Mechanical Sensing of Living Systems — From Statics to Dynamics

Living systems are fascinating sensing machines that outmatch all artificial machines. Our aim is to put a focus on the dynamics of mechanosensing in cellular systems through concepts and experimental approaches that have been developed during the past decades. By recognizing that a cellular system is not simply the intricate assembly of active and passive macromolecular actors but that it can also manifest scale-invariant and/or highly nonlinear global dynamics, biophysicists have opened a new domain of investigation of living systems. In this chapter, we review methods and techniques that have been implemented to decipher the cascade of temporal events which enable a cell to sense a mechanical stimulus and to elaborate a response to adapt or to counteract this perturbation. We mainly describe intrusive (mechanical probes) and nonintrusive (optical devices) experimental methods that have proved to be efficient for real-time characterization of stationary and nonstationary cellular dynamics. Finally, we discuss whether thermal fluctuations, which are inherent to living systems, are a source of coordination (e.g., synchronization) or randomization of the global dynamics of a cell

On Local Approximations to the Nonlinear Evolution of Large-Scale Structure

We present a comparative analysis of several methods, known as local Lagrangian approximations, which are aimed to the description of the nonlinear evolution of large-scale structure. We have investigated various aspects of these approximations, such as the evolution of a homogeneous ellipsoid, collapse time as a function of initial conditions, and asymptotic behavior. As one of the common features of the local approximations, we found that the calculated collapse time decreases asymptotically with the inverse of the initial shear. Using these approximations, we have computed the cosmological mass function, finding reasonable agreement with N-body simulations and the Press-Schechter formula.Comment: revised version with color figures, minor changes, accepted for publication in the Astrophysical Journal, 30 pages, 13 figure

A Compact Solid State Detector for Small Angle Particle Tracking

MIDAS (MIcrostrip Detector Array System) is a compact silicon tracking telescope for charged particles emitted at small angles in intermediate energy photonuclear reactions. It was realized to increase the angular acceptance of the DAPHNE detector and used in an experimental program to check the Gerasimov-Drell-Hearn sum rule at the Mainz electron microtron, MAMI. MIDAS provides a trigger for charged hadrons, p/pi identification and particle tracking in the region 7 deg < theta < 16 deg. In this paper we present the main characteristics of MIDAS and its measured performances.Comment: 13 pages (9 figures). Submitted to NIM

Hospital food service: a comparative analysis of systems and introducing the ‘Steamplicity’ concept

Background Patient meals are an integral part of treatment hence the provision and consumption of a balanced diet, essential to aid recovery. A number of food service systems are used to provide meals and the Steamplicity concept has recently been introduced. This seeks, through the application of a static, extended choice menu, revised patient ordering procedures, new cooking processes and individual patient food heated/cooked at ward level, to address some of the current hospital food service concerns. The aim of this small-scale study, therefore, was to compare a cook-chill food service operation against Steamplicity. Specifically, the goals were to measure food intake and wastage at ward level; ‘stakeholders’ (i.e. patients, staff, etc.) satisfaction with both systems; and patients’ acceptability of the food provided. Method The study used both quantitative (self-completed patient questionnaires, n = 52) and qualitative methods (semi-structured interviews, n = 16) with appropriate stakeholders including medical and food service staff, patients and their visitors. Results Patients preferred the Steamplicity system overall and in particular in terms of food choice, ordering, delivery and food quality. Wastage was considerably less with the Steamplicity system, although care must be taken to ensure that poor operating procedures do not negate this advantage. When the total weight of food consumed in the ward at each meal is divided by the number of main courses served, at lunch, the mean intake with the cook-chill system was 202 g whilst that for the Steamplicity system was 282 g and for the evening meal, 226 g compared with 310 g. Conclusions The results of this small study suggest that Steamplicity is more acceptable to patients and encourages the consumption of larger portions. Further evaluation of the Steamplicity system is warranted. The purpose of this study was to directly compare selected aspects (food wastage at ward level; satisfaction with systems and food provided) of a traditional cook-chill food service operation against ‘Steamplicity’. Results indicate that patients preferred the ‘Steamplicty’ system in all areas: food choice, ordering, delivery, food quality and overall. Wastage was considerably less with the ‘Steamplicity’ system; although care must be taken to ensure that poor operating procedures do not negate this advantage. When the total weight of food consumed in the ward at each meal is divided by the number of main courses served, results show that at lunch, mean intake with the cook-chill system was 202g whilst that for the ‘Steamplicity’ system was 282g and for the evening meal, 226g compared with 310g

Probabilistic annotation of protein sequences based on functional classifications

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background One of the most evident achievements of bioinformatics is the development of methods that transfer biological knowledge from characterised proteins to uncharacterised sequences. This mode of protein function assignment is mostly based on the detection of sequence similarity and the premise that functional properties are conserved during evolution. Most automatic approaches developed to date rely on the identification of clusters of homologous proteins and the mapping of new proteins onto these clusters, which are expected to share functional characteristics. Results Here, we inverse the logic of this process, by considering the mapping of sequences directly to a functional classification instead of mapping functions to a sequence clustering. In this mode, the starting point is a database of labelled proteins according to a functional classification scheme, and the subsequent use of sequence similarity allows defining the membership of new proteins to these functional classes. In this framework, we define the Correspondence Indicators as measures of relationship between sequence and function and further formulate two Bayesian approaches to estimate the probability for a sequence of unknown function to belong to a functional class. This approach allows the parametrisation of different sequence search strategies and provides a direct measure of annotation error rates. We validate this approach with a database of enzymes labelled by their corresponding four-digit EC numbers and analyse specific cases. Conclusion The performance of this method is significantly higher than the simple strategy consisting in transferring the annotation from the highest scoring BLAST match and is expected to find applications in automated functional annotation pipelines.Published versio

The Excursion Set Theory of Halo Mass Functions, Halo Clustering, and Halo Growth

I review the excursion set theory (EST) of dark matter halo formation and clustering. I recount the Press-Schechter argument for the mass function of bound objects and review the derivation of the Press-Schechter mass function in EST. The EST formalism is powerful and can be applied to numerous problems. I review the EST of halo bias and the properties of void regions. I spend considerable time reviewing halo growth in the EST. This section culminates with descriptions of two Monte Carlo methods for generating halo mass accretion histories. In the final section, I emphasize that the standard EST approach is the result of several simplifying assumptions. Dropping these assumptions can lead to more faithful predictions and a more versatile formalism. One such assumption is the constant height of the barrier for nonlinear collapse. I review implementations of the excursion set approach with arbitrary barrier shapes. An application of this is the now well-known improvement to standard EST that follows from the ellipsoidal-collapse barrier. Additionally, I emphasize that the statement that halo accretion histories are independent of halo environments is a simplifying assumption, rather than a prediction of the theory. I review the method for constructing correlated random walks of the density field in more general cases. I construct a simple toy model with correlated walks and I show that excursion set theory makes a qualitatively simple and general prediction for the relation between halo accretion histories and halo environments: regions of high density preferentially contain late-forming halos and conversely for regions of low density. I conclude with a brief discussion of this prediction in the context of recent numerical studies of the environmental dependence of halo properties. (Abridged)Comment: 62 pages, 19 figures. Review article based on lectures given at the Sixth Summer School of the Helmholtz Institute for Supercomputational Physics. Accepted for Publication in IJMPD. Comments Welcom

Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015.

BACKGROUND: The clinical care of people living with HIV changed fundamentally as a result of the development of effective antiretroviral therapy (ART). HIV infection is now a long-term treatable condition. We report a national audit to assess adherence to British HIV Association guidelines for the routine investigation and monitoring of adult HIV-1-infected individuals. METHODS: All UK sites known as providers of adult HIV outpatient services were invited to complete a case-note review and a brief survey of local clinic practices. Participating sites were asked to randomly select 50-100 adults, who attended for specialist HIV care during 2014 and/or 2015. Each site collected data electronically using a self-audit spreadsheet tool. This included demographic details (gender, ethnicity, HIV exposure, and age) and whether 22 standardised and pre-defined clinical audited outcomes had been recorded. RESULTS: Data were collected on 8258 adults from 123 sites, representing approximately 10% of people living with HIV reported in public health surveillance as attending UK HIV services. Sexual health screening was provided within 96.4% of HIV services, cervical cytology and influenza vaccination within 71.4% of HIV services. There was wide variation in resistance testing across sites. Only 44.9% of patients on ART had a documented 10-year CVD risk within the past three years and fracture risk had been assessed within the past three years for only 16.7% patients aged over 50 years. CONCLUSIONS: There was high participation in the national audit and good practice was identified in some areas. However improvements can be made in monitoring of cardiovascular risk, bone and sexual health

Constraints on the time-scale of nuclear breakup from thermal hard-photon emission

Measured hard photon multiplicities from second-chance nucleon-nucleon collisions are used in combination with a kinetic thermal model, to estimate the break-up times of excited nuclear systems produced in nucleus-nucleus reactions at intermediate energies. The obtained nuclear break-up time for the $^{129}${Xe} + $^{nat}${Sn} reaction at 50{\it A} MeV is $\Delta$$\tau$ $\approx$ 100 -- 300 fm/$c$ for all reaction centralities. The lifetime of the radiating sources produced in seven other different heavy-ion reactions studied by the TAPS experiment are consistent with $\Delta$$\tau$ $\approx$ 100 fm/$c$, such relatively long thermal photon emission times do not support the interpretation of nuclear breakup as due to a fast spinodal process for the heavy nuclear systems studied.Comment: 11 pages, 9 figures, submitted to EPJ