The role of oscillatory brain activity in object processing and figure-ground segmentation in human vision

The perception of an object as a single entity within a visual scene requires that its features are bound together and segregated from the background and/or other objects. Here, we used magnetoencephalography (MEG) to assess the hypothesis that coherent percepts may arise from the synchronized high frequency (gamma) activity between neurons that code features of the same object. We also assessed the role of low frequency (alpha, beta) activity in object processing. The target stimulus (i.e. object) was a small patch of a concentric grating of 3c/°, viewed eccentrically. The background stimulus was either a blank field or a concentric grating of 3c/° periodicity, viewed centrally. With patterned backgrounds, the target stimulus emerged--through rotation about its own centre--as a circular subsection of the background. Data were acquired using a 275-channel whole-head MEG system and analyzed using Synthetic Aperture Magnetometry (SAM), which allows one to generate images of task-related cortical oscillatory power changes within specific frequency bands. Significant oscillatory activity across a broad range of frequencies was evident at the V1/V2 border, and subsequent analyses were based on a virtual electrode at this location. When the target was presented in isolation, we observed that: (i) contralateral stimulation yielded a sustained power increase in gamma activity; and (ii) both contra- and ipsilateral stimulation yielded near identical transient power changes in alpha (and beta) activity. When the target was presented against a patterned background, we observed that: (i) contralateral stimulation yielded an increase in high-gamma (>55 Hz) power together with a decrease in low-gamma (40-55 Hz) power; and (ii) both contra- and ipsilateral stimulation yielded a transient decrease in alpha (and beta) activity, though the reduction tended to be greatest for contralateral stimulation. The opposing power changes across different regions of the gamma spectrum with 'figure/ground' stimulation suggest a possible dual role for gamma rhythms in visual object coding, and provide general support of the binding-by-synchronization hypothesis. As the power changes in alpha and beta activity were largely independent of the spatial location of the target, however, we conclude that their role in object processing may relate principally to changes in visual attention.

The impact of board independence and ownership structure on the timeliness of corporate internet reporting of Irish-listed companies

Purpose – This study seeks to provide valuable new insight into the timeliness of corporate internet reporting (TCIR) by a sample of Irish-listed companies. Design/methodology/approach – The authors apply an updated version of Abdelsalam et al. TCIR index to assess the timeliness of corporate internet reporting. The index encompasses 13 criteria that are used to measure the TCIR for a sample of Irish-listed companies. In addition, the authors assess the timeliness of posting companies’ annual and interim reports to their web sites. Furthermore, the study examines the influence of board independence and ownership structure on the TCIR behaviour. Board composition is measured by the percentage of independent directors, chairman’s dual role and average tenure of directors. Ownership structure is represented by managerial ownership and blockholder ownership. Findings – It is found that Irish-listed companies, on average, satisfy only 46 per cent of the timeliness criteria assessed by the timeliness index. After controlling for size, audit fees and firm performance, evidence that TCIR is positively associated with board of director’s independence and chief executive officer (CEO) ownership is provided. Furthermore, it is found that large companies are faster in posting their annual reports to their web sites. The findings suggest that board composition and ownership structure influence a firm’s TCIR behaviour, presumably in response to the information asymmetry between management and investors and the resulting agency costs. Practical implications – The findings highlight the need for improvement in TCIR by Irish-listed companies in many areas, especially in regard to the regular updates of information provided on their web sites. Originality/value – This study represents one of the first comprehensive examinations of the important dimension of the TCIR in Irish-listed companies.

A stakeholder perspective on buyer-supplier conflict

This study seeks to investigate how stakeholder power and an organization's pursuit of legitimacy influence its reaction to conflict with a supplier. We conducted an empirical study among travel agents and tour operators to test the relationship between conflict and stakeholder power and legitimacy derived from three different stakeholders. Our findings imply that power has a dual role. Whereas supplier power reduces buyer–supplier conflict, stakeholder power increases it. Moreover, this study shows that the quest to achieve greater legitimacy from the firm's competitive arena increases conflict. This study is one of the few that test stakeholder theory empirically. We demonstrate that stakeholder theory provides additional explanations above the hitherto taken dyadic approach toward understanding conflict. This study also shows that power can simultaneously reduce and increase conflict depending on which party possesses power. Greater supplier power decreases conflict, while greater stakeholder power and stakeholder-derived legitimacy increases it. Therefore, organizations have to balance their stakeholder and supplier interests.

University ranking as social exclusion

In this article we explore the dual role of global university rankings in the creation of a new, knowledge-identified, transnational capitalist class and in facilitating new forms of social exclusion.We examine how and why the practice of ranking universities has become widely defined by national and international organisations as an important instrument of political and economic policy. We consider how the development of university rankings into a global business combining social research, marketing and public relations, as a tangible policy tool that narrowly redefines the social purposes of higher education itself. Finally, it looks at how the influence of rankings on national funding for teaching and research constrains wider public debate about the meaning of ‘good’ and meaningful education in the UK and other national contexts, particularly by shifting the debate away from democratic publics upward into the elite networked institutions of global capital. We conclude by arguing that, rather than regarding world university rankings as a means to establish criteria of educational value, the practice may be understood as an exclusionary one that furthers the alignment of higher education with neoliberal rationalities at both national and global levels.

Multiple roles of charged amino acids in cytoplasmic loop 7 for expression and function of the multidrug and organic anion transporter MRP1 (ABCC1)

Multidrug resistance protein MRP1 mediates the ATP-dependent efflux of many chemotherapeutic agents and organic anions. MRP1 has two nucleotide binding sites (NBSs) and three membrane spanning domains (MSDs) containing 17 transmembrane helices linked by extracellular and cytoplasmic loops (CL). Homology models suggest that CL7 (amino acids 1141-1195) is in a position where it could participate in signaling between the MSDs and NBSs during the transport process. We have individually replaced eight charged residues in CL7 with Ala, and in some cases, an amino acid with the same charge, and then investigated the effects on MRP1 expression, transport activity, and nucleotide and substrate interactions. A triple mutant in which Glu(1169), Glu(1170), and Glu(1172) were all replaced with Ala was also examined. The properties of R1173A and E1184A were comparable with those of wild-type MRP1, whereas the remaining mutants were either poorly expressed (R1166A, D1183A) or exhibited reduced transport of one or more organic anions (E1144A, D1179A, K1181A, (1169)AAQA). Same charge mutant D1183E was also not expressed, whereas expression and activity of R1166K were similar to wild-type MRP1. The moderate substrate-selective changes in transport activity displayed by mutants E1144A, D1179A, K1181A, and (1169)AAQA were accompanied by changes in orthovanadate-induced trapping of [alpha-(32)P]azidoADP by NBS2 indicating changes in ATP hydrolysis or release of ADP. In the case of E1144A, estradiol glucuronide no longer inhibited trapping of azidoADP. Together, our results demonstrate the extreme sensitivity of CL7 to mutation, consistent with its critical and complex dual role in both the proper folding and transport activity of MRP1.

The impact of board independence and ownership structure on the timeliness of corporate internet reporting of Irish-listed companies

Purpose – This study seeks to provide valuable new insight into the timeliness of corporate internet reporting (TCIR) by a sample of Irish-listed companies. Design/methodology/approach – The authors apply an updated version of Abdelsalam et al. TCIR index to assess the timeliness of corporate internet reporting. The index encompasses 13 criteria that are used to measure the TCIR for a sample of Irish-listed companies. In addition, the authors assess the timeliness of posting companies’ annual and interim reports to their web sites. Furthermore, the study examines the influence of board independence and ownership structure on the TCIR behaviour. Board composition is measured by the percentage of independent directors, chairman’s dual role and average tenure of directors. Ownership structure is represented by managerial ownership and blockholder ownership. Findings – It is found that Irish-listed companies, on average, satisfy only 46 per cent of the timeliness criteria assessed by the timeliness index. After controlling for size, audit fees and firm performance, evidence that TCIR is positively associated with board of director’s independence and chief executive officer (CEO) ownership is provided. Furthermore, it is found that large companies are faster in posting their annual reports to their web sites. The findings suggest that board composition and ownership structure influence a firm’s TCIR behaviour, presumably in response to the information asymmetry between management and investors and the resulting agency costs. Practical implications – The findings highlight the need for improvement in TCIR by Irish-listed companies in many areas, especially in regard to the regular updates of information provided on their web sites. Originality/value – This study represents one of the first comprehensive examinations of the important dimension of the TCIR in Irish-listed companies.

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Cationic liposomes as adjuvants for subunit protein vaccines:their role in the depot effect and antigen processing by APCs

Introduction: The requirement of adjuvants in subunit protein vaccination is well known yet their mechanisms of action remain elusive. Of the numerous mechanisms suggested, cationic liposomes appear to fulfil at least three: the antigen depot effect, the delivery of antigen to antigen presenting cells (APCs) and finally the danger signal. We have investigated the role of antigen depot effect with the use of dual radiolabelling whereby adjuvant and antigen presence in tissues can be quantified. In our studies a range of cationic liposomes and different antigens were studied to determine the importance of physical properties such as liposome surface charge, antigen association and inherent lipid immunogenicity. More recently we have investigated the role of liposome size with the cationic liposome formulation DDA:TDB, composed of the cationic lipid dimethyldioctadecylammonium (DDA) and the synthetic mycobacterial glycolipid trehalose 6,6’-dibehenate (TDB). Vesicle size is a frequently investigated parameter which is known to result in different routes of endocytosis. It has been postulated that targeting different routes leads to different intracellular signaling pathway activation and it is certainly true that numerous studies have shown vesicle size to have an effect on the resulting immune responses (e.g. Th1 vs. Th2). Aim: To determine the effect of cationic liposome size on the biodistribution of adjuvant and antigen, the ensuing humoral and cell-mediated immune responses and the uptake and activation of antigen by APCs including macrophages and dendritic cells. Methods: DDA:TDB liposomes were made to three different sizes (~ 0.2, 0.5 and 2 µm) followed by the addition of tuberculosis antigen Ag85B-ESAT-6 therefore resulting in surface adsorption. Liposome formulations were injected into Balb/c or C57Bl/6 mice via the intramuscular route. The biodistribution of the liposome formulations was followed using dual radiolabelling. Tissues including muscle from the site of injection and local draining lymph nodes were removed and liposome and antigen presence quantified. Mice were also immunized with the different vaccine formulations and cytokine production (from Ag85B-ESAT-6 restimulated splenocytes) and antibody presence in blood assayed. Furthermore, splenocyte proliferation after restimulating with Ag85B-ESAT-6 was measured. Finally, APCs were compared for their ability to endocytose vaccine formulations and the effect this had on the maturation status of the cell populations was compared. Flow cytometry and fluorescence labelling was used to investigate maturation marker up-regulation and efficacy of phagocytosis. Results: Our results show that for an efficient Ag85B-ESAT-6 antigen depot at the injection site, liposomes composed of DDA and TDB are required. There is no significant change in the presence of liposome or antigen at 6hrs or 24hrs p.i, nor does liposome size have an effect. Approximately 0.05% of the injected liposome dose is detected in the local draining lymph node 24hrs p.i however protein presence is low (<0.005% dose). Preliminary in vitro data shows liposome and antigen endocytosis by macrophages; further studies on this will be presented in addition to the results of the immunisation study.

Managing crisis:the role of primary care for people with serious mental illness

Background and Objectives: More than 30% of patients with serious mental illness in the United Kingdom now receive all their health care solely from primary care. This study explored the process of managing acute mental health crises from the dual perspective of patients and primary care health professionals. Methods: Eighteen focus groups involving 45 patients, 39 general practitioners, and eight practice nurses were held between May and November 2002 in six Primary Care Trusts across the British West Midlands. The topic guide explored perceptions of gold standard care, current issues and critical incidents in receiving/providing care, and ideas on improving services. Results: Themes relevant to the management of acute crisis included issues of process, such as access, advocacy, communication, continuity, and coordination of care; the development of more structured care that might reduce the need for crisis responses; and issues raised by the development of a more structured approach to care. Conclusions: Access to services is a complicated yet crucial feature of managing care in a crisis, with patients identifying barriers at the level of primary care and health professionals at the interface with secondary care. The development of more structured systems as a solution may generate its own ethical and pragmatic challenges.

Rhythm makes the world go round:an MEG-TMS study on the role of right TPJ theta oscillations in embodied perspective taking

While some aspects of social processing are shared between humans and other species, some aspects are not. The former seems to apply to merely tracking another's visual perspective in the world (i.e., what a conspecific can or cannot perceive), while the latter applies to perspective taking in form of mentally “embodying” another's viewpoint. Our previous behavioural research had indicated that only perspective taking, but not tracking, relies on simulating a body schema rotation into another's viewpoint. In the current study we employed Magnetoencephalography (MEG) and revealed that this mechanism of mental body schema rotation is primarily linked to theta oscillations in a wider brain network of body-schema, somatosensory and motor-related areas, with the right posterior temporo-parietal junction (pTPJ) at its core. The latter was reflected by a convergence of theta oscillatory power in right pTPJ obtained by overlapping the separately localised effects of rotation demands (angular disparity effect), cognitive embodiment (posture congruence effect), and basic body schema involvement (posture relevance effect) during perspective taking in contrast to perspective tracking. In a subsequent experiment we interfered with right pTPJ processing using dual pulse Transcranial Magnetic Stimulation (dpTMS) and observed a significant reduction of embodied processing. We conclude that right TPJ is the crucial network hub for transforming the embodied self into another's viewpoint, body and/or mind, thus, substantiating how conflicting representations between self and other may be resolved and potentially highlighting the embodied origins of high-level social cognition in general.

DC power line communication based on power/signal dual modulation in phase shift full bridge converters

For intelligent DC distributed power systems, data communication plays a vital role in system control and device monitoring. To achieve communication in a cost effective way, power/signal dual modulation (PSDM), a method that integrates data transmission with power conversion, can be utilized. In this paper, an improved PSDM method using phase shift full bridge (PSFB) converter is proposed. This method introduces a phase control based freedom in the conventional PSFB control loop to realize communication using the same power conversion circuit. In this way, decoupled data modulation and power conversion are realized without extra wiring and coupling units, and thus the system structure is simplified. More importantly, the signal intensity can be regulated by the proposed perturbation depth, and so this method can adapt to different operating conditions. Application of the proposed method to a DC distributed power system composed of several PSFB converters is discussed. A 2kW prototype system with an embedded 5kbps communication link has been implemented, and the effectiveness of the method is verified by experimental results.