Control theory helps to resolve the measles paradox

Measles virus (MV) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. A crucial challenge in studying MV infection is to understand the so-called ‘measles paradox’—the progression of the infection to severe immunosuppression before clearance of acute viremia, which is also observed in canine distemper virus (CDV) infection. However, a lack of models that match in vivo data has restricted our understanding of this complex and counter-intuitive phenomenon. Recently, progress was made in the development of a model that fits data from acute measles infection in rhesus macaques. This progress motivates our investigations to gain additional insights from this model into the control mechanisms underlying the paradox. In this paper, we investigated analytical conditions determining the control and robustness of viral clearance for MV and CDV, to untangle complex feedback mechanisms underlying the dynamics of acute infections in their natural hosts. We applied control theory to this model to help resolve the measles paradox. We showed that immunosuppression is important to control and clear the virus. We also showed under which conditions T-cell killing becomes the primary mechanism for immunosuppression and viral clearance. Furthermore, we characterized robustness properties of T-cell immunity to explain similarities and differences in the control of MV and CDV. Together, our results are consistent with experimental data, advance understanding of control mechanisms of viral clearance across morbilliviruses, and will help inform the development of effective treatments. Further the analysis methods and results have the potential to advance understanding of immune system responses to a range of viral infections such as COVID-19

Manipulation of subsurface carbon nanoparticles in Bi2Sr2CaCu2O8+δ using a scanning tunneling microscope

We present evidence that subsurface carbon nanoparticles in Bi2Sr2CaCu2O8+δ can be manipulated with nanometer precision using a scanning tunneling microscope. High-resolution images indicate that most of the carbon particles remain subsurface after transport observable as a local increase in height as the particle pushes up on the surface. Tunneling spectra in the vicinity of these protrusions exhibit semiconducting characteristics with a band gap of approximately 1.8 eV, indicating that the incorporation of carbon locally alters the electronic properties near the surface

Implementing changes to hospital services: factors influencing the process and 'results' of reconfiguration

OBJECTIVES: Acute hospital reconfiguration is often presented as a problem to be solved by calculations of optimal design, a rational process amenable to influence by open and responsive consultation. We aimed to analyse factors in the process and 'results' of hospital reconfiguration in three case study sites in the English NHS. METHODS: In-depth semi-structured interviews were conducted with internal and external stakeholders at each site. Analysis within each case was complemented by cross-case analysis focusing on the relationships between the features of the origins and process of reconfiguration and progress in the implementation of plans. FINDINGS: We identified a number of inter-related factors operating in the process of implementation which influenced the 'results': the drivers for change, the reconfiguration, its content (particularly the extent to which services are withdrawn or made less accessible), the influence of stakeholders, such as local politicians, financial pressures, and the role of the management team. CONCLUSIONS: We argue that the differences in reconfiguration implementation between the three cases reflected the nature of the proposed changes and local politics, rather than the strength of the 'evidence' for change. National policy has tended to over-emphasise the importance of consultation using 'evidence' and underplays these influencing factors

Understanding the control of a vitamin B12 riboswitch

Within the life sciences switching mechanisms are pervasive at all levels, from molecules to cells and tissues. Their operation can be a key determinant of health or disease. Whilst the existence and importance of switches is widely acknowledged within the biological literature, many life scientists do not deal explicitly with the switching behaviour. Frequently, steady-state behaviour before and after switching is the primary focus. Here methods for analysis of switched systems from control engineering are applied to the modelling and analysis of a riboswitch. The model has been developed by studying the dynamics of the vitamin B12 riboswitch. The simulation results have been validated using in vivo experiments by checking the bacterial growth when using Escherichia coli and Salmonella enterica where the action of the vitamin B12 riboswitch is known to be a determinant of system behaviour. The paper first describes a simple model for the B12-riboswitch regulatory network in E. coli and applies the same analysis when changing the strain to S. enterica. Validation of the simulation results has been undertaken by linking the dynamics of the riboswitch to bacterial growth

Digital storytelling and Co-creative Media: The role of community arts and media in propagating and coordinating population-wide creative practice

How is creative expression and communication extended among whole populations? What is the social and cultural value of this activity? What roles do formal agencies, community-based organisations and content producer networks play? Specifically, how do participatory media and arts projects and networks contribute to building this capacity in the contemporary communications environment

Magnetic properties of Co2C and Co3C nanoparticles and their assemblies

Nano-composite material consisting of Co2C and Co3C nanoparticles has recently been shown to exhibit unusually large coercivities and energy products. Experimental studies that can delineate the properties of individual phases have been undertaken and provide information on how the coercivities and the energy product change with the size and composition of the nanoparticles. The studies indicate that while both phases are magnetic, the Co3C has higher magnetization and coercivity compared to Co2C. Through first principles electronic structure studies using a GGA+U functional, we provide insight on the role of C intercalation on enhancing the magnetic anisotropy of the individual phases

Unique metabolites protect earthworms against plant polyphenols

All higher plants produce polyphenols, for defence against above-ground herbivory. These polyphenols also influence the soil micro- and macro-fauna that break down plant leaf litter. Polyphenols therefore indirectly affect the fluxes of soil nutrients and, ultimately, carbon turnover and ecosystem functioning in soils. It is unknown how earthworms, the major component of animal biomass in many soils, cope with high-polyphenol diets. Here, we show that earthworms possess a class of unique surface-active metabolites in their gut, which we term ‘drilodefensins’. These compounds counteract the inhibitory effects of polyphenols on earthworm gut enzymes, and high-polyphenol diets increase drilodefensin concentrations in both laboratory and field populations. This shows that drilodefensins protect earthworms from the harmful effects of ingested polyphenols. We have identified the key mechanism for adaptation to a dietary challenge in an animal group that has a major role in organic matter recycling in soils worldwide

Computational modelling elucidates the mechanism of ciliary regulation in health and disease

<p>Abstract</p> <p>Background</p> <p>Ciliary dysfunction leads to a number of human pathologies, including primary ciliary dyskinesia, nephronophthisis, situs inversus pathology or infertility. The mechanism of cilia beating regulation is complex and despite extensive experimental characterization remains poorly understood. We develop a detailed systems model for calcium, membrane potential and cyclic nucleotide-dependent ciliary motility regulation.</p> <p>Results</p> <p>The model describes the intimate relationship between calcium and potassium ionic concentrations inside and outside of cilia with membrane voltage and, for the first time, describes a novel type of ciliary excitability which plays the major role in ciliary movement regulation. Our model describes a mechanism that allows ciliary excitation to be robust over a wide physiological range of extracellular ionic concentrations. The model predicts the existence of several dynamic modes of ciliary regulation, such as the generation of intraciliary Ca²⁺spike with amplitude proportional to the degree of membrane depolarization, the ability to maintain stable oscillations, monostable multivibrator regimes, all of which are initiated by variability in ionic concentrations that translate into altered membrane voltage.</p> <p>Conclusions</p> <p>Computational investigation of the model offers several new insights into the underlying molecular mechanisms of ciliary pathologies. According to our analysis, the reported dynamic regulatory modes can be a physiological reaction to alterations in the extracellular environment. However, modification of the dynamic modes, as a result of genetic mutations or environmental conditions, can cause a life threatening pathology.</p