Restoration of oligodendrocyte pools in a mouse model of chronic cerebral hypoperfusion

Chronic cerebral hypoperfusion, a sustained modest reduction in cerebral blood flow, is associated with damage to myelinated axons and cognitive decline with ageing. Oligodendrocytes (the myelin producing cells) and their precursor cells (OPCs) may be vulnerable to the effects of hypoperfusion and in some forms of injury OPCs have the potential to respond and repair damage by increased proliferation and differentiation. Using a mouse model of cerebral hypoperfusion we have characterised the acute and long term responses of oligodendrocytes and OPCs to hypoperfusion in the corpus callosum. Following 3 days of hypoperfusion, numbers of OPCs and mature oligodendrocytes were significantly decreased compared to controls. However following 1 month of hypoperfusion, the OPC pool was restored and increased numbers of oligodendrocytes were observed. Assessment of proliferation using PCNA showed no significant differences between groups at either time point but showed reduced numbers of proliferating oligodendroglia at 3 days consistent with the loss of OPCs. Cumulative BrdU labelling experiments revealed higher numbers of proliferating cells in hypoperfused animals compared to controls and showed a proportion of these newly generated cells had differentiated into oligodendrocytes in a subset of animals. Expression of GPR17, a receptor important for the regulation of OPC differentiation following injury, was decreased following short term hypoperfusion. Despite changes to oligodendrocyte numbers there were no changes to the myelin sheath as revealed by ultrastructural assessment and fluoromyelin however axon-glial integrity was disrupted after both 3 days and 1 month hypoperfusion. Taken together, our results demonstrate the initial vulnerability of oligodendroglial pools to modest reductions in blood flow and highlight the regenerative capacity of these cells

Convexity in partial cubes: the hull number

We prove that the combinatorial optimization problem of determining the hull number of a partial cube is NP-complete. This makes partial cubes the minimal graph class for which NP-completeness of this problem is known and improves some earlier results in the literature. On the other hand we provide a polynomial-time algorithm to determine the hull number of planar partial cube quadrangulations. Instances of the hull number problem for partial cubes described include poset dimension and hitting sets for interiors of curves in the plane. To obtain the above results, we investigate convexity in partial cubes and characterize these graphs in terms of their lattice of convex subgraphs, improving a theorem of Handa. Furthermore we provide a topological representation theorem for planar partial cubes, generalizing a result of Fukuda and Handa about rank three oriented matroids.Comment: 19 pages, 4 figure

The β3-integrin endothelial adhesome regulates microtubule-dependent cell migration

Integrin β3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely β3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the β3-dependent adhesome. We show that depletion of β3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. β3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when β3-integrin levels are reduced

Carbon clusters near the crossover to fullerene stability

The thermodynamic stability of structural isomers of $\mathrm{C}_{24}$, $\mathrm{C}_{26}$, $\mathrm{C}_{28}$ and $\mathrm{C}_{32}$, including fullerenes, is studied using density functional and quantum Monte Carlo methods. The energetic ordering of the different isomers depends sensitively on the treatment of electron correlation. Fixed-node diffusion quantum Monte Carlo calculations predict that a $\mathrm{C}_{24}$ isomer is the smallest stable graphitic fragment and that the smallest stable fullerenes are the $\mathrm{C}_{26}$ and $\mathrm{C}_{28}$ clusters with $\mathrm{C}_{2v}$ and $\mathrm{T}_{d}$ symmetry, respectively. These results support proposals that a $\mathrm{C}_{28}$ solid could be synthesized by cluster deposition.Comment: 4 pages, includes 4 figures. For additional graphics, online paper and related information see http://www.tcm.phy.cam.ac.uk/~prck

A radium assay technique using hydrous titanium oxide adsorbent for the Sudbury Neutrino Observatory

As photodisintegration of deuterons mimics the disintegration of deuterons by neutrinos, the accurate measurement of the radioactivity from thorium and uranium decay chains in the heavy water in the Sudbury Neutrino Observatory (SNO) is essential for the determination of the total solar neutrino flux. A radium assay technique of the required sensitivity is described that uses hydrous titanium oxide adsorbent on a filtration membrane together with a beta-alpha delayed coincidence counting system. For a 200 tonne assay the detection limit for 232Th is a concentration of 3 x 10^(-16) g Th/g water and for 238U of 3 x 10^(-16) g U/g water. Results of assays of both the heavy and light water carried out during the first two years of data collection of SNO are presented.Comment: 12 pages, 4 figure

From Social Data Mining to Forecasting Socio-Economic Crisis

Socio-economic data mining has a great potential in terms of gaining a better understanding of problems that our economy and society are facing, such as financial instability, shortages of resources, or conflicts. Without large-scale data mining, progress in these areas seems hard or impossible. Therefore, a suitable, distributed data mining infrastructure and research centers should be built in Europe. It also appears appropriate to build a network of Crisis Observatories. They can be imagined as laboratories devoted to the gathering and processing of enormous volumes of data on both natural systems such as the Earth and its ecosystem, as well as on human techno-socio-economic systems, so as to gain early warnings of impending events. Reality mining provides the chance to adapt more quickly and more accurately to changing situations. Further opportunities arise by individually customized services, which however should be provided in a privacy-respecting way. This requires the development of novel ICT (such as a self- organizing Web), but most likely new legal regulations and suitable institutions as well. As long as such regulations are lacking on a world-wide scale, it is in the public interest that scientists explore what can be done with the huge data available. Big data do have the potential to change or even threaten democratic societies. The same applies to sudden and large-scale failures of ICT systems. Therefore, dealing with data must be done with a large degree of responsibility and care. Self-interests of individuals, companies or institutions have limits, where the public interest is affected, and public interest is not a sufficient justification to violate human rights of individuals. Privacy is a high good, as confidentiality is, and damaging it would have serious side effects for society.Comment: 65 pages, 1 figure, Visioneer White Paper, see http://www.visioneer.ethz.c