The introduction of IMO, an integrated model for designing for open-­ended play

Designing for open-ended play poses specific new challenges to designers. Designing for closed games includes defining rules and goals to balanced the game properly. A design for open-ended play has no predefined rules and goals. The design needs to provide users with more freedom to continually change goals and rules of play, which distinguishes the field from designs of closed games. Gaining knowledge on the design process of creating this freedom is essential. For this purpose, an integrated model for open-ended play is proposed. This model is based on a combination of two existing models: Hunicke’s Mechanics Dynamics and Aesthetics (MDA) model and Grünvogel’s formal models for game design. Both of the above mentioned existing models are generalized to make them applicable for analyzing open-ended play. In the proposed combined model we distinguish between the perspectives of the design, and the perspective of play. It addresses how to handle changing rules and goals, instead of the assumptions that rules and goals do not change. Furthermore, the model was used to improve our understanding on progression and emergence, two key concepts that are commonly used in game design. The integrated model for open-ended play (IMO) was used in a preliminary case study with a digital play application, an interactive environment for open-ended play named the GlowSteps, to evaluate the model and to underline our insights on emergence and progression.Designing for open-ended play poses specific new challenges to designers. Designing for closed games includes defining rules and goals to balanced the game properly. A design for open-ended play has no predefined rules and goals. The design needs to provide users with more freedom to continually change goals and rules of play, which distinguishes the field from designs of closed games. Gaining knowledge on the design process of creating this freedom is essential. For this purpose, an integrated model for open-ended play is proposed. This model is based on a combination of two existing models: Hunicke’s Mechanics Dynamics and Aesthetics (MDA) model and Grünvogel’s formal models for game design. Both of the above mentioned existing models are generalized to make them applicable for analyzing open-ended play. In the proposed combined model we distinguish between the perspectives of the design, and the perspective of play. It addresses how to handle changing rules and goals, instead of the assumptions that rules and goals do not change. Furthermore, the model was used to improve our understanding on progression and emergence, two key concepts that are commonly used in game design. The integrated model for open-ended play (IMO) was used in a preliminary case study with a digital play application, an interactive environment for open-ended play named the GlowSteps, to evaluate the model and to underline our insights on emergence and progression

Hoogveenherstel in Nederland: meer dan een droom

Vernatten, de belangrijkste herstelmaatregel in hoogveenrestanten, heeft niet altijd het gewenste effect. Waarom dat zo is, is grotendeels nog onbekend. De auteurs beargumenteren dat recente inzichten uit empirische en experimentele studies in hoogveenherstelprojecten moeten worden gebruikt om de bestaande theoretische modellen uit te breiden, om deze vervolgens te kunnen gebruiken in het ontwikkelen van effectieve, gebiedspecifieke herstelplannen. Hierdoor kan de droom van zelfregulerende hoogvenen in Nederland wellicht op niet al te lange termijn werkelijkheid worden

The occurrence of Β-carbolines in man and rat, putative biochemical substrates responsible for psychosis

Many research groups have been putting effort in finding biochemical aberrations related to the etiology of psychoses, as discussed in Chapter I (Gillin, 1978; Smythies, 1982; Bruinvels and Peppinkhuizen, 1984). It has been suggested that excessive activity of methylation processes could result in the formation of abnormally methylated biogenic amines with hallucinogenic or even "psychotogenic" properties (Osmond and Smythies, 1952). Until now, these compounds have not been found in significant amounts, although some enzymatic abnormalities are present in different subgroups (Chapter I). In 1980 Pepplinkhuizen et al. published on a group of acute psychotic patients of the manicpsychedelic type, who showed a disturbance in serine- and glycine metabolism. These findings were used as a starting-point for this thesis. As described in Chapter I, an animal model was developed, based on an enhanced conversion of serine into glycine, in order to study the putative formation of beta-carbolines. The presence of these compounds was correlated with behavioural disturbances in these animals. Moreover, beta-carbolines were measured in plasma, prepared from blood from episodic psychotic patients. In the following paragraph, results from these studies are discussed

Grondprijskaarten 1998-2008

Dit rapport is onderdeel van het project ‘Actualisatie Grondprijs- en Eigendomskaart’. Het geeft grondprijskaarten voor de jaren 1998, 2000, 2002, 2004, 2006 en 2008 weer. Daarnaast geeft het rapport inzicht in de grondmobiliteit (per grondmarktsegment) alsmede in de lange termijnontwikkeling van de grondprijs

Pro-inflammatory cytokines in cryptoglandular anal fistulas

Background: Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1β and tumor necrosis factor α (TNF-α). Methods: Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistul

A non-canonical NRPS is involved in the synthesis of fungisporin and related hydrophobic cyclic tetrapeptides in Penicillium chrysogenum.

The filamentous fungus Penicillium chrysogenum harbors an astonishing variety of nonribosomal peptide synthetase genes, which encode proteins known to produce complex bioactive metabolites from simple building blocks. Here we report a novel non-canonical tetra-modular nonribosomal peptide synthetase (NRPS) with microheterogenicity of all involved adenylation domains towards their respective substrates. By deleting the putative gene in combination with comparative metabolite profiling various unique cyclic and derived linear tetrapeptides were identified which were associated with this NRPS, including fungisporin. In combination with substrate predictions for each module, we propose a mechanism for a 'trans-acting' adenylation domain

Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation.

BACKGROUND Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development. METHODS To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53(lox/lox)/FAK(+/+)/WapCre, p53(lox/lox)/FAK(flox/+)/WapCre and p53(lox/lox)/FAK(flox/-)/WapCre mice, and mice with WapCre-mediated conditional expression of p53(R270H), the mouse equivalent of human p53(R273H) hot spot mutation, together with conditional deletion of FAK, P53(R270H/+)/FAK(lox/+)/WapCre and p53(R270H/+)/FAK(flox/-)/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours. RESULTS Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53(R270H)-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures. CONCLUSIONS Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion kinase deletion reduced proliferative capacity of p53 null and p53(R270H) mammary epithelial cells but did not lead to increased apoptosis in vivo. Our data identify FAK as an important regulator in mammary epithelial cell proliferation in p53-mediated and p53(R270H)-induced mammary tumour development