A comparison of in-sample forecasting methods

In-sample forecasting is a recent continuous modification of well-known forecasting methods based on aggregated data. These aggregated methods are known as age-cohort methods in demography, economics, epidemiology and sociology and as chain ladder in non-life insurance. Data is organized in a two-way table with age and cohort as indices, but without measures of exposure. It has recently been established that such structured forecasting methods based on aggregated data can be interpreted as structured histogram estimators. Continuous in-sample forecasting transfers these classical forecasting models into a modern statistical world including smoothing methodology that is more efficient than smoothing via histograms. All in-sample forecasting estimators are collected and their performance is compared via a finite sample simulation study. All methods are extended via multiplicative bias correction. Asymptotic theory is being developed for the histogram-type method of sieves and for the multiplicatively corrected estimators. The multiplicative bias corrected estimators improve all other known in-sample forecasters in the simulation study. The density projection approach seems to have the best performance with forecasting based on survival densities being the runner-up

Silent synapses generate sparse and orthogonal action potential firing in adult-born hippocampal granule cells.

In adult neurogenesis young neurons connect to the existing network via formation of thousands of new synapses. At early developmental stages, glutamatergic synapses are sparse, immature and functionally 'silent', expressing mainly NMDA receptors. Here we show in 2- to 3-week-old young neurons of adult mice, that brief-burst activity in glutamatergic fibers is sufficient to induce postsynaptic AP firing in the absence of AMPA receptors. The enhanced excitability of the young neurons lead to efficient temporal summation of small NMDA currents, dynamic unblocking of silent synapses and NMDA-receptor-dependent AP firing. Therefore, early synaptic inputs are powerfully converted into reliable spiking output. Furthermore, due to high synaptic gain, small dendritic trees and sparse connectivity, neighboring young neurons are activated by different distinct subsets of afferent fibers with minimal overlap. Taken together, synaptic recruitment of young neurons generates sparse and orthogonal AP firing, which may support sparse coding during hippocampal information processing

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.

BackgroundWe reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later.ResultsThe early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia.ConclusionThis is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses

CP Violation in \tau ->\nu\pi K_S and D->\pi K_S: The Importance of K_S-K_L Interference

The $B$-factories have measured CP asymmetries in the $\tau\to\pi K_S\nu$ and $D\to K_S\pi$ modes. The $K_S$ state is identified by its decay to two pions at a time that is close to the $K_S$ lifetime. Within the Standard Model and many of its extensions, the asymmetries in these modes come from CP violation in $K^0-\bar{K}^0$ mixing. We emphasize that the interference between the amplitudes of intermediate $K_S$ and $K_L$ is as important as the pure $K_S$ amplitude. Consequently, the measured asymmetries depend on the times over which the relevant decay rates are integrated and on features of the experiment.Comment: 4 pages, 4 figure

Designing allostery-inspired response in mechanical networks

Recent advances in designing metamaterials have demonstrated that global mechanical properties of disordered spring networks can be tuned by selectively modifying only a small subset of bonds. Here, using a computationally efficient approach, we extend this idea to tune more general properties of networks. With nearly complete success, we are able to produce a strain between any two target nodes in a network in response to an applied source strain on any other pair of nodes by removing only ∼1% of the bonds. We are also able to control multiple pairs of target nodes, each with a different individual response, from a single source, and to tune multiple independent source/target responses simultaneously into a network. We have fabricated physical networks in macroscopic 2D and 3D systems that exhibit these responses. This work is inspired by the long-range coupled conformational changes that constitute allosteric function in proteins. The fact that allostery is a common means for regulation in biological molecules suggests that it is a relatively easy property to develop through evolution. In analogy, our results show that long-range coupled mechanical responses are similarly easy to achieve in disordered networks

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons

The Physics of Heavy Flavours at SuperB

This is a review of the SuperB project, covering the accelerator, detector, and highlights of the broad physics programme. SuperB is a flavour factory capable of performing precision measurements and searches for rare and forbidden decays of $B_{u,d,s}$, $D$, $\tau$ and $\Upsilon({\mathrm{nS}})$ particles. These results can be used to test fundamental symmetries and expectations of the Standard Model, and to constrain many different hypothesised types of new physics. In some cases these measurements can be used to place constraints on the existence of light dark matter and light Higgs particles with masses below $10GeV/c^2$. The potential impact of the measurements that will be made by SuperB on the field of high energy physics is also discussed in the context of data taken at both high energy in the region around the \Upsilon({\mathrm{4S}})$, and near charm threshold.Comment: 49 pages, topical review submitted to J. Phys

Measurements of Charmless Hadronic b->s Penguin Decays in the pi+pi-K+pi- Final State and First Observation of B0 -> rho0K+pi-

We report measurements of charmless hadronic B^0 decays into the pi+pi-K+pi+ final state. The analysis uses a sample of 657x10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider at the Y(4S) resonance. The decay B^0 -> rho0 Kpi is observed for the first time; the significance is 5.0sigma and the corresponding partial branching fraction for M_Kpi in (0.75,1.20) GeV/c^2 is [2.8 +- 0.5(stat) +-0.5(syst)] x 10^{-6}. We also obtain the first evidence for B^0 -> f0Kpi with 3.5sigma significance and for B^0 -> pi+pi-K*0 with 4.5sigma significance. For the two-body decays B^0 -> rho0K*0 and B^0 -> f0K*0, the significances are 2.7sigma and 2.5sigma, respectively, and the upper limits on the branching fractions are 3.4x10^{-6} and 2.2x10^{-6} at 90% confidence level.Comment: 6 pages, 3 figures. accepted by PRD(RC

Observation of B+ -> Dbar*0 tau+ nu_tau and Evidence for B+ -> Dbar^0 tau+ nu_tau at Belle

We present measurements of B+ -> Dbar*0 tau+ nu_tau and B+ -> Dbar^0 tau+ nu_tau decays in a data sample of 657 x 10^6 BBbar pairs collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. We find 446^{+58}_{-56} events of the decay B+ -> Dbar*0 tau+ nu_tau with a significance of 8.1 standard deviations, and 146^{+42}_{-41} events of the decay B+ -> Dbar0 tau+ nu_tau with a significance of 3.5 standard deviations. The latter signal provides the first evidence for this decay mode. The measured branching fractions are B(B+ -> Dbar*0 tau+ nu_tau)=(2.12^{+0.28}_{-0.27} (stat) +- 0.29 (syst)) % and B(B+ -> Dbar0 tau+ nu_tau)=(0.77 +- 0.22 (stat) +- 0.12 (syst)) %.Comment: 6 pages, 4 figures, submitted to Phys. Rev. Let