bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct Patterns of Dendritic Cell Cytokine Release Stimulated by Fungal β-Glucans and Toll-Like Receptor Agonists
Authors: Huang Haibin , Ostroff Gary R. , Lee Chrono K. , Wang Jennifer P. , Specht Charles A. , Levitz Stuart M. 
Published: March 2009

ABSTRACTβ-Glucans derived from fungal cell walls have potential uses as immunomodulating agents and vaccine adjuvants. Yeast glucan particles (YGPs) are highly purifiedSaccharomyces cerevisiaecell walls composed of β1,6-branched β1,3-d-glucan and free of mannans. YGPs stimulated secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) in wild-type murine bone marrow-derived myeloid dendritic cells (BMDCs) but did not stimulate interleukin-12p70 (IL-12p70) production. A purified soluble β1,6-branched β1,3-d-glucan, scleroglucan, also stimulated TNF-α in BMDCs. These two β-glucans failed to stimulate TNF-α in Dectin-1 (β-glucan receptor) knockout BMDCs. Costimulation of wild-type BMDCs with β-glucans and specific Toll-like receptor (TLR) ligands resulted in greatly enhanced TNF-α production but decreased IL-12p70 production compared with TLR agonists alone. The upregulation of TNF-α and downregulation of IL-12p70 required Dectin-1, but not IL-10. Gamma interferon (IFN-γ) priming did not overcome IL-12p70 reduction by β-glucans. Similar patterns of cytokine regulation were observed in human monocyte-derived dendritic cells (DCs) costimulated with YGPs and the TLR4 ligand lipopolysaccharide. Finally, costimulation of BMDCs with YGPs and either the TLR9 ligand, CpG, or the TLR2/1 ligand, Pam3CSK4, resulted in upregulated secretion of IL-1α and IL-10 and downregulated secretion of IL-1β, IL-6, and IFN-γ-inducible protein 10 but had no significant effects on IL-12p40, keratinocyte-derived chemokine, monocyte chemotactic protein 1, or macrophage inflammatory protein α, compared with the TLR ligand alone. Thus, β-glucans have distinct effects on cytokine responses following DC stimulation with different TLR agonists. These patterns of response might contribute to the skewing of immune responses during mycotic infections and have implications for the design of immunomodulators and vaccines containing β-glucans.
B- and T-Cell Responses in Group A Streptococcus M-Protein- or Peptide-Induced Experimental Carditis
Authors: Gorton Davina , Govan Brenda , Olive Colleen , Ketheesan Natkunam 
Published: March 2009

ABSTRACTThe etiology of rheumatic fever and rheumatic heart disease (RF/RHD) is believed to be autoimmune, involving immune responses initiated between streptococcal and host tissue proteins through a molecular mimicry mechanism(s). We sought to investigate the humoral and cellular responses elicited in a Lewis rat model of group A streptococcus M-protein- or peptide-induced experimental valvulitis/carditis, a recently developed animal model which may, in part, represent human rheumatic carditis. Recombinant streptococcal M5 protein elicited opsonic antibodies in Lewis rats, and anti-M5 antisera recognized epitopes within the B- and C-repeat regions of M5. One peptide from the streptococcal M5 protein B-repeat region (M5-B.6, amino acids 161 to 180) induced lymphocytes that responded to both recombinant M5 and cardiac myosin. Rats immunized with streptococcal M5 protein developed valvular lesions, distinguished by infiltration of CD3+, CD4+, and CD68+cells into valve tissue, consistent with human studies that suggest that RF/RHD are mediated by inflammatory CD4+T cells and CD68+macrophages. The current study provides additional information that supports the use of the rat autoimmune valvulitis model for investigating RF/RHD.
Functional Comparison of the Binding of Factor H Short Consensus Repeat 6 (SCR 6) to Factor H Binding Protein fromNeisseria meningitidisand the Binding of Factor H SCR 18 to 20 toNeisseria gonorrhoeaePorin
Authors: Shaughnessy Jutamas , Lewis Lisa A. , Jarva Hanna , Ram Sanjay 
Published: March 2009

ABSTRACTBothNeisseria meningitidisandNeisseria gonorrhoeaerecruit the alternative pathway complement inhibitory protein factor H (fH) to their surfaces to evade complement-dependent killing. Meningococci bind fH via fH binding protein (fHbp), a surface-exposed lipoprotein that is subdivided into three variant families based on one classification scheme. Chimeric proteins that comprise contiguous domains of fH fused to murine Fc were used to localize the binding site for all three fHbp variants on fH to short consensus repeat 6 (SCR 6). As expected, fH-like protein 1 (FHL-1), which contains fH SCR 6, also bound to fHbp-expressing meningococci. Using site-directed mutagenesis, we identified histidine 337 and histidine 371 in SCR 6 as important for binding to fHbp. These findings may provide the molecular basis for recent observations that demonstrated human-specific fH binding to meningococci. Differences in the interactions of fHbp variants with SCR 6 were evident. Gonococci bind fH via their porin (Por) molecules (PorB.1A or PorB.1B); sialylation of lipooligosaccharide enhances fH binding. Both sialylated PorB.1B- and (unsialylated) PorB.1A-bearing gonococci bind fH through SCR 18 to 20; PorB.1A can also bind SCR 6, but only weakly, as evidenced by a low level of binding of FHL-1 relative to that of fH. Using isogenic strains expressing either meningococcal fHbp or gonococcal PorB.1B, we discovered that strains expressing gonococcal PorB.1B in the presence of sialylated lipooligosaccharide bound more fH, more effectively limited C3 deposition, and were more serum resistant than their isogenic counterparts expressing fHbp. Differences in fH binding to these two related pathogens may be important for modulating their individual responses to host immune attack.
Children with the Le(a+b−) Blood Group Have Increased Susceptibility to Diarrhea Caused by Enterotoxigenic
Escherichia coli
Expressing Colonization Factor I Group Fimbriae
Authors: Ahmed Tanvir , Lundgren Anna , Arifuzzaman Mohammad , Qadri Firdausi , Teneberg Susann , Svennerholm Ann-Mari 
Published: March 2009

ABSTRACT

Recent studies have shown that children with blood group A have increased susceptibility to enterotoxigenic
Escherichia coli
(ETEC) diarrhea and that Lewis blood group “a” antigen (Le
a
) may be a candidate receptor for ETEC colonization factor (CF) antigen I (CFA/I) fimbriae. Based on these findings, we have attempted to determine if children with the Le(a+b−) phenotype may be more susceptible to diarrhea caused by ETEC, in particular ETEC expressing CFA/I and related fimbriae of the CFA/I group, than Le(a−b+) children. To test this hypothesis, we have determined the Lewis antigen expression in 179 Bangladeshi children from a prospective birth cohort study in urban Dhaka in which ETEC expressing major CFs such as CFA/I, CS3, CS5, and CS6 was the most commonly isolated diarrhea pathogen during the first 2 years of life. The Lewis blood group phenotypes were determined by a dot blot immunoassay using saliva samples and by a tube agglutination test using fresh red blood cells. The results indicate that Le(a+b−) children more often had symptomatic than asymptomatic ETEC infections (
P
< 0.001), whereas symptomatic and asymptomatic ETEC infections were equally frequent in Le(a−b+) children. We also show that children with the Le(a+b−) blood type had significantly higher incidences of diarrhea caused by ETEC expressing fimbriae of the CFA/I group than Le(a−b+) children (
P
< 0.001). In contrast, we did not find any association between the Lewis blood group phenotype and diarrhea caused by ETEC expressing CS6 or rotavirus.
ToeHold Artisans Collaborative: Building Entrepreneurial Capabilities to Tackle Poverty
Authors: Shanmugam Sindhu , Ramakrishna Velamuri S. 
Published: March 2009

Toehold Artisans Collaborative (TAC) is a project launched by the Asian Center for Entrepreneurship Initiatives (ASCENT), a non-profit organization based in Bangalore, to build entrepreneurial capacity in a community of footwear artisans of the small southern Indian town of Athani. Prior to ASCENT's involvement, which began in 1998, the artisans of Athani were making a subsistence wage, which did not even guarantee them two square meals a day. They could not send their children to school and were thus suffering from economic stagnation. TAC is an established Group Enterprise of 14 women Self Help Groups (SHG). Even though women's SHGs are the direct stakeholders, the men are not left out — they are treated as co-preneurs for all inputs, exposure to international fairs and production purposes. The front end of TAC is a customer-centric business enterprise that has taken the exquisite footwear brand 'ToeHold™' to challenging international mainstream markets. The backend is an artisan-centric social enterprise striving for improvement in the quality of life of about 400 artisans' families. The case documents how TAC was set up and evolved during the 1998–2006 period, the challenges it faced and continues to face, and the impact it has had on the artisan community. It is useful for examining the effective organization and running of social enterprises.
Maximum benefit from a minimal HTM
Authors: Hofmann Owen S. , Rossbach Christopher J. , Witchel Emmett 
Published: March 2009

A minimal, bounded hardware transactional memory implementation significantly improves synchronization performance when used in an operating system kernel. We add HTM to Linux 2.4, a kernel with a simple, coarse-grained synchronization structure. The transactional Linux 2.4 kernel can improve performance of user programs by as much as 40% over the non-transactional 2.4 kernel. It closes 68% of the performance gap with the Linux 2.6 kernel, which has had significant engineering effort applied to improve scalability.
We then extend our minimal HTM to a fast, unbounded transactional memory with a novel technique for coordinating hardware transactions and software synchronization. Overflowed transactions run in software, with only a minimal coupling between hardware and software systems. There is no performance penalty for overflow rates of less than 1%. In one instance, at 16 processors and an overflow rate of 4%, performance degrades from an ideal 4.3x to 3.6x.
Accelerating critical section execution with asymmetric multi-core architectures
Authors: Suleman M. Aater , Mutlu Onur , Qureshi Moinuddin K. , Patt Yale N. 
Published: March 2009

To improve the performance of a single application on Chip Multiprocessors (CMPs), the application must be split into threads which execute concurrently on multiple cores. In multi-threaded applications, critical sections are used to ensure that only one thread accesses shared data at any given time. Critical sections can serialize the execution of threads, which significantly reduces performance and scalability.
This paper proposes Accelerated Critical Sections (ACS), a technique that leverages the high-performance core(s) of an Asymmetric Chip Multiprocessor (ACMP) to accelerate the execution of critical sections. In ACS, selected critical sections are executed by a high-performance core, which can execute the critical section faster than the other, smaller cores. As a result, ACS reduces serialization: it lowers the likelihood of threads waiting for a critical section to finish. Our evaluation on a set of 12 critical-section-intensive workloads shows that ACS reduces the average execution time by 34% compared to an equal-area 32T-core symmetric CMP and by 23% compared to an equal-area ACMP. Moreover, for 7 out of the 12 workloads, ACS improves scalability by increasing the number of threads at which performance saturates.
Producing wrong data without doing anything obviously wrong!
Authors: Mytkowicz Todd , Diwan Amer , Hauswirth Matthias , Sweeney Peter F. 
Published: March 2009

This paper presents a surprising result: changing a seemingly innocuous aspect of an experimental setup can cause a systems researcher to draw wrong conclusions from an experiment. What appears to be an innocuous aspect in the experimental setup may in fact introduce a significant bias in an evaluation. This phenomenon is called measurement bias in the natural and social sciences.
Our results demonstrate that measurement bias is significant and commonplace in computer system evaluation. By significant we mean that measurement bias can lead to a performance analysis that either over-states an effect or even yields an incorrect conclusion. By commonplace we mean that measurement bias occurs in all architectures that we tried (Pentium 4, Core 2, and m5 O3CPU), both compilers that we tried (gcc and Intel's C compiler), and most of the SPEC CPU2006 C programs. Thus, we cannot ignore measurement bias. Nevertheless, in a literature survey of 133 recent papers from ASPLOS, PACT, PLDI, and CGO, we determined that none of the papers with experimental results adequately consider measurement bias.
Inspired by similar problems and their solutions in other sciences, we describe and demonstrate two methods, one for detecting (causal analysis) and one for avoiding (setup randomization) measurement bias.
StreamRay
Authors: Ramani Karthik , Gribble Christiaan P. , Davis Al 
Published: March 2009

The wide availability of commodity graphics processors has made real-time graphics an intrinsic component of the human/computer interface. These graphics cores accelerate the z-buffer algorithm and provide a highly interactive experience at a relatively low cost. However, many applications in entertainment, science, and industry require high quality lighting effects such as accurate shadows, reflection, and refraction. These effects can be difficult to achieve with z-buffer algorithms but are straightforward to implement using ray tracing. Although ray tracing is computationally more complex, the algorithm exhibits excellent scaling and parallelism properties. Nevertheless, ray tracing memory access patterns are difficult to predict and the parallelism speedup promise is therefore hard to achieve.
This paper highlights a novel approach to ray tracing based on stream filtering and presents StreamRay, a multicore wide SIMD microarchitecture that delivers interactive frame rates of 15-32 frames/second for scenes of high geometric complexity and exhibits high utilization for SIMD widths ranging from eight to 16 elements. StreamRay consists of two main components: the ray engine, which is responsible for stream assembly and employs address generation units that generate addresses to form large SIMD vectors, and the filter engine, which implements the ray tracing operations with programmable accelerators. Results demonstrate that separating address and data processing reduces data movement and resource contention. Performance improves by 56% while simultaneously providing 11.63% power savings per accelerator core compared to a design which does not use separate resources for address and data computations.
Hormone replacement therapy in women with systemic lupus erythematosus and risk of cardiovascular disease
Authors: Hochman J , Urowitz MB , Ibañez D , Gladman DD 
Published: March 2009

We sought to determine the impact of hormone replacement therapy (HRT) on the occurrence of coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE). Women in the University of Toronto lupus database who had taken HRT with no history of CAD were compared with all post-menopausal female patients with no history of HRT or CAD. Chi-squared and t-tests were used to compare the risk factors of CAD and Kaplan–Meier curve, log rank test and proportional hazard model with time-dependent covariates were used to compare the time from entry into the clinic to occurrence of CAD. A total of 114 HRT-user patients with no history of CAD were compared with 227 post-menopausal non-HRT user SLE controls. The groups were similar with respect to lupus anticoagulant, antiphospholipid antibody, cumulative steroid dose and classic cardiac risk factors. A similar percentage of patients developed CAD in the control (13.7%) and HRT (11.4%) groups. There was no difference in the time to development of CAD. In the multivariate analysis, HRT was not a risk factor for CAD. Only age ( P = 0.0001, HR = 1.11, 95% CI = 1.05, 1.17) and SLEDAI-2K ( P = 0.0001, HR = 1.10, 95% CI = 1.05, 1.16) were significantly associated with the risk of CAD. In this small group of patients with SLE, HRT alone did not appear to predispose to CAD.
Mitochondrial DNA polymorphisms are associated with susceptibility and phenotype of systemic lupus erythematosus
Authors: Jönsen A , Yu X , Truedsson L , Nived O , Sturfelt G , Ibrahim S , Bengtsson AA 
Published: March 2009

The objective of this study was to investigate the possible association between mitochondrial DNA polymorphisms and systemic lupus erythematosus (SLE). A cohort from the Department of Rheumatology, Lund University Hospital, Sweden, consisting of 166 unrelated SLE patients was investigated as well as 190 unrelated healthy blood donors. Mean age at SLE diagnosis was 39 years (range 10–83) and mean follow-up time was 16 years (range 1–44). There were 87% women among the lupus patients, and the control group consisted of 98 women and 92 men from the same geographical area and with a similar age and ethnicity. The mtDNA SNP nt16189C was associated with SLE (OR = 1.98, 95% CI 1.04–3.78, P = 0.05). In addition, SNP nt13708A was associated with SLE in males (OR = 3.46, 95% CI 1.08–11.1, P = 0.04), although the number of male patients was low. Furthermore, SNP nt10398A was associated with secondary anti-phospholipid syndrome ( P = 0.017, OR 8.2, 95% CI 1.1–63). In conclusion, in this study, we have for the first time investigated the possible association between SLE disease and mitochondrial DNA polymorphisms. Altogether, these novel results suggest that mtDNA polymorphisms may be associated with development of SLE and may potentially be of importance in SLE pathogenesis.
Severe tissue trauma triggers the autoimmune state systemic lupus erythematosus in the MRL/++ lupus-prone mouse
Authors: Anam K , Amare M , Naik S , Szabo KA , Davis TA 
Published: March 2009

Tissue damage associated with a severe injury can result in profound inflammatory responses that may trigger autoimmune development in lupus-prone individuals. In this study, we investigated the role of a large full-thickness cutaneous burn injury on the early onset of autoimmune disease in lupus-prone MRL/++ mice. MRL/++ mice (chronic model) exhibit autoimmune symptoms at >70 weeks of age, whereas MRL/-Faslpr mice (acute model) develop autoimmune disease in 17–22 weeks due to a lymphoproliferative mutation. Autoimmune disease developed in MRL/++ mice (4–15 weeks post injury) is manifested by skin lesions, vasculitis, epidermal ulcers, cellular infiltration, splenomegaly, lymphadenopathy, hypergammaglobulinemia, elevated autoantibodies and renal pathologies including proteinuria, glomerulonephritis and immune complex deposition; complications that contribute to reduced survival. Transcription studies of wound margin tissue show a correlation between the pathogenic effects of dysregulated IL-1β, IL-6, TNF-α and PGE2 synthesis during early wound healing and early onset of autoimmune disease. Interestingly, MRL/++ mice with healed wounds (30–40 days post burn) strongly rejected skin isografts. Conversely, skin isografts transplanted onto naive age-matched MRL/++ littermates achieved long-term survival. Collectively, these findings suggest that traumatic injury exacerbates inflammatory skin disease and severe multi-organ pathogenesis in lupus-prone mice.
Outcome of lupus nephritis in Indian children
Authors: Hari P , Bagga A , Mahajan P , Dinda A 
Published: March 2009

We report the clinicopathological features, treatment and outcome of 54 Indian children (14 boys) with biopsy-proven lupus nephritis followed over a 10-year period. The mean age (SD) at onset of disease was 9.6 ± 2.6 (range 2.5–14.4) years. Twenty-six (48.1%) patients had class IV nephritis, 7 (13.0%) had class V, whereas class I, II and III nephritis were present in 3 (5.6%), 10 (18.5%) and 6 (11.1%) patients, respectively. Hypertension, haematuria and nephrotic range proteinuria were present in 30 (55.6%), 31 (57.4%) and 28 (51.8%) patients, respectively. Compared with all the other classes combined, there were more boys among patients with class IV nephritis, and hypertension, haematuria, nephrotic syndrome and decreased glomerular filtration rate at presentation were more common. The mean duration of follow-up was 3.1 ± 2.9 years (median 2.5, range 0.2–10.3 years). Of the 39 patients who were followed-up for at least 1 year, 33 (84.6%) were in complete or partial remission, whereas six (15.4%) had no response to therapy. The incidence of serious infection was 1.5 episodes per 10 patient-years. Nine patients died, of whom four had serious infections or septicaemia, and three developed end-stage renal failure (ESRF). The patient survival rate at 3 years and at last follow-up visit was 88% and 83.3%, respectively, whereas the renal survival rates (without ESRF) were 92% and 94.4% respectively. Cox regression analysis showed no relation of gender, age of onset, presence of hypertension, haematuria and proteinuria, estimated glomerular filtration rate, renal histology and response to therapy to the outcome of death or ESRF. We found lower patient survival rate as compared with data from the developed countries but similar to that seen in developing countries. Serious infections were an important cause of mortality besides renal failure.
Circulating endothelial cells and angiogenic proteins in patients with systemic lupus erythematosus
Authors: Robak E , Kierstan M , Cebula B , Krawczynska A , Sysa-Jedrzejowska A , Wierzbowska A , Smolewski P , Robak T 
Published: March 2009

The aim of our study was to assess absolute counts of different subpopulations of circulating endothelial cells (CEC) in patients with active and inactive systemic lupus erythematosus (SLE). We have also investigated a potential correlation of CEC numbers with serum levels of angiogenic proteins as well as with clinical and laboratory symptoms of the disease. For the first time in SLE, CEC were enumerated directly, by the ‘single platform’ method. Resting (rCEC), activated (aCEC) and progenitor (pCEC) endothelial cells were identified in patients with SLE and healthy volunteers using four-colour flow cytometry. Serum concentrations of angiogenic proteins (vascular endothelial growth factor, placental growth factor (PIGF), soluble vascular cell adhesion molecule and endoglin) were evaluated by ELISA. The SLE activity was scored according to the Systemic Lupus Activity Measure system. We found that total CEC number in patients with SLE was significantly higher (median 14.2/μL) than in the control group (median 3.3/μL) ( P < 0.0001). Absolute counts of aCEC, rCEC and pCEC (medians 4.9/μL, 6.8/μL and 2.3/μL, respectively) were also higher in patients with SLE than in healthy persons (medians 0.9/μL, 1.6/μL and 0.1/μL, respectively), with P < 0.0001 for all comparisons. There was no correlation between CEC or their subpopulations and SLE activity. Strong positive correlations were found between CEC, rCEC and pCEC numbers and serum levels of PIGF. Moreover, aCEC, rCEC and pCEC counts were significantly higher in SLE patients with leukopenia. In conclusion, our results show that absolute CEC counts and angiogenic proteins levels are elevated in patients with SLE as compared with healthy controls. These data may suggest that angiogenic process is involved in the pathogenesis of this disease.