Leukocyte beta2-integrins; genes and disease

Integrins are heterodimeric transmembrane receptors that mediate cell-cell and cell-extracellular matrix interactions. Beta2-integrins are expressed exclusively in leukocytes and mediate many important functions in the immune system. Beta2-integrin genes are important in the pathologies of several diseases and genetic syndromes. These include Leukocyte Adhesion Deficiency (LAD) and Systemic Lupus Erythematosus (SLE), disorders which lie at opposite ends of the spectrum of immunological diseases. In LAD-I and LAD-III syndromes, beta2-integrin expression or function is reduced or absent. In SLE, genetic variants of the ITGAM gene, which encodes for the alpha M/CD11b chain of the beta2-integrin Mac-1,are associated with SLE development. In this mini review we summarise current knowledge regarding the involvement of beta2-integrins in LAD and SLE. Interestingly, dysfunctional beta2-integrins have been linked to both disorders, shedding light on the diverse roles of these receptors in the immune system

Let’s talk about placental sex, baby: Understanding mechanisms that drive female-and male-specific fetal growth and developmental outcomes

It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific “evolutionary advantage” likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.Ashley S. Meakin, James S. M. Cuffe, Jack R. T. Darby, Janna L. Morrison and Vicki L. Clifto

Radial orbit instability: review and perspectives

This paper presents elements about the radial orbit instability, which occurs in spherical self-gravitating systems with a strong anisotropy in the radial velocity direction. It contains an overview on the history of radial orbit instability. We also present the symplectic method we use to explore stability of equilibrium states, directly related to the dissipation induced instability mechanism well known in theoretical mechanics and plasma physics.Comment: 10 pages, submitted to Transport Theory and Statistical Physics, proceedings of Vlasovia 2009 International Conference. Corrected for typos, redaction, and references adde

Fracture in the Elderly Multidisciplinary Rehabilitation (FEMuR):study protocol for a phase II randomised feasibility study of a multidisciplinary rehabilitation package following hip fracture [ ISRCTN22464643 ]

Background Proximal femoral fracture is a common, major health problem in old age resulting in loss of functional independence and a high-cost burden on society, with estimated health and social care costs of £2.3 billion per year in the UK. Rehabilitation has the potential to maximise functional recovery and maintain independent living, but evidence of effectiveness is lacking. Usual rehabilitation care is delivered by a multi-disciplinary team in the hospital and in the community. An ‘enhanced rehabilitation’ intervention has been developed consisting of a workbook, goal-setting diary and extra therapy sessions, designed to improve self-efficacy and increase the amount and quality of the practice of physical exercise and activities of daily living. Methods/design This paper describes the design of a phase II study comprising an anonymous cohort of all proximal femoral fracture patients admitted to the three acute hospitals in Betsi Cadwaladr University Health Board over a 6-month period with a randomised feasibility study comparing the enhanced rehabilitation intervention with usual care. These will assess the feasibility of a future definitive randomised controlled trial and concurrent economic evaluation in terms of recruitment, retention, outcome measure completion, compliance with the intervention and fidelity of delivery, health service use data, willingness to be randomised and effect size for a future sample size calculation. Focus groups will provide qualitative data to contribute to the assessment of the acceptability of the intervention amongst patients, carers and rehabilitation professionals and the feasibility of delivering the planned intervention. The primary outcome measure is function assessed by the Barthel Index. Secondary outcomes measure the ability to perform activities of daily living, anxiety and depression, potential mediators of outcomes such as hip pain, self-efficacy and fear of falling, health utility, health service use, objectively assessed physical function and adverse events. Participants’ preference for rehabilitation services will be assessed in a discrete choice experiment. Discussion Phase II studies are an opportunity to not only assess the feasibility of trial methods but also to compare different methods of outcome measurement and novel methods of obtaining health service use data from routinely collected patient information. Trial registration Current Controlled Trials ISRCTN22464643, UKCRN16677

Structure and dynamics of Rh surfaces

Lattice relaxations, surface phonon spectra, surface energies, and work functions are calculated for Rh(100) and Rh(110) surfaces using density-functional theory and the full-potential linearized augmented plane wave method. Both, the local-density approximation and the generalized gradient approximation to the exchange-correlation functional are considered. The force constants are obtained from the directly calculated atomic forces, and the temperature dependence of the surface relaxation is evaluated by minimizing the free energy of the system. The anharmonicity of the atomic vibrations is taken into account within the quasiharmonic approximation. The importance of contributions from different phonons to the surface relaxation is analyzed.Comment: 9 pages, 7 figures, scheduled to appear in Phys. Rev. B, Feb. 15 (1998). Other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

Characterizing altruistic motivation in potential volunteers for SARS-CoV-2 challenge trials

In human challenge trials, volunteers are deliberately infected with a pathogen to accelerate vaccine development and answer key scientific questions. In the U.S., preparations for challenge trials with the novel coronavirus are complete, and in the U.K., challenge trials have recently begun. However, ethical concerns have been raised about the potential for invalid consent or exploitation. These concerns largely reflect worries that challenge trial volunteers may be unusually risk-seeking or too economically vulnerable to refuse the payments these trials provide, rather than being motivated primarily by altruistic goals. We conducted the first large-scale survey of intended human challenge trial volunteers and found that SARS-CoV-2 challenge trial volunteers exhibit high levels of altruistic motivations without any special indication of poor risk perception or economic vulnerability. Findings indicate that challenge trials with the novel coronavirus can attract volunteers with background conditions, attitudes, and motivations that should allay key ethical concerns

An optimization principle for deriving nonequilibrium statistical models of Hamiltonian dynamics

A general method for deriving closed reduced models of Hamiltonian dynamical systems is developed using techniques from optimization and statistical estimation. As in standard projection operator methods, a set of resolved variables is selected to capture the slow, macroscopic behavior of the system, and the family of quasi-equilibrium probability densities on phase space corresponding to these resolved variables is employed as a statistical model. The macroscopic dynamics of the mean resolved variables is determined by optimizing over paths of these probability densities. Specifically, a cost function is introduced that quantifies the lack-of-fit of such paths to the underlying microscopic dynamics; it is an ensemble-averaged, squared-norm of the residual that results from submitting a path of trial densities to the Liouville equation. The evolution of the macrostate is estimated by minimizing the time integral of the cost function. The value function for this optimization satisfies the associated Hamilton-Jacobi equation, and it determines the optimal relation between the statistical parameters and the irreversible fluxes of the resolved variables, thereby closing the reduced dynamics. The resulting equations for the macroscopic variables have the generic form of governing equations for nonequilibrium thermodynamics, and they furnish a rational extension of the classical equations of linear irreversible thermodynamics beyond the near-equilibrium regime. In particular, the value function is a thermodynamic potential that extends the classical dissipation function and supplies the nonlinear relation between thermodynamics forces and fluxes

Numerical Portrait of a Relativistic Thin Film BCS Superfluid

We present results of numerical simulations of the 2+1d Nambu - Jona-Lasinio model with a non-zero baryon chemical potential mu including the effects of a diquark source term. Diquark condensates, susceptibilities and masses are measured as functions of source strength j. The results suggest that diquark condensation does not take place in the high density phase mu>mu_c, but rather that the condensate scales non-analytically with j implying a line of critical points and long range phase coherence. Analogies are drawn with the low temperature phase of the 2d XY model. The spectrum of the spin-1/2 sector is also studied yielding the quasiparticle dispersion relation. There is no evidence for a non-zero gap; rather the results are characteristic of a normal Fermi liquid with Fermi velocity less than that of light. We conclude that the high density phase of the model describes a relativistic gapless thin film BCS superfluid.Comment: 37 pages, 16 figure

RG flows from Spin(7), CY 4-fold and HK manifolds to AdS, Penrose limits and pp waves

We obtain explicit realizations of holographic renormalization group (RG) flows from M-theory, from E^{2,1} \times Spin(7) at UV to AdS_4 \times \tilde{S^7} (squashed S^7) at IR, from E^{2,1} \times CY4 at UV to AdS_4 \times Q^{1,1,1} at IR, and from E^{2,1} \times HK (hyperKahler) at UV to AdS_4 \times N^{0,1,0} at IR. The dual type IIA string theory configurations correspond to D2-D6 brane systems where D6 branes wrap supersymmetric four-cycles. We also study the Penrose limits and obtain the pp-wave backgrounds for the above configurations. Besides, we study some examples of non-supersymmetric and supersymmetric flows in five-dimensional gauge theories.Comment: 42 pages, 6 eps figures, typos and misprints correcte