523 research outputs found

    Bulk reconstruction of metrics inside black holes by complexity

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    We provide a formula to reconstruct bulk spacetime metrics inside black holes by the time dependence of complexity in the dual quantum field theory, based on the complexity=volume (CV) conjecture in the holographic duality.Comment: 22 pages, 2 figure

    Clozapine Pharmacogenetic Studies in Schizophrenia: Efficacy and Agranulocytosis

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    Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis

    Clozapine Pharmacogenetic Studies in Schizophrenia

    Get PDF
    Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis

    PACAP is Implicated in the Stress Axes

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    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide that functions as a neurotransmitter, neuromodulator and neurotrophic factor. Accumulating evidence implicates PACAP as an important regulator of both central and/or peripheral components of the stress axes, particularly exposure to prolonged or traumatic stress. Indeed, PACAP and its cognate receptors are widely expressed in the brain regions and peripheral tissues that mediate stress-related responses. In the sympathoadrenomedullary system, PACAP is required for sustained epinephrine secretion during metabolic stress. It is likely that PACAP regulates autonomic function and contributes to peripheral homeostasis by maintaining a balance between sympathetic and parasympathetic activity, favoring stimulation of the sympathetic system. Furthermore, PACAP is thought to act centrally on the paraventricular nucleus of the hypothalamus to regulate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Intriguingly, PACAP is also active in brain structures that mediate anxiety- and fear-related behaviors, and the expression of PACAP and its receptors are dynamically altered under pathologic conditions. Thus PACAP may influence both hard-wired (genetically determined) stress responses and gene-environment interactions in stress-related psychopathology. This article aims to overview the molecular mechanisms and psychiatric implications of PACAP-dependent stress responses

    Additional kernel observer: privilege escalation attack prevention mechanism focusing on system call privilege changes

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    Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator privileges are acquired by an attacker through a privilege escalation attack, the attacker can operate the entire system and cause serious damage. In this paper, we propose an additional kernel observer (AKO) that prevents privilege escalation attacks that exploit operating system vulnerabilities. We focus on the fact that a process privilege can be changed only by specific system calls. AKO monitors privilege information changes during system call processing. If AKO detects a privilege change after system call processing, whereby the invoked system call does not originally change the process privilege, AKO regards the change as a privilege escalation attack and applies countermeasures against it. AKO can therefore prevent privilege escalation attacks. Introducing the proposed method in advance can prevent this type of attack by changing any process privilege that was not originally changed in a system call, regardless of the vulnerability type. In this paper, we describe the design and implementation of AKO for Linux x86 64-bit. Moreover, we show that AKO can be expanded to prevent the falsification of various data in the kernel space. Then, we present an expansion example that prevents the invalidation of Security-Enhanced Linux. Finally, our evaluation results show that AKO is effective against privilege escalation attacks, while maintaining low overhead

    Development of a low-alpha-emitting {\mu}-PIC for NEWAGE direction-sensitive dark-matter search

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    NEWAGE is a direction-sensitive dark-matter-search experiment that uses a micro-patterned gaseous detector, or {\mu}-PIC, as the readout. The main background sources are {\alpha}-rays from radioactive contaminants in the {\mu}-PIC. We have therefore developed a low-alpha-emitting {\mu}-PICs and measured its performances. We measured the surface {\alpha}-ray emission rate of the {\mu}-PIC in the Kamioka mine using a surface {\alpha}-ray counter based on a micro TPC.Comment: 6 pages, 4 figure

    Study of Negative-Ion TPC Using {\mu}-PIC for Directional Dark Matter Search

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    Negative-ion time projection chambers(TPCs) have been studied for low-rate and high-resolution applications such as dark matter search experiments. Recently, a full volume fiducialization in a self-triggering TPC was realized. This innovative technology demonstrated a significant reduction in the background with MWPC-TPCs. We studied negative-ion TPC using the {\mu}-PIC+GEM system and obtained sufficient gas gain with CS2_{2}gas and SF6_{6} gas at low pressures. We expect an improvement in detector sensitivity and angular resolution with better electronics
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