Oxygen sensors and energy sensors act synergistically to achieve a graded alteration in gene expression: Consequences for assessing the level of neuroprotection in response to stressors

Changes in gene expression are associated with switching to an autoprotected phenotype in response to environmental and physiological stress. Ubiquitous molecular chaperones from the heat shock protein (HSP) superfamily confer neuronal protection that can be blocked by antibodies. Recent research has focused on the interactions between the molecular sensors that affect the increased expression of neuroprotective HSPs above constitutive levels. An examination of the conditions under which the expression of heat shock protein 70 (Hsp70) was up regulated in a hypoxia and anoxia tolerant tropical species, the epaulette shark (Hemiscyllium ocellatum), revealed that up-regulation was dependent on exceeding a stimulus threshold for an oxidative stressor. While hypoxic-preconditioning confers neuroprotective changes, there was no increase in the level of Hsp70 indicating that its increased expression was not associated with achieving a neuroprotected state in response to hypoxia in the epaulette shark. Conversely, there was a significant increase in Hsp70 in response to anoxic-preconditioning, highlighting the presence of a stimulus threshold barrier and raising the possibility that, in this species, Hsp70 contributes to the neuroprotective response to extreme crises, such as oxidative stress. Interestingly, there was a synergistic effect of coincident stressors on Hsp70 expression, which was revealed when metabolic stress was superimposed upon oxidative stress. Brain energy charge was significantly lower when adenosine receptor blockade, provided by treatment with aminophylline, was present prior to the final anoxic episode, under these circumstances, the level of Hsp70 induced was significantly higher than in the pair-matched saline treated controls. An understanding of the molecular and metabolic basis for neuroprotective switches, which result in an up-regulation of neuroprotective Hsp70 expression in the brain, is needed so that intervention strategies can be devised to manage CNS pathologies and minimise damage caused by ischemia and trauma. In addition, the current findings indicate that measurements of HSP expression per se may provide a useful correlate of the level of neuroprotection achieved in the switch to an autoprotected phenotype.

Responsibility to protect or Trojan Horse? The crisis in darfur and humanitarian intervention after Iraq

What does the world's engagement with the unfolding crisis in Darfur tell us about the impact of the Iraq war on the norm of humanitarian intervention? Is a global consensus about a "responsibility to protect" more or less likely? There are at least three potential answers to these questions. Some argue that the merging of strategic interests and humanitarian goods amplified by the intervention in Afghanistan makes it more likely that the world's most powerful states will act to prevent or halt humanitarian crises. Others insist that the widespread perception that the United States and its allies "abused" humanitarian justifications to legitimate its invasion of Iraq has set back efforts to build a global consensus about humanitarian action. A third group argues that the "responsibility to protect" inhibits the potential for abuse and, as a result, consensus is likely to strengthen post-Iraq for precisely this reason. Through a detailed study of the international engagement with Darfur, I suggest that the latter two arguments have merit but need to be adjusted. I argue that the humanitarian intervention norm has changed in two subtle ways. First, while the strength of the norm itself has not changed, the credibility of the United States and U.K. as "norm carriers" has been significantly undermined. Second, while the "responsibility to protect" has been invoked to support international activism, it has also re-legitimated anti-interventionist arguments.

Evaluating boards and directors

The challenge for boards is to prevent crises in the organisations they govern. Performance evaluation is a key means by which boards can recognise and correct corporate governance problems and add real value to their organisations. Our paper provides a practical introduction to board and director evaluations. We discuss the reasons for governance failures and how board evaluations can help prevent them from occurring. We then review the performance pressures facing boards and the benefits of board evaluations in meeting these pressures. Finally, we introduce our framework for a successful board and/or individual director evaluation, whatever the company type. In this framework, we suggest there are seven key questions to consider when planning a board evaluation and discuss each of these seven decision areas.

Degrees of freedom and motor planning in purposive movement

This paper presents empirical evidence suggesting that healthy humans can perform a two degree of freedom visuo-motor pursuit tracking task with the same response time delay as a one degree of freedom task. In contrast, the time delay of the response is influenced markedly by the nature of the motor synergy required to produce it. We suggest a conceptual account of this evidence based on adaptive model theory, which combines theories of intermittency from psychology and adaptive optimal control from engineering. The intermittent response planning stage has a fixed period. It possesses multiple optimal trajectory generators such that multiple degrees of freedom can be planned concurrently, without requiring an increase in the planning period. In tasks which require unfamiliar motor synergies, or are deemed to be incompatible, internal adaptive models representing movement dynamics are inaccurate. This means that the actual response which is produced will deviate from the one which is planned. For a given target-response discrepancy, corrective response trajectories of longer duration are planned, consistent with the principle of speed-accuracy trade-off. Compared to familiar or compatible tasks, this results in a longer response time delay and reduced accuracy. From the standpoint of the intermittency approach, the findings of this study help make possible a more integral and predictive account of purposive action. (c) 2005 Elsevier B.V. All rights reserved.

Whither the responsibility to protect? Humanitarian intervention and the 2005 World Summit

At the 2005 World Summit, the world's leaders committed themselves to the "responsibility to protect", recognizing both that all states have a responsibility to protect their citizens from genocide, war crimes, ethnic cleansing and crimes against humanity and that the UN should help states to discharge this responsibility using either peaceful means or enforcement action. This declaration ostensibly marks an important milestone in the relationship between sovereignty and human rights but its critics argue that it will make little difference in practice to the world's most threatened people. The purpose of this article is to ask how consensus was reached on the responsibility to protect, given continuing hostility to humanitarian intervention expressed by many (if not most) of the world's states and whether the consensus will contribute to avoiding future Kosovos (cases where the Security Council is deadlocked in the face of a humanitarian crises) and future Rwandas (cases where states lack the political will to intervene). It suggests that four key factors contributed to the consensus: pressure from proponents of the International Commission on Intervention and State Sovereignty, its adoption by Kofi Annan and the UN's High Level Panel, an emerging consensus in the African Union, and the American position. Whilst these four factors contributed to consensus, each altered the meaning of the responsibility to protect in important ways, creating a doctrine that many states can sign up to but that does little to prevent future Kosovos and Rwandas and may actually inhibit attempts to build a consensus around intervention in future cases.

Tourism crisis and disasters: Enhancing understanding of system effects

This paper examines the definitions and conceptual foundations of crises and distinguishes between crises and disasters. It takes a systems view of these concepts and uses the perspective of systems as organizational networks to examine implications for tourism managers. A tourism destination is perceived as consisting of a network of interacting organizations. This perspective questions the boundaries that should be used to study crisis and disasters. The paper also discusses the possibility of a crisis having a positive outcome for a destination.

The Bali bombs and the tourism development cycle

This paper analyses the impact of the Bali bombings on international visitor arrivals in Bali and compares this crisis with previous crises with reference to Butler’s hypothetical tourism area life cycle. The paper demonstrates that the Bali bombings had by far the greatest impact on international tourism visitation than any other crisis in the island’s history. Such was the severity of the decline in Bali that both national and local measures were taken to restore confidence. Important though these measures were, they do not fully account for the strong resurgence in international arrivals, suggesting that the destination has not yet reached consolidation in accordance with Butler’s hypothesis and that the strength of the resurgence owes much to the underlying trend of the development phase associated with the general picture proposed by Butler.

JORNALISMO: TRAJETÓRIA, CRISES E O FENÔMENO DO METRO

Esta pesquisa tem o propósito de analisar a dupla crise do jornalismo financeira e paradigmática - que têm refletido no processo de mutação jornalística observada em alguns veículos da atualidade, como é o caso do jornal gratuito Metro, nosso objeto de estudo. O que se buscou foi entender como as características dos tempos atuais, tais como superficialidade das notícias, a velocidade, a instantaneidade, a forte presença da publicidade e o apelo direto o consumo, estão presentes no jornalismo impresso atual. Em um primeiro momento realizou-se revisão bibliográfica sobre a trajetória do jornalismo, história e crise enfrentada nas últimas décadas. A seguir, fez-se uma pesquisa exploratória sobre o Metro, objeto estudado, avaliando a presença de características que o fazem um veículo da atualidade, reflexo da mutação jornalística. A análise revelou a existência de uma crise conceitual agravada pela crise econômica e marcada pelas leis do capital.(AU)

Off-farm labour supply and labour markets in rapidly changing circumstances:Bulgaria during transition

This study examines off-farm labor supply in the rapidly changing conditions of Bulgaria during the 1990s. In doing so, we make use of three different waves of the Bulgarian Integrated Household Survey, each reflecting remarkably different environmental conditions. The results suggest that standard theories of off-farm labor supply provide little guidance in situations characterized by chronic excess supply in the off-farm labor market and/or rapidly changing circumstances. In particular, the results show (1) that off-farm employment throughout the transition was predominantly determined by demand rather than by supply, and (2) that the magnitude and statistical significance of the various determinants are very sensitive to changing environmental conditions. As such, the results can be extremely relevant for both theory and policy for the many countries which may still need to go through privatization and painful restructuring as a result of financial crises and globalization.

The Rover Task Force:a case study in proactive and reactive policy intervention?

The paper examines the policy responses in the UK West Midlands to the successive crises at the car maker MG-Rover. Whilst the firm’s eventual collapse in 2005 was a substantial shock to the West Midlands economy, the impact was much less than was anticipated when the firm was first threatened with closure in 2000 at the time of its break-up and sale by the German car firm BMW. Although the firm struggled as an independent producer, the five years of continued production until 2005 and the work of the initial Rover Task Force (RTF1), enabled many suppliers to adjust and diversify away from their hitherto dependence on MG-Rover resulting in as many as 10,000–12,000 jobs being ‘saved’. This first intervention was later followed by a programme to help ex-workers to find new jobs or re-train and assist supply firms to continue trading in the short term. Examination of the effectiveness of these emergency initiatives enables a wider discussion about the nature of industrial policy in the region and the work of the local regional development agency’s cluster-based approach to economic development and business support. Whilst the actions taken were successful in a number of aspects, there were a number of significant ‘failures’ at both national and local level. The MG-Rover case also illustrates a number of critical issues pertaining to regionally based cluster policies and the organization of cluster management groups where the ‘cluster’ in question not only crosses both administrative and ‘sector’ boundaries but is also subject to the imperatives of the global market car market.

Invalid ballots and the “crisis of representative democracy”:re-inventing protest at the 2012 Serbian elections

This article examines the ways in which invalidated electoral ballots may be articulated as acts of protest. We argue that some instances of ballot invalidation can be understood as protest and as a reaction to the broader “crises of democracy” which have also spurred on movements such as Occupy. We focus on Serbia’s 2012 elections as a case study, given the high increases in invalid ballots and calls for collective action calling for ballot invalidation. We discuss protest movements which coalesced around this election, calling for electoral ballot invalidation and using social media to frame this activity as protest. Through our case study, we explore the ways in which the ballot can become a tool of contention, and how protest can be expressed through an engagement with extant structures and institutions.

The interaction between metabolic disease and ageing

Two of the greatest crises that civilisation faces in the 21st century are the predicted rapid increases in the ageing population and levels of metabolic disorders such as obesity and type 2 diabetes. A growing amount of evidence now supports the notion that energy balance is a key determinant not only in metabolism but also in the process of cellular ageing. Much of genetic evidence for a metabolic activity-driven ageing process has come from model organisms such as worms and flies where inactivation of the insulin receptor signalling cascade prolongs lifespan. At its most simplistic, this poses a conundrum for ageing in humans – can reduced insulin receptor signalling really promote lifespan and does this relate to insulin resistance seen in ageing? In higher animals, caloric restriction studies have confirmed a longer lifespan when daily calorie intake is reduced to 60% of normal energy requirement. This suggests that for humans, it is energy excess which is a likely driver of metabolic ageing. Interventions that interfere with the metabolic fate of nutrients offer a potentially important target for delaying biological ageing.

Leaders' sensemaking under crises:emerging cognitive consensus over time within management teams

When facing a crisis, leaders' sensemaking can take a considerable amount of time due to the need to develop consensus in how to deal with it so that vision formation and sensegiving can take place. However, research into emerging cognitive consensus when leaders deal with a crisis over time is lacking. This is limiting a detailed understanding of how organizations respond to crises. The findings, based on a longitudinal analysis of cognitive maps within three management teams at a single organization, highlight considerable individual differences in cognitive content when starting to make sense of a crisis. Evidence for an emerging viable prescriptive mental model for the future was found, but not so much in the management as a whole. Instead, the findings highlight increasing cognitive consensus based on similarities in objectives and cause-effect beliefs within well-defined management teams over time.

On-off and multistate intermittencies in cascaded random distributed feedback fibre laser

A range of physical and engineering systems exhibit an irregular complex dynamics featuring alternation of quiet and burst time intervals called the intermittency. The intermittent dynamics most popular in laser science is the on-off intermittency [1]. The on-off intermittency can be understood as a conversion of the noise in a system close to an instability threshold into effective time-dependent fluctuations which result in the alternation of stable and unstable periods. The on-off intermittency has been recently demonstrated in semiconductor, Erbium doped and Raman lasers [2-5]. Recently demonstrated random distributed feedback (random DFB) fiber laser has an irregular dynamics near the generation threshold [6,7]. Here we show the intermittency in the cascaded random DFB fiber laser. We study intensity fluctuations in a random DFB fiber laser based on nitrogen doped fiber. The laser generates first and second Stokes components 1120 nm and 1180 nm respectively under an appropriate pumping. We study the intermittency in the radiation of the second Stokes wave. The typical time trace near the generation threshold of the second Stokes wave (Pth) is shown at Fig. 1a. From the number of long enough time-traces we calculate statistical distribution between major spikes in time dynamics, Fig. 1b. To eliminate contribution of high frequency components of spikes we use a low pass filter along with the reference value of the output power. Experimental data is fitted by power law, ~(P-Pth)y, where is a mean time between pikes. There are two different intermittency regimes. Just above Pth, the mean time is approximated by the -3/2 power law. The -3/2 power law is typical to the on-off intermittency with hopping between two states (first and second Stokes waves in our case) [7]. At higher power, the mean time is approximated by -4 power law, that indicates a change in intermittency type to multistate. Multistable dynamics is observed in erbium-doped fiber lasers [8]. The origin of multiples states in our system could be probably connected with polarization hopping or other reasons and should be further investigated. We have presented a first experimental statistical characterisation of the on-off and multistate intermittencies that occur in the generation of the second Stokes wave in nitrogen doped random DFB fiber laser. References [1] H. Fujisaka and T. Yamada, “A New Intermittency in Coupled Dynamical Systems,” Prog. Theor. Phys. 74, 918 (1985). [2] S. Osborne, A. Amann, D. Bitauld, and S. O’Brien, “On-off intermittency in an optically injected semiconductor laser,” Phys. Rev. E 85, 056204 (2012). [3] S. Sergeyev, K. O'Mahoney, S. Popov, and A. T. Friberg, “Coherence and anticoherence resonance in high-concentration erbium-doped fiber laser,” Opt. Lett. 35, 3736 (2010). [4] A.E. El-Taher, S.V. Sergeyev, E.G. Turitsyna, P. Harper, and S. K. Turitsyn, “Intermittent Self-Pulsing in a Fiber Raman Laser”, In proc. Conf. Nonlin. Photon., paper ID 1367139, Colorado Springs, USA, 2012 [5] S.K. Turitsyn, S.A. Babin, A.E. El-Taher, P. Harper, D.V. Churkin, S.I. Kablukov, J.D. Ania-Castañón, V. Karalekas, and E.V. Podivilov, “Random distributed feedback fibre laser”, Nat. Photon..4, 231 (2010). [6] I. D. Vatnik, D. V. Churkin, S. A. Babin, and S. K. Turitsyn, "Cascaded random distributed feedback Raman fiber laser operating at 1.2 μm," Opt. Express 19, 18486 (2011). [7] W. Feller, An introduction to probability theory and its applications, Vol. 1, 3rd ed. (Wiley, New-York, 1968). [8] G. Huerta-Cuellar, A.N. Pisarchik, and Y.O. Barmenkov, “Experimental characterization of hopping dynamics in a multistable fiber laser,” Phys. Rev. E 78, 035202(R) (2008).