Detection of Cathinone and Mephedrone in Plasma by LC-MS/MS Using Standard Addition Quantification Technique

Designer drugs are structural analogs of Drug Enforcement Agency (DEA) Schedule I and II substances. They are synthesized to mimic the effects of illegal drugs of abuse and to bypass the provisions of drug regulations. Despite the increased availability of designer drugs, few studies have focused on specific analytical extraction techniques for their detection and quantification in biological samples. Solid phase extraction (SPE) is the most commonly used technique for sample preparation. The purpose of this study is to evaluate the extraction efficiency of the various SPE columns with different sorbent materials for two designer drugs, cathinone and mephedrone in sheep plasma using LC-MS/MS as well as to evaluate the standard addition quantification technique. SPE columns used in this study were Phenomenex Strata X-C strong cation mixed mode column, Phenomenex Strata X Drug B strong cation mixed mode column and SupelTM HLB hydrophilic modified styrene polymer column. The Phenomenex Strata X-Drug B strong cation cartridge was found to have the best retention profile for our analytes. Percent recovery of initial cathinone concentration was 137.6, 93.6 and 103.6% for 10, 33 and 100ng/mL cathinone respectively using the standard addition method with the X-intercept and 120.9, 91.1 and 103.2% with calculations based on the Y-intercept. Percent recovery of initial mephedrone concentration was 191.9, 105.7 and 116.7% for 10, 33 and 100ng/mL mephedrone respectively using the standard addition method with the X-intercept and 153.5, 97.1 and 115.1% using the Y-intercept

Nanoparticle communications : from chemical signals in nature to wireless sensor networks

The need to convey information has always existed in both the animal and human kingdoms. The article offers a review of the latest developments in transporting information using nanosized particles. It begins by examining chemical signalling in nature, and goes on to discuss recent advances in mimicking this in bio-inspired engineering. It then points out the important difference between signalling and general communication, and explains why the latter is a more challenging problem. The existing research on mimicking chemical signalling in nature is a precurser to research into general chemical communication. A review of the latest theoretical research in general chemical communications is presented, along with the practical developments of the world’s first nanoparticle communications test-bed. In the parts of the article, the authors discuss the potential research challenges and identify three important areas for future development: robustness, miniaturization, and scalability

Quantifying the effects of antibiotic treatment on the extracellular polymer network of antimicrobial resistant and sensitive biofilms using multiple particle tracking

Novel therapeutics designed to target the polymeric matrix of biofilms requires innovative techniques to accurately assess their efficacy. Here, multiple particle tracking (MPT) was developed to characterize the physical and mechanical properties of antimicrobial resistant (AMR) bacterial biofilms and to quantify the effects of antibiotic treatment. Studies employed nanoparticles (NPs) of varying charge and size (40–500 nm) in Pseudomonas aeruginosa PAO1 and methicillin-resistant Staphylococcus aureus (MRSA) biofilms and also in polymyxin B (PMB) treated Escherichia coli biofilms of PMB-sensitive (PMBSens) IR57 and PMB-resistant (PMBR) PN47 strains. NP size-dependent and strain-related differences in the diffusion coefficient values of biofilms were evident between PAO1 and MRSA. Dose-dependent treatment effects induced by PMB in PMBSens E. coli biofilms included increases in diffusion and creep compliance (P < 0.05), not evident in PMB treatment of PMBR E. coli biofilms. Our results highlight the ability of MPT to quantify the diffusion and mechanical effects of antibiotic therapies within the AMR biofilm matrix, offering a valuable tool for the pre-clinical screening of anti-biofilm therapies

An adaptive grid refinement strategy for the simulation of negative streamers

The evolution of negative streamers during electric breakdown of a non-attaching gas can be described by a two-fluid model for electrons and positive ions. It consists of continuity equations for the charged particles including drift, diffusion and reaction in the local electric field, coupled to the Poisson equation for the electric potential. The model generates field enhancement and steep propagating ionization fronts at the tip of growing ionized filaments. An adaptive grid refinement method for the simulation of these structures is presented. It uses finite volume spatial discretizations and explicit time stepping, which allows the decoupling of the grids for the continuity equations from those for the Poisson equation. Standard refinement methods in which the refinement criterion is based on local error monitors fail due to the pulled character of the streamer front that propagates into a linearly unstable state. We present a refinement method which deals with all these features. Tests on one-dimensional streamer fronts as well as on three-dimensional streamers with cylindrical symmetry (hence effectively 2D for numerical purposes) are carried out successfully. Results on fine grids are presented, they show that such an adaptive grid method is needed to capture the streamer characteristics well. This refinement strategy enables us to adequately compute negative streamers in pure gases in the parameter regime where a physical instability appears: branching streamers.Comment: 46 pages, 19 figures, to appear in J. Comp. Phy

The European Union in the World — A Community of Values

These are momentous times in Europe. The Euro has been successfully introduced, the enlargement negotiations are approaching their climax, and the European Convention (“Convention”) is moving towards the drafting of a constitution for a new, continent-wide political entity. At the same time, unrest is manifest, particularly in two areas. On the one hand, many of our citizens, and not just the political elites, are dissatisfied with Europe\u27s performance on the world stage and are concerned about the maintenance of peace and security within the Union. In these areas they would like to see a strengthened, more effective entity-- “more Europe.” On the other hand, their disenchantment with the long reach of European Union (“EU” or “Union”) regulation in the first pillar area of economic policy is growing. The feeling of loss of local control over their destiny and a vague feeling of potential loss of identity within an ever more centralized polity is palpable. Here, they want “less Europe.” In the outside world, change is also the order of the day. The ice-sheet of bipolarity, which overlaid and hid the complexity of international relations during the Cold War, is breaking up at an ever-increasing speed and revealing a world in which two paradigms are competing to become the underlying ordering principles for the new century. The traditional paradigm of interacting Nation States, each pursuing its own separate interests, with alliances allowing the small to compete with the large, is alive and well, and its proponents like Machiavelli or Churchill continue to be in vogue in the literature of international relations and the rhetoric of world leaders. At the same time, there is a school of thought which points to the growing economic and ecological interdependence of our societies and the necessity for new forms of global governance to complement national action. It is also becoming abundantly clear that the concept of a “Nation State” is often a fiction, positing as it does an identity between the citizens of a State and the members of a culturally homogenous society. For both reasons, the concept of the Nation State as the principal actor on the world stage, is called into question. The experience of the Union with the sharing of State sovereignty is clearly related to the second paradigm and also to the EU\u27s firm support for the development of the United Nations (“U.N.”) as well as other elements of multilateral governance. It would hardly be wise to suggest that any foreign policy, and certainly not that of the EU, should be based only on this paradigm. Given the recurrent threats to security, which seem to be part of the human condition expressed by some as the “inevitability of war”--the defense of territorial integrity; action against threats of aggression; and resistance to crimes against humanity such as genocide--the ability to conduct a security policy based much more on the old paradigm of interacting interests will continue to be required. That the EU needs to develop such a capability will be taken here as a given. Such a crisis-management capability will be essential to the Union, but will be distinguished here from the more long-term elements of foreign policy, which can be thought of as being designed to reduce the need for crisis management in the context of a security policy to a minimum. The crisis-management area of policy will not be treated further here. The thesis of this Essay is that the same set of political concepts can serve as a guide to the future internal development of the EU and as the basis of such a long-term foreign policy. Furthermore, it suggests that neither should be seen in terms of the balancing of interests but rather, as the expression of a small list of fundamental values. The list is as follows: (1) the rule of law as the basis for relations between members of society; (2) the interaction between the democratic process and entrenched human rights in political decision-making; (3) the operation of competition within a market economy as the source of increasing prosperity; (4) the anchoring of the principle of solidarity among all members of society alongside that of the liberty of the individual; (5) the adoption of the principle of sustainability of all economic development; and (6) the preservation of separate identities and the maintenance of cultural diversity within society. These values can be seen as the answer to the question posed both, by citizens of the Union and by our fellow citizens of the world: “What does the EU stand for?” In exploring these values we should, however, remember that in the real world there will be occasions on which Realpolitik will intrude and the interest-based paradigm will prevail

Skyrmion Hall Effect Revealed by Direct Time-Resolved X-Ray Microscopy

Magnetic skyrmions are highly promising candidates for future spintronic applications such as skyrmion racetrack memories and logic devices. They exhibit exotic and complex dynamics governed by topology and are less influenced by defects, such as edge roughness, than conventionally used domain walls. In particular, their finite topological charge leads to a predicted "skyrmion Hall effect", in which current-driven skyrmions acquire a transverse velocity component analogous to charged particles in the conventional Hall effect. Here, we present nanoscale pump-probe imaging that for the first time reveals the real-time dynamics of skyrmions driven by current-induced spin orbit torque (SOT). We find that skyrmions move at a well-defined angle {\Theta}_{SH} that can exceed 30{\deg} with respect to the current flow, but in contrast to theoretical expectations, {\Theta}_{SH} increases linearly with velocity up to at least 100 m/s. We explain our observation based on internal mode excitations in combination with a field-like SOT, showing that one must go beyond the usual rigid skyrmion description to unravel the dynamics.Comment: pdf document arxiv_v1.1. 24 pages (incl. 9 figures and supplementary information

The uptake of tocopherols by RAW 264.7 macrophages

BACKGROUND: Alpha-Tocopherol and gamma-tocopherol are the two major forms of vitamin E in human plasma and the primary lipid soluble antioxidants. The dietary intake of gamma-tocopherol is generally higher than that of alpha-tocopherol. However, alpha-tocopherol plasma levels are about four fold higher than those of gamma-tocopherol. Among other factors, a preferential cellular uptake of gamma-tocopherol over alpha-tocopherol could contribute to the observed higher plasma alpha-tocopherol levels. In this investigation, we studied the uptake and depletion of both alpha-tocopherol and gamma-tocopherol (separately and together) in cultured RAW 264.7 macrophages. Similar studies were performed with alpha-tocopheryl quinone and gamma-tocopheryl quinone, which are oxidation products of tocopherols. RESULTS: RAW 264.7 macrophages showed a greater uptake of gamma-tocopherol compared to alpha-tocopherol (with uptake being defined as the net difference between tocopherol transported into the cells and loss due to catabolism and/or in vitro oxidation). Surprisingly, we also found that the presence of gamma-tocopherol promoted the cellular uptake of alpha-tocopherol. Mass balance considerations suggest that products other than quinone were formed during the incubation of tocopherols with macrophages. CONCLUSION: Our data suggests that gamma-tocopherol could play a significant role in modulating intracellular antioxidant defence mechanisms. Moreover, we found the presence of gamma-tocopherol dramatically influenced the cellular accumulation of alpha-tocopherol, i.e., gamma-tocopherol promoted the accumulation of alpha-tocopherol. If these results could be extrapolated to in vivo conditions they suggest that gamma-tocopherol is selectively taken up by cells and removed from plasma more rapidly than alpha-tocopherol. This could, in part, contribute to the selective maintenance of alpha-tocopherol in plasma compared to gamma-tocopherol

PACS: 29.30.-h; 29.30.Ep; 29.30.Kv

Abstract A large solid angle low-Z charged particle detector system was built in order to improve the quality of the identification and selection of evaporation channels for in-beam g-spectroscopy measurements. The array consists of 11 plastic phoswich telescopes closely packed in a 4p arrangement and to be used as an ancillary system for the Pelletron Laboratory g-ray spectrometer. The new system was tested in g-particle and g-g-particle coincidence measurements using the 27 Al þ 16 O and 100 Mo þ 11 B reactions, at 53 and 43 MeV incident beam energies, respectively. The values for the particle detection efficiency and improvement in the peak to background ratios are considered acceptable for the usefulness of the system.