Inherited susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes

Background: Susceptibility to bleomycin-induced chromatid breaks in cultured peripheral blood lymphocytes may reflect the way a person deals with carcinogenic challenges. This susceptibility (also referred to as mutagen sensitivity) has been found to be increased in patients with environmentally related cancers, including cancers of the head and neck, lung, and colon, and, in combination with carcinogenic exposure, this susceptibility can greatly influence cancer risk. The purpose of this study was to assess the heritability of mutagen sensitivity. Methods: Heritability was determined by use of a maximum likelihood method that employed the FISHER package of pedigree analysis. Bleomycin-induced breaks per cell values for 135 healthy volunteers without cancer were determined. These individuals were from 53 different pedigrees and included 25 monozygotic twin pairs (n = 50), 14 pairs of dizygotes (twin pairs and siblings, n = 28), and 14 families selected on the basis of a first-degree relative who was successfully treated for head and neck cancer and who had no sign of recurrence for at least 1 year. All data were analyzed simultaneously, and different models of familial resemblance were fitted to the data. All P values are two-sided. Results: Our results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks. Genetic influences, however, were statistically significant (P = .036) and accounted for 75% of the total variance. Conclusions: The high heritability estimate of the susceptibility to bleomycin-induced chromatid breaks indicates a clear genetic basis. The findings of this study support the notion that a common genetic susceptibility to DNA damage - and thereby a susceptibility to cancer - may exist in the general population

Long-term research challenges in wind energy – a research agenda by the European Academy of Wind Energy

The European Academy of Wind Energy (eawe), representing universities and institutes with a significant wind energy programme in 14 countries, has discussed the long-term research challenges in wind energy. In contrast to research agendas addressing short- to medium-term research activities, this eawe document takes a longer-term perspective, addressing the scientific knowledge base that is required to develop wind energy beyond the applications of today and tomorrow. In other words, this long-term research agenda is driven by problems and curiosity, addressing basic research and fundamental knowledge in 11 research areas, ranging from physics and design to environmental and societal aspects. Because of the very nature of this initiative, this document does not intend to be permanent or complete. It shows the vision of the experts of the eawe, but other views may be possible. We sincerely hope that it will spur an even more intensive discussion worldwide within the wind energy community

SUSTAINABLE DEVELOPMENT AND THE PROCESS OF JUSTIFYING CHOICES IN A CONTROVERSIAL UNIVERSE

All in all, neither the path of the generic principle nor that of the reduction to existing principles would appear to be fully satisfactory as the basis for establishing the legitimacy of sustainable development or as a way of making sustainability a principle of legitimacy by its own. We should probably resign ourselves to seeing in this idea a composite construction, still striving towards the formation of a new "superior common principle", without this principle yet being able to be completely clarified and validated. What we have here is an example of the sort of "compromise" described by Boltanski and Thévenot (1991, p.338): "In the compromise, the participants abandon the idea of clarifying the principle of their agreement but endeavour to maintain a frame of mind aiming at the common good." If we want to consolidate the compromise developing around sustainability, it would be well advised to seek the support of tests using well-formed objects. To this end, steps should be taken to move the emphasis away from long-term and unknowable sustainability requirements and closer to secondbest criteria focused on the transitional developments and possible risks of intentional human action, the ways of managing the linking of the different temporalities in play -- as regards the biophysical phenomena, their understanding and the main worlds of legitimacy (Godard, 1992) -- and the introduction of deliberation within the present generations as to what they feel best describes their identity, those things they would like to pass on

Mixed integer programming in production planning with backlogging and setup carryover : modeling and algorithms

This paper proposes a mixed integer programming formulation for modeling the capacitated multi-level lot sizing problem with both backlogging and setup carryover. Based on the model formulation, a progressive time-oriented decomposition heuristic framework is then proposed, where improvement and construction heuristics are effectively combined, therefore efficiently avoiding the weaknesses associated with the one-time decisions made by other classical time-oriented decomposition algorithms. Computational results show that the proposed optimization framework provides competitive solutions within a reasonable time

Analysis of FUS, PFN2, TDP-43, and PLS3 as potential disease severity modifiers in spinal muscular atrophy

Objective To investigate mutations in genes that are potential modifiers of spinal muscular atrophy (SMA) severity. Methods We performed a hypothesis-based search into the presence of variants in fused in sarcoma (FUS), transactive response DNA-binding protein 43 (TDP-43), plastin 3 (PLS3), and profilin 2 (PFN2) in a cohort of 153 patients with SMA types 1-4, including 19 families. Variants were detected with targeted next-generation sequencing and confirmed with Sanger sequencing. Functional effects of the identified variants were analyzed in silico and for PLS3, by analyzing expression levels in peripheral blood. Results We identified 2 exonic variants in FUS exons 5 and 6 (p.R216C and p.S135N) in 2 unrelated patients, but clinical effects were not evident. We identified 8 intronic variants in PLS3 in 33 patients. Five PLS3 variants (c.1511+82T>C; c.748+130 G>A; c.367+182C>T; c.891-25T>C (rs145269469); c.1355+17A>G (rs150802596)) potentially alter exonic splice silencer or exonic splice enhancer sites. The variant c.367+182C>T, but not RNA expression levels, corresponded with a more severe phenotype in 1 family. However, this variant or level of PLS3 expression did not consistently correspond with a milder or more severe phenotype in other families or the overall cohort. We found 3 heterozygous, intronic variants in PFN2 and TDP-43 with no correlation with clinical phenotype or effects on splicing. Conclusions PLS3 and FUS sequence variants do not modify SMA severity at the population level. Specific variants in individual patients or families do not consistently correlate with disease severity

Different approaches to research and innovation in physics education at college and university

In this article we report a Symposium organized by GTG-Physics Education Research at University (PERU) with different proposals that includes innovative educational approaches and research on problems of teaching-learning physics at university. In the second section, two research projects are described on teaching specific curriculum topics that present special difficulties for students. In the next section the third project on a work experience in the laboratory that takes into account the characteristics of scientific work, is presented. Finally, the fourth project presents a way to investigate the types of student reasoning. In the discussion, the importance of research projects that include not only conceptual understanding but also those areas such as laboratory work or "on-line physics courses" that involve practicing skills of scientific work, is highlighted.Publisher PD