On the Estimation of Euler Equations in the Presence of a Potential Regime Shift

The concept of a peso problem is formalized in terms of a linear Euler equation and a nonlinear marginal model describing the dynamics of the exogenous driving process. It is shown that, using a threshold autoregressive model as a marginal model, it is possible to produce time-varying peso premia. A Monte Carlo method and a method based on the numerical solution of integral equations are considered as tools for computing conditional future expectations in the marginal model. A Monte Carlo study illustrates the poor performance of the generalized method of moment (GMM) estimator in small and even relatively large samples. The poor performance is particularly acute in the presence of a peso problem but is also serious in the simple linear case.peso problem; Euler equations; GMM; threshold autoregressive models

Response to Comment on `Undamped electrostatic plasma waves' [Phys. Plasmas 19, 092103 (2012)]

Numerical and experimental evidence is given for the occurrence of the plateau states and concomitant corner modes proposed in \cite{valentini12}. It is argued that these states provide a better description of reality for small amplitude off-dispersion disturbances than the conventional Bernstein-Greene-Kruskal or cnoidal states such as those proposed in \cite{comment

Undamped electrostatic plasma waves

Electrostatic waves in a collision-free unmagnetized plasma of electrons with fixed ions are investigated for electron equilibrium velocity distribution functions that deviate slightly from Maxwellian. Of interest are undamped waves that are the small amplitude limit of nonlinear excitations, such as electron acoustic waves (EAWs). A deviation consisting of a small plateau, a region with zero velocity derivative over a width that is a very small fraction of the electron thermal speed, is shown to give rise to new undamped modes, which here are named {\it corner modes}. The presence of the plateau turns off Landau damping and allows oscillations with phase speeds within the plateau. These undamped waves are obtained in a wide region of the $(k,\omega_{_R})$ plane ($\omega_{_R}$ being the real part of the wave frequency and $k$ the wavenumber), away from the well-known `thumb curve' for Langmuir waves and EAWs based on the Maxwellian. Results of nonlinear Vlasov-Poisson simulations that corroborate the existence of these modes are described. It is also shown that deviations caused by fattening the tail of the distribution shift roots off of the thumb curve toward lower $k$-values and chopping the tail shifts them toward higher $k$-values. In addition, a rule of thumb is obtained for assessing how the existence of a plateau shifts roots off of the thumb curve. Suggestions are made for interpreting experimental observations of electrostatic waves, such as recent ones in nonneutral plasmas.Comment: 11 pages, 10 figure

Search for Point Sources of High Energy Neutrinos with AMANDA

This paper describes the search for astronomical sources of high-energy neutrinos using the AMANDA-B10 detector, an array of 302 photomultiplier tubes, used for the detection of Cherenkov light from upward traveling neutrino-induced muons, buried deep in ice at the South Pole. The absolute pointing accuracy and angular resolution were studied by using coincident events between the AMANDA detector and two independent telescopes on the surface, the GASP air Cherenkov telescope and the SPASE extensive air shower array. Using data collected from April to October of 1997 (130.1 days of livetime), a general survey of the northern hemisphere revealed no statistically significant excess of events from any direction. The sensitivity for a flux of muon neutrinos is based on the effective detection area for through-going muons. Averaged over the Northern sky, the effective detection area exceeds 10,000 m^2 for E_{mu} ~ 10 TeV. Neutrinos generated in the atmosphere by cosmic ray interactions were used to verify the predicted performance of the detector. For a source with a differential energy spectrum proportional to E_{nu}^{-2} and declination larger than +40 degrees, we obtain E^2(dN_{nu}/dE) <= 10^{-6}GeVcm^{-2}s^{-1} for an energy threshold of 10 GeV.Comment: 46 pages, 22 figures, 4 tables, submitted to Ap.

Inhibition of intestinal epithelial apoptosis improves survival in a murine model of radiation combined injury

World conditions place large populations at risk from ionizing radiation (IR) from detonation of dirty bombs or nuclear devices. In a subgroup of patients, ionizing radiation exposure would be followed by a secondary infection. The effects of radiation combined injury are potentially more lethal than either insult in isolation. The purpose of this study was to determine mechanisms of mortality and possible therapeutic targets in radiation combined injury. Mice were exposed to IR with 2.5 Gray (Gy) followed four days later by intratracheal methicillin-resistant Staphylococcus aureus (MRSA). While either IR or MRSA alone yielded 100% survival, animals with radiation combined injury had 53% survival (p = 0.01). Compared to IR or MRSA alone, mice with radiation combined injury had increased gut apoptosis, local and systemic bacterial burden, decreased splenic CD4 T cells, CD8 T cells, B cells, NK cells, and dendritic cells, and increased BAL and systemic IL-6 and G-CSF. In contrast, radiation combined injury did not alter lymphocyte apoptosis, pulmonary injury, or intestinal proliferation compared to IR or MRSA alone. In light of the synergistic increase in gut apoptosis following radiation combined injury, transgenic mice that overexpress Bcl-2 in their intestine and wild type mice were subjected to IR followed by MRSA. Bcl-2 mice had decreased gut apoptosis and improved survival compared to WT mice (92% vs. 42%; p<0.01). These data demonstrate that radiation combined injury results in significantly higher mortality than could be predicted based upon either IR or MRSA infection alone, and that preventing gut apoptosis may be a potential therapeutic target

Has VZV epidemiology changed in Italy? Results of a seroprevalence study

The aim of the study was to evaluate if and how varicella prevalence has changed in Italy. In particular a seroprevalence study was performed, comparing it to similar surveys conducted in pre-immunization era. During 2013–2014, sera obtained from blood samples taken for diagnostic purposes or routine investigations were collected in collaboration with at least one laboratory/center for each region, following the approval of the Ethics Committee. Data were stratified by sex and age. All samples were processed in a national reference laboratory by an immunoassay with high sensitivity and specificity. Statutory notifications, national hospital discharge database and mortality data related to VZV infection were analyzed as well. A total of 3707 sera were collected and tested. In the studied period both incidence and hospitalization rates decreased and about 5 deaths per year have been registered. The seroprevalence decreased in the first year of life in subjects passively protected by their mother, followed by an increase in the following age classes. The overall antibody prevalence was 84%. The comparison with surveys conducted with the same methodology in 1996–1997 and 2003–2004 showed significant differences in age groups 1–19&nbsp;y. The study confirms that in Italy VZV infection typically occurs in children. The impact of varicella on Italian population is changing. The comparison between studies performed in different periods shows a significant increase of seropositivity in age class 1–4&nbsp;years, expression of vaccine interventions already adopted in some regions

AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3 beta

Dysregulated cell cycling is a universal hallmark of cancer and is often mediated by abnormal activation of cyclin-dependent kinases (CDKs) and their cyclin partners. Overexpression of individual complexes are reported in multiple myeloma (MM), making them attractive therapeutic targets. In this study, we investigate the preclinical activity of a novel small-molecule multi-CDK inhibitor, AT7519, in MM. We show the anti-MM activity of AT7519 displaying potent cytotoxicity and apoptosis; associated with in vivo tumor growth inhibition and prolonged survival. At the molecular level, AT7519 inhibited RNA polymerase II (RNA pol II) phosphorylation, a CDK9, 7 substrate, associated with decreased RNA synthesis confirmed by [(3)H] Uridine incorporation. In addition, AT7519 inhibited glycogen synthase kinase 3beta (GSK-3beta) phosphorylation; conversely pretreatment with a selective GSK-3 inhibitor and shRNA GSK-3beta knockdown restored MM survival, suggesting the involvement of GSK-3beta in AT7519-induced apoptosis. GSK-3beta activation was independent of RNA pol II dephosphorylation confirmed by alpha-amanitin, a specific RNA pol II inihibitor, showing potent inhibition of RNA pol II phosphorylation without corresponding effects on GSK-3beta phosphorylation. These results offer new insights into the crucial, yet controversial role of GSK-3beta in MM and show significant anti-MM activity of AT7519, providing the rationale for its clinical evaluation in MM

Default perception of high-speed motion

When human observers are exposed to even slight motion signals followed by brief visual transients—stimuli containing no detectable coherent motion signals—they perceive large and salient illusory jumps. This novel effect, which we call “high phi”, challenges well-entrenched assumptions about the perception of motion, namely the minimal-motion principle and the breakdown of coherent motion perception with steps above an upper limit. Our experiments with transients such as texture randomization or contrast reversal show that the magnitude of the jump depends on spatial frequency and transient duration, but not on the speed of the inducing motion signals, and the direction of the jump depends on the duration of the inducer. Jump magnitude is robust across jump directions and different types of transient. In addition, when a texture is actually displaced by a large step beyond dmax, a breakdown of coherent motion perception is expected, but in the presence of an inducer observers again perceive coherent displacements at or just above dmax. In sum, across a large variety of stimuli, we find that when incoherent motion noise is preceded by a small bias, instead of perceiving little or no motion, as suggested by the minimal-motion principle, observers perceive jumps whose amplitude closely follows their own dmax limits