bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen-Pulsed Bone Marrow–Derived and Pulmonary Dendritic Cells Promote Th2 Cell Responses and Immunopathology in Lungs during the Pathogenesis of Murine Mycoplasma Pneumonia
Authors: Dobbs Nicole A. , Zhou Xia , Pulse Mark , Hodge Lisa M. , Schoeb Trenton R. , Simecka Jerry W.
Published: June 2014

Mycoplasmas are a common cause of pneumonia in humans and animals, and attempts to create vaccines have not only failed to generate protective host responses, but they have exacerbated the disease. Mycoplasma pulmonis causes a chronic inflammatory lung disease resulting from a persistent infection, similar to other mycoplasma respiratory diseases. Using this model, Th1 subsets promote resistance to mycoplasma disease and infection, whereas Th2 responses contribute to immunopathology. The purpose of the present study was to evaluate the capacity of cytokine-differentiated dendritic cell (DC) populations to influence the generation of protective and/or pathologic immune responses during M. pulmonis respiratory disease in BALB/c mice. We hypothesized that intratracheal inoculation of mycoplasma Ag–pulsed bone marrow–derived DCs could result in the generation of protective T cell responses during mycoplasma infection. However, intratracheal inoculation (priming) of mice with Ag-pulsed DCs resulted in enhanced pathology in the recipient mice when challenged with mycoplasma. Inoculation of immunodeficient SCID mice with Ag-pulsed DCs demonstrated that this effect was dependent on lymphocyte responses. Similar results were observed when mice were primed with Ag-pulsed pulmonary, but not splenic, DCs. Lymphocytes generated in uninfected mice after the transfer of either Ag-pulsed bone marrow–derived DCs or pulmonary DCs were shown to be IL-13+ Th2 cells, known to be associated with immunopathology. Thus, resident pulmonary DCs most likely promote the development of immunopathology in mycoplasma disease through the generation of mycoplasma-specific Th2 responses. Vaccination strategies that disrupt or bypass this process could potentially result in a more effective vaccination.
A Negative Feedback Loop Mediated by STAT3 Limits Human Th17 Responses
Authors: Purvis Harriet A. , Anderson Amy E. , Young David A. , Isaacs John D. , Hilkens Catharien M. U.
Published: June 2014

The transcription factor STAT3 is critically required for the differentiation of Th17 cells, a T cell subset involved in various chronic inflammatory diseases. In this article, we report that STAT3 also drives a negative-feedback loop that limits the formation of IL-17–producing T cells within a memory population. By activating human memory CD4+CD45RO+ T cells at a high density (HiD) or a low density (LoD) in the presence of the pro-Th17 cytokines IL-1β, IL-23, and TGF-β, we observed that the numbers of Th17 cells were significantly higher under LoD conditions. Assessment of STAT3 phosphorylation revealed a more rapid and stronger STAT3 activation in HiD cells than in LoD cells. Transient inhibition of active STAT3 in HiD cultures significantly enhanced Th17 cell numbers. Expression of the STAT3-regulated ectonucleotidase CD39, which catalyzes ATP hydrolysis, was higher in HiD, than in LoD, cell cultures. Interestingly, inhibition of CD39 ectonucleotidase activity enhanced Th17 responses under HiD conditions. Conversely, blocking the ATP receptor P2X7 reduced Th17 responses in LoD cultures. These data suggest that STAT3 negatively regulates Th17 cells by limiting the availability of ATP. This negative-feedback loop may provide a safety mechanism to limit tissue damage by Th17 cells during chronic inflammation. Furthermore, our results have relevance for the design of novel immunotherapeutics that target the STAT3-signaling pathway, because inhibition of this pathway may enhance, rather than suppress, memory Th17 responses.
Dengue Viral Protease Interaction with NF-κB Inhibitor α/β Results in Endothelial Cell Apoptosis and Hemorrhage Development
Authors: Lin Jung-Chen , Lin Shih-Ching , Chen Wen-Yu , Yen Yu-Ting , Lai Chin-Wen , Tao Mi-Hua , Lin Yi-Ling , Miaw Shi-Chuen , Wu-Hsieh Betty A.
Published: June 2014

Hemorrhagic manifestations occur frequently accompanying a wide range of dengue disease syndromes. Much work has focused on the contribution of immune factors to the pathogenesis of hemorrhage, but how dengue virus (DENV) participates in the pathogenic process has never been explored. Although there is no consensus that apoptosis is the basis of vascular permeability in human dengue infections, we showed in dengue hemorrhage mouse model that endothelial cell apoptosis is important to hemorrhage development in mice. To explore the molecular basis of the contribution of DENV to endothelial cell death, we show in this study that DENV protease interacts with cellular IκBα and IκBβ and cleaves them. By inducing IκBα and IκBβ cleavage and IκB kinase activation, DENV protease activates NF-κB, which results in endothelial cell death. Intradermal inoculation of DENV protease packaged in adenovirus-associated virus-9 induces endothelial cell death and dermal hemorrhage in mice. Although the H51 activity site is not involved in the interaction between DENV protease and IκB-α/β, the enzymatic activity is critical to the ability of DENV protease to induce IκBα and IκBβ cleavage and trigger hemorrhage development. Moreover, overexpression of IκBα or IκBβ protects endothelial cells from DENV-induced apoptosis. In this study, we show that DENV protease participates in the pathogenesis of dengue hemorrhage and discover IκBα and IκBβ to be the new cellular targets that are cleaved by DENV protease.
Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis
Authors: Maricic Igor , Halder Ramesh , Bischof Felix , Kumar Vipin
Published: June 2014

CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139–151/I-As–tetramer+ cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA–dependent therapeutic approaches to T cell–mediated autoimmune diseases.
Increased IFN-α–Producing Plasmacytoid Dendritic Cells (pDCs) in Human Th1-Mediated Type 1 Diabetes: pDCs Augment Th1 Responses through IFN-α Production
Authors: Xia Chang-Qing , Peng Ruihua , Chernatynskaya Anna V. , Yuan Lihui , Carter Carolyn , Valentine John , Sobel Eric , Atkinson Mark A. , Clare-Salzler Michael J.
Published: June 2014

Increasing evidence suggests that type 1 IFN (IFN-αβ) is associated with pathogenesis of Th1-mediated type 1 diabetes (T1D). A major source of IFN-αβ is plasmacytoid dendritic cells (pDCs). In this study, we analyzed peripheral blood pDC numbers and functions in at-risk, new-onset, and established T1D patients and controls. We found that subjects at risk for T1D and new-onset and established T1D subjects possessed significantly increased pDCs but similar number of myeloid DCs when compared with controls. pDC numbers were not affected by age in T1D subjects but declined with increasing age in control subjects. It was demonstrated that IFN-α production by PBMCs stimulated with influenza viruses was significantly higher in T1D subjects than in controls, and IFN-α production was correlated with pDC numbers in PBMCs. Of interest, only T1D-associated Coxsackievirus serotype B4 but not B3 induced majority of T1D PBMCs to produce IFN-α, which was confirmed to be secreted by pDCs. Finally, in vitro studies demonstrated IFN-α produced by pDCs augmented Th1 responses, with significantly greater IFN-γ–producing CD4+ T cells from T1D subjects. These findings indicate that increased pDCs and their IFN-αβ production may be associated with this Th1-mediated autoimmune disease, especially under certain viral infections linked to T1D pathogenesis.
Intestinal Inflammation Modulates Expression of the Iron-Regulating Hormone Hepcidin Depending on Erythropoietic Activity and the Commensal Microbiota
Authors: Shanmugam Nanda Kumar N. , Trebicka Estela , Fu Ling-lin , Shi Hai Ning , Cherayil Bobby J.
Published: June 2014

States of chronic inflammation such as inflammatory bowel disease are often associated with dysregulated iron metabolism and the consequent development of an anemia that is caused by maldistribution of iron. Abnormally elevated expression of the hormone hepcidin, the central regulator of systemic iron homeostasis, has been implicated in these abnormalities. However, the mechanisms that regulate hepcidin expression in conditions such as inflammatory bowel disease are not completely understood. To clarify this issue, we studied hepcidin expression in mouse models of colitis. We found that dextran sulfate sodium–induced colitis inhibited hepcidin expression in wild-type mice but upregulated it in IL-10–deficient animals. We identified two mechanisms contributing to this difference. Firstly, erythropoietic activity, as indicated by serum erythropoietin concentrations and splenic erythropoiesis, was higher in the wild-type mice, and pharmacologic inhibition of erythropoiesis prevented colitis-associated hepcidin downregulation in these animals. Secondly, the IL-10 knockout mice had higher expression of multiple inflammatory genes in the liver, including several controlled by STAT3, a key regulator of hepcidin. The results of cohousing and fecal transplantation experiments indicated that the microbiota was involved in modulating the expression of hepcidin and other STAT3-dependent hepatic genes in the context of intestinal inflammation. Our observations thus demonstrate the importance of erythropoietic activity and the microbiota in influencing hepcidin expression during colitis and provide insight into the dysregulated iron homeostasis seen in inflammatory diseases.
Mismatch Repair Proteins and AID Activity Are Required for the Dominant Negative Function of C-Terminally Deleted AID in Class Switching
Authors: Ucher Anna J. , Ranjit Sanjay , Kadungure Tatenda , Linehan Erin K. , Khair Lyne , Xie Elaine , Limauro Jennifer , Rauch Katherina S. , Schrader Carol E. , Stavnezer Janet
Published: June 2014

Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. The AID C terminus is required for CSR, but not for S-region DNA double-strand breaks (DSBs) during CSR, and it is not required for SHM. AID lacking the C terminus (ΔAID) is a dominant negative (DN) mutant, because human patients heterozygous for this mutant fail to undergo CSR. In agreement, we show that ΔAID is a DN mutant when expressed in AID-sufficient mouse splenic B cells. To have DN function, ΔAID must have deaminase activity, suggesting that its ability to induce DSBs is important for the DN function. Supporting this hypothesis, Msh2-Msh6 have been shown to contribute to DSB formation in S regions, and we find in this study that Msh2 is required for the DN activity, because ΔAID is not a DN mutant in msh2−/− cells. Our results suggest that the DNA DSBs induced by ΔAID are unable to participate in CSR and might interfere with the ability of full-length AID to participate in CSR. We propose that ΔAID is impaired in its ability to recruit nonhomologous end joining repair factors, resulting in accumulation of DSBs that undergo aberrant resection. Supporting this hypothesis, we find that the S–S junctions induced by ΔAID have longer microhomologies than do those induced by full-length AID. In addition, our data suggest that AID binds Sμ regions in vivo as a monomer.
Human Hematopoietic Reconstitution and HLA-Restricted Responses in Nonpermissive Alymphoid Mice
Authors: Serra-Hassoun Malika , Bourgine Maryline , Boniotto Michele , Berges Julien , Langa Francina , Michel Marie-Louise , Freitas Antonio A. , Garcia Sylvie
Published: June 2014

We generated a new humanized mouse model to study HLA-restricted immune responses. For this purpose, we created unique murine hosts by enforcing the expression of human SIRPα by murine phagocytes in murine MHC-deficient HLA-transgenic alymphoid hosts, an approach that allowed the immune reconstitution of nonpermissive mice following injection of human hematopoietic stem cells. We showed that these mouse/human chimeras were able to generate HLA-restricted responses to immunization. These new humanized mice may offer attractive models to study immune responses to human diseases, such as HIV and EBV infections, as well as to assay new vaccine strategies.
Critical Roles of TIPE2 Protein in Murine Experimental Colitis
Authors: Lou Yunwei , Sun Honghong , Morrissey Samantha , Porturas Thomas , Liu Suxia , Hua Xianxin , Chen Youhai H.
Published: June 2014

Both commensal bacteria and infiltrating inflammatory cells play essential roles in the pathogenesis of inflammatory bowel disease. The molecular mechanisms whereby these pathogenic factors are regulated during the disease are not fully understood. We report in this article that a member of the TNF-α–induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) plays a crucial role in regulating commensal bacteria dissemination and inflammatory cell function in experimental colitis induced by dextran sodium sulfate (DSS). Following DSS treatment, TIPE2-deficient mice, or chimeric mice that are deficient in TIPE2 only in their hematopoietic cells, lost less body weight and survived longer than wild-type controls. Consistent with this clinical observation, TIPE2-deficient mice exhibited significantly less severe colitis and colonic damage. This was associated with a marked reduction in the colonic expression of inflammatory cytokines, such as TNF-α, IL-6, and IL-12. Importantly, the ameliorated DSS-induced colitis in TIPE2−/− mice also was associated with reduced local dissemination of commensal bacteria and a weaker systemic inflammatory response. Combined with our previous report that TIPE2 is a negative regulator of antibacterial immunity, these results indicate that TIPE2 promotes colitis by inhibiting mucosal immunity to commensal bacteria.
Cutting Edge: CXCR4 Is Critical for CD8+ Memory T Cell Homeostatic Self-Renewal but Not Rechallenge Self-Renewal
Authors: Chaix Julie , Nish Simone A. , Lin Wen-Hsuan W. , Rothman Nyanza J. , Ding Lei , Wherry E. John , Reiner Steven L.
Published: June 2014

Central memory (CM) CD8+ T cells “remember” prior encounters because they maintain themselves through cell division in the absence of ongoing challenge (homeostatic self-renewal), as well as reproduce the CM fate while manufacturing effector cells during secondary Ag encounters (rechallenge self-renewal). We tested the consequence of conditional deletion of the bone marrow homing receptor CXCR4 on antiviral T cell responses. CXCR4-deficient CD8+ T cells have impaired memory cell maintenance due to defective homeostatic proliferation. Upon rechallenge, however, CXCR4-deficient T cells can re-expand and renew the CM pool while producing secondary effector cells. The critical bone marrow–derived signals essential for CD8+ T cell homeostatic self-renewal appear to be dispensable to yield self-renewing, functionally asymmetric cell fates during rechallenge.
CXCL17 Is a Major Chemotactic Factor for Lung Macrophages
Authors: Burkhardt Amanda M. , Maravillas-Montero José L. , Carnevale Christina D. , Vilches-Cisneros Natalia , Flores Juan P. , Hevezi Peter A. , Zlotnik Albert
Published: June 2014

Chemokines are a superfamily of chemotactic cytokines that direct the movement of cells throughout the body under homeostatic and inflammatory conditions. The mucosal chemokine CXCL17 was the last ligand of this superfamily to be characterized. Several recent studies have provided greater insight into the basic biology of this chemokine and have implicated CXCL17 in several human diseases. We sought to better characterize CXCL17’s activity in vivo. To this end, we analyzed its chemoattractant properties in vivo and characterized a Cxcl17 −/− mouse. This mouse has a significantly reduced number of macrophages in its lungs compared with wild-type mice. In addition, we observed a concurrent increase in a new population of macrophage-like cells that are F4/80+CDllcmid. These results indicate that CXCL17 is a novel macrophage chemoattractant that operates in mucosal tissues. Given the importance of macrophages in inflammation, these observations strongly suggest that CXCL17 is a major regulator of mucosal inflammatory responses.
Prolonged Triglyceride Storage in Macrophages: pHo Trumps pO2 and TLR4
Authors: Lu Mingfang , Kho Terry , Munford Robert S.
Published: June 2014

Lipid-laden macrophages contribute to pathologies as diverse as atherosclerosis and tuberculosis. Three common stimuli are known to promote macrophage lipid storage: low tissue oxygen tension (pO2), low extracellular pH (pHo), and exposure to agonists such as bacterial LPS. Noting that cells responding to low pO2 or agonistic bacterial molecules often decrease pHo by secreting lactic and other carboxylic acids, we studied how pHo influences the stimulation of triacylglycerol (TAG) storage by low pO2 and LPS. We found that TAG retention after incubation for 48–72 h was inversely related to pHo when primary macrophages were cultured in 21% oxygen, 4% oxygen, or with LPS at either oxygen concentration. Maintaining pHo at ∼7.4 was sufficient to prevent the increase in prolonged TAG storage induced by either low pO2 or LPS. The strong influence of pHo on TAG retention may explain why lipid-laden macrophages are found in some tissue environments and not in others. It is also possible that other long-term cellular changes currently attributed to low pO2 or bacterial agonists may be promoted, at least in part, by the decrease in pHo that these stimuli induce.
RAG1/2 Knockout Pigs with Severe Combined Immunodeficiency
Authors: Huang Jiao , Guo Xiaogang , Fan Nana , Song Jun , Zhao Bentian , Ouyang Zhen , Liu Zhaoming , Zhao Yu , Yan Quanmei , Yi Xiaoling , Schambach Axel , Frampton Jon , Esteban Miguel A. , Yang Dongshan , Yang Huaqiang , Lai Liangxue
Published: June 2014

Pigs share many physiological, biochemical, and anatomical similarities with humans and have emerged as valuable large animal models for biomedical research. Considering the advantages in immune system resemblance, suitable size, and longevity for clinical practical and monitoring purpose, SCID pigs bearing dysfunctional RAG could serve as important experimental tools for regenerative medicine, allograft and xenograft transplantation, and reconstitution experiments related to the immune system. In this study, we report the generation and phenotypic characterization of RAG1 and RAG2 knockout pigs using transcription activator-like effector nucleases. Porcine fetal fibroblasts were genetically engineered using transcription activator-like effector nucleases and then used to provide donor nuclei for somatic cell nuclear transfer. We obtained 27 live cloned piglets; among these piglets, 9 were targeted with biallelic mutations in RAG1, 3 were targeted with biallelic mutations in RAG2, and 10 were targeted with a monoallelic mutation in RAG2. Piglets with biallelic mutations in either RAG1 or RAG2 exhibited hypoplasia of immune organs, failed to perform V(D)J rearrangement, and lost mature B and T cells. These immunodeficient RAG1/2 knockout pigs are promising tools for biomedical and translational research.
On the growth of Betti numbers in $p$-adic analytic towers
Authors: Bergeron Nicolas , Linnell Peter , Lück Wolfgang , Sauer Roman
Published: July 2014

We study the asymptotic growth of Betti numbers in tower of finite covers and provide simple proofs of approximation results, which were previously obtained by Calegari and Emerton, in the generality of arbitrary

p

-adic analytic towers of covers. Further, we also obtain partial results about arbitrary pro-

p

towers.
Aperiodic tilings of manifolds of intermediate growth
Authors: Marcinkowski Michał , Nowak Piotr W.
Published: July 2014

We give a homological construction of aperiodic tiles for certain open Riemannian surfaces admitting actions of Grigorchuk groups of intermediate growth.
Depth of cohomology support loci for quasi-projective varieties via orbifold pencils
Authors: Artal Bartolo Enrique , Cogolludo-Agustín José Ignacio , Libgober Anatoly
Published: July 2014

We describe several relations between a homological invariant of characters of fundamental groups of projective manifolds called
depth
and maps onto orbicurves. This extends previously studied relations between families of local systems and holomorphic maps onto hyperbolic curves. First, we derive the existence of characters whose depth is bounded below by the number of independent orbifold pencils. Conversely, for some class of characters, we deduce the existence of as many independent pencils as the depth of the character. Second, we show a new relation between depth of characters of the fundamental group and solutions of a certain Diophantine equation (related to the Pell equation) over the field of rational functions. Finally we give a Hodge theoretical characterization of essential coordinate characters of the fundamental groups of the complements to plane curves, i.e., characters whose existence cannot be detected by considering the homology of branched abelian covers.
On trilinear oscillatory integrals
Authors: Christ Michael , Oliveira e Silva Diogo
Published: July 2014

We examine a certain class of trilinear integral operators which incorporate oscillatory factors

e^{iP}

, where

P

is a real-valued polynomial, and prove smallness of such integrals in the presence of rapid oscillations.
Research Report: Philippine Airlines – Flying in a Changing Landscape
Authors: O'Connell John F. , Vanoverbeke Karel
Published: June 2014

This paper discusses the issues facing Philippine Airlines in its ever evolving and changing landscape in the domestic, regional and international markets. The Philippine aviation industry had its safety status downgraded to Category 2 for six years by the International Civil Aviation Organization and the US Federal Aviation Administration. This downgrading of the status severely limited Philippine Airlines from expanding internationally, but its reinstatement provides huge opportunities for the incumbent. However, in the domestic and regional markets it faces a threat from rapidly encroaching low-cost carriers. The Philippines has the highest domestic low-cost carrier penetration rate in the world, while the incumbent has rebranded its low-cost subsidiary, AirPhil, to a full-service carrier, PAL Express, which has impacted its ability to compete in short-haul markets. Philippine Airlines' new routes to the Middle East and Europe have the potential to be profitable, but their success is hampered by the lack of domestic connectivity and no feeder traffic from partner airlines.
Mass Transfer During Osmotic Dehydration of Chub Mackerel Cylinders in Ternary Solution
Authors: Checamarev Gerardo , Yeannes Maria I. , Bevilacqua Alicia E. , Casales Maria R.
Published: June 2014

In the analysis, design and optimization of an osmotic dehydration process is important to know the kinetic of water loss and solutes gain. In this study, the mass transfer during osmotic dehydration of chub mackerel (Scomber japonicus) cylinders in ternary solution glycerol/salt/water was analyzed. The models of Zugarramurdi & Lupín and Azuara were used to describe mass transfer and to estimate equilibrium values. The radial effective diffusion coefficient was estimated using the analytical solution of Fick's second law. Diffusion coefficients were determined for a finite cylinder, for an infinite cylinder considering only the first term of the series and considering higher order terms of the series. The profiles of water and solutes during the osmotic dehydration were calculated by using the estimated water and solutes diffusivities. According to the results obtained, using three terms in the analytical solution of the Fick's second law is appropriate to determine the diffusion coefficients. The diffusion coefficient for infinite cylinder were 2.63×10-6, 4.11×10-6 and 4.25×10-6 cm2/s for water loss, salt and glycerol gain respectively. For a finite cylinder these values were 2.30×10-6, 3.67×10-6 and 3.78×10-6 cm2/s respectively. All the models proposed were in agreement with experimental data for solutes gain ((0.967<R2adj<0.986); (0.0016<RMSE<0.039) and (4.17<P<10.0)). The model based on the solution of Fick’s Law for an infinite cylinder with higher order terms was the best fit for water loss and solutes gain. The equilibrium values estimated with Azuara model agree with the experimental (0<relative error<9.8). Water and solute distributions as a function of time and location in the radial direction were plotted.
Valores no trabalho: visão do propagandista da região centro-oeste do Rio Grande do Sul
Authors: Lopes Luis Felipe Dias , Freitas Andrea Karla Breunig de , Tatsch Marcelo Pastoriza , Madruga Lucia Rejane da Rosa Gama , Imhoff Olair
Published: June 2014

The value can be defined as principles or beliefs about desirable goals or rewards, hierarchically organized, that people seek through their work and guide their evaluations of the results and the work context, as well as their behavior in work and make a choice of work. The development of studies using scales of values is still little, but on work values exists Scale the Work Values (SWV) that has been used in scientific work. A group of 40 propagandists of the center-west region of the state of Rio Grande do Sul answered this survey. These data were subjected to a reliability analysis, descriptive and correlational. The results indicated that the factors could be improved with regard to reliability, to the exclusion of any item, but according to the authors, all factors are within the acceptable tolerance limit, that is, all items are important in the formation factors and their opinion makers about the Work Relative Value (WRV).
Pesquisa Quantitativa em Finanças: Uma Análise das Técnicas Estatísticas Utilizadas por Artigos Científicos Publicados em Periódicos Qualificados no Triênio 2007-2009
Authors: Cordeiro Rebeca Albuquerque , Sanches Paula Luciana Bruschi , Cavalcante Keliane De Oliveira , Peixoto Amanna Ferreira , Leite José Carlos De Lacerda
Published: June 2014

This study aimed to examine whether there are differences, in terms of sophistication and accuracy, in statistical techniques used by finance articles published in journals classified by CAPES, from 2007 to 2009. The sample consisted of 100 articles from 40 journals, national and international, inserted between strata A1 and B5. We used descriptive statistics in order to characterize the sample, and the chi-square test of independence, by means of which was examined the degree of independence between variables. The results suggest that the higher the classification level of the stratum, the greater the sophistication of statistical techniques employed in the articles. However, regarding the accuracy in applying the techniques, there were no significant differences between one stratum and another. Most of the articles analyzed (57%) not validated or partially validated the assumptions required for their use. Thus, it was realized that there was not proper concern with this aspect, even in well qualified strata. We emphasize that the results are restricted to the sample used. We recommend that future studies use large samples, including other means of publication, like events, both in finance as in other areas of knowledge.
Aglomeração e Valor de Compra em Centros de Consumo de Baixa Renda
Authors: Quezado Izabelle , Costa Rômulo Bernardino Lopes da , Peñaloza Verónica
Published: June 2014

Considering the great potential of low-income consumption, this research is based on the scales developed by Babin, Darden and Griffin (1994) and by Machleit, Kellaris and Eroglu (1994), aiming to investigate hedonic and utilitarian consumer behavior and its relation with low-income perception of crowding. A research was performed with 404 consumers in real store environment and the results showed that consumers revealed being prone to utilitarian behavior in both centers. About crowding phenomenon, the consumers felt more uncomfortable by crowding at the commercial center with less infrastructure. There were indices that this discomfort was less intense in hedonic consumers.
Reflexões sobre o empreendedor: uma análise sob a perspectiva da economia das organizações
Authors: Bittar Fernando Shigueo Omoto , Bastos Livia Tiemi , Moreira Vivian Lemes
Published: June 2014

An emergent theoretic field in current business is the strategic theory of the firm, a result of the interests in unifying modern organization economics knowledge with the competitive advantages experience from strategy. Unification efforts comprise the quest for convergence between the key concepts that support the theory, out of which attention is drawn towards the agent of strategy: the entrepreneur. This article aims at identifying the main intersection and divergence points by relating classic economists (Say, Cantillón, Knight) with the most famous author in the theme (Schumpeter) and recent advances in strategic theory of the firm (Peter Klein), contextualizing historically the evolution of the concept. In order to do so, a bibliographic research was conducted by reviewing the literature around these main authors, highly considered in this theme, other than characterizing historically and socially each of the author's environments, providing a comparison and a critical analysis of key contributions.
Antitumor Effects of CD40 Ligand-Expressing Endothelial Progenitor Cells Derived From Human Induced Pluripotent Stem Cells in a Metastatic Breast Cancer Model
Authors: Purwanti Yovita Ida , Chen Can , Lam Dang Hoang , Wu Chunxiao , Zeng Jieming , Fan Weimin , Wang Shu
Published: June 2014

Given their intrinsic ability to home to tumor sites, endothelial progenitor cells (EPCs) are attractive as cellular vehicles for targeted cancer gene therapy. However, collecting sufficient EPCs is one of the challenging issues critical for effective clinical translation of this new approach. In this study, we sought to explore whether human induced pluripotent stem (iPS) cells could be used as a reliable and accessible cell source to generate human EPCs suitable for cancer treatment. We used an embryoid body formation method to derive CD133+CD34+ EPCs from human iPS cells. The generated EPCs expressed endothelial markers such as CD31, Flk1, and vascular endothelial-cadherin without expression of the CD45 hematopoietic marker. After intravenous injection, the iPS cell-derived EPCs migrated toward orthotopic and lung metastatic tumors in the mouse 4T1 breast cancer model but did not promote tumor growth and metastasis. To investigate their therapeutic potential, the EPCs were transduced with baculovirus encoding the potent T cell costimulatory molecule CD40 ligand. The systemic injection of the CD40 ligand-expressing EPCs stimulated the secretion of both tumor necrosis factor-α and interferon-γ and increased the caspase 3/7 activity in the lungs with metastatic tumors, leading to prolonged survival of the tumor bearing mice. Therefore, our findings suggest that human iPS cell-derived EPCs have the potential to serve as tumor-targeted cellular vehicles for anticancer gene therapy.
Noise statistics identification for Kalman filtering of the electron radiation belt observations: 2. Filtration and smoothing
Authors: Podladchikova T. V. , Shprits Y. Y. , Kellerman A. C. , Kondrashov D.
Published: June 2014

In this study we present the further improvement of data assimilation using the 1‐D radial diffusion model for relativistic electron phase space density (PSD) and observations of CRRES satellite. The main purpose of our study is estimation of the radiation belt dynamics for the prediction and mitigation of space weather effects in the hazardous space environment. We develop further noise statistics identification technique presented in the companion paper to estimate the observation error statistics that are crucially important for optimal performance of data assimilation. Assimilation of satellite observations into first‐principles physics model of radiation belts, when both model and observation error statistics are poorly known, may cause large errors in the PSD estimation and lead to failure of a data assimilation algorithm. We identify the coefficients of proportionality characterizing the dependence of observation errors on satellite observations. The effectiveness of the proposed identification technique is illustrated by applying the Kalman filter with optimal identified and nonoptimal observation errors statistics to the sparse CRRES observations over a period of 441 days, from 28 July 1990 to 11 October 1991. Further improvement and the accuracy increase of PSD reconstruction is demonstrated by the implementation of the backward smoothing procedure applied to the forward Kalman filter estimates.
Gravity wave effects on postsunset equatorial F region stability
Authors: Hysell D. L. , Jafari R. , Fritts D. C. , Laughman B.
Published: June 2014

The influence of gravity waves on the stability of the postsunset equatorial F region ionosphere is investigated numerically. For this investigation, we use the output of a direct numerical simulation of waves and turbulence in the mesosphere and lower thermosphere to force a simulation of ionospheric dynamics. Both simulations are cast in three dimensions. The effectiveness of the neutral‐plasma coupling involved is generally thought to depend on the dynamo efficiency and spatial resonance of the forcing, which we evaluate. In our simulations, the postsunset equatorial ionosphere could be deformed by neutral waves after 5–15 min most severely when the wavefronts were aligned approximately with the magnetic meridian, despite the fact that the dynamo efficiency is modest even in that case. However, poor spatial resonance limits the subsequent growth of the deformations in our simulations, and the seeding of interchange instabilities does not occur. The coupled simulations predict the formation of intermediate layers in the equatorial valley region (150–250 km apex altitude) under some circumstances that could serve as telltales in nature of the presence of the kind of neutral forcing we simulate.
Observations and simulations of the ionospheric lunar tide: Seasonal variability
Authors: Pedatella N. M.
Published: June 2014

The seasonal variability of the ionospheric lunar tide is investigated using a combination of Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) observations and thermosphere‐ionosphere‐mesosphere electrodynamics general circulation model (TIME‐GCM) simulations. The present study focuses on the seasonal variability of the lunar tide in the ionosphere and its potential connection to the occurrence of stratosphere sudden warmings (SSWs). COSMIC maximum F region electron density (NmF2) and total electron content observations reveal a primarily annual variation of the ionospheric lunar tide, with maximum amplitudes occurring at low latitudes during December–February. Simulations of the lunar tide climatology in TIME‐GCM display a similar annual variability as the COSMIC observations. This leads to the conclusion that the annual variability of the lunar tide in the ionosphere is not solely due to the occurrence of SSWs. Rather, the annual variability of the lunar tide in the ionosphere is generated by the seasonal variability of the lunar tide at E region altitudes. However, compared to the observations, the ionospheric lunar tide annual variability is weaker in the climatological simulations which is attributed to the occurrence of SSWs during the majority of the years included in the observations. Introducing a SSW into the TIME‐GCM simulation leads to an additional enhancement of the lunar tide during Northern Hemisphere winter, increasing the lunar tide annual variability and resulting in an annual variability that is more consistent with the observations. The occurrence of SSWs can therefore potentially bias lunar tide climatologies, and it is important to consider these effects in studies of the lunar tide in the atmosphere and ionosphere.
Global representation of aerosol vertical profiles by sums of lognormal modes: Consequences for the passive remote sensing of aerosol heights
Authors: Hollstein A. , Filipitsch F.
Published: June 2014

Aerosol extinction profiles from a climatology of CALIPSO measurements are analyzed with respect to their representation by truncated sums of up to three lognormal functions. Discussed are results for the climatological mean and a realistic profile, which is constructed from the climatological mean and its standard deviation. The realistic profile shows, in general, a more feature‐rich structure and is used as proxy for actual measurements. It was found that a single lognormal mode is on global scale able to explain 59% of the vertical profile, while a sum of two modes is able to explain 74%. Including a third lognormal mode leads only to a minor improvement to 79%. The strong regional and weaker seasonal dependency of the reconstruction accuracy with respect to the number of used lognormal modes is presented and discussed in detail. These findings have implications for the design of future operational aerosol height retrievals for upcoming instruments such as Tropospheric Monitoring Instrument on board European Space Agency's Sentinel 5 precursor or Sentinel 4.
Tuberculosis revisited: Cytological perspective
Authors: Chatterjee Debajyoti , Dey Pranab
Published: June 2014

Tuberculosis is a major public health problem, especially in developing countries. The clinical manifestations of tuberculosis are very nonspecific and may mimic many other conditions. An accurate diagnosis is extremely important as the disease is treatable with antituberculous therapy. Cytological examination can provide useful diagnostic material for routine and ancillary techniques for rapid and accurate diagnosis of tuberculosis. Here we review the different morphological patterns of tuberculosis, challenges, and application of ancillary techniques for cytological diagnosis of tuberculosis. Diagn. Cytopathol. 2014;42:993–1001. © 2014 Wiley Periodicals, Inc.
Parent feeding behavior and child appetite: Associations depend on feeding style
Authors: Carnell Susan , Benson Leora , Driggin Elissa , Kolbe Laura
Published: June 2014

Objective

Eating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers' appetitive traits.

Method

Four hundred thirty‐nine parents of UK 3–5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z‐scores were calculated based on measured heights and weights.

Results

Parental Restriction was significantly associated with greater child Food responsiveness (p < .001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p < .001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p < .001). All relationships were independent of child BMI z‐score.

Discussion

Prospective data are needed to determine whether the parent–child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross‐sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:705–709)
Sensitivity, effect and overdiagnosis in screening for cancers with detectable pre‐invasive phase
Authors: Hakama Matti , Pokhrel Arun , Malila Nea , Hakulinen Timo
Published: June 2014

Studies on cancer screening often evaluate the performance by indirect indicators. In case the screening detects pre‐invasive lesions, they may be a mixture of benefit of sensitivity and effect as well as of harm of overdiagnosis. Here, we develop the formulae for the sensitivity, the effect and overdiagnosis in screening for pre‐invasive lesions of cancer. Sensitivity is the ability of screening to identify a progressive lesion at the level of test (relevant for the laboratory), episode (relevant in the clinic) and programme (relevant at the population level). Effect is reduction of cancer incidence in those screened (efficacy) and in the target population (effectiveness). The sensitivity is estimated by interval cancers between two consecutive screens (incidence method) and the effect by interval cancers and cancers detected at the subsequent screen. Overdiagnosis is estimated as the detection rate of pre‐invasive lesions minus the rate of invasive cancer prevented by screening in one screening round. All the indicators are corrected for nonattendance and selective attendance by disease risk. The population to be followed and the period of follow‐up are defined for each indicator separately. Data on cervix cancer screening with Papnet® automation device are given as an example. Estimation of sensitivity and effect are consistent with the purpose of the screening to prevent invasive disease. We further define the purpose at the level of laboratory, clinical medicine and public health and derive six estimators corresponding to the specific purposes considered in our article.
Identification of microRNAs differentially expressed in prostatic secretions of patients with prostate cancer
Authors: Guzel Esra , Karatas Omer F. , Semercioz Atilla , Ekici Sinan , Aykan Serdar , Yentur Serhat , Creighton Chad J. , Ittmann Michael , Ozen Mustafa
Published: June 2014

Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. Since there are limited treatment options available for the advanced tumors, there is an urgent need for novel diagnostic tools for PCa. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) was performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse‐transcription PCR (qRT‐PCR). Statistical analysis was performed using Student's t‐test. ROC curves were plotted with SPSS‐15.0.

In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. MiRNA profiling of four PCa and four BPH patients with microarray revealed that miR‐361‐3p, miR‐133b and miR‐221 were significantly downregulated and miR‐203 was upregulated in PSS of PCa patients. Further qRT‐PCR analysis confirmed the altered expressions of these four miRNAs in PSS of 23 PCa and 25 BPH patients. Four miRNAs, together and individually have much power (AUC; 0.950) than PSA has (AUC; 0.463) to discriminate PCa from BPH patients.

We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non‐invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers.
In vitroandin vivocorrosion properties of new iron–manganese alloys designed for cardiovascular applications
Authors: Drynda Andreas , Hassel Thomas , Bach Friedrich Wilhelm , Peuster Matthias
Published: June 2014

The principle of biodegradation for the production of temporary implant materials (e.g. stents) plays an important role in the treatment of congenital heart defects. In the last decade several attempts have been made with different alloy materials—mainly based on iron and magnesium. None of the currently available materials in this field have demonstrated satisfying results and have therefore not found entry into broad clinical practice. While magnesium or magnesium alloy systems corrode too fast, the corrosion rate of pure iron‐stents is too slow for cardiovascular applications. In the last years FeMn alloy systems were developed with the idea that galvanic effects, caused by different electrochemical properties of Fe and Mn, would increase the corrosion rate.In vitrotests with alloys containing up to 30% Mn showed promising results in terms of biocompatibility. This study deals with the development of new FeMn alloy systems with lower Mn concentrations (FeMn 0.5 wt %, FeMn 2.7 wt %, FeMn 6.9 wt %) to avoid Mn toxicity. Our results show, that these alloys exhibit good mechanical features as well as suitablein vitrobiocompatibility and corrosion properties. In contrast, the evaluation of these alloys in a mouse model led to unexpected results—even after 9 months no significant corrosion was detectable. Preliminary SEM investigations showed that passivation layers (FeMn phosphates) might be the reason for corrosion resistance. If this can be proved in further experiments, strategies to prevent or dissolve those layers need to be developed to expedite thein vivocorrosion of FeMn alloys. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 649–660, 2015.
Chemical constituents ofMeconopsis horridulaand their simultaneous quantification by high‐performance liquid chromatography coupled with tandem mass spectrometry
Authors: Liu Jiajia , Wu Haimei , Zheng Feng , Liu Wenyuan , Feng Feng , Xie Ning
Published: June 2014

Meconopsis horridulaHook.f. Thoms has been used as a traditional Tibetan medicine to clear away heat, relieve pain, and mobilize static blood. In this study, a reliable method based on high‐performance liquid chromatography with diode array detection and electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry was established for the identification of components in this herb. A total of 40 compounds (including 17 flavonoids, 15 alkaloids, and eight phenylpropanoids) were identified or tentatively identified. Among them, 17 components were identified in the herb for the first time. Compound39appears to be a novel compound, which is confirmed as 3‐(kaempferol‐8‐yl)‐2,3‐epoxyflavanone by NMR spectroscopy and mass spectrometry. Moreover, seven major constituents were simultaneously quantified by the developed high‐performance liquid chromatography with tandem triple‐quadrupole mass spectrometry method. The quantitative method was validated and quality parameters were established. The study provides a comprehensive approach for understanding this herbal medicine.