Nonradiative interaction and entanglement between distant atoms

We show that nonradiative interactions between atomic dipoles placed in a waveguide can give rise to deterministic entanglement at ranges much larger than their resonant wavelength. The range increases as the dipole-resonance approaches the waveguide's cutoff frequency, caused by the giant density of photon modes near cutoff, a regime where the standard (perturbative) Markov approximation fails. We provide analytical theories for both the Markovian and non-Markovian regimes, supported by numerical simulations, and discuss possible experimental realizations.Comment: 9 pages, 2 figure

Generation of macroscopic quantum-superposition states by linear coupling to a bath

We demonstrate through an exactly solvable model that collective coupling to any thermal bath induces effectively nonlinear couplings in a quantum many-body (multi-spin) system. The resulting evolution can drive an uncorrelated large-spin system with high probability into a macroscopic quantum-superposition state. We discuss possible experimental realizations.Comment: 4 pages, 2 figures, Physical Review Letters (in press

Genome-Wide Mutagenesis Reveals That ORF7 Is a Novel VZV Skin-Tropic Factor

The Varicella Zoster Virus (VZV) is a ubiquitous human alpha-herpesvirus that is the causative agent of chicken pox and shingles. Although an attenuated VZV vaccine (v-Oka) has been widely used in children in the United States, chicken pox outbreaks are still seen, and the shingles vaccine only reduces the risk of shingles by 50%. Therefore, VZV still remains an important public health concern. Knowledge of VZV replication and pathogenesis remains limited due to its highly cell-associated nature in cultured cells, the difficulty of generating recombinant viruses, and VZV's almost exclusive tropism for human cells and tissues. In order to circumvent these hurdles, we cloned the entire VZV (p-Oka) genome into a bacterial artificial chromosome that included a dual-reporter system (GFP and luciferase reporter genes). We used PCR-based mutagenesis and the homologous recombination system in the E. coli to individually delete each of the genome's 70 unique ORFs. The collection of viral mutants obtained was systematically examined both in MeWo cells and in cultured human fetal skin organ samples. We use our genome-wide deletion library to provide novel functional annotations to 51% of the VZV proteome. We found 44 out of 70 VZV ORFs to be essential for viral replication. Among the 26 non-essential ORF deletion mutants, eight have discernable growth defects in MeWo. Interestingly, four ORFs were found to be required for viral replication in skin organ cultures, but not in MeWo cells, suggesting their potential roles as skin tropism factors. One of the genes (ORF7) has never been described as a skin tropic factor. The global profiling of the VZV genome gives further insights into the replication and pathogenesis of this virus, which can lead to improved prevention and therapy of chicken pox and shingles

AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy associated with Notch pathway mutations. While both normal activated and leukemic T cells can utilize aerobic glycolysis to support proliferation, it is unclear to what extent these cell populations are metabolically similar and if differences reveal T-ALL vulnerabilities. Here we show that aerobic glycolysis is surprisingly less active in T-ALL cells than proliferating normal T cells and that T-ALL cells are metabolically distinct. Oncogenic Notch promoted glycolysis but also induced metabolic stress that activated 5' AMP-activated kinase (AMPK). Unlike stimulated T cells, AMPK actively restrained aerobic glycolysis in T-ALL cells through inhibition of mTORC1 while promoting oxidative metabolism and mitochondrial Complex I activity. Importantly, AMPK deficiency or inhibition of Complex I led to T-ALL cell death and reduced disease burden. Thus, AMPK simultaneously inhibits anabolic growth signaling and is essential to promote mitochondrial pathways that mitigate metabolic stress and apoptosis in T-ALL

An association between Helicobacter pylori infection and cognitive function in children at early school age: a community-based study

<p>Abstract</p> <p>Background</p> <p><it>H. pylori </it>infection has been linked to iron deficiency anemia, a risk factor of diminished cognitive development. The hypothesis on an association between <it>H. pylori </it>infection and cognitive function was examined in healthy children, independently of socioeconomic and nutritional factors.</p> <p>Methods</p> <p>A community-based study was conducted among 200 children aged 6-9 years, from different socioeconomic background. <it>H. pylori </it>infection was examined by an ELISA kit for detection of <it>H. pylori </it>antigen in stool samples. Cognitive function of the children was blindly assessed using Stanford-Benit test 5^thedition, yielding IQ scores. Data on socioeconomic factors and nutritional covariates were collected through maternal interviews and from medical records. Multivariate linear regression analysis was performed to obtain adjusted beta coefficients.</p> <p>Results</p> <p><it>H. pylori </it>infection was associated with lower IQ scores only in children from a relatively higher socioeconomic community; adjusted beta coefficient -6.1 (95% CI -11.4, -0.8) (P = 0.02) for full-scale IQ score, -6.0 (95% CI -11.1, -0.2) (P = 0.04) for non-verbal IQ score and -5.7 (95% CI -10.8, -0.6) (P = 0.02) for verbal IQ score, after controlling for potential confounders.</p> <p>Conclusions</p> <p><it>H. pylori </it>infection might be negatively involved in cognitive development at early school age. Further studies in other populations with larger samples are needed to confirm this novel finding.</p

Efficacy and tolerability of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: sex and age effects and effect size across the day

<p>Abstract</p> <p>Background</p> <p>Efficacy and safety profiles by sex and age (6-9 vs 10-12 years) and magnitude and duration of effect by effect size overall and across the day of lisdexamfetamine dimesylate (LDX) vs placebo were assessed.</p> <p>Methods</p> <p>This study enrolled children (6-12 years) with attention-deficit/hyperactivity disorder (ADHD) in an open-label dose optimization with LDX (30-70 mg/d) followed by a randomized, double-blind, placebo-controlled, 2-way crossover phase. Post hoc analyses assessed interaction between sex or age and treatment and assessed effect sizes for Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) and Permanent Product Measure of Performance (PERMP) scales and ADHD Rating Scale IV measures. No corrections for multiple testing were applied on time points and subgroup statistical comparisons.</p> <p>Results</p> <p>129 participants enrolled; 117 randomized. Both sexes showed improvement on all assessments at postdose time points; females showed less impairment than males for SKAMP and PERMP scores in treatment and placebo groups at nearly all times. Both age groups improved on all assessments at postdose time points. Children 10-12 years had less impairment in SKAMP ratings than those 6-9 years. Treatment-by-sex interactions were observed at time points for SKAMP-D, SKAMP total, and PERMP scores; no consistent pattern across scales or time points was observed. LDX demonstrated significant improvement vs placebo, by effect size, on SKAMP-D from 1.5-13 hours postdose. The overall LS mean (SE) SKAMP-D effect size was -1.73 (0.18). In the dose-optimization phase, common (≥2%) treatment-emergent adverse events (TEAEs) in males were upper abdominal pain, headache, affect lability, initial insomnia, and insomnia; in females were nausea and decreased weight. During the crossover phase for those taking LDX, higher incidence (≥2% greater) was observed in males for upper abdominal pain and insomnia and in females for nausea and headache. Overall incidence of TEAEs in age groups was similar.</p> <p>Conclusion</p> <p>Apparent differences in impairment level between sex and age groups were noted. However, these results support the efficacy of LDX from 1.5 hours to 13 hours postdose in boys and girls with medium to large effect sizes across the day with some variability in TEAE incidence by sex.</p> <p>Trial Registration Number</p> <p>ClinicalTrials.gov Identifier: <a href="http://clinicaltrials.gov/ct2/show/NCT00500149">NCT00500149</a>.</p

LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

<p>Abstract</p> <p>Background</p> <p>The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (e<it>fficacy and tolerability of the combination of <b>LI</b>thium and <b>CA</b>rbamazepine compared to lithium and <b>VAL</b>proic acid in the treatment of young bipolar patients</it>) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs.</p> <p>Methods</p> <p>LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study.</p> <p>Results</p> <p>LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012.</p> <p>Conclusions</p> <p>Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00976794</p

Unique establishment of procephalic head segments is supported by the identification of cis-regulatory elements driving segment-specific segment polarity gene expression in Drosophila

Anterior head segmentation is governed by different regulatory mechanisms than those that control trunk segmentation in Drosophila. For segment polarity genes, both initial mode of activation as well as cross-regulatory interactions among them differ from the typical genetic circuitry in the trunk and are unique for each of the procephalic segments. In order to better understand the segment-specific gene network responsible for the procephalic expression of the earliest active segment polarity genes wingless and hedgehog, we started to identify and analyze cis-regulatory DNA elements of these genes. For hedgehog, we could identify a cis-regulatory element, ic-CRE, that mediates expression specifically in the posterior part of the intercalary segment and requires promoter-specific interaction for its function. The intercalary stripe is the last part of the metameric hedgehog expression pattern that appears during embryonic development, which probably reflects the late and distinct establishment of this segment. The identification of a cis-regulatory element that is specific for one head segment supports the mutant-based observation that the expression of segment polarity genes is governed by a unique gene network in each of the procephalic segments. This provides further indication that the anterior-most head segments represent primary segments, which are set up independently, in contrast to the secondary segments of the trunk, which resemble true repetitive units