216 research outputs found

    Cancer Salt Nostalgia

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    High-salt (sodium chloride) diets have been strongly associated with disease states and poor health outcomes. Traditionally, the impact of salt intake is primarily studied in cardiovascular diseases, hypertension and renal diseases; however, recently there has been increasing evidence demonstrating the role of salt in autoimmune diseases. Salt has been shown to modulate the inflammatory activation of immune cells leading to chronic inflammation-related ailments. To date, there is minimal evidence showing a direct correlation of salt with cancer incidence and/or cancer-related adverse clinical outcomes. In this review article, we will discuss the recent understanding of the molecular role of salt, and elucidate the apparent double-edged sword nature of the relationship between salt and cancer progression

    Granular Matter: Microstructural Evolution and Mechanical Response

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    Heterogeneous (nano) composites, manufactured by the densification of variously sized grains, represent an important and ubiquitous class of technologically relevant materials. Typical grain sizes in such materials range from macroscopic to a few nanometers. The morphology exhibited by such disordered materials is complex and intricately connected with its thermal and electrical transport properties. It is important to quantify the geometric features of these materials and simulate the fabrication process. Additionally, granular materials exhibit complex structural and mechanical properties that crucially govern their reliability during industrial use. In this work, we simulate the densification of soft deformable grains from a low-density fluid-state to a mechanically rigid solid-state. The simulation is performed via methods of structural optimization that minimize the system free energy in the athermal limit. The effect of grain shapes and sizes (and dispersity therein) is simulated in detail and their effect on the composite morphology is quantified. Furthermore, in the present simulations the composite materials are perturbed under external stress (strain) stimuli to understand the mechanical response and calculate the material stress-strain response, effective Poisson’s ratio and yield stress. A tool is created to simulate the consolidation and stress-perturbation of the different shaped and sized grains using techniques of computational geometry and gradient-based optimization routines to relax microstructures into minimum-energy stable phases. The tool uses MATLAB and C++, wrapped around xml for generating Graphical User Interface (GUI). The tool can be deployed online in nanoHUB platform of Network for Computational Nanotechnology (NCN). Besides computing the data like enthalpy of the system and internal stress, this tool also utilizes visualization technique like Visualization ToolKit (VTK) to graph and visualize the optimized microstructures. Hence, the creation of this tool allows the wider audiences simulate the consolidation and stress-perturbation of the different shaped and sized grains

    Effect of kappa-opioid receptor agonists U69593, U50488H, spiradoline and salvinorin A on cocaine-induced drug-seeking in rats

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    Our previous work indicated that pretreatment with the selective kappa opioid receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of cocaine to reinstate extinguished cocaine-seeking behavior. The present study expanded these initial tests to include other traditional KOPr agonists, U50488H, spiradoline (SPR), and salvinorin A (Sal A), an active constituent of the plant Salvia divinorum. Following acquisition and stabilization of cocaine self-administration, cocaine-produced drug-seeking was measured. This test was conducted in a single day and comprised an initial phase of self-administration, followed by a phase of extinguished responding. The final phase examined reinstatement of extinguished cocaine self-administration followed by a priming injection of cocaine (20.0 mg/kg, intraperitoneal (I.P.)) in combination with the various KOPr agonists. Cocaine-induced drug-seeking was attenuated by pretreatment with U69593 (0.3 mg/kg, subcutaneous (S.C.)), U50488H (30.0 mg/kg, I.P.), SPR (1.0, 3.0 mg/kg, I.P.) and Sal A (0.3, 1.0 mg/kg, I.P.). Sal A (0.3, 1.0 mg/kg, I.P.) had no effect on operant responding to obtain sucrose reinforcement or on cocaine induced hyperactivity. These findings show that Sal A, like other traditional KOPr agonists attenuates cocaine-induced drug seeking behavior

    Single injection of novel kappa opioid receptor agonist salvinorin A attenuates expression of cocaine induced behavioral sensitization in rats

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    Kappa opioid receptor (KOPr) activation antagonizes many cocaine-related behaviors but adverse side effects such as sedation, dysphoria and depression limit their therapeutic use. Recently, salvinorin A (Sal A), a naturally occurring KOPr agonist, has been shown to attenuate cocaineinduced drug-seeking in a model of relapse in rats. The present study evaluated the effects of acute Sal A exposure on cocaine-induced hyperactivity and cocaine sensitization in rats. Acute treatment with the dose of Sal A that decreased drug-seeking in a previous study (0.3 mg/kg), significantly attenuated the expression of cocaine sensitization. This dose of Sal A failed to affect spontaneous locomotion or to produce a conditioned taste aversion to a novel-tasting saccharin solution. However, Sal A decreased climbing and swimming time and increased time spent immobile in the forced swim test. These findings indicate that Sal A, just like traditional KOPr agonists, attenuates cocaine-induced behavioral sensitization but does not produce the adverse effect of conditioned aversion, suggesting improved potential compliance. However, pro-depressive effects were also produced and these effects may limit the therapeutic potential

    The 2-Methoxy methyl analogue of salvinorin A attenuates cocaine-induced drug seeking and sucrose reinforcements in rats

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    Îș opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene Îș opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxymethyl salvinorin B (MOM Sal B) is a longer acting Sal A analogue with high affinity for Îș opioid receptors. In this study, we tested MOM Sal B for its ability to modulate cocaine-seeking behavior in rats. MOM Sal B (0.3 mg/kg) successfully attenuated cocaine-seeking but also attenuated sucrose reinforcement. No change in activity was observed in either cocaine-induced hyperactivity or spontaneous open field activity tests but increased immobility and decreased swimming times in the forced swim test were observed. This study indicates that Îș opioid receptor activation by more potent Sal A analogues modulates cocaine-seeking behavior non-selectively without causing sedation, suggesting an improved side effects profile. However, pro-depressive effects are seen, which may limit the therapeutic potential of this compound. Future studies with Sal A analogues having affinities at other opioid receptors are warranted as they have the potential to identify compounds having effective anti-addiction properties

    Using dark modes for high-fidelity optomechanical quantum state transfer

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    In a recent publication [Y.D. Wang and A.A. Clerk, Phys. Rev. Lett. 108, 153603 (2012)], we demonstrated that one can use interference to significantly increase the fidelity of state transfer between two electromagnetic cavities coupled to a common mechanical resonator over a naive sequential-transfer scheme based on two swap operations. This involved making use of a delocalized electromagnetic mode which is decoupled from the mechanical resonator, a so-called "mechanically-dark" mode. Here, we demonstrate the existence of a new "hybrid" state transfer scheme which incorporates the best elements of the dark-mode scheme (protection against mechanical dissipation) and the double-swap scheme (fast operation time). Importantly, this new scheme also does not require the mechanical resonator to be prepared initially in its ground state. We also provide additional details on the previously-described interference-enhanced transfer schemes, and provide an enhanced discussion of how the interference physics here is intimately related to the optomechanical analogue of electromagnetically-induced transparency (EIT). We also compare the various transfer schemes over a wide range of relevant experimental parameters, producing a "phase diagram" showing the the optimal transfer scheme for different points in parameter space.Comment: 39 pages, 11 figures NJP 14 (Focus issue on Optomechanics