Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames.

Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around the clock and at high temporal and nucleotide resolution. We discovered, transcriptome-wide, extensive rhythms in ribosome occupancy and identified a core set of approximately 150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from nonoscillating transcripts revealed thus-far-unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of reinitiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ.

Epilepsy priorities in Europe: A report of the ILAE-IBE Epilepsy Advocacy Europe Task Force.

The European Forum on Epilepsy Research (ERF2013), which took place in Dublin, Ireland, on May 26-29, 2013, was designed to appraise epilepsy research priorities in Europe through consultation with clinical and basic scientists as well as representatives of lay organizations and health care providers. The ultimate goal was to provide a platform to improve the lives of persons with epilepsy by influencing the political agenda of the EU. The Forum highlighted the epidemiologic, medical, and social importance of epilepsy in Europe, and addressed three separate but closely related concepts. First, possibilities were explored as to how the stigma and social burden associated with epilepsy could be reduced through targeted initiatives at EU national and regional levels. Second, ways to ensure optimal standards of care throughout Europe were specifically discussed. Finally, a need for further funding in epilepsy research within the European Horizon 2020 funding programme was communicated to politicians and policymakers participating to the forum. Research topics discussed specifically included (1) epilepsy in the developing brain; (2) novel targets for innovative diagnostics and treatment of epilepsy; (3) what is required for prevention and cure of epilepsy; and (4) epilepsy and comorbidities, with a special focus on aging and mental health. This report provides a summary of recommendations that emerged at ERF2013 about how to (1) strengthen epilepsy research, (2) reduce the treatment gap, and (3) reduce the burden and stigma associated with epilepsy. Half of the 6 million European citizens with epilepsy feel stigmatized and experience social exclusion, stressing the need for funding trans-European awareness campaigns and monitoring their impact on stigma, in line with the global commitment of the European Commission and with the recommendations made in the 2011 Written Declaration on Epilepsy. Epilepsy care has high rates of misdiagnosis and considerable variability in organization and quality across European countries, translating into huge societal cost (0.2% GDP) and stressing the need for cost-effective programs of harmonization and optimization of epilepsy care throughout Europe. There is currently no cure or prevention for epilepsy, and 30% of affected persons are not controlled by current treatments, stressing the need for pursuing research efforts in the field within Horizon 2020. Priorities should include (1) development of innovative biomarkers and therapeutic targets and strategies, from gene and cell-based therapies to technologically advanced surgical treatment; (2) addressing issues raised by pediatric and aging populations, as well as by specific etiologies and comorbidities such as traumatic brain injury (TBI) and cognitive dysfunction, toward more personalized medicine and prevention; and (3) translational studies and clinical trials built upon well-established European consortia.

The impact of adopting a CLIL approach on EFL learners reading skills in Catalonia school

En els últims anys, un gran nombre de docents i escoles han estat introduint programes AICLE a les escoles catalanes. A la majoria d’escoles, però, només s'ensenya anglès com a llengua estrangera, la qual cosa, limita les oportunitats d'estar en contacte amb la llengua estrangera en un context diferent. L’objectiu d'aquest estudi és analitzar si els infants milloren en les seves habilitats lectores i comprovar si existeix un avantatge significatiu respecte els alumnes que només estudien anglès com a llengua estrangera. L’estudi empíric que us presento a continuació, compara els resultats obtinguts en dues proves de comprensió lectora. A les proves hi van participar dos grups d’alumnes de cinquè de d’Educació Primària. Un dels grups seguia un programa AICLE (1 hora a la setmana i , a més aprenia anglès coma llengua estrangera); l’altre grup només estudiava anglès com a llengua estrangera. L'objectiu principal d'aquest projecte d'investigació és esbrinar si els programes AICLE tenen un impacte en les habilitats lectores en llengua anglesa dels alumnes. Així doncs, humilment intentaré contribuir a la literatura existent sobre els beneficis de l’AICLE.

Connectivity and tissue microstructural alterations in right and left temporal lobe epilepsy revealed by diffusion spectrum imaging.

Focal epilepsy is increasingly recognized as the result of an altered brain network, both on the structural and functional levels and the characterization of these widespread brain alterations is crucial for our understanding of the clinical manifestation of seizure and cognitive deficits as well as for the management of candidates to epilepsy surgery. Tractography based on Diffusion Tensor Imaging allows non-invasive mapping of white matter tracts in vivo. Recently, diffusion spectrum imaging (DSI), based on an increased number of diffusion directions and intensities, has improved the sensitivity of tractography, notably with respect to the problem of fiber crossing and recent developments allow acquisition times compatible with clinical application. We used DSI and parcellation of the gray matter in regions of interest to build whole-brain connectivity matrices describing the mutual connections between cortical and subcortical regions in patients with focal epilepsy and healthy controls. In addition, the high angular and radial resolution of DSI allowed us to evaluate also some of the biophysical compartment models, to better understand the cause of the changes in diffusion anisotropy. Global connectivity, hub architecture and regional connectivity patterns were altered in TLE patients and showed different characteristics in RTLE vs LTLE with stronger abnormalities in RTLE. The microstructural analysis suggested that disturbed axonal density contributed more than fiber orientation to the connectivity changes affecting the temporal lobes whereas fiber orientation changes were more involved in extratemporal lobe changes. Our study provides further structural evidence that RTLE and LTLE are not symmetrical entities and DSI-based imaging could help investigate the microstructural correlate of these imaging abnormalities.

A new method for intraoperative localization of epilepsy focus by means of a gamma probe

Objective To evaluate the utility of a new multimodal image-guided intervention technique to detect epileptogenic areas with a gamma probe as compared with intraoperative electrocorticography. Materials and Methods Two symptomatic patients with refractory epilepsy underwent magnetic resonance imaging, videoelectroencephalography, brain SPECT scan, neuropsychological evaluation and were submitted to gamma probe-assisted surgery. Results In patient 1, maximum radioactive count was initially observed on the temporal gyrus at about 3.5 cm posteriorly to the tip of the left temporal lobe. After corticotomy, the gamma probe indicated maximum count at the head of the hippocampus, in agreement with the findings of intraoperative electrocorticography. In patient 2, maximum count was observed in the occipital region at the transition between the temporal and parietal lobes (right hemisphere). During the surgery, the area of epileptogenic activity mapped at electrocorticography was also delimited, demarcated, and compared with the gamma probe findings. After lesionectomy, new radioactive counts were performed both in the patients and on the surgical specimens (ex-vivo). Conclusion The comparison between intraoperative electrocorticography and gamma probe-assisted surgery showed similarity of both methods. The advantages of gamma probe include: noninvasiveness, low cost and capacity to demonstrate decrease in the radioactive activity at the site of excision after lesionectomy.

Automatic meter reading – benefits and applications

In liberalized electricity markets, which have taken place in many countries over the world, the electricity distribution companies operate in the competitive conditions. Therefore, accurate information about the customers’ energy consumption plays an essential role for the budget keeping of the distribution company and for correct planning and operation of the distribution network. This master’s thesis is focused on the description of the possible benefits for the electric utilities and residential customers from the automatic meter reading system usage. Major benefits of the AMR, illustrated in the thesis, are distribution network management, power quality monitoring, load modelling, and detection of the illegal usage of the electricity. By the example of the power system state estimation, it was illustrated that even the partial installation of the AMR in the customer side leads to more accurate data about the voltage and power levels in the whole network. The thesis also contains the description of the present situation of the AMR integration in Russia.

Patriarchal hauntings : re-reading villainy and gender in Daphne du Maurier’s 'Rebecca'

Daphne du Maurier’s popular classic Rebecca (1938) was traditionally marketed as a Gothic romance in which two lovers conquered the evil women that separated them. In more recent years, some feminist critics have provided a very different view of the story as a Gothic narrative about the dangers women suffer under patriarchal control. In this thesis, I propose, through a Gothic Studies and a Gender Studies reading, that the victim/abuser statuses in du Maurier’s novel cannot be equated to femininity and masculinity, respectively. Instead, I argue that villainy in Rebecca comes from being in a powerful position within patriarchy—a position that is occupied by both male and female characters

Utilization of Automatic Meter Reading in the Improvement of a District Heating System

A district heating system comprises production facilities, a distribution network, and heat consumers. The utilization of new energy metering and reading system (AMR) is increasing constantly in district heating systems. This heuristic study shows how the AMR system can be exploited in finding optimization opportunities in district heating system. In this study, the district heating system is mainly considered from the viewpoint of operational optimization. The focus is on the core processes, heat production and distribution. Three objectives were set to this study. The first one was to examine general optimization opportunities in district heating systems. Second, to figure out the benefits of AMR for general optimization opportunities. Finally, to define a methodology for process improvement endeavors. This study shows, through a case study, the usefulness of AMR in specifying current deficiencies in a district heating system. Based on a literature review, the methodology for the improvement of business processes is presented. Additionally, some issues related to future competitiveness of district heating are concerned. As a conclusion, some optimization objectives are considered more desirable than others. Study shows that AMR is useful in the specification of optimization targets in the district heating system. Further steps in optimization process were not examined in detail. That would seem to be interesting topic for further studies.

Reading Development During Elementary School Years. Evidence from Eye Movements

The present dissertation examined reading development during elementary school years by means of eye movement tracking. Three different but related issues in this field were assessed. First of all, the development of parafoveal processing skills in reading was investigated. Second, it was assessed whether and to what extent sublexical units such as syllables and morphemes are used in processing Finnish words and whether the use of these sublexical units changes as a function of reading proficiency. Finally, the developmental trend in the speed of visual information extraction during reading was examined. With regard to parafoveal processing skills, it was shown that 2nd graders extract letter identity information approx. 5 characters to the right of fixation, 4th graders approx. 7 characters to the right of fixation, and 6th graders and adults approx. 9 characters to the right of fixation. Furthermore, it was shown that all age groups extract more parafoveal information within compound words than across adjectivenoun pairs of similar length. In compounds, parafoveal word information can be extracted in parallel with foveal word information, if the compound in question is of high frequency. With regard to the use of sublexical units in Finnish word processing, it was shown that less proficient 2nd graders use both syllables and morphemes in the course of lexical access. More proficient 2nd graders as well as older readers seem to process words more holistically. Finally, it was shown that 60 ms is enough for 4th graders and adults to extract visual information from both 4-letter and 8-letter words, whereas 2nd graders clearly needed more than 60 ms to extract all information from 8- letter words for processing to proceed smoothly. The present dissertation demonstrates that Finnish 2nd graders develop their reading skills rapidly and are already at an adult level in some aspects of reading. This is not to say that there are no differences between less proficient (e.g., 2nd graders) and more proficient readers (e.g., adults) but in some respects it seems that the visual system used in extracting information from the text is matured by the 2nd grade. Furthermore, the present dissertation demonstrates that the allocation of attention in reading depends much on textual properties such as word frequency and whether words are spatially unified (as in compounds) or not. This flexibility of the attentional system naturally needs to be captured in word processing models. Finally, individual differences within age groups are quite substantial but it seems that by the end of the 2nd grade practically all Finnish children have reached a reasonable level of reading proficiency.

Identifying first graders at risk of reading and writing difficulties : creating a group-based screening tool in kiswahili in Tanzania

Early identification of beginning readers at risk of developing reading and writing difficulties plays an important role in the prevention and provision of appropriate intervention. In Tanzania, as in other countries, there are children in schools who are at risk of developing reading and writing difficulties. Many of these children complete school without being identified and without proper and relevant support. The main language in Tanzania is Kiswahili, a transparent language. Contextually relevant, reliable and valid instruments of identification are needed in Tanzanian schools. This study aimed at the construction and validation of a group-based screening instrument in the Kiswahili language for identifying beginning readers at risk of reading and writing difficulties. In studying the function of the test there was special interest in analyzing the explanatory power of certain contextual factors related to the home and school. Halfway through grade one, 337 children from four purposively selected primary schools in Morogoro municipality were screened with a group test consisting of 7 subscales measuring phonological awareness, word and letter knowledge and spelling. A questionnaire about background factors and the home and school environments related to literacy was also used. The schools were chosen based on performance status (i.e. high, good, average and low performing schools) in order to include variation. For validation, 64 children were chosen from the original sample to take an individual test measuring nonsense word reading, word reading, actual text reading, one-minute reading and writing. School marks from grade one and a follow-up test half way through grade two were also used for validation. The correlations between the results from the group test and the three measures used for validation were very high (.83-.95). Content validity of the group test was established by using items drawn from authorized text books for reading in grade one. Construct validity was analyzed through item analysis and principal component analysis. The difficulty level of most items in both the group test and the follow-up test was good. The items also discriminated well. Principal component analysis revealed one powerful latent dimension (initial literacy factor), accounting for 93% of the variance. This implies that it could be possible to use any set of the subtests of the group test for screening and prediction. The K-Means cluster analysis revealed four clusters: at-risk children, strugglers, readers and good readers. The main concern in this study was with the groups of at-risk children (24%) and strugglers (22%), who need the most assistance. The predictive validity of the group test was analyzed by correlating the measures from the two school years and by cross tabulating grade one and grade two clusters. All the correlations were positive and very high, and 94% of the at-risk children in grade two were already identified in the group test in grade one. The explanatory power of some of the home and school factors was very strong. The number of books at home accounted for 38% of the variance in reading and writing ability measured by the group test. Parents´ reading ability and the support children received at home for schoolwork were also influential factors. Among the studied school factors school attendance had the strongest explanatory power, accounting for 21% of the variance in reading and writing ability. Having been in nursery school was also of importance. Based on the findings in the study a short version of the group test was created. It is suggested for use in the screening processes in grade one aiming at identifying children at risk of reading and writing difficulties in the Tanzanian context. Suggestions for further research as well as for actions for improving the literacy skills of Tanzanian children are presented.

The effectiveness of short-term literacy skills intervention on children at risk of reading and writing difficulties in Tanzania : a study of grade one children with dynamic assessment approach

The aim of the study was to create and evaluate an intervention programme for Tanzanian children from a low-income area who are at risk of reading and writing difficulties. The learning difficulties, including reading and writing difficulties, are likely to be behind many of the common school problems in Tanzania, but they are not well understood, and research is needed. The design of the study included an identification and intervention phase with follow-up. A group based dynamic assessment approach was used in identifying children at risk of difficulties in reading and writing. The same approach was used in the intervention. The study was a randomized experiment with one experimental and two control groups. For the experimental and the control groups, a total of 96 (46 girls and 50 boys) children from grade one were screened out of 301 children from two schools in a low income urban area of Dar-es-Salaam. One third of the children, the experimental group, participated in an intensive training programme in literacy skills for five weeks, six hours per week, aimed at promoting reading and writing ability, while the children in the control groups had a mathematics and art programme. Follow-up was performed five months after the intervention. The intervention programme and the tests were based on the Zambian BASAT (Basic Skill Assessment Tool, Ketonen & Mulenga, 2003), but the content was drawn from the Kiswahili school curriculum in Tanzania. The main components of the training and testing programme were the same, only differing in content. The training process was different from traditional training in Tanzanian schools in that principles of teaching and training in dynamic assessment were followed. Feedback was the cornerstone of the training and the focus was on supporting the children in exploring knowledge and strategies in performing the tasks. The experimental group improved significantly more (p = .000) than the control groups during the intervention from pre-test to follow-up (repeated measures ANOVA). No differences between the control groups were noticed. The effect was significant on all the measures: phonological awareness, reading skills, writing skills and overall literacy skills. A transfer effect on school marks in Kiswahili and English was found. Following a discussion of the results, suggestions for further research and adaptation of the programme are presented.

Witness is presence : reading Stanley Hauerwas in a Nordic setting

I en postsekulär situation har förutsättningarna för att förstå och kommunicera en kristen tradition förändrats. De etablerade religionerna kan inte längre anta att de har monopol på den ”religiösa marknaden”. Ett centralt påstående i denna studie är att en postsekulär situation, som kännetecknas av minskande medlemskap i etablerade kyrkor och en ny synlighet av alternativa religiösa uttryck, medför ett behov av att reflektera över alternativa förståelser av kristenheten i sin kontext. Denna studie frågar hur man kan meningsfullt kommunicera en kristen tradition i en postsekulär situation. Traditionellt uttryckt: hur kan man förstå kristet vittnesbörd i vår situation? Det är till denna problematik som denna studie hävdar att Stanley Hauerwas ecklesiologi tillför ett viktigt perspektiv. Hauerwas ses som ett kritiskt korrektiv till vissa synsätt som ofta möter hos Nordiska, i denna studie främst finska och svenska, lutherska teologer. Det perspektiv som utvecklas i denna studie anses vara relevant eftersom kristna kyrkor i en postsekulär situation inte längre kan anta en makt- eller majoritetsposition. Därmed uppstår ett behov av att fråga sig hur man kan förstå kristenhet som en gemenskap i en minoritetsposition som bär vittnesbörd utan samhällelig makt. Denna studie hävdar att förkroppsligande av kristna övertygelser intar en central roll i en meningsfull postsekulär förståelse av vittnesbörd.