Laboratory studies in cross-species lung transplantation

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.     

Compositional constraints in the extremely GC-poor genome of Plasmodium falciparum

We have analyzed the compositional properties of coding (protein encoding) and non-coding sequences of Plasmodium falciparum, a unicellular parasite characterized by an extremely AT-rich genome. GC% levels, base and dinucleotide frequencies were studied. We found that among the various factors that contribute to the properties of the sequences analyzed, the most relevant are the compositional constraints which operate on the whole genome.     

Inflammation and bone metabolism in rheumatoid arthritis. Pathogenetic viewpoints and therapeutic possibilities

BACKGROUND: Systemic osteoporosis is a common and pathogenetically heterogenous complication in rheumatoid arthritis. Various factors such as disease activity, dosage and duration of glucocorticoid treatment and immobilization are involved in pathogenesis of osteoporosis in rheumatoid arthritis. INFLAMMATION AND BONE METABOLISM: Proinflammatory cytokines secreted by immunocompetent cells have a role in the regulation of the activity of osteoblasts and osteoclasts. The effects of these proinflammatory cytokines include the inhibition of bone formation and an increase in bone resorption. Interleukin-6 and nitric oxide induced in osteoblasts by proinflammatory cytokines are likely to be important mediators between these cytokines and the function of osteoblasts and osteoclasts. Furthermore, disease activity dependent changes in the secretion of glucocorticoids and in vitamin D metabolism may be involved in the pathogenesis of osteoporosis in this disease. Alteration of bone remodeling associated with immobilization is an important factor of systemic bone loss in rheumatoid arthritis. CONCLUSION: The inflammatory process in rheumatoid arthritis may cause penarticular and systemic bone loss by various cytokine and hormone mediated mechanisms. Concluding from these pathogenetic mechanisms, bisphosphonates and active vitamin D metabolites are likely to be effective therapeutic options in osteoporosis associated with rheumatoid arthritis.     

IEEE 802.11-saturation throughput analysis

To satisfy the emerging need of wireless data communications, the IEEE is currently standardizing the 802.11 protocol for wireless local area networks. This standard adopts a CSMA/CA medium access control protocol with exponential backoff. We present a simple analytical model to compute the saturation throughput performance in the presence of a finite number of terminals and in the assumption of ideal channel conditions. The model applies to both basic and request-to-send/clear-to-send (RTS/CTS) access mechanisms. Comparison with simulation results shows that the model is extremely accurate in predicting the system throughput     

Elastic-plastic indentation stress fieldsusing the finite-element method

The finite-element method is used to model the elastic-plastic indentation response of a flat extensive specimen for the case of a spherical indenter. The work highlights several interesting finite-element modelling techniques and provides insight into the physical processes involved in elastic-plastic indentation of certain structural ceramics. Full details of the stress distribution are given and compared with the results of elastic formulae. This work has particular application to the modelling of physical phenomena of deformation in ceramic materials in machining, wear, bearings and hardness testing. This revised version was published online in November 2006 with corrections to the Cover Date.     

A T42A Ran mutation: differential interactions with effectors and regulators, and defect in nuclear protein import

Ran, the small, predominantly nuclear GTPase, has been implicated in the regulation of a variety of cellular processes including cell cycle progression, nuclear-cytoplasmic trafficking of RNA and protein, nuclear structure, and DNA synthesis. It is not known whether Ran functions directly in each process or whether many of its roles may be secondary to a direct role in only one, for example, nuclear protein import. To identify biochemical links between Ran and its functional target(s), we have generated and examined the properties of a putative Ran effector mutation, T42A-Ran. T42A-Ran binds guanine nucleotides as well as wild-type Ran and responds as well as wild-type Ran to GTP or GDP exchange stimulated by the Ran-specific guanine nucleotide exchange factor, RCC1. T42A-Ran.GDP also retains the ability to bind p10/NTF2, a component of the nuclear import pathway. In contrast to wild-type Ran, T42A-Ran.GTP binds very weakly or not detectably to three proposed Ran effectors, Ran-binding protein 1 (RanBP1), Ran-binding protein 2 (RanBP2, a nucleoporin), and karyopherin beta (a component of the nuclear protein import pathway), and is not stimulated to hydrolyze bound GTP by Ran GTPase-activating protein, RanGAP1. Also in contrast to wild-type Ran, T42A-Ran does not stimulate nuclear protein import in a digitonin permeabilized cell assay and also inhibits wild-type Ran function in this system. However, the T42A mutation does not block the docking of karyophilic substrates at the nuclear pore. These properties of T42A-Ran are consistent with its classification as an effector mutant and define the exposed region of Ran containing the mutation as a probable effector loop.     

Method for preventing delay ambiguity

A detection error mechanism termed delay ambiguity is identified as one of the main causes of the irreducible bit error rate observed for data detection over fast fading communication channels. A periodic sequence of phase rotations applied to the phase shift keyed (PSK) transmit data symbols is proposed to prevent this type of detection error     

Using MineSet for knowledge discovery

MineSet aids knowledge discovery and supports decision making based on relational data. It uses visualization and data mining to arrive at interesting results. Providing diverse visualization tools lets users choose the most appropriate method for a given problem. The client-server architecture performs most of the computationally intensive tasks on a server, while the processed results return to the client for visualization. The paper discusses MineSet database visualization and data mining visualization     

STRL33, A novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1

The chemokine receptors CXCR4, CCR2B, CCR3, and CCR5 have recently been shown to serve along with CD4 as coreceptors for HIV-1. The tropisms of HIV-1 strains for subgroups of CD4(+) cells can be explained, at least partly, by the selective use of G protein-coupled receptors (GPCRs). We have identified a novel human gene, STRL33, located on chromosome 3 that encodes a GPCR with sequence similarity to chemokine receptors and to chemokine receptor-like orphan receptors. STRL33 is expressed in lymphoid tissues and activated T cells, and is induced in activated peripheral blood lymphocytes. When transfected into nonhuman NIH 3T3 cells expressing human CD4, the STRL33 cDNA rendered these cells competent to fuse with cells expressing HIV-1 envelope glycoproteins (Envs). Of greatest interest, STRL33, in contrast with CXCR4 or CCR5, was able to function as a cofactor for fusion mediated by Envs from both T cell line-tropic and macrophage-tropic HIV-1 strains. STRL33-transfected Jurkat cell lines also supported enhanced productive infection with HIV-1 compared with control Jurkat cells. Despite the sequence similarities between STRL33 and chemokine receptors, STRL33-transfected cell lines did not respond to any in a panel of chemokines. Based on the pattern of tissue expression of the STRL33 mRNA, and given the ability of STRL33 to function with Envs of differing tropisms, STRL33 may play a role in the establishment and/or progression of HIV-1 infection.