Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.

Human liver contains an Eomes(hi) population of NK cells that is not present in the blood. In this study, we show that these cells are characterized by a molecular signature that mediates their retention in the liver. By examining liver transplants where donors and recipients are HLA mismatched, we distinguish between donor liver-derived and recipient-derived leukocytes to show that Eomes(lo) NK cells circulate freely whereas Eomes(hi) NK cells are unable to leave the liver. Furthermore, Eomes(hi) NK cells are retained in the liver for up to 13 y. Therefore, Eomes(hi) NK cells are long-lived liver-resident cells. We go on to show that Eomes(hi) NK cells can be recruited from the circulation during adult life and that circulating Eomes(lo) NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. This suggests that circulating NK cells are a precursor of their liver-resident counterparts

Magnetization of Mn_12 Ac in a slowly varying magnetic field: an ab initio study

Beginning with a Heisenberg spin Hamiltonian for the manganese ions in the Mn_12 Ac molecule, we find a number of low-energy states of the system. We use these states to solve the time-dependent Schrodinger equation and find the magnetization of the molecule in the presence of a slowly varying magnetic field. We study the effects of the field sweep rate, fourth order anisotropic spin interactions and a transverse field on the weights of the different states as well as the magnetization steps which are known to occur in the hysteresis plots in this system. We find that the fourth order term and a slow field sweep rate are crucial for obtaining prominent steps in magnetization in the hysteresis plots.Comment: LaTeX, 11 pages, 12 eps figure

Brittle Cornea Syndrome ZNF469 mutation carrier phenotype and segregation analysis of rare ZNF469 variants in familial Keratoconus.

Purpose: Brittle cornea syndrome 1 (BCS1) is a rare recessive condition characterised by extreme thinning of the cornea and sclera, caused by mutations in ZNF469. Keratoconus is a relatively common disease characterised by progressive thinning and ectasia of the cornea. The aetiology of keratoconus is complex and not yet understood, but rare ZNF469 variants have recently been associated with disease. We investigated the phenotype of BCS1 carriers with known pathogenic ZNF469 mutations, and recruited families in which aggregation of keratoconus was observed to establish if rare variants in ZNF469 segregated with disease. Methods: Patients and family members were recruited and underwent comprehensive anterior segment examination including corneal topography. Blood samples were donated and genomic DNA was extracted. The coding sequence and splice sites of ZNF469 were PCR amplified and Sanger sequenced. Results: Four carriers of three BCS1-associated ZNF469 loss-of-function mutations (p.[ Glu1392Ter], p.[Gln1930Argfs*6], p.[Gln1930fs*133]) were examined and none had keratoconus. One carrier had partially penetrant features of BCS1, including joint hypermobility. ZNF469 sequencing in 11 keratoconus families identified 9 rare (MAF≤0.025) variants predicted to be potentially damaging. However, in each instance the rare variant(s) identified, including two previously reported as potentially keratoconus-associated, did not segregate with the disease. Conclusions: The presence of heterozygous loss-of-function alleles in the ZNF469 gene did not cause keratoconus in the individuals examined. None of the rare non-synonymous ZNF469 variants identified in the familial cohort conferred a high risk of keratoconus, therefore, genetic variants contributing to disease pathogenesis in these 11 families remain to be identified

Funneled Landscape Leads to Robustness of Cell Networks: Yeast Cell Cycle

We uncovered the underlying energy landscape for a cellular network. We discovered that the energy landscape of the yeast cell-cycle network is funneled towards the global minimum (G0/G1 phase) from the experimentally measured or inferred inherent chemical reaction rates. The funneled landscape is quite robust against random perturbations. This naturally explains robustness from a physical point of view. The ratio of slope versus roughness of the landscape becomes a quantitative measure of robustness of the network. The funneled landscape can be seen as a possible realization of the Darwinian principle of natural selection at the cellular network level. It provides an optimal criterion for network connections and design. Our approach is general and can be applied to other cellular networks

Surgical treatment of zygomatic bone fracture using two points fixation versus three point fixation-a randomised prospective clinical trial

<p>Abstract</p> <p>Background</p> <p>The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements which in turn require protocol management and long-term follow up. The preference for open reduction and internal fixation of zygomatic fractures at three points has continued to grow in response to observations of inadequate results from two point and one point fixation techniques.</p> <p>The objectives of this study were to compare the efficacy of zygomatic bone after treatment with ORIF using 2 point fixation and ORIF using 3 point fixation and compare the outcome of two procedures.</p> <p>Methods</p> <p>100 patients were randomly divided equally into two groups. In group A, 50 patients were treated by ORIF using two point fixation by miniplates and in group B, 50 patients were treated by ORIF using three point fixation by miniplates. They were evaluated for their complications during and after surgery with their advantages and disadvantages and the difference between the two groups was observed.</p> <p>Results</p> <p>A total of 100 fractures were sustained. We found that postoperative complication like decreased malar height and vertical dystopia was more common in those patients who were treated by two point fixation than those who were treated with three point fixation.</p> <p>Conclusions</p> <p>Based on this study open reduction and internal fixation using three point fixation by miniplates is the best available method for the treatment zygomatic bone fractures.</p

Potential Landscape and Probabilistic Flux of a Predator Prey Network

Predator-prey system, as an essential element of ecological dynamics, has been recently studied experimentally with synthetic biology. We developed a global probabilistic landscape and flux framework to explore a synthetic predator-prey network constructed with two Escherichia coli populations. We developed a self consistent mean field method to solve multidimensional problem and uncovered the potential landscape with Mexican hat ring valley shape for predator-prey oscillations. The landscape attracts the system down to the closed oscillation ring. The probability flux drives the coherent oscillations on the ring. Both the landscape and flux are essential for the stable and coherent oscillations. The landscape topography characterized by the barrier height from the top of Mexican hat to the closed ring valley provides a quantitative measure of global stability of system. The entropy production rate for the energy dissipation is less for smaller environmental fluctuations or perturbations. The global sensitivity analysis based on the landscape topography gives specific predictions for the effects of parameters on the stability and function of the system. This may provide some clues for the global stability, robustness, function and synthetic network design

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Dynamical Boson Stars

The idea of stable, localized bundles of energy has strong appeal as a model for particles. In the 1950s John Wheeler envisioned such bundles as smooth configurations of electromagnetic energy that he called {\em geons}, but none were found. Instead, particle-like solutions were found in the late 1960s with the addition of a scalar field, and these were given the name {\em boson stars}. Since then, boson stars find use in a wide variety of models as sources of dark matter, as black hole mimickers, in simple models of binary systems, and as a tool in finding black holes in higher dimensions with only a single killing vector. We discuss important varieties of boson stars, their dynamic properties, and some of their uses, concentrating on recent efforts.Comment: 79 pages, 25 figures, invited review for Living Reviews in Relativity; major revision in 201