Agent-based computational modeling of wounded epithelial cell monolayers

Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

The biomechanics of tree frogs climbing curved surfaces: a gripping problem

The adhesive mechanisms of climbing animals have become an important research topic because of their biomimetic implications. We examined the climbing abilities of hylid tree frogs on vertical cylinders of differing diameter and surface roughness to investigate the relative roles of adduction forces (gripping) and adhesion. Tree frogs adhere using their toe pads and subarticular tubercles, the adhesive joint being fluid-filled. Our hypothesis was that, on an effectively flat surface (adduction forces on the largest 120 mm diameter cylinder were insufficient to allow climbing), adhesion would effectively be the only means by which tree frogs could climb, but on the two smaller diameter cylinders (44 mm and 13 mm), frogs could additionally utilise adduction forces by gripping the cylinder either with their limbs outstretched or by grasping around the cylinder with their digits, respectively. The frogs' performance would also depend on whether the surfaces were smooth (easy to adhere to) or rough (relatively non-adhesive). Our findings showed that climbing performance was highest on the narrowest smooth cylinder. Frogs climbed faster, frequently using a 'walking trot' gait rather than the 'lateral sequence walk' used on other cylinders. Using an optical technique to visualize substrate contact during climbing on smooth surfaces, we also observed an increasing engagement of the subarticular tubercles on the narrower cylinders. Finally, on the rough substrate, frogs were unable to climb the largest diameter cylinder, but were able to climb the narrowest one slowly. These results support our hypotheses and have relevance for the design of climbing robots

Helioseismology of Sunspots: A Case Study of NOAA Region 9787

Various methods of helioseismology are used to study the subsurface properties of the sunspot in NOAA Active Region 9787. This sunspot was chosen because it is axisymmetric, shows little evolution during 20-28 January 2002, and was observed continuously by the MDI/SOHO instrument. (...) Wave travel times and mode frequencies are affected by the sunspot. In most cases, wave packets that propagate through the sunspot have reduced travel times. At short travel distances, however, the sign of the travel-time shifts appears to depend sensitively on how the data are processed and, in particular, on filtering in frequency-wavenumber space. We carry out two linear inversions for wave speed: one using travel-times and phase-speed filters and the other one using mode frequencies from ring analysis. These two inversions give subsurface wave-speed profiles with opposite signs and different amplitudes. (...) From this study of AR9787, we conclude that we are currently unable to provide a unified description of the subsurface structure and dynamics of the sunspot.Comment: 28 pages, 18 figure

The role of science in physical natural hazard assessment : report to the UK Government by the Natural Hazard Working Group

Following the tragic Asian tsunami on 26 December 2004, the Prime Minister asked the Government’s Chief Scientific Adviser, Sir David King, to convene a group of experts (the Natural Hazard Working Group) to advise on the mechanisms that could and should be established for the detection and early warning of global physical natural hazards. 2. The Group was asked to examine physical hazards which have high global or regional impact and for which an appropriate early warning system could be put in place. It was also asked to consider the global natural hazard frameworks currently in place and under development and their effectiveness in using scientific evidence; to consider whether there is an existing appropriate international body to pull together the international science community to advise governments on the systems that need to be put in place, and to advise on research needed to fill current gaps in knowledge. The Group was asked to make recommendations on whether a new body was needed, or whether other arrangements would be more effective

No Evidence Supporting Flare Driven High-Frequency Global Oscillations

The underlying physics that generates the excitations in the global low-frequency, < 5.3 mHz, solar acoustic power spectrum is a well known process that is attributed to solar convection; However, a definitive explanation as to what causes excitations in the high-frequency regime, > 5.3 mHz, has yet to be found. Karoff and Kjeldsen (Astrophys. J. 678, 73-76, 2008) concluded that there is a correlation between solar flares and the global high-frequency solar acoustic waves. We have used the Global Oscillations Network Group (GONG) helioseismic data in an attempt to verify Karoff and Kjeldsen (2008) results as well as compare the post-flare acoustic power spectrum to the pre-flare acoustic power spectrum for 31 solar flares. Among the 31 flares analyzed, we observe that a decrease in acoustic power after the solar flare is just as likely as an increase. Furthermore, while we do observe variations in acoustic power that are most likely associated with the usual p-modes associated with solar convection, these variations do not show any significant temporal association with flares. We find no evidence that consistently supports flare driven high-frequency waves.Comment: 20 pages, 9 figures, Accepted for publication in Solar Physic

The Sub-Surface Structure of a Large Sample of Active Regions

We employ ring-diagram analysis to study the sub-surface thermal structure of active regions. We present results using a large number of active regions over the course of Solar Cycle 23. We present both traditional inversions of ring-diagram frequency differences, with a total sample size of 264, and a statistical study using Principal Component Analysis. We confirm earlier results on smaller samples that sound speed and adiabatic index are changed below regions of strong magnetic field. We find that sound speed is decreased in the region between approximately r=0.99R_sun and r=0.995R_sun (depths of 3Mm to 7Mm), and increased in the region between r=0.97R_sun and r=0.985R_sun (depths of 11Mm to 21Mm). The adiabatic index is enhanced in the same deeper layers that sound-speed enhancement is seen. A weak decrease in adiabatic index is seen in the shallower layers in many active regions. We find that the magnitudes of these perturbations depend on the strength of the surface magnetic field, but we find a great deal of scatter in this relation, implying other factors may be relevant.Comment: 16 pages, 11 figures, accepted for publication in Solar Physic

Refractive-index changes in fused silica produced by heavy-ion implantation followed by photobleaching

The changes in refractive index, optical absorption, and volume of synthetic fused silica resulting from the implantation of germanium and silicon ions at energies of 3 and 5 MeV are reported. Implantation changes the density and generates ultraviolet color centers in the silica, which increases the refractive index at visible wavelengths by ∼1%. Irradiation of the implanted samples with 249-nm light from a KrF excimer laser photobleaches the color centers and reduces the index by more than 0.1%. Photobleaching is used to write a 4.3-μm pitch diffraction grating in the implanted silica

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but &lt;60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) &gt;20 mg/mmol or eGFR ≥20 but &lt;45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Optical Hall conductivity of systems with gapped spectral nodes

We calculate the optical Hall conductivity within the Kubo formalism for systems with gapped spectral nodes, where the latter have a power-law dispersion with exponent n. The optical conductivity is proportional to n and there is a characteristic logarithmic singularity as the frequency approaches the gap energy. The optical Hall conductivity is almost unaffected by thermal fluctuations and disorder for n=1, whereas disorder has a stronger effect on transport properties if n=2