Proton driver optimization for new generation neutrino superbeams to search for sub-leading numu->nue oscillations (θ13\theta_{13} angle)

We perform a systematic study of particle production and neutrino yields for different incident proton energies $E_p$ and baselines $L$, with the aim of optimizing the parameters of a neutrino beam for the investigation of $\theta_{13}$-driven neutrino oscillations in the $\Delta m^2$ range allowed by Superkamiokande results. We study the neutrino energy spectra in the ``relevant'' region of the first maximum of the oscillation at a given baseline $L$. We find that to each baseline $L$ corresponds an ``optimal'' proton energy $E_p$ which minimizes the required integrated proton intensity needed to observe a fixed number of oscillated events. In addition, we find that the neutrino event rate in the relevant region scales approximately linearly with the proton energy. Hence, baselines $L$ and proton energies $E_p$ can be adjusted and the performance for neutrino oscillation searches will remain approximately unchanged provided that the product of the proton energy times the number of protons on target remains constant. We apply these ideas to the specific cases of 2.2, 4.4, 20, 50 and 400 GeV protons. We simulate focusing systems that are designed to best capture the secondary pions of the ``optimal'' energy. We compute the expected sensitivities to $\sin^22\theta_{13}$ for the various configurations by assuming the existence of new generation accelerators able to deliver integrated proton intensities on target times the proton energy of the order of ${\cal O}(5\times 10^{23})\rm\ GeV\times\rm pot/year$.Comment: 39 pages, 17 figure

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th

Coordinated Regulation of Niche and Stem Cell Precursors by Hormonal Signaling

In the developing Drosophila ovary, the ecdysone signaling pathway controls the differentiation of both niche and germ line stem cell precursors

Peripheral administration of lactate produces antidepressant-like effects.

In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression

Gene Expression Profiling of a Mouse Model of Pancreatic Islet Dysmorphogenesis

In the past decade, several transcription factors critical for pancreas organogenesis have been identified. Despite this success, many of the factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor Hnf6 specifically in the pancreatic endocrine cell lineage resulted in disruptions in islet morphogenesis, including dysfunctional endocrine cell sorting, increased individual islet size, increased number of peripheral endocrine cell types, and failure of islets to migrate away from the ductal epithelium. The mechanisms whereby maintained Hnf6 causes defects in islet morphogenesis have yet to be elucidated.We exploited the dysmorphic islets in Hnf6 transgenic animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal total pancreas tissue from wild type and Hnf6 transgenic animals. Here we report the identification of genes with an altered expression in Hnf6 transgenic animals and highlight factors with potential importance in islet morphogenesis. Importantly, gene products involved in cell adhesion, cell migration, ECM remodeling and proliferation were found to be altered in Hnf6 transgenic pancreata, revealing specific candidates that can now be analyzed directly for their role in these processes during islet development.This study provides a unique dataset that can act as a starting point for other investigators to explore the role of the identified genes in pancreatogenesis, islet morphogenesis and mature beta cell function

Neurod1 is essential for the survival and maturation of adult-born neurons

The transcriptional program that controls adult neurogenesis is unknown. We generated mice with an inducible stem cell–specific deletion of Neurod1, resulting in substantially fewer newborn neurons in the hippocampus and olfactory bulb. Thus, Neurod1 is cell-intrinsically required for the survival and maturation of adult-born neurons