bluuebunny/crossref_metadata_2025 huggingface dataset:
Solution structures of DEAD-box RNA chaperones reveal conformational changes and nucleic acid tethering by a basic tail
Authors: Mallam Anna L. , Jarmoskaite Inga , Tijerina Pilar , Del Campo Mark , Seifert Soenke , Guo Liang , Russell Rick , Lambowitz Alan M.
Published: July 2011

The mitochondrial DEAD-box proteins Mss116p of
Saccharomyces cerevisiae
and CYT-19 of
Neurospora crassa
are ATP-dependent helicases that function as general RNA chaperones. The helicase core of each protein precedes a C-terminal extension and a basic tail, whose structural role is unclear. Here we used small-angle X-ray scattering to obtain solution structures of the full-length proteins and a series of deletion mutants. We find that the two core domains have a preferred relative orientation in the open state without substrates, and we visualize the transition to a compact closed state upon binding RNA and adenosine nucleotide. An analysis of complexes with large chimeric oligonucleotides shows that the basic tails of both proteins are attached flexibly, enabling them to bind rigid duplex DNA segments extending from the core in different directions. Our results indicate that the basic tails of DEAD-box proteins contribute to RNA-chaperone activity by binding nonspecifically to large RNA substrates and flexibly tethering the core for the unwinding of neighboring duplexes.
The Etv1/Er81 transcription factor orchestrates activity-dependent gene regulation in the terminal maturation program of cerebellar granule cells
Authors: Abe Haruka , Okazawa Makoto , Nakanishi Shigetada
Published: July 2011

In the postnatal period, cerebellar granule cells express a set of the maturation gene battery in an activity-dependent manner and establish synaptic function in the cerebellar circuitry. Using primary cultures combined with specific inhibition of signaling cascades, the present investigation revealed that the expression of the maturation genes, including the NMDA glutamate receptor
NR2C
and GABA
A
receptor

GABA
A
Rα6

genes, is controlled by strikingly unified signaling mechanisms that operate sequentially through stimulation of AMPA and NMDA receptors, Na
+
channels [voltage-gated Na channel type II (Nav1.2)], and voltage-dependent Ca
2+
channels. This signaling then induces the Ets variant gene 1 (Etv1/Er81) transcription factor of the ETS family in an activity-dependent manner. Consistent with the culture study, the ChIP assay indicated that Etv1 up-regulates the maturation genes in a developmentally regulated manner. This activation, as revealed by the luciferase assay, occurrs by interacting with the Etv1-interacting motifs present in the promoter region. Importantly, in vivo knockdown of Etv1 by DNA electroporation in the developing cerebellum prevents the up-regulation of the maturation genes but has no effects on preceding developmental processes occurring in the granule cells. Etv1 thus orchestrates the activity-dependent gene regulation in the terminal maturation program and specifies the identity of cerebellar granule cells.
Co-Constructing Community Forests in Nepal: Mutual Constraint in a Transnational Aid Network
Authors: Thoms Christopher A.
Published: July 2011

Community forests in Nepal are co-constructed by multiple actors working together in a way that is mutually constraining for those involved in the network. Each network actor has goals/intentions that are mediated at the network level until the network as a whole develops a common, relatively “weak” goal sometimes far removed from individual starting goals. This mutual constraint prevents significant breakthroughs in restructuring local-level wealth and power disparities, which in turn play a role in depressing the livelihoods of marginalized households in rural Nepal.
Global Networks in Conservation: The Politics of Engagement between States, Civil Society and the World Bank
Authors: Duffy Rosaleen
Published: July 2011

This article examines the vertical nature of global networks that encompass civil society organizations (CSOs), Governments, donors and the private sector. It focuses on the power dynamics in environmental governance to cast light on how complex networks are able to define, prescribe and implement particular conservation policies at the national and sub-national levels. This article uses the case of conservation non-government organizations (NGOs) in Madagascar to reveal the ways that CSOs act as a conduit for global interests played out at national and local scales.
Learning to Lobby: Civil Society Networks in Mali
Authors: Benjamin Charles E.
Published: July 2011

This article examines two civil society networks—CNOP and GDRN5—involved in natural resource policy advocacy and policy formulation in Mali, after the initiation of democratic reform in 1991. Focusing on their influence on Mali's forest code, pastoral charter, and agricultural law, the article shows how the networks learned to engage the policy process, particularly policy formulation and adoption. The cases illustrate how representativeness and resources shaped their strategies in policy advocacy. They also illustrate how resource dependencies can open networks to ideological and governance pressures from donors.
The CALFED Bay-Delta Program: Lessons from the Rise and Fall of a Large-Scale Ecosystem Management Network
Authors: Lurie Susan D.
Published: July 2011

Ecosystem management, especially at the large/regional scale, typifies the public sector organizational environment of interconnectedness. Networks as complex organizational models can have significant advantages for intricate joint planning and management. There are, however, considerable challenges to establishing and sustaining such organizations in an institutional environment. The complex case study of CALFED, formed to integrate water management for the hub of California's water supply system, examines issues of network formation and survival in a high-stakes, high-conflict task environment. The lessons regarding conditions and events that led to CALFED's collapse should be of interest to policy makers, practitioners and scholars.
Spatial organization of RYRs and BK channels underlying the activation of STOCs by Ca2+ sparks in airway myocytes
Authors: Lifshitz Lawrence M. , Carmichael Jeffrey D. , Lai F. Anthony , Sorrentino Vincenzo , Bellvé Karl , Fogarty Kevin E. , ZhuGe Ronghua
Published: July 2011

Short-lived, localized Ca2+ events mediate Ca2+ signaling with high efficiency and great fidelity largely as a result of the close proximity between Ca2+-permeable ion channels and their molecular targets. However, in most cases, direct evidence of the spatial relationship between these two types of molecules is lacking, and, thus, mechanistic understanding of local Ca2+ signaling is incomplete. In this study, we use an integrated approach to tackling this issue on a prototypical local Ca2+ signaling system composed of Ca2+ sparks resulting from the opening of ryanodine receptors (RYRs) and spontaneous transient outward currents (STOCs) caused by the opening of Ca2+-activated K+ (BK) channels in airway smooth muscle. Biophysical analyses of STOCs and Ca2+ sparks acquired at 333 Hz demonstrate that these two events are associated closely in time, and approximately eight RYRs open to give rise to a Ca2+ spark, which activates ∼15 BK channels to generate a STOC at 0 mV. Dual immunocytochemistry and 3-D deconvolution at high spatial resolution reveal that both RYRs and BK channels form clusters and RYR1 and RYR2 (but not RYR3) localize near the membrane. Using the spatial relationship between RYRs and BK channels, the spatial-temporal profile of [Ca2+] resulting from Ca2+ sparks, and the kinetic model of BK channels, we estimate that an average Ca2+ spark caused by the opening of a cluster of RYR1 or RYR2 acts on BK channels from two to three clusters that are randomly distributed within an ∼600-nm radius of RYRs. With this spatial organization of RYRs and BK channels, we are able to model BK channel currents with the same salient features as those observed in STOCs across a range of physiological membrane potentials. Thus, this study provides a mechanistic understanding of the activation of STOCs by Ca2+ sparks using explicit knowledge of the spatial relationship between RYRs (the Ca2+ source) and BK channels (the Ca2+ target).
Quo Vadis? Catholic Perceptions of Flight and the Revolt of the Low Countries, 1566–1609*
Authors: Janssen Geert H.
Published: July 2011

This article examines Catholic views of flight, exile, and displacement during the Dutch Revolt. It argues that the civil war in the sixteenth-century Low Countries generated a new imagery of exile among Catholics, a process that was to some extent similar to what had happened to Protestant refugees a few decades earlier. Yet the Dutch case also demonstrates that the contrasting outcomes of the revolts in the Northern and Southern Netherlands led to very different appreciations of exile in Catholic communities in both areas. Habsburg triumph and Tridentine militancy sparked a Counter-Reformation movement in the Southern Netherlands that glorified exile and presented refugees as exemplary forces of an international militant church. In the northern Dutch Republic the revolt created a more ambiguous Catholic identity, in which loyalty to an officially Protestant state could coincide with commitment to the Church of Rome.
Periods of Eisenstein series and some applications
Authors: Kent Zachary
Published: July 2011

Bringmann, Guerzhoy, Ono, and the author developed an Eichler-Shimura theory for weakly holomorphic modular forms by studying associated period polynomials. Here we include the Eisenstein series in this theory.
Presentation length and Simon’s conjecture
Authors: Agol Ian , Liu Yi
Published: July 2011

In this paper, we show that any knot group maps onto at most finitely many knot groups. This gives an affirmative answer to a conjecture of J. Simon. We also bound the diameter of a closed hyperbolic 3-manifold linearly in terms of the presentation length of its fundamental group, improving a result of White.
Metaphor and Criticism
Authors: Grant James
Published: July 2011

The prevalence of colourful metaphors and figurative language in critics’ descriptions of artworks has long attracted attention. Talk of ‘liquid melodies’, ‘purple prose’, ‘soaring arches’, and the use of still more elaborate figurative descriptions, is not uncommon. My aim in this paper is to explain why metaphor is so prevalent in critical description. Many have taken the prevalence of art-critical metaphors to reveal something important about aesthetic experience and aesthetic properties. My focus is different. I attempt to determine what metaphor enables critics to achieve and why it is so well suited to helping them achieve it. I begin by outlining my account of what metaphors communicate and defend it against objections to the effect that it does not apply to art-critical metaphors. I then distinguish between two kinds of art-critical metaphor. This distinction is not normally drawn, but drawing it is essential to understanding why critics use metaphor. I then explain why each kind of metaphor is so common in criticism.
Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance
Authors: Brazhe A. R. , Maksimov G. V. , Mosekilde E. , Sosnovtseva O. V.
Published: July 2011

The myelinated nerve fibre is formed by an axon and Schwann cells or oligodendrocytes that sheath the axon by winding around it in tight myelin layers. Repetitive stimulation of a fibre is known to result in accumulation of extracellular potassium ions, especially between the axon and the myelin. Uptake of potassium leads to Schwann cell swelling and myelin restructuring that impacts the electrical properties of the myelin. In order to further understand the dynamic interaction that takes place between the myelin and the axon, we have modelled submyelin potassium accumulation and related changes in myelin resistance during prolonged high-frequency stimulation. We predict that potassium-mediated decrease in myelin resistance leads to a functional excitation block with various patterns of altered spike trains. The patterns are found to depend on stimulation frequency and amplitude and to range from no block (less than 100 Hz) to a complete block (greater than 500 Hz). The transitional patterns include intermittent periodic block with interleaved spiking and non-spiking intervals of different relative duration as well as an unstable regime with chaotic switching between the spiking and non-spiking states. Intermittent conduction blocks are accompanied by oscillations of extracellular potassium. The mechanism of conductance block based on myelin restructuring complements the already known and modelled block via hyperpolarization mediated by the axonal sodium pump and potassium depolarization.
Significance of microvascular remodelling for the vascular flow reserve in hypertension
Authors: Jacobsen Jens Christian Brings , Hornbech Morten Sonne , Holstein-Rathlou Niels-Henrik
Published: July 2011

Vascular flow reserve (VFR) is the relative increase in tissue perfusion from the resting state to a state with maximum vasodilatation. Longstanding hypertension reduces the VFR, which in turn reduces the maximum working capacity of the tissue. In principle, both inward arteriolar remodelling and rarefaction of the microvascular network may contribute to this reduction. These processes are known to occur simultaneously in the microcirculation of the hypertensive individual and both cause a reduction in the luminal trans-sectional area available for perfusion. Which of them is the main factor responsible for the reduction in VFR is, however, not known. Here we present simulations performed on large microvascular networks to assess the VFR in various situations. Particular attention is paid to the VFR in networks in which the vessels have structurally adapted to a sustained increase in pressure by inward eutrophic remodelling (IER), i.e. by redistributing the same amount of wall material around a smaller lumen. Collectively, the results indicate that the IER may not
per se
be the main factor responsible for the hypertensive reduction in VFR. Rather, it may be explained by the presence of arteriolar and capillary rarefaction.
Balance equations can buffer noisy and sustained environmental perturbations of circadian clocks
Authors: Domijan Mirela , Rand David A.
Published: July 2011

We present a new approach to understanding how regulatory networks such as circadian clocks might evolve robustness to environmental fluctuations. The approach is in terms of new balance equations that we derive. We use it to describe how an entrained clock can buffer the effects of daily fluctuations in light and temperature levels. We also use it to study a different approach to temperature compensation where instead of considering a free-running clock, we study temperature buffering of the phases in a light-entrained clock, which we believe is a more physiological setting.
What it takes to understand and cure a living system: computational systems biology and a systems biology-driven pharmacokinetics–pharmacodynamics platform
Authors: Swat Maciej , Kiełbasa Szymon M. , Polak Sebastian , Olivier Brett , Bruggeman Frank J. , Tulloch Mark Quinton , Snoep Jacky L. , Verhoeven Arthur J. , Westerhoff Hans V.
Published: July 2011

The utility of model repositories is discussed in the context of systems biology (SB). It is shown how such repositories, and in particular their live versions, can be used for computational SB: we calculate the robustness of the yeast glycolytic network with respect to perturbations of one of its enzyme activities and one transport system. The robustness with respect to perturbations in the key enzyme phosphofructokinase is surprisingly large. We then note the upcoming convergence of pharmacokinetics–pharmacodynamics (PK–PD) and bottom-up SB. In PK alone, quite a few one-, two- or more compartment models provide valuable initial guesses and insights into the absorption, distribution, metabolism and excretion of particular drugs. These models are phenomenological however, forbidding implementation of molecule-based tools and network information. In order to facilitate a fruitful synergy between SB and PK–PD, and between PK and PD, we present a new platform that combines standard phenomenological models used in the PK/PD field with mechanism-based SB models and approaches.
Multi-scale process and supply chain modelling: from lignocellulosic feedstock to process and products
Authors: Hosseini Seyed Ali , Shah Nilay
Published: July 2011

There is a large body of literature regarding the choice and optimization of different processes for converting feedstock to bioethanol and bio-commodities; moreover, there has been some reasonable technological development in bioconversion methods over the past decade. However, the eventual cost and other important metrics relating to sustainability of biofuel production will be determined not only by the performance of the conversion process, but also by the performance of the entire supply chain from feedstock production to consumption. Moreover, in order to ensure world-class biorefinery performance, both the network and the individual components must be designed appropriately, and allocation of resources over the resulting infrastructure must effectively be performed. The goal of this work is to describe the key challenges in bioenergy supply chain modelling and then to develop a framework and methodology to show how multi-scale modelling can pave the way to answer holistic supply chain questions, such as the prospects for second generation bioenergy crops.
Next-generation cellulosic ethanol technologies and their contribution to a sustainable Africa
Authors: van Zyl W. H. , Chimphango A. F. A. , den Haan R. , Görgens J. F. , Chirwa P. W. C.
Published: July 2011

The world is currently heavily dependent on oil, especially in the transport sector. However, rising oil prices, concern about environmental impact and supply instability are among the factors that have led to greater interest in renewable fuel and green chemistry alternatives. Lignocellulose is the only foreseeable renewable feedstock for sustainable production of transport fuels. The main technological impediment to more widespread utilization of lignocellulose for production of fuels and chemicals in the past has been the lack of low-cost technologies to overcome the recalcitrance of its structure. Both biological and thermochemical second-generation conversion technologies are currently coming online for the commercial production of cellulosic ethanol concomitantly with heat and electricity production. The latest advances in biological conversion of lignocellulosics to ethanol with a focus on consolidated bioprocessing are highlighted. Furthermore, integration of cellulosic ethanol production into existing bio-based industries also using thermochemical processes to optimize energy balances is discussed. Biofuels have played a pivotal yet suboptimal role in supplementing Africa's energy requirements in the past. Capitalizing on sub-Saharan Africa's total biomass potential and using second-generation technologies merit a fresh look at the potential role of bioethanol production towards developing a sustainable Africa while addressing food security, human needs and local wealth creation.
Boundary conditions of patient-specific fluid dynamics modelling of cavopulmonary connections: possible adaptation of pulmonary resistances results in a critical issue for a virtual surgical planning
Authors: Pennati Giancarlo , Corsini Chiara , Cosentino Daria , Hsia Tain-Yen , Luisi Vincenzo S. , Dubini Gabriele , Migliavacca Francesco
Published: July 2011

Cavopulmonary connections are surgical procedures used to treat a variety of complex congenital cardiac defects. Virtual pre-operative planning based on
in silico
patient-specific modelling might become a powerful tool in the surgical decision-making process. For this purpose, three-dimensional models can be easily developed from medical imaging data to investigate individual haemodynamics. However, the definition of patient-specific boundary conditions is still a crucial issue. The present study describes an approach to evaluate the vascular impedance of the right and left lungs on the basis of pre-operative clinical data and numerical simulations. Computational fluid dynamics techniques are applied to a patient with a bidirectional cavopulmonary anastomosis, who later underwent a total cavopulmonary connection (TCPC). Multi-scale models describing the surgical region and the lungs are adopted, while the flow rates measured in the venae cavae are used at the model inlets. Pre-operative and post-operative conditions are investigated; namely, TCPC haemodynamics, which are predicted using patient-specific pre-operative boundary conditions, indicates that the pre-operative balanced lung resistances are not compatible with the TCPC measured flows, suggesting that the pulmonary vascular impedances changed individually after the surgery. These modifications might be the consequence of adaptation to the altered pulmonary blood flows.
Audited credential delegation: a usable security solution for the virtual physiological human toolkit
Authors: Haidar Ali N. , Zasada Stefan J. , Coveney Peter V. , Abdallah Ali E. , Beckles Bruce , Jones Mike A. S.
Published: July 2011

We present applications of audited credential delegation (ACD), a usable security solution for authentication, authorization and auditing in distributed virtual physiological human (VPH) project environments that removes the use of digital certificates from end-users' experience. Current security solutions are based on public key infrastructure (PKI). While PKI offers strong security for VPH projects, it suffers from serious usability shortcomings in terms of end-user acquisition and management of credentials which deter scientists from exploiting distributed VPH environments. By contrast, ACD supports the use of local credentials. Currently, a local ACD username–password combination can be used to access grid-based resources while Shibboleth support is underway. Moreover, ACD provides seamless and secure access to shared patient data, tools and infrastructure, thus supporting the provision of personalized medicine for patients, scientists and clinicians participating in e-health projects from a local to the widest international scale.
Left ventricular modelling: a quantitative functional assessment tool based on cardiac magnetic resonance imaging
Authors: Conti C. A. , Votta E. , Corsi C. , De Marchi D. , Tarroni G. , Stevanella M. , Lombardi M. , Parodi O. , Caiani E. G. , Redaelli A.
Published: July 2011

We present the development and testing of a semi-automated tool to support the diagnosis of left ventricle (LV) dysfunctions from cardiac magnetic resonance (CMR). CMR short-axis images of the LVs were obtained in 15 patients and processed to detect endocardial and epicardial contours and compute volume, mass and regional wall motion (WM). Results were compared with those obtained from manual tracing by an expert cardiologist. Nearest neighbour tracking and finite-element theory were merged to calculate local myocardial strains and torsion. The method was tested on a virtual phantom, on a healthy LV and on two ischaemic LVs with different severity of the pathology. Automated analysis of CMR data was feasible in 13/15 patients: computed LV volumes and wall mass correlated well with manually extracted data. The detection of regional WM abnormalities showed good sensitivity (77.8%), specificity (85.1%) and accuracy (82%). On the virtual phantom, computed local strains differed by less than 14 per cent from the results of commercial finite-element solver. Strain calculation on the healthy LV showed uniform and synchronized circumferential strains, with peak shortening of about 20 per cent at end systole, progressively higher systolic wall thickening going from base to apex, and a 10° torsion. In the two pathological LVs, synchronicity and homogeneity were partially lost, anomalies being more evident for the more severely injured LV. Moreover, LV torsion was dramatically reduced. Preliminary testing confirmed the validity of our approach, which allowed for the fast analysis of LV function, even though future improvements are possible.
On the formalization of multi-scale and multi-science processes for integrative biology
Authors: Díaz-Zuccarini Vanessa , Pichardo-Almarza César
Published: July 2011

The aim of this work is to introduce the general concept of ‘Bond Graph’ (BG) techniques applied in the context of multi-physics and multi-scale processes. BG modelling has a natural place in these developments. BGs are inherently coherent as the relationships defined between the ‘elements’ of the graph are strictly defined by causality rules and power (energy) conservation. BGs clearly show how power flows between components of the systems they represent. The ‘effort’ and ‘flow’ variables enable bidirectional information flow in the BG model. When the power level of a system is low, BGs degenerate into signal flow graphs in which information is mainly one-dimensional and power is minimal, i.e. they find a natural limitation when dealing with populations of individuals or purely kinetic models, as the concept of energy conservation in these systems is no longer relevant. The aim of this work is twofold: on the one hand, we will introduce the general concept of BG techniques applied in the context of multi-science and multi-scale models and, on the other hand, we will highlight some of the most promising features in the BG methodology by comparing with examples developed using well-established modelling techniques/software that could suggest developments or refinements to the current state-of-the-art tools, by providing a consistent framework from a structural and energetic point of view.
Computational modelling and evaluation of cardiovascular response under pulsatile impeller pump support
Authors: Shi Yubing , Brown Alistair G. , Lawford Patricia V. , Arndt Andreas , Nuesser Peter , Hose D. Rodney
Published: July 2011

This study presents a numerical simulation of cardiovascular response in the heart failure condition under the support of a Berlin Heart INCOR impeller pump-type ventricular assist device (VAD). The model is implemented using the CellML modelling language. To investigate the potential of using the Berlin Heart INCOR impeller pump to produce physiologically meaningful arterial pulse pressure within the various physiological constraints, a series of VAD-assisted cardiovascular cases are studied, in which the pulsation ratio and the phase shift of the VAD motion profile are systematically changed to observe the cardiovascular responses in each of the studied cases. An optimization process is proposed, including the introduction of a cost function to balance the importance of the characteristic cardiovascular variables. Based on this cost function it is found that a pulsation ratio of 0.35 combined with a phase shift of 200° produces the optimal cardiovascular response, giving rise to a maximal arterial pulse pressure of 12.6 mm Hg without inducing regurgitant pump flow while keeping other characteristic cardiovascular variables within appropriate physiological ranges.
Visualization and simulated surgery of the left ventricle in the virtual pathological heart of the Virtual Physiological Human
Authors: McFarlane N. J. B. , Lin X. , Zhao Y. , Clapworthy G. J. , Dong F. , Redaelli A. , Parodi O. , Testi D.
Published: July 2011

Ischaemic heart failure remains a significant health and economic problem worldwide. This paper presents a user-friendly software system that will form a part of the virtual pathological heart of the Virtual Physiological Human (VPH2) project, currently being developed under the European Commission Virtual Physiological Human (VPH) programme. VPH2 is an integrated medicine project, which will create a suite of modelling, simulation and visualization tools for patient-specific prediction and planning in cases of post-ischaemic left ventricular dysfunction. The work presented here describes a three-dimensional interactive visualization for simulating left ventricle restoration surgery, comprising the operations of cutting, stitching and patching, and for simulating the elastic deformation of the ventricle to its post-operative shape. This will supply the quantitative measurements required for the post-operative prediction tools being developed in parallel in the same project.
Biofuels and land-use changes: searching for the top model
Authors: Nassar Andre M. , Harfuch Leila , Bachion Luciane C. , Moreira Marcelo R.
Published: July 2011

The use of agricultural-based biofuels has expanded. Discussions on how to assess green house gas (GHG) emissions from biofuel policies, specifically on (non-observed) land-use change (LUC) effects involve two main topics: (i) the limitations on the existing methodologies, and (ii) how to isolate the effects of biofuels. This paper discusses the main methodologies currently used by policy-makers to take decisions on how to quantify LUCs owing to biofuel production expansion. It is our opinion that the concerns regarding GHG emissions associated with LUCs should focus on the agricultural sector as a whole rather than concentrating on biofuel production. Actually, there are several limitations of economic models and deterministic methodologies for simulating and explaining LUCs resulting from the expansion of the agricultural sector. However, it is equally true that there are avenues of possibilities to improve models and make them more accurate and precise in order to be used for policy-making. Models available need several improvements to reach perfection. Any top model requires a concentration of interdisciplinary designers in order to replicate empirical evidence and capture correctly the agricultural sector dynamics for different countries and regions. Forgetting those limitations means that models will be used for the wrong purposes.
euHeart: personalized and integrated cardiac care using patient-specific cardiovascular modelling
Authors: Smith Nic , de Vecchi Adelaide , McCormick Matthew , Nordsletten David , Camara Oscar , Frangi Alejandro F. , Delingette Hervé , Sermesant Maxime , Relan Jatin , Ayache Nicholas , Krueger Martin W. , Schulze Walther H. W. , Hose Rod , Valverde Israel , Beerbaum Philipp , Staicu Cristina , Siebes Maria , Spaan Jos , Hunter Peter , Weese Juergen , Lehmann Helko , Chapelle Dominique , Rezavi Reza
Published: July 2011

The loss of cardiac pump function accounts for a significant increase in both mortality and morbidity in Western society, where there is currently a one in four lifetime risk, and costs associated with acute and long-term hospital treatments are accelerating. The significance of cardiac disease has motivated the application of state-of-the-art clinical imaging techniques and functional signal analysis to aid diagnosis and clinical planning. Measurements of cardiac function currently provide high-resolution datasets for characterizing cardiac patients. However, the clinical practice of using population-based metrics derived from separate image or signal-based datasets often indicates contradictory treatments plans owing to inter-individual variability in pathophysiology. To address this issue, the goal of our work, demonstrated in this study through four specific clinical applications, is to integrate multiple types of functional data into a consistent framework using multi-scale computational modelling.
Synchronization and entrainment of coupled circadian oscillators
Authors: Komin N. , Murza A. C. , Hernández-García E. , Toral R.
Published: July 2011

Circadian rhythms in mammals are controlled by the neurons located in the suprachiasmatic nucleus of the hypothalamus. In physiological conditions, the system of neurons is very efficiently entrained by the 24 h light–dark cycle. Most of the studies carried out so far emphasize the crucial role of the periodicity imposed by the light–dark cycle in neuronal synchronization. Nevertheless, heterogeneity as a natural and permanent ingredient of these cellular interactions seemingly plays a major role in these biochemical processes. In this paper, we use a model that considers the neurons of the suprachiasmatic nucleus as chemically coupled modified Goodwin oscillators, and introduce non-negligible heterogeneity in the periods of all neurons in the form of quenched noise. The system response to the light–dark cycle periodicity is studied as a function of the interneuronal coupling strength, external forcing amplitude and neuronal heterogeneity. Our results indicate that the right amount of heterogeneity helps the extended system to respond globally in a more coherent way to the external forcing. Our proposed mechanism for neuronal synchronization under external periodic forcing is based on heterogeneity-induced oscillator death, damped oscillators being more entrainable by the external forcing than the self-oscillating neurons with different periods.
Influence of different computational approaches for stent deployment on cerebral aneurysm haemodynamics
Authors: Bernardini Annarita , Larrabide Ignacio , Morales Hernán G. , Pennati Giancarlo , Petrini Lorenza , Cito Salvatore , Frangi Alejandro F.
Published: July 2011

Cerebral aneurysms are abnormal focal dilatations of artery walls. The interest in virtual tools to help clinicians to value the effectiveness of different procedures for cerebral aneurysm treatment is constantly growing. This study is focused on the analysis of the influence of different stent deployment approaches on intra-aneurysmal haemodynamics using computational fluid dynamics (CFD). A self-expanding stent was deployed in an idealized aneurysmatic cerebral vessel in two initial positions. Different cases characterized by a progression of simplifications on stent modelling (geometry and material) and vessel material properties were set up, using finite element and fast virtual stenting methods. Then, CFD analysis was performed for untreated and stented vessels. Haemodynamic parameters were analysed qualitatively and quantitatively, comparing the cases and the two initial positions. All the cases predicted a reduction of average wall shear stress and average velocity of almost 50 per cent after stent deployment for both initial positions. Results highlighted that, although some differences in calculated parameters existed across the cases based on the modelling simplifications, all the approaches described the most important effects on intra-aneurysmal haemodynamics. Hence, simpler and faster modelling approaches could be included in clinical workflow and, despite the adopted simplifications, support clinicians in the treatment planning.
Ultrasonic colour Doppler imaging
Authors: Evans David H. , Jensen Jørgen Arendt , Nielsen Michael Bachmann
Published: July 2011

Ultrasonic colour Doppler is an imaging technique that combines anatomical information derived using ultrasonic pulse-echo techniques with velocity information derived using ultrasonic Doppler techniques to generate colour-coded maps of tissue velocity superimposed on grey-scale images of tissue anatomy. The most common use of the technique is to image the movement of blood through the heart, arteries and veins, but it may also be used to image the motion of solid tissues such as the heart walls. Colour Doppler imaging is now provided on almost all commercial ultrasound machines, and has been found to be of great value in assessing blood flow in many clinical conditions. Although the method for obtaining the velocity information is in many ways similar to the method for obtaining the anatomical information, it is technically more demanding for a number of reasons. It also has a number of weaknesses, perhaps the greatest being that in conventional systems, the velocities measured and thus displayed are the components of the flow velocity directly towards or away from the transducer, while ideally the method would give information about the magnitude and direction of the three-dimensional flow vectors. This review briefly introduces the principles behind colour Doppler imaging and describes some clinical applications. It then describes the basic components of conventional colour Doppler systems and the methods used to derive velocity information from the ultrasound signal. Next, a number of new techniques that seek to overcome the vector problem mentioned above are described. Finally, some examples of vector velocity images are presented.
Continuous wave ultrasonic Doppler tomography
Authors: Liang Haidong-Dong , Tsui Chun Sing Louis , Halliwell Michael , Wells Peter N. T.
Published: July 2011

In continuous wave ultrasonic Doppler tomography (DT), the ultrasonic beam moves relative to the scanned object to acquire Doppler-shifted frequency spectra which correspond to cross-range projections of the scattering and reflecting structures within the object. The relative motion can be circular or linear. These data are then backprojected to reconstruct the two-dimensional image of the object cross section. By using coherent processing, the spatial resolution of ultrasonic DT is close to an order of magnitude better than that of traditional pulse-echo imaging at the same ultrasound frequency.
The Virtual Physiological Human
Authors: Coveney Peter V. , Diaz Vanessa , Hunter Peter , Kohl Peter , Viceconti Marco
Published: July 2011

The Virtual Physiological Human is synonymous with a programme in computational biomedicine that aims to develop a framework of methods and technologies to investigate the human body as a whole. It is predicated on the transformational character of information technology, brought to bear on that most crucial of human concerns, our own health and well-being.
Micro-ultrasound for preclinical imaging
Authors: Foster F. Stuart , Hossack John , Adamson S. Lee
Published: July 2011

Over the past decade, non-invasive preclinical imaging has emerged as an important tool to facilitate biomedical discovery. Not only have the markets for these tools accelerated, but the numbers of peer-reviewed papers in which imaging end points and biomarkers have been used have grown dramatically. High frequency ‘micro-ultrasound’ has steadily evolved in the post-genomic era as a rapid, comparatively inexpensive imaging tool for studying normal development and models of human disease in small animals. One of the fundamental barriers to this development was the technological hurdle associated with high-frequency array transducers. Recently, new approaches have enabled the upper limits of linear and phased arrays to be pushed from about 20 to over 50 MHz enabling a broad range of new applications. The innovations leading to the new transducer technology and scanner architecture are reviewed. Applications of preclinical micro-ultrasound are explored for developmental biology, cancer, and cardiovascular disease. With respect to the future, the latest developments in high-frequency ultrasound imaging are described.
Characterization of the pore structure of metakaolin-derived geopolymers by neutron scattering and electron microscopy
Authors: Maitland C. F. , Buckley C. E. , O'Connor B. H. , Butler P. D. , Hart R. D.
Published: July 2011

The pore–solid structure of selected high-compressive-strength metakaolin geopolymers has been characterized to facilitate quantitative prediction of their physical properties. Geopolymers are multiphase materials with pore widths ranging from subnanometre to several tenths of a millimetre. Ultramicrotoming of resin-embedded grains was found to be an effective method for producing electron-transparent sections. Scanning and transmission electron microscopy showed the existence of a bi-level pore system and heterogeneity of the pore morphology. Ultra-small-angle neutron scattering, of sufficiently thin specimens, was found to be useful in detecting the length scales on which statistically significant structural changes occur as the geopolymer chemical composition is varied. Contrast variation experiments confirmed that the small-angle neutron scattering from an Si:Al:Na = 2.5:1:1.2 geopolymer before and after dehydration was dominated by scattering from pores. These experiments suggested the presence of closed (under current experimental conditions) pores in the dehydrated geopolymer. A three-phase analysis was developed for this system, and the scattering of the solid, open pore and closed pore phases was determined as a function of scattering length density ρ. The scattering from all three phases had the sameqdependence over the range of likely ρ within the uncertainties. A lower limit of 4.21 (6) × 1010 cm−2was determined for the scattering length density ρwof the nondehydrated geopolymer by assuming the pore fluid to be water. This scattering length density is significantly higher than the expected value of approximately 3.4 × 1010 cm−2. Small-angle neutron scattering from the dehydrated and nondehydrated Si:Al:Na = 2.5:1:1.2 geopolymer showed that dehydration does not cause a severe change in morphology of the nanoporosity on the length scale probed.
High-pressure single-crystal neutron diffraction to 10 GPa by angle-dispersive techniques
Authors: Bull Craig L. , Guthrie Malcolm , Archer John , Fernandez-Diaz Maria-Teresa , Loveday John S. , Komatsu Kazuki , Hamidov Hayrullo , Nelmes Richard J.
Published: July 2011

Techniques have been developed that allow the measurement of accurate single-crystal neutron-diffraction data at pressures up to 10 GPa, using angle-dispersive methods. High-quality data have been collected up to 10 GPa, to a resolution of sinθ/λ ≃ 1.5 Å−1, from samples of size 3–4 mm^{3}. This article presents the methods developed to mount and centre the sample accurately on the instrument; to reduce the background and hence increase the precision of the measured reflection intensities; and to increase further the accessible region of reciprocal space with a single sample loading. Developments are also highlighted, with a view to increasing the range of both science and pressures that can be achieved at the Institut Laue–Langevin reactor source using single-crystal techniques.
A new approach for the determination of multiple cation locations and ordering, using the example of natural and heat-treated columbites
Authors: Kinast E. J. , Isnard O. , da Cunha J. B. M. , de Vasconcellos M. A. Z. , dos Santos C. A.
Published: July 2011

A new approach is proposed to determine unambiguously the location of four cations within the crystal structure of a naturalAB2O6columbite-type compound and derivatives, when submitted to order–disorder transitions caused by heat treatments. This method is based on the successive use of electron microprobe analysis to determine the cation concentration, Mössbauer spectroscopy to identify the Fe occupation, and a crystal structure determination of the samples combining Rietveld refinements of both neutron and X-ray diffraction. This approach is tested successfully to investigate (Fe, Mn, Nb, Ta) natural minerals as well as oxides obtained by heat treatment of the initialAB2O6columbite-type compound.
Crystalline perfection of an aluminium single crystal determined by neutron diffraction
Authors: Metairon Sabrina , Parente Carlos Benedicto Ramos , Mazzocchi Vera Lucia , Lemaire Thierry Jacques
Published: July 2011

In this work, a study of the crystalline perfection of an aluminium single crystal is presented. The study shows that, from three-dimensional neutron diffraction rocking curves, it is possible to characterize the individual crystalline domains of a multidomain crystal. From a macroscopic point of view, the determination of the domains allows an evaluation of the crystalline perfection of the crystal under study. Three-dimensional rocking curves have been obtained by neutron diffraction from a large mosaic aluminium crystal. Construction of a contour map of individual domains made it easier to determine the breadth and relative intensity of each domain. The angular distances between domains were also determined.
Evidence for correlated structural and electrical changes in a Ge2Sb2Te5thin film from combined synchrotron X-ray techniques and sheet resistance measurements duringin situthermal annealing
Authors: Putero Magali , Ouled-Khachroum Toufik , Coulet Marie-Vanessa , Deleruyelle Damien , Ziegler Eric , Muller Christophe
Published: July 2011

The temperature-induced phase transition in an as-deposited amorphous Ge2Sb2Te5(GST) thin film was studied by a unique combination ofin situsynchrotron techniques (diffraction and reflectivity of X-rays) and sheet resistance measurements. The combination of these characterization techniques allowed the simultaneous extraction of structural (density and film thickness) and electrical characteristics of the GST film during its thermal annealing. It is shown that, at 425 (3) K, the appearance of diffraction peaks associated with a metastable crystalline cubic phase is unambiguously correlated to a density increase in combination with a layer thickness reduction and a resistivity switch towards a lower-resistance state. Under the present annealing conditions, the Ge2Sb2Te5film consists of a polycrystalline layer capped by an amorphous layer that strongly degrades the electrical conductivity.
The scope for replacing seclusion with time out in acute inpatient psychiatry in England
Authors: Bowers Len , Ross Jamie , Nijman Henk , Muir‐Cochrane Eimear , Noorthoorn Eric , Stewart Duncan
Published: July 2011

bowers l., ross j., nijman h., muir‐cochrane e., noorthoorn e. & stewart d. (2011) The scope for replacing seclusion with time out in acute inpatient psychiatry in England. Journal of Advanced Nursing 68(4), 826–835.

Background.  The use of seclusion is unpalatable to nurses and frequently unpleasant for patients. Time out is rated by nurses and patients as more acceptable. Several countries have initiated exercises to reduce the use of seclusion, but England has not.

Methods.  In this study, data were collected on the sequence of conflict (aggression, rule breaking, absconding etc.) and containment (coerced medication, restraint, special observation etc., including time out and seclusion) for the first 2 weeks of 522 acute admissions on 84 wards in 31 English hospitals between June 2009 and March 2010. Data were analysed to describe what preceded and followed time out and seclusion episodes in a nursing shift.

Results.  Seclusion was used with 7·5% of patients, and time out with 15·5%. Both containment methods were used with similar patients in similar circumstances, and both brought disturbed behaviour to a close in half of the cases. Some seclusion appeared to follow less serious disturbed behaviour. There was an important variation in rates of seclusion between hospitals. Seclusion and time out had equally good outcomes in the management of physical violence to others.

Conclusions.  There is good evidence that seclusion rates can be reduced safely, and time out can sometimes be used as a substitute. A national registration and reporting system should be introduced in England, and serious efforts made to reduce seclusion use in hospitals where rates are high.