Orthodontics in the era of big data analytics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/1/ocr12279_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/2/ocr12279.pd

Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation

Network analysis became a powerful tool in recent years. Heat shock is a well-characterized model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a "stratus-cumulus" type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes.Comment: 24 pages, 6 figures, 2 tables, 70 references + 22 pages 8 figures, 4 tables and 8 references in the enclosed Supplemen

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts

Uncovering the mechanisms of research capacity development in health and social care: a realist synthesis

BACKGROUND: Research capacity development (RCD) is considered fundamental to closing the evidence-practice gap, thereby contributing to health, wealth and knowledge for practice. Numerous frameworks and models have been proposed for RCD, but there is little evidence of what works for whom and under what circumstances. There is a need to identify mechanisms by which candidate interventions or clusters of interventions might achieve RCD and contribute to societal impact, thereby proving meaningful to stakeholders. METHODS: A realist synthesis was used to develop programme theories for RCD. Structured database searches were conducted across seven databases to identify papers examining RCD in a health or social care context (1998-2013). In addition, citation searches for 10 key articles (citation pearls) were conducted across Google Scholar and Web of Science. Of 214 included articles, 116 reported on specific interventions or initiatives or their evaluation. The remaining 98 articles were discussion papers or explicitly sought to make a theoretical contribution. A core set of 36 RCD theoretical and conceptual papers were selected and analysed to generate mechanisms that map across macro contexts (individual, team, organisational, network). Data were extracted by means of 'If-Then' statements into an Excel spreadsheet. Models and frameworks were deconstructed into their original elements. RESULTS: Eight overarching programme theories were identified featuring mechanisms that were triggered across multiple contexts. Three of these fulfilled a symbolic role in signalling the importance of RCD (e.g. positive role models, signal importance, make a difference), whilst the remainder were more functional (e.g. liberate talents, release resource, exceed sum of parts, learning by doing and co-production of knowledge). Outcomes from one mechanism produced changes in context to stimulate mechanisms in other activities. The eight programme theories were validated with findings from 10 systematic reviews (2014-2017). CONCLUSIONS: This realist synthesis is the starting point for constructing an RCD framework shaped by these programme theories. Future work is required to further test and refine these findings against empirical data from intervention studies