Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

Institutionalization process of service innovation: Overcoming competing institutional logics in service ecosystems

Service science is concerned with the question of how systems can co-create value in an optimal way. In essence, innovations aim at enabling better value co-creation; but at the same time, cause disruption and tensions in the service ecosystem by challenging prevailing practices. This chapter examines the development and diffusion of a broad scale heath care service innovation—the Electronic Prescription system (eRX)—as a process of institutionalization within a service ecosystem. This case represents an innovation process that attempts to solve a major societal challenge, rationalization of medication and reduction of medication errors and abuse. This change requires commitment and adaptation by diverse actors in multiple service systems affected by the eRX, but is nearly disabled by these actors’ competing and even conflicting institutional logics. We examine how diverse stakeholders slowly move towards a convergent institutional logic as the innovation is gradually institutionalized in the broader service ecosystem, and discuss the major challenges along this process. This chapter highlights the dilemma of change in service ecosystems and highlights the role of institutions therein.Post-print / Final draf

Steering for Sustainable Development Goals: A Typology of Sustainable Innovation

Process and product innovation are defined as an organizational ability to discover and translate creative approaches to solve multiple organizational problems. The process and product innovation contribute to the supply of economic, social, and environmental benefits, thus ensuring sustainable environmental growth. It helps companies to achieve greater profits, reduce environmental burden, and use a material that can be more resource-efficient. Process and product innovation have become ubiquitous and part of everyday life. Sustainable process and product innovation are contemplated as an essential means for addressing infrastructure resilience for sustainability challenges. Although the perspective is huge, the governance and capability structure eventually dictate what innovation is likely to be developed.Post-print / Final draf

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC. © 2013 Worm et al.; licensee BioMed Central Ltd

[catalog] Momentum, Maastricht 1985-2002 /

Publ. bij de tentoonstelling Momentum georganiseerd bij het afscheid van mr. Philip Houben als burgemeester van Maastricht (1985-2002)

Function assertive community treatment (FACT) and psychiatric service use in patients diagnosed with severe mental illness

Aim. Previous work suggests that the Dutch variant of assertive community treatment (ACT), known as Function ACT (FACT), may be effective in increasing symptomatic remission rates when replacing a system of hospital-based care and separate community-based facilities. FACT guidelines propose a different pattern of psychiatric service consumption compared to traditional services, which should result in different costing parameters than care as usual (CAU). Methods. South-Limburg FACT patients, identified through the local psychiatric case register, were matched with patients from a non-FACT control region in the North of the Netherlands (NN). Matching was accomplished using propensity scoring including, among others, total and outpatient care consumption. Assessment, as an important ingredient of FACT, was the point of departure of the present analysis. Results. FACT patients, compared to CAU, had five more outpatient contacts after the index date. Cost-effectiveness was difficult to assess. Conclusion. Implementation of FACT results in measurable changes in mental health care use