Privacy and security of consumer IoT devices for the pervasive monitoring of vulnerable people

The Internet of Things (IoT) promises highly innovative solutions to a wide range of activities. However, simply being a technology company does not exempt an IoT company from needing to comply with the legislation applicable to their operating region that safeguards personal information. This will result in security and privacy requirements for healthcare solutions. There are several mature frameworks that address these issues, but they have been developed within the context of organised hospitals and care providers, where there is the expertise, processing power, communications and electrical power to support highly robust security. However, for IoT solutions aimed at vulnerable people, either at home or within their local environment, there are significant additional constraints that must be overcome. These include technical (low processing capability, power constrained, intermittent communications) organisational (how to enrol and revoke users and devices, distribution of cryptographic keys) and user constraints (how does a patient with physical and/or mental challenges configure and update their devices). This paper considers at the legal frameworks and the security and privacy requirements for healthcare solutions. An overview of some of the primary frameworks is then provided followed by an assessment of how this is constrained within an IoT system

Improving access to healthcare in rural communities - IoT as part of the solution

AAL has benefitted tremendously from the near-ubiquity of powerful smartphones and very high data rates available over broadband and mobile networks. However, this is beyond the reach of many users. IoT systems offer the potential to extend some of the benefits to disadvantaged users. Such solutions will need to secure personal health information and provide a sufficient quality of service even when operating constrained user devices and communications

Interactions between RAMP2 and CRF receptors: The effect of receptor subtypes, splice variants and cell context.

Corticotrophin releasing factor (CRF) acts via two family B G-protein-coupled receptors, CRFR1 and CRFR2. Additional subtypes exist due to alternative splicing. CRFR1α is the most widely expressed subtype and lacks a 29-residue insert in the first intracellular loop that is present in CRFR1β. It has been shown previously that co-expression of CRFR1β with receptor activity modifying protein 2 (RAMP2) in HEK 293S cells increased the cell-surface expression of both proteins suggesting a physical interaction as seen with RAMPs and calcitonin receptor-like receptor (CLR). This study investigated the ability of CRFR1α, CRFR1β and CRFR2β to promote cell-surface expression of FLAG-tagged RAMP2. Four different cell-lines were utilised to investigate the effect of varying cellular context; COS-7, HEK 293T, HEK 293S and [ΔCTR]HEK 293 (which lacks endogenous calcitonin receptor). In all cell-lines, CRFR1α and CRFR1β enhanced RAMP2 cell-surface expression. The magnitude of the effect on RAMP2 was dependent on the cell-line ([ΔCTR]HEK 293 > COS-7 > HEK 293T > HEK 293S). RT-PCR indicated this variation may relate to differences in endogenous RAMP expression between cell types. Furthermore, pre-treatment with CRF resulted in a loss of cell-surface FLAG-RAMP2 when it was co-expressed with CRFR1 subtypes. CRFR2β co-expression had no effect on RAMP2 in any cell-line. Molecular modelling suggests that the potential contact interface between the extracellular domains of RAMP2 and CRF receptor subtypes is smaller than that of RAMP2 and CRL, the canonical receptor:RAMP pairing, assuming a physical interaction. Furthermore, a specific residue difference between CRFR1 subtypes (glutamate) and CRFR2β (histidine) in this interface region may impair CRFR2β:RAMP2 interaction by electrostatic repulsion

Vulnerability Disclosure: Best Practice Guidelines

It is vital to the commercial interests of providers of Internet of Things (IoT) products and solutions and to the security of their customers, that vulnerabilities are discovered and remediated as soon as possible. Third party security researchers are a valuable adjunct to a provider’s internal resources in addressing this goal. To ensure effective co-operation and maintain good relations with external security researchers, it is important for providers to define and communicate vulnerability disclosure processes that not only describe how they would like vulnerabilities to be reported confidentially to them, but also set expectations as to how they will process and act upon such reports. This process should include provision of feedback to the discovering researcher, and the public announcement of the security vulnerability, usually after the release of a software patch, hardware fix, or other remediation. The ETSI 303 645 standard [4], which lays down baseline security requirements for the consumer IoT, includes requirement 5.2, to “Implement a means to manage reports of vulnerabilities”. This states that “The manufacturer shall make a vulnerability disclosure policy publicly available.”, adding that “A vulnerability disclosure policy clearly specifies the process through which security researchers and others are able to report issues.” This document provides manufacturers, integrators, distributors, and retailers of IoT products and services with a set of guidelines for handling the disclosure of security vulnerabilities, based on best practice and international standards

Receptor activity modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors

The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through association of the calcitonin receptor-like receptor (CLR) and one of three receptor activitymodifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM) or intermedin/adrenomedullin2 (AM2) is well known to result in a Gαs-mediated increase in cAMP. Here we use modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα$_{s}$ and Gα$_{q}$ but also identify a Gα$_{i}$ component to CLR signaling in both yeast and HEK- 293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand and RAMP-dependent signaling bias between Gα$_{s}$, Gα$_{i}$ and Gα$_{q/11}$ pathways. The results are discussed in the context of RAMP interactions probed through molecular modelling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology, and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology.This work was supported by the National Heart Foundation of New Zealand (H.W.), the School of Biological Sciences, University of Auckland seed fund (H.W.), the BBSRC (G.L. - BB/M00015X/1), (D.P. - BB/M000176/1), (C.A.R. - BB/M006883/1), a BBSRC Doctoral Training Partnership (M.H. – BB/JO14540/1), an MRC Doctoral Training Partnership (I.W. - MR/J003964/1), a Warwick Impact Fund (C.W., G.L.), a Warwick Research Development Fund (C.W., G.L.) grant number (RD13301) and the Warwick Undergraduate Research Scholarship Scheme (A.S and R.H).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by the American Society for Biochemistry and Molecular Biology

The Role of ICL1 and H8 in Class B1 GPCRs; Implications for Receptor Activation.

The first intracellular loop (ICL1) of G protein-coupled receptors (GPCRs) has received little attention, although there is evidence that, with the 8th helix (H8), it is involved in early conformational changes following receptor activation as well as contacting the G protein β subunit. In class B1 GPCRs, the distal part of ICL1 contains a conserved R12.48KLRCxR2.46b motif that extends into the base of the second transmembrane helix; this is weakly conserved as a [R/H]12.48KL[R/H] motif in class A GPCRs. In the current study, the role of ICL1 and H8 in signaling through cAMP, iCa2+ and ERK1/2 has been examined in two class B1 GPCRs, using mutagenesis and molecular dynamics. Mutations throughout ICL1 can either enhance or disrupt cAMP production by CGRP at the CGRP receptor. Alanine mutagenesis identified subtle differences with regard elevation of iCa2+, with the distal end of the loop being particularly sensitive. ERK1/2 activation displayed little sensitivity to ICL1 mutation. A broadly similar pattern was observed with the glucagon receptor, although there were differences in significance of individual residues. Extending the study revealed that at the CRF1 receptor, an insertion in ICL1 switched signaling bias between iCa2+ and cAMP. Molecular dynamics suggested that changes in ICL1 altered the conformation of ICL2 and the H8/TM7 junction (ICL4). For H8, alanine mutagenesis showed the importance of E3908.49b for all three signal transduction pathways, for the CGRP receptor, but mutations of other residues largely just altered ERK1/2 activation. Thus, ICL1 may modulate GPCR bias via interactions with ICL2, ICL4 and the Gβ subunit