Submission to standards committee consultation on lobbying the Scottish Parliament, 28 February

The Stirling Media Research Institute has been engaged in an ongoing programme of research into the public relations and lobbying industry in Scotland, the UK and Europe since 1996 . We have been encouraged by the Standards Committee's recognition of the importance of lobbying as a matter of both professional and public concern, and we welcome the opportunity to respond to the consultation paper. Our contribution is offered in the spirit of independent academic analysis. We have monitored the growth and development of the lobbying industry in Scotland and interviewed a wide range of lobbyists and public relations professionals ranging across the commercial (consultancy and in-house) and voluntary sectors. As part of our research activity, the SMRI has been a corporate member of ASPA since its inception. When we joined, it was made clear we were researchers and not in any way engaged in professional lobbying. Our research at the UK and European levels has also brought us into contact with commercial and voluntary sector lobbyists who work in other jurisdictions, and has broadened our perspective on the issues relating to lobbying

Mechanisms of action of hESC-secreted proteins that enhance human and mouse myogenesis.

Adult stem cells grow poorly in vitro compared to embryonic stem cells, and in vivo stem cell maintenance and proliferation by tissue niches progressively deteriorates with age. We previously reported that factors produced by human embryonic stem cells (hESCs) support a robust regenerative capacity for adult and old mouse muscle stem/progenitor cells. Here we extend these findings to human muscle progenitors and investigate underlying molecular mechanisms. Our results demonstrate that hESC-conditioned medium enhanced the proliferation of mouse and human muscle progenitors. Furthermore, hESC-produced factors activated MAPK and Notch signaling in human myogenic progenitors, and Delta/Notch-1 activation was dependent on MAPK/pERK. The Wnt, TGF-β and BMP/pSmad1,5,8 pathways were unresponsive to hESC-produced factors, but BMP signaling was dependent on intact MAPK/pERK. c-Myc, p57, and p18 were key effectors of the enhanced myogenesis promoted by the hECS factors. To define some of the active ingredients of the hESC-secretome which may have therapeutic potential, a comparative proteomic antibody array analysis was performed and identified several putative proteins, including FGF2, 6 and 19 which as ligands for MAPK signaling, were investigated in more detail. These studies emphasize that a youthful signaling of multiple signaling pathways is responsible for the pro-regenerative activity of the hESC factors

hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding.

This work builds upon our findings that proteins secreted by hESCs exhibit pro-regenerative activity, and determines that hESC-conditioned medium robustly enhances the proliferation of both muscle and neural progenitor cells. Importantly, this work establishes that it is the proteins that bind heparin which are responsible for the pro-myogenic effects of hESC-conditioned medium, and indicates that this strategy is suitable for enriching the potentially therapeutic factors. Additionally, this work shows that hESC-secreted proteins act independently of the mitogen FGF-2, and suggests that FGF-2 is unlikely to be a pro-aging molecule in the physiological decline of old muscle repair. Moreover, hESC-secreted factors improve the viability of human cortical neurons in an Alzheimers disease (AD) model, suggesting that these factors can enhance the maintenance and regeneration of multiple tissues in the aging body

Atomistic Insight into the Role of Threonine 127 in the Functional Mechanism of Channelrhodopsin-2

Channelrhodopsins (ChRs) belong to the unique class of light-gated ion channels. The structure of channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) has been resolved, but the mechanistic link between light-induced isomerization of the chromophore retinal and channel gating remains elusive. Replacements of residues C128 and D156 (DC gate) resulted in drastic effects in channel closure. T127 is localized close to the retinal Schiff base and links the DC gate to the Schiff base. The homologous residue in bacteriorhodopsin (T89) has been shown to be crucial for the visible absorption maximum and dark–light adaptation, suggesting an interaction with the retinylidene chromophore, but the replacement had little effect on photocycle kinetics and proton pumping activity. Here, we show that the T127A and T127S variants of CrChR2 leave the visible absorption maximum unaffected. We inferred from hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and resonance Raman spectroscopy that the hydroxylic side chain of T127 is hydrogen-bonded to E123 and the latter is hydrogen-bonded to the retinal Schiff base. The C=N–H vibration of the Schiff base in the T127A variant was 1674 cm−1, the highest among all rhodopsins reported to date. We also found heterogeneity in the Schiff base ground state vibrational properties due to different rotamer conformations of E123. The photoreaction of T127A is characterized by a long-lived P2380 state during which the Schiff base is deprotonated. The conservative replacement of T127S hardly affected the photocycle kinetics. Thus, we inferred that the hydroxyl group at position 127 is part of the proton transfer pathway from D156 to the Schiff base during rise of the P3530 intermediate. This finding provides molecular reasons for the evolutionary conservation of the chemically homologous residues threonine, serine, and cysteine at this position in all channelrhodopsins known so far

The Meaning of Memory Safety

We give a rigorous characterization of what it means for a programming language to be memory safe, capturing the intuition that memory safety supports local reasoning about state. We formalize this principle in two ways. First, we show how a small memory-safe language validates a noninterference property: a program can neither affect nor be affected by unreachable parts of the state. Second, we extend separation logic, a proof system for heap-manipulating programs, with a memory-safe variant of its frame rule. The new rule is stronger because it applies even when parts of the program are buggy or malicious, but also weaker because it demands a stricter form of separation between parts of the program state. We also consider a number of pragmatically motivated variations on memory safety and the reasoning principles they support. As an application of our characterization, we evaluate the security of a previously proposed dynamic monitor for memory safety of heap-allocated data.Comment: POST'18 final versio

Programming Protocol-Independent Packet Processors

P4 is a high-level language for programming protocol-independent packet processors. P4 works in conjunction with SDN control protocols like OpenFlow. In its current form, OpenFlow explicitly specifies protocol headers on which it operates. This set has grown from 12 to 41 fields in a few years, increasing the complexity of the specification while still not providing the flexibility to add new headers. In this paper we propose P4 as a strawman proposal for how OpenFlow should evolve in the future. We have three goals: (1) Reconfigurability in the field: Programmers should be able to change the way switches process packets once they are deployed. (2) Protocol independence: Switches should not be tied to any specific network protocols. (3) Target independence: Programmers should be able to describe packet-processing functionality independently of the specifics of the underlying hardware. As an example, we describe how to use P4 to configure a switch to add a new hierarchical label

Joint astrometric solution of Hipparcos and Gaia: A recipe for the Hundred Thousand Proper Motions project

The first release of astrometric data from Gaia is expected in 2016. It will contain the mean stellar positions and magnitudes from the first year of observations. For more than 100 000 stars in common with the Hipparcos Catalogue it will be possible to compute very accurate proper motions due to the time difference of about 24 years between the two missions. This Hundred Thousand Proper Motions (HTPM) project will be part of the first release. Our aim is to investigate how early Gaia data can be optimally combined with information from the Hipparcos Catalogue in order to provide the most accurate and reliable results for HTPM. The Astrometric Global Iterative Solution (AGIS) was developed to compute the astrometric core solution based on the Gaia observations and will be used for all releases of astrometric data from Gaia. We adapt AGIS to process Hipparcos data in addition to Gaia observations, and use simulations to verify and study the joint solution method. For the HTPM stars we predict proper motion accuracies between 14 and 134 muas/yr, depending on stellar magnitude and amount of Gaia data available. Perspective effects will be important for a significant number of HTPM stars, and in order to treat these effects accurately we introduce a scaled model of kinematics. We define a goodness-of-fit statistic which is sensitive to deviations from uniform space motion, caused for example by binaries with periods of 10-50 years. HTPM will significantly improve the proper motions of the Hipparcos Catalogue well before highly accurate Gaia- only results become available. Also, HTPM will allow us to detect long period binary and exoplanetary candidates which would be impossible to detect from Gaia data alone. The full sensitivity will not be reached with the first Gaia release but with subsequent data releases. Therefore HTPM should be repeated when more Gaia data become available.Comment: Revised manuscript following referee report. Accepted for publication in A&