Hysteresis of <i>fo</i>F2 at European middle latitudes

International audienceThe hysteresis of foF2 is studied for several European stations over the whole 24-hour diurnal interval for the equinoctial months of the years just before and just after the solar cycle minimum for solar cycles 20 and 21. Based on previous results, the hysteresis is expected to develop best just for the equinoctial months and near the solar cycle minimum. The hysteresis is generally found to be negative, i.e. higher foF2 for the rising branch compared to the falling branch of solar cycle. However, this is not the case in some individual months of some years. The noontime hysteresis represents the hysteresis at other times of the day qualitatively (as to sign) but not quantitatively. The hysteresis appears to be relatively persistent from one solar cycle to another solar cycle in spring but not in autumn. A typical value for springtime hysteresis is about 0.5 MHz. The inclusion of hysteresis into long-term ionospheric and radio wave propagation predictions remains questionable

Lit up and left dark: Failures of imagination in urban broadband networks

The design and deployment of urban broadband infrastructures inscribe particular imaginations of Internet access onto city streets. The different manifestations and locations of these networks, their uses, and access points often expose material excesses of urban broadband networks, as well as failures of Internet service providers, urban planners, and public officials to imagine the diverse ways that people incorporate Internet connection into their everyday lives. We approach the study of urban broadband networks through the juxtaposition of invisible networks that are buried under the streets and have always been “turned off” (dark fiber) versus hypervisible that are “turned on” and prominently displayed on city streets (LinkNYC). In our analysis of these two case studies, we critique themes of visibility and invisibility as indexes of power and access. Our findings are meant to provide a critical analysis of urban technology policy as well as theories of infrastructure, visibility, and access

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies:A pilot study

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community

A quantitative, multi-national and multi-stakeholder assessment of barriers to the adoption of cell therapies

Cellular therapies, such as stem cell based treatments, have been widely researched and numerous products and treatments have been developed. Despite this, there has been relatively limited use of these technologies in the healthcare sector. This study sought to investigate the perceived barriers to this more widespread adoption. An anonymous online questionnaire was developed, based on the findings of a pilot study. This was distributed to an audience of clinicians, researchers, and commercial experts in 13 countries. The results were analysed for all respondents, and also sub-grouped by geographical region, and by profession of respondents. The results of the study showed that the most significant barrier was manufacturing, with other factors such as efficacy, regulation, and cost-effectiveness being identified by the different groups. This study further demonstrates the need for these important issues to be addressed during the development of cellular therapies to enable more widespread adoption of these treatments.JS is funded by an MRC UK Studentship

Estimating confidence intervals in predicted responses for oscillatory biological models

BACKGROUND: The dynamics of gene regulation play a crucial role in a cellular control: allowing the cell to express the right proteins to meet changing needs. Some needs, such as correctly anticipating the day-night cycle, require complicated oscillatory features. In the analysis of gene regulatory networks, mathematical models are frequently used to understand how a network’s structure enables it to respond appropriately to external inputs. These models typically consist of a set of ordinary differential equations, describing a network of biochemical reactions, and unknown kinetic parameters, chosen such that the model best captures experimental data. However, since a model’s parameter values are uncertain, and since dynamic responses to inputs are highly parameter-dependent, it is difficult to assess the confidence associated with these in silico predictions. In particular, models with complex dynamics - such as oscillations - must be fit with computationally expensive global optimization routines, and cannot take advantage of existing measures of identifiability. Despite their difficulty to model mathematically, limit cycle oscillations play a key role in many biological processes, including cell cycling, metabolism, neuron firing, and circadian rhythms. RESULTS: In this study, we employ an efficient parameter estimation technique to enable a bootstrap uncertainty analysis for limit cycle models. Since the primary role of systems biology models is the insight they provide on responses to rate perturbations, we extend our uncertainty analysis to include first order sensitivity coefficients. Using a literature model of circadian rhythms, we show how predictive precision is degraded with decreasing sample points and increasing relative error. Additionally, we show how this method can be used for model discrimination by comparing the output identifiability of two candidate model structures to published literature data. CONCLUSIONS: Our method permits modellers of oscillatory systems to confidently show that a model’s dynamic characteristics follow directly from experimental data and model structure, relaxing assumptions on the particular parameters chosen. Ultimately, this work highlights the importance of continued collection of high-resolution data on gene and protein activity levels, as they allow the development of predictive mathematical models

Novel Television-Based Cognitive Training Improves Working Memory and Executive Function

The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60\u201387 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants' reports of \u201cadequate\u201d to \u201chigh\u201d system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition

Scalable purification of viral vectors for gene therapy: An appraisal of downstream processing approaches

Process concerns associated with viral-vectors gene delivery currently focus on effective purification, as described by these authors from the Centre for the Advancement of Sustainable Medical Innovation and Sartorius Stedim Biotech. For research into cell-delivered gene therapy platforms to continue toward development, process characterization and development work are still in need of refinement

Scalable purification of viral vectors for gene therapy: An appraisal of downstream processing approaches

Process concerns associated with viral-vectors gene delivery currently focus on effective purification, as described by these authors from the Centre for the Advancement of Sustainable Medical Innovation and Sartorius Stedim Biotech. For research into cell-delivered gene therapy platforms to continue toward development, process characterization and development work are still in need of refinement