Periodic solutions and refractory periods in the soliton theory for nerves and the locust femoral nerve

Close to melting transitions it is possible to propagate solitary electromechanical pulses which reflect many of the experimental features of the nerve pulse including mechanical dislocations and reversible heat production. Here we show that one also obtains the possibility of periodic pulse generation when the boundary condition for the nerve is the conservation of the overall length of the nerve. This condition generates an undershoot beneath the baseline (`hyperpolarization') and a `refractory period', i.e., a minimum distance between pulses. In this paper, we outline the theory for periodic solutions to the wave equation and compare these results to action potentials from the femoral nerve of the locust (locusta migratoria). In particular, we describe the frequently occurring minimum-distance doublet pulses seen in these neurons and compare them to the periodic pulse solutions.Comment: 10 pages, 6 Figure

Mechanical strain causes adaptive change in bronchial fibroblasts enhancing profibrotic and inflammatory responses

Asthma is characterized by periodic episodes of bronchoconstriction and reversible airway obstruction; these symptoms are attributable to a number of factors including increased mass and reactivity of bronchial smooth muscle and extracellular matrix (ECM) in asthmatic airways. Literature has suggested changes in cell responses and signaling can be elicited via modulation of mechanical stress acting upon them, potentially affecting the microenvironment of the cell. In this study, we hypothesized that mechanical strain directly affects the (myo)fibroblast phenotype in asthma. Therefore, we characterized responses of bronchial fibroblasts, from 6 normal and 11 asthmatic non-smoking volunteers, exposed to cyclical mechanical strain using flexible silastic membranes. Samples were analyzed for proteoglycans, ?-smooth muscle actin (?SMA), collagens I and III, matrix metalloproteinase (MMP) 2 &amp; 9 and interleukin-8 (IL-8) by qRT-PCR, Western blot, zymography and ELISA. Mechanical strain caused a decrease in ?SMA mRNA but no change in either ?SMA protein or proteoglycan expression. In contrast the inflammatory mediator IL-8, MMPs and interstitial collagens were increased at both the transcriptional and protein level. The results demonstrate an adaptive response of bronchial fibroblasts to mechanical strain, irrespective of donor. The adaptation involves cytoskeletal rearrangement, matrix remodelling and inflammatory cytokine release. These results suggest that mechanical strain could contribute to disease progression in asthma by promoting inflammation and remodelling responses.<br/

Abundances and density structure of the inner circumstellar ring around SN 1987A

We present optical spectroscopic data of the inner circumstellar ring around SN 1987A from the Anglo-Australian Telescope (AAT) and the Very Large Telescope (VLT) between ~1400 and ~5000 days post-explosion. We also assembled the available optical and near-infrared line fluxes from the literature between ~300 and ~2000 days. These line light curves were fitted with a photoionization model to determine the density structure and the elemental abundances for the inner ring. We found densities ranging from 1x10^3 to 3x10^4 atoms cm^-3 and a total mass of the ionized gas of ~0.058 Msun within the inner ring. Abundances inferred from the optical and near-infrared data were also complemented with estimates of Lundqvist & Fransson (1996) based on ultraviolet lines. This way we found an He/H-ratio (by number of atoms) of 0.17+-0.06 which is roughly 30% lower than previously estimated and twice the solar and the Large Magellanic Cloud (LMC) value. We found an N/O-ratio of 1.5+-0.7, and the total (C+N+O)/(H+He) abundance about 1.6 times its LMC value or roughly 0.6 times the most recent solar value. An iron abundance of 0.20+-0.11 times solar was found which is within the range of the estimates for the LMC. We also present late time (~5000 - 7500 days) line light curves of [O III], [Ne III], [Ne IV], [Ar III], [Ar IV], and [Fe VII] from observations with the VLT. We compared these with model fluxes and found that an additional 10^2 atoms cm^-3 component was required to explain the data of the highest ionization lines. Such low density gas is expected in the H II-region interior to the inner ring which likely extends also to larger radii at higher latitudes (out of the ring plane). At epochs later than ~5000 days our models underproduce the emission of most of these lines as expected due to the contribution from the interaction of the supernova ejecta with the ring.Comment: 17 pages, 8 figures, accepted for publication in Ap

Transforming growth factor-beta promotes rhinovirus replication in bronchial epithelial cells by suppressing the innate immune response

Rhinovirus (RV) infection is a major cause of asthma exacerbations which may be due to a deficient innate immune response in the bronchial epithelium. We hypothesized that the pleiotropic cytokine, TGF-?, influences interferon (IFN) production by primary bronchial epithelial cells (PBECs) following RV infection. Exogenous TGF-?(2) increased RV replication and decreased IFN protein secretion in response to RV or double-stranded RNA (dsRNA). Conversely, neutralizing TGF-? antibodies decreased RV replication and increased IFN expression in response to RV or dsRNA. Endogenous TGF-?(2) levels were higher in conditioned media of PBECs from asthmatic donors and the suppressive effect of anti-TGF-? on RV replication was significantly greater in these cells. Basal SMAD-2 activation was reduced when asthmatic PBECs were treated with anti-TGF-? and this was accompanied by suppression of SOCS-1 and SOCS-3 expression. Our results suggest that endogenous TGF-? contributes to a suppressed IFN response to RV infection possibly via SOCS-1 and SOCS-3

Protocol for the Mindful Student Study: a randomised controlled trial of the provision of a mindfulness intervention to support university students' well-being and resilience to stress.

INTRODUCTION: Levels of stress in UK university students are high, with an increase in the proportion of students seeking help in recent years. Academic pressure is reported as a major trigger. Mindfulness training has been shown to reduce stress and is popular among students, but its effectiveness in this context needs to be ascertained. In this pragmatic randomised controlled trial, we hypothesise that the provision of a preventative mindfulness intervention in universities could reduce students' psychological distress during the examination period (primary outcome), improve their resilience to stress up to at least 1 year later, reduce their use of mental health support services and improve academic performance. METHODS AND ANALYSIS: At least 550 University of Cambridge students free from active crises or severe mental illness will be randomised to joining an 8-week mindfulness course or to mental health provision as usual (one-to-one allocation rate). Psychological distress will be measured using the Clinical Outcomes in Routine Evaluation Outcome Measure at baseline, postintervention, examination term and 1-year follow-up. Other outcomes are use of mental health services, inability to sit examinations or special circumstance requests, examination grades, well-being, altruism and coping measured with ecological momentary assessment. Outcome assessment and intention-to-treat primary analysis using linear mixed models adjusted for baseline scores will be blind to intervention allocation. We will also conduct per-protocol, subgroup and secondary outcome analyses. An Independent Data Monitoring and Ethics Committee will be set up. We will systematically monitor for, and react to, possible adverse events. An advisory reference group will comprise student representatives, members of the University Counselling Service and other student welfare staff. ETHICS AND DISSEMINATION: Approval has been obtained from Cambridge Psychology Research Ethics Committee (PRE.2015.060). Results will be published in peer-reviewed journals. A lay summary will be disseminated to a wider audience including other universities. TRIAL REGISTRATION NUMBER: ACTRN12615001160527; pre-results.University of Cambridge Vice-Chancellor’s Endowment Fund, University Counselling Service, National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East of England, at Cambridgeshire and Peterborough NHS Foundation TrustThis is the final version of the article. It first appeared from BMJ Publishing Group via https://doi.org/10.1136/bmjopen-2016-01230

Genetic and cellular studies highlight that A Disintegrin and Metalloproteinase 19 is a protective biomarker in human prostate cancer

Background: Prostate cancer is the second most frequently diagnosed cancer in men worldwide. Current treatments include surgery, androgen ablation and radiation. Introduction of more targeted therapies in prostate cancer, based on a detailed knowledge of the signalling pathways, aims to reduce side effects, leading to better clinical outcomes for the patient. ADAM19 (A Disintegrin And Metalloproteinase 19) is a transmembrane and soluble protein which can regulate cell phenotype through cell adhesion and proteolysis. ADAM19 has been positively associated with numerous diseases, but has not been shown to be a tumor suppressor in the pathogenesis of any human cancers. Our group sought to investigate the role of ADAM19 in human prostate cancer. Methods: ADAM19 mRNA and protein levels were assessed in well characterised human prostate cancer cohorts. ADAM19 expression was assessed in normal prostate epithelial cells (RWPE-1) and prostate cancer cells (LNCaP, PC3) using western blotting and immunocytochemistry. Proliferation assays were conducted in LNCaP cells in which ADAM19 was over-expressed. In vitro scratch assays were performed in PC3 cells over-expressing ADAM19. Results: Immunohistochemical studies highlighted that ADAM19 protein levels were elevated in normal prostate tissue compared to prostate cancer biopsies. Results from the clinical cohorts demonstrated that high levels of ADAM19 in microarrays are positively associated with lower stage (p = 0.02591) and reduced relapse (p = 0.00277) of human prostate cancer. In vitro, ADAM19 expression was higher in RWPE-1 cells compared to LNCaP cells. In addition, human ADAM19 over-expression reduced LNCaP cell proliferation and PC3 cell migration. Conclusions: Taken together, our immunohistochemical and microarray results and cellular studies have shown for the first time that ADAM19 is a protective factor for human prostate cancer. Further, this study suggests that upregulation of ADAM19 expression could be of therapeutic potential in human prostate cancer

Limits from the Hubble Space Telescope on a Point Source in SN 1987A

We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September, and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. No point source is observed in the remnant. We obtain a limiting flux of F_opt < 1.6 x 10^{-14} ergs/s/cm^2 in the wavelength range 2900-9650 Angstroms for any continuum emitter at the center of the supernova remnant (SNR). It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Taking into account dust absorption in the remnant, we find a limit of L_opt < 8 x 10^{33} ergs/s. We compare this upper bound with empirical evidence from point sources in other supernova remnants, and with theoretical models for possible compact sources. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Of the young pulsars known to be associated with SNRs, those with ages < 5000 years are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out, and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 10^{10} cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant.Comment: 40 pages, 5 figures. AAStex. Accepted, ApJ 04/28/200

A dusty pinwheel nebula around the massive star WR 104

Wolf-Rayet (WR) stars are luminous massive blue stars thought to be immediate precursors to the supernova terminating their brief lives. The existence of dust shells around such stars has been enigmatic since their discovery some 30 years ago; the intense radiation field from the star should be inimical to dust survival. Although dust-creation models, including those involving interacting stellar winds from a companion star, have been put forward, high-resolution observations are required to understand this phenomena. Here we present resolved images of the dust outflow around Wolf-Rayet WR 104, obtained with novel imaging techniques, revealing detail on scales corresponding to about 40 AU at the star. Our maps show that the dust forms a spatially confined stream following precisely a linear (or Archimedian) spiral trajectory. Images taken at two separate epochs show a clear rotation with a period of 220 +/- 30 days. Taken together, these findings prove that a binary star is responsible for the creation of the circumstellar dust, while the spiral plume makes WR 104 the prototype of a new class of circumstellar nebulae unique to interacting wind systems.Comment: 7 pages, 2 figures, Appearing in Nature (1999 April 08

A review of the tolerability and safety of levocabastine eye drops and nasal spray. Implications for patient management

Levocabastine is a highly potent and selective H1-receptor antagonist specifically developed for topical administration by ocular and nasal routes. The clinical effects of levocabastine occur rapidly and are predominantly due to local antihistaminic effects at the site of application. Clinically, levocabastine is well tolerated with an adverse effect profile comparable with that of sodium cromoglycate and placebo. As might be expected from the route of drug administration, local irritation is the most frequent adverse event seen with levocabastine eye drops and nasal spray with an incidence comparable with that in placebo-treated controls. Intranasal application of levocabastine has been shown to have no adverse effect on ciliary activity both in vitro and in vivo, while ocular administration has not been shown to have any significant or consistent adverse effect in both animal and human studies. At therapeutic doses, levocabastine appears to be devoid of significant systemic activity producing no apparent effects on cardiovascular, psychomotor and cognitive function. Since levocabastine undergoes little hepatic metabolism, and only low plasma levels of the drug are attained following topical administration, drug interactions are unlikely

Eddy correlation measurements of oxygen fluxes in permeable sediments exposed to varying current flow and light

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2013. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography 58 (2013): 1329–1343, doi:10.4319/lo.2013.58.4.1329.Based on noninvasive eddy correlation measurements at a marine and a freshwater site, this study documents the control that current flow and light have on sediment–water oxygen fluxes in permeable sediments. The marine sediment was exposed to tidal-driven current and light, and the oxygen flux varied from night to day between −29 and 78 mmol m−2 d−1. A fitting model, assuming a linear increase in oxygen respiration with current flow, and a photosynthesis–irradiance curve for light-controlled production reproduced measured fluxes well (R2 = 0.992) and revealed a 4-fold increase in oxygen uptake when current velocity increased from ∼ 0 to 20 cm s−1. Application of the model to a week-long measured record of current velocity and light showed that net ecosystem metabolism varied substantially among days, between −27 and 31 mmol m−2 d−1, due to variations in light and current flow. This variation is likely typical of many shallow-water systems and highlights the need for long-term flux integrations to determine system metabolism accurately. At the freshwater river site, the sediment–water oxygen flux ranged from −360 to 137 mmol m−2 d−1. A direct comparison during nighttime with concurrent benthic chamber incubations revealed a 4.1 times larger eddy flux than that obtained with chambers. The current velocity during this comparison was 31 cm s−1, and the large discrepancy was likely caused by poor imitation by the chambers of the natural pore-water flushing at this high current velocity. These results emphasize the need for more noninvasive oxygen flux measurements in permeable sediments to accurately assess their role in local and global carbon budgets.Support for this study was provided by the following National Science Foundation grants: OCE-0420575, OCE- 0536431, and OCE-1061364