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.

Multi-population genetic algorithm to solve the synchronized and integrated two-level lot sizing and scheduling problem

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coupling biomechanics to a cellular level model: An approach to patient-specific image driven multi-scale and multi-physics tumor simulation

Modeling of tumor growth has been performed according to various approaches addressing different biocomplexity levels and spatiotemporal scales. Mathematical treatments range from partial differential equation based diffusion models to rule-based cellular level simulators, aiming at both improving our quantitative understanding of the underlying biological processes and, in the mid- and long term, constructing reliable multi-scale predictive platforms to support patient-individualized treatment planning and optimization. The aim of this paper is to establish a multi-scale and multi-physics approach to tumor modeling taking into account both the cellular and the macroscopic mechanical level. Therefore, an already developed biomodel of clinical tumor growth and response to treatment is self-consistently coupled with a biomechanical model. Results are presented for the free growth case of the imageable component of an initially point-like glioblastoma multiforme tumor. The composite model leads to significant tumor shape corrections that are achieved through the utilization of environmental pressure information and the application of biomechanical principles. Using the ratio of smallest to largest moment of inertia of the tumor material to quantify the effect of our coupled approach, we have found a tumor shape correction of 20\% by coupling biomechanics to the cellular simulator as compared to a cellular simulation without preferred growth directions. We conclude that the integration of the two models provides additional morphological insight into realistic tumor growth behavior. Therefore, it might be used for the development of an advanced oncosimulator focusing on tumor types for which morphology plays an important role in surgical and/or radio-therapeutic treatment planning.

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy. A Multi-Institutional Analysis.

PURPOSE The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.

Use of phosphorous mapping and sea-level change data in assessing coastal activity zones and establishing site chronology : A case study from the Icelandic multi-period site of Vatnsfjörður

This paper forms part of Lukasz Mikolajczyk's PhD dissertation, which is supervised by Karen Milek

Consequences of twenty-first-century policy for multi-millennial climate and sea-level change

Most of the policy debate surrounding the actions needed to mitigate and adapt to anthropogenic climate change has been framed by observations of the past 150 years as well as climate and sea-level projections for the twenty-first century. The focus on this 250-year window, however, obscures some of the most profound problems associated with climate change. Here, we argue that the twentieth and twenty-first centuries, a period during which the overwhelming majority of human-caused carbon emissions are likely to occur, need to be placed into a long-term context that includes the past 20 millennia, when the last Ice Age ended and human civilization developed, and the next ten millennia, over which time the projected impacts of anthropogenic climate change will grow and persist. This long-term perspective illustrates that policy decisions made in the next few years to decades will have profound impacts on global climate, ecosystems and human societies — not just for this century, but for the next ten millennia and beyond.

Multi-scale approaches to Food Sciences: computational QM and MM explorations at the microscopic level

L'obiettivo principale della politica di sicurezza alimentare è quello di garantire la salute dei consumatori attraverso regole e protocolli di sicurezza specifici. Al fine di rispondere ai requisiti di sicurezza alimentare e standardizzazione della qualità, nel 2002 il Parlamento Europeo e il Consiglio dell'UE (Regolamento (CE) 178/2002 (CE, 2002)), hanno cercato di uniformare concetti, principi e procedure in modo da fornire una base comune in materia di disciplina degli alimenti e mangimi provenienti da Stati membri a livello comunitario. La formalizzazione di regole e protocolli di standardizzazione dovrebbe però passare attraverso una più dettagliata e accurata comprensione ed armonizzazione delle proprietà globali (macroscopiche), pseudo-locali (mesoscopiche), ed eventualmente, locali (microscopiche) dei prodotti alimentari. L'obiettivo principale di questa tesi di dottorato è di illustrare come le tecniche computazionali possano rappresentare un valido supporto per l'analisi e ciò tramite (i) l’applicazione di protocolli e (ii) miglioramento delle tecniche ampiamente applicate. Una dimostrazione diretta delle potenzialità già offerte dagli approcci computazionali viene offerta nel primo lavoro in cui un virtual screening basato su docking è stato applicato al fine di valutare la preliminare xeno-androgenicità di alcuni contaminanti alimentari. Il secondo e terzo lavoro riguardano lo sviluppo e la convalida di nuovi descrittori chimico-fisici in un contesto 3D-QSAR. Denominata HyPhar (Hydrophobic Pharmacophore), la nuova metodologia così messa a punto è stata usata per esplorare il tema della selettività tra bersagli molecolari strutturalmente correlati e ha così dimostrato di possedere i necessari requisiti di applicabilità e adattabilità in un contesto alimentare. Nel complesso, i risultati ci permettono di essere fiduciosi nel potenziale impatto che le tecniche in silico potranno avere nella identificazione e chiarificazione di eventi molecolari implicati negli aspetti tossicologici e nutrizionali degli alimenti.

Multi-scale score level fusion of local descriptors for gender classification in the wild

The 2015 FRVT gender classification (GC) report evidences the problems that current approaches tackle in situations with large variations in pose, illumination, background and facial expression. The report suggests that both commercial and research solutions are hardly able to reach an accuracy over 90% for The Images of Groups dataset, a proven scenario exhibiting unrestricted or in the wild conditions. In this paper, we focus on this challenging dataset, stepping forward in GC performance by observing: 1) recent literature results combining multiple local descriptors, and 2) the psychophysics evidences of the greater importance of the ocular and mouth areas to solve this task...

Multi-purpose adaptable business tier components based on Call Level Interfaces

Call Level Interfaces (CLI) play a key role in business tiers of relational and on some NoSQL database applications whenever a fine tune control between application tiers and the host databases is a key requirement. Unfortunately, in spite of this significant advantage, CLI are low level API, this way not addressing high level architectural requirements. Among the examples we emphasize two situations: a) the need to decouple or not to decouple the development process of business tiers from the development process of application tiers and b) the need to automatically adapt business tiers to new business and/or security needs at runtime. To tackle these CLI drawbacks, and simultaneously keep their advantages, this paper proposes an architecture relying on CLI from which multi-purpose business tiers components are built, herein referred to as Adaptable Business Tier Components (ABTC). Beyond the reference architecture, this paper presents a proof of concept based on Java and Java Database Connectivity (an example of CLI).

ABTC: multi-purpose adaptable business tier components based on Call Level Interfaces

Call Level Interfaces (CLI) are low level API that play a key role in database applications whenever a fine tune control between application tiers and the host databases is a key requirement. Unfortunately, in spite of this significant advantage, CLI were not designed to address organizational requirements and contextual runtime requirements. Among the examples we emphasize the need to decouple or not to decouple the development process of business tiers from the development process of application tiers and also the need to automatically adapt to new business and/or security needs at runtime. To tackle these CLI drawbacks, and simultaneously keep their advantages, this paper proposes an architecture relying on CLI from which multi-purpose business tiers components are built, herein referred to as Adaptable Business Tier Components (ABTC). This paper presents the reference architecture for those components and a proof of concept based on Java and Java Database Connectivity (an example of CLI).

Multi-Scale Governance of Sustainable Natural Resource Use—Challenges and Opportunities for Monitoring and Institutional Development at the National and Global Level

In a globalized economy, the use of natural resources is determined by the demand of modern production and consumption systems, and by infrastructure development. Sustainable natural resource use will require good governance and management based on sound scientific information, data and indicators. There is a rich literature on natural resource management, yet the national and global scale and macro-economic policy making has been underrepresented. We provide an overview of the scholarly literature on multi-scale governance of natural resources, focusing on the information required by relevant actors from local to global scale. Global natural resource use is largely determined by national, regional, and local policies. We observe that in recent decades, the development of public policies of natural resource use has been fostered by an “inspiration cycle” between the research, policy and statistics community, fostering social learning. Effective natural resource policies require adequate monitoring tools, in particular indicators for the use of materials, energy, land, and water as well as waste and GHG emissions of national economies. We summarize the state-of-the-art of the application of accounting methods and data sources for national material flow accounts and indicators, including territorial and product-life-cycle based approaches. We show how accounts on natural resource use can inform the Sustainable Development Goals (SDGs) and argue that information on natural resource use, and in particular footprint indicators, will be indispensable for a consistent implementation of the SDGs. We recognize that improving the knowledge base for global natural resource use will require further institutional development including at national and international levels, for which we outline options.

How can the land managers and his multi-stakeholder network at the farm level influence the multifunctional transitions pathways?

The changing role of agriculture is at the core of transition pathways in many rural areas. Productivism, post-productivism and multifunctionality have been targeted towards a possible conceptualization of the transition happening in rural areas. The factors of change, including productivist and post-productivist trends, are combined in various ways and have gone in quite diverse directions and intensities, in individual regions and localities. Even, in the same holding, productivist and post-productivist strategies can co-exist spatially, temporally, structurally, leading to a higher complexity in changing patterns. In south Portugal extensive landscapes, dominated by traditionally managed agro-forestry systems under a fuzzy land use pattern, multifunctionality at the farm level is indeed conducted by different stakeholders whose interests may or not converge: a multifunctional land management may indeed incorporate post-productivist and productivist agents. These stakeholders act under different levels of ownership, management and use, reflecting a particular land management dynamic, in which different interests may exist, from commercial production to a variety of other functions (hunting, bee-keeping, subsistence farming, etc.), influencing management at the farm level and its supposed transition trajectory. This multistakeholder dynamic is composed by the main land-manager (the one who takes the main decisions), sub land-managers (land-managers under the rules of the main land-manager), workers and users (locals or outsiders), whose interest and action within the holding may vary differently according to future (policy, market, etc.) trends, and therefore reflect more or less resilient systems. The goal of the proposed presentation is to describe the multi-stakeholder relations at the farm level, its spatial expression and the factors influencing the land management system resilience in face of the transition trends in place.