Cell cycle regulation of a Xenopus Wee1-like kinase

Using a polymerase chain reaction-based strategy, we have isolated a gene encoding a Wee1-like kinase from Xenopus eggs. The recombinant Xenopus Wee1 protein efficiently phosphorylates Cdc2 exclusively on Tyr- 15 in a cyclin-dependent manner. The addition of exogenous Wee1 protein to Xenopus cell cycle extracts results in a dose-dependent delay of mitotic initiation that is accompanied by enhanced tyrosine phosphorylation of Cdc2. The activity of the Wee1 protein is highly regulated during the cell cycle: the interphase, underphosphorylated form of Wee1 (68 kDa) phosphorylates Cdc2 very efficiently, whereas the mitotic, hyperphosphorylated version (75 kDa) is weakly active as a Cdc2-specific tyrosine kinase. The down-modulation of Wee1 at mitosis is directly attributable to phosphorylation, since dephosphorylation with protein phosphatase 2A restores its kinase activity. During interphase, the activity of this Wee1 homolog does not vary in response to the presence of unreplicated DNA. The mitosis-specific phosphorylation of Wee1 is due to at least two distinct kinases: the Cdc2 protein and another activity (kinase X) that may correspond to an MPM-2 epitope kinase. These studies indicate that the down-regulation of Wee1-like kinase activity at mitosis is a multistep process that occurs after other biochemical reactions have signaled the successful completion of S phase

Usable, secure and deployable graphical passwords

PhD ThesisEvaluations of the usability and security of alphanumeric passwords and Personal Identification Numbers (PINs) have shown that users cannot remember credentials considered to be secure. However, the continued reliance upon these methods of user authentication has placed end-users and system designers in a coevolutionary struggle, with each defending competing concerns of usability and security. Graphical passwords have been proposed as an alternative, and their use is supported by cognitive theories such as the picture superiority effect which suggest that pictures, rather than words or numbers, could provide a stronger foundation upon which to design usable and secure knowledge-based authentication. Indeed, early usability studies of novel systems harnessing this effect appear to show promise, however, the uptake of graphical passwords in real-world systems is low. This inertia is likely related to uncertainty regarding the challenges that novel systems might bring to the already delicate interplay between usability and security; particularly the new challenges faced in scaffolding user behaviours that comply with context-specific security policies, uncertainty regarding the nature of new socio-technical attacks, and the impact of images themselves upon usability and security. In this thesis we present a number of case studies incorporating new designs, empirical methods and results, that begin to explore these aspects of representative graphical password systems. Specifically, we explore: (i) how we can implicitly support security-focused behaviours such as choosing high entropy graphical passwords and defending against observation attack; (ii) how to capture the likely extent of insecure behaviour in the social domain such as graphical password sharing and observation attack; and (iii) how through the selection of appropriate properties of the images themselves we can provide security and usability benefits. In doing so, we gen- erate new insights into the potential of graphical passwords to provide usable, secure and deployable user authentication.Microsoft Research

BallotShare:an exploration of the design space for digital voting in the workplace

Digital voting is used to support group decision-making in a variety of contexts ranging from politics to mundane everyday collaboration, and the rise in popularity of digital voting has provided an opportunity to re-envision voting as a social tool that better serves democracy. A key design goal for any group decision-making system is the promotion of participation, yet there is little research that explores how the features of digital voting systems themselves can be shaped to configure participation appropriately. In this paper we propose a framework that explores the design space of digital voting from the perspective of participation. We ground our discussion in the design of a social media polling tool called BallotShare; a first instantiation of our proposed framework designed to facilitate the study of decision-making practices in a workplace environment. Across five weeks, participants created and took part in non-standard polls relating to events and other spontaneous group decisions. Following interviews with participants we identified significant drivers and limitations of individual and collective participation in the voting process: social visibility, social inclusion, commitment and delegation, accountability, influence and privacy

Invisible design: exploring insights and ideas through ambiguous film scenarios

Invisible Design is a technique for generating insights and ideas with workshop participants in the early stages of concept development. It involves the creation of ambiguous films in which characters discuss a technology that is not directly shown. The technique builds on previous work in HCI on scenarios, persona, theatre, film and ambiguity. The Invisible Design approach is illustrated with three examples from unrelated projects; Biometric Daemon, Panini and Smart Money. The paper presents a qualitative analysis of data from a series of workshops where these Invisible Designs were discussed. The analysis outlines responses to the films in terms of; existing problems, concerns with imagined technologies and design speculation. It is argued that Invisible Design can help to create a space for critical and creative dialogue during participatory concept development

Citizen or consumer? Reconsidering energy citizenship

The transition to more sustainable energy systems has set about redefining the social roles and responsibilities of citizens. Implicit in this are expectations around participation, though the precise contours of what this might mean remain open. Debates around the energy transition have been skewed towards a normative construct of what it means to be a ‘good citizen’, the parameters for which are shaped by predetermined visions of statist and/or market-driven determinations of the energy systems of the future. This article argues that concepts such as ‘energy citizen’ are co-opted to reflect popular neoliberal discourses, and ignore crucial questions of unequal agency and access to resources. Paradoxically, official discourses that push responsibility for the energy transition onto the ‘citizen-as-consumer’ effectively remove agency from citizens, leaving them largely disconnected and disempowered. Consequently, energy citizenship needs to be reconceptualised to incorporate more collective and inclusive contexts for action. Considering how much energy consumption occurs in (traditionally female) domestic spheres, do conventional notions of citizenship (especially with regards to its associated rights and duties) need to be recalibrated in order for the concept to be usefully applied to the energy transition

The Arf6 GEF GEP100/BRAG2 Regulates Cell Adhesion by Controlling Endocytosis of β1 Integrins

SummaryThe small GTPase Arf6 has been shown to regulate the post-endocytic trafficking of a subset of membrane proteins, including β1 integrins, and inhibition of Arf6 function impairs both cell adhesion and motility [1]. The activity of Arf GTPases is regulated by a large family of guanine nucleotide exchange factors (GEFs) [2]. Arf-GEP100/BRAG2 is a GEF with reported specificity for Arf6 in vitro [3], but it is otherwise poorly characterized. Here we report that BRAG2 exists in two ubiquitously expressed isoforms, which we call BRAG2a and BRAG2b, both of which can activate Arf6 in vivo. Depletion of endogenous BRAG2 by siRNA leads to dramatic effects in the cell periphery; one such effect is an accumulation of β1 integrin on the cell surface and a corresponding enhancement of cell attachment and spreading on fibronectin-coated substrates. In contrast, depletion of Arf6 leads to intracellular accumulation of β1 integrin and reduced adhesion and spreading. These findings suggest that Arf6 regulates both endocytosis and recycling of β1 integrins and that BRAG2 functions selectively to activate Arf6 during integrin internalization

HCI for Blockchain: Studying, Designing, Critiquing and Envisioning Distributed Ledger Technologies

This workshop aims to develop an agenda within the CHI community to address the emergence of blockchain, or distributed ledger technologies (DLTs). As blockchains emerge as a general purpose technology, with applications well beyond cryptocurrencies, DLTs present exciting challenges and opportunities for developing new ways for people and things to transact, collaborate, organize and identify themselves. Requiring interdisciplinary skills and thinking, the field of HCI is well placed to contribute to the research and development of this technology. This workshop will build a community for human-centred researchers and practitioners to present studies, critiques, design-led work, and visions of blockchain applications

Identification of Protein Biomarker Signatures for Acute Myeloid Leukemia (AML) Using Both Nontargeted and Targeted Approaches

Acute myeloid leukemia (AML) is characterized by an increasing number of clonal myeloid blast cells which are incapable of differentiating into mature leukocytes. AML risk stratification is based on genetic background, which also serves as a means to identify the optimal treatment of individual patients. However, constant refinements are needed, and the inclusion of significant measurements, based on the various omics approaches that are currently available to researchers/clinicians, have the potential to increase overall accuracy with respect to patient management. Using both nontargeted (label-free mass spectrometry) and targeted (multiplex immunoassays) proteomics, a range of proteins were found to be significantly changed in AML patients with different genetic backgrounds. The inclusion of validated proteomic biomarker panels could be an important factor in the prognostic classification of AML patients. The ability to measure both cellular and secreted analytes, at diagnosis and during the course of treatment, has advantages in identifying transforming biological mechanisms in patients, assisting important clinical management decisions.Peer reviewe

Understanding the Experience-Centeredness of Privacy and Security Technologies

The joint study of computer security, privacy and human-computer interaction (HCI) over the last two decades has shaped a research agenda focused upon usable privacy & security. However, in HCI research more generally there has long been an awareness of the need to understand and design for user experience, in recognition of the complex and multi-faceted role that technology now plays in our lives. In this paper we add to the growing discussion by introducing the notion of experience-centered privacy and security. We argue that in order to engage users of technology around issues related to experiences of privacy and security, research methods are required that may be outside of the normal repertoire of methods that we typically call upon. We describe three projects that developed non-typical research methods to reveal experiential insights into user interactions with privacy and security-related technologies. We conclude by proposing a research agenda that begins to illustrate how the discourse and methods of experience-centered design might serve to provide valuable alternative perspectives on new and enduring user-facing privacy and security problems