Consensus Based Networking of Distributed Virtual Environments

Distributed Virtual Environments (DVEs) are challenging to create as the goals of consistency and responsiveness become contradictory under increasing latency. DVEs have been considered as both distributed transactional databases and force-reflection systems. Both are good approaches, but they do have drawbacks. Transactional systems do not support Level 3 (L3) collaboration: manipulating the same degree-of-freedom at the same time. Force-reflection requires a client-server architecture and stabilisation techniques. With Consensus Based Networking (CBN), we suggest DVEs be considered as a distributed data-fusion problem. Many simulations run in parallel and exchange their states, with remote states integrated with continous authority. Over time the exchanges average out local differences, performing a distribued-average of a consistent, shared state. CBN aims to build simulations that are highly responsive, but consistent enough for use cases such as the piano-movers problem. CBN's support for heterogeneous nodes can transparently couple different input methods, avoid the requirement of determinism, and provide more options for personal control over the shared experience. Our work is early, however we demonstrate many successes, including L3 collaboration in room-scale VR, 1000's of interacting objects, complex configurations such as stacking, and transparent coupling of haptic devices. These have been shown before, but each with a different technique; CBN supports them all within a single, unified system

Superbase ionic liquids for effective cellulose processing from dissolution to carbonisation

This is the author accepted manuscript. The final version is available from Royal Society of Chemistry via the DOI in this recordA range of superbase derived ionic liquids (SILs) was synthesised and characterised. Their ability to dissolve cellulose and the characteristics of the produced fibres were correlated to their specific structural and solvent properties. 17 ionic liquids (ILs) (including 9 novel) were analysed and six ILs were selected to produce fibres: 1-ethyl-3-methylimidazolium acetate [C2C1im][OAc], 1-ethyl-3-methylimidazolium diethyl phosphate [C2C1im][DEP] and the SILs 1-ethyl-1,8-diazabicyclo[5.4.0]undec-7-enium diethylphosphate [DBUEt][DEP], 1,8-diazabicyclo[5.4.0]undec-7-enium acetate [DBUH][OAc], 1,5-diazabicyclo[4.3.0]non-5-enium acetate [DBNH][OAc] and 1-ethyl-1,5-diazabicyclo[4.3.0]non-5-enium diethylphsophate [DBNEt][DEP]. The mechanical properties of these fibres were investigated. The obtained fibres were then carbonised to explore possible application as carbon fibre precursors. The fibres obtained using a mixture of 1,5-diazabicyclo[4.3.0]non-5-enium based SILs with acetate and hexanoate anions (9 : 1), [DBNH][OAc][Hex], showed a promising combination of strength, stiffness and strain at failure values for applications in textiles and fibre reinforcement in renewable composites. Using Raman spectroscopy it is demonstrated that these fibres exhibit a relatively high degree of structural order, with fewer defects than the other materials. On the other hand, analogous fibres based on imidazolium cation with acetate and hexanoate anions (9 : 1), [C2C1im][OAc][Hex] showed a decline in the quality of the produced fibres compared to the fibres produced from [C2C1im][OAc], [C2C1im][DEP] or [DBNH][OAc][Hex].We would like to thank the EPSRC grant number EP/L017679/01 for financial support (AERO RB1717)

Global parameter search reveals design principles of the mammalian circadian clock

Background: Virtually all living organisms have evolved a circadian (~24 hour) clock that controls physiological and behavioural processes with exquisite precision throughout the day/night cycle. The suprachiasmatic nucleus (SCN), which generates these ~24 h rhythms in mammals, consists of several thousand neurons. Each neuron contains a gene-regulatory network generating molecular oscillations, and the individual neuron oscillations are synchronised by intercellular coupling, presumably via neurotransmitters. Although this basic mechanism is currently accepted and has been recapitulated in mathematical models, several fundamental questions about the design principles of the SCN remain little understood. For example, a remarkable property of the SCN is that the phase of the SCN rhythm resets rapidly after a 'jet lag' type experiment, i.e. when the light/ dark (LD) cycle is abruptly advanced or delayed by several hours. Results: Here, we describe an extensive parameter optimization of a previously constructed simplified model of the SCN in order to further understand its design principles. By examining the top 50 solutions from the parameter optimization, we show that the neurotransmitters' role in generating the molecular circadian rhythms is extremely important. In addition, we show that when a neurotransmitter drives the rhythm of a system of coupled damped oscillators, it exhibits very robust synchronization and is much more easily entrained to light/dark cycles. We were also able to recreate in our simulations the fast rhythm resetting seen after a 'jet lag' type experiment. Conclusion: Our work shows that a careful exploration of parameter space for even an extremely simplified model of the mammalian clock can reveal unexpected behaviours and non-trivial predictions. Our results suggest that the neurotransmitter feedback loop plays a crucial role in the robustness and phase resetting properties of the mammalian clock, even at the single neuron level

Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling

Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size

CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments

We study electroweak baryogenesis and electric dipole moments in the presence of the two leading-order, non-renormalizable operators in the Higgs sector of the MSSM. Significant qualitative and quantitative differences from MSSM baryogenesis arise due to the presence of new CP-violating phases and to the relaxation of constraints on the supersymmetric spectrum (in particular, both stops can be light). We find: (1) spontaneous baryogenesis, driven by a change in the phase of the Higgs vevs across the bubble wall, becomes possible; (2) the top and stop CP-violating sources can become effective; (3) baryogenesis is viable in larger parts of parameter space, alleviating the well-known fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole moments should be measured if experimental sensitivities are improved by about one order of magnitude.Comment: 33 pages, 6 figure

Delivery of sTRAIL variants by MSCs in combination with cytotoxic drug treatment leads to p53-independent enhanced antitumor effects

Mesenchymal stem cells (MSCs) are able to infiltrate tumor tissues and thereby effectively deliver gene therapeutic payloads. Here, we engineered murine MSCs (mMSCs) to express a secreted form of the TNF-related apoptosis-inducing ligand (TRAIL), which is a potent inducer of apoptosis in tumor cells, and tested these MSCs, termed MSC.sTRAIL, in combination with conventional chemotherapeutic drug treatment in colon cancer models. When we pretreated human colorectal cancer HCT116 cells with low doses of 5-fluorouracil (5-FU) and added MSC.sTRAIL, we found significantly increased apoptosis as compared with single-agent treatment. Moreover, HCT116 xenografts, which were cotreated with 5-FU and systemically delivered MSC.sTRAIL, went into remission. Noteworthy, this effect was protein 53 (p53) independent and was mediated by TRAIL-receptor 2 (TRAIL-R2) upregulation, demonstrating the applicability of this approach in p53-defective tumors. Consequently, when we generated MSCs that secreted TRAIL-R2-specific variants of soluble TRAIL (sTRAIL), we found that such engineered MSCs, labeled MSC.sTRAIL DR5, had enhanced antitumor activity in combination with 5-FU when compared with MSC.sTRAIL. In contrast, TRAIL-resistant pancreatic carcinoma PancTu1 cells responded better to MSC.sTRAIL DR4 when the antiapoptotic protein XIAP (X-linked inhibitor of apoptosis protein) was silenced concomitantly. Taken together, our results demonstrate that TRAIL-receptor selective variants can potentially enhance the therapeutic efficacy of MSC-delivered TRAIL as part of individualized and tumor-specific combination treatments. © 2013 Macmillan Publishers Limited All rights reserved

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications