Molecular cloning and characterization of B-cadherin, a novel chick cadherin.

Calcium-dependent cell-cell adhesion is mediated in large part by a set of homologous integral membrane glycoproteins termed cadherins. In this report, antibodies to conserved domains in previously described cadherins have been used to isolate cDNAs encoding a novel chick cadherin. The deduced primary structure of this novel molecule, assigned the name B-cadherin, contains 726 amino acid residues which include five extracellular domains characteristic of this class of adhesion molecules, a single putative transmembrane spanning region, and a cytoplasmic tail. In each domain, B-cadherin shares extensive homologies with other cadherins, but is more closely related to E-cadherin, P-cadherin, and L-CAM than to N-cadherin. It is expressed in a wide variety of chick tissues at embryonic day 13. In particular, immunohistochemical staining and in situ hybridization localize B-cadherin protein and mRNA to the epithelial lining of the choroid plexus and to cells in specific layers of the optic tectum in chick brain. Levels of the protein and RNA transcript change dramatically as development proceeds in chick brain. These results suggest that B-cadherin has important functions in neurogenesis, in at least some epithelia, and in embryogenesis

Adhesion of a chicken myeloblast cell line to fibrinogen and vitronectin through a beta 1-class integrin.

The adhesive interactions of circulating blood cells are tightly regulated, receptor-mediated events. To establish a model for studies on regulation of cell adhesion, we have examined the adhesive properties of the HD11 chick myeloblast cell line. Function-perturbing antibodies were used to show that integrins containing the beta 1 subunit mediate HD11 cell attachment to several distinct extracellular matrix proteins, specifically fibronectin, collagen, vitronectin, and fibrinogen. This is the first evidence that an integrin heterodimer in the beta 1 family functions as a receptor for fibrinogen. While the alpha v beta 1 heterodimer has been shown to function as a vitronectin receptor on some cells, this heterodimer could not be detected on HD11 cells. Instead, results suggest that the beta 1 subunit associates with different, unidentified alpha subunit(s) to form receptors for vitronectin and fibrinogen. Results using function-blocking antibodies also demonstrate that on these cells, additional receptors for vitronectin are formed by alpha v beta 3 and alpha v associated with an unidentified 100-kD beta subunit. The adhesive interactions of HD11 cells with these extracellular matrix ligands were shown to be regulated by lipopolysaccharide treatment, making the HD11 cell line attractive for studies of mechanisms regulating cell adhesion. In contrast to primary macrophage which rapidly exhibit enhanced adhesion to laminin and collagen upon activation, activated HD11 cells exhibited reduced adhesion to most extracellular matrix constituents

Developing A Model Approximation Method and Parameter Estimates for Solid State Reaction Kinetics

The James S. Markiewicz Solar Energy Research Facility was built to research solar chemistry and currently being used to research the change in metal oxides such as iron or magnesium oxide that act as a medium for the production of hydrogen from water. This is significant because hydrogen can be used in vehicles equipped with appropriate fuel cells and due the decreased cost of producing hydrogen with this method. The shrinking core model which governs this process has proved difficult to solve due to the high number of unknown constants and its non-linearity. We detail in this work the implementation of less common heuristics, mainly Particle Swarm Optimization. This technique was used because of its wide unbiased search for the possible constants. The development and method we are using to solve these unknown constants will be shown

Effector Functions of Natural Killer Cell Subsets in the Control of Hematological Malignancies.

Treatment of hematological malignant disorders has been improved over the last years, but high relapse rate mainly attributable to the presence of minimal residual disease still persists. Therefore, it is of great interest to explore novel therapeutic strategies to obtain long-term remission. Immune effector cells, and especially natural killer (NK) cells, play a crucial role in the control of hematological malignancies. In this regard, the efficiency of allogeneic stem cell transplantation clearly depends on the immune-mediated graft versus leukemia effect without the risk of inducing graft versus host disease. Alloreactive donor NK cells generated following hematopoietic stem cell transplantation ameliorate the outcome of leukemia patients; in addition, in vivo transfer of in vitro expanded NK cells represents a crucial tool for leukemia treatment. To improve NK cell effector functions against resistant leukemia cells, novel immunotherapeutic strategies are oriented to the identification, isolation, expansion, and administration of particular NK cell subsets endowed with multifunctional anti-tumor potential and tropism toward tumor sites. Moreover, the relationship between the emergence and persistence of distinct NK cell subsets during post-graft reconstitution and the maintenance of a remission state is still rather unclear

Developing A Model Approximation Method and Parameter Estimates for Solid State Reaction Kinetics

The James S. Markiewicz Solar Energy Research Facility was built to research solar chemistry and currently being used to research the change in metal oxides such as iron or magnesium oxide that act as a medium for the production of hydrogen from water. This is significant because hydrogen can be used in vehicles equipped with appropriate fuel cells and due the decreased cost of producing hydrogen with this method. The shrinking core model which governs this process has proved difficult to solve due to the high number of unknown constants and its non-linearity. We detail in this work the implementation of less common heuristics, mainly Particle Swarm Optimization. This technique was used because of its wide unbiased search for the possible constants. The development and method we are using to solve these unknown constants will be shown

Distribution of a brain-specific extracellular matrix protein in developing and adult zebrafish

A monoclonal antibody (IgG) that recognizes a 53-kDa zebrafishnext brain protein was isolated and used to characterize the distribution of this protein in zebrafish.next (1) The antigen was found only in the brain and not in any other tissues such as muscle, dermis and cartilage. Within the brain, the antibody recognized extracellular matrix (ECM) outside neuronal cells. (2) Digestion by hyaluronidase released the antigen from brain tissue, and the monoclonal antibody staining was also decreased by the digestion by hyaluronidase. (3) The pattern of antigen distribution is not perineuronal, as the density of the antigen at the periphery of the cells was practically identical to that of the empty intercellular spaces. Therefore, this monoclonal antibody does not recognize the perineuronal glycocortex. (4) The antigen is distributed only in limited areas of the brain, namely in the periphery of the forebrain, the hypothalamus, the optic tectum, the interpeduncular nucleus, the cerebellum and the ventricular rim of the medulla. In the optic tectum, the antibody strongly stained the most superficial layer, and in the cerebellum, it stained the molecular but not the granular layer. These patterns of distribution are very different from those of other typical brain ECM proteins and suggest that this protein may play quite distinct roles in brain development and maintenance.</p

Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation

Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation

Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies

Pancreatic Islet Transplantation

Islet transplantation offers hope to many patients with diabetes, who envision a life free of glucose checks and insulin injections. What are the barriers to its widespread implementation

ES2008-54098 STUDY OF A QUENCH DEVICE FOR SYNTHESIS AND HYDROLYSIS of Zn NANOPARTICLES: MODELING AND EXPERIMENTS

ABSTRACT The synthesis and hydrolysis of zinc nanoparticles are carried out in a tubular reactor. A key component of the reactor is a coaxial jet quench device. Three co-axial and multi-inlet confined jets mix Zn(g), steam and argon to produce and hydrolyze zinc nanoparticles. The performance of the quench device is assessed with computational fluid dynamic modeling and measurements of hydrogen conversion and particle size and composition. Numerical data elucidate the impact of varying jet flow rates on temperature and velocity distributions within the reactor. Experiments produce hydrogen conversions of 61 to 79 %. Particle deposition on sections of the reactor surface above 650 K favors hydrolysis. Residence time for in-flight particles is less than one second and these particles are partially hydrolyzed