Blessing or curse? Proteomics in granzyme research

Granzymes (gzms) are a group of serine proteases that play an important role in innate and adaptive immunity, blood coagulation, apoptosis, and inflammation, but are also connected to atherosclerosis, diabetes, cardiovascular and inflammatory lung diseases, cancer, and sepsis. Humans have five gzms (gzms A, B, H, K, and M), which differ in their substrate specificity. It is widely accepted that they are delivered from cytotoxic lymphocytes via perforin into the cytoplasm of target cells where they initiate cell death, modulate cytokine signaling, or inactivate pathogen proteins. However, more recent evidence indicates gzms also act extracellularly in noncytotoxic processes. Proteomic approaches are directed at mapping gzm cleavage specificity, identifying substrates, and unraveling the (patho-) physiological role of these proteases. These studies have refined our understanding of gzm species specificity, and collectively uncovered an enormous number of new substrates. However, with the exception of a very few human gzmB substrates supported by independent data (Bid, DNA-PK, PARP, ICAD, and procaspase 7), it is presently unclear which are physiologically relevant. This review aims to summarize and analyze the different proteomic approaches used and discuss both their convincing and controversial outcomes.     

Involving older people with dementia and their carers in designing computer based support systems: some methodological considerations

Older people with dementia are a particularly challenging user group to involve in the process of designing interactive systems that could assist them. It may also be difficult to involve family caregivers of people with dementia, as they are most likely to be older themselves and uncertain about technology. Paid care staff, whilst younger, may be unclear about the benefits of technology and lack confidence in their ability to incorporate it into their work. Over the past 7 years, the authors of this paper have worked closely with people with dementia, their families and professional care staff to develop and evaluate a multimedia computer system to support communication between people with dementia and caregivers. To achieve this, a number of user involvement issues were addressed, ranging from legal and ethical considerations of working with people with dementia to the reluctance of hard-pressed staff to add to their workload for a research project. In addition, developing and conducting evaluations and eliciting the views of people with dementia who have working memory impairment plus additional cognitive and social difficulties emerged as a central issue. A variety of approaches were explored within this project, which are described in this paper, including familiarizing the whole team with the unique difficulties posed by dementia, continuous confirmation of participants’ consent, and ways to measure enjoyment, engagement, and joint interaction using observation.     

One‐Step Multipurpose Surface Functionalization by Adhesive Catecholamine

Surface modification is one of the most important techniques in modern science and engineering. The facile introduction of a wide variety of desired properties onto virtually any material surface is an ultimate goal in surface chemistry. To achieve this goal, the incorporation of structurally diverse molecules onto any material surface is an essential capability for ideal surface modification. Here, a general strategy for surface modification is presented in which many diverse surfaces can be functionalized by immobilizing a wide variety of molecules. This strategy functionalizes surfaces by a one‐step immersion of substrates in a one‐pot mixture of a molecule and a catecholamine surface modification agent. This one‐step procedure for surface modification represents a standard protocol to control interfacial properties.     

Toward a formalization of affordance modeling for engineering design

When developing an artifact, designers must first capture and represent user needs. These needs can then be transformed into system requirements or objectives. The contribution of this work is rooted in the formalization of the affordance-based approach for capturing user needs in the early stages of design. This formalization comes in three forms: the first affordance basis for engineering design (a defined set of affordances), a formal structure for affordance statements, and a new relational model structure. This formalization is intended to improve model quality and consistency, while managing model creation resources. Further, this affordance-based approach to capturing user needs imposes a level of abstraction that forces solution independence yet is capable of capturing the large range of user needs. As such, the approach provides a structured approach to problem abstraction—the process of specifying user needs without reference to specific solutions. This affordance-based problem representation relies on other design process tools to help develop the actual artifact, which is also discussed.     

Green maintenance for historic masonry buildings: an emerging concept

Maintenance is essential for long-term performance of any building. It enables the simultaneous retention of value in a structure and contributes to a country's gross domestic product. The efficacy of maintenance interventions for historic buildings can be assessed based on cost, conformity to building conservation philosophy and, increasingly, environmental sustainability. Carbon and energy savings in historic buildings are considered difficult to achieve due to limited retrofitting capability. Maintenance is one mechanism by which it may be possible to achieve carbon savings, initiated through necessary proactive and reactive regimes. A model for evaluating the efficacy of maintenance interventions is proposed, utilizing material life cycle data and ‘cradle-to-site’ techniques for embodied CO₂ determination. Additionally, formulaic expressions can be used to calculate the relative merits of any selected maintenance intervention over a given timeframe. Internationally, the model represents a framework for selection of maintenance interventions in relation to cost, philosophy and carbon emissions. The strength of this integrated multi-criteria approach to decision-making is that it enables carbon emissions to be accounted for in the determination of efficacy of masonry repair types.

L'entretien est indispensable pour les performances à long terme de tout bâtiment. Il permet simultanément de conserver ce qui fait la valeur d'une structure et de contribuer au produit intérieur brut d'un pays. L'efficacité des interventions d'entretien sur des bâtiments historiques peut être évaluée en se fondant sur le coût, sur la conformité avec la philosophie de conservation des bâtiments et, de plus en plus, sur la durabilité environnementale. Les économies de carbone et d'énergie dans les bâtiments historiques sont considérées comme difficiles à réaliser en raison de capacités de modernisation limitées. L'entretien est un mécanisme par lequel il peut être possible de réaliser des économies de carbone, initiées en recourant aux régimes proactifs et réactifs nécessaires. Un modèle permettant d'évaluer l'efficacité des interventions d'entretien est proposé, utilisant les données du cycle de vie des matériaux et les techniques dites « du berceau au site » pour déterminer le CO₂ intrinsèque. En outre, des expressions conventionnelles peuvent être utilisées pour calculer les mérites relatifs de toute intervention d'entretien sélectionnée dans un laps de temps donné. Sur le plan international, le modèle représente un cadre permettant de sélectionner les interventions en fonction du coût, de la philosophie et des émissions de carbone. La force de cette approche intégrée multicritère pour la prise de décision tient au fait qu'elle permet la prise en compte des émissions de carbone pour déterminer l'efficacité des types de réparation de maçonneries.

Mots clés: entretien des bâtiments?réduction de carbone?énergie intrinsèque?entretien écologique?longévité?évaluation du cycle de vie?réparation des maçonneries