Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing

The advance of rapid prototyping techniques has significantly improved control over the pore network architecture of tissue engineering scaffolds. In this work we assessed the influence of scaffold pore architecture on cell seeding and static culturing, by comparing a computer‐designed gyroid architecture fabricated by stereolithography to a random‐pore architecture resulting from salt‐leaching. The scaffold types showed comparable porosity and pore size values, but the gyroid type showed a more than tenfold higher permeability due to the absence of size‐limiting pore interconnections. The higher permeability significantly improved the wetting properties of the hydrophobic scaffolds, and increased the settling speed of cells upon static seeding of immortalised mesenchymal stem cells. After dynamic seeding followed by 5 days of static culture, gyroid scaffolds showed large cell populations in the centre of the scaffold, while salt‐leached scaffolds were covered with a cell‐sheet on the outside and no cells were found in the scaffold centre. It was shown that interconnectivity of the pores and permeability of the scaffold prolongs the time of static culture before overgrowth of cells at the scaffold periphery occurs. Furthermore, novel scaffold designs are proposed to further improve the transport of oxygen and nutrients throughout the scaffolds, and to create tissue engineering grafts with designed, pre‐fabricated vasculature.

Apoptosis is induced in Chlamydia trachomatis infected HEp-2 cells by the addition of a combination innate immune activation compounds and the inhibitor wedelolactone

Problem: Innate immune activation of human cells, for some intracellular pathogens, is advantageous for vacuole morphology and pathogenic viability. It is unknown whether innate immune activation is advantageous to Chlamydia trachomatis viability. ----- ----- Method of study: Innate immune activation of HEp-2 cells during Chlamydia infection was conducted using lipopolysaccharide (LPS), polyI:C, and wedelolactone (innate immune inhibitor) to investigate the impact of these conditions on viability of Chlamydia. ----- ----- Results: The addition of LPS and polyI:C to stimulate activation of the two distinct innate immune pathways (nuclear factor kappa beta and interferon regulatory factor) had no impact on the viability of Chlamydia. However, when compounds targeting either pathway were added in combination with the specific innate immune inhibitor (wedelolactone) a major impact on Chlamydia viability was observed. This impact was found to be due to the induction of apoptosis of the HEp-2 cells under these conditions. ----- ----- Conclusion: This is the first time that induction of apoptosis has been reported in C. trachomatis-infected cells when treated with a combination of innate immune activators and wedelolactone.

State convergence and the effectiveness of time-memory-data tradeoffs

Various time-memory tradeoffs attacks for stream ciphers have been proposed over the years. However, the claimed success of these attacks assumes the initialisation process of the stream cipher is one-to-one. Some stream cipher proposals do not have a one-to-one initialisation process. In this paper, we examine the impact of this on the success of time-memory-data tradeoff attacks. Under the circumstances, some attacks are more successful than previously claimed while others are less. The conditions for both cases are established.

Provotypes for participatory innovation

Central to multi-stakeholder processes of participatory innovation is to generate knowledge about ‘users’ and to identify business opportunities accordingly. In these processes of collaborative analysis and synthesis, conflicting perceptions within and about a field of interest are likely to surface. Instead of the natural tendency to avoid these tensions, we demonstrate how tensions can be utilized by embodying them in provocative types (provotypes). Provotypes expose and embody tensions that surround a field of interest to support collaborative analysis and collaborative design explorations across stakeholders. In this paper we map how provotyping contributes to four related areas of contemporary Interaction Design practice. Through a case study that brings together stakeholders from the field of indoor climate, we provide characteristics of design provocations and design guidelines for provotypes for participatory innovation.

The cell surface glycoprotein CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor-mediated cell migration

Epidermal growth factor (EGF) activation of the EGF receptor (EGFR) is an important mediator of cell migration, and aberrant signaling via this system promotes a number of malignancies including ovarian cancer. We have identified the cell surface glycoprotein CDCP1 as a key regulator of EGF/EGFR-induced cell migration. We show that signaling via EGF/EGFR induces migration of ovarian cancer Caov3 and OVCA420 cells with concomitant up-regulation of CDCP1 mRNA and protein. Consistent with a role in cell migration CDCP1 relocates from cell-cell junctions to punctate structures on filopodia after activation of EGFR. Significantly, disruption of CDCP1 either by silencing or the use of a function blocking antibody efficiently reduces EGF/EGFR-induced cell migration of Caov3 and OVCA420 cells. We also show that up-regulation of CDCP1 is inhibited by pharmacological agents blocking ERK but not Src signaling, indicating that the RAS/RAF/MEK/ERK pathway is required downstream of EGF/EGFR to induce increased expression of CDCP1. Our immunohistochemical analysis of benign, primary, and metastatic serous epithelial ovarian tumors demonstrates that CDCP1 is expressed during progression of this cancer. These data highlight a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling including those resistant to anti-EGFR drugs because of activating mutations in the RAS/RAF/MEK/ERK pathway.

Materialities influencing the design process

The use of material artefacts within the design process is a long-standing and continuing characteristic of interaction design. Established methods, such as prototyping, which have been widely adopted by educators and practitioners, are seeing renewed research interest and being reconsidered in light of the evolving needs of the field. Alongside this, the past decade has seen the introduction and adoption of a diverse range of novel design methods into interaction design, such as cultural probes, technology probes, context mapping, and provotypes.

Challenging industry conceptions with provotypes

Design researchers have an important role to play when engaged with user-driven design projects in industry. Design researchers can craft ethnographic material to facilitate transfers of user-knowledge to industry, and demonstrate how this material can be used in the design of new products and services. However, ethnographic findings can reveal issues that are in tension with conceptions of the project members from industry. Instead of brushing these tensions aside, we propose provotyping (provocative prototyping) as an approach to constructively build on them as a resource for change. Provotypes are ethnographically rooted, technically working, robust artefacts that deliberately challenge stakeholder conceptions by reifying and exposing tensions that surround a field of organisational interest. The daily and local experience of provotypes aims to stir dialectical processes of reflection on how conceptions currently are, and fuel the front end of a development process by speculating how conceptions could be different. In this article we start by making explicit the relation between provotypes, practices of critical design and organisational sense-making. We then illustrate, through a multi-stakeholder project concerning the field of indoor climate, how provotypes facilitate transfers of user knowledge to industry, and how they contribute to the development of new products and services. We end by framing the role of the design researcher and discuss the politics that are inherent to design provocations.

Role of resting metabolic rate and energy expenditure in hunger and appetite control : a new formulation

A long-running issue in appetite research concerns the influence of energy expenditure on energy intake. More than 50 years ago, Otto G. Edholm proposed that "the differences between the intakes of food [of individuals] must originate in differences in the expenditure of energy". However, a relationship between energy expenditure and energy intake within any one day could not be found, although there was a correlation over 2 weeks. This issue was never resolved before interest in integrative biology was replaced by molecular biochemistry. Using a psychobiological approach, we have studied appetite control in an energy balance framework using a multi-level experimental system on a single cohort of overweight and obese human subjects. This has disclosed relationships between variables in the domains of body composition [fat-free mass (FFM), fat mass (FM)], metabolism, gastrointestinal hormones, hunger and energy intake. In this Commentary, we review our own and other data, and discuss a new formulation whereby appetite control and energy intake are regulated by energy expenditure. Specifically, we propose that FFM (the largest contributor to resting metabolic rate), but not body mass index or FM, is closely associated with self-determined meal size and daily energy intake. This formulation has implications for understanding weight regulation and the management of obesity.