bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of arthritis by macrophage depletion and immunomodulation: Testing an apoptosis‐mediated therapy in a humanized death receptor mouse model
Authors: Li Jun , Hsu Hui‐Chen , Yang PingAr , Wu Qi , Li Hao , Edgington Laura E. , Bogyo Matthew , Kimberly Robert P. , Mountz John D. 
Published: October 2011

AbstractObjectiveTo determine the therapeutic efficacy and immunomodulatory effect of an anti‐human death receptor 5 (DR5) antibody, TRA‐8, in eliminating macrophage subsets in a mouse model of type II collagen–induced arthritis (CIA).MethodsA human/mouse‐chimeric DR5‐transgenic mouse, under the regulation of a mouse 3‐kb promoter and a loxP‐flanked STOP cassette, was generated and crossed with an ubiquitous Cre (Ubc.Cre) mouse and a lysozyme M–Cre (LysM.Cre)–transgenic mouse to achieve inducible or macrophage‐specific expression. Chicken type II collagen was used to induce CIA in mice, which were then treated with an anti‐human DR5 antibody, TRA‐8. Clinical scores, histopathologic severity, macrophage apoptosis and depletion, and T cell subset development were evaluated.ResultsIn human/mouse DR5‐transgenic Ubc.Cre mice with CIA, transgenic DR5 was most highly expressed on CD11b+ macrophages, with lower expression on CD4+ T cells. In human/mouse DR5‐transgenic LysM.Cre mice, transgenic DR5 was restrictively expressed on macrophages. Both in vivo near‐infrared imaging of caspase activity and TUNEL staining demonstrated that TRA‐8 rapidly induced apoptosis of macrophages in inflamed synovium. Depletion of pathogenic macrophages by TRA‐8 led to significantly reduced clinical scores for arthritis; decreased macrophage infiltration, synovial hyperplasia, osteoclast formation, joint destruction, cathepsin activity, and inflammatory cytokine expression in joints; reduced numbers of Th17 cells; and an increased number of Treg cells in draining lymph nodes.ConclusionThe anti‐human DR5 antibody TRA‐8 was efficacious in reducing the severity of arthritis via targeted depletion of macrophages and immunomodulation. Our data provide preclinical evidence that TRA‐8 is a potential novel biologic agent for rheumatoid arthritis therapy.
Socioeconomic status and prevalence of congenital heart defects: Does universal access to health care system eliminate the gap?
Authors: Agha Mohammad M. , Glazier Richard H. , Moineddin Rahim , Moore Aideen M. , Guttmann Astrid 
Published: October 2011

AbstractBACKGROUND: A twofold increase in the prevalence of congenital heart defects (CHDs) has been reported since the early 1970s with higher rates among children from low socioeconomic status (SES). This increase and the observed SES gap are postulated to be reflective of higher ascertainment, especially increased use of ultrasound and echography. The purpose of this study was to examine if trends over time in the prevalence of CHD were the same for high and low SES groups. METHODS: Using the child's health number as a unique identifier and through record linkage, children born in Ontario between 1994 and 2007 were followed for the diagnosis of CHD. Using postal codes and census information, SES quintiles were assigned to each child. We used adjusted rates and used multivariate models to compare trends in the prevalence rate among children born in different SES groups. RESULTS: Children born in low SES areas (23% of all births) had significantly higher rates of CHDs (rate ratio = 1.20; 95% confidence interval [CI] = 1.15–1.24). While prevalence of nonsevere CHDs declined in all SES groups since 2000, severe CHDs, especially atrial septal defects were on the rise during the study period. DISCUSSION: It is assumed that increased ascertainment is responsible for observed increase in the prevalence of CHD, especially minor defects. While the trend and pattern over time changed for severe and nonsevere CHDs, the SES gap remained consistent during the study period. Our results indicate that even free and universal access to a health care system does not eliminate the SES gap observed in the prevalence of CHD. Birth Defects Research (Part A) 2011. © 2011 Wiley Periodicals, Inc.
Bioelectrochemical stimulation of petroleum hydrocarbon degradation in saline soil using U‐tube microbial fuel cells
Authors: Wang Xin , Cai Zhang , Zhou Qixing , Zhang Zhineng , Chen Cuihong 
Published: October 2011

AbstractBioremediation is a cost‐effective and eco‐friendly approach to decontaminate soils polluted by petroleum hydrocarbons. However, this technique usually requires a long time due to the slow degradation rate by bacteria. By applying U‐tube microbial fuel cells (MFCs) designed here, the degradation rate of petroleum hydrocarbons close to the anode (<1 cm) was enhanced by 120% from 6.9 ± 2.5% to 15.2 ± 0.6% with simultaneous 125 ± 7 C of charge output (0.85 ± 0.05 mW/m2, 1 kΩ) in the tested period (25 days). Hydrocarbon fingerprint analysis showed that the degradation rate of both alkanes and polycyclic aromatic hydrocarbons (PAHs) was accelerated. The decrease of initial water content from 33% to 28% and 23% resulted in a decrease on charge output and hydrocarbon degradation rate, which could be attributed to the increase of internal resistance. A salt accumulation was observed in each reactor due to the evaporation of water from the air‐cathode, possibly inhibited the activity of exoelectrogenic bacteria (EB) and resulted in the elimination of the current at the end of the tested period. The number of hydrocarbon degradation bacteria (HDB) in soil close to the anode increased by nearly two orders of magnitude in the MFC assisted system (373 ± 56 × 103 CFU/g‐soil) than that in the disconnected control (8 ± 2 × 103 CFU/g‐soil), providing a solid evidence for in situ biostimulation of HDB growth by colonization of EB in the same system. Biotechnol. Bioeng. 2012; 109:426–433. © 2011 Wiley Periodicals, Inc.
Development of an HPLC method to analyze and prepare elsinochrome C and hypocrellin A in the submerged fermentation broth of Shiria sp. SUPER‐H168
Authors: Hu Mingming , Cai Yujie , Liao Xiangru , Hao Zhikui , Liu Jiayang 
Published: October 2011

ABSTRACTA rapid and sensitive analytical method based on reverse‐phase high‐performance liquid chromatography was first developed to simultaneously determine elsinochrome C (EC) and hypocrellin A (HA) in the submerged fermentation. The mobile phase consisted of acetonitrile–water 60:40 (v/v) with a flow‐rate of 1 mL/min. The calibration curves were as follows: y = 37,625x + 249,775 for EC, y = 30,813x + 556,409 for HA and linear at the investigated concentration. The correlation coefficients (R2) were 0.9989 and 0.9998 respectively for EC and HA. The limits of detection and quantification were 175 and 585 µg/L for EC and 205 and 610 µg/L for HA. The precisions of concentration and retention times were less than 2.5 and 0.3%. The recovery of the method was greater than 95.0%. The methodology was applied to analyze simultaneously EC and HA concentrations in a submerged fermentation, and was adequate for analysis of biosynthesis of perylenequinones. The method was also amplified to separate and purify EC and HA using a semi‐preparative C18 column. In addition, elsinochrome C was first identified in the submerged fermentation broth of Shiraia sp. SUPER‐H168. Copyright © 2011 John Wiley & Sons, Ltd.
The cell adhesion molecule L1 regulates the expression of choline acetyltransferase and the development of septal cholinergic neurons
Authors: Cui Xuezhi , Weng Ying‐Qi , Frappé Isabelle , Burgess Alison , Girão da Cruz M. Teresa , Schachner Melitta , Aubert Isabelle 
Published: October 2011

AbstractMutations in the L1 gene cause severe brain malformations and mental retardation. We investigated the potential roles of L1 in the regulation of choline acetyltransferase (ChAT) and in the development of septal cholinergic neurons, which are known to project to the hippocampus and play key roles in cognitive functions. Using stereological approaches, we detected significantly fewer ChAT‐positive cholinergic neurons in the medial septum and vertical limb of the diagonal band of Broca (MS/VDB) of 2‐week‐old L1‐deficient mice compared to wild‐type littermates (1644 ± 137 vs. 2051 ± 165, P= 0.038). ChAT protein levels in the septum were 53% lower in 2‐week‐old L1‐deficient mice compared to wild‐type littermates. ChAT activity in the septum was significantly reduced in L1‐deficient mice compared to wild‐type littermates at 1 (34%) and 2 (40%) weeks of age. In vitro, increasing doses of L1‐Fc induced ChAT activity in septal neurons with a significant linear trend (*P= 0.0065). At 4 weeks of age in the septum and at all time points investigated in the caudate‐putamen (CPu), the number of ChAT‐positive neurons and the levels of ChAT activity were not statistically different between L1‐deficient mice and wild‐type littermates. The total number of cells positive for the neuronal nuclear antigen (NeuN) in the MS/VDB and CPu was not statistically different in L1‐deficient mice compared to wild‐type littermates, and comparable expression of the cell cycle marker Ki67 was observed. Our results indicate that L1 is required for the timely maturation of septal cholinergic neurons and that L1 promotes the expression and activity of ChAT in septal neurons.
Fucosylated haptoglobin is a novel type of cancer biomarker linked to the prognosis after an operation in colorectal cancer
Authors: Takeda Yuri , Shinzaki Shinichiro , Okudo Kumiko , Moriwaki Kenta , Murata Kohei , Miyoshi Eiji 
Published: October 2011

AbstractBACKGROUND:Fucosylation is a crucial oligosaccharide modification in cancer and inflammation. Total cellular proteins of cancer cells and the sera of patients with cancer both show increased fucosylation levels. Certain kinds of fucosylated proteins can be applied as novel cancer biomarkers in glyco‐proteomic analyses. We previously identified fucosylated haptoglobin (Fuc‐Hpt) as a serologic marker for pancreatic cancer, and recently developed a lectin‐antibody enzyme‐linked immunosorbent assay system for quantifying Fuc‐Hpt. In the present study, we investigated the clinical outcome of Fuc‐Hpt levels in patients with colorectal cancer (CRC), and examined the mechanisms underlying Fut‐Hpt production using a murine tumor transplantation model.METHODS:The relationship between Fuc‐Hpt levels and clinical parameters was investigated in 77 patients with CRC, all of whom underwent primary resection. Serum Fuc‐Hpt levels were examined in athymic nude mice injected with colon cancer cell lines that lacked fucosylation.RESULTS:Fuc‐Hpt levels were significantly associated with overall and relapse‐free survival, distant metastasis, clinical stage, and curability. Multivariate analysis revealed that distant metastasis was an independent factor for increased Fuc‐Hpt levels. The combination of Fuc‐Hpt and CEA might be a better serologic marker to predict prognosis. Fuc‐Hpt levels were higher in mice with direct injection of tumor cells into the spleen than in those injected subcutaneously.CONCLUSIONS:Fuc‐Hpt might be a useful marker for the prognosis of CRC. Fuc‐Hpt could be produced by the tissue surrounding tumor cells, which might be the mechanism underlying Fuc‐Hpt elevation associated with distant metastasis. Cancer 2012;118: 3036–43. © 2011 American Cancer Society.
Lack of benefit of central nervous system prophylaxis for diffuse large B‐cell lymphoma in the rituximab era
Authors: Kumar Anita , Vanderplas Ann , LaCasce Ann S. , Rodriguez Maria A. , Crosby Allison L. , Lepisto Eva , Czuczman Myron S. , Nademanee Auayporn , Niland Joyce , Gordon Leo I. , Millenson Michael , Zelenetz Andrew D. , Friedberg Jonathan W. , Abel Gregory A. 
Published: October 2011

AbstractBACKGROUND:Little is known about the utility of central nervous system (CNS) prophylaxis for diffuse large B‐cell lymphoma (DLBCL) in the rituximab era. The objective of this study was to characterize patterns of CNS prophylaxis for patients who received combined rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) chemotherapy using the National Comprehensive Cancer Network Non‐Hodgkin Lymphoma Outcomes Database, a prospective cohort study that collects clinical and outcomes data for patients at 7 participating centers.METHODS:Patients who were eligible for this analysis presented with newly diagnosed DLBCL between January 2001 and July 2008, had no evidence of baseline CNS disease, and had received R‐CHOP within 180 days of diagnosis. The authors assessed incidence and covariates of prophylaxis, prophylaxis modality, and, using propensity score analysis, outcomes such as overall survival.RESULTS:Of 989 eligible patients, 117 received CNS prophylaxis (11.8%), most intrathecally (71.8%). Involvement of bone marrow, other high‐risk site, >1 extranodal site, higher International Prognostic Index score, and higher stage were associated individually with the receipt of prophylaxis (all P < .0001). At a median follow‐up of 2.5 years, there were 20 CNS recurrences (2% [95% confidence interval, 1.1%‐2.9%]) among all patients, and overall survival was not affected by prophylaxis.CONCLUSIONS:Given the overall low rate of CNS recurrence and lack of prophylaxis‐associated survival benefit, the current data called into question the practice of CNS prophylaxis in the rituximab era. Cancer 2011. © 2011 American Cancer Society.
High‐throughput genotyping in osteosarcoma identifies multiple mutations in phosphoinositide‐3‐kinase and other oncogenes
Authors: Choy Edwin , Hornicek Francis , MacConaill Laura , Harmon David , Tariq Zeeshan , Garraway Levi , Duan Zhenfeng 
Published: October 2011

AbstractBACKGROUND:The identification of new genes that are mutated in osteosarcomas is critical to developing a better understanding of the molecular pathogenesis of this disease and discovering new targets for therapeutic development.METHODS:The authors identified somatic nonsynonymous coding mutations in oncogenes associated with human cancers and hotspot mutations from tumor suppressor genes that were either well described in the literature or observed multiple times in human cancer sequencing efforts. Then, 961 mutations in 89 genes were systematically characterized across 98 osteosarcoma tumor samples and cell lines. All identified mutations were replicated on an independent platform using homogeneous mass extend matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry.RESULTS:In total, 14 mutations were identified in at least 1 osteosarcoma tumor sample or cell line. Some of the genetic changes identified were in tumor suppressor genes previously identified as altered in osteosarcoma: p53 (arginine→histidine at codon 273 [R273H], R→cysteine at codon 723 [R273C], and tyrosine→C at codon 163 [Y163C]) and retinoblastoma 1 (RB1) (glutamic acid→* at codon 137 [E137*]). Notably, multiple mutations were identified in phosphoinositide‐3‐kinase (PI3K), catalytic, alpha polypeptide (PIK3CA) (H1047R, E→lysine at codon 545 [E545K], and H→proline at codon 701 [H701P]) that were not observed previously in osteosarcoma. In addition, mutations in v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) (glycine→serine at codon 12 [G12S]); cubilin (CUBN) (isolucine→valine at codon 3189 [I3189V]; observed in 2 separate tumor samples); cadherin 1, type 1, epithelial (CDH1) (alanine→threonine at codon 617 [A617T]; observed in 2 separate tumor samples); catenin (cadherin‐associated protein), beta 1, 88 kDa (CTNNB1) (asparagine→S at codon 287 [N287S]); and fibrous sheath CABYR binding protein (FSCB) (S→leucine at codon 775 [S775L]) were observed.CONCLUSIONS:In this largest mutational profiling of osteosarcoma to date, the authors identified for the first time several mutations involving the PI3K pathway, adding osteosarcoma to the growing list of malignancies with PI3K mutations. In addition, they initiated a mutational map detailing DNA sequence changes across a variety of osteosarcoma subtypes and offered new candidates for therapeutic targeting. Cancer 2011. © 2011 American Cancer Society.
Performance study on CUDA GPUs for parallelizing the local ensemble transformed Kalman filter algorithm
Authors: Blattner Timothy , Yang Shiming 
Published: October 2011

SUMMARYModern graphics cards provide computational capabilities that exceed current CPUs. As one of the computational intensive problems, numerical weather prediction has the opportunity to benefit from the massive number of threads and large memory throughput in the graphics architecture. In this paper, we present the key steps to integrate the Compute Unified Device Architecture (CUDA) programming framework for one key component in numerical weather prediction, the data assimilation algorithm, which incorporates the observational data into the model to produce the best initial condition in the next prediction. The data assimilation algorithm we studied in this paper exhibits good localization and favors parallelism. To maximize the throughput of the graphics card, over a million CUDA threads, global memory coalescing, and fast graphics shared memory are utilized. We also demonstrate the differences in the advancement of GPU architectures from the GTX 200 series to Fermi. The experiments are carried out separately on a GTX 260 (GTX 200 series) and a GTX 460 (Fermi) graphics card. Results show an improvement of 72.1× speedup running on the GTX 260 and 92.7×speedup on the GTX 460. The results provide attractive evidence for applying CUDA GPUs to high demanding scientific computation realms. Copyright © 2011 John Wiley & Sons, Ltd.
Distributed data mining patterns and services: an architecture and experiments
Authors: Cesario Eugenio , Talia Domenico 
Published: October 2011

SUMMARYDistributed data mining implements techniques for analyzing data on distributed computing systems by exploiting data distribution and parallel algorithms. The grid is a computing infrastructure for implementing distributed high‐performance applications and solving complex problems, offering effective support to the implementation and use of data mining and knowledge discovery systems. The Web Services Resource Framework has become the standard for the implementation of grid services and applications, and it can be exploited for developing high‐level services for distributed data mining applications. This paper describes how distributed data mining patterns, such as collective learning, ensemble learning, and meta‐learning models, can be implemented as Web Services Resource Framework mining services by exploiting the grid infrastructure. The goal of this work was to design a distributed architectural model that can be exploited for different distributed mining patterns deployed as grid services for the analysis of dispersed data sources. In order to validate such an approach, we presented also the implementation of two clustering algorithms on the developed architecture. In particular, the distributed k‐means and distributed expectation maximization were exploited as pilot examples to show the suitability of the implemented service‐oriented framework. An extensive evaluation of its performance was provided. Copyright © 2011 John Wiley & Sons, Ltd.
Effect of neonatal respiratory infection on adult BALB/c hippocampal glucocorticoid and mineralocorticoid receptors
Authors: Wynne O. , Horvat J.C. , Smith R. , Hansbro P.M. , Clifton V.L. , Hodgson D.M. 
Published: October 2011

AbstractThe current study investigated the effects of neonatal infection with Chlamydia muridarum bacteria on glucocorticoid (GR) and mineralocorticoid (MR) receptors in the adult mouse hippocampus. In male adults infected at birth, circulating corticosterone was significantly increased when compared to same sex controls; while neonatal infection resulted in female adults with significantly increased GR mRNA compared to same sex controls. When comparing males and females after neonatal infection, males had significantly less GR protein than females. Interestingly, after control treatment, males had significantly more GR mRNA, MR mRNA, and GR protein with significantly lower corticosterone than females. Neonatal respiratory infection significantly impacts adult hippocampal GR and MR, and circulating corticosterone in a sex‐specific manner potentially altering stress responsivity. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 568–575, 2012.
Elevated effector cell sensitivity to Treg‐cell suppression that is not associated with reduced Th17‐cell expression distinguishes HIV+ asymptomatic subjects from progressors
Authors: Thorborn Georgina S. , Pomeroy Laura , Ishohanni Heidi , Peters Barry S. , Vyakarnam Annapurna 
Published: October 2011

AbstractSuppression mediated by Treg cells is a balance between Treg‐cell suppressive potency versus sensitivity of effector cells to Treg‐cell suppression. We assessed if this balance, along with Treg‐cell number relative to the Treg‐cell counter‐regulatory cytokine IL‐17, differs between asymptomatic HIV+ subjects versus those who progress onto disease. Cross‐over studies comparing Treg‐cell potency, measured by effector cell proliferation or IFN‐γ expression, from HIV‐infected versus control subjects to suppress the proliferation of allogeneic control effector cells demonstrated increased sensitivity of CD4+CD25− effector cells from asymptomatic HIV+ subjects to suppression, rather than an increase in the suppressive potential of their CD4+CD25+ Treg cells. In contrast, HIV+ progressors did not differ from controls in Treg‐cell potency or effector cell sensitivity to Treg‐cell suppression. Both CD4+CD25+Foxp3+ Treg and effector IL‐17 absolute cell numbers were significantly lower in all HIV+ subjects tested and not restored by antiviral therapy. Thus, these novel data suggest that elevated Treg‐cell‐mediated suppression due to increased sensitivity of effectors to Treg cells may be a natural host response in chronic asymptomatic HIV infection, which is lost as disease progresses and that this feature of CD25− effector cells is not inextricably linked to reduced production of the Treg‐cell counter‐regulatory cytokine IL‐17.
F4/80 and the related adhesion‐GPCRs
Authors: Gordon Siamon , Hamann Jörg , Lin Hsi‐Hsien , Stacey Martin 
Published: October 2011

AbstractThe F4/80 monoclonal antibody was first reported in this journal 30 years ago (Eur. J. Immunol. 1981. 11: 805–815). F4/80 has become a widely used marker for monocytes and many, but not all, tissue macrophages in the mouse. F4/80 is a member of the EGF‐TM7 family of leukocyte plasma membrane heptahelical molecules, which includes CD97 and EMR2. This Viewpoint summarises current knowledge of the expression, structure and functions of the EGF‐TM7 family, as part of a larger family of tissue adhesion‐GPCRs.
Regulatory macrophages: Setting the Threshold for Therapy
Authors: Fleming Bryan D. , Mosser David M. 
Published: October 2011

AbstractMacrophages exhibit remarkable plasticity and can change their phenotype in response to different environmental cues. They can become activated to kill intracellular microbes or they can assume regulatory properties to modulate immune responses. Regulatory macrophages are fundamentally different from classically activated, and we propose from non‐classically activated macrophages; they arise in response to different stimuli and perform different physiological functions. They are likely to express unique biochemical markers that could be exploited to identify and potentially target these macrophage subsets in tissue. Furthermore, inducers of regulatory macrophages may have the potential to be used as anti‐inflammatory therapeutics. Therefore, a better understanding of the various macrophage phenotypes may pave the way for new therapies that are directed at modulating macrophage functions or manipulating individual macrophage subsets.