Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

BackgroundMajor histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy.Hypothesis/objectivesTo determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM.AnimalsTwenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]).MethodsImmunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed.ResultsSarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles.Conclusions and clinical importanceDeficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates

Cortico-striatal beta oscillations as a reward-related signal

The value associated with reward is sensitive to external factors, such as the time between the choice and reward delivery as classically manipulated in temporal discounting tasks. Subjective preference for two reward options is dependent on objective variables of reward magnitude and reward delay. Single neuron correlates of reward value have been observed in regions, including ventral striatum, orbital, and medial prefrontal cortex. Brain imaging studies show cortico-striatal-limbic network activity related to subjective preferences. To explore how oscillatory dynamics represent reward processing across brain regions, we measured local field potentials of rats performing a temporal discounting task. Our goal was to use a data-driven approach to identify an electrophysiological marker that correlates with reward preference. We found that reward-locked oscillations at beta frequencies signaled the magnitude of reward and decayed with longer temporal delays. Electrodes in orbitofrontal/medial prefrontal cortex, anterior insula, ventral striatum, and amygdala individually increased power and were functionally connected at beta frequencies during reward outcome. Beta power during reward outcome correlated with subjective value as defined by a computational model fit to the discounting behavior. These data suggest that cortico-striatal beta oscillations are a reward signal correlated, which may represent subjective value and hold potential to serve as a biomarker and potential therapeutic target

The Effects of Cariprazine and Aripiprazole on PCP-Induced Deficits on Attention Assessed in the 5-Choice Serial Reaction Time Task

Attentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia. We sought to test the ability of partial dopamine D-2/D-3 agonists, cariprazine and aripiprazole, to attenuate PCP-induced deficits in attentional performance. The objective of this study is to determine whether systemic administration of cariprazine or aripiprazole attenuated 5-choice serial reaction time task (5-CSRTT) deficits induced by repeated exposure to PCP. We utilized a repeated PCP-treatment regimen (2 mg/kg, subcutaneous [s.c.], once daily for 5 days) in rats to induce deficits in the 5-CSRTT. Rats were pre-treated with cariprazine (0.03, 0.1, or 0.3 mg/kg, oral [p.o.]) or aripiprazole (1, 3, or 10 mg/kg, p.o.) to determine whether they prevented PCP-induced deficits in the 5-CSRTT performance. PCP treatment increased inappropriate responding in the 5-CSRTT, elevating incorrect, premature, and timeout responses. Cariprazine treatment reduced PCP-induced increases in inappropriate responding. However, at higher doses, cariprazine produced non-specific response suppression, confounding interpretation of the attenuated PCP-induced deficits. Aripiprazole treatment also attenuated PCP-induced deficits; however, unlike cariprazine treatment, aripiprazole reduced correct responding and increased omissions. Cariprazine and aripiprazole both demonstrated potential in attenuating PCP-induced deficits in the 5-CSRTT performance. While both compounds produced non-specific response suppression, these effects were absent when 0.03 mg/kg cariprazine was administered

Laminar dynamics of high amplitude beta bursts in human motor cortex

Motor cortical activity in the beta frequency range is one of the strongest and most studied movement-related neural signals. At the single trial level, beta band activity is often characterized by transient, high amplitude, bursting events rather than slowly modulating oscillations. The timing of these bursting events is tightly linked to behavior, suggesting a more dynamic functional role for beta activity than previously believed. However, the neural mechanisms underlying beta bursts in sensorimotor circuits are poorly understood. To address this, we here leverage and extend recent developments in high precision MEG for temporally resolved laminar analysis of burst activity, combined with a neocortical circuit model that simulates the biophysical generators of the electrical currents which drive beta bursts. This approach pinpoints the generation of beta bursts in human motor cortex to distinct excitatory synaptic inputs to deep and superficial cortical layers, which drive current flow in opposite directions. These laminar dynamics of beta bursts in motor cortex align with prior invasive animal recordings within the somatosensory cortex, and suggest a conserved mechanism for somatosensory and motor cortical beta bursts. More generally, we demonstrate the ability for uncovering the laminar dynamics of event-related neural signals in human non-invasive recordings. This provides important constraints to theories about the functional role of burst activity for movement control in health and disease, and crucial links between macro-scale phenomena measured in humans and micro-circuit activity recorded from animal models

Design Principles for Plasmonic Nanoparticle Devices

For all applications of plasmonics to technology it is required to tailor the resonance to the optical system in question. This chapter gives an understanding of the design considerations for nanoparticles needed to tune the resonance. First the basic concepts of plasmonics are reviewed with a focus on the physics of nanoparticles. An introduction to the finite element method is given with emphasis on the suitability of the method to nanoplasmonic device simulation. The effects of nanoparticle shape on the spectral position and lineshape of the plasmonic resonance are discussed including retardation and surface curvature effects. The most technologically important plasmonic materials are assessed for device applicability and the importance of substrates in light scattering is explained. Finally the application of plasmonic nanoparticles to photovoltaic devices is discussed.Comment: 29 pages, 15 figures, part of an edited book: "Linear and Non-Linear Nanoplasmonics

Ages for exoplanet host stars

Age is an important characteristic of a planetary system, but also one that is difficult to determine. Assuming that the host star and the planets are formed at the same time, the challenge is to determine the stellar age. Asteroseismology provides precise age determination, but in many cases the required detailed pulsation observations are not available. Here we concentrate on other techniques, which may have broader applicability but also serious limitations. Further development of this area requires improvements in our understanding of the evolution of stars and their age-dependent characteristics, combined with observations that allow reliable calibration of the various techniques.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018

The application of nitric oxide to control biofouling of membrane bioreactors

© 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology. A novel strategy to control membrane bioreactor (MBR) biofouling using the nitric oxide (NO) donor compound PROLI NONOate was examined. When the biofilm was pre-established on membranes at transmembrane pressure (TMP) of 88-90kPa, backwashing of the membrane module with 80μM PROLI NONOate for 45min once daily for 37 days reduced the fouling resistance (Rf) by 56%. Similarly, a daily, 1h exposure of the membrane to 80μM PROLI NONOate from the commencement of MBR operation for 85 days resulted in reduction of the TMP and Rf by 32.3% and 28.2%. The microbial community in the control MBR was observed to change from days 71 to 85, which correlates with the rapid TMP increase. Interestingly, NO-treated biofilms at 85 days had a higher similarity with the control biofilms at 71 days relative to the control biofilms at 85 days, indicating that the NO treatment delayed the development of biofilm bacterial community. Despite this difference, sequence analysis indicated that NO treatment did not result in a significant shift in the dominant fouling species. Confocal microscopy revealed that the biomass of biopolymers and microorganisms in biofilms were all reduced on the PROLI NONOate-treated membranes, where there were reductions of 37.7% for proteins and 66.7% for microbial cells, which correlates with the reduction in TMP. These results suggest that NO treatment could be a promising strategy to control biofouling in MBRs

Vagueness and Quantification

This paper deals with the question of what it is for a quantifier expression to be vague. First it draws a distinction between two senses in which quantifier expressions may be said to be vague, and provides an account of the distinction which rests on independently grounded assumptions. Then it suggests that, if some further assumptions are granted, the difference between the two senses considered can be represented at the formal level. Finally, it outlines some implications of the account provided which bear on three debated issues concerning quantification

Υ\Upsilon absorption in hadronic matter

The cross sections of $\Upsilon$ absorption by $\pi$ and $\rho$ mesons are evaluated in a meson-exchange model. Including form factors with a cutoff parameter of 1 or 2 GeV, we find that due to the large threshold of these reactions the thermal average of their cross sections is only about 0.2 mb at a temperature of 150 MeV. Our results thus suggest that the absorption of directly produced $\Upsilon$ by hadronic comovers in high energy heavy ion collisions is unimportant.Comment: 11 pages, revtex, 3 figures, added references and discussion on higher BBbar state

Smoking Gun or Circumstantial Evidence? Comparison of Statistical Learning Methods using Functional Annotations for Prioritizing Risk Variants

Although technology has triumphed in facilitating routine genome sequencing, new challenges have been created for the data-analyst. Genome-scale surveys of human variation generate volumes of data that far exceed capabilities for laboratory characterization. By incorporating functional annotations as predictors, statistical learning has been widely investigated for prioritizing genetic variants likely to be associated with complex disease. We compared three published prioritization procedures, which use different statistical learning algorithms and different predictors with regard to the quantity, type and coding. We also explored different combinations of algorithm and annotation set. As an application, we tested which methodology performed best for prioritizing variants using data from a large schizophrenia meta-analysis by the Psychiatric Genomics Consortium. Results suggest that all methods have considerable (and similar) predictive accuracies (AUCs 0.64-0.71) in test set data, but there is more variability in the application to the schizophrenia GWAS. In conclusion, a variety of algorithms and annotations seem to have a similar potential to effectively enrich true risk variants in genome-scale datasets, however none offer more than incremental improvement in prediction. We discuss how methods might be evolved for risk variant prediction to address the impending bottleneck of the new generation of genome re-sequencing studies