Single-trial multiwavelet coherence in application to neurophysiological time series

A method of single-trial coherence analysis is presented, through the application of continuous muldwavelets. Multiwavelets allow the construction of spectra and bivariate statistics such as coherence within single trials. Spectral estimates are made consistent through optimal time-frequency localization and smoothing. The use of multiwavelets is considered along with an alternative single-trial method prevalent in the literature, with the focus being on statistical, interpretive and computational aspects. The multiwavelet approach is shown to possess many desirable properties, including optimal conditioning, statistical descriptions and computational efficiency. The methods. are then applied to bivariate surrogate and neurophysiological data for calibration and comparative study. Neurophysiological data were recorded intracellularly from two spinal motoneurones innervating the posterior,biceps muscle during fictive locomotion in the decerebrated cat

Emergence of the Shackleton Range from beneath the Antarctic Ice Sheet due to glacial erosion

This paper explores the long-term evolution of a subglacial fjord landscape in the Shackleton Range, Antarctica. We propose that prolonged ice-sheet erosion across a passive continental margin caused troughs to deepen and lower the surrounding ice-sheet surface, leaving adjacent mountains exposed. Geomorphological evidence suggests a change in the direction of regional ice flow accompanied emergence. Simple calculations suggest that isostatic compensation caused by the deepening of bounding ice-stream troughs lowered the ice-sheet surface relative to the mountains by ~800m. Use of multiple cosmogenic isotopes on bedrock and erratics (26Al, 10Be, 21Ne) provides evidence that overriding of the massif and the deepening of the adjacent troughs occurred earlier than the Quaternary. Perhaps this occurred in the mid-Miocene, as elsewhere in East Antarctica in the McMurdo Dry Valleys and the Lambert basin. The implication is that glacial erosion instigates feedback that can change ice-sheet thickness, extent, and direction of flow. Indeed, as the subglacial troughs evolve over millions of years, they increase topographic relief; and this changes the dynamics of the ice sheet. © 2013 Elsevier B.V

Student perspectives on using Google Glass recordings to assess their communicative and clinical skills with standardized patients

Introduction This exploratory study evaluated student perceptions of their ability to self- and peer assess (i) interpersonal communication skills and (ii) clinical procedures (a head and neck examination) during standardised patient (SP) interactions recorded by Google Glass compared to a static camera. Methods Students compared the Google Glass and static camera recordings using an instrument consisting of 20 Likert-type items and four open- and closed-text items. The Likert-type items asked students to rate how effectively they could assess specific aspects of interpersonal communication and a head and neck examination in these two different types of recordings. The interpersonal communication items included verbal, paraverbal and non-verbal subscales. The open- and closed-text items asked students to report on more globally the differences between the two types of recordings. Descriptive and inferential statistical analyses were conducted for all survey items. An inductive thematic analysis was conducted to determine qualitative emergent themes from the open-text questions. Results Students found the Glass videos more effective for assessing verbal (t22 = 2.091, P = 0.048) and paraverbal communication skills (t22 = 3.304, P = 0.003), whilst they reported that the static camera video was more effective for assessing non-verbal communication skills (t22 = −2.132, P = 0.044). Four principle themes emerged from the students' open-text responses comparing Glass to static camera recordings for self- and peer assessment: (1) first-person perspective, (2) assessment of non-verbal communication, (3) audiovisual experience and (4) student operation of Glass. Discussion and conclusion Our findings suggest that students perceive that Google Glass is a valuable tool for facilitating self- and peer assessment of SP examinations because of students’ perceived ability to emphasise and illustrate communicative and clinical activities from a first-person perspective

Dendritic Cell Autophagy Contributes to Herpes Simplex Virus-Driven Stromal Keratitis and Immunopathology

Herpetic stromal keratitis (HSK) is a blinding ocular disease that is initiated by HSV-1 and characterized by chronic inflammation in the cornea. Although HSK immunopathology of the cornea is well documented in animal models, events preceding this abnormal inflammatory cascade are poorly understood. In this study, we have examined the activation of pathological CD4T cells in the development of HSK. Dendritic cell autophagy (DC-autophagy) is an important pathway regulating ma- jor histocompatibility complex class II (MHCII)-dependent antigen presentation and proper CD4T cell activation during infectious diseases. Using DC-autophagy-deficient mice, we found that DC-autophagy significantly and specifically contributes to HSK disease without impacting early innate immune infiltration, viral clearance, or host survival. Instead, the observed phe- notype was attributable to the abrogated activation of CD4T cells and reduced inflammation in HSK lesions. We conclude that DC-autophagy is an important contributor to primary HSK immunopathology upstream of CD4T cell activation. IMPORTANCE Herpetic stromal keratitis (HSK) is the leading cause of infectious blindness in the United States and a rising cause worldwide. HSK is induced by herpes simplex virus 1 but is considered a disease of inappropriately sustained inflammation driven by CD4T cells. In this study, we investigated whether pathways preceding CD4T cell activation affect disease outcome. We found that autophagy in dendritic cells significantly contributed to the incidence of HSK. Dendritic cell autophagy did not alter immune control of the virus or neurological disease but specifically augmented CD4T cell activation and pathological corneal inflammation. This study broadens our understanding of the immunopathology that drives HSK and implicates the autophagy pathway as a new target for therapeutic intervention against this incurable form of infectious blindness

Ibrutinib inhibits SDF1/CXCR4 mediated migration in AML

Pharmacological targeting of BTK using ibrutinib has recently shown encouraging clinical activity in a range of lymphoid malignancies. Recently we reported that ibrutinib inhibits human acute myeloid leukemia (AML) blast proliferation and leukemic cell adhesion to the surrounding bone marrow stroma cells. Here we report that in human AML ibrutinib, in addition, functions to inhibit SDF1/CXCR4-mediated AML migration at concentrations achievable in vivo. It has previously been shown that SDF1/CXCR4-induced migration is dependent on activation of downstream BTK in chronic lymphocytic leukaemia (CLL) and multiple myeloma. Here we show that SDF-1 induces BTK phosphorylation and downstream MAPK signalling in primary AML blast. Furthermore, we show that ibrutinib can inhibit SDF1-induced AKT and MAPK activation. These results reported here provide a molecular mechanistic rationale for clinically evaluating BTK inhibition in AML patients and suggests that in some AML patients the blasts count may initially rise in response to ibrutinib therapy, analgous to similar clinical observations in CLL

Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

Effective dynamics for solitons in the nonlinear Klein Gordon Maxwell system and the Lorentz force law

We consider the nonlinear Klein Gordon Maxwell system on four dimensional Minkowski space-time. For appropriate nonlinearities the system admits soliton solutions which are gauge invariant generalizations of the non-topological solitons introduced and studied by T.D. Lee and collaborators for pure complex scalar fields. We develop a rigorous dynamical perturbation theory for these solitons in the small e limit, where e is the electromagnetic coupling constant. The main theorems assert the long time stability of the solitons with respect to perturbation by an external electromagnetic field produced by the background current, and compute their effective dynamics to O(e). The effective dynamical equation is the equation of motion for a relativistic particle acted on by the Lorentz force law familiar from classical electrodynamics