Burden of genetic risk variants in multiple sclerosis families in the Netherlands

Background: Approximately 20% of multiple sclerosis patients have a family history of multiple sclerosis. Studies of multiple sclerosis aggregation in families are inconclusive. Objective: To investigate the genetic burden based on currently discovered genetic variants for multiple sclerosis risk in patients from Dutch multiple sclerosis multiplex families versus sporadic multiple sclerosis cases, and to study its influence on clinical phenotype and disease prediction. Methods: Our study population consisted of 283 sporadic multiple sclerosis cases, 169 probands from multiplex families and 2028 controls. A weighted genetic risk score based on 102 non-human leukocyte antigen loci and HLA-DRB1*1501 was calculated. Results: The weighted genetic risk score based on all loci was significantly higher in familial than in sporadic cases. The HLA-DRB1*1501 contributed significantly to the difference in genetic burden between the groups. A high weighted genetic risk score was significantly associated with a low age of disease onset in all multiple sclerosis patients, but not in the familial cases separately. The genetic risk score was significantly but modestly better in discriminating familial versus sporadic multiple sclerosis from controls. Conclusion: Familial multiple sclerosis patients are more loaded with the common genetic variants than sporadic cases. The difference is mainly driven by HLA-DRB1*1501. The predictive capacity of genetic loci is poor and unlikely to be useful in clinical settings.</p

TEGGHESAN MACAPAT LAYANG JATISWARA PADA UPACARA NYADH�R KETIGA DESA PINGGIR PAPAS SUMENEP (KAJIAN TRADISI LISAN ALBERT B. LORD)

A research �The Tegghesan Layang Jatiswara Macapat in the Third Nyadhâr Ceremony at Pinggir Papas Village, Sumenep� is based on conservation and transformation of religious and social values contained in the oral tradition. Oral tradition is a means of communication and expression language of society that can be used to express and project the people for a certain time. The theory used in this study is the oral tradition theory of Albert B. Lord that describes some aspects of the creation of the oral tradition: 1) Formula and formulaic expression. Formula is a group of words that are regularly used in similar dimension to reveal certain basic ideas. Formulaic expression is the parts or array half prepared in accordance with the formula pattern. 2) The theme or group of ideas, are events or scenes that repeated and contained the descriptive passages in the narration. 3) Inheritance or transmission procedures. Therefore, the objective of this study is to describe tokang tegghes, their process and the factors related to tokang tegghes in performing tegghesan. It consists of: 1) Formulas and formulaic expressions of tegghesan that tokang tegghes have said. 2) The pattern of inheritance or the way (of) for someone being tokang tegghes. 3) The theme or main idea contained in the Layang Jatiswara that have sing in macapatan at nyadhâr ceremony. The result of the study leads to the conclusion: 1) the inherent regulation to be tokang tegghes. The candidate of tokang tegghes is demanded to have the capability of: a) understanding of the song (tembang), b) conceiving of the Java language vocabularies, c) getting right of the storyline, and d) having a good personality and a mature age. Whereas the theme is often repeated in macapat nyadar is Jatiswara travel story in seeking of the truth meaning of life. In performing tegghesan, tokang tegghes utilize the phrases, clauses, and sentence that become formulas and formulaic expressions, such as: a) repetition of the end line in tegghesan, b) repetition of all or part tegghesan, c) description of figure and his honour, d) adding of the word 'èngghi ka'�into', e) adding of of the word 'ka'�into', f) adding of the word panotèng 'èpon'

Grain Protectant Potential of Annona muricata and A. senegalensis against Cowpea Seed Bruchid Callosobruchus maculatus Fab. (Coleoptera: Bruchidae)

Annona muricata and Annona senegalensis powders were evaluated for their insecticidal potency against adult Callosobruchus maculatus. Toxicity test was conducted by contact bioassay at different concentrations of the treatment plants viz: 0.0 g, 0.5 g, 1.0 g, 2.0 g and 3.0 g was tested as well as their anti-ovipository activities, adult F1 progeny emergence suppression activities and anti-feedant activities which possibly result in the grain’ weight loss and grain damage was also tested. The results revealed that the treatment plants at all concentrations showed a significant (P&gt;0.05) insecticidal potency, by recording higher mortality rates, suppression of egg laying and adult emergence, and reduced weight loss as well as grain damage when compared with the untreated control. The root bark of A. senegalensis at 3.0 g powder per 20 g grain had the higher mortality rate (98.5). The leaf and root bark powder of A. muricata at 3.0 g reduced oviposition minimum (1.4 respectively); leaf powder of A. muricata at 3.0 g powder per 20 g grain also reduced F1 generation emergence minimum (9.3) and root bark powder of A. muricata at 3.0 grams w/w reduced grain damage minimum (0.7). The results revealed that A. muricata at 3.0 g powder per &nbsp;&nbsp;20 g grain for the leaf and root bark powders to be more effective in controlling C. maculatus than A. senegalensis. Therefore, it is recommended that farmers should put the practice of using Annona species, especially, A. muricata as an alternative to the dangerous and highly persistent chemical insecticides in the control of C. maculatus on stored cowpea

Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles

Contains fulltext : 182484.pdf (publisher's version ) (Open Access)Enteroviruses reorganize cellular endomembranes into replication organelles (ROs) for genome replication. Although enterovirus replication depends on phosphatidylinositol 4-kinase type IIIbeta (PI4KB), its role, and that of its product, phosphatidylinositol 4-phosphate (PI4P), is only partially understood. Exploiting a mutant coxsackievirus resistant to PI4KB inhibition, we show that PI4KB activity has distinct functions both in proteolytic processing of the viral polyprotein and in RO biogenesis. The escape mutation rectifies a proteolytic processing defect imposed by PI4KB inhibition, pointing to a possible escape mechanism. Remarkably, under PI4KB inhibition, the mutant virus could replicate its genome in the absence of ROs, using instead the Golgi apparatus. This impaired RO biogenesis provided an opportunity to investigate the proposed role of ROs in shielding enteroviral RNA from cellular sensors. Neither accelerated sensing of viral RNA nor enhanced innate immune responses was observed. Together, our findings challenge the notion that ROs are indispensable for enterovirus genome replication and immune evasion

Turbine Design and Optimization for a Supercritical CO2 Cycle Using a Multifaceted Approach Based on Deep Neural Network

Turbine as a key power unit is vital to the novel supercritical carbon dioxide cycle (sCO2-BC). At the same time, the turbine design and optimization process for the sCO2-BC is complicated, and its relevant investigations are still absent in the literature due to the behavior of supercritical fluid in the vicinity of the critical point. In this regard, the current study entails a multifaceted approach for designing and optimizing a radial turbine system for an 8 MW sCO2 power cycle. Initially, a base design of the turbine is calculated utilizing an in-house radial turbine design and analysis code (RTDC), where sharp variations in the properties of CO2 are implemented by coupling the code with NIST&rsquo;s Refprop. Later, 600 variants of the base geometry of the turbine are constructed by changing the selected turbine design geometric parameters, i.e., shroud ratio (rs4r3), hub ratio (rs4r3), speed ratio (&nu;s) and inlet flow angle (&alpha;3) and are investigated numerically through 3D-RANS simulations. The generated CFD data is then used to train a deep neural network (DNN). Finally, the trained DNN model is employed as a fitting function in the multi-objective genetic algorithm (MOGA) to explore the optimized design parameters for the turbine&rsquo;s rotor geometry. Moreover, the off-design performance of the optimized turbine geometry is computed and reported in the current study. Results suggest that the employed multifaceted approach reduces computational time and resources significantly and is required to completely understand the effects of various turbine design parameters on its performance and sizing. It is found that sCO2-turbine performance parameters are most sensitive to the design parameter speed ratio (&nu;s), followed by inlet flow angle (&alpha;3), and are least receptive to shroud ratio (rs4r3). The proposed turbine design methodology based on the machine learning algorithm is effective and substantially reduces the computational cost of the design and optimization phase and can be beneficial to achieve realistic and efficient design to the turbine for sCO2-BC