Microscopic biophysical model of self-organization in tissue due to feedback between cell- and macroscopic-scale forces

We develop a microscopic biophysical model for self-organization and reshaping of artificial tissue, that is codriven by microscopic active forces between cells and an extracellular matrix (ECM), and macroscopic forces that develop within the tissue, finding close agreement with experiment. Microscopic active forces are stimulated by μm-scale interactions between cells and the ECM within which they exist, and when large numbers of cells act together these forces drive, and are affected by, macroscopic-scale self-organization and reshaping of tissues in a feedback loop. To understand this loop, there is a need to (1) construct microscopic biophysical models that can simulate these processes for the very large number of cells found in tissues, (2) validate and calibrate those models against experimental data, and (3) understand the active feedback between cells and the extracellular matrix, and its relationship to macroscopic self-organization and reshaping of tissue. Our microscopic biophysical model consists of a contractile network representing the ECM, that interacts with a large number of cells via dipole forces, to describe macroscopic self-organization and reshaping of tissue. We solve the model using simulated annealing, finding close agreement with experiments on artificial neural tissue. We discuss the calibration of model parameters. We conclude that feedback between microscopic cell-ECM dipole interactions and tissue-scale forces is a key factor in driving macroscopic self-organization and reshaping of tissue. We discuss the application of the biophysical model to the simulation and rational design of artificial tissues

Exact solution and interfacial tension of the six-vertex model with anti-periodic boundary conditions

We consider the six-vertex model with anti-periodic boundary conditions across a finite strip. The row-to-row transfer matrix is diagonalised by the `commuting transfer matrices' method. {}From the exact solution we obtain an independent derivation of the interfacial tension of the six-vertex model in the anti-ferroelectric phase. The nature of the corresponding integrable boundary condition on the $XXZ$ spin chain is also discussed.Comment: 18 pages, LaTeX with 1 PostScript figur

Three dimensional numerical simulations of the UPS-292-SC engine

We present and analyze three-dimensional calculations of the spray, mixing and combustion in the UPS-292 stratified charge engine for three different operating conditions, corresponding to overall air-fuel ratios between 22.4 and 61.0. The numerical calculations are performed with KIVA, a multidimensional arbitrary-mesh, finite-difference hydrodynamics program for internal combustion engine applications. The calculations use a mesh of 10,000 computational cells, which conform to the shape of the piston bowl and cylinder and move to follow piston motion. Each operating condition is calculated from intake valve closure at 118/sup 0/ BTDC to 90/sup 0/ ATDC and requires approximately three hours of CRAY-XMP computer time

An attempt to observe economy globalization: the cross correlation distance evolution of the top 19 GDP's

Economy correlations between the 19 richest countries are investigated through their Gross Domestic Product increments. A distance is defined between increment correlation matrix elements and their evolution studied as a function of time and time window size. Unidirectional and Bidirectional Minimal Length Paths are generated and analyzed for different time windows. A sort of critical correlation time window is found indicating a transition for best observations. The mean length path decreases with time, indicating stronger correlations. A new method for estimating a realistic minimal time window to observe correlations and deduce macroeconomy conclusions from such features is thus suggested.Comment: to be published in the Dyses05 proceedings, in Int. J. Mod Phys C 15 pages, 5 figures, 1 tabl

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate).

Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P < 0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P < 0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity

Effective treatment of malignant hypercalcaemia with a single intravenous infusion of clodronate.

Thirty patients with hypercalcaemia due to malignancy that persisted following rehydration, were treated with a single dose of the bisphosphonate, clodronate. Clodronate (1.5 g) was administered intravenously in 500 ml normal saline over 4 h. Serum and urine biochemistry were measured before and after treatment and the results were compared with data from 15 patients given the recommended regimen 300 mg intravenous clodronate daily for 5 consecutive days. The single infusion induced a rapid and significant fall in serum calcium, apparent at day 3 (P < 0.0001) that persisted to the end of follow-up at day 10 (P < 0.001). Eighty per cent (24/30) of patients became normocalcaemic. The response was associated with a significant decrease in fasting urinary calcium excretion, and no change in renal function, as judged by serum creatinine. The same dose of clodronate, given as 5 daily infusions, induced a comparable decrease in serum calcium, but was less rapid in onset so that at day 3 the serum calcium was significantly lower with the single infusion (P = 0.02). The calcium lowering effect of both regimens depended on the tumour type. We conclude that the single infusion of 1500 mg clodronate is as effective in reducing serum calcium as the same dose given over 5 days. The single infusion has a more rapid onset of effect, is more convenient than multiple infusions, and has no adverse effect on renal function

Monoclonal Antibodies to the V2 Domain of MN-rgp120: Fine Mapping of Epitopes and Inhibition of α4β7 Binding

BACKGROUND: Recombinant gp120 (MN-rgp120) was a major component of the AIDSVAX B/E vaccine used in the RV144 trial. This was the first clinical trial to show that vaccination could prevent HIV infection in humans. A recent RV144 correlates of protection study found that protection correlated with the presence of antibodies to the V2 domain. It has been proposed that antibodies to the α4β7 binding site in the V2 domain might prevent HIV-1 infection by blocking the ability of virions to recognize α4β7 on activated T-cells. In this study we investigated the specificity of monoclonal antibodies (MAbs) to the V2 domain of MN-rgp120 and examined the possibility that these antibodies could inhibit the binding of MN-rgp120 to the α4β7 integrin. METHODOLOGY/PRINCIPAL FINDINGS: Nine MAbs to the V2 domain were isolated from mice immunized with recombinant envelope proteins. The ability of these MAbs to inhibit HIV infection, block the binding of gp120 to CD4, and block the binding of MN-rgp120 to the α4β7 integrin was measured. Mutational analysis showed that eight of the MAbs recognized two immunodominant clusters of amino acids (166-168 and 178-183) located at either end of the C strand within the four-strand anti-parallel sheet structure comprising the V1/V2 domain. CONCLUSIONS/SIGNIFICANCE: These studies showed that the antigenic structure of the V2 domain is exceedingly complex and that MAbs isolated from mice immunized with MN-rgp120 exhibited a high level of strain specificity compared to MAbs to the V2 domain isolated from HIV-infected humans. We found that immunization with MN-rgp120 readily elicits antibodies to the V2 domain and some of these were able to block the binding of MN-rgp120 to the α4β7 integrin

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

<p>Abstract</p> <p>Background</p> <p>Classical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrP^Sc) in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrP^Schas been detected in peripheral blood mononuclear cells (PBMCs), plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay.</p> <p>Results</p> <p>Serial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrP^Scimmunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15), CD72⁺B lymphocytes (3/3), CD21⁺B lymphocytes (3/3) or platelet-rich plasma (2/3) fractions. As expected, whole blood (11/13) and buffy coat (5/5) recipients showed positive PrP^Sclabeling in lymphoid follicles. However, at 549 days post-transfusion, PrP^Scwas not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction.</p> <p>Conclusions</p> <p>Prion infectivity was detected in circulating PBMCs, CD72⁺pan B lymphocytes, the CD21⁺subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrP^Scdetection levels in blood samples.</p