139 research outputs found
GMA: A Pareto Optimal Distributed Resource-Allocation Algorithm
To address the rising demand for strong packet delivery guarantees in
networking, we study a novel way to perform graph resource allocation. We first
introduce allocation graphs, in which nodes can independently set local
resource limits based on physical constraints or policy decisions. In this
scenario we formalize the distributed path-allocation (PAdist) problem, which
consists in allocating resources to paths considering only local on-path
information -- importantly, not knowing which other paths could have an
allocation -- while at the same time achieving the global property of never
exceeding available resources.
Our core contribution, the global myopic allocation (GMA) algorithm, is a
solution to this problem. We prove that GMA can compute unconditional
allocations for all paths on a graph, while never over-allocating resources.
Further, we prove that GMA is Pareto optimal with respect to the allocation
size, and it has linear complexity in the input size. Finally, we show with
simulations that this theoretical result could be indeed applied to practical
scenarios, as the resulting path allocations are large enough to fit the
requirements of practically relevant applications
Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein
The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning” the host's immune response in demyelinating plaques, thus continuously eliciting new lesion
Fracking - Gefahr für das Trinkwasser?
Fracking-Vorhaben sind zum aktuellen Zeitpunkt nicht mit dem rechtlichen Schutz des Trinkwassers vereinbar. Dies zeigt eine Studie, die diese Tage auf sui.generis publiziert wurde
Codeine accumulation and elimination in larvae, pupae, and imago of the blowfly Lucilia sericata and effects on its development
The aim of this study was to evaluate the reliability of insect larvae as samples for toxicological investigations. For this purpose, larvae of Lucilia sericata were reared on samples of minced pig liver treated with different concentrations of codeine: therapeutic, toxic, and potentially lethal doses. Codeine was detected in all tested larvae, confirming the reliability of these specimens for qualitative toxicology analysis. Furthermore, concentrations measured in larvae were correlated with levels in liver tissue. These observations bring new elements regarding the potential use of opiates concentrations in larvae for estimation of drug levels in human tissues. Morphine and norcodeine, two codeine metabolites, have been also detected at different concentrations depending on the concentration of codeine in pig liver and depending on the substance itself. The effects of codeine on the development of L. sericata were also investigated. Results showed that a 29-h interval bias on the evaluation of the larval stage duration calculated from the larvae weight has to be considered if codeine was present in the larvae substrate. Similarly, a 21-h interval bias on the total duration of development, from egg to imago, has to be considered if codeine was present in the larvae substrat
G-SINC: Global Synchronization Infrastructure for Network Clocks
Many critical computing applications rely on secure and dependable time which is reliably synchronized across large distributed systems. Today's time synchronization architectures are commonly based on global navigation satellite systems at the considerable risk of being exposed to outages, malfunction, or attacks against availability and accuracy. This paper describes a practical instantiation of a new global, Byzantine fault-tolerant clock synchronization approach that does not place trust in any single entity and is able to tolerate a fraction of faulty entities while still maintaining synchronization on a global scale among otherwise sovereign network topologies. Leveraging strong resilience and security properties provided by the path-aware SCION networking architecture, the presented design can be implemented as a backward compatible active standby solution for existing time synchronization deployments. Through extensive evaluation, we demonstrate that over 94% of time servers reliably minimize the offset of their local clocks to real-time in the presence of up to 20% malicious nodes, and all time servers remain synchronized with a skew of only 2 ms even after one year of reference clock outage
Acoustic stimulation during sleep predicts long-lasting increases in memory performance and beneficial amyloid response in older adults.
BACKGROUND
Sleep and neurodegeneration are assumed to be locked in a bi-directional vicious cycle. Improving sleep could break this cycle and help to prevent neurodegeneration. We tested multi-night phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) as a non-invasive method to improve SWS, memory performance and plasma amyloid levels.
METHODS
32 healthy older adults (agemean: 68.9) completed a between-subject sham-controlled three-night intervention, preceded by a sham-PLAS baseline night.
RESULTS
PLAS induced increases in sleep-associated spectral-power bands as well as a 24% increase in slow wave-coupled spindles, known to support memory consolidation. There was no significant group-difference in memory performance or amyloid-beta between the intervention and control group. However, the magnitude of PLAS-induced physiological responses were associated with memory performance up to 3 months post intervention and beneficial changes in plasma amyloid. Results were exclusive to the intervention group.
DISCUSSION
Multi-night PLAS is associated with long-lasting benefits in memory and metabolite clearance in older adults, rendering PLAS a promising tool to build upon and develop long-term protocols for the prevention of cognitive decline
Inconsistency of interacting, multi-graviton theories
We investigate, in any spacetime dimension >=3, the problem of consistent
couplings for a finite collection of massless, spin-2 fields described, in the
free limit, by a sum of Pauli-Fierz actions. We show that there is no
consistent (ghost-free) coupling, with at most two derivatives of the fields,
that can mix the various "gravitons". In other words, there are no
Yang-Mills-like spin-2 theories. The only possible deformations are given by a
sum of individual Einstein-Hilbert actions. The impossibility of
cross-couplings subsists in the presence of scalar matter. Our approach is
based on the BRST-based deformation point of view and uses results on the
so-called "characteristic cohomology" for massless spin-2 fields which are
explained in detail.Comment: 44+1 pages, no figures. Case of an infinite number of gravitons
treated more completely, comparison with work by Aragone and Deser on
gravitational coupling of a single massless spin-2 field discusse
New evidence of dominant processing effects in standard and oxygenated silicon diodes after neutron irradiation
Abstract Silicon diodes processed on standard and oxygenated silicon substrates by three different manufacturers have been irradiated by neutrons in a nuclear reactor. The leakage current density ( J D ) increase is linear with the neutron fluence. J D and its annealing curve at 80°C do not present any sizeable dependence on substrate oxygenation and/or manufacturing process. The acceptor introduction rate ( β ) of the effective substrate doping concentration ( N eff ) is independent from the oxygen concentration when standard and oxygenated devices from the same manufacturer are considered. On the contrary, β significantly varies from one manufacturer to another showing that the β dependence on the particular process can be important, overtaking the small substrate oxygenation effect. Finally, the average saturation value of the N eff reverse annealing is slightly lower for the oxygenated samples, pointing out a positive effect of the substrate oxygenation even for devices irradiated by neutrons
Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein
The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, “outrunning” the host’s immune response in demyelinating plaques, thus continuously eliciting new lesions
Disease-Causing 7.4 kb Cis-Regulatory Deletion Disrupting Conserved Non-Coding Sequences and Their Interaction with the FOXL2 Promotor: Implications for Mutation Screening
To date, the contribution of disrupted potentially cis-regulatory conserved non-coding sequences (CNCs) to human disease is most likely underestimated, as no systematic screens for putative deleterious variations in CNCs have been conducted. As a model for monogenic disease we studied the involvement of genetic changes of CNCs in the cis-regulatory domain of FOXL2 in blepharophimosis syndrome (BPES). Fifty-seven molecularly unsolved BPES patients underwent high-resolution copy number screening and targeted sequencing of CNCs. Apart from three larger distant deletions, a de novo deletion as small as 7.4 kb was found at 283 kb 5′ to FOXL2. The deletion appeared to be triggered by an H-DNA-induced double-stranded break (DSB). In addition, it disrupts a novel long non-coding RNA (ncRNA) PISRT1 and 8 CNCs. The regulatory potential of the deleted CNCs was substantiated by in vitro luciferase assays. Interestingly, Chromosome Conformation Capture (3C) of a 625 kb region surrounding FOXL2 in expressing cellular systems revealed physical interactions of three upstream fragments and the FOXL2 core promoter. Importantly, one of these contains the 7.4 kb deleted fragment. Overall, this study revealed the smallest distant deletion causing monogenic disease and impacts upon the concept of mutation screening in human disease and developmental disorders in particular
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