A distributed multi-disciplinary design optimization benchmark test suite with constraints and multiple conflicting objectives

Collaborative optimization (CO) is an architecture within the multi-disciplinary design optimization (MDO) paradigm that partitions a constrained optimization problem into system and subsystem problems, with couplings between them. Multi-objective CO has multiple objectives at the system level and inequality constraints at the subsystem level. Whilst CO is an established technique, there are currently no scalable, constrained benchmark problems for multi-objective CO. In this study, we extend recent methods for generating scalable MDO benchmarks to propose a new benchmark test suite for multi-objective CO that is scalable in disciplines and variables, called `CO-ZDT'. We show that overly-constraining the number of generations in each iteration of the system-level optimizer leads to poor consistency constraint satisfaction. Increasing the number of subsystems in each of the problems leads to increasing system-level constraint violation. In problems with two subsystems, we find that convergence to the global Pareto front is very sensitive to the complexity of the landscape of the original non-decomposed problem. As the number of subsystems increases, convergence issues are encountered even for the simpler problem landscapes

Assignment of disulphide bridges in Par j 2.0101, a major allergen of Parietaria judaica pollen.

Par j 2.0101, a major allergen of the Parietaria judaica pollen, was expressed in E. coli, purified to homogeneity and fully characterised both at the structural and the functional level. The recombinant rPar j 2.0101 protein showed an allergenic activity in histamine release, skin prick tests and capacity to bind IgE, almost identical to that of the native allergens purified from aqueous pollen extract. The complete pattern of S-S bridges of rPar j 2.0101 was determined by enzymatic digestion with endoproteinase Lys-C followed by mass spectrometric analysis of the resulting peptide mixtures. The eight cysteines occurring in the allergenic protein were found to be paired into the following four disulphides: Cys35-Cys83, Cys45-Cys6O, Cys61-Cys106 and Cys81-Cys121. This structural information probes Par j 2.0101 to attain a 3-D fold consistent with that of the non-specific lipid transfer protein (ns-LTP) family and it represents an effective molecular basis to develop modified antigens by selective site-directed mutagenesis for immunotherapy

Proceedings of the First Annual Workshop of the HORIZON 2020 CEBAMA Project (KIT Scientific Reports ; 7734)

The Proceedings of the First Annual Workshop of the Collaborative Project CEBAMA addresses key scientific questions related to the use of cement-based materials in nuclear waste disposal applications. Progress beyond the state-of-the-art is achieved by providing basic knowledge, new experimental data, improved modeling and arguments for the Nuclear Waste Disposal Safety Case. CEBAMA is funded by the European Commission under the Horizon 2020 frame of EURATOM

Electrophoresis of proteins and DNA on horizontal sodium dodecyl sulfate polyacrylamide gels

An inexpensive Plexiglas apparatus which allows a simple and rapid preparation of horizontal polyacrylamide gels of different dimensions for different purposes, is described. Preparation of such gels is as easy and rapid as agarose gel preparation, and polymerized polyacrylamide gels are used to fractionate proteins or small DNA fragments using a common horizontal electrophoretic tank. This apparatus was used to electrophoretically fractionate proteins or DNA for immuno-blot analyses, particularirly in the study of the allergenic response to Parietaria judaica pollen in senescence, for Southern-blot hybridizations and in the study of DNA polymorphisms

Inter-familial and intra-familial phenotypic variability in three Sicilian families with Anderson-Fabry disease.

Abstract BACKGROUND: Anderson-Fabry disease (AFD) is an inborn lysosomal enzymopathy resulting from the deficient or absent activity of the lysosomal exogalactohydrolase, α-galactosidase A. This deficiency, results in the altered metabolism of glycosphingolipids which leads to their accumulation in lysosomes, thus to cellular and vascular dysfunction. To date, numerous mutations (according to recent data more than 1000 mutations) have been reported in the GLA intronic and exonic mutations. Traditionally, clinical manifestations are more severe in affected hemizygous males than in females. Nevertheless, recent studies have described severe organ dysfunction in women. THE AIM OF THE STUDY: This study reports clinical, biochemical, and molecular findings of the members of three Sicilian families. The clinical history of these patients highlights a remarkable interfamilial and intrafamilial phenotypic variability which characterizes Fabry disease relative to target organs and severity of clinical manifestations. DISCUSSION: Our findings, in agreement with previous data, report a little genotype-phenotype correlation for the disease, suggesting that the wide phenotypic variability of Anderson-Fabry disease is not completely ascribable to different gene mutations but other factors and mechanisms seem to be involved in the pathogenesis and clinical expression of the disease. Moreover, this study emphasies the importance of pedigree analysis in the family of each proband for identifying other possibly affected relatives

Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

Alzheimer’s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment. Copyrigh

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

Development of the Critical Thinking Toolkit (CriTT): a measure of student attitudes and beliefs about critical thinking

Critical thinking is an important focus in higher education and is essential for good academic achievement. We report the development of a tool to measure critical thinking for three purposes: (i) to evaluate student perceptions and attitudes about critical thinking, (ii) to identify students in need of support to develop their critical thinking, and (iii) to predict academic performance. Seventy-seven items were generated from focus groups, interviews and the critical thinking literature. Data were collected from 133 psychology students. Factor Analysis revealed three latent factors based on a reduced set of 27 items. These factors were characterised as: Confidence in Critical Thinking; Valuing Critical Thinking; and Misconceptions. Reliability analysis demonstrated that the sub-scales were reliable. Convergent validity with measures of grade point average and argumentation skill was shown, with significant correlations between subscales and validation measures. Most notably, in multiple regression analysis, the three sub-scales from the new questionnaire substantially increased the variance in grade point average accounted for by measures of reflective thinking and argumentation. To sum, the resultant scale offers a measure that is simple to administer, can be used as a diagnostic tool to identify students who need support in developing their critical thinking skills, and can also predict academic performance