Rethinking project reliability using the ambidexterity and mindfulness perspectives

Purpose The purpose of this paper is to bring together two seemingly disparate bodies of literature – ambidexterity (the ability both to exploit and explore) and mindfulness – to take a fresh perspective on the management of uncertainty. The authors differentiate between “rule-based” and “mindfulness-based” reliability and explore project risk responses in environments characterised by varying degrees of uncertainty. Design/methodology/approach Five case organisations across a range of industries are used to illustrate how uncertainty may be prepared for and suitable responses activated. This also adds to the understanding of the nature of ambidexterity, which has previously been characterised primarily at the organisational level with relatively few studies looking at managerial actions and “switches” between modes. The data consist of initial survey responses to indicate the level of mindfulness under conditions of normality, followed by interviews studying particular incidents and the nature of the responses. Findings Key practices are identified that support high reliability in complex projects, with four managerial modes (“Traditional”, “Just-in-time”, “Infusion”, and “Entrepreneurial”) that emerged from the data. Practical implications The findings offer managers a practical framework to choose between different modes of reliable performance by considering the uncertainty of the environment and whether the primary driver of the work is efficiency or effectiveness. This allows managers to reflect on their own organisations and practices and identify whether their current approach is suitable. Originality/value This work offers new insight into risk responses in complex environments and shows how the mindfulness and ambidexterity literatures may be used as beneficial lenses to increase understanding. Blending these two schools also offers opportunities for future research

J Biol Chem

Collagen XXIII is a member of the transmembranous subfamily of collagens containing a cytoplasmic domain, a membrane-spanning hydrophobic domain, and three extracellular triple helical collagenous domains interspersed with non-collagenous domains. We cloned mouse, chicken, and human{alpha}1(XXIII) collagen cDNAs and showed that this non-abundant collagen has a limited tissue distribution in non-tumor tissues. Lung, cornea, brain, skin, tendon, and kidney are the major sites of expression. In contrast, five transformed cell lines were tested for collagen XXIII expression, and all expressed the mRNA. In vivo the {alpha}1(XXIII) mRNA is found in mature and developing organs, the latter demonstrated using stages of embryonic chick cornea and mouse embryos. Polyclonal antibodies were generated in guinea pig and rabbit and showed that collagen XXIII has a transmembranous form and a shed form. Comparison of collagen XXIII with its closest relatives in the transmembranous subfamily of collagens, types XIII and XXV, which have the same number of triple helical and non-collagenous regions, showed that there is a discontinuity in the alignment of domains but that striking similarities remain despite this

The charcoal trap: Miombo forests and the energy needs of people

<p>Abstract</p> <p>Background</p> <p>This study evaluates the carbon dioxide and other greenhouse gas fluxes to the atmosphere resulting from charcoal production in Zambia. It combines new biomass and flux data from a study, that was conducted in a <it>miombo </it>woodland within the Kataba Forest Reserve in the Western Province of Zambia, with data from other studies.</p> <p>Results</p> <p>The measurements at Kataba compared protected area (3 plots) with a highly disturbed plot outside the forest reserve and showed considerably reduced biomass after logging for charcoal production. The average aboveground biomass content of the reserve (Plots 2-4) was around 150 t ha^-1, while the disturbed plot only contained 24 t ha^-1. Soil carbon was not reduced significantly in the disturbed plot. Two years of eddy covariance measurements resulted in net ecosystem exchange values of -17 ± 31 g C m^-2y^-1, in the first and 90 ± 16 g C m^-2in the second year. Thus, on the basis of these two years of measurement, there is no evidence that the <it>miombo </it>woodland at Kataba represents a present-day carbon sink. At the country level, it is likely that deforestation for charcoal production currently leads to a per capita emission rate of 2 - 3 t CO₂y^-1. This is due to poor forest regeneration, although the resilience of <it>miombo </it>woodlands is high. Better post-harvest management could change this situation.</p> <p>Conclusions</p> <p>We argue that protection of <it>miombo </it>woodlands has to account for the energy demands of the population. The production at national scale that we estimated converts into 10,000 - 15,000 GWh y^-1of energy in the charcoal. The term "Charcoal Trap" we introduce, describes the fact that this energy supply has to be substituted when woodlands are protected. One possible solution, a shift in energy supply from charcoal to electricity, would reduce the pressure of forests but requires high investments into grid and power generation. Since Zambia currently cannot generate this money by itself, the country will remain locked in the charcoal trap such as many other of its African neighbours. The question arises whether and how money and technology transfer to increase regenerative electrical power generation should become part of a post-Kyoto process. Furthermore, better inventory data are urgently required to improve knowledge about the current state of the woodland usage and recovery. Net greenhouse gas emissions could be reduced substantially by improving the post-harvest management, charcoal production technology and/or providing alternative energy supply.</p

Refined high-content imaging-based phenotypic drug screening in zebrafish xenografts

Zebrafish xenotransplantation models are increasingly applied for phenotypic drug screening to identify small compounds for precision oncology. Larval zebrafish xenografts offer the opportunity to perform drug screens at high-throughput in a complex in vivo environment. However, the full potential of the larval zebrafish xenograft model has not yet been realized and several steps of the drug screening workflow still await automation to increase throughput. Here, we present a robust workflow for drug screening in zebrafish xenografts using high-content imaging. We established embedding methods for high-content imaging of xenografts in 96-well format over consecutive days. In addition, we provide strategies for automated imaging and analysis of zebrafish xenografts including automated tumor cell detection and tumor size analysis over time. We also compared commonly used injection sites and cell labeling dyes and show specific site requirements for tumor cells from different entities. We demonstrate that our setup allows us to investigate proliferation and response to small compounds in several zebrafish xenografts ranging from pediatric sarcomas and neuroblastoma to glioblastoma and leukemia. This fast and cost-efficient assay enables the quantification of anti-tumor efficacy of small compounds in large cohorts of a vertebrate model system in vivo. Our assay may aid in prioritizing compounds or compound combinations for further preclinical and clinical investigations

Towards a standardized processing of net ecosystem exchange measured with eddy covariance technique : algorithms and uncertainly estimation

Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements.Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements.Eddy covariance technique to measure CO2, water and energy fluxes between biosphere and atmosphere is widely spread and used in various regional networks. Currently more than 250 eddy covariance sites are active around the world measuring carbon exchange at high temporal resolution for different biomes and climatic conditions. In this paper a new standardized set of corrections is introduced and the uncertainties associated with these corrections are assessed for eight different forest sites in Europe with a total of 12 yearly datasets. The uncertainties introduced on the two components GPP (Gross Primary Production) and TER (Terrestrial Ecosystem Respiration) are also discussed and a quantitative analysis presented. Through a factorial analysis we find that generally, uncertainties by different corrections are additive without interactions and that the heuristic u(*)-correction introduces the largest uncertainty. The results show that a standardized data processing is needed for an effective comparison across biomes and for underpinning interannual variability. The methodology presented in this paper has also been integrated in the European database of the eddy covariance measurements.Peer reviewe

Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1

Combination antiretroviral therapy (cART) can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704) which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2). 57704 also increased HIV-1 expression in 3 of 4 CD8+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110a isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency. © 2014 Doyon et al

Complexity in water and carbon dioxide fluxes following rain pulses in an African savanna

The idea that many processes in arid and semi-arid ecosystems are dormant until activated by a pulse of rainfall, and then decay from a maximum rate as the soil dries, is widely used as a conceptual and mathematical model, but has rarely been evaluated with data. This paper examines soil water, evapotranspiration (ET), and net ecosystem CO2 exchange measured for 5 years at an eddy covariance tower sited in an Acacia–Combretum savanna near Skukuza in the Kruger National Park, South Africa. The analysis characterizes ecosystem flux responses to discrete rain events and evaluates the skill of increasingly complex “pulse models”. Rainfall pulses exert strong control over ecosystem-scale water and CO2 fluxes at this site, but the simplest pulse models do a poor job of characterizing the dynamics of the response. Successful models need to include the time lag between the wetting event and the process peak, which differ for evaporation, photosynthesis and respiration. Adding further complexity, the time lag depends on the prior duration and degree of water stress. ET response is well characterized by a linear function of potential ET and a logistic function of profile-total soil water content, with remaining seasonal variation correlating with vegetation phenological dynamics (leaf area). A 1- to 3-day lag to maximal ET following wetting is a source of hysteresis in the ET response to soil water. Respiration responds to wetting within days, while photosynthesis takes a week or longer to reach its peak if the rainfall was preceded by a long dry spell. Both processes exhibit nonlinear functional responses that vary seasonally. We conclude that a more mechanistic approach than simple pulse modeling is needed to represent daily ecosystem C processes in semiarid savannas

T-Cell Immune Dysregulation and Mortality in Women with Human Immunodeficiency Virus

Summary: In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Background: Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Methods: Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. Results: At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Conclusions: Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression