Three parallel programming paradigms: Comparisons on an archetypal PDE computation

Three paradigms for distributed-memory parallel computation that free the application programmer from the details of message passing are compared for an archetypal structured scientific computation -- a nonlinear, structured-grid partial differential equation boundary value problem -- using the same algorithm on the same hardware. All of the paradigms -- parallel languages represented by the Portland Group's HPF, (semi-)automated serial-to-parallel source-to-source translation represented by CAP-Tools from the University of Greenwich, and parallel libraries represented by Argonne's PETSc -- are found to be easy to use for this problem class, and all are reasonably effective in exploiting concurrency after a short learning curve. The level of involvement required by the application programmer under any paradigm includes specification of the data partitioning, corresponding to a geometrically simple decomposition of the domain of the PDE. Programming in SPMD style for the PETSc library requires writing only the routines that discretize the PDE and its Jacobian, managing subdomain-to-processor mappings (affine global-to-local index mappings), and interfacing to library solver routines. Programming for HPF requires a complete sequential implementation of the same algorithm as a starting point, introduction of concurrency through subdomain blocking (a task similar to the index mapping), and modest experimentation with rewriting loops to elucidate to the compiler the latent concurrency. Programming with CAPTools involves feeding the same sequential implementation to the CAPTools interactive parallelization system, and guiding the source-to-source code transformation by responding to various queries about quantities knowable only at runtime. Results representative of "the state of the practice" for a scaled sequence of structured grid problems are given on three of the most important contemporary high-performance platforms: the IBM SP, the SGI Origin 2000, and the CRAYY T3E.

Call admission control algorithms in OFDM-based wireless multiservice networks

Orthogonal frequency division multiplexing(OFDM) is becoming a fundamental technology in future generation wireless communications. Call admission control is an effective mechanism to guarantee resilient, efficient, and quality-of-service (QoS) services in wireless mobile networks. In this paper, we present several call admission control algorithms for OFDM-based wireless multiservice networks. Call connection requests are differentiated into narrow-band calls and wide-band calls. For either class of calls, the traffic process is characterized as batch arrival since each call may request multiple subcarriers to satisfy its QoS requirement. The batch size is a random variable following a probability mass function (PMF) with realistically maximum value. In addition, the service times for wide-band and narrow-band calls are different. Following this, we perform a tele-traffic queueing analysis for OFDM-based wireless multiservice networks. The formulae for the significant performance metrics call blocking probability and bandwidth utilization are developed. Numerical investigations are presented to demonstrate the interaction between key parameters and performance metrics. The performance tradeoff among different call admission control algorithms is discussed. Moreover, the analytical model has been validated by simulation. The methodology as well as the result provides an efficient tool for planning next-generation OFDM-based broadband wireless access systems.

Questions of 'h' in Northern Ireland: Breathing New Life on the Aspiration Theory

This paper considers existing ideas concerning pronunciation of the letter name for (LNH) in Northern Irish English (NIE). Traditionally, the status of LNH realisation as an ethnic marker has gone unquestioned: Catholics are thought to say [het&Mac186;] while the Protestant norm is assumed to be [etS]. The phonetic difference between these realisations is consistently described as word-initial aspiration versus non-aspiration, with aspiration attributed exclusively to Irish language influence. Here, we show that an explanation based on aspiration alone is phonologically unsatisfying and question whether aspiration is, in fact, an Irish language or ethnically dictated phenomenon. It is further suggested here that the overwhelming stigmatisation of LNH realisation may be responsible for blocking a potential sound change in NIE. While this paper is not intended as a detailed account of ethnolinguistic differences in NI phonology, it engages critically with the over-simplistic and widespread notion that LNH realisation is a result of transfer from the Irish language to the English used by Catholics in Northern Ireland.

IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.

Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.

Role of Stromal Cell-Derived Factor-1 in Neoangiogenesis in Endometriosis Lesions

Endometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Treatment for endometriosis primarily focuses on symptom relief, is short term with severe side effects and often leads to recurrence of the condition. Establishing new blood supply is a fundamental requirement for endometriosis lesions growth. This has led to the idea that antiangiogenic therapy may be a successful approach for inhibiting endometriosis. Recent evidence indicates that endothelial progenitor cells (EPCs) contribute to neoangiogenesis of endometriotic lesions. These EPCs are recruited to the lesion site by stromal cell-derived factor-1 (SDF-1). We hypothesize that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions and that administration of SDF-1 blocking antibody will inhibit lesion growth by inhibiting angiogenesis in a murine model of endometriosis. Immunohistochemistry for SDF-1 and CD34 was performed on human endometriosis and normal endometrial samples. Quantification of SDF-1 and EPCs was performed in the blood of endometriosis patients and controls using ELISA and flow cytometry, respectively. A new mouse model of endometriosis was developed using BALB/c-Rag2-/-/IL2rg-/- mice to investigate role of SDF-1 in neoangiogenesis. Either SDF-1 blocking antibody or an isotype control was administered on a weekly basis for four weeks. Weekly samples of peripheral blood from mice were analyzed for SDF-1, other cytokines of interest and EPCs. Mice were euthanized at seven weeks to observe lesion growth and blood vessel development. Our results indicate overabundance of SDF-1 and CD34+ progenitor cells in human endometriotic lesions compared to eutopic endometrium. In the mouse model, SDF-1 and circulating EPC levels decreased from pre-treatment levels after one week, and remained constant over the course of the treatment in both SDF-1 blocking antibody and isotype control groups. In the SDF-1 blocking group, reduced vascularity of lesions, identified by immunofluorescence staining for CD31, was revealed compared to isotype controls. These findings suggest that SDF-1 may be responsible for CD34+ progenitor cell recruitment to the neoangiogenic sites in endometriosis. Blocking of SDF-1 reduces neovascularization of human endometriotic lesions in a mouse model. Further studies on blocking SDF-1 in combination with other antiangiogenic agents are needed.

BRCA1 Regulates IFN-γ Signaling through a Mechanism Involving the Type I IFNs

BRCA1 encodes a tumor suppressor gene that is mutated in the germ line of women with a genetic predisposition to breast and ovarian cancer. BRCA1 has been implicated in a number of important cellular functions including DNA damage repair, transcriptional regulation, cell cycle control, and ubiquitination. Using an Affymetrix U95A microarray, IRF-7 was identified as a BRCA1 transcriptional target and was also shown to be synergistically up-regulated by BRCA1 specifically in the presence of IFN-gamma, coincident with the synergistic induction of apoptosis. We show that BRCA1, signal transducer and activator of transcription (STAT)-1, and STAT2 are all required for the induction of IRF-7 following stimulation with IFN-gamma. We also show that the induction of IRF-7 by BRCA1 and IFN-gamma is dependent on the type I IFNs, IFN-alpha and IFN-beta. We show that BRCA1 is required for the up-regulation of STAT1, STAT2, and the type I IFNs in response to IFN-gamma. We show that BRCA1 is localized at the promoters of the molecules involved in type I IFN signaling leading to their up-regulation. Blocking this intermediary type I IFN step using specific antisera shows the requirement for IFN-alpha and IFN-beta in the induction of IRF-7 and apoptosis. Finally, we outline a mechanism for the BRCA1/IFN-gamma regulation of target genes involved in the innate immune response, which is dependent on type I IFN signaling.

Chondrogenic Differentiation Alters the Immunosuppressive Property of Bone Marrow-Derived Mesenchymal Stem Cells, and the Effect is Partially due to the Upregulated Expression of B7 Molecules

To investigate the immunosuppressive properties of mesenchymal stem cells (MSCs), in the present study we examined the immunogenicity of undifferentiated and tri-lineage (chondrocytes, osteoblasts and adipocytes) differentiated rat bone marrow-derived MSCs under xenogeneic conditions. After chondrogenic-differentiation, rat bone marrow-derived MSCs stimulated human peripheral blood monocyte-derived DCs (hDCs), leading to 8- and 4-fold higher lymphocyte proliferation and cytotoxicity than that of undifferentiated MSCs. The Chondrogenic-differentiated MSCs were chemotactic to hDCs in Dunn chamber chemotaxis system and were rosetted by hDCs inrosette assays. Flow cytometry analysis revealed that chondrogenic-differentiated MSCs had promoted hDCs maturation causing higher CD83 expression in hDCs, whereas undifferentiated MSCs, osteogenic-and adipogenic-differentiated MSCs showed inhibitory effect on hDCs maturation. The co-stimulatory molecules B7 were up-regulated only in the chondrogenic-differentiated MSCs. After blocking B7 molecules with specific monoclonal antibodies in the chondrogenic-differentiated MSCs, CD83 expression of co-cultured hDCs was greatly reduced. In conclusion, chondrogenic differentiation may increase the immunogenicity of MSCs, leading to stimulation of DCs. The up-regulated expression of B7 molecules on the chondrogenic differentiated MSCs may be partially responsible for this event.

Filling Ability and Passing Ability of Self-Consolidating Concrete

This paper reviews statistical models obtained from a composite factorial design study, which was carried out to determine the influence of three key parameters of mixture composition on filling ability and passing ability of self-consolidating concrete (SCC). This study was a part of the European project “Testing SCC”- GRD2-2000-30024. The parameters considered in this study were the dosages of water and high-range water-reducing admixture (HRWRA), and the volume of coarse aggregates. The responses of the derived statistical models were slump flow, T50 , T60, V-funnel flow time, Orimet flow time, and blocking ratio (L-box). The retention of these tests was also measured at 30 and 60 minutes after adding the first water. The models are valid for mixtures made with 188 to 208 L/m3 (317 to 350 lb/yd3) of water, 3.8 to 5.8 kg/m3 (570 to 970 mL/100 kg of binder) of HRWRA, and 220 to 360 L/m3 (5.97 to 9.76 ft3/yd3) of coarse aggregates. The utility of such models to optimize concrete mixtures and to achieve a good balance between filling ability and passing ability is discussed. Examples highlighting the usefulness of the models are presented using isoresponse surfaces to demonstrate single and coupled effects of mixture parameters on slump flow, T50 , T60 , V-funnel flow time, Orimet flow time, and blocking ratio. The paper also illustrates the various trade-offs between the mixture parameters on the derived responses that affected the filling and the passing ability.

The PD-1/PD-L1 Axis: An Immune-Mediated Mechanism of Chemoresistance in Cancer

The ability of tumour cells to avoid immune destruction (immune escape) and their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. The interaction between specific molecules on the surface of tumour cells with their corresponding receptors on immune effector cells can result in inhibition of these effector cells, consequently allowing tumour cells to evade the host’s anti-tumour immune response. The interaction of the Programmed Death Ligand 1 (PD-L1) on the surface of tumour cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors, and is a specific example of an immune escape mechanism tumour cells use to avoid immune destruction. Clinically, antibodies capable of blocking the PD-1/PD-L1 interaction have demonstrated significant therapeutic benefit, and are currently being used to help bolster patients’ immune response against malignant cells in a variety of cancer types. Here we show that the PD-1/PD-L1 interaction also leads to tumour cell resistance to conventional chemotherapeutic agents. Incubation of PD-L1-expressing human and mouse tumour cells with PD-1-expressing Jurkat T cells or purified recombinant PD-1 resulted in tumour cell resistance to doxorubicin and docetaxel. Interference with the PD-1/PD-L1 interaction using blocking anti-PD-1 or anti-PD-L1 antibody or shRNA-mediated gene silencing resulted in attenuation of PD-1/PD-L1-mediated drug resistance. Moreover, inhibition of the PD-1/PD-L1 signalling axis using anti-PD-1 antibody enhanced the effect of doxorubicin chemotherapy to inhibit 4T1 tumour cell metastasis in an in vivo mouse model of mammary carcinoma. These findings indicate that blockade of the PD-1/PD-L1 axis may be a useful approach to immunosensitize and chemosensitize tumours in cancer patients and provide a rationale for the use of anti-PD-1/PD-L1 antibodies as adjuvants to chemotherapy.

Limitations in using peptide drugs to characterize calcitonin gene-related peptide receptors

Calcitonin gene-related peptide (CGRP) is an endogenous vasodilator peptide that produces its effects by activation of CGRP(1) and CGRP(2) receptor subtypes, These receptor subtypes are characterized in functional studies using the agonist Cys(Acm)(2,7)-human-alpha-calcitonin gene-related peptide (Cys(ACM)(2,7)-h-alpha-CGRP), which activates CGRP(2) receptors, and the antagonist h-alpha CGRP(8-37) which has a high affinity for CGRP, receptors and a low affinity for CGRP(2) receptors. Our aim was to identify factors that may limit the use of these drugs to characterize CGRP receptor subtypes. We studied CGRP receptors using isolated ring segments of pig coronary and basilar arteries studied in vitro. The affinity of the antagonist h-alpha CGRP(8-37) for inhibiting h-alpha CGRP-induced relaxation of coronary arteries (log(10) of the antagonist equilibrium dissociation constant = -5.33) was determined from Schild plots that had steep slopes. Therefore, we used capsaicin to investigate the role of endogenous CGRP in confounding affinity measurements for h-alpha CGRP(8-37). After capsaicin treatment, the slopes of the Schild plots were not different from one, and a higher affinity of h-CGRP(8-37) in blocking relaxation was obtained (log(10) of the antagonist equilibrium dissociation constant = -6.01). We also investigated the agonist activity of the putative CGRP, receptor selective agonist Cys(Acm)(2,7)-h-alpha-CGRP. We found that maximal relaxation of coronary arteries caused by Cys(Acm)(2,7)-h-alpha CGRP was dependent upon the level of contractile tone induced by KCI. We also determined the K-A for Cys(Acm)(2,7)-h-alpha CGRP and found that the K-A (817 nM) was not significantly different from the EC50 (503 nM) for this drug in causing relaxation, indicating that Cys(Acm)(2,7)-h-alpha CGRP is a partial agonist. Because experimental conditions affect the actions of h-CGRP(8-37) and Cys(Acm)(2,7)-h-alpha CGRP, the conditions must be carefully controlled to reliably identify CGRP receptor subtypes.

Characterization of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide

A novel N-terminally substituted Pro(3) analogue of glucose-dependent insulinotropic polypeptide (GIP) was synthesized and tested for plasma stability and biological activity both in vitro and in vivo. Native GIP was rapidly degraded by human plasma with only 39 +/- 6% remaining intact after 8 h, whereas (Pro(3))GIP was completely stable even after 24 h. In CHL cells expressing the human GIP receptor, (Pro(3))GIP antagonized the cyclic adenosine monophosphate (cAMP) stimulatory ability of 10(-7)M native GIP, with an IC50 value of 2.6 muM. In the clonal pancreatic beta cell line BRIN-BD11, (Pro(3))GIP over the concentration range 10(-13) to 10(-8) M dose dependently inhibited GIP-stimulated (10(-7) M) insulin release (1.2- to 1.7-fold; P <0.05 to P <0.001). In obese diabetic (ob/ob) mice, intraperitoneal administration of (Pro(3))GIP (25 nmol/kg body wt) countered the ability of native GIP to stimulate plasma insulin (2.4-fold decrease; P <0.001) and lower the glycemic excursion (1.5-fold decrease; P <0.001) induced by a glucose load (18 mmol/kg body wt). Collectively these data demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor antagonist capable of blocking the ability of native GIP to increase cAMP, stimulate insulin secretion, and improve glucose homeostasis in a commonly employed animal model of type 2 diabetes. (C) 2002 Elsevier Science (USA).

Modulating the selectivity for CO and butane oxidation over heterogeneous catalysis through amorphous catalyst coatings

The preparation of porous films directly deposited onto the surface of catalyst particles is attracting increasing attention. We report here for the first time a method that can be carried out at ambient pressure for the preparation of porous films deposited over 3 mm diameter catalyst particles of silica-supported Pt-Fe. Characterization of the sample prepared at ambient pressure (i.e., open air, OA) and its main structural differences as compared with a Na-A (LTA) coated catalyst made using an autoclave-based method are presented. The OA-coated material predominantly exhibited an amorphous film over the catalyst surface with between 4 and 13% of crystallinity as compared with fully crystallized LTA zeolite crystals. This coated sample was highly selective for CO oxidation in the presence of butane with no butane oxidation observed up to 350 degrees C. This indicates, for the first time, that the presence of a crystalline membrane is not necessary for the difference in light off temperature between CO and butane to be achieved and that amorphous films may also produce this effect. An examination of the space velocity dependence and adsorption of Na+ on the catalysts indicates that the variation in CO and butane oxidation activity is not caused by site blocking predominantly, although the Pt activity was lowered by contact with this alkali.

Atomistic studies of interactions between the dominant lattice dislocations and γ/γ-lamellar boundaries in lamellar γ-TiAl

This paper reports on atomistic simulations of the interactions between the dominant lattice dislocations in ?-TiAl (<1 0 1] superdislocations) with all three kinds of ?/?-lamellar boundaries in polysynthetically twinned (PST) TiAl. The purpose of this study is to clarify the early stage of lamellar boundary controlled plastic deformation in PST TiAl. The interatomic interactions in our simulations are described by a bond order potential for L10-TiAl which provides a proper quantum mechanical description of the bonding. We are interested in the dislocation core geometries that the lattice produces in proximity to lamellar boundaries and the way in which these cores are affected by the elastic and atomistic effects of dislocation-lamellar boundary interaction. We study the way in which the interfaces affect the activation of ordinary dislocation and superdislocation slip inside the ?-lamellae and transfer of plastic deformation across lamellar boundaries. We find three new phenomena in the atomic-scale plasticity of PST TiAl, particularly due to elastic and atomic mismatch associated with the 60° and 120° ?/?-interfaces: (i) two new roles of the ?/?-interfaces, i.e. decomposition of superdislocations within 120° and 60° interfaces and subsequent detachment of a single ordinary dislocation and (ii) blocking of ordinary dislocations by 60° and 120° interfaces resulting in the emission of a twinning dislocation.

Prediction of Fresh and Hardened Properties of Self-Consolidating Concrete Using Neurofuzzy Approach

Self-consolidating concrete (SCC) developed in Japan in the late 80s has enabled the construction industry to reduce demand on the resources, improve the work conditions and also reduce the impact on the environment by elimination of the need for compaction. This investigation aimed at exploring the potential use of the neurofuzzy (NF) approach to model the fresh and hardened properties of SCC containing pulverised fuel ash (PFA) as based on experimental data investigated in this paper. Twenty six mixes were made with water-to-binder ratio ranging from 0.38 to 0.72, cement content ranging from 183 to 317 kg/m3 , dosage of PFA ranging from 29 to 261 kg/m3 , and percentage of superplasticizer, by mass of powder, ranging from 0 to 1%. Nine properties of SCC mixes modeled by NF were the slump flow, JRing combined to the Orimet, JRing combined to cone, V-funnel, L-box blocking ratio, segregation ratio, and the compressive strength at 7, 28, and 90 days. These properties characterized the filling ability, the passing ability, the segregation resistance of fresh SCC, and the compressive strength. NF model is constructed by training and testing data using the experimental results obtained in this study. The results of NF models were compared with experimental results and were found to be quite accurate. The proposed NF models offers useful modeling approach of the fresh and hardened properties of SCC containing PFA.

Genetic programming based formulation for fresh and hardened properties of self-compacting concrete containing pulverised fuel ash

Self-compacting concrete (SCC) flows into place and around obstructions under its own weight to fill the formwork completely and self-compact without any segregation and blocking. Elimination of the need for compaction leads to better quality concrete and substantial improvement of working conditions. This investigation aimed to show possible applicability of genetic programming (GP) to model and formulate the fresh and hardened properties of self-compacting concrete (SCC) containing pulverised fuel ash (PFA) based on experimental data. Twenty-six mixes were made with 0.38 to 0.72 water-to-binder ratio (W/B), 183–317 kg/m³ of cement content, 29–261 kg/m³ of PFA, and 0 to 1% of superplasticizer, by mass of powder. Parameters of SCC mixes modelled by genetic programming were the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength at 7, 28 and 90 days. GP is constructed of training and testing data using the experimental results obtained in this study. The results of genetic programming models are compared with experimental results and are found to be quite accurate. GP has showed a strong potential as a feasible tool for modelling the fresh properties and the compressive strength of SCC containing PFA and produced analytical prediction of these properties as a function as the mix ingredients. Results showed that the GP model thus developed is not only capable of accurately predicting the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength used in the training process, but it can also effectively predict the above properties for new mixes designed within the practical range with the variation of mix ingredients.