Orthotopic heart transplantation in a transgenic pig-to-primate model

BACKGROUND: Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examines orthotopic transplantation of hDAF transgenic pig hearts into baboon recipients. METHODS: Orthotopic xenogeneic heart transplantation was performed using piglets, transgenic for hDAF, as donors. Ten baboons were used as recipients and were immunosuppressed with a combination of cyclophosphamide, cyclosporine, and steroids. RESULTS: Five grafts failed within 18 hr without any histological signs of hyperacute rejection. Pulmonary artery thrombosis induced by a size mismatch was observed in two of these animals. The other three recipients died because of failure to produce even a low cardiac output and/or dysrhythmia. The remaining five animals survived between four and nine days. One animal died of bronchopneumonia on day 4. Three xenografts stopped beating on day 5 due to acute vascular rejection. The longest survivor was killed on day 9 with a beating, histologically normal xenograft, because of pancytopenia. CONCLUSIONS: The results reported here demonstrate that hDAF transgenic pig hearts are not hyperacutely rejected when transplanted into baboon recipients. Orthotopically transplanted transgenic pig hearts are capable of maintaining cardiac output in baboons. An optimum immunosuppressive regimen is the subject of ongoing research.     

Observations of nodule growth during the oxidation of pure binary iron-aluminum alloys

Oxidation studies were carried out in oxygen at 800°C, on a series of pure binary iron-based alloys with between 1.9 and 9.8 wt. % aluminum. The results are presented in conjunction with the existing literature and these permit the development of a classification of scale morphologies based on alloy composition. Alloys with less than about 2.4 wt. % aluminum form bulky stratified scales composed of Fe₂O₃ and Fe₃O₄ with FeAl₂O₄ and Al₂O₃ at the scale-metal interface. Alloys with between 2.4 and 6.9 wt. % form an external Al₂O₃ scale but this is interspersed with iron oxide nodules that penetrate the alloy substrate. Only alloys with greater than 6.9 wt. % aluminum form completely protective Al₂O₃ scales. Models based on oxide nucleation are presented for the growth of bulky scales and also the iron oxide nodules.     

The oxidation of high-purity iron-chromium-aluminum alloys at 800°C

A systematic study is presented of the oxidation of pure iron-chromium-aluminum alloys at 800°C, in pure oxygen, at a pressure of 200 Torr. Oxidation characteristics are described with reference to kinetic measurements, scale topographies and morphologies, and also possible growth mechanisms. An oxide map is used to show that alloys may be classified into four categories depending on the external scale that forms: Fe₂O₃, Cr₂O₃, Al₂O₃, or Al₂O₃ with iron-oxide nodules. Alloys containing less than 2–2.5 wt. % aluminum formed either Fe₂O₃ or Cr₂O₃ as an external scale, depending on the chromium content, and internal, rod-like protrusions of Al₂O₃. At higher aluminum concentrations, Al₂O₃ was always present as an external scale, although this was interspersed by iron-oxide nodules at chromium concentrations of less than 5 wt. %. A model based on Wagner's secondary getter concept is proposed for eliminating nodule nucleation. Evidence is also present that indicates that at 800°C, alumina scale decohesion occurs prior to void formation and that voids are the result of thermal etching beneath lifted scales.     

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.     

High‐order Higdon‐like boundary conditions for exterior transient wave problems

Recently developed non‐reflecting boundary conditions are applied for exterior time‐dependent wave problems in unbounded domains. The linear time‐dependent wave equation, with or without a dispersive term, is considered in an infinite domain. The infinite domain is truncated via an artificial boundary ??, and a high‐order non‐reflecting boundary condition (NRBC) is imposed on ??. Then the problem is solved numerically in the finite domain bounded by ??. The new boundary scheme is based on a reformulation of the sequence of NRBCs proposed by Higdon. We consider here two reformulations: one that involves high‐order derivatives with a special discretization scheme, and another that does not involve any high derivatives beyond second order. The latter formulation is made possible by introducing special auxiliary variables on ??. In both formulations the new NRBCs can easily be used up to any desired order. They can be incorporated in a finite element or a finite difference scheme; in the present paper the latter is used. In contrast to previous papers using similar formulations, here the method is applied to a fully exterior two‐dimensional problem, with a rectangular boundary. Numerical examples in infinite domains are used to demonstrate the performance and advantages of the new method. In the auxiliary‐variable formulation long‐time corner instability is observed, that requires special treatment of the corners (not addressed in this paper). No such difficulties arise in the high‐derivative formulation. Published in 2005 by John Wiley & Sons, Ltd.     

Development of a Position Sensitive Neutron Detector with High Efficiency and Energy Resolution for Use at High-Flux Beam Sources

We are developing a high-efficiency neutron detector with 1 cm position resolution and coarse energy resolution for use at high-flux neutron source facilities currently proposed or under construction. The detector concept integrates a segmented ³He ionization chamber with the position sensitive, charged particle collection methods of a MicroMegas detector. Neutron absorption on the helium produces protons and tritons that ionize the fill gas. The charge is amplified in the field region around a wire mesh and subsequently detected in current mode by wire strips mounted on a substrate. One module consisting of a high-voltage plate, a field-shaping high-voltage plate, a grid and wire strips defines a detection region. For 100 % efficiency, detector modules are consecutively placed along the beam axis. Analysis over several regions with alternating wire strip orientation provides a two-dimensional beam profile. By using ³He, a 1/v absorption gas, each axial region captures neutrons of a different energy range, providing an energy-sensitive detection scheme especially useful at continuous beam sources.     

Group Study of Simulated Driving fMRI Data by Multiset Canonical Correlation Analysis

In this work, we apply a novel statistical method, multiset canonical correlation analysis (M-CCA), to study a group of functional magnetic resonance imaging (fMRI) datasets acquired during simulated driving task. The M-CCA method jointly decomposes fMRI datasets from different subjects/sessions into brain activation maps and their associated time courses, such that the correlation in each group of estimated activation maps across datasets is maximized. Therefore, the functional activations across all datasets are extracted in the order of consistency across different dataset. On the other hand, M-CCA preserves the uniqueness of the functional maps estimated from each dataset by avoiding concatenation of different datasets in the analysis. Hence, the cross-dataset variation of the functional activations can be used to test the hypothesis of functional-behavioral association. In this work, we study 120 simulated driving fMRI datasets and identify parietal-occipital regions and frontal lobe as the most consistently engaged areas across all the subjects and sessions during simulated driving. The functional-behavioral association study indicates that all the estimated brain activations are significantly correlated with the steering operation during the driving task. M-CCA thus provides a new approach to investigate the complex relationship between the brain functions and multiple behavioral variables, especially in naturalistic tasks as demonstrated by the simulated driving study.     

Finite satisfiability for guarded fixpoint logic

The finite satisfiability problem for guarded fixpoint logic is decidable and complete for 2ExpTime (resp. ExpTime for formulas of bounded width).