On the spectrum of stochastic perturbations of the shift and Julia sets

We extend the Killeen-Taylor study in \cite{KT} by investigating in different Banach spaces ($\ell^\alpha(\N), c_0(\N),c_c(\N)$) the point, continuous and residual spectra of stochastic perturbations of the shift operator associated to the stochastic adding machine in base 2 and in Fibonacci base. For the base 2, the spectra are connected to the Julia set of a quadratic map. In the Fibonacci case, the spectra involve the Julia set of an endomorphism of \C^2.Comment: 24 pages, 8 figures and 10 reference

Nonlinear optical mechanism of forming periodical nanostructures in large bandgap dielectrics

Nonlinear excitation mechanisms of plasmons and their influence on femtosecond-laser induced sub-wavelength ripple generation on dielectric and semiconducting transparent materials are discussed. The agreement of theoretical and experimental data indicates the relevance of the model

Vaccine-induced skewing of T cell responses protects against Chikungunya virus disease

Chikungunya virus (CHIKV) infections can cause severe and debilitating joint and muscular pain that can be long lasting. Current CHIKV vaccines under development rely on the generation of neutralizing antibodies for protection; however, the role of T cells in controlling CHIKV infection and disease is still unclear. Using an overlapping peptide library, we identified the CHIKV-specific T cell receptor epitopes recognized in C57BL/6 infected mice at 7 and 14 days post-infection. A fusion protein containing peptides 451, 416, a small region of nsP4, peptide 47, and an HA tag (CHKVf5) was expressed using adenovirus and cytomegalovirus-vectored vaccines. Mice vaccinated with CHKVf5 elicited robust T cell responses to higher levels than normally observed following CHIKV infection, but the vaccine vectors did not elicit neutralizing antibodies. CHKVf5-vaccinated mice had significantly reduced infectious viral load when challenged by intramuscular CHIKV injection. Depletion of both CD

The architecture of the simian varicella virus transcriptome

Primary infection with varicella-zoster virus (VZV) causes varicella and the establishment of lifelong latency in sensory ganglion neurons. In one-third of infected individuals VZV reactivates from latency to cause herpes zoster, often complicated by difficult-to-treat chronic pain. Experimental infection of non-human primates with simian varicella virus (SVV) recapitulates most features of human VZV disease, thereby providing the opportunity to study the pathogenesis of varicella and herpes zoster in vivo. However, compared to VZV, the transcriptome and the full coding potential of SVV remains incompletely understood. Here, we performed nanopore direct RNA sequencing to annotate the SVV transcriptome in lytically SVV-infected African green monkey (AGM) and rhesus macaque (RM) kidney epithelial cells. We refined structures of canonical SVV transcripts and uncovered numerous RNA isoforms, splicing events, fusion transcripts and non-coding RNAs, mostly unique to SVV. We verified the expression of canonical and newly identified SVV transcripts in vivo, using lung samples from acutely SVV-infected cynomolgus macaques. Expression of selected transcript isoforms, including those located in the unique left-end of the SVV genome, was confirmed by reverse transcription PCR. Finally, we performed detailed characterization of the SVV homologue of the VZV latency-associated transcript (VLT), located antisense to ORF61. Analogous to VZV VLT, SVV VLT is multiply spliced and numerous isoforms are generated using alternative transcription start sites and extensive splicing. Conversely, low level expression of a single spliced SVV VLT isoform defines in vivo latency. Notably, the genomic location of VLT core exons is highly conserved between SVV and VZV. This work thus highlights the complexity of lytic SVV gene expression and provides new insights into the molecular biology underlying lytic and latent SVV infection. The identification of the SVV VLT homolog further underlines the value of the SVV non-human primate model to develop new strategies for prevention of herpes zoster

Does a reduction in alcohol use by Dutch high school students relate to higher use of tobacco and cannabis?

Background: Substance use of adolescents was investigated in a region around Amsterdam, the Netherlands, in the period 2005-2009. The study was intended to find out to what extent behaviour related to different substances are interrelated and how trends develop in different subgroups. Methods: Two cross-sectional surveys were conducted among Dutch students in the second and fourth year of secondary school, aged 13-16 [n = 1,854 in 2005; n = 2,088 in 2009] by making use of an online questionnaire including questions about alcohol consumption, tobacco use (smoking behaviour) and cannabis use. Two educational levels were included. Results: Decreases in alcohol consumption, tobacco and cannabis use were found between 2005 and 2009. The strongest decline was seen in alcohol consumption. Last month drinking decreased from 61.8 % in 2005 to 36.5 % in 2009. Last month binge drinking decreased from 38.7 % in 2005 to 24.0 % in 2009. Reduced alcohol consumption was found among boys and girls, for all ages and in both educational levels. Changes were strongest among 13-year-olds. Weekly or daily smoking declined between 2005 and 2009 among 13-year-olds, girls and students in the lower schooling level. Last month cannabis use decreased among girls and students in the higher schooling level. In both 2005 and 2009 clustering with alcohol consumption was found for the use of other substances. Conclusions: Between 2005 and 2009 alcohol consumption strongly decreased among high school students. This may be due to the national prevention campaign which in the same period highlighted the importance of not drinking before the age of 16. The decrease in smoking and cannabis use between 2005 and 2009 may be due to clustering with alcohol consumption. A reduction in the use of alcohol in adolescence did not lead to replacement by tobacco or cannabis use

Cardiomyocyte-specific estrogen receptor alpha increases angiogenesis, lymphangiogenesis and reduces fibrosis in the female mouse heart post-myocardial infarction

Experimental studies showed that 17{beta}-estradiol (E2) and activated Estrogen Receptors (ER) protect the heart from ischemic injury. However, the underlying molecular mechanisms are not well understood. To investigate the role of ER{alpha} in cardiomyocytes in the setting of myocardial ischemia, we generated transgenic mice with cardiomyocyte-specific overexpression of ER-{alpha} (ER{alpha}-OE) and subjected them to Myocardial Infarction (MI). At the basal level, female and male ER{alpha}-OE mice showed increased Left Ventricular (LV) mass, LV volume and cardiomyocyte length. Two weeks after MI, LV volume was significantly increased and LV wall thickness decreased in female and male WT-mice and male ER{alpha}-OE, but not in female ER{alpha}-OE mice. ER{alpha}-OE enhanced expression of angiogenesis and lymphangiogenesis markers (Vegf, Lyve-1), and neovascularization in the peri-infarct area in both sexes. However, attenuated level of fibrosis and higher phosphorylation of JNK signaling pathway could be detected only in female ER{alpha}-OE after MI. In conclusion, our study indicates that ER{alpha} protects female mouse cardiomyocytes from the sequelae of ischemia through induction of neovascularization in a paracrine fashion and impaired fibrosis, which together may contribute to the attenuation of cardiac remodelling

Single cell analysis reveals similar functional competence of dominant and nondominant CD8 T-cell clonotypes.

Immune protection from infectious diseases and cancer is mediated by individual T cells of different clonal origin. Their functions are tightly regulated but not yet fully characterized. Understanding the contribution of each T cell will improve the prediction of immune protection based on laboratory assessment of T-cell responses. Here we developed techniques for simultaneous molecular and functional assessment of single CD8 T cells directly ex vivo. We studied two groups of patients with melanoma after vaccination with two closely related tumor antigenic peptides. Vaccination induced T cells with strong memory and effector functions, as found in virtually all T cells of the first patient group, and fractions of T cells in the second group. Interestingly, high functionality was not restricted to dominant clonotypes. Rather, dominant and nondominant clonotypes acquired equal functional competence. In parallel, this was also found for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may contribute similarly to immunity as their dominant counterparts