bluuebunny/crossref_metadata_2025 huggingface dataset:
Noise to signal: A microtremor study at liquefaction sites in the New Madrid Seismic Zone
Authors: Hardesty Kelli , Wolf Lorraine W. , Bodin Paul
Published: April 2010

Understanding how sedimentary basins respond to seismic-wave energy generated by large earthquake events is a significant concern for seismic-hazard estimation. This study explores the use of microtremors, or ambient noise, for evaluating strong-motion site effects. The study focuses on the Mississippi Embayment in the New Madrid Seismic Zone, where widespread liquefaction and ground failure occurred during the 1811–1812 earthquake sequence. Spectral analyses of microtremor data at sites representing different environments of deposition (and sedimentary facies), different embayment thicknesses, and varying liquefaction susceptibility show correlations between (1) calculated vulnerability indices and evidence of liquefaction, (2) sediment thickness and fundamental resonant frequency, and (3) subsurface stratigraphic boundaries and observed peaks in horizontal-to-vertical spectral ratios. Results of the study suggest that the microtremor method could be helpful in identifying those areas most vulnerable to ground amplification in intraplate sedimentary basins, where large earthquakes are infrequent but potentially damaging.
Idiopathic pulmonary arterial hypertension
Authors: Firth Amy L. , Mandel Jess , Yuan Jason X.-J.
Published: April 2010

Despite improved understanding of the pathobiology of pulmonary arterial hypertension (PAH), it remains a severe and progressive disease, usually culminating in right heart failure, significant morbidity and early mortality. Over the last decade, some major advances have led to substantial improvements in the management of PAH. Much of this progress was pioneered by work in animal models. Although none of the current animal models of pulmonary hypertension (PH) completely recapitulate the human disease, they do provide insight into the cellular pathways contributing to its development and progression. There is hope that future work in model organisms will help to define its underlying cause(s), identify risk factors and lead to better treatment of the currently irreversible damage that results in the lungs of afflicted patients. However, the difficulty in defining the etiology of idiopathic PAH (IPAH, previously known as primary pulmonary hypertension) makes this subset of the disease particularly difficult to model. Although there are some valuable existing models that are relevant for IPAH research, the area would value from the development of new models that more closely mimic the clinical pathophysiology of IPAH.
Tumor suppressor interactions with microtubules: keeping cell polarity and cell division on track
Authors: Hernandez Paula , Tirnauer Jennifer S.
Published: April 2010

Tumor suppressor proteins protect cells and tissues from malignant transformation. Among their diverse actions, many of these proteins interact with the microtubule cytoskeleton. This review focuses on the interactions of several tumor suppressors with microtubules and speculates on how disruption of microtubule-dependent processes may contribute to cancer development and spread. We conclude that several tumor suppressors stabilize microtubules and organize microtubule arrays, functions that are likely to be important in preventing tumorigenesis. How tumor suppressors link microtubule stability with cell fate, and how their mutation affects the response of cancer cells to anti-microtubule chemotherapy drugs, remains unclear; these should prove fertile areas for future research.
Insights into the role of DNA methylation in disease through the use of mouse models
Authors: Conerly Melissa , Grady William M.
Published: April 2010

Epigenetics was originally defined as the interaction of genes with their environment that brings the phenotype into being. It now refers to the study of heritable changes in gene expression that occur without a change in DNA sequence. To date, the best understood epigenetic mechanisms are CpG DNA methylation and histone modifications. DNA methylation in particular has been the subject of intense interest because of its recently recognized role in disease, as well as in the development and normal function of organisms. Much of the focus of disease-related research has been on cancer because of the recognition that epigenetic alterations are common in cancer and probably cooperate with genetic alterations to drive cancer formation. Our understanding of epigenetic mechanisms in controlling gene expression has resulted from the study of cell line systems and simple model systems, such as Arabidopsis thaliana. We are now moving into an era of more complex model systems, such as transgenic and knockout mouse models, which will lead to further insight into epigenetics in development and human disease. The current models have revealed complex, tissue-specific effects of epigenetic mechanisms and have further informed our understanding of the role of DNA methylation and histone modifications on disease and development. The current state of these models is the subject of this Commentary.
Funding scientific discovery: an interview with Sir Mark Walport
Authors: Kain Kristin H.
Published: April 2010

Sir Mark Walport is Director of the Wellcome Trust, one of the world’s largest funders of scientific research. Here he talks about the qualities of a successful scientist and how informatics might advance the future of medicine.
High-resolution electron backscatter diffraction: An emerging tool for studying local deformation
Authors: Wilkinson A J , Clarke E E , Britton T B , Littlewood P , Karamched P S
Published: April 2010

Electron backscatter diffraction (EBSD) is a widely available and relatively easy-to-use scanning-electron-microscopy-based diffraction technique. Recently, Wilkinson, Meaden, and Dingley presented two papers on a new cross-correlation-based analysis of EBSD patterns which allow variations in the elastic strain and lattice rotation tensors to be measured at a sensitivity of about 10×4 at high spatial resolution. This paper briefly describes the basis of the technique and how the resulting lattice curvatures can be used to estimate the geometrically necessary dislocation (GND) content in a sample. To illustrate the utility of the method for microscale deformation studies the following examples are described: first, nanoindentation near a grain boundary in α-Ti; second, transformation-induced GNDs in a dual-phase steel; third, thermally-induced and mechanically-induced deformation near carbides in a superalloy; fourth, GND accumulation during fatigue of a polycrystalline Ti–6Al–4V alloy.
A study of dynamic testing of single solder joints and its application to finite element modelling
Authors: Liu J F , Shim V P W , Tan V B C
Published: April 2010

Intermetallic compounds, impurities, voids, and other inhomogeneities are formed in solder joints of integrated-circuit packages. Consequently, the mechanical response of these interconnections may not be well modelled if the properties of bulk solder alloy alone are used. This investigation explores the feasibility of eliciting the dynamic response of single-solder-joint specimens through split-Hopkinson-bar (SHB) testing. As solder joints are extremely small, contact between such specimens and the input–output bars of an SHB results in high stress localization. Numerical simulation of SHB testing of a small specimen, the size of a solder joint, is undertaken using Abaqus to validate the assumption of one-dimensional plane wave propagation in the input–output bars, as well as the accuracy of results derived from the strain signals associated with the midpoints of the bars. Uniaxial compression and tensile tests on single-solder-joint specimens are also conducted at deformation rates ranging from 0.000 15 mm/s to 1.4 m/s. The rate sensitivity is observed and force–deformation curves are obtained, as the actual solder joints possess a barrel-like geometry. In order to apply the force–deformation responses in finite element method (FEM) modelling, a numerical study is also undertaken to investigate the possibility of idealizing the barrel-like solder joint geometry by a cylinder. Subsequently, experimentally measured force–deformation responses of single solder joints are converted into ‘normalized’ or ‘equivalent’ stress–strain material properties. Equivalent stress–strain curves for uniaxial tension at strain rates of 0.0005–1000 s×1, and uniaxial compression at strain rates of 0.0005–5000 s×1 are derived. The variation in the equivalent yield stress with the strain rate is identified and a curve fit is applied. Initial implementation of the equivalent stress–strain curves, together with an idealized cylindrical solder connection, into FEM modelling demonstrates that this is able to predict the mechanical response of solder joints in tension, compression, and shear with reasonable accuracy.
Analysis of Stress and Deformation in Plastic Gears Used in Gerotor Pumps
Authors: Biernacki K , Stryczek J
Published: April 2010

The mechanism of induction of stresses and deformations in plastic cycloidal gears used in gerotor pumps has been analysed using the finite element method and the ABAQUS program. It has been found that the gear system remains under the influence of the mechanical load resulting from the torque on the pump shaft and the hydraulic load resulting from the activity of pressure in the intertooth displacement chambers. It has also been discovered that the intertooth forces and stresses are formed only in the part of the gear that can be referred to as ‘active’. In the other part of the gear, forces and stresses do not occur, and the part can be referred to as ‘passive’. Another finding of the research is that gear deformations occur such that the teeth of the external gear are deformed and moved in the direction of the active part of the mesh, and the teeth of the internal gear in the direction of the passive part. Thus, radial and axial intertooth clearances are formed, which result in internal leakages in the pump, as well as in lower working pressure and efficiency of the machine. A way of determining the load range for plastic gears used in gerotor pumps has been specified. It has also been observed that the loading of the pump should not result in reduced stresses
Prediction of Coolant Deflection Tendencies in Rotating Film Cooling
Authors: Yang B , Xu G , Childs P , Tao Z , Ding S
Published: April 2010

Film cooling is commonly used as an effective cooling technique to protect turbine blades from the thermal failure caused by operation in a high-temperature environment. The cooler air is injected into the high-temperature mainstream boundary layer on a blade surface and it generates a thin coolant film, which acts as a buffer to isolate the thermal loads effectively. In the present study, the classical boundary-layer theory is introduced into the analysis of the governing equations of film cooling under rotating operating conditions, and boundary-layer equations for film cooling are derived. Through simplification of the governing equations, it is demonstrated that four major governing parameters, the pressure gradient, viscosity, the Coriolis force and the centrifugal force, can significantly influence the coolant deflection phenomenon. Near the suction surface, the coolant deflects towards the high-radius locations noticeably. While near the pressure surface, the coolant can be driven to deflect centripetally and centrifugally according to the integrated effect of centrifugal force and Coriolis force. To judge the deflective direction of coolant flow near the pressure surface, a deflection ratio defined by the tangential to instantaneous ejection velocity components is proposed and validated numerically and experimentally. The experimental data and their comparison with the theoretical values indicate that this ratio provides an approach for distinguishing the coolant flow deflection in film cooling in regimes where the Coriolis and centrifugal forces are dominant in the flow field compared to the other forces. Use of the deflection ratio provides a design parameter for the arrangement of film-hole orientation on turbine blades.
Experimental Study of Pumping Performance of Rotating Helical Pump as a Gas—Liquid Transporter
Authors: Mohseni M S , Miripour-Fard B , Zajkani A
Published: April 2010

A rotating helical pump is introduced in this article. This pump can transport gas—liquid two-phase flow. A prototype of the pump was manufactured, and its operational performance was determined experimentally. The influence of the pump geometric parameters on its performance was investigated. Dimensionless parameters were derived from the Buckingham π-theorem to find the effect of a wide range of parameters. Results provide some useful information about the performance of the rotating helical pump.
Two-Phase Flow through Corrugated U-Tube
Authors: Shannak B , Damseh R , Al-Odat M , Al-Shannag M , Azzi A
Published: April 2010

New measurements of the frictional pressure drop of air—water two-phase flow in a flexible corrugated U-tube have been carried out. Experiments were performed under the following conditions of two-phase parameters: mass flux of 300—800 kg/m2 s, gas quality of 1—60 per cent, and system pressure of 3—7 bar. The inner diameter of the U-tubes tested was 40 mm, with a ratio of curvature radius to inner diameter varying from 3 to 7.5. The results demonstrate that the two-phase flow resistance, energy dissipation, friction losses, and interaction of the two phases in flexible corrugated U-tubes are perceptible about two to five times greater than those in smooth U-tubes. Hence, the two-phase friction factor of such tubes increases from 0.65 to 1.4, depending on the influencing flow and geometrical parameters. The available correlations in the open literature present a similar trend and behaviour. However, they predict the data presented poorly because of the complex geometry of the flexible corrugated U-tube. Based on the energy balance and the presented experimental results, a new model has been developed to calculate the frictional two-phase pressure drop and hence the friction factor of the flexible U-tube. The model includes the relevant primary parameter, fits the experimental data well, and is sufficiently accurate for engineering purposes. The standard deviation of the data is less than 7 per cent. The reported results enable a practical design with standard products and optimization of the geometry of the flexible corrugated U-tube for specific conditions.
Design of a master and slave transluminal endoscopic robot for natural orifice transluminal endoscopic surgery
Authors: Phee S J , Kencana A P , Huynh V A , Sun Z L , Low S C , Yang K , Lomanto D , Ho K Y
Published: April 2010

Natural orifice transluminal endoscopic surgery (NOTES) is an endoscopic surgical intervention technique for treatment within the intraperitoneal cavity, which utilizes natural orifices (i.e. mouth, vagina, anus, etc.) as the entry point. In line with minimally invasive surgery (MIS), NOTES aims to perform surgical procedures without skin incisions, thus eliminating unsightly scars. In this article, a master—slave robotic system is proposed to enable the endoscopist to perform demanding NOTES procedures, which are currently performed by surgeons in an opened or keyhole surgery setting. The robotic system consists of a master console and slave manipulators driven by tendon—sheath actuation. Force prediction at the slave end is also introduced in this article to provide force feedback to the surgeon. Using the developed robotic system, liver wedge resection has been conducted in animal trials with promising results.
A sensory-guided surgical micro-drill
Authors: Taylor R , Du X , Proops D , Reid A , Coulson C , Brett P N
Published: April 2010

This article describes a surgical robotic device that is able to discriminate tissue interfaces and other controlling parameters ahead of the drill tip. The advantage in such a surgery is that the tissues at the interfaces can be preserved. A smart tool detects ahead of the tool point and is able to control the interaction with respect to the flexing tissue, to avoid penetration or to control the extent of protrusion with respect to the position of the tissue. For surgical procedures, where precision is required, the tool offers significant benefit. To interpret the drilling conditions and the conditions leading up to breakthrough at a tissue interface, a sensing scheme is used that discriminates between the variety of conditions posed in the drilling environment. The result is a fully autonomous system, which is able to respond to the tissue type, behaviour, and deflection in real-time. The system is also robust in terms of disturbances encountered in the operating theatre. The device is pragmatic. It is intuitive to use, efficient to set up, and uses standard drill bits. The micro-drill, which has been used to prepare cochleostomies in the theatre, was used to remove the bone tissue leaving the endosteal membrane intact. This has enabled the preservation of sterility and the drilling debris to be removed prior to the insertion of the electrode. It is expected that this technique will promote the preservation of hearing and reduce the possibility of complications. The article describes the device (including simulated drill progress and hardware set-up) and the stages leading up to its use in the theatre.
In vivo and in situ image guidance and modelling in robotic assisted surgery
Authors: Lee S-L , Huntbatch A , Pratt P , Lerotic M , Yang G-Z
Published: April 2010

The increase in the use of robotic assisted surgery has provided benefits to both the patient and the surgeon. There are possibilities for training and surgical planning and guidance within this framework but work is needed for this to reach a patient-specific level. Medical images obtained prior to surgery are used clinically to plan operations and there has been much research in their use to build models, giving further knowledge of tissue and organ structures. The incorporation of this data into the surgical environment is a recent development, assisting the surgeon with orientation information, but motion due to respiration or changes to morphology due to intervention begets a need for the incorporation of real-time imaging into the modelling. The current work on pre-operative and intra-operative imaging and modelling methods for robotic assisted surgery has to be reviewed and then the Image Constrained Biomechanical Modelling has to be introduced, whereby patient-specific biomechanical modelling is based on the underlying medical images, reducing the computational complexity involved with traditional biomechani-cal modelling. This article concludes with a discussion of the possible and promising future directions of this work.
Static and Free Vibration Analyses of Doubly Curved Composite Sandwich Panels with Soft Core Based on a New Three-Layered Mixed Theory
Authors: Biglari H , Jafari A A
Published: April 2010

In this paper, a closed-form solution of static problems and free vibrations of a doubly curved sandwich shell with flexible core based on a newly developed three-layered high-order sandwich panel theory (mixed theory) is presented for the first time. In this theory, displacements and transverse stresses at the interface of the core and face sheets are primary unknowns. Linear distribution of transverse normal and shear stresses through the core thickness is considered in the present model. This model accounts for non-linear distribution of displacements through the core thickness. Hamilton's principle is employed to obtain equations of motion. The formulation includes Donnell's shallow shell theory. In the case of static problems and free vibrations, the results of the present model are validated by a three-dimensional elasticity solution and analytical and numerical results published in the literatures. A parametric study is also included in this paper to investigate the effects of radius of curvature, thickness, and flexibility of the core. New results for thin and thick spherical and cylindrical sandwich shells are established, which can be considered as a basic reference for future investigations.
A Kinetic Theory-Based First-Order Slip Boundary Condition for Gas Micro/Nano-Flows with Heat Transfer
Authors: Kamali R , Kharazmi A , Akbari M
Published: April 2010

A kinetic theory-based first-order slip boundary condition for micro/nano-gas flows with heat transfer is presented analytically using the Chapman—Enskog solution of the Boltzmann equation. This slip model is investigated by studying heat transfer for laminar Newtonian fluid in a Poiseuille flow. The problem is solved for two different thermal boundary conditions, namely, constant heat flux and constant wall temperature with different Knudsen numbers. The interactive effects of the Knudsen number on the Nusselt numbers are determined analytically, and for both cases, the temperature profile and the Nusselt number are compared with previous published results.
Volumetric Error Modelling, Measurement, and Compensation for an Integrated Measurement-Processing Machine Tool
Authors: Wang K , Sheng X , Kang R
Published: April 2010

The volumetric error of a measurement-processing integrated machine tool was studied by using a complicated surface workpiece grinding machine as a special example. The model of volumetric error was established by using homogeneous transformation matrices, and the effect of volumetric error on coordinate transformation between the measurement and the processing work station was analysed. Various error components of the machine tool were measured with a laser interferometer and an electronic level, and the volumetric error was compensated by external software. With a ball bar system and grinding experiments, the volumetric position accuracy was tested after compensation. The experiment results illustrated that both the volumetric position accuracy and machining precision were improved dramatically after compensation.
Tilting Trains: Benefits and Motion Sickness
Authors: Persson R
Published: April 2010

Carbody tilting is today a mature and inexpensive technology that allows higher speeds on curves, thus shortening travel time. The technology has been accepted by many train operators, but some issues are still holding back the full potential of tilting trains. This paper focuses on improving the benefits and limiting the drawbacks of tilting trains. This is done by quantifying the possible running time benefits compared with today's tilting trains, identifying what motion components have an influence on motion sickness, and finally quantifying the influence from the increased speed on these motion components.

A running time analysis was made to show what potential there is to further improve running times by optimizing tracks and trains. Relations between cant deficiency, top speed, tractive performance, and running times are shown for a tilting train. About 9 per cent running time may be gained on the Stockholm-Gothenburg (457 km) main line in Sweden if cant deficiency, top speed, and tractive performance are improved compared with existing tilting trains. Introduction of non-tilting high-speed trains is not an option on this line due to the large number of 1000 m curves.

However, tilting trains run a greater risk of causing motion sickness than non-tilting trains. Roll velocity and vertical acceleration are the two motion components that show the largest increase, but the amplitudes are lower than those used in laboratory tests that caused motion sickness. Higher curve speeds will increase carbody motions still further, but there are some possibilities to trade between vertical and lateral carbody acceleration by increasing or decreasing roll.
Improving railway switch system reliability with innovative condition monitoring algorithms
Authors: Silmon J A , Roberts C
Published: April 2010

INNOTRACK is a project funded under the European Commission Sixth Framework research programme. The project aims to develop approaches capable of achieving a 30 per cent reduction in track life-cycle costs (LCCs). As part of a cost consolidation exercise within the project, it was identified that switch and crossing maintenance and inspections account for around 19 per cent of the total maintenance costs. Improved condition monitoring can be used as part of a condition-based maintenance regime, which saves money over traditional periodic maintenance. This paper presents a novel algorithm that has been developed, which uses qualitative trend analysis (QTA) to detect and diagnose incipient faults in switches, which have been difficult to detect using current commercial methods. The algorithm is demonstrated using fault simulation data collected from DC electric switch actuators of a type widespread in the UK. The increased fault diagnosis capability has the potential to contribute significantly towards the achievement of the 30 per cent reduction in track LCCs.
Determination of the Stress State Developed within a Non-Cushioned Rail Yoke and the Prediction of the Theoretical Fatigue Life
Authors: Smyth A , Reiling J , Ely S
Published: April 2010

During service, freight railroad coupling systems experience heavy loading owing to various train actions. For non-cushioned railcars, the primary tensile component utilized to transfer these forces to the draft system is the yoke. The stress state developed within a yoke was analysed using both strain gauge data and non-linear finite-element methods for both static maximal loads and pseudo-static cyclic loads accounting for the non-linear material behaviour, including plasticity and strain hardening. From the stress profile developed within a yoke, the critical locations were determined and the theoretical fatigue life was calculated using various strain life fatigue analysis methods considering both the uniaxial and biaxial stress conditions that exist. Using these data, a possible failure mode is presented.
Design Life Prediction of a Heavy Haul Track Foundation
Authors: Gräbe P J , Shaw F J
Published: April 2010

Transnet Freight Rail monitors the behaviour of a new track foundation, constructed in 2004, on the South African Coal Line. This site forms part of a major rehabilitation project, aimed at increasing the capacity of the line to sustain future growth in annual tonnage. Sophisticated instrumentation is used to measure resilient and permanent deformation of the track foundation. Preliminary results of this research were published shortly after the construction of the new track foundation. Results of the permanent deformation, gathered over a period of 5 years, are now presented to provide new insight into the long-term behaviour of track foundations. Permanent deformation measurements are used to calculate the expected design life of a track foundation. The results are used to predict permanent deformation and ultimately the design life of the track foundation under heavy haul loading conditions. The research provides a scientific basis for planning foundation rehabilitation in the light of sustained capital expansion and projected tonnage increase on the Coal Line and other heavy haul lines.
Wear and Creep of Highly Crosslinked Polyethylene against Cobalt Chrome and Ceramic Femoral Heads
Authors: Galvin A L , Jennings L M , Tipper J L , Ingham E , Fisher J
Published: April 2010

The wear and creep characteristics of highly crosslinked ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against large-diameter (36 mm) ceramic and cobalt chrome femoral heads have been investigated in a physiological anatomical hip joint simulator for 10 million cycles. The crosslinked UHMWPE/ceramic combination showed higher volume deformation due to creep plus wear during the first 2 million cycles, and a steady-state wear rate 40 per cent lower than that of the crosslinked UHMWPE/cobalt chrome combination. Wear particles were isolated and characterized from the hip simulator lubricants. The wear particles were similar in size and morphology for both head materials. The particle isolation methodology used could not detect a statistically significant difference between the particles produced by the cobalt chrome and alumina ceramic femoral heads.
Theoretical and Experimental Study of a Novel Microfabricated Fibrillar Structure
Authors: Parsaiyan H , Barazandeh F , Nejad Nazari S , Rezaei S M , Kabganian M , Parsaiyan M , Safdari M
Published: April 2010

Survival of species such as geckos, spiders, flies, and crickets crucially depends on the interaction between hundreds of thousands of hairs or setae on their feet. Recently, many efforts have been made to fabricate adhesive pads inspired by natural biological systems. Fibres developed from nano molding can mimic the hairs of these species’ feet and act as a dry adhesive pad. In this study, for the nanocasting of nano fibres, several porous silicon structures with desired dimensional and morphological characteristics were made by an electrochemical etching system. The adhesive strengths of produced adhesive pads were measured about 0.07 N/cm2 in the normal direction and about 0.045 N/cm2 in the shear direction in contact with a glass surface. Besides the experimental work, a quantitative model has been developed to model van der Waals interactions in adhesive pads. The results from the theoretical model show consistency with experiments.
MicroRNAs, macrocontrol: Regulation of miRNA processing
Authors: Slezak-Prochazka Izabella , Durmus Selvi , Kroesen Bart-Jan , van den Berg Anke
Published: April 2010

MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. Maturation of miRNAs comprises several regulated steps resulting in ∼22-nucleotide single-stranded mature miRNAs. Regulation of miRNA expression can occur both at the transcriptional level and at the post-transcriptional level during miRNA processing. Recent studies have elucidated specific aspects of the well-regulated nature of miRNA processing involving various regulatory proteins, editing of miRNA transcripts, and cellular location. In addition, single nucleotide polymorphisms in miRNA genes can also affect the processing efficiency of primary miRNA transcripts. In this review we present an overview of the currently known regulatory pathways of miRNA processing and provide a basis to understand how aberrant miRNA processing may arise and may be involved in pathophysiological conditions such as cancer.
Training in the management of TMJ disorders at the College
Authors: Speculand Bernie
Published: April 2010

For most people the experience of a temporomandibular joint (TMJ) disorder is no more serious than having a sprained ankle. The most common cluster of symptoms (pain, clicking of the joint, sticking or locking, and reduced mouth opening) is known as TMJ dysfunction. Up to 25% of the general population will experience some or all of these symptoms at some stage in their lives. Usually these settle spontaneously. If help is requested, then simple treatments such as reassurance, analgesics, provision of a soft bite guard to be worn over the lower teeth at night and/or possibly physiotherapy will help about 75% of patients over a three to six-month period.
The Conservatives and Surgery
Authors: Lansley Andrew
Published: April 2010

Nearly four years ago David Cameron spelt out his priorities in three letters: NHS. Since then we have consistently fought to protect the values the NHS stands for and have campaigned to defend the service from Labour's cuts and reorganisations.
‘School's a big part of your life …’: Adolescent Perspectives of Their School Participation Following Traumatic Brain Injury
Authors: Mealings Margaret , Douglas Jacinta
Published: April 2010

Sustaining a traumatic brain injury (TBI) as an adolescent has a significant impact on life roles and most notably on that of school participation. In the literature there is a wide range of studies that provide clinicians with information regarding recommendations for assisting students in their return to school. However this information has predominantly been provided from the perspectives of educators and rehabilitation staff. The aim of this preliminary project was to hear the stories of three male adolescent students as they reflected on their own experiences of what it was like to go back to school after sustaining a severe TBI. Using a qualitative research design and in-depth interviews, the students' stories were transcribed and coded using grounded theory principles. Despite persisting communication difficulties, the students were able to provide rich stories indicative of their personal experiences. Three key themes emerged from the interviews: theadolescent student's sense of self, changesthe students noted; andsupportsthe students identified. A tentative model illustrating the relationship between these areas was developed. It is anticipated that this model will assist clinicians and educators to develop a holistic picture of a student's school participation from transition to ongoing school life.
Young Adults With Traumatic Brain Injury in Long-Term Care Homes: A Population-Based Study
Authors: Colantonio Angela , Howse Dana , Patel Jigisha
Published: April 2010

The aim of this research was to identify the number and characteristics of adults under the age of 65 with a diagnosis of traumatic brain injury (TBI) living in long-term care homes (nursing homes, homes for the aged and charitable homes) in Ontario, Canada. Methods: The study used a cross-sectional design. Secondary data analysis of a comprehensive provincial database of long-term care homes was conducted. Results: Of the 399 residents coded as having a TBI, 154 were < 65 years of age. Virtually all residents were limited in personal care and required assistance for eating (94.2%), toileting (92.2%) and dressing (99.4%). A large percentage also required care for challenging behaviours, while care needs due to substance abuse was common among 12.3% of TBI residents. Conclusion: As similar research in Australia has found, young persons in long-term care homes in Ontario, Canada, have high level personal health needs, however the appropriateness of this environment is questionable.
Everyday Memory for Everyday Tasks: Prospective Memory as an Outcome Measure Following TBI in Older Adults
Authors: Kinsella Glynda J.
Published: April 2010

Traumatic brain injury in older adults is an increasing problem in our aging community. Traditional functional outcome measures, such as return to work or academic achievement, as used with younger samples following traumatic brain injury are of limited use for older people. Although challenging to assess reliably, evaluation of prospective memory is gradually being included in outcome assessments following traumatic brain injury in younger samples and may be a useful index of cognitive competence in everyday life when assessing older adults following traumatic brain injury.
Europeanization and political parties: the Partido Popular and its transnational relations with the European People's Party
Authors: Van Hecke Steven
Published: April 2010

Despite some recent studies addressing the Europeanization of political parties, we know very little about the relationship between national political parties and transnational party federations. By contrast, the framework for analysis developed in this article considers the active
role of national parties in transnational politics and the specific nature of transnational party federations. This model is then applied to the Partido Popular and the European People's Party, of which the first has been a member since 1991. It shows that, between the foundation of
the Partido Popular in 1989 and 2004, when it lost power at the national level, there have been mutual patterns of Europeanization but concrete indications of Europeanization in partygovernment relations are lacking. It is therefore still far from constituting a Europeanized party.
Book Reviews
Authors: Graham Helen , de Meneses Filipe Ribeiro
Published: April 2010

Teaching Representations of the Spanish Civil War, Nol Valis (ed.), (2007), New York: The Modern Language Association of America (MLA), xi 601 pp., ISBN 978-0-873-52824-5, Paperback, 22, ISBN 978-0-873-52823-8, Hardback, 40

Franco and the Axis Stigma, David
Wingeate Pike, (2008), London: Palgrave Macmillan, 220 pp., ISBN 13: 978-0-230-20289-4, Hardback, 45
CNS/PNS Boundary Transgression by Central Glia in the Absence of Schwann Cells or Krox20/Egr2 Function
Authors: Coulpier Fanny , Decker Laurence , Funalot Benoît , Vallat Jean-Michel , Garcia-Bragado Federico , Charnay Patrick , Topilko Piotr
Published: April 2010

CNS/PNS interfaces constitute cell boundaries, because they delimit territories with different neuronal and glial contents. Despite their potential interest in regenerative medicine, the mechanisms restricting oligodendrocytes and astrocytes to the CNS and Schwann cells to the PNS in mammals are not known. To investigate the involvement of peripheral glia and myelin in the maintenance of the CNS/PNS boundary, we have first made use of different mouse mutants. We show that depletion of Schwann cells and boundary cap cells or inactivation ofKrox20/Egr2, a master regulatory gene for myelination in Schwann cells, results in transgression of the CNS/PNS boundary by astrocytes and oligodendrocytes and in myelination of nerve root axons by oligodendrocytes. In contrast, such migration does not occur with theTremblerJmutation, which prevents PNS myelination without affectingKrox20expression. Altogether, these data suggest that maintenance of the CNS/PNS boundary requires a Krox20 function separable from myelination control. Finally, we have analyzed a human patient affected by a congenital amyelinating neuropathy, associated with the absence of the KROX20 protein in Schwann cells. In this case, the nerve roots were also invaded by oligodendrocytes and astrocytes. This indicates that transgression of the CNS/PNS boundary by central glia can occur in pathological situations in humans and suggests that the underlying mechanisms are common with the mouse.
Fibrinogen Triggers Astrocyte Scar Formation by Promoting the Availability of Active TGF-β after Vascular Damage
Authors: Schachtrup Christian , Ryu Jae K. , Helmrick Matthew J. , Vagena Eirini , Galanakis Dennis K. , Degen Jay L. , Margolis Richard U. , Akassoglou Katerina
Published: April 2010

Scar formation in the nervous system begins within hours after traumatic injury and is characterized primarily by reactive astrocytes depositing proteoglycans that inhibit regeneration. A fundamental question in CNS repair has been the identity of the initial molecular mediator that triggers glial scar formation. Here we show that the blood protein fibrinogen, which leaks into the CNS immediately after blood–brain barrier (BBB) disruption or vascular damage, serves as an early signal for the induction of glial scar formation via the TGF-β/Smad signaling pathway. Our studies revealed that fibrinogen is a carrier of latent TGF-β and induces phosphorylation of Smad2 in astrocytes that leads to inhibition of neurite outgrowth. Consistent with these findings, genetic or pharmacologic depletion of fibrinogen in mice reduces active TGF-β, Smad2 phosphorylation, glial cell activation, and neurocan deposition after cortical injury. Furthermore, stereotactic injection of fibrinogen into the mouse cortex is sufficient to induce astrogliosis. Inhibition of the TGF-β receptor pathway abolishes the fibrinogen-induced effects on glial scar formationin vivoandin vitro. These results identify fibrinogen as a primary astrocyte activation signal, provide evidence that deposition of inhibitory proteoglycans is induced by a blood protein that leaks in the CNS after vasculature rupture, and point to TGF-β as a molecular link between vascular permeability and scar formation.
Aβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61
Authors: Kurup Pradeep , Zhang Yongfang , Xu Jian , Venkitaramani Deepa V. , Haroutunian Vahram , Greengard Paul , Nairn Angus C. , Lombroso Paul J.
Published: April 2010

Amyloid β (Aβ) is involved in the etiology of Alzheimer's disease (AD) and may contribute to cognitive deficits by increasing internalization of ionotropic glutamate receptors. Striatal-enriched protein tyrosine phosphatase 61 (STEP61), which is targeted in part to the postsynaptic terminal, has been implicated in this process. Here we show that STEP61levels are progressively increased in the cortex of Tg2576 mice over the first year, as well as in prefrontal cortex of human AD brains. The increased STEP61was associated with greater STEP activity, dephosphorylation of phospho-tyr1472of the NR2B subunit, and decreased NR1 and NR2B subunits on neuronal membranes. Treatment with Aβ-enriched medium also increased STEP61levels and decreased NR1/NR2B abundance in mouse cortical cultures as determined by biotinylation experiments. In STEP knock-out cultures, Aβ treatment failed to induce NMDA receptor internalization. The mechanism for the increase in STEP61levels appears to involve the ubiquitin proteasome system. Blocking the proteasome resulted in elevated levels of STEP61. Moreover, STEP61–ubiquitin conjugates were increased in wild-type cortical slices upon Aβ treatment as well as in 12 month Tg2576 cortex. These findings reveal a novel mechanism by which Aβ-mediated accumulation of STEP61results in increased internalization of NR1/NR2B receptor that may contribute to the cognitive deficits in AD.
Cellular and Synaptic Mechanisms of Anti-NMDA Receptor Encephalitis
Authors: Hughes Ethan G. , Peng Xiaoyu , Gleichman Amy J. , Lai Meizan , Zhou Lei , Tsou Ryan , Parsons Thomas D. , Lynch David R. , Dalmau Josep , Balice-Gordon Rita J.
Published: April 2010

We recently described a severe, potentially lethal, but treatment-responsive encephalitis that associates with autoantibodies to the NMDA receptor (NMDAR) and results in behavioral symptoms similar to those obtained with models of genetic or pharmacologic attenuation of NMDAR function. Here, we demonstrate that patients' NMDAR antibodies cause a selective and reversible decrease in NMDAR surface density and synaptic localization that correlates with patients' antibody titers. The mechanism of this decrease is selective antibody-mediated capping and internalization of surface NMDARs, as Fab fragments prepared from patients' antibodies did not decrease surface receptor density, but subsequent cross-linking with anti-Fab antibodies recapitulated the decrease caused by intact patient NMDAR antibodies. Moreover, whole-cell patch-clamp recordings of miniature EPSCs in cultured rat hippocampal neurons showed that patients' antibodies specifically decreased synaptic NMDAR-mediated currents, without affecting AMPA receptor-mediated currents. In contrast to these profound effects on NMDARs, patients' antibodies did not alter the localization or expression of other glutamate receptors or synaptic proteins, number of synapses, dendritic spines, dendritic complexity, or cell survival. In addition, NMDAR density was dramatically reduced in the hippocampus of female Lewis rats infused with patients' antibodies, similar to the decrease observed in the hippocampus of autopsied patients. These studies establish the cellular mechanisms through which antibodies of patients with anti-NMDAR encephalitis cause a specific, titer-dependent, and reversible loss of NMDARs. The loss of this subtype of glutamate receptors eliminates NMDAR-mediated synaptic function, resulting in the learning, memory, and other behavioral deficits observed in patients with anti-NMDAR encephalitis.
Integration of Goal- and Stimulus-Related Visual Signals Revealed by Damage to Human Parietal Cortex
Authors: Bays Paul M. , Singh-Curry Victoria , Gorgoraptis Nikos , Driver Jon , Husain Masud
Published: April 2010

Where we look is determined both by our current intentions and by the tendency of visually salient items to “catch our eye.” After damage to parietal cortex, the normal process of directing attention is often profoundly impaired. Here, we tracked parietal patients' eye movements during visual search to separately map impairments in goal-directed orienting to targets versus stimulus-driven gaze shifts to salient but task-irrelevant probes. Deficits in these two distinct types of attentional selection are shown to be identical in both magnitude and spatial distribution, consistent with damage to a “priority map” that integrates goal- and stimulus-related signals to select visual targets. When goal-relevant and visually salient items compete for attention, the outcome depends on a biased competition in which the priority of contralesional targets is undervalued. On the basis of these findings, we further demonstrate that parietal patients' spatial bias (neglect) in goal-directed visual exploration can be corrected and even reversed by systematically manipulating the spatial distribution of stimulus salience in the visual array.
Soluble Neuregulin-1 Has Bifunctional, Concentration-Dependent Effects on Schwann Cell Myelination
Authors: Syed Neeraja , Reddy Kavya , Yang David P. , Taveggia Carla , Salzer James L. , Maurel Patrice , Kim Haesun A.
Published: April 2010

Members of the neuregulin-1 (Nrg1) growth factor family play important roles during Schwann cell development. Recently, it has been shown that the membrane-bound type III isoform is required for Schwann cell myelination. Interestingly, however, Nrg1 type II, a soluble isoform, inhibits the process. The mechanisms underlying these isoform-specific effects are unknown. It is possible that myelination requires juxtacrine Nrg1 signaling provided by the membrane-bound isoform, whereas paracrine stimulation by soluble Nrg1 inhibits the process. To investigate this, we asked whether Nrg1 type III provided in a paracrine manner would promote or inhibit myelination. We found that soluble Nrg1 type III enhanced myelination in Schwann cell-neuron cocultures. It improved myelination of Nrg1 type III+/−neurons and induced myelination on normally nonmyelinated sympathetic neurons. However, soluble Nrg1 type III failed to induce myelination on Nrg1 type III−/−neurons. To our surprise, low concentrations of Nrg1 type II also elicited a similar promyelinating effect. At high doses, however, both type II and III isoforms inhibited myelination and increased c-Jun expression in a manner dependent on Mek/Erk (mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) activation. These results indicate that paracrine Nrg1 signaling provides concentration-dependent bifunctional effects on Schwann cell myelination. Furthermore, our studies suggest that there may be two distinct steps in Schwann cell myelination: an initial phase dependent on juxtacrine Nrg1 signaling and a later phase that can be promoted by paracrine stimulation.