Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays

Background Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat (‘artificial animal’) applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Results Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. Conclusions We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain tissues support emerging, exploitable commonalities between in vivo and in vitro preparations. We conclude that experimental manipulation of endogenous cholinergic tone could offer a novel opportunity to improve the use of cortical cultures for studies of network-level mechanisms in a manner that remains largely consistent with its functional role.

Photoproduction of heavy quarks in next-to-leading order QCD with longitudinally polarized initial states

We present all relevant details of our calculation of the complete next-to-leading order O(αS2α) QCD corrections to heavy flavor photoproduction with longitudinally polarized point-like photons and hadrons. In particular we provide analytical results for the virtual plus soft gluon cross section. We carefully address the relevance of remaining theoretical uncertainties by varying, for instance, the factorization and renormalization scales independently. Such studies are of importance for a meaningful first direct determination of the polarized gluon density Δg from the total charm production spin asymmetry by the upcoming COMPASS experiment. It is shown that the scale uncertainty is considerably reduced in next-to-leading order, but the dependence on the charm quark mass is sizable at fixed target energies. Finally, we study several differential single-inclusive heavy quark distributions and, for the polarized HERA option, the total bottom spin asymmetry.

The Empirical Forcing Function as a tool for the diagnosis of large-scale atmospheric anomalies

The time-mean quasi-geostrophic potential vorticity equation of the atmospheric flow on isobaric surfaces can explicitly include an atmospheric (internal) forcing term of the stationary-eddy flow. In fact, neglecting some non-linear terms in this equation, this forcing can be mathematically expressed as a single function, called Empirical Forcing Function (EFF), which is equal to the material derivative of the time-mean potential vorticity. Furthermore, the EFF can be decomposed as a sum of seven components, each one representing a forcing mechanism of different nature. These mechanisms include diabatic components associated with the radiative forcing, latent heat release and frictional dissipation, and components related to transient eddy transports of heat and momentum. All these factors quantify the role of the transient eddies in forcing the atmospheric circulation. In order to assess the relevance of the EFF in diagnosing large-scale anomalies in the atmospheric circulation, the relationship between the EFF and the occurrence of strong North Atlantic ridges over the Eastern North Atlantic is analyzed, which are often precursors of severe droughts over Western Iberia. For such events, the EFF pattern depicts a clear dipolar structure over the North Atlantic; cyclonic (anticyclonic) forcing of potential vorticity is found upstream (downstream) of the anomalously strong ridges. Results also show that the most significant components are related to the diabatic processes. Lastly, these results highlight the relevance of the EFF in diagnosing large-scale anomalies, also providing some insight into their interaction with different physical mechanisms.

Introduction: some notes on the generative study of L3 acquisition.

This article serves as a state-of the-science review of the blossoming field of generative third language (L3) acquisition as well as an introduction to this special issue on the same topic. We present and argue for the relevance of adult L3/Ln acquisition for many perennial questions that have sat at the core of linguistic approaches to adult language acquisition since the Principles and Parameters framework was first adopted into second language acquisition (SLA; e.g. Flynn, 1985, 1987; Liceras, 1985; White, 1985a, 1985b; Schwartz, 1986). Furthermore, we highlight the unique, specific questions that have emerged from studying L3/Ln from a generative perspective thus far while suggesting refinements to these questions and additional ones that should emerge in future inquiry.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Credit and liquidity components of corporate CDS spreads

This paper investigates the role of credit and liquidity factors in explaining corporate CDS price changes during normal and crisis periods. We find that liquidity risk is more important than firm-specific credit risk regardless of market conditions. Moreover, in the period prior to the recent “Great Recession” credit risk plays no role in explaining CDS price changes. The dominance of liquidity effects casts serious doubts on the relevance of CDS price changes as an indicator of default risk dynamics. Our results show how multiple liquidity factors including firm specific and aggregate liquidity proxies as well as an asymmetric information measure are critical determinants of CDS price variations. In particular, the impact of informed traders on the CDS price increases when markets are characterised by higher uncertainty, which supports concerns of insider trading during the crisis.

Hippurate: the natural history of a mammalian-microbial co-metabolite

Hippurate, the glycine conjugate of benzoic acid, is a normal constituent of the endogenous urinary metabolite profile and has long been associated with the microbial degradation of certain dietary components, hepatic function and toluene exposure, and is also commonly used as a measure of renal clearance. Here we discuss the potential relevance of hippurate excretion with regards to normal endogenous metabolism and trends in excretion relating to gender, age, and the intestinal microbiota. Additionally, the significance of hippurate excretion with regards to disease states including obesity, diabetes, gastrointestinal diseases, impaired renal function, psychological disorders and autism, as well as toxicity and parasitic infection, are considered.

The Copenhagen principles on the handling of detainees: implications for the procedural regulation of internment

The Copenhagen Principles on the Handling of Detainees in International Military Operations were released in October 2012 after a five-year long process involving states and certain organizations. The Principles address a number of issues concerning the handling and transfer of detainees. They apply in military operations conducted by states abroad in the context of non-international armed conflicts and peace operations. This article focuses on those principles that address the procedural regulation of internment (ie preventive, security detention), as it is here that the current law is particularly unclear. On the one hand, the treaty provisions applicable in non-international armed conflicts contain no rules on the procedural regulation of internment, in comparison with the law of international armed conflict. On the other hand, the relevant rules under international human rights law (IHRL) appear derogable in such situations. This article demonstrates that the approach taken to this issue in the Copenhagen Principles is one which essentially draws on the procedural rules applicable to civilian internment in the international armed conflicts. These rules adopt standards that are lower than those under IHRL. Reference is then made to other recent practice, which illustrates that the Copenhagen Principles do not apply in a legal vacuum. In particular, two recent judicial developments highlight the continued relevance of human rights law and domestic law, respectively, in regulating detention operations in the context of international military operations. Compliance with the Copenhagen Principles may not, therefore, be sufficient for detention to be lawful.

Farmers' views on the future of olive farming in Andalusia, Spain

Andalusia, located in southern Spain, is the major olive production area worldwide. Due to the relevance of this agricultural sector on the regional income, this article investigates olive farmer's perspectives regarding olive production after their retirement and potential factors affecting these including economic, social, environmental and spatial factors. We use data from a survey conducted to 431 olive farmers in Andalusia in 2010. Our findings show spatial dependence in explaining farmer's views on the future of olive farming at relatively small distances. In addition other factors such as bad economic performance, erosion or olive diseases affect farmer's perception. We make propositions on what elements should be taking into account when designing agricultural policies aiming at guaranteeing the sustainability of olive farming in future.

Reconstruction of geomagnetic activity and near-Earth interplanetary conditions over the past 167 yr - Part 3: improved representation of solar cycle 11

Svalgaard (2014) has recently pointed out that the calibration of the Helsinki magnetic observatory’s H component variometer was probably in error in published data for the years 1866–1874.5 and that this makes the interdiurnal variation index based on daily means, IDV(1d), (Lockwood et al., 2013a), and the interplanetary magnetic field strength derived from it (Lockwood et al., 2013b), too low around the peak of solar cycle 11. We use data from the modern Nurmijarvi station, relatively close to the site of the original Helsinki Observatory, to confirm a 30% underestimation in this interval and hence our results are fully consistent with the correction derived by Svalgaard. We show that the best method for recalibration uses the Helsinki Ak(H) and aa indices and is accurate to ±10 %. This makes it preferable to recalibration using either the sunspot number or the diurnal range of geomagnetic activity which we find to be accurate to ±20 %. In the case of Helsinki data during cycle 11, the two recalibration methods produce very similar corrections which are here confirmed using newly digitised data from the nearby St Petersburg observatory and also using declination data from Helsinki. However, we show that the IDV index is, compared to later years, too similar to sunspot number before 1872, revealing independence of the two data series has been lost; either because the geomagnetic data used to compile IDV has been corrected using sunspot numbers, or vice versa, or both. We present corrected data sequences for both the IDV(1d) index and the reconstructed IMF (interplanetary magnetic field).We also analyse the relationship between the derived near-Earth IMF and the sunspot number and point out the relevance of the prior history of solar activity, in addition to the contemporaneous value, to estimating any “floor” value of the near-Earth interplanetary field.

Hypothetical choice, egalitarianism, and the separateness of persons

Luck egalitarians claim that disadvantage is worse when it emerges from an unchosen risk than when it emerges from a chosen risk. I argue that disadvantage is also worse when it emerges from an unchosen risk that the disadvantaged agent would have declined to take, had he or she been able to do so, than when it emerges from an unchosen risk that the disadvantaged agent would not have declined to take. Such a view is significant because it allows both luck egalitarians and prioritarians to respond to Voorhoeve and Fleurbaey's charge that they fail to accommodate intuitions about the moral relevance of interpersonal boundaries – the so-called separateness of persons objection. I argue that the view is plausible independently of its ability to answer the separateness of persons objection, and is a natural extension of the luck egalitarian concern with the impact of unchosen circumstance.

First contribution of mites (Acari) to the forensic analysis of hanged corpses: a case study from Spain

This case study from North Spain, highlights the importance of the collection of mites in addition to insects, from crime scenes or corpses subjected to environmental constraints that reduce or minimise insect activity, such as hanged corpses. In addition, this analysis highlights the relevance of arthropods’ collection in the field, even after the corpse has been moved away for autopsy. Four species of mites, phoretic on carrion (Silphidae) and rove (Staphylinidae) beetles, complemented and reinforced the autopsy analysis as well as the scarce information provided by insect activity. Poecilochirus carabi Canestrini & Canestrini, 1882 and Poecilochirus (Physoparasitus) davydovae Hyatt, 1980 (Mesostigmata: Parasitidae) were found in association with two Silphidae, Nicrophorus Fabricius, 1775 and Necrodes Leach, 1815, only when sampled in the autopsy room; this is suggestive of host-switching of mites and was likely due to the lack of availability of specific carriers in the field. The interpretation of the activity of Parasitidae mites both in the field and the autopsy room allows a better understanding of the timing and circumstances of decomposition. Phoretic deutonymphs of Pelzneria Scheucher 1957 (Astigmata: Histiostomatidae) were highly abundant, mostly P. crenulata Oudemans, 1909 and are reported for the first time on a Staphylinidae rove beetle, Creophilus maxillosus (L., 1758). Surprisingly, in this case study no Pelzneria were associated with the Silphidae found, which are their most common hosts, such as Necrodes littoralis (L., 1758) and Nicrophorus interruptus (Stephens, 1830). All histiostomatids were removed from the staphylinid (rove beetle) collected from the soil, at the scene of death, suggesting a recent arrival of the beetle. The occurrence of Staphylinidae beetles and their associated mites, such as Parasitidae and Pelzneria, and the information they provided would have been easily overlooked or lost if only the autopsy sampling would have been considered in the analysis of the case. The four mite species are reported for the first time for the Iberian Peninsula.

Finding the 'first voice' in rural England: the challenges of safeguarding intangible heritage in a national museum

This paper is an attempt to explore the challenges of defining intangible heritage and ‘community’ in England. It uses as its case study the Museum of English Rural Life, University of Reading: an urban museum with a rural theme. The paper examines current theoretical discourse around the concept of the ‘first voice’ and debate about the role of museums in the preservation of intangible heritage. It then examines the relevance of these concepts to the identification of ‘rural’ intangible heritage stake holders in England. In this way, it shows the potential for concepts of intangible heritage to influence national museums. However, by applying theory and practice which is designed to support work with well-defined ‘originating communities’ to a national museum, it also highlights the challenges of initiating community engagement in a multicultural society.

On the structure and dynamics of Indian monsoon depressions

ERA-Interim reanalysis data from the past 35 years have been used with a newly-developed feature tracking algorithm to identify Indian monsoon depressions originating in or near the Bay of Bengal. These were then rotated, centralised and combined to give a fully three-dimensional 106-depression composite structure – a considerably larger sample than any previous detailed study on monsoon depressions and their structure. Many known features of depression structure are confirmed, particularly the existence of a maximum to the southwest of the centre in rainfall and other fields, and a westward axial tilt in others. Additionally, the depressions are found to have significant asymmetry due to the presence of the Himalayas; a bimodal mid-tropospheric potential vorticity core; a separation into thermally cold- (~–1.5K) and neutral- (~0K) cores near the surface with distinct properties; and that the centre has very large CAPE and very small CIN. Variability as a function of background state has also been explored, with land/coast/sea, diurnal, ENSO, active/break and Indian Ocean Dipole contrasts considered. Depressions are found to be markedly stronger during the active phase of the monsoon, as well as during La Niña. Depressions on land are shown to be more intense and more tightly constrained to the central axis. A detailed schematic diagram of a vertical cross-section through a composite depression is also presented, showing its inherent asymmetric structure.

The EU societal awareness of landscape indicator: a review of its meaning, utility and performance across different scales

There is increasing recognition that agricultural landscapes meet multiple societal needs and demands beyond provision of economic and environmental goods and services. Accordingly, there have been significant calls for the inclusion of societal, amenity and cultural values in agri-environmental landscape indicators to assist policy makers in monitoring the wider impacts of land-based policies. However, capturing the amenity and cultural values that rural agrarian areas provide, by use of such indicators, presents significant challenges. The EU social awareness of landscape indicator represents a new class of generalized social indicator using a top-down methodology to capture the social dimensions of landscape without reference to the specific structural and cultural characteristics of individual landscapes. This paper reviews this indicator in the context of existing agri-environmental indicators and their differing design concepts. Using a stakeholder consultation approach in five case study regions, the potential and limitations of the indicator are evaluated, with a particular focus on its perceived meaning, utility and performance in the context of different user groups and at different geographical scales. This analysis supplements previous EU-wide assessments, through regional scale assessment of the limitations and potentialities of the indicator and the need for further data collection. The evaluation finds that the perceived meaning of the indicator does not vary with scale, but in common with all mapped indicators, the usefulness of the indicator, to different user groups, does change with scale of presentation. This indicator is viewed as most useful when presented at the scale of governance at which end users operate. The relevance of the different sub-components of the indicator are also found to vary across regions.