 3GPP, 3GPP2 and IEEE based networks are clearly explained. How the EPC is designed to deliver multimedia and facilitate interworking is also explained. Moreover, the seamless handover needed to perform this interworking efficiently is described briefly. This study showed that interoperability and interworking between existing networks and E-UTRAN are highly recommended as an interim solution before the transition to full 4G. Furthermore, wireless operators have to consider a clear interoperability and interworking plan for their existing networks before making a decision to migrate completely to LTE. Interworking provides not only communication between different wireless networks; in many scenarios it contributes to add technical enhancements to one or both environments.

Modeling migratory grazing of zooplankton on toxic and non-toxic phytoplankton

Migratory grazing of zooplankton between non-toxic phytoplankton (NTP) and toxic phytoplankton (TPP) is a realistic phenomena unexplored so far. The present article is a first step in this direction. A mathematical model of NTP–TPP-zooplankton with constant and variable zooplankton migration is proposed and analyzed. The asymptotic dynamics of the model system around the biologically feasible equilibria is explored through local stability analysis. The dynamics of the proposed system is explored and displayed for different combination of migratory parameters and toxin inhibition parameters. Our analysis suggests that the migratory grazing of zooplankton has a significant role in determining the dynamic stability and oscillation of phytoplankton zooplankton systems.

Fractional order and non-linear system identification algorithms for biomedical applications

We discuss the modelling of dielectric responses of amorphous biological samples. Such samples are commonly encountered in impedance spectroscopy studies as well as in UV, IR, optical and THz transient spectroscopy experiments and in pump-probe studies. In many occasions, the samples may display quenched absorption bands. A systems identification framework may be developed to provide parsimonious representations of such responses. To achieve this, it is appropriate to augment the standard models found in the identification literature to incorporate fractional order dynamics. Extensions of models using the forward shift operator, state space models as well as their non-linear Hammerstein-Wiener counterpart models are highlighted. We also discuss the need to extend the theory of electromagnetically excited networks which can account for fractional order behaviour in the non-linear regime by incorporating nonlinear elements to account for the observed non-linearities. The proposed approach leads to the development of a range of new chemometrics tools for biomedical data analysis and classification.

Fat and fatty acid composition of cooked meat from UK retail chickens labelled as from organic and non-organic production systems

This study compared fat and fatty acids in cooked retail chicken meat from conventional and organic systems. Fat contents were 1.7, 5.2, 7.1 and 12.9 g/100 g cooked weight in skinless breast, breast with skin, skinless leg and leg with skin respectively, with organic meat containing less fat overall (P < 0.01). Meat was rich in cis-monounsaturated fatty acids, although organic meat contained less than did conventional meat (1850 vs. 2538 mg/100 g; P < 0.001). Organic meat was also lower (P < 0.001) in 18:3 n−3 (115 vs. 180 mg/100 g) and, whilst it contained more (P < 0.001) docosahexaenoic acid (30.9 vs. 13.7 mg/100 g), this was due to the large effect of one supermarket. This system by supermarket interaction suggests that poultry meat labelled as organic is not a guarantee of higher long chain n−3 fatty acids. Overall there were few major differences in fatty acid contents/profiles between organic and conventional meat that were consistent across all supermarkets.

Interpreters’ perception of linguistic and non linguistic factors affecting quality: a survey through the World Wide Web

This paper will present and discuss the results of an empirical study on perception of quality in interpretation carried out on a sample of 286 interpreters across five continents. Since the 1980’s the field of Interpreting Studies has been witnessing an ever growing interest in the issue of quality in interpretation both in academia and in professional circles, but research undertaken so far is surprisingly lacking in methodological rigour. This survey is an attempt to revise previous studies on interpreters’ perception of quality through the implementation of new Information Technology which allowed us to administer a traditional research tool such as a questionnaire, in a highly innovative way; i.e., through the World Wide Web. Using multidimensional scaling, a perceptual map based upon the results of the manner in which interpreters ranked a list of linguistic and nonlinguistic criteria according to their perception of importance in the interpretative process,was devised.

Formulaic sequences in native and non-native argumentative writing in German

Whereas there is substantial scholarship on formulaic language in L1 and L2 English, there is less research on formulaicity in other languages. The aim of this paper is to contribute to learner corpus research into formulaic language in native and non-native German. To this effect, a corpus of argumentative essays written by advanced British students of German (WHiG) was compared with a corpus of argumentative essays written by German native speakers (Falko-L1). A corpus-driven analysis reveals a larger number of 3-grams in WHiG than in Falko-L1, which suggests that British advanced learners of German are more likely to use formulaic language in argumentative writing than their native-speaker counterparts. Secondly, by classifying the formulaic sequences according to their functions, this study finds that native speakers of German prefer discourse-structuring devices to stance expressions, whilst British advanced learners display the opposite preferences. Thirdly, the results show that learners of German make greater use of macro-discourse-structuring devices and cautious language, whereas native speakers favour micro-discourse structuring devices and tend to use more direct language. This study increases our understanding of formulaic language typical of British advanced learners of German and reveals how diverging cultural paradigms can shape written native speaker and learner output.

Preferred response of the East Asian summer monsoon to local and non-local anthropogenic sulphur dioxide emissions

In this study, the atmospheric component of a state-of-the-art climate model (HadGEM2-ES) that includes earth system components such as interactive chemistry and eight species of tropospheric aerosols considering aerosol direct, indirect, and semi-direct effects, has been used to investigate the impacts of local and non-local emissions of anthropogenic sulphur dioxide on the East Asian summer monsoon (EASM). The study focuses on the fast responses (including land surface feedbacks, but without sea surface temperature feedbacks) to sudden changes in emissions from Asia and Europe. The initial responses, over days 1–40, to Asian and European emissions show large differences. The response to Asian emissions involves a direct impact on the sulphate burden over Asia, with immediate consequences for the shortwave energy budget through aerosol–radiation and aerosol–cloud interactions. These changes lead to cooling of East Asia and a weakening of the EASM. In contrast, European emissions have no significant impact on the sulphate burden over Asia, but they induce mid-tropospheric cooling and drying over the European sector. Subsequently, however, this cold and dry anomaly is advected into Asia, where it induces atmospheric and surface feedbacks over Asia and the Western North Pacific (WNP), which also weaken the EASM. In spite of very different perturbations to the local aerosol burden in response to Asian and European sulphur dioxide emissions, the large scale pattern of changes in land–sea thermal contrast, atmospheric circulation and local precipitation over East Asia from days 40 onward exhibits similar structures, indicating a preferred response, and suggesting that emissions from both regions likely contributed to the observed weakening of the EASM. Cooling and drying of the troposphere over Asia, together with warming and moistening over the WNP, reduces the land–sea thermal contrast between the Asian continent and surrounding oceans. This leads to high sea level pressure (SLP) anomalies over Asia and low SLP anomalies over the WNP, associated with a weakened EASM. In response to emissions from both regions warming and moistening over the WNP plays an important role and determines the time scale of the response.

How is the balance of a forecast ensemble affected by adaptive and non-adaptive localization schemes?

This paper investigates the effect on balance of a number of Schur product-type localization schemes which have been designed with the primary function of reducing spurious far-field correlations in forecast error statistics. The localization schemes studied comprise a non-adaptive scheme (where the moderation matrix is decomposed in a spectral basis), and two adaptive schemes, namely a simplified version of SENCORP (Smoothed ENsemble COrrelations Raised to a Power) and ECO-RAP (Ensemble COrrelations Raised to A Power). The paper shows, we believe for the first time, how the degree of balance (geostrophic and hydrostatic) implied by the error covariance matrices localized by these schemes can be diagnosed. Here it is considered that an effective localization scheme is one that reduces spurious correlations adequately but also minimizes disruption of balance (where the 'correct' degree of balance or imbalance is assumed to be possessed by the unlocalized ensemble). By varying free parameters that describe each scheme (e.g. the degree of truncation in the schemes that use the spectral basis, the 'order' of each scheme, and the degree of ensemble smoothing), it is found that a particular configuration of the ECO-RAP scheme is best suited to the convective-scale system studied. According to our diagnostics this ECO-RAP configuration still weakens geostrophic and hydrostatic balance, but overall this is less so than for other schemes.

A review of Islamic mutual funds’ financial performance and investment style in Muslim and non-Muslim countries

Islamic finance has grown beyond its reputation of providing small-scale banking options and now provides investment and financing options for complex large-scale commercial transactions. Islamic investments are one area that has attracted the attention of investors due to its performance, especially during the economic downturn. The Shari’ah compliance nature of Islamic funds provides an opportunity for those Muslim investors to be part of the global investment sector who have previously been reluctant to invest in conventional mutual funds. The fact that the funds’ managers are prohibited from investing in activities such as weapons production, alcohol production and interest-bearing finance operations, makes Islamic mutual funds also attractive for those Non-Muslim investors who wish to invest ethically. Today there are hundreds of Islamic equity indices offered by Dow Jones, FTSE, MSCI and S&P. Despite the growing importance of Islamic funds, there have been limited studies exploring the performance of Islamic funds worldwide. Due to very limited data sets and not too rigorous analytical methods, these existent studies have neither investigated Islamic funds’ financial performance in noticeable detail nor analysed the investment style of more than six funds. For instance, relevant questions such as the financial performance of Islamic mutual funds’ beyond their investment styles or a difference in performance between funds from Muslim and non-Muslim countries have nearly not been investigated at all. Very recently, a study by Hoepner, Rammal and Rezec (2011) analysed the financial performance and investment style of 262 Islamic equity funds from 20 countries in five regions (Africa, Asia-Pacific, Europe, Gulf Cooperative Council-GCC, and North America). As comparison, previous studies did not even analyse 60 funds. Hoepner et al.’s study sampled a period of two decades and was therefore able to test the performance of the funds during economic booms as well as economic downturns. The findings of the study provide new insights into the performance of Islamic mutual funds in Muslim and Western markets and during financial crisis.