Searching for plasticity in dissociated cortical cultures on multi-electrode arrays

We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation

Enhancing competitive island cooperative neuro - evolution through backpropagation for pattern classification

Cooperative coevolution is a promising method for training neural networks which is also known as cooperative neuro-evolution. Cooperative neuro-evolution has been used for pattern classification, time series prediction and global optimisation problems. In the past, competitive island based cooperative coevolution has been proposed that employed different instances of problem decomposition methods for competition. Neuro-evolution has limitations in terms of training time although they are known as global search methods. Backpropagation algorithm employs gradient descent which helps in faster convergence which is needed for neuro-evolution. Backpropagation suffers from premature convergence and its combination with neuro-evolution can help eliminate the weakness of both the approaches. In this paper, we propose a competitive island cooperative neuro-evolutionary method that takes advantage of the strengths of gradient descent and neuro-evolution. We use feedforward neural networks on benchmark pattern classification problems to evaluate the performance of the proposed algorithm. The results show improved performance when compared to related methods

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Magnetic Reconnection With a Fast Perpendicular Sheared Flow

Magnetic reconnection at the Earth\u27s low‐latitude magnetopause near the flank region is likely associated with a large sheared flow, being frequently quasi‐perpendicular to the antiparallel magnetic field components. The magnitude of a fast sheared flow can be super‐Alfvénic and even overcome the local fast mode speed. A scaling analysis implies a contradiction between the Walén relation and the balance of the total pressure for magnetic reconnection with a supercritical perpendicular sheared flow. This study uses one‐ and two‐dimensional magnetohydrodynamic (MHD) simulations to demonstrate that the traditional reconnection layer violates the Walén relation but still maintains the total pressure balance in such a configuration. The results show an expanded outflow region, consistent with the presence of divergent normal flow, and a significant decrease of the plasma density as well as the thermal pressure in the outflow region. In contrast, the magnitude of the magnetic field in the outflow region matches the value in the inflow region due to the total pressure balance, which is fundamentally different from the classical reconnection layer under sub‐Alfvénic perpendicular sheared flow conditions. In three‐dimensional geometry, the fast sheared flow without being stabilized by the magnetic field is expected to be Kelvin‐Helmholtz unstable. However, the three‐dimensional MHD simulation suggests that such structure can be KH stable. Although, the presence of surface waves modulates some two‐dimensional features, the major characteristics of the expanded outflow region are likely to be observed by in situ satellites

Organisational response to the 2007 Ruapehu Crater Lake breakout lahar in New Zealand: Use of communication in creating an effective response

When Mt. Ruapehu erupted in 1995-1996 in New Zealand, a tephra barrier was created alongside Crater Lake on the top of Mt. Ruapehu. This barrier acted as a dam, with Crater Lake rising behind it over time. In 2007 the lake breached the dam and a lahar occurred down the Whangaehu Valley and across the volcano’s broad alluvial ring-plain. Given the lahar history from Ruapehu, the risk from the 2007 event was identified beforehand and steps taken to reduce the risks to life and infrastructure. An early warning system was set up to notify when the dam had broken and the lahar had occurred. Physical works to mitigate the risk were put in place. A planning group was also formed and emergency management plans were put in place to respond to the risk. To assess the effectiveness of planning for and responding to the lahar, semi-structured interviews were undertaken with personnel from key organisations both before and after the lahar event. This chapter discusses the findings from the interviews in the context of communications, and highlights how good communications contributed to an effective emergency management response. As the potential for a lahar was identifiable, approximately 10 years of lead-up time was available to install warning system hardware, implement physical mitigation measures, create emergency management plans, and practice exercises for the lahar. The planning and exercising developed effective internal communications, engendered relationships, and moved individuals towards a shared mental model of how a respond to the event. Consequently, the response played out largely as planned with only minor communication issues occurring on the day of the lahar. The minor communication issues were due to strong personal connections leading to at least one case of the plan being bypassed. Communication levels during the lahar event itself were also different from that experienced in exercises, and in some instances communications were seen to increase almost three-fold. This increase in level of communication, led to some difficulty in getting through to the main Incident Control Point. A final thought regarding public communications prior to the event was that more effort could have been given to developing and integrating public information about the lahar, to allow for ease of understanding about the event and integration of information across agencies.falseSubmitte

Long Term Prognostic Impact of Sex-specific Longitudinal Changes in Blood Pressure. The EPIC-Norfolk Prospective Population Cohort Study

AIMS: We aimed to determine the sex differences in longitudinal systolic and diastolic blood pressure (SBP and DBP) trajectories in mid-life and delineate the associations between these and mortality (all-cause, cardiovascular, and non-cardiovascular) and incident cardiovascular disease (CVD) in old age. METHODS AND RESULTS: Participants were selected from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) cohort study. Sex-specific trajectories were determined using group-based trajectory models using three clinic BP measurements acquired between 1993 and 2012 (mean exposure ∼12.9 years). Multivariable Cox regressions determined the associations between trajectories and incident outcomes over the follow-up (median follow-up 9.4 years). A total of 2897 men (M) and 3819 women (F) were included. At baseline, women were younger (F-55.5, M-57.1), had a worse cardiometabolic profile and were less likely to receive primary CVD prevention including antihypertensive treatment (F-36.0%, M-42.0%). Over the exposure period, women had lower SBP trajectories while men exhibited more pronounced SBP decreases over this period. Over the follow-up period, women had lower mortality (F-11.9%, M-20.5%) and CVD incidence (F-19.8%, M-29.6%). Compared to optimal SBP (≤120 mmHg) and DBP (≤70 mmHg) trajectories, hypertensive trajectories were associated with increased mortality and incident CVD in both men and women during follow-up at univariable level. These associations were nevertheless not maintained upon extensive confounder adjustment including antihypertensive therapies. CONCLUSION: We report sex disparities in CVD prevention which may relate to worse cardiometabolic profiles and less pronounced longitudinal SBP decreases in women. Effective anti-hypertensivetherapy may offset the adverse outcomes associated with prolonged exposure to high blood pressure

The J-triplet Cooper pairing with magnetic dipolar interactions

Recently, cold atomic Fermi gases with the large magnetic dipolar interaction have been laser cooled down to quantum degeneracy. Different from electric-dipoles which are classic vectors, atomic magnetic dipoles are quantum-mechanical matrix operators proportional to the hyperfine-spin of atoms, thus provide rich opportunities to investigate exotic many-body physics. Furthermore, unlike anisotropic electric dipolar gases, unpolarized magnetic dipolar systems are isotropic under simultaneous spin-orbit rotation. These features give rise to a robust mechanism for a novel pairing symmetry: orbital p-wave (L=1) spin triplet (S=1) pairing with total angular momentum of the Cooper pair J=1. This pairing is markedly different from both the $^3$He-B phase in which J=0 and the $^3$He-$A$ phase in which $J$ is not conserved. It is also different from the p-wave pairing in the single-component electric dipolar systems in which the spin degree of freedom is frozen

Evaluating regional emission estimates using the TRACE-P observations

Measurements obtained during the NASA Transport and Chemical Evolution over the Pacific (TRACE-P) experiment are used in conjunction with regional modeling analysis to evaluate emission estimates for Asia. A comparison between the modeled values and the observations is one method to evaluate emissions. Based on such analysis it is concluded that the inventory performs well for the light alkanes, CO, ethyne, SO2, and NOₓ. Furthermore, based on model skill in predicting important photochemical species such as O₃, HCHO, OH, HO₂, and HNO₃, it is found that the emissions inventories are of sufficient quality to support preliminary studies of ozone production. These are important finding in light of the fact that emission estimates for many species (such as speciated NMHCs and BC) for this region have only recently been estimated and are highly uncertain. Using a classification of the measurements built upon trajectory analysis, we compare observed species distributions and ratios of species to those modeled and to ratios estimated from the emissions inventory. It is shown that this technique can reconstruct a spatial distribution of propane/benzene that looks remarkably similar to that calculated from the emissions inventory. A major discrepancy between modeled and observed behavior is found in the Yellow Sea, where modeled values are systematically underpredicted. The integrated analysis suggests that this may be related to an underestimation of emissions from the domestic sector. The emission is further tested by comparing observed and measured species ratios in identified megacity plumes. Many of the model derived ratios (e.g., BC/CO, SOₓ/C₂H₂) fall within ∼25% of those observed and all fall outside of a factor of 2.5. (See Article file for details of the abstract.)Department of Civil and Environmental EngineeringAuthor name used in this publication: Wang, T

Net primary productivity of forest stands in New Hampshire estimated from Landsat and MODIS satellite data

© 2007 Potter et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients