Platelet-Associated Matrix Metalloproteinases Regulate Thrombus Formation and Exert Local Collagenolytic Activity

Objective Platelets are increasingly implicated in processes beyond hemostasis and thrombosis, such as vascular remodeling. Members of the matrix metalloproteinase (MMP) family not only remodel the extracellular matrix but also modulate platelet function. Here, we made a systematic comparison of the roles of MMP family members in acute thrombus formation under flow conditions and assessed platelet-dependent collagenolytic activity over time. Approach and Results Pharmacological inhibition of MMP-1 or MMP-2 (human) or deficiency in MMP-2 (mouse) suppressed collagen-dependent platelet activation and thrombus formation under flow, whereas MMP-9 inhibition/deficiency stimulated these processes. The absence of MMP-3 was without effect. Interestingly, MMP-14 inhibition led to the formation of larger thrombi, which occurred independently of its capacity to activate MMP-2. Platelet thrombi exerted local collagenolytic activity capable of cleaving immobilized dye-quenched collagen and fibrillar collagen fibers within hours, with loss of the majority of the platelet adhesive properties of collagen as a consequence. This collagenolytic activity was redundantly mediated by platelet-associated MMP-1, MMP-2, MMP-9, and MMP-14 but occurred independently of platelet -granule release (Nbeal2(-/-) mice). The latter was in line with subcellular localization experiments, which indicated a granular distribution of MMP-1 and MMP-2 in platelets, distinct from -granules. Whereas MMP-9 protein could not be detected inside platelets, activated platelets did bind plasma-derived MMP-9 to their plasma membrane. Overall, platelet MMP activity was predominantly membrane-associated and influenced by platelet activation status. Conclusions Platelet-associated MMP-1, MMP-2, MMP-9, and MMP-14 differentially modulate acute thrombus formation and at later time points limit thrombus formation by exerting collagenolytic activity

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment

Purpose: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. Methods: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post-surgery. Results: Breast cancer patients’ experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. Conclusions: bWell, a novel app for arm and shoulder exercises was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. Implications for Cancer Survivors: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care

Better security and privacy for web browsers: A survey of techniques, and a new implementation

The web browser is one of the most security critical software components today. It is used to interact with a variety of important applications and services, including social networking services, e-mail services, and e-commerce and e-health applications. But the same browser is also used to visit less trustworthy sites, and it is unreasonable to make it the end-user's responsibility to "browse safely". So it is an important design goal for a browser to provide adequate privacy and security guarantees, and to make sure that potentially malicious content from one web site can not compromise the browser, violate the user's privacy, or interfere with other web sites that the user interacts with. Hence, browser security has been a very active topic of research over the past decade, and many proposals have been made for new browser security techniques or architectures. In the first part of this paper, we provide a survey of some important problems and some proposed solutions. We start with a very broad view on browser security problems, and then zoom in on the issues related to the security of JavaScript scripts on the Web. We discuss three important classes of techniques: fine-grained script access control, capability-secure scripting and information flow security for scripts, focusing on techniques with a solid formal foundation. In the second part of the paper, we describe a novel implementation of one information flow security technique. We discuss how we have implemented the technique of secure multi-execution in the Mozilla Firefox browser, and we report on some preliminary experiments with this implementation. © 2012 Springer-Verlag.status: publishe

Security and privacy of online social network applications

© 2013, IGI Global. All rights reserved. An important recent innovation on social networking sites is the support for plugging in third-party social applications. Together with the ever-growing number of social network users, social applications come with privacy and security risks for those users. While basic mechanisms for isolating applications are well understood, these mechanisms fall short for social-enabled applications. It is an interesting challenge to design and develop application platforms for social networks that enable the necessary functionality of social applications without compromising both users' security and privacy. This chapter will identify and discuss the current security and privacy problems related to social applications and their platforms. Next, it will zoom in on proposals on how to address those problems.edition: 1ststatus: publishe

FlowFox: A web browser with flexible and precise information flow control

We present FlowFox, the first fully functional web browser that implements a precise and general information flow control mechanism for web scripts based on the technique of secure multi-execution. We demonstrate how FlowFox subsumes many ad-hoc script containment countermeasures developed over the last years. We also show that FlowFox is compatible with the current web, by investigating its behavior on the Alexa top-500 web sites, many of which make intricate use of JavaScript. The performance and memory cost of FlowFox is substantial (a performance cost of around 20% on macro benchmarks for a simple two level policy), but not prohibitive. Our prototype implementation shows that information flow enforcement based on secure multi-execution can be implemented in full-scale browsers. It can support powerful, yet precise policies refining the same-origin-policy in a way that is compatible with existing websites. Copyright © 2012 ACM.status: publishe

Information flow control for web scripts

© Springer International Publishing Switzerland 2014. Modern web applications heavily rely on JavaScript code executing in the browser. These web scripts are useful for instance for improving the interactivity and responsiveness of web applications, and for gathering web analytics data. However, the execution of server-provided code in the browser also brings substantial security and privacy risks. Web scripts can access a fair amount of sensitive information, and can leak this information to anyone on the Internet. This tutorial paper discusses information flow control mechanisms for countering these threats. We formalize both a static, type-system based and a dynamic, multiexecution based enforcement mechanism, and show by means of examples how these mechanisms can enforce the security of information flows in web scripts.status: publishe

MMP-3 deficiency does not influence the length and number of CA1 dendrites of hippocampus of adult mice

Over the past two decades, metalloproteinases (MMPs), including MMP‑2, MMP‑3, and MMP‑9, have been implicated as important players in mechanisms underlying various forms of neuroplasticity. In particular, MMP‑3 was found to be involved in both cognitive functions and in plasticity phenomena, but the underlying molecular mechanisms remain largely elusive. In general, it is believed that functional plasticity of neurons is associated with morphological alterations. Interestingly, MMP‑9, in addition to playing a key role in synaptic plasticity, was found to affect plasticity‑related spine morphology changes. Whereas the involvement of MMP‑3 in shaping synapse morphology upon induction of synaptic plasticity awaits determination, it has been demostrated that MMP‑3 knockout results in clearly altered apical dendrite morphology in pyramidal neurons in mouse visual cortex. Considering that the involvement of MMP‑3 in synaptic plasticity has been most extensively documented for the CA1 hippocampal region, we decided to investigate whether genetic deletion of MMP‑3 affects neuronal morphology in this area. To this end, we used Golgi staining to compare dendritic morphology of pyramidal neurons in the CA1 region in MMP‑3‑deficient and wild‑type mice. Surprisingly, in contrast to the results obtained in cortex, extensive analysis of dendritic morphology in the CA1 region revealed no significant differences between MMP‑3 knockout and wild‑type groups. These results suggest that the impact of MMP‑3 on neuronal morphology may be region‑specific.status: publishe