Developing Absorptive Capacity Theory for Public Service Organizations:Emerging UK Empirical Evidence

A strong public policy focus on high performance means that utilizing management knowledge effectively is at a premium for UK public service organizations. This study empirically examined two English public agencies to explore the inter-sectoral transfer of a strategic management model originally developed in the private sector – absorptive capacity – which is one way of conceptualizing an organizational competence in such knowledge mobilization. Two theoretical contributions are made. First, a new absorptive capacity framework for public service organizations is developed which recognizes the participation of public agency project teams during an innovation process proceeding over time with phases of co-creation, testing, metamorphosis and diffusion. Second, our novel framework modifies an early influential model of absorptive capacity. Counter to this model, we argue that realized absorptive capacity requires agency from skilled and embedded actors to turn ‘curbing routines’ into ‘enabling routines’ in all four stages. Project (middle) managers have flexibility in their roles to seize episodic moments of opportunity to innovate and achieve service delivery goals, and to build absorptive capacity capability. Absorptive capacity capability develops organically over time. Future research directions are discussed

Punctuated equilibrium theory in Brazilian public policy: the case of Ceará

Este artigo faz uma análise do processo de decisão orçamental dos municípios do Estado do Ceará. Através deste estudo, procura-se perceber em que medida a distribuição dos orçamentos aos governos locais sofrem (ou não) variações. Já em um segundo momento, tenta-se depreender quais as receitas de cada um dos municípios (as variáveis independentes) que melhor descrevem e auxiliam a opção política de investimento local (esta será a variável dependente). Considerando o período de 2006 a 2010 e fazendo uso de um desenho de pesquisa de tipo transversal, conclui-se que nos governos locais do Ceará o investimento público apresenta períodos de estabilidade seguido por períodos de grande alteração dos orçamentos – confirmando a hipótese de pesquisa. Estas conclusões confirmam os pressupostos da teoria do equilíbrio pontuado. Conclui-se igualmente que o investimento público que vem sendo realizado é dependente das transferências que a União faz para os governos locais do Estado do Ceará e das receitas de capital. Face a estas condições, é pertinente equacionar até que nível e grau o endividamento pode ocorrer em virtude da escassez cada vez maior do financiamento público.This research aims to analyze the budget decision process in Ceará municipalities in order to understand in which way budget distributions change (or not) during the research period under consideration. This research also aims to understand which revenues (the independent variables) of each municipality better expla in the political choices for local government investments (the dependent variable). Making use of data from 2006 to 2010 and using a cross - sectional research design, the study concludes a stability in local government investments periods of stress where su ch investments have both positive and negative significant fluctuations – confirming our working hypothesis. These results confirm punctuated Equilibrium Theory assumptions and also find that local government public investment is dependent on money transfe rs from the central government and also from capital revenues. Thus, it is important to question to what degree public indebtedness should be allowed, due to a scarcity of public fundsinfo:eu-repo/semantics/publishedVersio

The Role of EZH2 in the Regulation of the Activity of Matrix Metalloproteinases in Prostate Cancer Cells

Degradation of the extracellular matrix (ECM), a critical step in cancer metastasis, is determined by the balance between MMPs (matrix metalloproteinases) and their inhibitors TIMPs (tissue inhibitors of metalloproteinases). In cancer cells, this balance is shifted towards MMPs, promoting ECM degradation. Here, we show that EZH2 plays an active role in this process by repressing the expression of TIMP2 and TIMP3 in prostate cancer cells. The TIMP genes are derepressed by knockdown of EZH2 expression in human prostate cancer cells but repressed by overexpression of EZH2 in benign human prostate epithelial cells. EZH2 catalyzes H3K27 trimethylation and subsequent DNA methylation of the TIMP gene promoters. Overexpression of EZH2 confers an invasive phenotype on benign prostate epithelial cells; however, this phenotype is suppressed by cooverexpression of TIMP3. EZH2 knockdown markedly reduces the proteolytic activity of MMP-9, thereby decreasing the invasive activity of prostate cancer cells. These results suggest that the transcriptional repression of the TIMP genes by EZH2 may be a major mechanism to shift the MMPs/TIMPs balance in favor of MMP activity and thus to promote ECM degradation and subsequent invasion of prostate cancer cells

Information Routing Driven by Background Chatter in a Signaling Network

Living systems are capable of processing multiple sources of information simultaneously. This is true even at the cellular level, where not only coexisting signals stimulate the cell, but also the presence of fluctuating conditions is significant. When information is received by a cell signaling network via one specific input, the existence of other stimuli can provide a background activity –or chatter– that may affect signal transmission through the network and, therefore, the response of the cell. Here we study the modulation of information processing by chatter in the signaling network of a human cell, specifically, in a Boolean model of the signal transduction network of a fibroblast. We observe that the level of external chatter shapes the response of the system to information carrying signals in a nontrivial manner, modulates the activity levels of the network outputs, and effectively determines the paths of information flow. Our results show that the interactions and node dynamics, far from being random, confer versatility to the signaling network and allow transitions between different information-processing scenarios

Osteopontin Impairs Host Defense during Established Gram-Negative Sepsis Caused by Burkholderia pseudomallei (Melioidosis)

Melioidosis is a severe tropical disease caused by infection with the bacterium Burkholderia (B.) pseudomallei. In northeast Thailand infection with this bacterium is the major cause of community-acquired septicemia with a mortality rate up to 40%. Extending the knowledge on the mechanisms of host defense against B. pseudomallei infection would be helpful to improve treatment of this severe illness. Osteopontin (OPN) is a cytokine that is involved in several immune responses that occur during bacterial infection. In this study, we investigated levels of OPN in patients with melioidosis, and studied the function of OPN during experimental melioidosis in mice. We found that OPN concentrations were elevated in patients with severe melioidosis, and that high OPN concentrations are associated with poor outcome in patients with melioidosis. In experimental melioidosis in mice plasma and lung OPN levels were also increased. Moreover, mice with melioidosis that were deficient for OPN demonstrated reduced bacterial numbers in their lungs, diminished pulmonary tissue injury, and decreased neutrophil infiltration into the lungs during established melioidosis. Moreover, these mice displayed a delayed mortality as compared to control mice. In conclusion, sustained production of OPN impairs host defense during melioidosis

Computational Models of the Notch Network Elucidate Mechanisms of Context-dependent Signaling

The Notch signaling pathway controls numerous cell fate decisions during development and adulthood through diverse mechanisms. Thus, whereas it functions as an oscillator during somitogenesis, it can mediate an all-or-none cell fate switch to influence pattern formation in various tissues during development. Furthermore, while in some contexts continuous Notch signaling is required, in others a transient Notch signal is sufficient to influence cell fate decisions. However, the signaling mechanisms that underlie these diverse behaviors in different cellular contexts have not been understood. Notch1 along with two downstream transcription factors hes1 and RBP-Jk forms an intricate network of positive and negative feedback loops, and we have implemented a systems biology approach to computationally study this gene regulation network. Our results indicate that the system exhibits bistability and is capable of switching states at a critical level of Notch signaling initiated by its ligand Delta in a particular range of parameter values. In this mode, transient activation of Delta is also capable of inducing prolonged high expression of Hes1, mimicking the “ON” state depending on the intensity and duration of the signal. Furthermore, this system is highly sensitive to certain model parameters and can transition from functioning as a bistable switch to an oscillator by tuning a single parameter value. This parameter, the transcriptional repression constant of hes1, can thus qualitatively govern the behavior of the signaling network. In addition, we find that the system is able to dampen and reduce the effects of biological noise that arise from stochastic effects in gene expression for systems that respond quickly to Notch signaling