Flow characteristics and exchange in complex biological systems as observed by pulsed-field-gradient magnetic-resonance imaging

Water flow through model porous media was studied in the presence of surface relaxation, internal magnetic field inhomogeneities and exchange with stagnant water pools with different relaxation behavior, demonstrating how the apparent flow parameters average velocity, volume flow and flow conducting area in these situations depend on the observation time. To investigate the water exchange process a two component biological model system consisting of water flowing through a biofilm reactor (column packed with methanogenic granular sludge beads) was used, before and after a heat treatment to introduce exchange. We show that correction of the stagnant fluid signal amplitude for relaxation at increasing observation time using the observed relaxation times reveals exchange between the two fractions in the system. Further it is demonstrated how this exchange can be quantifie

Ergodic averages of commuting transformations with distinct degree polynomial iterates

We prove mean convergence, as $N\to\infty$, for the multiple ergodic averages $\frac{1}{N}\sum_{n=1}^N f_1(T_1^{p_1(n)}x)... f_\ell(T_\ell^{p_\ell(n)}x)$, where $p_1,...,p_\ell$ are integer polynomials with distinct degrees, and $T_1,...,T_\ell$ are commuting, invertible measure preserving transformations, acting on the same probability space. This establishes several cases of a conjecture of Bergelson and Leibman, that complement the case of linear polynomials, recently established by Tao. Furthermore, we show that, unlike the case of linear polynomials, for polynomials of distinct degrees, the corresponding characteristic factors are mixtures of inverse limits of nilsystems. We use this particular structure, together with some equidistribution results on nilmanifolds, to give an application to multiple recurrence and a corresponding one to combinatorics.Comment: 44 pages, small correction in the proof of Lemma 7.5, appeared in the Proceedings of the London Mathematical Societ

Descriptive Anatomy and Three-Dimensional Reconstruction of the Skull of the Early Tetrapod Acanthostega gunnari Jarvik, 1952

The early tetrapod Acanthostega gunnari is an iconic fossil taxon exhibiting skeletal morphology reflecting the transition of vertebrates from water onto land. Computed tomography data of two Acanthostega skulls was segmented using visualization software to digitally separate bone from matrix and individual bones of the skull from each other. A revised description of cranial and lower jaw anatomy in this taxon based on CT data includes new details of sutural morphology, the previously undescribed quadrate and articular bones, and the mandibular symphysis. Sutural morphology is used to infer loading regime in the skull during feeding, and suggests Acanthostega used its anterior jaws to initially seize prey while smaller posterior teeth were used to restrain struggling prey during ingestion. Novel methods were used to repair and retrodeform the skull, resulting in a three-dimensional digital reconstruction that features a longer postorbital region and more strongly hooked anterior lower jaw than previous attempts while supporting the presence of a midline gap between the nasals and median rostrals

Microchimerism, dendritic cell progenitors and transplantation tolerance

The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow‐derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen‐presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM‐CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T‐dependent areas of host lymphoid tissue, where some at least upregulate cell surface MHC class II. These donor‐derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver. A key finding is that in mice, progeny of these donor‐derived DC progenitors can be propagated ex vivo from the bone marrow and other lymphoid tissues of nonimmunosuppressed spontaneously tolerant liver allograft recipients. In humans, donor DC can also be grown from the blood of organ allograft recipients whose organ‐source chimerism is augmented with donor bone marrow infusion. DC progenitors cannot, however, be propagated from the lymphoid tissue of nonimmunosuppressed cardiac‐allografted mice that reject their grafts. These findings are congruent with the possibility that bidirectional leukocyte migration and donor cell chimerism play key roles in acquired transplantation tolerance. Although the cell interactions are undoubtedly complex, a discrete role can be identified for DC under well‐defined experimental conditions. Bone marrow‐derived DC progenitors (MHC class II+, B7–1dim, B7–2−) induce alloantigen‐specific hyporesponsiveness (anergy) in naive T cells in vitro. Moreover, costimulatory molecule‐deficient DC progenitors administered systemically prolong the survival of mouse heart or pancreatic islet allografts. How the regulation of donor DC phenotype and function relates to the balance between the immunogenicity and tolerogenicity of organ allografts remains to be determined. Copyright © 1995 AlphaMed Pres

Chimerism and xenotransplantation: New concepts

In both transplant and infectious circumstances, the immune response is governed by migration and localization of the antigen. If the antigenic epitopes of transgenic xenografts are sufficiently altered to avoid evoking the destructive force of innate immunity, the mechanisms of engraftment should be the same as those that permit the chimerism-dependent immunologic confrontation and resolution that is the basis of alIograft acceptance. In addition to 'humanizing' the epitopes, one of the unanswered questions is whether the species restriction of complement described in 1994 by Valdivia and colleagues also necessitates the introduction of human complement regulatory genes in animal donors. Because the liver is the principal or sole source of most complement components, the complement quickly is transformed to that of the donor after hepatic transplantation. Thus, the need for complementary regulatory transgenes may vary according to the kind of xenograft used. Much evidence shows that physiologically important peptides produced by xenografts (e.g., insulin, clotting factors, and enzymes) are incorporated into the metabolic machinery of the recipient body. To the extent that this is not true, xenotransplantation could result in the production of diseases that are analogous to inborn errors of metabolism. In the climate of pessimism that followed the failures of baboon to human liver xenotransplantation in 1992-1993, it seemed inconceivable that the use of even more discordant donors, such as the pig, could ever be seriously entertained; however, this preceded insight into the xenogeneic and allogeneic barriers that has brought transplantation infectious immunity to common ground. With this new insight and the increasing ease of producing transgenic donors, the goal of clinical xenotransplantation may not be so distant