Mechanisms linking volcanic aerosols to the Atlantic meridional overturning circulation

This study examines the sensitivity of the climate system to volcanic aerosol forcing in the third climate configuration of the Met Office Unified Model (HadCM3). The main test case was based on the 1880s when there were several volcanic eruptions, the well-known Krakatau being the largest. These eruptions increased atmospheric aerosol concentrations and induced a period of global cooling surface temperatures. In this study, an ensemble of HadCM3 has been integrated with the standard set of radiative forcings and aerosols from the Intergovernmental Panel on Climate Change Fourth Assessment Report simulations, from 1860 to present. A second ensemble removes the volcanic aerosols from 1880 to 1899. The all-forcings ensemble shows an attributable 1.2-Sv (1 Sv ≡ 106 m3 s−1) increase in the Atlantic meridional overturning circulation (AMOC) at 45°N—with a 0.04-PW increase in meridional heat transport at 40°N and increased northern Atlantic SSTs—starting around 1894, approximately 11 years after the first eruption, and lasting a further 10 years at least. The mechanisms responsible are traced to the Arctic, with suppression of the global water cycle (high-latitude precipitation), which leads to an increase in upper-level Arctic and Greenland Sea salinities. This then leads to increased convection in the Greenland–Iceland–Norwegian (GIN) Seas, enhanced Denmark Strait overflows, and AMOC changes with density anomalies traceable southward along the western Atlantic boundary. The authors investigate whether a similar response to the Pinatubo eruption in 1991 could still be ongoing, but do not find strong evidence.

The potential mechanisms involved in the anti-carcinogenic action of probiotics

Probiotic bacteria are live microbial food ingredients that provide a health benefit to the consumer. In the past it was suggested that they served to benefit the host primarily through the prevention of intestinal infections. More recent studies have implicated probiotic bacteria in a number of other beneficial effects within the host including: *The suppression of allergies. *Control of blood cholesterol levels. *Modulation of immune function. *And the prevention of cancers of the colon. The reputed anti-carcinogenic effect of probiotics arises from in vivo studies in both animals and to a limited extent in man; this evidence is supported by in vitro studies with carcinoma cell lines and anti-mutagenicity assays. However, the mechanisms involved in any effect have thus far been difficult to elucidate; studies offer evidence for a variety of mechanisms; we have reviewed these and come to the opinion that, the anti-carcinogenic effect may not be attributable to a single mechanism but rather to a combination of events not yet fully elucidated or understood.

Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture

Growth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.

A comparative study of the main mechanisms controlling indoor air pollution in residential flats

The relative contribution of the main mechanisms that control indoor air quality in residential flats was examined. Indoor and outdoor concentration measurements of different type pollutants (black carbon, SO2, O3, NO, NO2,) were monitored in three naturally ventilated residential flats in Athens, Greece. At each apartment, experiments were conducted during the cold as well as during the warm period of the year. The controlling parameters of transport and deposition mechanisms were calculated from the experimental data. Deposition rates of the same pollutant differ according to the site (different construction characteristics) and to the measuring period for the same site (variations in relative humidity and differences in furnishing). Differences in the black carbon deposition rates were attributed to different black carbon size distributions. The highest deposition rates were observed for O3 in the residential flats with the older construction and the highest humidity levels. The calculated parameters as well as the measured outdoor concentrations were used as input data of a one-compartment indoor air quality model, and the indoor concentrations, the production, and loss rates of the different pollutants were calculated. The model calculated concentrations are in good agreement with the measured values. Model simulations revealed that the mechanism that mainly affected the change rate of indoor black carbon concentrations was the transport from the outdoor environment, while the removal due to deposition was insignificant. During model simulations, it was also established that that the change rate of SO2 concentrations was governed by the interaction between the transport and the deposition mechanisms while NOX concentrations were mainly controlled through photochemical reactions and the transport from outdoors.

Olive leaf phenolics and cardiovascular risk reduction: Physiological effects and mechanisms of action

Olive oil, an important component of the Mediterranean diet, is rich in polyphenols and is known to possess positive health effects relative to other dietary fats. In addition, the leaves of the olive plant (Olea europaea) contain similar phenolics (oleuropein, luteolin-7-glucoside, apigenin-7-glucoside, verbascoside and hydroxytyrosol) to those of olives and olive oil, although at higher concentrations. For example, the most abundant is the secoiridoid, oleuropein, representing 1–14% of olive leaf weight vs. 0.005–0.12% in olive oil. Although currently considered a waste product of the olive oil industry, recent research has suggested beneficial effects of phenolic-rich olive leaf extracts (OLE) in modifying cardiovascular risk biomarkers such as blood pressure, hyperglycaemia, oxidative stress and inflammation, as well as improving vascular function and lipid profiles. Despite this, data regarding the biological actions of OLE has mostly derived from animal, in vitro and ex vivo studies, with limited evidence deriving from human trials. Although the absorption and metabolism of olive oil phenolics has been investigated, less is known about the bioavailability of phenolics from OLE, limiting the interpretation of existing in vitro and ex vivo data. The current review will begin by describing the phenolic composition of olive leaves in comparison with that of the better studied olive oil. It will then review the effects of OLE on cardiovascular risk factors, covering both animal and human studies and will end by considering potential mechanisms of action

Protease-activated receptor 2 sensitizes TRPV1 by protein kinase Cepsilon- and A-dependent mechanisms in rats and mice

Proteases that are released during inflammation and injury cleave protease-activated receptor 2 (PAR2) on primary afferent neurons to cause neurogenic inflammation and hyperalgesia. PAR2-induced thermal hyperalgesia depends on sensitization of transient receptor potential vanilloid receptor 1 (TRPV1), which is gated by capsaicin, protons and noxious heat. However, the signalling mechanisms by which PAR2 sensitizes TRPV1 are not fully characterized. Using immunofluorescence and confocal microscopy, we observed that PAR2 was colocalized with protein kinase (PK) Cepsilon and PKA in a subset of dorsal root ganglia neurons in rats, and that PAR2 agonists promoted translocation of PKCepsilon and PKA catalytic subunits from the cytosol to the plasma membrane of cultured neurons and HEK 293 cells. Subcellular fractionation and Western blotting confirmed this redistribution of kinases, which is indicative of activation. Although PAR2 couples to phospholipase Cbeta, leading to stimulation of PKC, we also observed that PAR2 agonists increased cAMP generation in neurons and HEK 293 cells, which would activate PKA. PAR2 agonists enhanced capsaicin-stimulated increases in [Ca2+]i and whole-cell currents in HEK 293 cells, indicating TRPV1 sensitization. The combined intraplantar injection of non-algesic doses of PAR2 agonist and capsaicin decreased the latency of paw withdrawal to radiant heat in mice, indicative of thermal hyperalgesia. Antagonists of PKCepsilon and PKA prevented sensitization of TRPV1 Ca2+ signals and currents in HEK 293 cells, and suppressed thermal hyperalgesia in mice. Thus, PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. These mechanisms may underlie inflammatory pain, where multiple proteases are generated and released.

New insights into probiotic mechanisms: a harvest from functional and metagenomic studies

There has been continued and expanding recognition of probiotic approaches for treating gastrointestinal and systemic disease, as well as increased acceptance of probiotic therapies by both the public and the medical community. A parallel development has been the increasing recognition of the diverse roles that the normal gut microbiota plays in the normal biology of the host. This advance has in turn has been fed by implementation of novel investigative technologies and conceptual paradigms focused on understanding the fundamental role of the microbiota and indeed all commensal bacteria, on known and previously unsuspected aspects of host physiology in health and disease. This review discusses current advances in the study of the host-microbiota interaction, especially as it relates to potential mechanisms of probiotics. It is hoped these new approaches will allow more rational selection and validation of probiotic usage in a variety of clinical conditions.

Intermittently-visual tracking experiments reveal the roles of error-correction and predictive mechanisms in the human visual-motor control system

Prediction mechanism is necessary for human visual motion to compensate a delay of sensory-motor system. In a previous study, “proactive control” was discussed as one example of predictive function of human beings, in which motion of hands preceded the virtual moving target in visual tracking experiments. To study the roles of the positional-error correction mechanism and the prediction mechanism, we carried out an intermittently-visual tracking experiment where a circular orbit is segmented into the target-visible regions and the target-invisible regions. Main results found in this research were following. A rhythmic component appeared in the tracer velocity when the target velocity was relatively high. The period of the rhythm in the brain obtained from environmental stimuli is shortened more than 10%. The shortening of the period of rhythm in the brain accelerates the hand motion as soon as the visual information is cut-off, and causes the precedence of hand motion to the target motion. Although the precedence of the hand in the blind region is reset by the environmental information when the target enters the visible region, the hand motion precedes the target in average when the predictive mechanism dominates the error-corrective mechanism.

The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

Kinematical analysis of redundant drive wire mechanisms with velocity constraint

In this paper, we propose a new velocity constraint type for Redundant Drive Wire Mechanisms. The purpose of this paper is to demonstrate that the proposed velocity constraint module can fix the orientation of the movable part and to use the kinematical analysis method to obtain the moving direction of the movable part. First, we discuss the necessity of using this velocity constraint type and the possible applications of the proposed mechanism. Second, we derive the basic equations of a wire mechanism with this constraint type. Next, we present a method of motion analysis on active and passive constraint spaces, which is used to find the moving direction of a movable part. Finally, we apply the above analysis method on a wire mechanism with a velocity constraint module and on a wire mechanism with four double actuator modules. By evaluating the results, we prove the validity of the proposed constraint type.

Midlatitude Forcing Mechanisms for Glacier Mass Balance Investigated Using General Circulation Models

A process-oriented modeling approach is applied in order to simulate glacier mass balance for individual glaciers using statistically downscaled general circulation models (GCMs). Glacier-specific seasonal sensitivity characteristics based on a mass balance model of intermediate complexity are used to simulate mass balances of Nigardsbreen (Norway) and Rhonegletscher (Switzerland). Simulations using reanalyses (ECMWF) for the period 1979–93 are in good agreement with in situ mass balance measurements for Nigardsbreen. The method is applied to multicentury integrations of coupled (ECHAM4/OPYC) and mixed-layer (ECHAM4/MLO) GCMs excluding external forcing. A high correlation between decadal variations in the North Atlantic oscillation (NAO) and mass balance of the glaciers is found. The dominant factor for this relationship is the strong impact of winter precipitation associated with the NAO. A high NAO phase means enhanced (reduced) winter precipitation for Nigardsbreen (Rhonegletscher), typically leading to a higher (lower) than normal annual mass balance. This mechanism, entirely due to internal variations in the climate system, can explain observed strong positive mass balances for Nigardsbreen and other maritime Norwegian glaciers within the period 1980–95. It can also partly be responsible for recent strong negative mass balances of Alpine glaciers.

Corporate governance, accountability and mechanisms of accountability: an overview

Purpose – This paper aims to review traditional corporate governance and accountability research, to suggest opportunities for future research in this field. Design/methodology/approach – The first part adopts an analytical frame of reference based on theory, accountability mechanisms, methodology, business sector/context, globalisation and time horizon. The second part of the paper locates the seven papers in the special issue in a framework of analysis showing how each one contributes to the field. The paper presents a frame of reference which may be used as a “roadmap” for researchers to navigate their way through the prior literature and to position their work on the frontiers of corporate governance research. The paper is primarily discursive and conceptual. Findings – The paper encourages broader approaches to corporate governance and accountability research beyond the traditional and primarily quantitative approaches of prior research. Broader theoretical perspectives, methodological approaches, accountability mechanism, sectors/contexts, globalisation, and time horizons are identified. Research limitations/implications – Greater use of qualitative research methods are suggested, which present challenges particularly of access to the “black box” of corporate boardrooms. Originality/value – Drawing on the analytical framework, and the papers in the special issue, the paper identifies opportunities for further research of accountability and corporate governance. Keywords Corporate governance, Management accountability, Research Paper type General review

Exploring business and IT alignment mechanisms: toward a learning perspective

Numerous studies have attempted to develop strategic alignment mechanisms. The strategic alignment mechanism is broken down into two categories namely: strategy process and strategy content. Our review shows that alignment research has been carried out in isolation. We see this as having had the effect of limiting the extent to which executives can understand elements of performance. We confer with a number of researchers in postulating that using a mechanism such as multilevel learning to combine strategy content and strategy process under one metaphor can greatly facilitate, through exploration and exploitation, the understanding not only of human interactions within a firm, but also of the interaction existent between a firm and its environment. The findings in this study further support the idea of integrating strategy process and content to have a better understating of alignment maturity and impact on business performance. It also elaborates the affect of misalignment in companies on performance.

Mechanisms for tropical upwelling in the stratosphere

The dynamics of the tropical upwelling branch of the stratospheric Brewer–Dobson circulation are examined, with a particular focus on the role of the middle-atmosphere Hadley circulation. Upwelling is examined in terms of both the diabatic circulation and Lagrangian trajectories using a zonally symmetric balance model. The behavior of the wave-driven circulation in the presence of angular momentum redistribution by the Hadley circulation is also considered. The results of the zonally symmetric model are compared with fields from a middle-atmosphere GCM. It is found that the Hadley circulation makes a significant contribution to annual mean tropical upwelling at the upwelling maximum in the vicinity of the stratopause, and can account for most of the annual mean upwelling seen in the GCM. In the mid- to lower stratosphere, the role of the Hadley circulation is much weaker and wave drag appears to be required to explain the observed upwelling, although the Hadley circulation makes a nonnegligible contribution to the annual cycle of the upwelling. Subtropical wave drag can produce annual mean upwelling through a nonlinear mechanism; viscosity is not required. However, the magnitude of the observed upwelling suggests that wave drag must penetrate quite close to the equator.