4,140 research outputs found
Computation-Aware Data Aggregation
Data aggregation is a fundamental primitive in distributed computing wherein a network computes a function of every nodes\u27 input. However, while compute time is non-negligible in modern systems, standard models of distributed computing do not take compute time into account. Rather, most distributed models of computation only explicitly consider communication time.
In this paper, we introduce a model of distributed computation that considers both computation and communication so as to give a theoretical treatment of data aggregation. We study both the structure of and how to compute the fastest data aggregation schedule in this model. As our first result, we give a polynomial-time algorithm that computes the optimal schedule when the input network is a complete graph. Moreover, since one may want to aggregate data over a pre-existing network, we also study data aggregation scheduling on arbitrary graphs. We demonstrate that this problem on arbitrary graphs is hard to approximate within a multiplicative 1.5 factor. Finally, we give an O(log n ? log(OPT/t_m))-approximation algorithm for this problem on arbitrary graphs, where n is the number of nodes and OPT is the length of the optimal schedule
Brownian molecular motors driven by rotation-translation coupling
We investigated three models of Brownian motors which convert rotational
diffusion into directed translational motion by switching on and off a
potential. In the first model a spatially asymmetric potential generates
directed translational motion by rectifying rotational diffusion. It behaves
much like a conventional flashing ratchet. The second model utilizes both
rotational diffusion and drift to generate translational motion without spatial
asymmetry in the potential. This second model can be driven by a combination of
a Brownian motor mechanism (diffusion driven) or by powerstroke (drift driven)
depending on the chosen parameters. In the third model, elements of both the
Brownian motor and powerstroke mechanisms are combined by switching between
three distinct states. Relevance of the model to biological motor proteins is
discussed.Comment: 11 pages, 8 figure
Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors
The NMDA type of ligand-gated glutamate receptor requires the presence of both glutamate and glycine for gating. These receptors are hetero-oligomers of NR1 and NR2 subunits. Previously it was thought that the binding sites for glycine and glutamate were formed by residues on the NR1 subunit. Indeed, it has been shown that the effects of glycine are controlled by residues on the NR1 subunit, and a “Venus flytrap” model for the glycine binding site has been suggested by analogy with bacterial periplasmic amino acid binding proteins. By analysis of 10 mutant NMDA receptors, we now show that residues on the NR2A subunit control glutamate potency in recombinant NR1/NR2A receptors, without affecting glycine potency. Furthermore, we provide evidence that, at least for some mutated residues, the reduced potency of glutamate cannot be explained by alteration of gating but has to be caused primarily by impairing the binding of the agonist to the resting state of the receptor. One NR2A mutant, NR2A(T671A), had anEC50for glutamate 1000-fold greater than wild type and a 255-fold reduced affinity for APV, yet it had single-channel openings very similar to those of wild type. Therefore we propose that the glutamate binding site is located on NR2 subunits and (taking our data together with previous work) is not on the NR1 subunit. Our data further imply that each NMDA receptor subunit possesses a binding site for an agonist (glutamate or glycine).</jats:p
Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles
Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes.
Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1.
Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay.
Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques
Long-Term Outcomes of Cognitive-Behavioral Therapy for Adolescent Body Dysmorphic Disorder
Emerging evidence suggests that cognitive-behavioral therapy (CBT) is an efficacious treatment for adolescent body dysmorphic disorder (BDD) in the short term, but longer-term outcomes remain unknown. The current study aimed to follow up a group of adolescents who had originally participated in a randomized controlled trial of CBT for BDD to determine whether treatment gains were maintained. Twenty-six adolescents (mean age = 16.2, SD = 1.6) with a primary diagnosis of BDD received a course of developmentally tailored CBT and were followed up over 12 months. Participants were assessed at baseline, midtreatment, posttreatment, 2-, 6-, and 12-month follow-up. The primary outcome measure was the clinician-rated Yale-Brown Obsessive-Compulsive Scale Modified for BDD. Secondary outcomes included measures of insight, depression, quality of life, and global functioning. BDD symptoms decreased significantly from pre- to posttreatment and remained stable over the 12-month follow-up. At this time point, 50% of participants were classified as responders and 23% as remitters. Participants remained significantly improved on all secondary outcomes at 12-month follow-up. Neither baseline insight nor baseline depression predicted long-term outcomes. The positive effects of CBT appear to be durable up to 12-month follow-up. However, the majority of patients remained symptomatic and vulnerable to a range of risks at 12-month follow-up, indicating that longer-term monitoring is advisable in this population. Future research should focus on enhancing the efficacy of CBT in order to improve long-term outcomes.Full Tex
A Bayesian palaeoenvironmental transfer function model for acidified lakes
A Bayesian approach to palaeoecological environmental reconstruction deriving from the unimodal responses generally exhibited by organisms to an environmental gradient is described. The approach uses Bayesian model selection to calculate a collection of probability-weighted, species-specific response curves (SRCs) for each taxon within a training set, with an explicit treatment for zero abundances. These SRCs are used to reconstruct the environmental variable from sub-fossilised assemblages. The approach enables a substantial increase in computational efficiency (several orders of magnitude) over existing Bayesian methodologies. The model is developed from the Surface Water Acidification Programme (SWAP) training set and is demonstrated to exhibit comparable predictive power to existing Weighted Averaging and Maximum Likelihood methodologies, though with improvements in bias; the additional explanatory power of the Bayesian approach lies in an explicit calculation of uncertainty for each individual reconstruction. The model is applied to reconstruct the Holocene acidification history of the Round Loch of Glenhead, including a reconstruction of recent recovery derived from sediment trap data.The Bayesian reconstructions display similar trends to conventional (Weighted Averaging Partial Least Squares) reconstructions but provide a better reconstruction of extreme pH and are more sensitive to small changes in diatom assemblages. The validity of the posteriors as an apparently meaningful representation of assemblage-specific uncertainty and the high computational efficiency of the approach open up the possibility of highly constrained multiproxy reconstructions
A microscopic theory of gauge mediation
We construct models of indirect gauge mediation where the dynamics
responsible for breaking supersymmetry simultaneously generates a weakly
coupled subsector of messengers. This provides a microscopic realization of
messenger gauge mediation where the messenger and hidden sector fields are
unified into a single sector. The UV theory is SQCD with massless and massive
quarks plus singlets, and at low energies it flows to a weakly coupled quiver
gauge theory. One node provides the primary source of supersymmetry breaking,
which is then transmitted to the node giving rise to the messenger fields.
These models break R-symmetry spontaneously, produce realistic gaugino and
sfermion masses, and give a heavy gravitino.Comment: 24 pages, 2 figures, accepted to JHEP for publicatio
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Measurement of Λ (1520) production in pp collisions at √s=7TeV and p–Pb collisions at √sNN=5.02TeV
The production of the Λ (1520) baryonic resonance has been measured at midrapidity in inelastic pp collisions at s=7TeV and in p–Pb collisions at sNN=5.02TeV for non-single diffractive events and in multiplicity classes. The resonance is reconstructed through its hadronic decay channel Λ (1520) → pK - and the charge conjugate with the ALICE detector. The integrated yields and mean transverse momenta are calculated from the measured transverse momentum distributions in pp and p–Pb collisions. The mean transverse momenta follow mass ordering as previously observed for other hyperons in the same collision systems. A Blast-Wave function constrained by other light hadrons (π, K, KS0, p, Λ) describes the shape of the Λ (1520) transverse momentum distribution up to 3.5GeV/c in p–Pb collisions. In the framework of this model, this observation suggests that the Λ (1520) resonance participates in the same collective radial flow as other light hadrons. The ratio of the yield of Λ (1520) to the yield of the ground state particle Λ remains constant as a function of charged-particle multiplicity, suggesting that there is no net effect of the hadronic phase in p–Pb collisions on the Λ (1520) yield
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