Dynamic association with donor cell filopodia and lipid-modification are essential features of Wnt8a during patterning of the zebrafish neuroectoderm

BACKGROUND: Wnt proteins are conserved signaling molecules that regulate pattern formation during animal development. Many Wnt proteins are post-translationally modified by addition of lipid adducts. Wnt8a provides a crucial signal for patterning the anteroposterior axis of the developing neural plate in vertebrates. However, it is not clear how this protein propagates from its source, the blastoderm margin, to the target cells in the prospective neural plate, and how lipid-modifications might influence Wnt8a propagation and activity. RESULTS: We have dynamically imaged biologically active, fluorescently tagged Wnt8a in living zebrafish embryos. We find that Wnt8a localizes to membrane-associated, punctate structures in live tissue. In Wnt8a expressing cells, these puncta are found on filopodial cellular processes, from where the protein can be released. In addition, Wnt8a is found colocalized with Frizzled receptor-containing clusters on signal receiving cells. Combining in vitro and in vivo assays, we compare the roles of conserved Wnt8a residues in cell and non-cell-autonomous signaling activity and secretion. Non-signaling Wnt8 variants show these residues can regulate Wnt8a distribution in producing cell membranes and filopodia as well as in the receiving tissue. CONCLUSIONS: Together, our results show that Wnt8a forms dynamic clusters found on filopodial donor cell and on signal receiving cell membranes. Moreover, they demonstrate a differential requirement of conserved residues in Wnt8a protein for distribution in producing cells and receiving tissue and signaling activity during neuroectoderm patterning

Novel 3D Pixel Sensors for the Upgrade of the ATLAS Inner Tracker

The ATLAS experiment will undergo a full replacement of its inner detector to face the challenges posed by the High Luminosity upgrade of the Large Hadron Collider (HL-LHC). The new Inner Tracker (ITk) will have to deal with extreme particle fluences. Due to its superior radiation hardness the 3D silicon sensor technology has been chosen to instrument the innermost pixel layer of ITk, which is the most exposed to radiation damage. Three foundries (CNM, FBK, and SINTEF), have developed and fabricated novel 3D pixel sensors to meet the specifications of the new ITk pixel detector. These are produced in a single-side technology on either Silicon On Insulator (SOI) or Silicon on Silicon (Si-on-Si) bonded wafers by etching both n- and p-type columns from the same side. With respect to previous generations of 3D sensors they feature thinner active substrates and smaller pixel cells of 50 × 50 and 25 × 100 µm2. This paper reviews the main design and technological issues of these novel 3D sensors, and presents their characterization before and after exposure to large radiation doses close to the one expected for the innermost layer of ITk. The performance of pixel modules, where the sensors are interconnected to the recently developed RD53A chip prototype for HL-LHC, has been investigated in the laboratory and at beam tests. The results of these measurements demonstrate the excellent radiation hardness of this new generation of 3D pixel sensors that enabled the project to proceed with the pre-production for the ITk tracker.publishedVersio

High through-put sequencing of the Parhyale hawaiensis mRNAs and microRNAs to aid comparative developmental studies

Understanding the genetic and evolutionary basis of animal morphological diversity will require comparative developmental studies that use new model organisms. This necessitates development of tools for the study of genetics and also the generation of sequence information of the organism to be studied. The development of next generation sequencing technology has enabled quick and cost effective generation of sequence information. Parhyale hawaiensis has emerged as a model organism of choice due to the development of advanced molecular tools, thus P. hawaiensis genetic information will help drive functional studies in this organism. Here we present a transcriptome and miRNA collection generated using next generation sequencing platforms. We generated approximately 1.7 million reads from a P. hawaiensis cDNA library constructed from embryos up to the germ band stage. These reads were assembled into a dataset comprising 163,501 transcripts. Using the combined annotation of Annot8r and pfam2go, Gene Ontology classifications was assigned to 20,597 transcripts. Annot8r was used to provide KEGG orthology to our transcript dataset. A total of 25,292 KEGG pathway assignments were defined and further confirmed with reciprocal blast against the NCBI nr protein database. This has identified many P. hawaiensis gene orthologs of key conserved signalling pathways involved in development. We also generated small RNA sequences from P. hawaiensis, identifying 55 conserved miRNAs. Sequenced small RNAs that were not annotated by stringent comparison to mirBase were used to search the Daphnia pulex for possible novel miRNAs. Using a conservative approach, we have identified 51 possible miRNA candidates conserved in the Daphnia pulex genome, which could be potential crustacean/arthropod specific miRNAs. Our study presents gene and miRNA discovery in a new model organism that does not have a sequenced genome. The data provided by our work will be valuable for the P. hawaiensis community as well as the wider evolutionary developmental biology community

Data from an International Multi-Centre Study of Statistics and Mathematics Anxieties and Related Variables in University Students (the SMARVUS Dataset)

This large, international dataset contains survey responses from N = 12,570 students from 100 universities in 35 countries, collected in 21 languages. We measured anxieties (statistics, mathematics, test, trait, social interaction, performance, creativity, intolerance of uncertainty, and fear of negative evaluation), self-efficacy, persistence, and the cognitive reflection test, and collected demographics, previous mathematics grades, self-reported and official statistics grades, and statistics module details. Data reuse potential is broad, including testing links between anxieties and statistics/mathematics education factors, and examining instruments’ psychometric properties across different languages and contexts. Data and metadata are stored on the Open Science Framework website [https://osf.io/mhg94/]

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Measurement of associated W plus charm production in pp collisions at √s=7 TeV

Peer reviewe

Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer

To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L−1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4°C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature