Resolution theory, and static and frequency-dependent cross-talk in piezoresponse force microscopy

Probing the functionality of materials locally by means of scanning probe microscopy (SPM) requires a reliable framework for identifying the target signal and separating it from the effects of surface morphology and instrument non-idealities, e.g. instrumental and topographical cross-talk. Here we develop a linear resolution theory framework in order to describe the cross-talk effects, and apply it for elucidation of frequency-dependent cross-talk mechanisms in piezoresponse force microscopy. The use of a band excitation method allows electromechanical/electrical and mechanical/topographic signals to be unambiguously separated. The applicability of a functional fit approach and multivariate statistical analysis methods for identification of data in band excitation SPM is explored.

Guest sorption and desorption in the metal-organic framework [Co(INA)(2)] (INA = isonicotinate) - evidence of intermediate phases during desorption

The metal-organic framework [Co(INA)(2)].0.5EtOH (INA = isonicotinate, NC5H4-4-CO2-), 1 was synthesised under solvothermal conditions. Its X-ray crystal structure shows channels containing ethanol guests which are hydrogen-bonded to carboxylate oxygens of the framework. The pyridyl rings of the framework alternate between `open' and `closed' positions along the channels resulting in large variation in the channel cross-sectional area from ca. 1.4 by 2.3 at the narrowest point to 4.9 by 5.3 at the widest. Despite the very small windows, the ethanol guests (of van der Waals diameter ca. 4.2-6.1 Angstrom) may be reversibly desorbed and sorbed into the structure quantitatively, as shown by in situ variable-temperture IR spectroscopy and XRPD. The single-crystal structure of the desolvated form [Co(INA)(2)]2 shows that there is no change in the overall connectivity on desolvation, but the rotational positions of the pyridine rings are altered. This suggests that pyridyl rotation may occur to allow guests to pass in and out. When the synthesis was conducted in 1-propanol solvent [Co(INA)(2)].0.5Pr(n)OH.H2O 3, was obtained, and a single-crystal X-ray structure revealed the same overall connectivity as in 1 but with pyridine rings disordered over closed and open positions. There was no evidence of included guests from X-ray crystallography, suggesting that they are also highly disordered. Variable-temperature XRPD performed on bulk samples showed peaks which were unsymmetrical and exhibited shoulders, suggesting that for each pattern obtained the material actually consisted of several closely-related phases. The movements of the peaks during desolvation showed the presence of intermediate phases before the final desolvated product was formed. The peak positions of the intermediate phases matched more closely with the calculated pattern for 3 than with 1 or 2, suggesting that they may have disordered structures similar to 3. The results also suggest that the intermediate phase represents an initial increase in volume before a larger decrease in volume occurs to give the final desolvated material.

Beaufort trout MicroPlex:A high-throughput multiplex platform comprising 38 informative microsatellite loci for use in resident and anadromous (sea trout) brown trout Salmo trutta genetic studies

A flexible panel consisting of 38 informative microsatellite markers for Salmo trutta is described. These markers were selected from a pool of over 150 candidate loci that can be readily amplified in four multiplex PCR groups but other permutations are also possible. The basic properties of each markers were assessed in six population samples from both the Burrishoole catchment, in the west of Ireland, and Lough Neagh, in Northern Ireland. A method to assess the relative utility of individual markers for the detection of population genetic structuring is also described. Given its flexibility, technical reliability and high degree of informativeness, the use of this panel of markers is advocated as a standard for S. trutta genetic studies. © 2013 The Authors. Journal of Fish Biology © 2013 The Fisheries Society of the British Isles.

The Outcomes of Cross-Cultural Adjustment: A Case of British Expatriates Working on International Architectural, Engineering and Construction Assignments

The main aim of this study is to investigate the consequences of cross-cultural adjustment in an under researched sample of British expatriates working on International Architectural, Engineering and Construction (AEC) assignments. Adjustment is the primary outcome of an expatriate assignment. According to Bhaskar-Srinivas et al., (2005), Harrison et al., (2004) it is viewed to affect other work related outcomes which could eventually predict expatriate success. To address the scarcity of literature on expatriate management in the AEC sector, an exploratory design was adopted. Phase one is characterised by extensive review of extant literature, whereas phase two was qualitative exploration from British expatriates’ perspective; here seven unstructured interviews were carried out. Further, cognitive mapping analysis through Banaxia decision explorer software was conducted to develop a theoretical framework and propose various hypotheses. The findings imply that British AEC firms could sustain their already established competitive advantage in the global marketplace by acknowledging the complexity of international assignments, prioritising expatriate management and offering a well-rounded support to facilitate expatriate adjustment and ultimately achieve critical outcomes like performance, assignment completion and job satisfaction.

The outcomes of cross-cultural adjustment: A case of British expatriates working on international architectural, engineering and construction assignments

The main aim of this study is to investigate the consequences of cross-cultural adjustment in an under researched sample of British expatriates working on International Architectural, Engineering and Construction (AEC) assignments. Adjustment is the primary outcome of an expatriate assignment. According to Bhaskar-Srinivas et al., (2005), Harrison et al., (2004) it is viewed to affect other work related outcomes which could eventually predict expatriate success. To address the scarcity of literature on expatriate management in the AEC sector, an exploratory design was adopted. Phase one is characterised by extensive review of extant literature, whereas phase two was qualitative exploration from British expatriatesÕ perspective; here seven unstructured interviews were carried out. Further, cognitive mapping analysis through Banaxia decision explorer software was conducted to develop a theoretical framework and propose various hypotheses. The findings imply that British AEC firms could sustain their already established competitive advantage in the global marketplace by acknowledging the complexity of international assignments, prioritising expatriate management and offering a well-rounded support to facilitate expatriate adjustment and ultimately achieve critical outcomes like performance, assignment completion and job satisfaction.

Dissolving Microneedle Delivery of Nanoparticle Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells

Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.

HERQULES:System level cross-layer design exploration for efficient energy-quality trade-offs

In this paper, we present a unique cross-layer design framework that allows systematic exploration of the energy-delay-quality trade-offs at the algorithm, architecture and circuit level of design abstraction for each block of a system. In addition, taking into consideration the interactions between different sub-blocks of a system, it identifies the design solutions that can ensure the least energy at the "right amount of quality" for each sub-block/system under user quality/delay constraints. This is achieved by deriving sensitivity based design criteria, the balancing of which form the quantitative relations that can be used early in the system design process to evaluate the energy efficiency of various design options. The proposed framework when applied to the exploration of energy-quality design space of the main blocks of a digital camera and a wireless receiver, achieves 58% and 33% energy savings under 41% and 20% error increase, respectively. © 2010 ACM.

Rough Waters, Dark Shadows and Cross-Cutting Winds:the impact of European Union enlargement on Turkey’s EU accession negotiations

For a multiplicity of socio-economic, geo-political, strategic and identity-based reasons, Turkey’s progress towards EU membership is often treated as a sui generis case. Yet although Turkey’s accession negotiations with the European Union (EU) are essentially a bilateral – and often stormy – affair, they take place within a wider and dynamic process of enlargement in which not only can the gloomy – sometimes dark – shadows of past and prospective enlargements be clearly detected, but so too can the often chill winds from ongoing, parallel negotiations with other candidates. How the EU negotiates accession and what it expects from candidates has continued to evolve since the EU began drawing up its framework for negotiations with Turkey ten years ago. This paper charts this evolution by first identifying changes in the light of Croatia’s negotiating experience, the ‘lessons learnt’ by the EU in meeting the challenges of Bulgarian and Romanian accession, the EU’s handling of Iceland’s membership bid and accession negotiations, and the revised approach to negotiating accession evident in the more recent frameworks for accession negotiations with Montenegro and Serbia. The paper then explores the extent to which these changes have impacted on the approach the EU has adopted in framing and progressing accession negotiations with Turkey. In doing so, it questions both the consistency with which the EU’s negotiates accession and the extent to which Turkey’s progress towards EU membership is conditioned by the broader dynamics of EU enlargement as opposed to simply the dynamics within EU-Turkey relations and domestic Turkish reform efforts.

A Cross-Layer Optimized Scheme and Its Application in Mobile Multimedia Networks with QoS Provision

To cope with the rapid growth of multimedia applications that requires dynamic levels of quality of service (QoS), cross-layer (CL) design, where multiple protocol layers are jointly combined, has been considered to provide diverse QoS provisions for mobile multimedia networks. However, there is a lack of a general mathematical framework to model such CL scheme in wireless networks with different types of multimedia classes. In this paper, to overcome this shortcoming, we therefore propose a novel CL design for integrated real-time/non-real-time traffic with strict preemptive priority via a finite-state Markov chain. The main strategy of the CL scheme is to design a Markov model by explicitly including adaptive modulation and coding at the physical layer, queuing at the data link layer, and the bursty nature of multimedia traffic classes at the application layer. Utilizing this Markov model, several important performance metrics in terms of packet loss rate, delay, and throughput are examined. In addition, our proposed framework is exploited in various multimedia applications, for example, the end-to-end real-time video streaming and CL optimization, which require the priority-based QoS adaptation for different applications. More importantly, the CL framework reveals important guidelines as to optimize the network performance

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.

METHODS: Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).

FINDINGS: 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc.

INTERPRETATION: Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.

FUNDING: Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research.

A Scalable Runtime for the ECOSCALE Heterogeneous Exascale Hardware Platform

Exascale computation is the next target of high performance computing. In the push to create exascale computing platforms, simply increasing the number of hardware devices is not an acceptable option given the limitations of power consumption, heat dissipation, and programming models which are designed for current hardware platforms. Instead, new hardware technologies, coupled with improved programming abstractions and more autonomous runtime systems, are required to achieve this goal. This position paper presents the design of a new runtime for a new heterogeneous hardware platform being developed to explore energy efficient, high performance computing. By combining a number of different technologies, this framework will both simplify the programming of current and future HPC applications, as well as automating the scheduling of data and computation across this new hardware platform. In particular, this work explores the use of FPGAs to achieve both the power and performance goals of exascale, as well as utilising the runtime to automatically effect dynamic configuration and reconfiguration of these platforms. 

Cross-border Movement of Patients in the EU: A Re-Appraisal

The national welfare state, so it seems, has come under attack by European integration. This article focuses on one facet of the welfare state, that is, health care and on one specific dimension, that is, cross-border movement of patients. The institution which has played a pivotal role in the development of the framework regulating the migration of patients is the European Court of Justice (ECJ). The Court’s activity in this sensitive area has not remained without critics. This was even more so since the Court invoked Treaty (primary) law which not only has made it difficult to overturn case law but also has left the legislator with very little room for manoeuvre in relation to any future (secondary) EU law. What is therefore of special interest in terms of legitimacy is the legal reasoning by which the Court has made its contribution to the development of this framework. This article is a re-appraisal of the legal development in this field.

Dynalog: an automated dynamic analysis framework for characterizing android applications

Android is becoming ubiquitous and currently has the largest share of the mobile OS market with billions of application downloads from the official app market. It has also become the platform most targeted by mobile malware that are becoming more sophisticated to evade state-of-the-art detection approaches. Many Android malware families employ obfuscation techniques in order to avoid detection and this may defeat static analysis based approaches. Dynamic analysis on the other hand may be used to overcome this limitation. Hence in this paper we propose DynaLog, a dynamic analysis based framework for characterizing Android applications. The framework provides the capability to analyse the behaviour of applications based on an extensive number of dynamic features. It provides an automated platform for mass analysis and characterization of apps that is useful for quickly identifying and isolating malicious applications. The DynaLog framework leverages existing open source tools to extract and log high level behaviours, API calls, and critical events that can be used to explore the characteristics of an application, thus providing an extensible dynamic analysis platform for detecting Android malware. DynaLog is evaluated using real malware samples and clean applications demonstrating its capabilities for effective analysis and detection of malicious applications.