Experience with statically-generated proxies for facilitating Java runtime specialisation

Issues pertaining to mechanisms which can be used to change the behaviour of Java classes at runtime are discussed. The proxy mechanism is compared to, and contrasted with other standard approaches to this problem. Some of the problems the proxy mechanism is subject to are expanded upon. The question of whether statically-developed proxies are a viable alternative to bytecode rewriting was investigated by means of the JavaCloak system, which uses statically-generated proxies to alter the runtime behaviour of externally-developed code. The issues addressed include ensuring the type safety, dealing with the self problem, object encapsulation, and issues of object identity and equality. Some performance figures are provided which demonstrate the load the JavaCloak proxy mechanism places on the system

Expansion of pinched hypersurfaces of the Euclidean and hyperbolic space by high powers of curvature

We prove convergence results for expanding curvature flows in the Euclidean and hyperbolic space. The flow speeds have the form $F^{-p}$, where $p>1$ and $F$ is a positive, strictly monotone and 1-homogeneous curvature function. In particular this class includes the mean curvature $F=H$. We prove that a certain initial pinching condition is preserved and the properly rescaled hypersurfaces converge smoothly to the unit sphere. We show that an example due to Andrews-McCoy-Zheng can be used to construct strictly convex initial hypersurfaces, for which the inverse mean curvature flow to the power $p>1$ loses convexity, justifying the necessity to impose a certain pinching condition on the initial hypersurface.Comment: 18 pages. We included an example for the loss of convexity and pinching. In the third version we dropped the concavity assumption on F. Comments are welcom

Concurrent hypercube system with improved message passing

A network of microprocessors, or nodes, are interconnected in an n-dimensional cube having bidirectional communication links along the edges of the n-dimensional cube. Each node's processor network includes an I/O subprocessor dedicated to controlling communication of message packets along a bidirectional communication link with each end thereof terminating at an I/O controlled transceiver. Transmit data lines are directly connected from a local FIFO through each node's communication link transceiver. Status and control signals from the neighboring nodes are delivered over supervisory lines to inform the local node that the neighbor node's FIFO is empty and the bidirectional link between the two nodes is idle for data communication. A clocking line between neighbors, clocks a message into an empty FIFO at a neighbor's node and vica versa. Either neighbor may acquire control over the bidirectional communication link at any time, and thus each node has circuitry for checking whether or not the communication link is busy or idle, and whether or not the receive FIFO is empty. Likewise, each node can empty its own FIFO and in turn deliver a status signal to a neighboring node indicating that the local FIFO is empty. The system includes features of automatic message rerouting, block message transfer and automatic parity checking and generation

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

Astrophysical Ionizing Radiation and the Earth: A Brief Review and Census of Intermittent Intense Sources

Cosmic radiation backgrounds are a constraint on life, and their distribution will affect the Galactic Habitable Zone. Life on Earth has developed in the context of these backgrounds, and characterizing event rates will elaborate the important influences. This in turn can be a base for comparison with other potential life-bearing planets. In this review we estimate the intensities and rates of occurrence of many kinds of strong radiation bursts by astrophysical entities ranging from gamma-ray bursts at cosmological distances to the Sun itself. Many of these present potential hazards to the biosphere: on timescales long compared with human history, the probability of an event intense enough to disrupt life on the land surface or in the oceans becomes large. We enumerate the known sources of radiation and characterize their intensities at the Earth and rates or upper limits on these quantities. When possible, we estimate a "lethal interval", our best estimate of how often a major extinction-level event is probable given the current state of knowledge; we base these estimates on computed or expected depletion of stratospheric ozone. In general, moderate level events are dominated by the Sun, but the far more severe infrequent events are probably dominated by gamma-ray bursts and supernovae. We note for the first time that so-called "short-hard" gamma-ray bursts are a substantial threat, comparable in magnitude to supernovae and greater than that of the higher-luminosity long bursts considered in most past work. Given their precursors, short bursts may come with little or no warning.Comment: to be published in Astrobiolog

Study of the acoustic signature of UHE neutrino interactions in water and ice

The production of acoustic signals from the interactions of ultra-high energy (UHE) cosmic ray neutrinos in water and ice has been studied. A new computationally fast and efficient method of deriving the signal is presented. This method allows the implementation of up to date parameterisations of acoustic attenuation in sea water and ice that now includes the effects of complex attenuation, where appropriate. The methods presented here have been used to compute and study the properties of the acoustic signals which would be expected from such interactions. A matrix method of parameterising the signals, which includes the expected fluctuations, is also presented. These methods are used to generate the expected signals that would be detected in acoustic UHE neutrino telescopes.Comment: 21 pages and 13 figure

Selfsimilar solutions in a sector for a quasilinear parabolic equation

We study a two-point free boundary problem in a sector for a quasilinear parabolic equation. The boundary conditions are assumed to be spatially and temporally "self-similar" in a special way. We prove the existence, uniqueness and asymptotic stability of an expanding solution which is self-similar at discrete times. We also study the existence and uniqueness of a shrinking solution which is self-similar at discrete times.Comment: 23 page

Green's functions for parabolic systems of second order in time-varying domains

We construct Green's functions for divergence form, second order parabolic systems in non-smooth time-varying domains whose boundaries are locally represented as graph of functions that are Lipschitz continuous in the spatial variables and 1/2-H\"older continuous in the time variable, under the assumption that weak solutions of the system satisfy an interior H\"older continuity estimate. We also derive global pointwise estimates for Green's function in such time-varying domains under the assumption that weak solutions of the system vanishing on a portion of the boundary satisfy a certain local boundedness estimate and a local H\"older continuity estimate. In particular, our results apply to complex perturbations of a single real equation.Comment: 25 pages, 0 figur

Locomotor hyperactivity in 14-3-3Zeta KO mice is associated with dopamine transporter dysfunction

Dopamine (DA) neurotransmission requires a complex series of enzymatic reactions that are tightly linked to catecholamine exocytosis and receptor interactions on pre- and postsynaptic neurons. Regulation of dopaminergic signalling is primarily achieved through reuptake of extracellular DA by the DA transporter (DAT) on presynaptic neurons. Aberrant regulation of DA signalling, and in particular hyperactivation, has been proposed as a key insult in the presentation of schizophrenia and related neuropsychiatric disorders. We recently identified 14-3-3ζ as an essential component of neurodevelopment and a central risk factor in the schizophrenia protein interaction network. Our analysis of 14-3-3ζ-deficient mice now shows that baseline hyperactivity of knockout (KO) mice is rescued by the antipsychotic drug clozapine. 14-3-3ζ KO mice displayed enhanced locomotor hyperactivity induced by the DA releaser amphetamine. Consistent with 14-3-3ζ having a role in DA signalling, we found increased levels of DA in the striatum of 14-3-3ζ KO mice. Although 14-3-3ζ is proposed to modulate activity of the rate-limiting DA biosynthesis enzyme, tyrosine hydroxylase (TH), we were unable to identify any differences in total TH levels, TH localization or TH activation in 14-3-3ζ KO mice. Rather, our analysis identified significantly reduced levels of DAT in the absence of notable differences in RNA or protein levels of DA receptors D1–D5. Providing insight into the mechanisms by which 14-3-3ζ controls DAT stability, we found a physical association between 14-3-3ζ and DAT by co-immunoprecipitation. Taken together, our results identify a novel role for 14-3-3ζ in DA neurotransmission and provide support to the hyperdopaminergic basis of pathologies associated with schizophrenia and related disorders.H Ramshaw, X Xu, EJ Jaehne, P McCarthy, Z Greenberg, E Saleh, B McClure, J Woodcock, S Kabbara, S Wiszniak, Ting-Yi Wang, C Parish, M van den Buuse, BT Baune, A Lopez and Q Schwar

Does \u2018bigger\u2019mean \u2018better\u2019? Pitfalls and shortcuts associated with big data for social research

\u2018Big data is here to stay.\u2019 This key statement has a double value: is an assumption as well as the reason why a theoretical reflection is needed. Furthermore, Big data is something that is gaining visibility and success in social sciences even, overcoming the division between humanities and computer sciences. In this contribution some considerations on the presence and the certain persistence of Big data as a socio-technical assemblage will be outlined. Therefore, the intriguing opportunities for social research linked to such interaction between practices and technological development will be developed. However, despite a promissory rhetoric, fostered by several scholars since the birth of Big data as a labelled concept, some risks are just around the corner. The claims for the methodological power of bigger and bigger datasets, as well as increasing speed in analysis and data collection, are creating a real hype in social research. Peculiar attention is needed in order to avoid some pitfalls. These risks will be analysed for what concerns the validity of the research results \u2018obtained through Big data. After a pars distruens, this contribution will conclude with a pars construens; assuming the previous critiques, a mixed methods research design approach will be described as a general proposal with the objective of stimulating a debate on the integration of Big data in complex research projecting