bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Short Space–Time-Scale Variability of Oceanic Rain Using TOPEX/Jason
Authors: Tournadre J. , Bhandari S. 
Published: July 2008

Abstract
Information on the spatial and temporal variability of rain rate is important not only for meteorology and hydrology but also for the design of remote sensing and in situ measuring or of millimeter wave communication systems. The Ocean Topography Experiment (TOPEX)/Jason Tandem Mission (TM) collocated rain dataset is used in this study to determine the small space-scale (5 km) and time-scale (70 s) rain variability. TOPEX and Jason dual-frequency (Ku and C bands) radar altimeter data have been extensively used during the past decade to detect and study oceanic precipitations. During the TM, designed to intercalibrate and validate the two altimeters, the two satellites were put on the same orbit with a 70-s time separation. With combined use of altimeter and passive microwave radiometers (also available on board altimeter missions), rain intensity, rain attenuation, rain layer height, rain event length, and surface winds can also be estimated and provide valuable coincident geophysical contextual information. The size of the TM collocated rain database (140 000 samples) is large enough to allow a meaningful statistical analysis of the time–space variability of rain over the World Ocean. The analysis of the different terms contributing to the variability of rain attenuation, from which rain rate is inferred, shows that the geophysical and/or instrumental noise is small enough to allow a meaningful estimation of the variability of the measured rain rate. The analysis of the time and space variabilities and their relation reveals two well-defined regimes. The first one, corresponding to convective rain cells (i.e., rain rate greater than 3–4 mm h−1, length smaller than 50 km, and freezing level greater than 3.5 km), is characterized by high temporal and spatial variabilities (greater than 2–3 mm h−1) that increase with increasing rain intensity and decreasing cell length. Horizontal variability is significantly larger than the temporal one and surface wind has a very limited impact. The second regime corresponds to stratiform and/or weak rain cells. The temporal and spatial variabilities are relatively low (on the order of 1–2 mm h−1) and vary little with rain intensity and cell length. The temporal variability increases with surface wind and largely exceeds the spatial variability (ratio of 2 or more); the ratio strongly increases with increasing wind speed.
Defects in Notch1 upregulation upon activation of T Cells from patients with systemic lupus erythematosus are related to lupus disease activity
Authors: Sodsai P , Hirankarn N , Avihingsanon Y , Palaga T 
Published: July 2008

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of autoantibodies and deposition of immune complexes in various organs. T cells play a central role in driving disease progression, and multiple defects in T cells from patients with SLE have been uncovered. Notch signalling is an evolutionarily well-conserved signalling cascade involved in the proliferation, differentiation and apoptosis of T lymphocytes during development and peripheral effector functions. In this study, we investigated the correlation between expression of Notch receptor and the severity of SLE disease. On the contrary to T lymphocytes from healthy controls ( n = 11), Tlymphocytes from patients with active SLE ( n = 12) failed to upregulate Notch1 upon in-vitro stimulation as quantified by quantitative real time RT-PCR ( P ≤ 0.025). Among patients with inactive SLE ( n = 10), those with late onset of flare exhibited significantly less Notch1 upregulation compared with SLE patients with remission. Expression of the Notch target genes, Hes1 and deltex, was also lower in patients with active SLE. The decrease in Notch1 mRNA expression was consistent with less Notch1 protein expression in patients with active SLE. The defects in Notch1 upregulation correlated with decreased proliferation, CD25 and Foxp3 expression upon stimulation in vitro. Taken together, the failure of T cells to upregulate Notch1 upon activation may be a key feature of active SLE and a potential therapeutic target.
Genetic susceptibility and haplotype analysis between Fcγ receptor IIB and IIIA gene with systemic lupus erythematosus in Chinese population
Authors: Pan F , Tang X , Zhang K , Li X , Xu J , Chen H , Ye DQ 
Published: July 2008

The objective of this study is to understand the role of FcγRIIB and FcγRIIIA gene in susceptibility to systemic lupus erythematosus (SLE), and to examine possible susceptible haplotypes between two genes. A total of 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, were selected according to 1997 criteria of American College of Rheumatology. In addition, 316 family members of these patients were also genotyped. A family-based association study was used to explore the relationship between gene polymorphism and SLE. We studied 13 single-nucleotide polymorphisms (SNPs) encoding non-synonymous substitution in the FcγRIIB and FcγRIIIA gene (four SNPs in the FcγRIIB gene and nine SNPs in the FcγRIIIA gene) with respect to genetic susceptibility to SLE. All SNPs were genotyped by restriction fragment length polymorphism method. Among 13 SNPs, univariate (single-marker) family-based association tests showed that variant alleles at only four SNPs (rs10917661 and rs1050501, in exon 2 and exon 5 of FcγRIIB gene, rs403016 and rs428888, in exon3 of FcγRIIIA gene respectively) were significantly associated with genetic susceptibility to SLE. Furthermore, the haplotype-specific FBATs showed 50Ter-225Thr (34.1%, in FcγRIIB gene) and 72Arg-118Asn (40%, in the FcγRIIIA gene) haplotype were more frequently transmitted in SLE than other haplotypes ( Z = 3.539, P = 0.00042; Z = 2.678, P = 0.007412 respectively). But haplotypes were not found between FcγRIIB and FcγRIIIA gene Our results suggest that there were meaningful haplotype in FcγRIIIA and FcγRIIB gene respectively. FcγRIIIA and FcγRIIB genes in the pathogenesis of SLE may play an independent role in Chinese population.
Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression
Authors: Jin Ou , Kavikondala Sushma , Sun Lingyun , Fu Rong , Mok Mo-Yin , Chan Albert , Yeung Joseph , Lau Chak-Sing 
Published: July 2008

AbstractDendritic cells (DCs) are functionally abnormal in systemic lupus erythematosus (SLE). However, previous studies have involved in-vitro cytokine-induced DCs. In this investigation, directly isolated circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in SLE were studied. Blood dendritic cell antigen (BDCA)-4 and BDCA-1 magnetic isolation kits were used to isolate blood pDCs and mDCs from 30 SLE patients and 36 controls. Their number and surface markers, and their relationship with lupus disease activity were evaluated. The percentage of pDCs per peripheral blood mononuclear cells was higher in SLE (0.33 ± 0.14) than in controls (0.16 ± 0.09, P < 0.01), but that of mDCs was lower in SLE (0.43 ± 0.14) than in controls (0.63 ± 0.32; P < 0.01). In controls, both pDCs and mDCs expressed high levels of MHC-II, however, the expression of CD86, CD83 and CCR7 on pDCs were significantly lower than that on mDCs (all P < 0.05). mDCs from patients with SLE, particularly those with active disease, expressed lower CD83 than controls. In health, circulating mDCs may be more efficient than pDCs in stimulating T cells. In SLE, the increased number of circulating pDCs supports a pathogenic role for these cells, and the decreased mDC number and CD83 expression may explain the susceptibility to infections in these patients.
A prospective multicentre study of mycophenolate mofetil combined with prednisolone as induction therapy in 213 patients with active lupus nephritis
Authors: F Lu , Y Tu , X Peng , L Wang , H Wang , Z Sun , H Zheng , Z Hu 
Published: July 2008

Mycophenolate mofetil (MMF) with prednisolone has been associated with high remission rates when used as induction treatment for lupus nephritis. This prospective, multicentre, cohort study investigates the efficacy and safety of this regimen over 24 weeks in 213 Chinese patients with active lupus nephritis (Classes III, IV, V or combination). Baseline activity index (AI) was 6.91 ± 3.33 and chronicity index (CI) was 1.9 ± 1.2. The remission rate was 82.6% at 24 weeks (complete remission, 34.3%; partial remission, 48.4%). There were significant ( P < 0.01) improvements in kidney function shown by reductions in proteinuria, serum albumin, serum creatinine and creatinine clearance, as well as in systemic lupus erythematosus disease activity index (SLEDAI) scores. Independent risk factors influencing remission were pathological classification (including Class V and III or Class V and IV nephritis) and elevated serum creatinine at baseline (OR 2.967, 95% CI: 1.479–6.332, P = 0.001 and OR 1.007, 95% CI: 1.002–1.011, P = 0.001, respectively). Patients with concomitant membranous features on biopsy had a lower remission rate than those with Class III and IV nephritis (66.7% vs 87.3%, P = 0.002). Renal biopsy was repeated in 25 patients following treatment. There was a transition to less severe pathological morphologies in majority of subjects. Infections were monitored throughout treatment: eight patients (3.8%) experienced bacterial infections, whereas herpes zoster occurred in seven patients. Nine patients (4.2%) suffered from gastrointestinal upset, which resolved without discontinuation of MMF. One patient became leucopenic, whereas another died from active disease unrelated to kidney symptoms. MMF combined with prednisolone is an effective and well-tolerated induction treatment for patients with active lupus nephritis and for controlling SLE systemic activity.
Kidney transplantation in lupus patients: a case–control study from a single centre
Authors: Lionaki S , Kapitsinou PP , Iniotaki A , Kostakis A , Moutsopoulos HM , Boletis JN 
Published: July 2008

This study was conducted to determine kidney transplantation (KTx) outcomes for Greek patients with renal failure caused by lupus nephritis (LN) compared with matched controls, kidney recipients with other causes of end-stage renal disease (ESRD). Twenty-six patients with systemic lupus erythematosus (SLE) subjected to 26 kidney transplants were studied. For comparative purposes a case–control group was selected, matched for gender, source of donor, age and time of KTx. Patient and graft survival estimates were calculated with the Kaplan–Meier product limit estimator and survival estimates were compared with the log-rank test. All patients received cyclosporine or tacrolimus in combination with azathioprine or mycophenolate mofetil for chronic immunosuppression in addition to steroids. Fourteen transplants were from living-related donors and 12 were from deceased donors. The graft survival rates for lupus patients were 88% at 1 year, 67% at 5 years, 38% at 10 years, poorer than the control survival rates of 92%, 92% and 84% ( P = 0.004). Patient survival in the lupus group did not differ from that of the controls. Survival in the lupus group was 92% at 1 year, 77% at 5 years and 77% at 10 years vs. 96%, 92% and 92% ( P = 0.26). Chronic allograft nephropathy was the major cause of graft loss. Recurrent LN was detected in two patients, but only one lead to graft failure. SLE patients compared with controls had significantly higher rates of hypertension, cardiovascular disease, infections and malignancies. Compared with matched controls, SLE patients had inferior but still satisfactory graft survival rates, whereas patient survival rates were similar.
Childhood agricultural and adult occupational exposures to organic dusts in a population-based case–control study of systemic lupus erythematosus
Authors: Parks CG , Cooper GS , Dooley MA , Park MM , Treadwell EL , Gilkeson GS 
Published: July 2008

Organic dust exposure can influence the development and symptoms of immune-related diseases such as atopy and asthma, but has rarely been examined in relation to systemic autoimmunity. The present analyses explore the association of lifetime farm and occupational organic dust exposures with systemic lupus erythematosus (SLE) in recently diagnosed patients ( n = 265) compared with controls ( n = 355) frequency matched by age, sex and state. Questionnaire data included childhood farm residence, childhood and adult experience with specific crops, and adult work in textiles, hog or poultry processing and paper or furniture manufacture. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression models including age, sex, state, race, education and silica exposure. Overall childhood or adult farm contact and childhood farm residence were not associated with SLE. Farm contact with livestock was inversely associated with SLE (OR = 0.55, 95% CI 0.35, 0.88). This effect was most pronounced among those with childhood farm residence and both childhood and adult livestock exposure (OR = 0.19; 95% CI 0.06, 0.63), but was difficult to separate from adult exposure to grains or corn. Other adult occupational exposures were not associated with SLE risk overall, regardless of childhood farm residence or livestock exposure, although an inverse association was seen among non-smokers (OR = 0.59; 95% CI 0.33, 1.1), particularly for textile work (OR = 0.34; 95% CI 0.19, 0.64). These exploratory findings support the development of studies to specifically investigate the effects of organic dust exposure on SLE risk, with particular attention to exposure assessment and characterization of demographics, smoking and other occupational exposures.
Haemolytic anaemia in a multi-ethnic cohort of lupus patients: a clinical and serological perspective
Authors: Jeffries M , Hamadeh F , Aberle T , Glenn S , Kamen DL , Kelly JA , Reichlin M , Harley JB , Sawalha AH 
Published: July 2008

Systemic lupus erythematosus is a chronic autoimmune disease that can be associated with a variety of haematological manifestations. We identified 76 patients with haemolytic anaemia in a cohort of 1251 unrelated female lupus patients enrolled in our studies. The presence of the various American College of Rheumatology clinical criteria for lupus and serological specificities were determined in lupus patients with haemolytic anaemia and compared with a group of race-matched control lupus patients without haemolytic anaemia. Clinical data were obtained from medical records, and serological specificities were determined in our clinical immunology laboratory at OMRF. The presence of haemolytic anaemia in lupus patients was associated with a higher frequency of proteinuria (OR = 2.70, P = 0.000031), urinary cellular casts (OR = 2.83, P = 0.000062), seizures (OR = 2.96, P = 0.00024), pericarditis (OR = 2.21, P = 0.0019), pleuritis (OR = 1.72, P = 0.028) and lymphopenia (OR = 1.79, P = 0.015). These findings were independent of the presence of thrombocytopenia, which was approximately five times more common in lupus patients with haemolytic anaemia. Lupus patients with haemolytic anaemia were about 8 years younger than lupus patients without haemolytic anaemia at the time of disease onset ( P = 0.000001). In the absence of thrombocytopenia, lupus patients with haemolytic anaemia were approximately two times more likely to have anti-dsDNA antibodies ( P = 0.024). The presence of haemolytic anaemia is associated with a subset of lupus characterized by a younger age of disease onset, and a more severe disease with a higher likelihood of renal involvement, seizures, serositis and other cytopenias.
Differences in lymphocyte developmental potential between human embryonic stem cell and umbilical cord blood–derived hematopoietic progenitor cells
Authors: Martin Colin H. , Woll Petter S. , Ni Zhenya , Zúñiga-Pflücker Juan Carlos , Kaufman Dan S. 
Published: July 2008

Abstract
Hematopoietic progenitor cells derived from human embryonic stem cells (hESCs) develop into diverse mature hematopoietic lineages, including lymphocytes. Whereas functional natural killer (NK) cells can be efficiently generated in vitro from hESC-derived CD34+ cells, studies of T- and B-cell development from hESCs have been much more limited. Here, we demonstrate that despite expressing functional Notch-1, CD34+ cells from hESCs did not derive T cells when cocultured with OP9 cells expressing Delta-like 1, or in fetal thymus organ culture. hESC-derived CD34+ cells also did not produce B cells in vitro. In contrast, CD34+ cells isolated from UCB routinely generated T and B cells when cultured in the same conditions. Notably, both undifferentiated hESCs, and sorted hESC-derived populations with hematopoietic developmental potential exhibited constitutive expression of ID family genes and of transcriptional targets of stem cell factor–induced signaling. These pathways both inhibit T-cell development and promote NK-cell development. Together, these results demonstrate fundamental differences between hESC-derived hematopoietic progenitors and analogous primary human cells. Therefore, hESCs can be more readily supported to differentiate into certain cell types than others, findings that have important implications for derivation of defined lineage-committed populations from hESCs.
A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease
Authors: Flowers Mary E. D. , Apperley Jane F. , van Besien Koen , Elmaagacli Ahmet , Grigg Andrew , Reddy Vijay , Bacigalupo Andrea , Kolb Hans-Jochem , Bouzas Luis , Michallet Mauricette , Prince H. Miles , Knobler Robert , Parenti Dennis , Gallo Jose , Greinix Hildegard T. 
Published: July 2008

Abstract
Chronic graft-versus-host disease (cGVHD) is a major limitation of successful hematopoietic cell transplantation. The safety and efficacy of extracorporeal photopheresis (ECP) for 12 to 24 weeks together with standard therapy was compared with standard therapy alone in patients with cutaneous manifestations of cGVHD that could not be adequately controlled by corticosteroid treatment. The primary efficacy end point was a blinded quantitative comparison of percent change from baseline in Total Skin Score (TSS) of 10 body regions at week 12. Ninety-five patients were randomized to either ECP and standard therapy (n = 48) or standard therapy alone (n = 47). The median percentage improvement in TSS at week 12 was 14.5% for the ECP arm and 8.5% for the control arm (P = .48). The proportion of patients who had at least a 50% reduction in steroid dose and at least a 25% decrease from baseline in TSS was 8.3% in the ECP arm at week 12 and 0% in the control arm (P = .04). The nonblinded investigator assessment of skin complete or partial responses revealed a significant improvement in favor of ECP (P < .001). ECP was generally well tolerated. These results suggest that ECP may have a steroid-sparing effect in the treatment of cGVHD. Clinical trials registered at www.ClinicalTrials.gov as NCT00054613.
A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein–DVT Dose-Ranging Study
Authors: Buller Harry R. , Lensing Anthonie W. A. , Prins Martin H. , Agnelli Giancarlo , Cohen Alexander , Gallus Alexander S. , Misselwitz Frank , Raskob Gary , Schellong Sebastian , Segers Annelise 
Published: July 2008

Abstract
We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).
Development of methods for the genetic manipulation of Flavobacterium columnare
Authors: Staroscik Andrew M , Hunnicutt David W , Archibald Kate E , Nelson David R 
Published: July 2008

Abstract

Background

Flavobacterium columnare is the causative agent of columnaris disease, a disease affecting many freshwater fish species. Methods for the genetic manipulation for some of the species within the Bacteroidetes, including members of the genus Flavobacterium, have been described, but these methods were not adapted to work with F. columnare.

Results
As a first step toward developing a robust set of genetic tools for F. columnare, a protocol was developed to introduce the E. coli – Flavobacterium shuttle vector pCP29 into F. columnare strain C#2 by conjugal mating at an efficiency of 1.5 × 10-3 antibiotic-resistant transconjugants per recipient cell. Eight of eleven F. columnare strains tested were able to receive pCP29 using the protocol. pCP29 contains the cfxA and ermF genes, conferring both cefoxitin and erythromycin resistance to recipient cells. Selection for pCP29 introduction into F. columnare was dependent on cfxA, as ermF was found not to provide strong resistance to erythromycin. This is in contrast to other Flavobacterium species where ermF-based erythromycin resistance is strong. The green fluorescent protein gene (gfp) was introduced into F. columnare strains under the control of two different native Flavobacterium promoters, demonstrating the potential of this reporter system for the study of gene expression. The transposon Tn4351 was successfully introduced into F. columnare, but the method was dependent on selecting for erythromycin resistance. To work, low concentrations of antibiotic (1 μg ml-1) were used, and high levels of background growth occurred. These results demonstrate that Tn4351 functions in F. columnare but that it is not an effective mutagenesis tool due to its dependence on erythromycin selection. Attempts to generate mutants via homologous recombination met with limited success, suggesting that RecA dependent homologous recombination is rare in F. columnare.

Conclusion
The conjugation protocol developed as part of this study represents a significant first step towards the development of a robust set of genetic tools for the manipulation of F. columnare. The availability of this protocol will facilitate studies aimed at developing a deeper understanding of the virulence mechanisms of this important pathogen.