1,021 research outputs found

    Using Multiple Linear Regression to Estimate Volatility in the Stock Market

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    This project entails an in-depth analysis on the current mathematical methods used to calculate volatility in the stock market like the Black-Scholes Stochastic Partial Differential Equation (PDE). Expanding upon the faculty mentor’s previously published work, a new method for calculating volatility using multiple linear regression on key macroeconomic factors was tested in predicting the price for the Standard and Poor’s 500 Index (S&P 500) for a given month. The results from the new volatility model were then compared with the well-known Chicago Board Options Exchange Volatility Index (VIX) since the VIX’s creation in 1991. While the new models for volatility could not be used to adequately price S&P 500 options for the future, it performed similar to VIX over time, and while the value for VIX was always high, the values for new volatility only spiked significantly when there was a potential crash in the market caused by weak fundamentals, like the dot com crash in 2001. With this information in hand, one could use a disparity between the regression model and the actual S&P 500 value to forecast a future crash caused by poor fundamentals in the market

    Position and Stiffness Control of One DoF Revolute Joint Using a Biphasic Media Variable Stiffness Actuator

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    At this time, several industrial processes and service tasks need safe interactions between humans and robots. This safety can be achieved using compliance design and control of mechanisms. This paper presents a compliant revolute joint mechanism using a variable stiffness actuator. The method for adapting the stiffness in the actuator includes a member onfigured to transmit motion that is connected to a fluidic circuit, into which a biphasic control fluid circulates. Actuator's stiffness is controlled by changing pressure of control fluid into distribution lines. The used control fluid is biphasic, composed of separated gas and liquid fractions with predefined ratio. A mathematical model of the actuator is presented, a modelbased control method is implemented to track the desired position and stiffness, and equations relating to the dynamics of the mechanism are provided. Results from force loaded and unloaded simulations and experiments with a physical prototype are discussed

    Ultrafast all-optical switching enabled by epsilon-near-zero-tailored absorption in metal-insulator nanocavities

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    Ultrafast control of light-matter interactions is fundamental in view of new technological frontiers of information processing. However, conventional optical elements are either static or feature switching speeds that are extremely low with respect to the time scales at which it is possible to control light. Here, we exploit the artificial epsilon-near-zero (ENZ) modes of a metal-insulator-metal nanocavity to tailor the linear photon absorption of our system and realize a nondegenerate all-optical ultrafast modulation of the reflectance at a specific wavelength. Optical pumping of the system at its high energy ENZ mode leads to a strong redshift of the low energy mode because of the transient increase of the local dielectric function, which leads to a sub-3-ps control of the reflectance at a specific wavelength with a relative modulation depth approaching 120%

    How do MNC R&D laboratory roles affect employee international assignments?

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    Research and development (R&D) employees are important human resources for multinational corporations (MNCs) as they are the driving force behind the advancement of innovative ideas and products. International assignments of these employees can be a unique way to upgrade their expertise; allowing them to effectively recombine their unique human resources to progress existing knowledge and advance new ones. This study aims to investigate the effect of the roles of R&D laboratories in which these employees work on the international assignments they undertake. We categorise R&D laboratory roles into those of the support laboratory, the locally integrated laboratory and the internationally interdependent laboratory. Based on the theory of resource recombinations, we hypothesise that R&D employees in support laboratories are not likely to assume international assignments, whereas those in locally integrated and internationally interdependent laboratories are likely to assume international assignments. The empirical evidence, which draws from research conducted on 559 professionals in 66 MNC subsidiaries based in Greece, provides support to our hypotheses. The resource recombinations theory that extends the resource based view can effectively illuminate the international assignment field. Also, research may provide more emphasis on the close work context of R&D scientists rather than analyse their demographic characteristics, the latter being the focus of scholarly practice hitherto

    Redox modulation by plant polyphenols targeting vitagenes for chemoprevention and therapy: Relevance to novel anti-cancer interventions and mini-brain organoid technology

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    The scientific community, recently, has focused notable attention on the chemopreventive and therapeutic effects of dietary polyphenols for human health. Emerging evidence demonstrates that polyphenols, flavonoids and vitamins counteract and neutralize genetic and environmental stressors, particularly oxidative stress and inflammatory process closely connected to cancer initiation, promotion and progression. Interestingly, polyphenols can exert antioxidant or pro-oxidant cytotoxic effects depending on their endogenous concentration. Notably, polyphenols at high dose act as pro-oxidants in a wide type of cancer cells by inhibiting Nrf2 pathway and the expression of antioxidant vitagenes, such as NAD(P)H-quinone oxidoreductase (NQO1), glutathione transferase (GT), GPx, heme oxygenase-1 (HO-1), sirtuin-1 (Sirt1) and thioredoxin (Trx) system which play an essential role in the metabolism of reactive oxygen species (ROS), detoxification of xenobiotics and inhibition of cancer progression, by inducing apoptosis and cell cycle arrest according to the hormesis approach. Importantly, mutagenesis of Nrf2 pathway can exacerbate its "dark side" role, representing a crucial event in the initiation stage of carcinogenesis. Herein, we review the hormetic effects of polyphenols and nanoincapsulated-polyphenols in chemoprevention and treatment of brain tumors via activation or inhibition of Nrf2/vitagenes to suppress carcinogenesis in the early stages, and thus inhibit its progression. Lastly, we discuss innovative preclinical approaches through mini-brain tumor organoids to study human carcinogenesis, from basic cancer research to clinical practice, as promising tools to recapitulate the arrangement of structural neuronal tissues and biological functions of the human brain, as well as test drug toxicity and drive personalized and precision medicine in brain cancer

    Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

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    <p>Abstract</p> <p>Background</p> <p>Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry.</p> <p>Methods</p> <p>A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV).</p> <p>Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD.</p> <p>Results</p> <p>The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia.</p> <p>Conclusion</p> <p>The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.</p

    The Large Zinc Finger Protein ZAS3 Is a Critical Modulator of Osteoclastogenesis

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    Mice deficient in the large zinc finger protein, ZAS3, show postnatal increase in bone mass suggesting that ZAS3 is critical in the regulation of bone homeostasis. Although ZAS3 has been shown to inhibit osteoblast differentiation, its role on osteoclastogenesis has not been determined. In this report we demonstrated the role of ZAS3 in bone resorption by examining the signaling mechanisms involved in osteoclastogenesis.Comparison of adult wild-type and ZAS3 knockout (ZAS3-/-) mice showed that ZAS3 deficiency led to thicker bones that are more resistant to mechanical fracture. Additionally, ZAS3-/- bones showed fewer osteoclasts and inefficient M-CSF/sRANKL-mediated osteoclastogenesis ex vivo. Utilizing RAW 264.7 pre-osteoclasts, we demonstrated that overexpression of ZAS3 promoted osteoclastogenesis and the expression of crucial osteoclastic molecules, including phospho-p38, c-Jun, NFATc1, TRAP and CTSK. Contrarily, ZAS3 silencing by siRNA inhibited osteoclastogenesis. Co-immunoprecipitation experiments demonstrated that ZAS3 associated with TRAF6, the major receptor associated molecule in RANK signaling. Furthermore, EMSA suggested that nuclear ZAS3 could regulate transcription by binding to gene regulatory elements.Collectively, the data suggested a novel role of ZAS3 as a positive regulator of osteoclast differentiation. ZAS3 deficiency caused increased bone mass, at least in part due to decreased osteoclast formation and bone resorption. These functions of ZAS3 were mediated via activation of multiple intracellular targets. In the cytoplasmic compartment, ZAS3 associated with TRAF6 to control NF-kB and MAP kinase signaling cascades. Nuclear ZAS3 acted as a transcriptional regulator for osteoclast-associated genes. Additionally, ZAS3 activated NFATc1 required for the integration of RANK signaling in the terminal differentiation of osteoclasts. Thus, ZAS3 was a crucial molecule in osteoclast differentiation, which might potentially serve as a target in the design of therapeutic interventions for the treatment of bone diseases related to increased osteoclast activity such as postmenopausal osteoporosis, Paget's disease, and rheumatoid arthritis

    Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

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    Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans

    Biomechanical factors in atherosclerosis: mechanisms and clinical implications†

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    Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors—mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current ‘state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future researc

    RasGRP4 Is a Novel Ras Activator Isolated from Acute Myeloid Leukemia

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    Although a number of genetic defects are commonly associated with acute myeloid leukemia (AML), a large percentage of AML cases are cytogenetically normal. This suggests a functional screen for transforming genes is required to identify genetic mutations that are missed by cytogenetic analyses. We utilized a retrovirus-based cDNA expression system to identify transforming genes expressed in cytogenetically normal AML patients. We identified a new member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors, designating it RasGRP4. Subsequently, cDNA sequences encoding rodent and human RasGRP4 proteins were deposited in GenBank. RasGRP4 contains the same protein domain structure as other members of the RasGRP family, including a Ras exchange motif, a CDC25 homology domain, a C1/diacyglycerol-binding domain, and putative calcium-binding EF hands. We show that expression of RasGRP4 induces anchorage-independent growth of Rat1 fibroblasts. RasGRP4 is a Ras-specific activator and, interestingly, is highly expressed in peripheral blood leukocytes and myeloid cell lines. Unlike other RasGRP proteins, RasGRP4 is not expressed in the brain or in lymphoid cells. We demonstrated that 32D myeloid cells expressing RasGRP4 have elevated levels of activated Ras compared with control cells, and phorbol 12-myristate 13-acetate (PMA) treatment greatly enhanced Ras activation. PMA induced membrane localization of RasGRP4 and 32D cells expressing RasGRP4 were capable of cytokine-independent proliferation in the presence of PMA. We conclude that RasGRP4 is a member of the RasGRP family of Ras guanine nucleotide exchange factors that may play a role in myeloid cell signaling growth regulation pathways that are responsive to diacylglycerol levels
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