Generic systolic array for genetic algorithms

The authors present a systolic design for a simple GA mechanism which provides high throughput and unidirectional pipelining by exploiting the inherent parallelism in the genetic operators. The design computes in O(N+G) time steps using O(N2) cells where N is the population size and G is the chromosome length. The area of the device is independent of the chromosome length and so can be easily scaled by replicating the arrays or by employing fine-grain migration. The array is generic in the sense that it does not rely on the fitness function and can be used as an accelerator for any GA application using uniform crossover between pairs of chromosomes. The design can also be used in hybrid systems as an add-on to complement existing designs and methods for fitness function acceleration and island-style population management

The story of Temple Bar: creating Dublin's cultural quarter

The paper conceptualises and explores the links between cities, commerce, urbanism and cultural planning by drawing on Temple Bar in Dublin as an example of how, by linking these concepts to practice in real concrete situations urban life or urban culture can be created and/or revitalised. Temple Bar is Dublin's emerging cultural quarter, an experiment in urban revitalisation which is deliberately focused on culture and urbanism as ways of rediscovering the good city. It has attracted considerable interest from across Europe, and has secured EC funding to kick-start the process of renewal. The author was appointed by the Irish Government to prepare the area management and development strategy for Temple Bar in 1990. Wary of the dangers of property led regeneration, of the destructive impacts of sudden or cataclysmic change, the agencies in Temple Bar have deliberately adopted a strategic management approach to the area. This is referred to as 'urban stewardship', a process of looking after and respecting a place, and helping it to help itself. The paper explores whether there is a 'culture of cities' and whether it is possible to recreate an urban culture. Following Raymond Williams, an anthropological definition of culture is employed, "... a particular way of life, which expresses certain meaning and values not only in art and learning but also in institutional and ordinary behaviour". Rather than being simply an add-on to the serious concerns of economic development and the built environment, culture has both helped shape, and continues to develop in, the streets, spaces and buildings of the city.

G protein-coupled receptors: what a difference a 'partner' makes

G protein-coupled receptors (GPCRs) are important cell signaling mediators, involved in essential physiological processes. GPCRs respond to a wide variety of ligands from light to large macromolecules, including hormones and small peptides. Unfortunately, mutations and dysregulation of GPCRs that induce a loss of function or alter expression can lead to disorders that are sometimes lethal. Therefore, the expression, trafficking, signaling and desensitization of GPCRs must be tightly regulated by different cellular systems to prevent disease. Although there is substantial knowledge regarding the mechanisms that regulate the desensitization and down-regulation of GPCRs, less is known about the mechanisms that regulate the trafficking and cell-surface expression of newly synthesized GPCRs. More recently, there is accumulating evidence that suggests certain GPCRs are able to interact with specific proteins that can completely change their fate and function. These interactions add on another level of regulation and flexibility between different tissue/cell-types. Here, we review some of the main interacting proteins of GPCRs. A greater understanding of the mechanisms regulating their interactions may lead to the discovery of new drug targets for therapy.

Contextualisation and authenticity in TBLT: voices from Chinese classrooms

In view of ongoing debates about the future of TBLT in EFL contexts (Thomas & Reinders, 2015; Zheng & Borg, 2014), we present a detailed case study of teacher beliefs and practices regarding TBLT conducted in a secondary school in mainland China with a long history of communicative and task-based teaching approaches. We used a mixed-methods approach to gather a broad range of triangulated data, combining individual interviews, material analysis and observations coded using a novel task-focused version of the COLT scheme (Littlewood, 2011; Spada & Fröhlich, 1995). Quantitative and qualitative findings revealed positive beliefs about TBLT principles in general, reflecting strong institutional support for communicative teaching. However, there was marked variability between beliefs and practices in using tasks, especially with beginner-level learners. Most teachers demonstrated an intrinsic lack of confidence in using tasks as more than a communicative ‘add-on’ to standard form-focused teaching. We argue this demonstrates a need for building teacher autonomy (Aoki, 2002; Benson, 2007), in implementing TBLT, even in supportive settings, to support successful authentic contextualising TBLT principles in different EFL contexts.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Impact of coronal mass ejections, interchange reconnection, and disconnection on heliospheric magnetic field strength

An update of Owens et al. (2008) shows that the relationship between the coronal mass ejection (CME) rate and the heliospheric magnetic field strength predicts a field floor of less than 4 nT at 1 AU. This implies that the record low values measured during this solar minimum do not necessarily contradict the idea that open flux is conserved. The results are consistent with the hypothesis that CMEs add flux to the heliosphere and interchange reconnection between open flux and closed CME loops subtracts flux. An existing model embracing this hypothesis, however, overestimates flux during the current minimum, even though the CME rate has been low. The discrepancy calls for reasonable changes in model assumptions.

Does active management add any value?

The question as to whether active management adds any value above that of the funds investment policy is one of continual interest to investors. In order to investigate this issue in the UK real estate market we examine a number of related questions. First, how much return variability is explained by investment policy? Second, how similar are the policies across funds? Third, how much of a fund’s return is determined by investment policy? Finally, how was this added value achieved? Using data for 19 real estate funds we find that investment policy explains less than half of the variability in returns over time, nothing of the variation across funds and that more than 100% of a level of return is attributed to investment policy. The results also show UK real estate fund focus exclusively on trying to pick winners to add value and that in pursuit of active return fund mangers incur high tracking error risk, consequently, successful active management is very difficult to achieve. In addition, the results are dependent on the benchmark used to represent the investment policy of the fund. Nonetheless, active management can indeed add value to a real estate funds performance. This is the good news. The bad news is adding value is much more difficult to achieve than is generally accepted.

A note on the use of spreadsheet optimisers in real estate analysis

Modern Portfolio Theory (MPT) has been advocated as a more rational approach to the construction of real estate portfolios. The application of MPT can now be achieved with relative ease using the powerful facilities of modern spreadsheet, and does not necessarily need specialist software. This capability is to be found in the use of an add-in Tool now found in several spreadsheets, called an Optimiser or Solver. The value in using this kind of more sophisticated analysis feature of spreadsheets is increasingly difficult to ignore. This paper examines the use of the spreadsheet Optimiser in handling asset allocation problems. Using the Markowitz Mean-Variance approach, the paper introduces the necessary calculations, and shows, by means of an elementary example implemented in Microsoft's Excel, how the Optimiser may be used. Emphasis is placed on understanding the inputs and outputs from the portfolio optimisation process, and the danger of treating the Optimiser as a Black Box is discussed.

Resting state cortico-thalamic-striatal connectivity predicts pesponse to dorsomedial prefrontal rTMS in major depressive disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for Major Depressive Disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting state functional connectivity predicted response to treatment with rapid transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased sgACC-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Does connectivity add value to commercial real estate? The case of managed and conventional offices

This research is a preliminary study which examines the impact of connectivity on value in the managed office and conventional office sectors. The research is based on an extensive literature review, online survey and case studies carried out during 2005. The research shows, for the first time in the UK, how connectivity can increase value in office buildings, and how technology is priced in the market place.

Consideration of persuasive technology on users acceptance of e-commerce: exploring perceived persuasiveness

Persuasive technologies, used within in the domain of interactive technology, are used broadly in social contexts to encourage customers towards positive behavior change. In the context of e-commerce, persuasive technologies have already been extensively applied in the area of marketing to enhancing system credibility, however the issue of ‘persuasiveness’, and its role on positive user acceptance of technology, has not been investigated in the technology acceptance literature. This paper reviews theories and models of users’ acceptance and use in relation with persuasive technology, and identifies their limitation when considering the impact of persuasive technology on users’ acceptance of technology; thus justifying a need to add consideration of ‘perceived persuasiveness’. We conclude by identifying variables associated with perceived persuasiveness, and suggest key research directions for future research.

The perceived impact of the National Health Service on personalised nutrition service delivery among the UK public

Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the 'framework approach' described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.

Effects of forage source and extruded linseed supplementation on methane emissions from growing dairy cattle of differing body weights

Changes in diet carbohydrate amount and type (i.e., starch vs. fiber) and dietary oil supplements can affect ruminant methane emissions. Our objectives were to measure methane emissions, whole-tract digestibility, and energy and nitrogen utilization from growing dairy cattle at 2 body weight (BW) ranges, fed diets containing either high maize silage (MS) or high grass silage (GS), without or with supplemental oil from extruded linseed (ELS). Four Holstein-Friesian heifers aged 13 mo (BW range from start to finish of 382 to 526 kg) were used in experiment 1, whereas 4 lighter heifers aged 12 mo (BW range from start to finish of 292 to 419 kg) were used in experiment 2. Diets were fed as total mixed rations with forage dry matter (DM) containing high MS or high GS and concentrates in proportions (forage:concentrate, DM basis) of either 75:25 (experiment 1) or 60:40 (experiment 2), respectively. Diets were supplemented without or with ELS (Lintec[AU1: Add manufacturer name and location.]; 260 g of oil/ kg of DM) at 6% of ration DM. Each experiment was a 4 × 4 Latin square design with 33-d periods, with measurements during d 29 to 33 while animals were housed in respiration chambers. Heifers fed MS at a heavier BW (experiment 1) emitted 20% less methane per unit of DM intake (yield) compared with GS (21.4 vs. 26.6, respectively). However, when repeated with heifers of a lower BW (experiment 2), methane yield did not differ between the 2 diets (26.6 g/kg of DM intake). Differences in heifer BW had no overall effect on methane emissions, except when expressed as grams per kilogram of digestible organic matter (OMD) intake (32.4 vs. 36.6, heavy vs. light heifers). Heavier heifers fed MS in experiment 1 had a greater DM intake (9.4 kg/d) and lower OMD (755 g/kg), but no difference in N utilization (31% of N intake) compared with heifers fed GS (7.9 kg/d and 799 g/kg, respectively). Tissue energy retention was nearly double for heifers fed MS compared with GS in experiment 1 (15 vs. 8% of energy intake, respectively). Heifers fed MS in experiment 2 had similar DM intake (7.2 kg/d) and retention of energy (5% of intake energy) and N (28% of N intake), compared with GS-fed heifers, but OMD was lower (741 vs. 765 g/kg, respectively). No effect of ELS was noted on any of the variables measured, irrespective of animal BW, and this was likely due to the relatively low amount of supplemental oil provided. Differences in heifer BW did not markedly influence dietary effects on methane emissions. Differences in methane yield were attributable to differences in dietary starch and fiber composition associated with forage type and source.