39 research outputs found

    Detection of Geometric Phases in Superconducting Nanocircuits

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    When a quantum mechanical system undergoes an adiabatic cyclic evolution it acquires a geometrical phase factor in addition to the dynamical one. This effect has been demonstrated in a variety of microscopic systems. Advances in nanotechnologies should enable the laws of quantum dynamics to be tested at the macroscopic level, by providing controllable artificial two-level systems (for example, in quantum dots and superconducting devices). Here we propose an experimental method to detect geometric phases in a superconducting device. The setup is a Josephson junction nanocircuit consisting of a superconducting electron box. We discuss how interferometry based on geometrical phases may be realized, and show how the effect may applied to the design of gates for quantum computation.Comment: 12 page

    Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

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    Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA

    A Controversy That Has Been Tough to Swallow: Is the Treatment of Achalasia Now Digested?

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    Esophageal achalasia is a rare neurodegenerative disease of the esophagus and the lower esophageal sphincter that presents within a spectrum of disease severity related to progressive pathological changes, most commonly resulting in dysphagia. The pathophysiology of achalasia is still incompletely understood, but recent evidence suggests that degeneration of the postganglionic inhibitory nerves of the myenteric plexus could be due to an infectious or autoimmune mechanism, and nitric oxide is the neurotransmitter affected. Current treatment of achalasia is directed at palliation of symptoms. Therapies include pharmacological therapy, endoscopic injection of botulinum toxin, endoscopic dilation, and surgery. Until the late 1980s, endoscopic dilation was the first line of therapy. The advent of safe and effective minimally invasive surgical techniques in the early 1990s paved the way for the introduction of laparoscopic myotomy. This review will discuss the most up-to-date information regarding the pathophysiology, diagnosis, and treatment of achalasia, including a historical perspective. The laparoscopic Heller myotomy with partial fundoplication performed at an experienced center is currently the first line of therapy because it offers a low complication rate, the most durable symptom relief, and the lowest incidence of postoperative gastroesophageal reflux

    Sustaining remission of psychotic depression: Rationale, design and methodology of STOP-PD II

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    Background: Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.Methods/design: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.Discussion: This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.Trial registration and URL: NCT: NCT01427608. © 2013 Flint et al; licensee BioMed Central Ltd

    Long term follow-up in a patient with papillary glioneuronal tumor

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    We report a case of a young female patient with a rare and recently described form of brain tumor. This patient had a history of headache, hemiparesis and motor simple partial seizures. Her investigation revealed a brain tumor involving the left frontal and parietal lobes. The radiological images showed a cystic mass with multiple nodular masses and a rim of contrast enhancement extending from the right parietal cortex to the ipsilateral ventricle and corpus callosum. The patient underwent gross resection of the lesion and the histological analysis of the surgical specimen revealed a pseudopapillary structure formed by delicate vessels intermixed with a fibrillary pattern and bordered by intense astrocytic reaction with Rosenthal fibers. These features correspond to the recently described mixed neuronal-glial neoplasm, the papillary glioneuronal tumor. The patient has been followed for five years since the surgical treatment, without evidence of tumor recurrence, confirming the indolent behavior of this type of tumor.623B86987

    Thrombosis of the internal carotid artery secondary to soft palate injury in children and childhood - Report of two cases

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    Trauma to the soft palate is a uncommon event during childhood. Stroke following intraoral trauma is also rare, but has been well documented by the current literature as a potentially serious complication, In this article, we report 2 cases of posttraumatic internal carotid artery thrombosis depicted by imaging studies, We discuss pathogenesis, and the literature is reviewed, Copyright (C) 2000 S.Karger AG, Basel.32315015
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