Accessibility appraisal of integrated land-use-transport strategies: methodology and case study for the Netherlands Randstad area

Conventional approaches to measuring accessibility benefits are not capable of fully measuring the total accessibility benefits of integrated land-use-transport strategies, in which both land-use and transport changes form part of the policy strategy. In this paper a comprehensive methodology for analysing accessibility impacts and accessibility benefits, which is based on location-based and utility-based accessibility measures within an integrated land-use-transport interaction modelling framework, is described and applied in a case study. The case study examines the accessibility benefits and related user benefits of intensive mixed-use strategies aimed at increasing the density and diversity of activities around railway stations for the Randstad area of the Netherlands for the 1996-2030 period. A heavy concentration of activities near railway stations is shown to result in decreasing marginal returns for public-transport users and disbenefits for car users. © 2006 a Pion publication printed in Great Britain

Experimental validation of a new biphasic model of the contact mechanics of the porcine hip

Hip models that incorporate the biphasic behaviour of articular cartilage can improve understanding of the joint function, pathology of joint degeneration and effect of potential interventions. The aim of this study was to develop a specimen-specific biphasic finite element model of a porcine acetabulum incorporating a biphasic representation of the articular cartilage and to validate the model predictions against direct experimental measurements of the contact area in the same specimen. Additionally, the effect of using a different tension-compression behaviour for the solid phase of the articular cartilage was investigated. The model represented different radial clearances and load magnitudes. The comparison of the finite element predictions and the experimental measurement showed good agreement in the location, size and shape of the contact area, and a similar trend in the relationship between contact area and load was observed. There was, however, a deviation of over 30% in the magnitude of the contact area, which might be due to experimental limitations or to simplifications in the material constitutive relationships used. In comparison with the isotropic solid phase model, the tension-compression solid phase model had better agreement with the experimental observations. The findings provide some confidence that the new biphasic methodology for modelling the cartilage is able to predict the contact mechanics of the hip joint. The validation provides a foundation for future subject-specific studies of the human hip using a biphasic cartilage model

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres

Medication Use Patterns among Urban Youth Participating in School-Based Asthma Education

Although pharmaceutical management is an integral part of asthma control, few community-based analyses have focused on this aspect of disease management. The primary goal of this analysis was to assess whether participation in the school-based Kickin’ Asthma program improved appropriate asthma medication use among middle school students. A secondary goal was to determine whether improvements in medication use were associated with subsequent improvements in asthma-related symptoms among participating students. Students completed an in-class case-identification questionnaire to determine asthma status. Eligible students were invited to enroll in a school-based asthma curriculum delivered over four sessions by an asthma health educator. Students completed a pre-survey and a 3-month follow-up post-survey that compared symptom frequency and medication use. From 2004 to 2007, 579 participating students completed pre- and post-surveys. Program participation resulted in improvements in appropriate use across all three medication use categories: 20.0% of students initiated appropriate reliever use when “feeling symptoms” (p < 0.001), 41.6% of students reporting inappropriate medication use “before exercise” initiated reliever use (p < 0.001), and 26.5% of students reporting inappropriate medication use when “feeling fine” initiated controller use (p < 0.02). More than half (61.6%) of participants reported fewer symptoms at post-survey. Symptom reduction was not positively associated with improvements in medication use in unadjusted and adjusted analysis, controlling for sex, asthma symptom classification, class attendance, season, and length of follow-up. Participation in a school-based asthma education program significantly improved reliever medication use for symptom relief and prior-to-exercise and controller medication use for maintenance. However, given that symptom reduction was not positively associated with improvement in medication use, pharmaceutical education must be just one part of a comprehensive asthma management agenda that addresses the multifactorial nature of asthma-related morbidity

“Did I bring it on myself?” An exploratory study of the beliefs that adolescents referred to mental health services have about the causes of their depression

Background: The causal beliefs which adults have regarding their mental health difficulties have been linked to help-seeking behaviour, treatment preferences and the outcome of therapy; yet the topic remains a relatively unexplored one in the adolescent literature. Aims: This exploratory study aims to explore the causal beliefs regarding depression among a sample of clinically referred adolescents. Design: 77 adolescents, aged between 11 and 17, all diagnosed with moderate to severe depression, were interviewed using a semi-structured interview schedule, at the beginning of their participation in a randomised controlled trial. Data were analysed qualitatively using Framework Analysis. Findings: The study identified three themes related to causal beliefs: 1) Bewilderment about why they were depressed; 2) Depression as a result of rejection, victimisation and stress; and 3) Something inside is to blame. Conclusion: Although some adolescents struggled to identify the causes of their depression, many identified stressful life experiences as the cause of their current depression. They also tended to emphasise their own negative ways of interpreting those events, and some believed that their depression was caused by something inside them. Adolescents’ causal beliefs are likely to have implications for the way they seek help and engage in treatment, making it important to understand how adolescents understand their difficulties

Two different point mutations in ABL gene ATP-binding domain conferring Primary Imatinib resistance in a Chronic Myeloid Leukemia (CML) patient: A case report

Imatinib (Gleevec) is the effective therapy for BCR-ABL positive CML patients. Point mutations have been detected in ATP-binding domain of ABL gene which disturbs the binding of Gleevec to this target leading to resistance. Detection of mutations is helpful in clinical management of imatinib resistance. We established a very sensitive (ASO) PCR to detect mutations in an imatinib-resistant CML patient. Mutations C944T and T1052C were detected which cause complete partial imatinib resistance, respectively. This is the first report of multiple point mutations conferring primary imatinib resistance in same patient at the same time. Understanding the biological reasons of primary imatinib resistance is one of the emerging issues of pharmacogenomics and will be helpful in understanding primary resistance of molecularly-targeted cancer therapies. It will also be of great utilization in clinical management of imatinib resistance. Moreover, this ASO-PCR assay is very effective in detecting mutations related to imatinib resistance