Biomedical Applications of Proton Induced X-Ray Emission

Apart from studies on aerosols, the majority of applications of proton induced X-ray emission (PIXE) with a normal beam or a microprobe (micro-PIXE) is found in biology and medicine. Two aspects of broad beam PIXE are often decisive for the choice of this analytical technique. Compared to other techniques capable of analysis down beyond the ppm level, PIXE can be carried out with a very small amount of material and minute fractions of the composite samples, even in the scale of micrometers and quite often with minimal sample preparation, which are important requirements for biomedical investigations. Secondly, the speed of the total analysis opens the possibility to analyze large numbers of samples in a reasonable time, which is often necessary in biomedical studies in order to obtain sufficiently significant correlations between trace element concentrations and biomedical phenomena. Few, if any, techniques can compete with micro-PIXE; quantitative trace element analysis on a micrometer scale still represent a challenging problem. The electron microprobe normally lacks the sensitivity while the laser induced techniques suffer as yet from quantification problems. This paper describes recent developments especially in micro-PIXE in biomedical research

The effects of pulse stimulation on biota - Research in relation to ICES advice - Effects on dogfish

Onderzoek naar het welzijn van hondshaaien bij de vangst. Er is onderzocht of de methode van het gebruik van stroom wel diervriendelijk is. De conclusie is dat dit geen beletsel voor de diervriendelijkheid oplever

Patch behaviour and predictability properties of modelled finite-amplitude sand ridges on the inner shelf

The long-term evolution of shoreface-connected sand ridges is investigated with a nonlinear spectral model which governs the dynamics of waves, currents, sediment transport and the bed level on the inner shelf. Wave variables are calculated with a shoaling-refraction model instead of using a parameterisation. The spectral model describes the time evolution of amplitudes of known eigenmodes of the linearised system. Bottom pattern formation occurs if the transverse bottom slope of the inner shelf, β, exceeds a critical value β<sub>c</sub>. For fixed model parameters the sensitivity of the properties of modelled sand ridges to changes in the number (<i>N</i>−1) of resolved subharmonics (of the initially fastest growing mode) is investigated. For any <i>N</i> the model shows the growth and subsequent saturation of the height of the sand ridges. The saturation time scale is several thousands of years, which suggests that observed sand ridges have not reached their saturated stage yet. The migration speed of the ridges and the average longshore spacing between successive crests in the saturated state differ from those in the initial state. Analysis of the potential energy balance of the ridges reveals that bed slope-induced sediment transport is crucial for the saturation process. In the transient stage the shoreface-connected ridges occur in patches. The overall characteristics of the bedforms (saturation time, final maximum height, average longshore spacing, migration speed) hardly vary with <i>N</i>. However, individual time series of modal amplitudes and bottom patterns strongly depend on <i>N</i>, thereby implying that the detailed evolution of sand ridges can only be predicted over a limited time interval. Additional experiments show that the critical bed slope β<sub>c</sub> increases with larger offshore angles of wave incidence, larger offshore wave heights and longer wave periods, and that the corresponding maximum height of the ridges decreases whilst the saturation time increases

Algebraic equations of state for the liquid crystalline phase behavior of hard rods

Based on simplifications of previous numerical calculations [Graf and L\"{o}wen, Phys. Rev. E \textbf{59}, 1932 (1999)], we propose algebraic free energy expressions for the smectic-A liquid crystal phase and the crystal phases of hard spherocylinders. Quantitative agreement with simulations is found for the resulting equations of state. The free energy expressions can be used to straightforwardly compute the full phase behavior for all aspect ratios and to provide a suitable benchmark for exploring how attractive interrod interactions mediate the phase stability through perturbation approaches such as free-volume or van der Waals theory.Comment: 12 pages,accepted for publication in Phys. Rev.

Defying the Gibbs Phase Rule: Evidence for an Entropy-Driven Quintuple Point in Colloid-Polymer Mixtures

Using a minimal algebraic model for the thermodynamics of binary rod--polymer mixtures, we provide evidence for a quintuple phase equilibrium; an observation that seems to be at odds with the Gibbs phase rule for two-component systems. Our model is based on equations of state for the relevant liquid crystal phases that are in quantitative agreement with computer simulations. We argue that the appearance of a quintuple equilibrium, involving an isotropic fluid, a nematic and smectic liquid crystal, and two solid phases can be reconciled with a generalized Gibbs phase rule in which the two intrinsic length scales of the athermal colloid--polymer mixture act as additional field variables

Ultrasmall silica nanoparticles directly ligate the T cell receptor complex.

The impact of ultrasmall nanoparticles (<10-nm diameter) on the immune system is poorly understood. Recently, ultrasmall silica nanoparticles (USSN), which have gained increasing attention for therapeutic applications, were shown to stimulate T lymphocytes directly and at relatively low-exposure doses. Delineating underlying mechanisms and associated cell signaling will hasten therapeutic translation and is reported herein. Using competitive binding assays and molecular modeling, we established that the T cell receptor (TCR):CD3 complex is required for USSN-induced T cell activation, and that direct receptor complex-particle interactions are permitted both sterically and electrostatically. Activation is not limited to αβ TCR-bearing T cells since those with γδ TCR showed similar responses, implying that USSN mediate their effect by binding to extracellular domains of the flanking CD3 regions of the TCR complex. We confirmed that USSN initiated the signaling pathway immediately downstream of the TCR with rapid phosphorylation of both ζ-chain-associated protein 70 and linker for activation of T cells protein. However, T cell proliferation or IL-2 secretion were only triggered by USSN when costimulatory anti-CD28 or phorbate esters were present, demonstrating that the specific impact of USSN is in initiation of the primary, nuclear factor of activated T cells-pathway signaling from the TCR complex. Hence, we have established that USSN are partial agonists for the TCR complex because of induction of the primary T cell activation signal. Their ability to bind the TCR complex rapidly, and then to dissolve into benign orthosilicic acid, makes them an appealing option for therapies targeted at transient TCR:CD3 receptor binding.These studies were supported by grants from the UK Medical Research Council (Grant number MR/R005699/1) and the Natural Sciences and Engineering Research Council of Canada, as well as through sponsorship from HS Pharmaceuticals LLC

The effectiveness of non-native fish removal techniques in freshwater ecosystems: a systematic review

In aquatic systems, biological invasions can result in adverse ecological effects. Man-agement techniques available for non-native fish removal programs (including eradica-tion and population size control) vary widely, but include chemicals, harvest regimes, physical removal, or biological control. For management agencies, deciding on what non-native fish removal program to use has been challenging because there is little reliable information about the relative effectiveness of these measures in controlling or eradicat-ing non-native fish. We conducted a systematic review, including a critical appraisal of study validity, to assess the effectiveness of different non-native fish removal methods, and to identify the factors that influence the overall success rate of each type of method. We found 95 relevant studies, generating 158 data sets. The evidence base was dominated by poorly documented studies with inadequate experimental designs (76% of removal projects). When the management goal was non-native fish eradication, chemical treat-ments were relatively successful (antimycin 89%; rotenone 75%) compared to other in-terventions. Electrofishing and passive removal measure studies indicated successful eradication was possible (58% each respectively) but required intensive effort and multi-ple treatments over a number of years. Of these studies with sufficient information, elec-trofishing had the highest success for population size control (56% of data sets). Overall, inadequate data quality and completeness severely limited our ability to make strong con-clusions about the relationships between non-native fish abundance and different methods of eradication and population control, and the factors influencing the overall success rate of each method. Our review highlights that there is considerable scope for improving our evaluations of non-native fish removal methods. It is recommended that programs should have explicitly stated objectives, better data reporting, and study designs that (when pos-sible and appropriate) incorporate replicated and controlled investigations with rigorous, long-term quantitative monitoring. Future research on the effectiveness of non-native fish removal methods should focus on: (1) the efficacy of existing or potentially new removal measures in larger, more complex environments; (2) a broader range of removal measures in general, and (3) phenotypic characteristics of individual fish within a population that fail to be eradicated or controlled

Systematic overviews of partnership principles and strategies identified from health research about spinal cord injury and related health conditions:A scoping review

Study design: Scoping review.Objective: To identify and provide systematic overviews of partnership principles and strategies identified from health research about spinal cord injury (SCI) and related health conditions.Methods: Four health electronic databases (Medline, Embase, CINAHL, PsycINFO) were searched from inception to March 2019. We included articles that described, reflected, and/or evaluated one or more collaborative research activities in health research about SCI, stroke, multiple sclerosis, Parkinson's disease, amputation, cerebral palsy, spina bifida, amyotrophic lateral sclerosis, acquired brain injury, or wheelchair-users. Partnership principles (i.e. norms or values) and strategies (i.e. observable actions) were extracted and analyzed using directed qualitative content analysis.Results: We included 39 articles about SCI (n = 13), stroke (n = 15), multiple sclerosis (n = 5), amputation (n = 2), cerebral palsy (n = 2), Parkinson's disease (n = 1), and wheelchair users (n = 1). We extracted 110 principles and synthesized them into 13 overarching principles. Principles related to building and maintaining relationships between researchers and research users were most frequently reported. We identified 32 strategies that could be applied at various phases of the research process and 26 strategies that were specific to a research phase (planning, conduct, or dissemination).Conclusion: We provided systematic overviews of principles and strategies for research partnerships. These could be used by researchers and research users who want to work in partnership to plan, conduct and/or disseminate their SCI research. The findings informed the development of the new SCI Integrated Knowledge Translation Guiding Principles (www.iktprinciples.com) and will support the implementation of these Principles within the SCI research system.</p

Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey

Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury. Here, we investigated the presence of oxidative injury in another NHP EAE model, i.e. in rhesus macaques, which yields an acute demyelinating disease, which may more closely resemble acute disseminated encephalomyelitis (ADEM) than MS. Rhesus monkey EAE diverges from marmoset EAE by abundant neutrophil recruitment into the CNS and destructive injury to white matter. This difference prompted us to investigate to which extent the oxidative pathway features elicited in MS and marmoset EAE are reflected in the acute rhesus monkey EAE model. The rhesus EAE brain was characterized by widespread demyelination and active lesions containing numerous phagocytic cells and to a lesser extent T cells. We observed induction of the oxidative stress pathway, including injury, with a predilection of p22phox expression in neutrophils and macrophages/microglia. In addition, changes in iron were observed. These results indicate that pathogenic mechanisms in the rhesus EAE model may differ from the marmoset EAE and MS brain due to the neutrophil involvement, but may in the end lead to similar induction of oxidative stress and injury.</p