Patterning and detailed study of human hNT astrocytes on parylene-C/silicon dioxide substrates to the single cell level.

It is estimated that the adult human brain contains 100 billion neurons with 5-10 times as many astrocytes. Although it has been generally considered that the astrocyte is a simple supportive cell to the neuron, recent research has revealed new functionality of the astrocyte in the form of information transfer to neurons of the brain. In our previous work we developed a protocol to pattern the hNT neuron (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/SiO(2) substrates. In this work, we report how we have managed to pattern hNT astrocytes, on parylene-C/SiO(2) substrates to single cell resolution. This article disseminates the nanofabrication and cell culturing steps necessary for the patterning of such cells. In addition, it reports the necessary strip lengths and strip width dimensions of parylene-C that encourage high degrees of cellular coverage and single cell isolation for this cell type. The significance in patterning the hNT astrocyte on silicon chip is that it will help enable single cell and network studies into the undiscovered functionality of this interesting cell, thus, contributing to closer pathological studies of the human brain.

La Teoría del Diseño Inteligente : un análisis desde el tomismo

Resumen: Michael Behe y William Dembski son dos de los líderes de la Teoría del Diseño Inteligente, una propuesta surgida como respuesta a los modelos evolucionistas y anti-finalistas prevalentes en ciertos ambientes académicos e intelectuales, especialmente del mundo anglosajón. Las especulaciones de Behe descansan en el concepto de “sistema de complejidad irreductible”, entendido como un conjunto ordenado de partes cuya funcionalidad depende estrictamente de su indemnidad estructural, y que su origen resulta, por tanto, refractario a explicaciones gradualistas. Estos sistemas, según Behe, están presentes en los vivientes, lo que permitiría inferir que ellos no son el producto de mecanismos ciegos y azarosos, sino el resultado de un diseño. Dembski, por su parte, ha abordado el problema desde una perspectiva más cuantitativa, desarrollando un algoritmo probabilístico conocido como “filtro explicatorio”, que permitiría, según el autor, inferir científicamente la presencia de un diseño, tanto en entidades artificiales como naturales. Trascendiendo las descalificaciones del neodarwinismo, examinamos la propuesta de estos autores desde los fundamentos filosóficos de la escuela tomista. A nuestro parecer, hay en el trabajo de estos autores algunas intuiciones valiosas, las que sin embargo suelen pasar desapercibidas por la escasa formalidad en que vienen presentadas, y por la aproximación eminentemente mecanicista y artefactual con que ambos enfrentan la cuestión. Es precisamente a la explicitación de tales intuiciones a las que se dirige el artículo.

El viaje omnipresente : su funcionalidad discursiva en los relatos culturales de la segunda modernidad

Número monográfico: El viaje y sus discursos

Régimen jurídico de las lenguas y reconocimiento de la diversidad lingüística en el Tratado por el que se establece una Constitución para Europa

The territory of the European Union is made up of a rich and wide-ranging universe of languages, which is not circumscribed to the «State languages». The existence of multilingualism is one of Europe’s defining characteristics and it should remain so in the constantly evolving model of Europe’s political structure. Nonetheless, until now, the official use of languages has been limited to the «State languages» and has been based on a concept of state monolingualism that has led to a first level of hierarchization among the languages of Europe. This has affected the very concept of European language diversity. The draft of the treaty establishing a European Constitution contains various language-related references that can be grouped in two major categories: on the one hand, those references having to do the constitutional status of languages, and on the other, those regarding the recognition of European language diversity. Both issues are dealt with in this article. In analyzing the legal regime governing languages set forth in the draft of the constitutional treaty, we note that the draft is not based on the concept of the official status of languages. The language regulation contained in the draft of the constitutional treaty is limited in character. The constitutional language regime is based on the concept of Constitutional languages but the official status of languages is not governed by this rule. The European Constitution merely enunciates rights governing language use for European citizens vis-à-vis the languages of the Constitution and refers the regulation of the official status of languages to the Council, which is empowered to set and modify that status by unanimous decision. Because of its broad scope, this constitutes a regulatory reservation. In the final phase of the negotiation process a second level of constitutional recognition of languages would be introduced, linked to those that are official languages in the member states (Catalan, Basque, Galician, etc.). These languages, however, would be excluded from the right to petition; they would constitute a tertium genus, an intermediate category between the lan guages benefiting from the language rights recognized under the Constitution and those other languages for which no status is recognized in the European institutional context. The legal functionality of this second, intermediate category will depend on the development of standards, i.e., it will depend on the entrée provided such languages in future reforms of the institutional language regime. In a later section, the article reflects on European Union language policy with regard to regional or minority languages, concluding that the Union has not acted in accordance with defined language policy guidelines when it has been confronted, in the exercise of its powers, with regional or minority languages (or domestic legislation having to do with language demands). The Court of Justice has endeavoured to resolve on a case by case basis the conflicts raised between community freedoms and the normative measures that protect languages. Thus, using case law, the Court has set certain language boundaries for community freedoms. The article concludes by reflecting on the legal scope of the recognition of European language diversity referred to in Article II-82 of the European Constitution and the possible measures to implement the precept that might constitute the definition of a true European language policy on regional or minority languages. Such a policy has yet to be defined.

"I'm on it 24/7 at the moment" : A qualitative examination of multi-screen viewing behaviours among UK 10-11 year olds

Background: Screen-viewing has been associated with increased body mass, increased risk of metabolic syndrome and lower psychological well-being among children and adolescents. There is a shortage of information about the nature of contemporary screen-viewing amongst children especially given the rapid advances in screen-viewing equipment technology and their widespread availability. Anecdotal evidence suggests that large numbers of children embrace the multi-functionality of current devices to engage in multiple forms of screen-viewing at the same time. In this paper we used qualitative methods to assess the nature and extent of multiple forms of screen-viewing in UK children. Methods: Focus groups were conducted with 10-11 year old children (n = 63) who were recruited from five primary schools in Bristol, UK. Topics included the types of screen-viewing in which the participants engaged; whether the participants ever engaged in more than one form of screen-viewing at any time and if so the nature of this multiple viewing; reasons for engaging in multi-screen-viewing; the room within the house where multi-screen-viewing took place and the reasons for selecting that room. All focus groups were transcribed verbatim, anonymised and thematically analysed. Results: Multi-screen viewing was a common behaviour. Although multi-screen viewing often involved watching TV, TV viewing was often the background behaviour with attention focussed towards a laptop, handheld device or smart-phone. There were three main reasons for engaging in multi-screen viewing: 1) tempering impatience that was associated with a programme loading; 2) multi-screen facilitated filtering out unwanted content such as advertisements; and 3) multi-screen viewing was perceived to be enjoyable. Multi-screen viewing occurred either in the child's bedroom or in the main living area of the home. There was considerable variability in the level and timing of viewing and this appeared to be a function of whether the participants attended after-school clubs. Conclusions: UK children regularly engage in two or more forms of screen-viewing at the same time. There are currently no means of assessing multi-screen viewing nor any interventions that specifically focus on reducing multi-screen viewing. To reduce children's overall screen-viewing we need to understand and then develop approaches to reduce multi-screen viewing among children.

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

19 p.

La funcionalidad de las creencias

[ES]Este trabajo muestra de forma comparativa la simbología existente con relación a la muerte en dos comunidades gallegas. Aquí presento unas breves reflexiones sobre los estereotipos, todo ello articulado en los silencios que se producen en los saltos generacionales. Finalizando con la delimitación de los espacios físicos correspondientes a las diferencias simbólicas en la construcción de los “unos” y los “otros”.

Communities in complex networks

The study of complex networks has attracted the attention of the scientific community for many obvious reasons. A vast number of systems, from the brain to ecosystems, power grid, and the Internet, can be represented as large complex networks, i.e, assemblies of many interacting components with nontrivial topological properties. The link between these components can describe a global behaviour such as the Internet traffic, electricity supply service, market trend, etc. One of the most relevant topological feature of graphs representing these complex systems is community structure which aims to identify the modules and, possibly, their hierarchical organization, by only using the information encoded in the graph topology. Deciphering network community structure is not only important in order to characterize the graph topologically, but gives some information both on the formation of the network and on its functionality.

A neural extracellular matrix-based method for in vitro hippocampal neuron culture and dopaminergic differentiation of neural stem cells

Background: The ability to recreate an optimal cellular microenvironment is critical to understand neuronal behavior and functionality in vitro. An organized neural extracellular matrix (nECM) promotes neural cell adhesion, proliferation and differentiation. Here, we expanded previous observations on the ability of nECM to support in vitro neuronal differentiation, with the following goals: (i) to recreate complex neuronal networks of embryonic rat hippocampal cells, and (ii) to achieve improved levels of dopaminergic differentiation of subventricular zone (SVZ) neural progenitor cells. Methods: Hippocampal cells from E18 rat embryos were seeded on PLL- and nECM-coated substrates. Neurosphere cultures were prepared from the SVZ of P4-P7 rat pups, and differentiation of neurospheres assayed on PLL- and nECM-coated substrates. Results: When seeded on nECM-coated substrates, both hippocampal cells and SVZ progenitor cells showed neural expression patterns that were similar to their poly-L-lysine-seeded counterparts. However, nECM-based cultures of both hippocampal neurons and SVZ progenitor cells could be maintained for longer times as compared to poly-L-lysine-based cultures. As a result, nECM-based cultures gave rise to a more branched neurite arborization of hippocampal neurons. Interestingly, the prolonged differentiation time of SVZ progenitor cells in nECM allowed us to obtain a purer population of dopaminergic neurons. Conclusions: We conclude that nECM-based coating is an efficient substrate to culture neural cells at different stages of differentiation. In addition, neural ECM-coated substrates increased neuronal survival and neuronal differentiation efficiency as compared to cationic polymers such as poly-L-lysine.

Report on Knowledge Exchange workshop Cost models for keeping knowledge: economic models for digital preservation

Organised by Knowledge Exchange & the Nordbib programme 11 June 2012, 8:30-12:30, Copenhagen Adjacent to the Nordbib conference 'Structural frameworks for open, digital research' Participants in break out discussion during the workshop on cost modelsThe Knowledge Exchange and the Nordbib programme organised a workshop on cost models for the preservation and management of digital collections. The rapid growth of the digital information which a wide range of institutions must preserve emphasizes the need for robust cost modelling. Such models should enable these institutions to assess both what resources are needed to sustain their digital preservation activities and allow comparisons of different preservation solutions in order to select the most cost-efficient alternative. In order to justify the costs institutions also need to describe the expected benefits of preserving digital information. This workshop provided an overview of existing models and demonstrated the functionality of some of the current cost tools. It considered the specific economic challenges with regard to the preservation of research data and addressed the benefits of investing in the preservation of digital information. Finally, the workshop discussed international collaboration on cost models. The aim of the workshop was to facilitate understanding of the economies of data preservation and to discuss the value of developing an international benchmarking model for the costs and benefits of digital preservation. The workshop took place in the Danish Agency for Culture and was planned directly prior to the Nordbib conference 'Structural frameworks for open, digital research'

Evaluación de la política de Espacios Naturales Protegidos: una propuesta metodológica para la Comunidad Autónoma del País Vasco

395 p.

Kalman Filtering in R

Support in R for state space estimation via Kalman filtering was limited to one package, until fairly recently. In the last five years, the situation has changed with no less than four additional packages offering general implementations of the Kalman filter, including in some cases smoothing, simulation smoothing and other functionality. This paper reviews some of the offerings in R to help the prospective user to make an informed choice.

Global Self-Organization of the Cellular Metabolic Structure

Background: Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using "metabolic networks models'' are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used "dissipative metabolic networks'' (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings: Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance: This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures.

Membrane Deformability and Membrane Tension of Single Isolated Mitochondria

Mitochondria dynamics is crucial to many biological processes such as mitochondria fusion and fission, which is highly correlated to the mechanics of single mitochondria. However, the mechanobiological coupling of mitochondria has been poorly understood. Here membrane deformability and membrane tension of individual mitochondria isolated from MtDsRed labeled human embryonic T-Rex-293 kidney cells were measured using a micropipette aspiration assay. The results demonstrated that membrane deformation of isolated mitochondria exhibited an elastic transition phase followed by an equilibrium phase, and mitochondrial membrane tension was proportional to the area compressibility. It was also indicated that mitochondrial membrane deformability was significantly affected by physical chemical factors such as osmotic pressure or pH value, and was further correlated to mitochondrial functionality in different respiratory states and Ca2+ regulation. These findings provide a new insight into understanding the mechanical regulation of mitochondrial physiology.

Dense, efficient chip-to-chip communication at the extremes of computing

The scalability of CMOS technology has driven computation into a diverse range of applications across the power consumption, performance and size spectra. Communication is a necessary adjunct to computation, and whether this is to push data from node-to-node in a high-performance computing cluster or from the receiver of wireless link to a neural stimulator in a biomedical implant, interconnect can take up a significant portion of the overall system power budget. Although a single interconnect methodology cannot address such a broad range of systems efficiently, there are a number of key design concepts that enable good interconnect design in the age of highly-scaled CMOS: an emphasis on highly-digital approaches to solving ‘analog’ problems, hardware sharing between links as well as between different functions (such as equalization and synchronization) in the same link, and adaptive hardware that changes its operating parameters to mitigate not only variation in the fabrication of the link, but also link conditions that change over time. These concepts are demonstrated through the use of two design examples, at the extremes of the power and performance spectra.

A novel all-digital clock and data recovery technique for high-performance, high density interconnect has been developed. Two independently adjustable clock phases are generated from a delay line calibrated to 2 UI. One clock phase is placed in the middle of the eye to recover the data, while the other is swept across the delay line. The samples produced by the two clocks are compared to generate eye information, which is used to determine the best phase for data recovery. The functions of the two clocks are swapped after the data phase is updated; this ping-pong action allows an infinite delay range without the use of a PLL or DLL. The scheme's generalized sampling and retiming architecture is used in a sharing technique that saves power and area in high-density interconnect. The eye information generated is also useful for tuning an adaptive equalizer, circumventing the need for dedicated adaptation hardware.

On the other side of the performance/power spectra, a capacitive proximity interconnect has been developed to support 3D integration of biomedical implants. In order to integrate more functionality while staying within size limits, implant electronics can be embedded onto a foldable parylene (‘origami’) substrate. Many of the ICs in an origami implant will be placed face-to-face with each other, so wireless proximity interconnect can be used to increase communication density while decreasing implant size, as well as facilitate a modular approach to implant design, where pre-fabricated parylene-and-IC modules are assembled together on-demand to make custom implants. Such an interconnect needs to be able to sense and adapt to changes in alignment. The proposed array uses a TDC-like structure to realize both communication and alignment sensing within the same set of plates, increasing communication density and eliminating the need to infer link quality from a separate alignment block. In order to distinguish the communication plates from the nearby ground plane, a stimulus is applied to the transmitter plate, which is rectified at the receiver to bias a delay generation block. This delay is in turn converted into a digital word using a TDC, providing alignment information.