Surface modification of pig endothelial cells with a branched heparin conjugate improves their compatibility with human blood

Corline Heparin Conjugate (CHC), a compound of multiple unfractionated heparin chains, coats cells with a glycocalyx-like layer and may inhibit (xeno) transplant-associated activation of the plasma cascade systems. Here, we investigated the use of CHC to protect WT and genetically modified (GTKO. hCD46. hTBM) pig aortic endothelial cells (PAEC) in two pig-to-human in vitro xenotransplantation settings. Model 1: incubation of untreated or hTNFa-treated PAEC with 10% human plasma induced complement C3b/c and C5b-9 deposition, cellular activation and coagulation activation in WT and GTKO. hCD46. hTBM PAEC. Coating of untreated or hTNFa-treated PAEC with CHC (100 mu g/ml) protected against human plasma-induced endothelial activation and damage. Model 2: PAEC were grown on microcarrier beads, coated with CHC, and incubated with non-anticoagulated whole human blood. Genetically modified PAEC significantly prolonged clotting time of human blood (115.0 +/- 16.1 min, p < 0.001) compared to WT PAEC (34.0 +/- 8.2 min). Surface CHC significantly improved the human blood compatibility of PAEC, as shown by increased clotting time (WT: 84.3 +/- 11.3 min, p < 0.001;GTKO. hCD46. hTBM: 146.2 +/- 20.4 min, p < 0.05) and reduced platelet adhesion, complement activation, coagulation activation and inhibition of fibrinolysis. The combination of CHC coating and genetic modification provided the greatest compatibility with human blood, suggesting that pre-transplant perfusion of genetically modified porcine organs with CHC may benefit post-transplant xenograft function

Optimal protocols for Hamiltonian and Schr\"odinger dynamics

For systems in an externally controllable time-dependent potential, the optimal protocol minimizes the mean work spent in a finite-time transition between given initial and final values of a control parameter. For an initially thermalized ensemble, we consider both Hamiltonian evolution for classical systems and Schr\"odinger evolution for quantum systems. In both cases, we show that for harmonic potentials, the optimal work is given by the adiabatic work even in the limit of short transition times. This result is counter-intuitive because the adiabatic work is substantially smaller than the work for an instantaneous jump. We also perform numerical calculations of the optimal protocol for Hamiltonian dynamics in an anharmonic quartic potential. For a two-level spin system, we give examples where the adiabatic work can be reached in either a finite or an arbitrarily short transition time depending on the allowed parameter space.Comment: submitted to J. Stat. Mech.: Theor. Exp

Free particle scattering off two oscillating disks

We investigate the two-dimensional classical dynamics of the scattering of point particles by two periodically oscillating disks. The dynamics exhibits regular and chaotic scattering properties, as a function of the initial conditions and parameter values of the system. The energy is not conserved since the particles can gain and loose energy from the collisions with the disks. We find that for incident particles whose velocity is on the order of the oscillating disk velocity, the energy of the exiting particles displays non-monotonic gaps of allowed energies, and the distribution of exiting particle velocities shows significant fluctuations in the low energy regime. We also considered the case when the initial velocity distribution is Gaussian, and found that for high energies the exit velocity distribution is Gaussian with the same mean and variance. When the initial particle velocities are in the irregular regime the exit velocity distribution is Gaussian but with a smaller mean and variance. The latter result can be understood as an example of stochastic cooling. In the intermediate regime the exit velocity distribution differs significantly from Gaussian. A comparison of the results presented in this paper to previous chaotic static scattering problems is also discussed.Comment: 9 doble sided pages 13 Postscript figures, REVTEX style. To appear in Phys. Rev.

Primates in Peril: The world's 25 most endangered primates 2008-2010

Introduction Here we report on the fifth iteration of the biennial listing of a consensus of 25 primate species considered to be amongst the most endangered worldwide and the most in need of urgent conservation measures. The first was drawn up in 2000 by the IUCN/SSC Primate Specialist Group, together with Conservation International (Mittermeier et al. 2000). The list was subsequently reviewed and updated in 2002 during an open meeting held during the 19th Congress of the International Primatological Society (IPS) in Beijing, China (Mittermeier et al. 2002). That occasion provided for debate among primatologists working in the field who had first-hand knowledge of the causes of threats to primates, both in general and in particular with the species or communities they study. The meeting and the review of the list of the World’s 25 Most Endangered Primates resulted in its official endorsement by the IPS, and became as such a combined endeavor of the Primate Specialist Group, the IPS, and Conservation International. A third revision was carried out at a meeting in August 2004, at the 20th Congress of the IPS in Torino, Italy (Mittermeier et al. 2006). The fourth, covering the biennium 2006–2008, was the result of a meeting held during the 21st Congress of the International Primatological Society (IPS), in Entebbe, Uganda, 26–30 June 2006 (Mittermeier et al. 2007)

Infrared spectroscopy of NGC 1068: Probing the obscured ionizing AGN continuum

The ISO-SWS 2.5-45 um infrared spectroscopic observations of the nucleus of the Seyfert 2 galaxy NGC 1068 (see companion paper) are combined with a compilation of UV to IR narrow emission line data to determine the spectral energy distribution (SED) of the obscured extreme-UV continuum that photoionizes the narrow line emitting gas in the active galactic nucleus. We search a large grid of gas cloud models and SEDs for the combination that best reproduces the observed line fluxes and NLR geometry. Our best fit model reproduces the observed line fluxes to better than a factor of 2 on average and is in general agreement with the observed NLR geometry. It has two gas components that are consistent with a clumpy distribution of dense outflowing gas in the center and a more extended distribution of less dense and more clumpy gas farther out that has no net outflow. The best fit SED has a deep trough at ~4 Ryd, which is consistent with an intrinsic Big Blue Bump that is partially absorbed by ~6x10^19 cm^-2 of neutral hydrogen interior to the NLR.Comment: 15 pp, 4 figures, ApJ accepte

Primates in peril: The world's 25 most endangered primates, 2006-2008

From first paragraph: Here we report on the fourth iteration of the biennial listing of a consensus of 25 primate species considered to be amongst the most endangered worldwide and the most in need of urgent conservation measures. The first was drawn up in 2000 by the IUCN/SSC Primate Specialist Group, together with Conservation International (Mittermeier et al. 2000). The list was subsequently reviewed and updated in 2002 during an open meeting held during the 19th Congress of the International Primatological Society (IPS) in Beijing, China (Mittermeier et al. 2002). That occasion provided for debate among primatologists working in the field who had first-hand knowledge of the causes of threats to primates, both in general and in particular with the species or communities they study

Primates in peril: The world's 25 most endangered primates, 2006-2008

From first paragraph: Here we report on the fourth iteration of the biennial listing of a consensus of 25 primate species considered to be amongst the most endangered worldwide and the most in need of urgent conservation measures. The first was drawn up in 2000 by the IUCN/SSC Primate Specialist Group, together with Conservation International (Mittermeier et al. 2000). The list was subsequently reviewed and updated in 2002 during an open meeting held during the 19th Congress of the International Primatological Society (IPS) in Beijing, China (Mittermeier et al. 2002). That occasion provided for debate among primatologists working in the field who had first-hand knowledge of the causes of threats to primates, both in general and in particular with the species or communities they study

Mutation or loss of Wilms' tumor gene 1 (WT1) are not major reasons for immune escape in patients with AML receiving WT1 peptide vaccination

<p>Abstract</p> <p>Background</p> <p>Efficacy of cancer vaccines may be limited due to immune escape mechanisms like loss or mutation of target antigens. Here, we analyzed 10 HLA-A2 positive patients with acute myeloid leukemia (AML) for loss or mutations of the WT1 epitope or epitope flanking sequences that may abolish proper T cell recognition or epitope presentation.</p> <p>Methods</p> <p>All patients had been enrolled in a WT1 peptide phase II vaccination trial (NCT00153582) and ultimately progressed despite induction of a WT1 specific T cell response. Blood and bone marrow samples prior to vaccination and during progression were analyzed for mRNA expression level of WT1. Base exchanges within the epitope sequence or flanking regions (10 amino acids N- and C-terminal of the epitope) were assessed with melting point analysis and sequencing. HLA class I expression and WT1 protein expression was analyzed by flow cytometry.</p> <p>Results</p> <p>Only in one patient, downregulation of WT1 mRNA by 1 log and loss of WT1 detection on protein level at time of disease progression was observed. No mutation leading to a base exchange within the epitope sequence or epitope flanking sequences could be detected in any patient. Further, no loss of HLA class I expression on leukemic blasts was observed.</p> <p>Conclusion</p> <p>Defects in antigen presentation caused by loss or mutation of WT1 or downregulation of HLA molecules are not the major basis for escape from the immune response induced by WT1 peptide vaccination.</p