Photonic transistor and router using a single quantum-dotconfined spin in a single-sided optical microcavity

The future Internet is very likely the mixture of all-optical Internet with low power consumption and quantum Internet with absolute security guaranteed by the laws of quantum mechanics. Photons would be used for processing, routing and com-munication of data, and photonic transistor using a weak light to control a strong light is the core component as an optical analogue to the electronic transistor that forms the basis of modern electronics. In sharp contrast to previous all-optical tran-sistors which are all based on optical nonlinearities, here I introduce a novel design for a high-gain and high-speed (up to terahertz) photonic transistor and its counterpart in the quantum limit, i.e., single-photon transistor based on a linear optical effect: giant Faraday rotation induced by a single electronic spin in a single-sided optical microcavity. A single-photon or classical optical pulse as the gate sets the spin state via projective measurement and controls the polarization of a strong light to open/block the photonic channel. Due to the duality as quantum gate for quantum information processing and transistor for optical information processing, this versatile spin-cavity quantum transistor provides a solid-state platform ideal for all-optical networks and quantum networks

Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

Nos2 Inactivation Promotes the Development of Medulloblastoma in Ptch1+/− Mice by Deregulation of Gap43–Dependent Granule Cell Precursor Migration

Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs) of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1+/− mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1+/− mice with mice lacking inducible nitric oxide synthase (Nos2) to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1+/− Nos2−/− mice compared to Ptch1+/− Nos2+/+ mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1+/+ Nos2−/− mice but not from Ptch1+/− Nos2−/− mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43). Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1+/+ Nos2−/− mice but increased in Ptch1+/− Nos2−/− mice relative to Ptch1+/− Nos2+/+ mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1+/− mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during morphogenesis is crucial for their malignant progression

Increased Membrane Cholesterol in Lymphocytes Diverts T-Cells toward an Inflammatory Response

Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40–50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4+ Foxp3+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response

Quantum Spacetime Phenomenology

I review the current status of phenomenological programs inspired by quantum-spacetime research. I stress in particular the significance of results establishing that certain data analyses provide sensitivity to effects introduced genuinely at the Planck scale. And my main focus is on phenomenological programs that managed to affect the directions taken by studies of quantum-spacetime theories.Comment: 125 pages, LaTex. This V2 is updated and more detailed than the V1, particularly for quantum-spacetime phenomenology. The main text of this V2 is about 25% more than the main text of the V1. Reference list roughly double

The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention

Klein JP, Berger T, Schroeder J, et al. The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention. BMC Psychiatry. 2013;13(1): 239.Background: Depressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression. Methods/Design: This study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in-and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments. Discussion: The study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry

Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction

A robust nanopillar platform with increased spatial resolution reveals that perinuclear forces, originating from stress fibres spanning the nucleus of fibroblasts, are significantly higher on these nanostructured substrates than the forces acting on peripheral adhesions. Many perinuclear adhesions embrace several nanopillars at once, pulling them into β1-integrin- and zyxin-rich clusters, which are able to translocate in the direction of cell motion without losing their tensile strength. The high perinuclear forces are greatly reduced upon inhibition of cell contractility or actin polymerization and disruption of the actin cap by KASH dominant-negative mutant expression. LMNA null fibroblasts have higher peripheral versus perinuclear forces, impaired perinuclear β1-integrin recruitment, as well as YAP nuclear translocation, functional alterations that can be rescued by lamin A expression. These highly tensed actin-cap fibres are required for YAP nuclear signalling and thus play far more important roles in sensing nanotopographies and mechanochemical signal conversion than previously thought.ISSN:1465-7392ISSN:1476-467

Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics

Disturbances of the sleep-wake cycle are highly prevalent and diverse. The aetiology of some sleep disorders, such as circadian rhythm sleep-wake disorders, is understood at the conceptual level of the circadian and homeostatic regulation of sleep and in part at a mechanistic level. Other disorders such as insomnia are more difficult to relate to sleep regulatory mechanisms or sleep physiology. To further our understanding of sleep-wake disorders and the potential of novel therapeutics, we discuss recent findings on the neurobiology of sleep regulation and circadian rhythmicity and its relation with the subjective experience of sleep and the quality of wakefulness. Sleep continuity and to some extent REM sleep emerge as determinants of subjective sleep quality and waking performance. The effects of insufficient sleep primarily concern subjective and objective sleepiness as well as vigilant attention, whereas performance on higher cognitive functions appears to be better preserved albeit at the cost of increased effort. We discuss age-related, sex and other trait-like differences in sleep physiology and sleep need and compare the effects of existing pharmacological and non-pharmacological sleep- and wake-promoting treatments. Successful non-pharmacological approaches such as sleep restriction for insomnia and light and melatonin treatment for circadian rhythm sleep disorders target processes such as sleep homeostasis or circadian rhythmicity. Most pharmacological treatments of sleep disorders target specific signalling pathways with no well-established role in either sleep homeostasis or circadian rhythmicity. Pharmacological sleep therapeutics induce changes in sleep structure and the sleep EEG which are specific to the mechanism of action of the drug. Sleep- and wake-promoting therapeutics often induce residual effects on waking performance and sleep, respectively. The need for novel therapeutic approaches continues not at least because of the societal demand to sleep and be awake out of synchrony with the natural light-dark cycle, the high prevalence of sleep-wake disturbances in mental health disorders and in neurodegeneration. Novel approaches, which will provide a more comprehensive description of sleep and allow for large-scale sleep and circadian physiology studies in the home environment, hold promise for continued improvement of therapeutics for disturbances of sleep, circadian rhythms and waking performance