Impairment of calcium ATPases by high glucose and potential pharmacological protection

The review deals with impairment of Ca2+-ATPases by high glucose or its derivatives in vitro, as well as in human diabetes and experimental animal models. Acute increases in glucose level strongly correlate with oxidative stress. Dysfunction of Ca2+-ATPases in diabetic and in some cases even in nondiabetic conditions may result in nitration of and in irreversible modification of cysteine-674. Nonenyzmatic protein glycation might lead to alteration of Ca2+-ATPase structure and function contributing to Ca2+ imbalance and thus may be involved in development of chronic complications of diabetes. The susceptibility to glycation is probably due to the relatively high percentage of lysine and arginine residues at the ATP binding and phosphorylation domains. Reversible glycation may develop into irreversible modifications (advanced glycation end products, AGEs). Sites of SERCA AGEs are depicted in this review. Finally, several mechanisms of prevention of Ca2+-pump glycation, and their advantages and disadvantages are discussed. © 2013 Informa UK, Ltd.

Driving licensing renewal policy using neural network-based probabilistic decision support system

This paper investigates neural network-based probabilistic decision support system to assess drivers' knowledge for the objective of developing a renewal policy of driving licences. The probabilistic model correlates drivers' demographic data to their results in a simulated written driving exam (SWDE). The probabilistic decision support system classifies drivers' into two groups of passing and failing a SWDE. Knowledge assessment of drivers within a probabilistic framework allows quantifying and incorporating uncertainty information into the decision-making system. The results obtained in a Jordanian case study indicate that the performance of the probabilistic decision support systems is more reliable than conventional deterministic decision support systems. Implications of the proposed probabilistic decision support systems on the renewing of the driving licences decision and the possibility of including extra assessment methods are discussed.

Fibre impairment compensation using artificial neural network equalizer for high-capacity coherent optical OFDM signals

We propose an artificial neural network (ANN) equalizer for transmission performance enhancement of coherent optical OFDM (C-OOFDM) signals. The ANN equalizer showed more efficiency in combating both chromatic dispersion (CD) and single-mode fibre (SMF)-induced non-linearities compared to the least mean square (LMS). The equalizer can offer a 1.5 dB improvement in optical signal-to-noise ratio (OSNR) compared to LMS algorithm for 40 Gbit/s C-OOFDM signals when considering only CD. It is also revealed that ANN can double the transmission distance up to 320 km of SMF compared to the case of LMS, providing a nonlinearity tolerance improvement of ∼0.7 dB OSNR.

Az európai uniós tagság mint modernizációs hajtóerő. Gondolatok a kelet-közép-európai országok EU-tagságának 10. évfordulóján = EU membership as a driving force of modernization. Ideas on the 10th anniversary of EU membership of East Central European countries

A szerző az Európai Unióhoz az elmúlt évtizedben csatlakozott országok felzárkózásának összefüggéseit vizsgálja, rámutatva arra, hogy a kelet-közép-európai térség országainak természetes modernizációs központja az Európai Unió. Az európai integrációba történő szerves beépülésnek nem volt és a jövőben sincs reális alternatívája. Annak ellenére, hogy a nemzetközi pénzügyi és gazdasági válság rendkívül kedvezőtlen fordulatot hozott, az új tagországok többségében jelentős ütemű felzárkózási folyamat indult el: egy évtizeden belül relatív pozíciójuk az uniós átlaghoz képest átlagosan 15 százalékpont javult a vásárlóerő-paritáson mért egy főre jutó GDP-t tekintve. A tagság számos előnye közül ki kell emelni, hogy az uniós költségvetésből származó közvetlen transzferek hatására az új tagállamok számottevő külső forráshoz jutottak, aminek révén hosszú távú fejlődésüket és versenyképességüket befolyásoló területeken jelentős beruházásokat hajthattak végre. E transzferek kapcsán a szerző felhívja a figyelmet arra, hogy a szűk látókörűen számított nettó haszonélvezői pozíció valójában kölcsönös előnyöket rejt: az EU fejlettebb országai számára is komoly előnyök származnak a megnövekedett importkeresletből és általában a bővülés kereskedelemteremtő hatásaiból. _____ The author analyses some catch-up aspects of countries joining the EU in 2004 and 2007, pointing out that the EU is an obvious centre of modernization for the countries in East Central Europe. There was no realistic alternative to participating in the European integration process and this applies also to the future. Contrary to the extremely bad general environment caused by the international financial and economic crisis, most new member-states were able to converge on the EU average quite fast: within a decade the relative regional level of development measured in GDP per capita terms and compared with the EU average increased by 15 per cent. It should be stressed that among several advantages of EU membership, direct transfers from the EU-level budget played a crucial role in improving competitiveness through investment. Looking beyond narrow-minded net budgetary positions, the author sees mutual comprehensive benefits: the more developed member-states can enjoy additional demand for their products, and in general benefit from the trade-creating effects of enlargement.

The drivers of perception: Identifying the driving factors of resident perceptions of municipal service quality in cities of South Florida

The idea of comparative performance assessment is crucial. Recent study findings show that in South Florida the use by most municipalities of external benchmarks for performance comparison is virtually non-existent. On one level this study sought to identify the factors impacting resident perceptions of municipal service quality. On a different and more practical level, this study sought to identify a core set of measures that could serve for multi jurisdictional comparisons of performance. ^ This study empirically tested three groups of hypotheses. Data were collected via custom designed survey instruments from multiple jurisdictions, representing diverse socioeconomic backgrounds, and across two counties. A second layer of analysis was conducted on municipal budget documents for the presence of performance measures. A third layer of analysis was conducted via face-to-face interviews with residents at the point of service delivery. Research questions were analyzed using descriptive and inferential statistic methodologies. ^ Results of survey data yielded inconsistent findings. In absolute aggregated terms, the use of sociological determinants to guide inquiry failed to yield conclusive answers regarding the factors impacting resident perceptions of municipal service quality. At disaggregated community levels, however, definite differences emerged but these had weak predictive ability. More useful were the findings of performance measures reporting via municipal budget documents and analyses of interviews with residents at the point of service delivery. Regardless of socio-economic profile, neighborhood characteristics, level of civic engagement or type of community, the same aspects were important to citizens when making assessments of service quality. For parks and recreation, respondents most frequently cited maintenance, facility amenities, and program offerings as important while for garbage collection services timely and consistent service delivery mattered most. Surprisingly municipalities participating in the study track performance data on items indicated as important by citizen assessments but regular feed back from residents or reporting to the same is rarely done. ^ The implications of these findings suggest that endeavors, such as the one undertaken in this study, can assist in determining a core set of measures for cross jurisdictional comparisons of municipal service quality, improving municipal delivery of services, and to communicate with the public. ^

An evaluation of functional impairment among children with anxiety disorders

Despite a considerable progress in developing and testing psychosocial treatments to reduce youth anxiety disorders, much remains to learn about the relation between anxiety symptom reduction and change in youth functional impairment. The specific aims of this dissertation thus were to examine: (1) the relation between different levels of anxiety and youth functional impairment ratings; (2) incremental validity of the Children Global Assessment Scale (CGAS); (3) the mediating role of anxiety symptom reduction on youth functional impairment ratings; (4) the directionality of change between anxiety symptom reduction and youth functional impairment; (5) the moderating effects of youth age, sex, and ethnicity on the mediated relation between youth anxiety symptom reduction and change in functional impairment; and (6) an agreement (or lack thereof) between youths and their parents in their views of change in youth functional impairment vis-à-vis anxiety symptom reduction. ^ The results were analyzed using archival data set acquired from 183 youths and their mothers. Research questions were tested using SPSS and structural equation modeling techniques in Mplus. ^ The results supported the efficacy of psychosocial treatments to reduce the severity of youth anxiety symptoms and its associated functional impairment. Moreover, the results revealed that at posttreatment, youths who scored either low or medium on anxiety levels scored significantly lower on impairment, than youths who scored high on anxiety levels. Incremental validity of the CGAS was also revealed across all assessment points and informants in my sample. In addition, the results indicated the mediating role of anxiety symptom reduction with respect to change in youth functional impairment at posttest, regardless of the youth’s age, sex, and ethnicity. No significant findings were observed with regard to the bidirectionality and an informant disagreement vis-à-vis the relation between anxiety symptom reduction and change in functional impairment. ^ The study’s main contributions and potential implications on theoretical, empirical, and clinical levels are further discussed. The emphasis is on the need to enhance existing evidence-based treatments and develop innovative treatment models that will not only reduce youth’s symptoms (such anxiety) but also evoke genuine and palpable improvements in lives of youths and their families.^

The influence of neurocognitive impairment, alcohol and other drug (AOD) use, and psychosocial factors on antiretroviral treatment adherence, service utilization and viral load among HIV-seropositive adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p<0.01) at 6 months, but not 3 months, post-intervention. Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

The influence of gene environment interaction on the risk of cognitive impairment: Reducing sexual risk behaviors and alcohol use in HIV-infected adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. ^ A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p^

Factors driving territory size and breeding success in a threatened migratory songbird, the Canada Warbler

Successful conservation of migratory birds demands we understand how habitat factors on the breeding grounds influences breeding success. Multiple factors are known to directly influence breeding success in territorial songbirds. For example, greater food availability and fewer predators can have direct effects on breeding success. However, many of these same habitat factors can also result in higher conspecific density that may ultimately reduce breeding success through density dependence. In this case, there is a negative indirect effect of habitat on breeding success through its effects on conspecific density and territory size. Therefore, a key uncertainty facing land managers is whether important habitat attributes directly influence breeding success or indirectly influence breeding success through territory size. We used radio-telemetry, point-counts, vegetation sampling, predator observations, and insect sampling over two years to provide data on habitat selection of a steeply declining songbird species, the Canada Warbler (Cardellina canadensis). These data were then applied in a hierarchical path modeling framework and an AIC model selection approach to determine the habitat attributes that best predict breeding success. Canada Warblers had smaller territories in areas with high shrub cover, in the presence of red squirrels (Tamiasciurus hudsonicus), at shoreline sites relative to forest-interior sites and as conspecific density increased. Breeding success was lower for birds with smaller territories, which suggests competition for limited food resources, but there was no direct evidence that food availability influenced territory size or breeding success. The negative relationship between shrub cover and territory size in our study may arise because these specific habitat conditions are spatially heterogeneous, whereby individuals pack into patches of preferred breeding habitat scattered throughout the landscape, resulting in reduced territory size and an associated reduction in resource availability per territory. Our results therefore highlight the importance of considering direct and indirect effects for Canada warblers; efforts to increase the amount of breeding habitat may ultimately result in lower breeding success if habitat availability is limited and negative density dependent effects occur.

Argument structure and specific language impairment: retrospect and prospect

This article reflects a collaboration between the Universities of Groningen and Reading of which Frans Zwarts was the promoter. One of the outcomes was a close attention to the learning of various aspects of argument structure by children with specific language impairment (SLI) in Dutch and English. At that time and since, the focus on deficits in grammatical morphology in these children has left verb complementation as something of a syntactic Cinderella. Here we review the findings from our studies in the 1990s. We confirm that children with SLI in both languages have problems with verb specificity, with argument structure alternations and with resultative verb predicates. The very limited number of subsequent studies on verb syntax appear to support our findings. We conclude that this is an area which will repay further scrutiny – it is high time argument structure received an invitation to the ball.

Investigation of factors driving the costs of operating the 2020 Irish power system with large-scale wind generation

The main goal of this work is to determine the true cost incurred by the Republic of Ireland and Northern Ireland in order to meet their EU renewable electricity targets. The primary all-island of Ireland policy goal is that 40% of electricity will come from renewable sources in 2020. From this it is expected that wind generation on the Irish electricity system will be in the region of 32-37% of total generation. This leads to issues resulting from wind energy being a non-synchronous, unpredictable and variable source of energy use on a scale never seen before for a single synchronous system. If changes are not made to traditional operational practices, the efficient running of the electricity system will be directly affected by these issues in the coming years. Using models of the electricity system for the all-island grid of Ireland, the effects of high wind energy penetration expected to be present in 2020 are examined. These models were developed using a unit commitment, economic dispatch tool called PLEXOS which allows for a detailed representation of the electricity system to be achieved down to individual generator level. These models replicate the true running of the electricity system through use of day-ahead scheduling and semi-relaxed use of these schedules that reflects the Transmission System Operator's of real time decision making on dispatch. In addition, it carefully considers other non-wind priority dispatch generation technologies that have an effect on the overall system. In the models developed, three main issues associated with wind energy integration were selected to be examined in detail to determine the sensitivity of assumptions presented in other studies. These three issues include wind energy's non-synchronous nature, its variability and spatial correlation, and its unpredictability. This leads to an examination of the effects in three areas: the need for system operation constraints required for system security; different onshore to offshore ratios of installed wind energy; and the degrees of accuracy in wind energy forecasting. Each of these areas directly impact the way in which the electricity system is run as they address each of the three issues associated with wind energy stated above, respectively. It is shown that assumptions in these three areas have a large effect on the results in terms of total generation costs, wind curtailment and generator technology type dispatch. In particular accounting for these issues has resulted in wind curtailment being predicted in much larger quantities than had been previously reported. This would have a large effect on wind energy companies because it is already a very low profit margin industry. Results from this work have shown that the relaxation of system operation constraints is crucial to the economic running of the electricity system with large improvements shown in the reduction of wind curtailment and system generation costs. There are clear benefits in having a proportion of the wind installed offshore in Ireland which would help to reduce variability of wind energy generation on the system and therefore reduce wind curtailment. With envisaged future improvements in day-ahead wind forecasting from 8% to 4% mean absolute error, there are potential reductions in wind curtailment system costs and open cycle gas turbine usage. This work illustrates the consequences of assumptions in the areas of system operation constraints, onshore/offshore installed wind capacities and accuracy in wind forecasting to better inform the true costs associated with running Ireland's changing electricity system as it continues to decarbonise into the near future. This work also proposes to illustrate, through the use of Ireland as a case study, the effects that will become ever more prevalent in other synchronous systems as they pursue a path of increasing renewable energy generation.

Investigating relative clauses in children with specific language impairment

Background: It is well documented that children with Specific Language Impairment (SLI) experience significant grammatical deficits. While much of the focus in the past has been on their morphosyntactic difficulties, less is known about their acquisition of complex syntactic structures such as relative clauses. The role of memory in language performance has also become increasingly prominent in the literature. Aims: This study aims to investigate the control of an important complex syntactic structure, the relative clause, by school age children with SLI in Ireland, using a newly devised sentence recall task. It also aims to explore the role of verbal and short-termworking memory in the performance of children with SLI on the sentence recall task, using a standardized battery of tests based on Baddeley’s model of working memory. Methods and Procedures: Thirty two children with SLI, thirty two age matched typically developing children (AM-TD) between the ages of 6 and 7,11 years and twenty younger typically developing (YTD) children between 4,7 and 5 years, completed the task. The sentence recall (SR) task included 52 complex sentences and 17 fillers. It included relative clauses that are used in natural discourse and that reflect a developmental hierarchy. The relative clauses were also controlled for length and varied in syntactic complexity, representing the full range of syntactic roles. There were seven different relative clause types attached to either the predicate nominal of a copular clause (Pn), or to the direct object of a transitive clause (Do). Responses were recorded, transcribed and entered into a database for analysis. TheWorkingMemory Test Battery for children (WMTB-C—Pickering & Gathercole, 2001) was administered in order to explore the role of short-term memory and working memory on the children’s performance on the SR task. Outcomes and Results: The children with SLI showed significantly greater difficulty than the AM-TD group and the YTD group. With the exception of the genitive subject clauses, the children with SLI scored significantly higher on all sentences containing a Pn main clause than those containing a transitive main clause. Analysis of error types revealed the frequent production of a different type of relative clause than that presented in the task—with a strong word order preference in the NVN direction indicated for the children with SLI. The SR performance for the children with SLI was most highly correlated with expressive language skills and digit recall. Conclusions and Implications: Children with SLI have significantly greater difficulty with relative clauses than YTD children who are on average two years younger—relative clauses are a delay within a delay. Unlike the YTD children they show a tendency to simplify relative clauses in the noun verb noun (NVN) direction. They show a developmental hierarchy in their production of relative clause constructions and are highly influenced by the frequency distribution of the relative clauses in the ambient language.

The Influence of Gene Environment Interaction on the Risk of Cognitive Impairment: Reducing Sexual Risk Behaviors and Alcohol Use in HIV-infected Adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p