Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids

The influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments: In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. TRAIL-resistant layers form at the interface of proliferating and quiescent cells and lack both TRAILR1 and TRAILR2 protein expression. In contrast, oxygen, and nutrient deprivation promote high amounts of TRAILR2 expression in TRAIL-hypersensitive cells in inner spheroid layers. COX-II inhibitor celecoxib further enhanced TRAILR2 expression in spheroids, likely resulting from increased ER stress, and thereby re-sensitized TRAIL-resistant cell layers to treatment. Our analyses explain how TRAIL response heterogeneities manifest within well-defined multicellular environments, and how spatial barriers of TRAIL resistance can be minimized and eliminated

Evaluation Beyond Usability

The evaluation of research artefacts is an important step to validate research contributions. Sub-disciplines of HCI often pursue primary goals other than usability, such as Sustainable HCI (SHCI), HCI for development, or health and wellbeing. For such disciplines, established evaluation methods are not always appropriate or sufficient, and new conventions for identifying, discussing, and justifying suitable evaluation methods need to be established. In this paper, we revisit the purpose and goals of evaluation in HCI and SHCI, and elicit five key elements that can provide guidance to identifying evaluation methods for SHCI research. Our essay is meant as a starting point for discussing current and improving future evaluation practice in SHCI; we also believe it holds value for other subdisciplines in HCI that encounter similar challenges while evaluating their research

A case study of the D4R laptop

The D4R (Design for recycling, repair, refurbishment and reuse) laptop was developed in conjunction with MicroPro Computers (MPC), a Dublin-based computer manufacturer. MPC formed an industrial network with end-of-life information technology (IT) asset management firms, IT refurbishers, component manufacturers and local industries to produce a new design that has created a new use for their wastes, thus turning waste into resources. This has been made possible through: D4R product design features that facilitate integration of by-product materials and components into the manufacturing process; the creation of an industrial network of suppliers and local assembly agencies permitting industrial metabolism of by-product materials and components into state-of-the-art laptop products; and the creation of a resource exchange platform that increases the visibility of by-products to be incorporated in newly manufactured systems. MPC has been able to successfully manufacture a universal shell composed of a motherboard and a six-cell lithium battery, encapsulated in a wooden housing structure. The shell is capable of accepting new laptop system components and also has the ability to integrate various diverse parts and components, and parts and components of different specifications. The proposed manufacturing model illustrates an entirely novel approach to industrial networking in computer manufacturing for the purpose of eliminating waste and creating valuable by-products