51 research outputs found
Theoretical development and empirical examination of a three-roles model of responsible leadership
This article develops theory on responsible leadership based on a model involving three leadership roles: an expert who displays organizational expertise, a facilitator who cares for and motivates employees and a citizen who considers the consequences of her or his decisions for society. It draws on previous responsible leadership research, stakeholder theory and theories of behavioral complexity to conceptualize the roles model of responsible leadership. Responsible leadership is positioned as a concept that requires leaders to show behavioral complexity in addressing all three roles. In three studies, we provide a first empirical test of antecedents and outcomes of the roles model of responsible leadership. The results of the studies indicate that responsible leadership is positively related to the leader’s perceived effectiveness, favorable stakeholder evaluations and employee engagement with the organization and society. Responsible leadership behavior, in turn, seems to be facilitated by leader empathy, positive affect and universal value orientation
Integrating life cycle costs and environmental impacts of composite rail car-bodies for a Korean train
Background, aim, and scope: A coupled Life Cycle Costing and life cycle assessment has been performed for car-bodies of the Korean Tilting Train eXpress (TTX) project using European and Korean databases, with the objective of assessing environmental and cost performance to aid materials and process selection. More specifically, the potential of polymer composite car-body structures for the Korean Tilting Train eXpress (TTX) has been investigated. Materials and methods: This assessment includes the cost of both carriage manufacturing and use phases, coupled with the life cycle environmental impacts of all stages from raw material production, through carriage manufacture and use, to end-of-life scenarios. Metallic carriages were compared with two composite options: hybrid steel-composite and full-composite carriages. The total planned production for this regional Korean train was 440 cars, with an annual production volume of 80 cars. Results and discussion: The coupled analyses were used to generate plots of cost versus energy consumption and environmental impacts. The results show that the raw material and manufacturing phase costs are approximately half of the total life cycle costs, whilst their environmental impact is relatively insignificant (3-8%). The use phase of the car-body has the largest environmental impact for all scenarios, with near negligible contributions from the other phases. Since steel rail carriages weigh more (27-51%), the use phase cost is correspondingly higher, resulting in both the greatest environmental impact and the highest life cycle cost. Compared to the steel scenario, the hybrid composite variant has a lower life cycle cost (16%) and a lower environmental impact (26%). Though the full composite rail carriage may have the highest manufacturing cost, it results in the lowest total life cycle costs and lowest environmental impacts. Conclusions and recommendations: This coupled cost and life cycle assessment showed that the full composite variant was the optimum solution. This case study showed that coupling of technical cost models with life cycle assessment offers an efficient route to accurately evaluate economic and environmental performance in a consistent wa
Association of Agricultural, Occupational, and Military Inhalants With Autoantibodies and Disease Sevrity in U.S. Veterans with Rheumatioid Arthritis
A contingency analysis of precarious organizational temporariness
This paper extends our current understanding of organizational temporariness. The life of a temporary British trade union branch established to recruit Eastern European migrant workers reveals ‘precarious temporariness’, which is less predictable than the ‘planned temporariness’ typically portrayed in the literature. This different type of temporariness was associated with four key contingencies affecting the branch: dispersed governance, bottom-up initiatives, uncertain resourcing, and an effectuation logic. Analysis of the case extends our existing understanding of organizational temporariness and points to an extension of existing theorizing by highlighting the contingent nature of temporariness. The broader managerial implication of the findings is that for projects facing contingencies of the kind studied, the conventional linear approach of target setting and performance management will be less effective than an ongoing process of communication and consultation
Post-automation
Tremendous research, policy, and investment is directed towards a new wave of automation in modern societies. Most notable within discourse for the Fourth Industrial Revolution, but also in radical ideas for Fully Automated Luxury Communism, automation appears essential to the future. Advocates claim it will renew capital accumulation, boost labour productivity, and extend managerial control in sustainable systems of production and consumption. Noting criticism about future essentialism in this automation advocacy, this essay will turn to innovations in marginal industrious spaces within industrial societies. Here people are hacking, subverting and appropriating ostensibly automating technologies for purposes of creativity, collaboration, and care. Social capabilities in post-automation are being cultivated. Perhaps greater attention to the politics implied in post-automation can help open our futures to more democratic deliberation
Selective autophagy degrades DICER and AGO2 and regulates miRNA activity.
MicroRNAs (miRNAs) form a class of short RNAs (∼ 21 nucleotides) that post-transcriptionally regulate partially complementary messenger RNAs. Each miRNA may target tens to hundreds of transcripts to control key biological processes. Although the biochemical reactions underpinning miRNA biogenesis and activity are relatively well defined and the importance of their homeostasis is increasingly evident, the processes underlying regulation of the miRNA pathway in vivo are still largely elusive. Autophagy, a degradative process in which cytoplasmic material is targeted into double-membrane vacuoles, is recognized to critically contribute to cellular homeostasis. Here, we show that the miRNA-processing enzyme, DICER (also known as DICER1), and the main miRNA effector, AGO2 (also known as eukaryotic translation initiation factor 2C, 2 (EIF2C2)), are targeted for degradation as miRNA-free entities by the selective autophagy receptor NDP52 (also known as calcium binding and coiled-coil domain 2 (CALCOCO2)). Autophagy establishes a checkpoint required for continued loading of miRNA into AGO2; accordingly, NDP52 and autophagy are required for homeostasis and activity of the tested miRNAs. Autophagy also engages post-transcriptional regulation of the DICER mRNA, underscoring the importance of fine-tuned regulation of the miRNA pathway. These findings have implications for human diseases linked to misregulated autophagy, DICER- and miRNA-levels, including cancer
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
No association of genetic variants in TLR4, TNF-alpha, IL10, IFN-gamma, and IL37 in cytomegalovirus-positive renal allograft recipients with active CMV infection-Subanalysis of the prospective randomised VIPP study
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