bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Impermeable Shale Streaks on Production
Authors: Uguru C. I. , Obiuwevbi H. A. , Oni J.
Published: July 2011

The presence of intra-reservoir shales in reservoirs otherwise thought of as homogeneous plays a key role in reservoir production performance. The presence of these shales effectively subdivides these reservoirs into different flow units. These shales impede vertical flow across the flow units of the reservoir thereby resulting in bypassed hydrocarbon. It has become necessary to review well completion strategy to target every identifiable flow zone in a reservoir in order to optimise hydrocarbon recovery.

Examples provided in this paper were drawn from a brown field with over forty years of active production. The completion strategy applied to these reservoirs played an important part in the hydrocarbon recovery. An established analytical method for predicting permeability (and the ratios of horizontal to vertical permeability) already in use in Shell Petroleum Development Company (SPDC) in Nigeria was used to validate acquired saturation logs. In addition, production data from wells were used in confirming the procedure.
Modelling System Failures of Electric Submersible Pumps in Sand Producing Wells
Authors: Kalu-Ulu T. C , Andrawus J. A , George I. P.
Published: July 2011

Electrical Submersible Pumps (ESPs) are used to boost production in hydrocarbon and enhance investment recovery in the oil and gas industry is affected by solid particles. Sanding reduces the integrity and reliability of ESPs with enormous consequences. Better knowledge of the performance of Electric Submersible pumps in sand producing well through system failure modelling ensures effective planning and good operational philosophy. Life-failure-data were collated and analysed in this paper using Weibull Distribution to determine the shape (β) and the scale (ή) parameters of ESP system components. The system failure mode analysis carried out highlighted the failure patterns of ESPs. Mechanical based failure components displayed constant failure pattern while electrical based failure components displayed decreasing failure pattern.

A simple Reliability Block Diagram is designed to model the system failure. This is simulated to ascertain the reliability, availability and maintainability of ESPs in sand prone wells.
Prediction of Stuck Pipe in Iranian South Oil Fields Using Multivariate Statistical Analysis
Authors: Shoraka S. A. , Shadizadeh S. R. , Pordel Shahri M.
Published: July 2011

Stuck pipe is a common problem accounts for losses hundreds of millions of dollars each year in the petroleum industry and have been the cause of very problems while drilling. Therefore efforts have been made to determine the causes of stuck pipe and that will minimize the occurrence of the problem.

This problem is known to occur as several major mechanisms including: wellbore instability, differential sticking forces, improper hole cleaning and the forming of drill-cutting beds, especially in high angle wells. The obvious effect of stuck pipe is lost time and an increase in well cost. Also, losing a section of the hole and downhole tools and having to plug back to redrill or sidetracking would be the worst case scenario.

In this study an attempt is made to develop a model for stuck pipe in Iranian southern oil field drilling wells. For this purpose drilling data including: measured depth, mud weight, plastic viscosity, yield point, 10 second gel, 10 minute gel, PH, percent solid, etc. from forty well drilled in one of the field are selected. Using the multivariate statistical regression and discriminated analysis representing stuck pipe is developed. The developed equations can be used for prevention or reducing risk due to the stuck drill string and avoided from increases of drilling cost and lost time.
Extending the Human Life Span: An Exploratory Study of Pro- and Anti-Longevity Attitudes
Authors: Kogan Nathan , Tucker Jennifer , Porter Matthew
Published: July 2011

Successful efforts by biologists to substantially increase the life span of non-human animals has raised the possibility of extrapolation to humans, which in turn has given rise to bioethical argumentation, pro and con. The present study converts these arguments into pro- and anti-longevity items on a questionnaire and examines the structure and correlates of the resultant life-extension domain. A 35-item Life-Extension Questionnaire (LEQ) was administered to a mixed-age sample of 164 respondents and a more age-homogeneous sample of 101 well-educated older adults. Demographic information (age, sex, ethnicity, education, marital status) was also obtained. In both samples, exploratory factor analysis of the LEQ (with Promax rotation) yielded three factors labeled Utopian Vision (UV), Personal Emotion Rejection (PER), and Social Economic Burden (SEB). Of the 35 LEQ items, 24 manifested similar factor loading patterns across the two samples—11 for UV, 9 for PER, and 4 for SEB. Coefficients of congruence further supported the case for factorial replication across the two samples. Chronological age correlated positively with UV factor scores in both samples, indicating a trend toward stronger prolongevity attitudes in older relative to younger cohorts. Individual differences in life-extension attitudes are seen as mirroring the differences among bioethicists in the domain.
Ethnically Diverse Older Adults' Beliefs about Staying Mentally Sharp
Authors: Friedman Daniela B. , Laditka Sarah B. , Laditka James N. , Wu Bei , Liu Rui , Price Anna E. , Tseng Winston , Corwin Sara J. , Ivey Susan L. , Hunter Rebecca , Sharkey Joseph R.
Published: July 2011

This study examined diverse older adults' ( n = 396, ages 50+) views about how to stay mentally sharp. We conducted 42 focus groups in four languages at nine United States locations using a standardized discussion guide and methods. The groups represented African Americans, American Indians, Chinese Americans, Latinos, Whites other than Latinos, and Vietnamese Americans. All groups mentioned benefits of social interaction. All groups, especially Chinese and African Americans, mentioned benefits of community engagement. Participants in all groups expressed their belief that mental stimulation, particularly reading, promoted cognitive health; African Americans and Whites were especially likely to say that mental exercises (e.g., puzzles) were useful. Results suggest opportunities for education about potential cognitive health benefits of being socially connected through senior center activities and volunteer programs.
Not Quite Color Blind: Ethnic and Gender Differences in Attitudes toward Older People among College Students
Authors: Laditka Sarah B. , Laditka James N. , Houck Margaret M. , Olatosi Bankole A.
Published: July 2011

Attitudes toward older people can influence how they are treated and their cognitive and physical health. The populations of the United States and many other countries have become more ethnically diverse, and are aging. Yet little research examines how ethnic diversity affects attitudes toward older people. Our study addresses this research gap. Using the Aging Semantic Differential, 592 university students expressed their attitudes toward older African-American, Hispanic, and White women and men. Repeated measures analysis of variance examined attitude differences by participant ethnicity and gender, and by the ethnicity and gender of evaluated individuals. Both African-American and White students had more positive attitudes toward older women and men of their own ethnic group. Participants had more positive attitudes toward older women than they did toward older men. Findings suggest in-group favoritism, and the usefulness of training those in service industries and public service to treat older individuals equitably.
Cultural Perspectives on Aging and Well-Being: A Comparison of Japan and the United States
Authors: Karasawa Mayumi , Curhan Katherine B. , Markus Hazel Rose , Kitayama Shinobu S. , Love Gayle Dienberg , Radler Barry T. , Ryff Carol D.
Published: July 2011

This study investigated age differences in multiple aspects of psychological well-being among midlife and older adults in Japan ( N = 482) and the United States ( N = 3,032) to test the hypothesis that older Japanese adults would rate aspects of their well-being (personal growth, purpose in life, positive relations with others) more highly that older U.S. adults. Partial support was found: older adults in Japan showed higher scores on personal growth compared to midlife adults, whereas the opposite age pattern was found in the United States. However, purpose in life showed lower scores for older adults in both cultural contexts. Interpersonal well-being, as hypothesized, was rated significantly higher, relative to the overall well-being, among Japanese compared to U.S. respondents, but only among younger adults. Women in both cultures showed higher interpersonal well-being, but also greater negative affect compared with men. Suggestions for future inquiries to advance understanding of aging and well-being in distinct cultural contexts are detailed.
Regional Variation in Medication Adherence
Authors: Gibson Teresa B , Landrum Mary Beth , Batata Amber , Fendrick A. Mark , Wang Sara , Chernew Michael E.
Published: July 2011

An extensive literature has demonstrated geographic variation in medical services and this variation has been largely attributed to the health care system and not to regional differences in patient behavior. We use empirical Bayes shrinkage models, conditional on patient, firm, and market covariates, to investigate geographic variation in adherence to prescription medications across hospital referral regions (HRRs). Models are estimated for commercially insured patients in 11 combinations of chronic diseases and drug classes. We use factor analysis to create a market-level composite measure of adherence that we relate to adjusted market-level spending on non-drug services. We find that there is a very small amount of variation in adherence to prescription drugs across HRRs supporting the widely held assumption that geographic variation is attributable to the health system. Markets with high adherence have systematically lower medical spending, and this inverse correlation is more likely due to unobserved market traits.
CFD Modelling of Global Mixing Parameters in a Peirce-Smith Converter with Comparison to Physical Modelling
Authors: Chibwe Deside K , Akdogan Guven , Aldrich Chris , Eric Rauf H
Published: July 2011

The flow pattern and mixing in an industrial Peirce-Smith converter (PSC) has been experimentally and numerically studied using cold model simulations. The effects of air volumetric flow rate and presence of overlaying slag phase on matte on the flow structure and mixing were investigated. The 2-D and 3-D simulations of the three phase system were carried out using volume of fluid (VOF) and realizable k - ɛ turbulence model to account for the multiphase and turbulence nature of the flow respectively. These models were implemented using commercial Computational Fluid Dynamics (CFD) numerical code FLUENT. The cold model for physical simulations was a 1:5 horizontal cylindrical container made of Perspex with seven tuyeres on one side of the cylinder typifying a Peirce-Smith converter. Compressed air was blown into the cylinder through the tuyeres, simulating air or oxygen enriched air injection into the PSC. The matte and slag phases were simulated with water and kerosene respectively in this study. The influence of varying blowing conditions and simulated slag quantities on the bulk mixing was studied with five different air volumetric flow rates and five levels of simulated slag thickness. Mixing time results were evaluated in terms of total specific mixing power and two mixing time correlations were proposed for estimating mixing times in the model of PSC for low slag and high slag volumes. Both numerical and experimental simulations were in good agreement to predict the variation characteristics of the system in relation to global flow field variables set up in the converter through mathematical calculation of relevant integrated quantities of turbulence, Volume Fraction (VF) and velocity magnitudes. The findings revealed that both air volumetric flow rate and presence of the overlaying slag layer have profound effects on the mixing efficiency of the converter.
Hormesis Pervasiveness and its Potential Implications for Pharmaceutical Research and Development
Authors: Maynard Kenneth I.
Published: July 2011

This mini-review illustrates that hormesis is not only confined to the areas of biochemistry, radiation biology and toxicology, where it is traditionally known, but illustrates, by citing published scientific literature, that it is found across a wide range of biomedical science and clinical medicine such as neuroscience, cardiology and oncology. The use of techniques and technology, including high through-put screening, micro-dosing or phase 0 studies, pharmacometrics and adaptive trial design in the clinic, are proposed to illustrate how acknowledging the potential impact of hormesis throughout different stages of drug discovery and development, including hurdles related to efficacy and safety, could help the pharmaceutical industry address some of its major and frequently mentioned challenges.
Codes and designs from triangular graphs and their line graphs
Authors: Fish Washiela , Kumwenda Khumbo , Mwambene Eric
Published: July 2011

For any prime p, we consider p-ary linear codes obtained from the span over $\mathbb{F}_p $
p of rows of incidence matrices of triangular graphs, differences of the rows and adjacency matrices of line graphs of triangular graphs. We determine parameters of the codes, minimum words and automorphism groups. We also show that the codes can be used for full permutation decoding.
Geokinematics in GGOS - Different Relations and Dependences
Authors: Pachelski Wojciech , Paśnicka Małgorzata , Szafranek Karolina , Zwirowicz-Rutkowska Agnieszka
Published: July 2011

Geokinematics in GGOS - Different Relations and Dependences

The paper presents the preliminary results of the analysis of fundamental dependencies between different geodetic concepts related to the one of the GGOS (Global Geodetic Observation System) pillars called Geometry and Kinematics. These relationships are described using UML (Unified Modelling Language) - one of the graphical notations that can be used for information modelling. Concepts are represented as classes with their names, attributes, and different kinds of links between them. The main purpose of this paper is to introduce the full description of connections between all GGOS components.
One Contribution to the Friction Investigation in Bulk Metal Forming
Authors: Kačmarčik Igor , Movrin Dejan , Ivanišević Aljoša
Published: July 2011

One Contribution to the Friction Investigation in Bulk Metal Forming

Friction is resistance to relative motion when one body slides over another. In metal forming operations, both sheet metal and bulk metal forming, friction is undesirable but also unavoidable occurrence. It has negative impact on main process parameters as well as on workpiece quality. In order to obtain accurate results in metal forming experiments or simulations, the precise value of friction has to be known. In this paper several methods for friction evaluations, such as ring test, forward bar extrusion, backward - forward hollow extrusion, twist extrusion are presented and analyzed. A new double backward extrusion model is proposed.
Selected Applications of Virtual Reality in Manufacturing
Authors: Novak-Marcincin Jozef
Published: July 2011

Selected Applications of Virtual Reality in Manufacturing

Virtual reality (VR) has become an important and useful tool in science and engineering. VR applications cover a wide range of industrial areas from product design to analysis, from product prototyping to manufacturing. The design and manufacturing of a product can be viewed, evaluated and improved in a virtual environment before its prototype is made, which is an enormous cost saving. Virtual Manufacturing (VM) is the use of computer models and simulations of manufacturing processes to aid in the design and production of manufactured products. VM is the use of manufacturing-based simulations to optimize the design of product and processes for a specific manufacturing goal such as: design for assembly; quality; lean operations; and/or flexibility.
Caracterisation of Titanium Nitride Layers Deposited by Reactive Plasma Spraying
Authors: Roşu Radu , Şerban Viorel-Aurel , Bucur Alexandra , Popescu Mihaela , Uţu Dragoş
Published: July 2011

Caracterisation of Titanium Nitride Layers Deposited by Reactive Plasma Spraying

Forming and cutting tools are subjected to the intense wear solicitations. Usually, they are either subject to superficial heat treatments or are covered with various materials with high mechanical properties. In recent years, thermal spraying is used increasingly in engineering area because of the large range of materials that can be used for the coatings. Titanium nitride is a ceramic material with high hardness which is used to cover the cutting tools increasing their lifetime. The paper presents the results obtained after deposition of titanium nitride layers by reactive plasma spraying (RPS). As deposition material was used titanium powder and as substratum was used titanium alloy (Ti6Al4V). Macroscopic and microscopic (scanning electron microscopy) images of the deposited layers and the X ray diffraction of the coatings are presented. Demonstration program with layers deposited with thickness between 68,5 and 81,4 μm has been achieved and presented.
Experimental Tooling for Contact Stress Measurement in Bulk Metal Forming Processes
Authors: Vilotić Dragiša , Plančak Miroslav
Published: July 2011

Experimental Tooling for Contact Stress Measurement in Bulk Metal Forming Processes

Knowledge of contact stresses in metal forming operations is essential not only for optimal die design, but also for theoretical and numerical analysis of the metal forming processes. Determination of contact stresses can be performed theoretically and experimentally. This paper presents a tool construction with built-in pin-load cells for experimental determination of contact stresses and friction coefficient at upsetting of prismatic specimen with cylindrical dies. This construction allows measurement of contact stresses in any point of the contact surface of specimen, due to adjustable location of pin-load cells. The adjustments are performed by turning cylindrical dies around its own axis in combination with the change of axial position of the specimen. Experimental determination of contact stresses in upsetting of Ck35 prismatic specimens using cylindrical tools was performed at the Laboratory for technology of plasticity, FTN Novi Sad.
Technology-Based Sheet Metal Classification and Coding System
Authors: Šugár Peter , Šugárová J. , Kolník M.
Published: July 2011

Technology-Based Sheet Metal Classification and Coding System

Group technology (GT) concept uses design similarity measure to identify the most similar design and retrieve a useful process plan. One of the existing formal methods of machine parts classifying for the group technology applications is the coding and classification. The researchers have developed many different GT coding schemes, which very precisely describe the design characteristics of the parts, but many of them do not explicitly describe the process plan. The paper presents a new approach to the sheet metal part coding and classification with plan-based attributes implementation in accordance with the technical standard STN 226001.
Switching Schools
Authors: Gasper Joseph , DeLuca Stefanie , Estacion Angela
Published: July 2011

Youth who switch schools are more likely to demonstrate a wide array of negative behavioral and educational outcomes, including dropping out of high school. However, whether switching schools actually puts youth at risk for dropout is uncertain, since youth who switch schools are similar to dropouts in their levels of prior school achievement and engagement, which suggests that switching schools may be part of the same long-term developmental process of disengagement that leads to dropping out. Using data from the National Longitudinal Survey of Youth 1997, this study uses propensity score matching to pair youth who switched high schools with similar youth who stayed in the same school. We find that while over half the association between switching schools and dropout is explained by observed characteristics prior to ninth grade, switching schools is still associated with dropout. Moreover, the relationship between switching schools and dropout varies depending on a youth’s propensity for switching schools.
Scholars as Policy Actors
Authors: Welner Kevin G.
Published: July 2011

Courts, students are told, will protect minorities’ legal rights against popular sentiment and political pressure. But courts can be expected to protect rights only within boundaries shaped in part by popular and political opinion. This suggests that litigation outcomes regarding education rights issues will depend on shifting the policymaking context through broad societal changes in perspective about the importance of equitable schooling. This dynamic of courts carrying out their limited countermajoritarian role within contextual constraints has substantial implications concerning the largely unrealized capacity of social science to affect judicial decision making. Accordingly, this article explores that dynamic and those implications, building on existing concepts from political science scholarship and introducing the concept of a zone of judicial constraints.
A Critical Analysis of the Research on Student Homelessness
Authors: Miller Peter M.
Published: July 2011

Since the onset of the economic recession, rates of student homelessness have increased rapidly in urban, suburban, and rural school districts throughout the United States. Despite the widespread urgency of the issue, there is a lack of general coherence in the research about how diverse conditions of homelessness affect students and how schools and communities can best serve them. This literature review attempts to deepen scholars’ understandings of such matters by examining (a) homeless students’ school experience in comparison to that of other students, (b) federal policy’s shaping of homeless students’ rights and opportunities, and (c) homeless students’ key support mechanisms. The author suggests that these three focus areas provide foundational insights into the nature and extent of students’ opportunities to succeed in school. Although homeless students’ experiences are noted to be similar to those of residentially stable low-income students, they appeared to be distinguishable based on their high rates of isolation and school mobility. The McKinney-Vento Homeless Assistance Act was found to have profound formative influences on the wider field of practice, but its full implementation is limited by the disconnected nature of students’ diverse support mechanisms. Based on the findings, the author suggests that researchers and practitioners consider the people, places, and policies that affect students in more holistic manners—as networks of practice.
IL-1R–Associated Kinase-1 Mediates Protein Kinase Cδ-Induced IL-1β Production in Monocytes
Authors: Tiwari Rajiv Lochan , Singh Vishal , Singh Ankita , Barthwal Manoj Kumar
Published: July 2011

The role of IL-1R–associated kinase (IRAK)1 and its interaction with protein kinase C (PKC)δ in monocytes to regulate IL-1β production has not been reported so far. The present study thus investigates such mechanisms in the THP1 cell line and human monocytes. PMA treatment to THP1 cells induced CD11b, TLR2, TLR4, CD36, IRAK1, IRAK3, and IRAK4 expression, IRAK1 kinase activity, PKCδ and JNK phosphorylation, AP-1 and NF-κB activation, and secretory IL-1β production. Moreover, PMA-induced IL-1β production was significantly reduced in the presence of TLR2, TLR4, and CD11b Abs. Rottlerin, a PKCδ-specific inhibitor, significantly reduced PMA-induced IL-1β production as well as CD11b, TLR2 expression, and IRAK1–JNK activation. In PKCδ wild-type overexpressing THP1 cells, IRAK1 kinase activity and IL-1β production were significantly augmented, whereas recombinant inactive PKCδ and PKCδ small interfering RNA significantly inhibited basal and PMA-induced IRAK1 activation and IL-1β production. Endogenous PKCδ–IRAK1 interaction was observed in quiescent cells, and this interaction was regulated by PMA. IRAK1/4 inhibitors, their small interfering RNAs, and JNK inhibitor also attenuated PMA-induced IL-1β production. NF-κB activation inhibitor and SN50 peptide inhibitor, however, failed to affect PMA-induced IL-1β production. A similar role of IRAK1 in IL-1β production and its regulation by PKCδ was evident in the primary human monocytes, thus signifying the importance of our finding. To our knowledge, the results obtained demonstrate for the first time that IRAK1 and PKCδ functionally interact to regulate IL-1β production in monocytic cells. A novel mechanism of IL-1β production that involves TLR2, CD11b, and the PKCδ/IRAK1/JNK/AP-1 axis is thus being proposed.
IL-13 Induces Connective Tissue Growth Factor in Rat Hepatic Stellate Cells via TGF-β–Independent Smad Signaling
Authors: Liu Yan , Meyer Christoph , Müller Alexandra , Herweck Frank , Li Qi , Müllenbach Roman , Mertens Peter R. , Dooley Steven , Weng Hong-Lei
Published: July 2011

Connective tissue growth factor (CTGF) plays a central role in stimulating extracellular matrix deposition in the liver, and hence is considered a critical mediator of TGF-β–dependent fibrogenesis. Hepatic stellate cells (HSCs) are known as the major source of CTGF in damaged liver. However, previous studies revealed that IL-13, rather than TGF-β, represents the predominant inducer of CTGF expression in HSCs. We now dissected IL-13 downstream signaling that modulates CTGF expression in HSCs. IL-13 induces a time- and dosage-dependent increase of CTGF in a TGF-β–independent manner. This process requires participation of different Smad proteins and their upstream receptor kinases (activin receptor-like kinases). Smad1 and Smad2 were identified as the key mediators of IL-13–dependent CTGF expression. Furthermore, IL-13 induces Stat6 phosphorylation in HSCs, but Stat6 was not involved in CTGF induction. Instead, the Erk1/2-MAPK pathway was found to be responsible for IL-13–induced early Smad phosphorylation and CTGF synthesis. We demonstrate that IL-13 induces CTGF expression in HSCs by activating TGF-β–independent activin receptor-like kinase/Smad signaling via the Erk-MAPK pathway rather than via its canonical JAK/Stat6 pathway. These results provide an improved new insight into the molecular mechanisms of profibrotic IL-13 activities in the liver.
Discovery of the DIGIRR Gene from Teleost Fish: A Novel Toll–IL-1 Receptor Family Member Serving as a Negative Regulator of IL-1 Signaling
Authors: Gu Yi-feng , Fang Yu , Jin Yang , Dong Wei-ren , Xiang Li-xin , Shao Jian-zhong
Published: July 2011

Toll–IL-1R (TIR) family members play crucial roles in a variety of defense, inflammatory, injury, and stress responses. Although they have been widely investigated in mammals, little is known about TIRs in ancient vertebrates. In this study, we report a novel double Ig IL-1R related molecule (DIGIRR) from three model fish (Tetraodon nigroviridis, Gasterosteus aculeatus, and Takifugu rubripes), adding a previously unknown homolog to the TIR family. This DIGIRR molecule contains two Ig-like domains in the extracellular region, one Arg-Tyr–mutated TIR domain in the intracellular region, and a unique subcellular distribution within the Golgi apparatus. These characteristics distinguish DIGIRR from other known family members. In vitro injection of DIGIRR into zebrafish embryos dramatically inhibited LPS-induced and IL-1β–induced NF-κB activation. Moreover, in vivo knockdown of DIGIRR by small interfering RNA significantly promoted the expression of IL-1β–stimulated proinflammatory cytokines (IL-6 and IL-1β) in DIGIRR-silenced liver and kidney tissues and in leukocytes. These results strongly suggest that DIGIRR is an important negative regulator of LPS-mediated and IL-1β–mediated signaling pathways and inflammatory responses. The Arg-Tyr–mutated site disrupted the signal transduction ability of DIGIRR TIR. Evolutionally, we propose a hypothesis that DIGIRR and single Ig IL-1R related molecule (SIGIRR) might originate from a common ancient IL-1R–like molecule that lost one (in DIGIRR) or two (in SIGIRR) extracellular Ig-like domains and intracellular Ser and Arg-Tyr amino acids. DIGIRR might be an evolutionary “transitional molecule” between IL-1R and SIGIRR, representing a shift from a potent receptor to a negative regulator. These results help define the evolutionary history of TIR family members and their associated signaling pathways and mechanisms.
Cytotoxic Dendritic Cells Generated from Cancer Patients
Authors: Lakomy Daniela , Janikashvili Nona , Fraszczak Jennifer , Trad Malika , Audia Sylvain , Samson Maxime , Ciudad Marion , Vinit Julien , Vergely Catherine , Caillot Denis , Foucher Pascal , Lagrost Laurent , Chouaib Salem , Katsanis Emmanuel , Larmonier Nicolas , Bonnotte Bernard
Published: July 2011

Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.
Antiasthmatic Drugs Targeting the Cysteinyl Leukotriene Receptor 1 Alleviate Central Nervous System Inflammatory Cell Infiltration and Pathogenesis of Experimental Autoimmune Encephalomyelitis
Authors: Wang Liefeng , Du Changsheng , Lv Jie , Wei Wei , Cui Ye , Xie Xin
Published: July 2011

Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and are considered to play a key role in inflammatory diseases such as asthma. Antagonists targeting the receptor of CysLTs (CysLT1) are currently used as antiasthmatic drugs. CysLTs have also been implicated in other inflammatory reactions. In this study, we report that in experimental autoimmune encephalomyelitis animals, CysLT1 is upregulated in immune tissue and the spinal cord, and CysLT levels in the blood and cerebrospinal fluid are also higher than in normal mice. Two clinically used antiasthma drugs, montelukast and zafirlukast, both targeting CysLT1, effectively block the CNS infiltration of inflammatory cells and thus reduce the incidence, peak severity, and cumulative clinical scores. Further study indicated that CysLT1 signaling does not affect the differentiation of pathogenic T helper cells. It might affect the pathogenesis of experimental autoimmune encephalomyelitis by increasing the secretion of IL-17 from myelin oligodendrocyte glycoprotein-specific T cells, increasing the permeability of the blood–brain barrier and inducing chemotaxis of T cells. These effects can be blocked by CysLT1 antagonists. Our findings indicate that the antiasthmatic drugs against CysLT1 can also be used to treat multiple sclerosis.
Coordinated Host Responses during Pyroptosis: Caspase-1–Dependent Lysosome Exocytosis and Inflammatory Cytokine Maturation
Authors: Bergsbaken Tessa , Fink Susan L. , den Hartigh Andreas B. , Loomis Wendy P. , Cookson Brad T.
Published: July 2011

Activation of caspase-1 leads to pyroptosis, a program of cell death characterized by cell lysis and inflammatory cytokine release. Caspase-1 activation triggered by multiple nucleotide-binding oligomerization domain-like receptors (NLRs; NLRC4, NLRP1b, or NLRP3) leads to loss of lysosomes via their fusion with the cell surface, or lysosome exocytosis. Active caspase-1 increased cellular membrane permeability and intracellular calcium levels, which facilitated lysosome exocytosis and release of host antimicrobial factors and microbial products. Lysosome exocytosis has been proposed to mediate secretion of IL-1β and IL-18; however, blocking lysosome exocytosis did not alter cytokine processing or release. These studies indicate two conserved secretion pathways are initiated by caspase-1, lysosome exocytosis, and a parallel pathway resulting in cytokine release, and both enhance the antimicrobial nature of pyroptosis.
The Role of Intermediary Domain of MyD88 in Cell Activation and Therapeutic Inhibition of TLRs
Authors: Avbelj Monika , Horvat Simon , Jerala Roman
Published: July 2011

Adaptor MyD88 has a pivotal role in TLR and IL-1R signaling and is involved in mediating excessive inflammation. MyD88 is composed of a death domain and a Toll/IL-1R domain connected by an intermediary domain (INT). The alternatively spliced form of MyD88 lacking the INT prevents signaling through MyD88-dependent TLRs. We designed a peptide from the INT and showed that it inhibits TLR4 activation by LPS when linked to a cell-penetrating peptide. As a new approach for the delivery of signaling-inhibitory peptides, INT peptide acylation also provided efficient cell translocation and inhibition of activation. We determined that INT peptide targets IL-1R–associated kinase 4. Furthermore, MyD88 mutant and molecular modeling refines the MyD88– IL-1R–associated kinase 4 interaction model based on the Myddosome structure. In addition to TLR4, INT peptide also inhibited TLR5, TLR2, TLR9, and IL-1R signaling but not TLR3, which uses Toll/IL-1R domain-containing adapter inducing IFN-β signaling adaptor. Inhibition of signaling in murine and human cells was observed by decreased NF-κB activation, cytokine mRNA synthesis, and phosphorylation of downstream kinases. In the endotoxemic mouse model, INT peptide suppressed production of inflammatory cytokines and improved survival, supporting therapeutic application of INT peptides for the suppression of inflammatory conditions mediated by MyD88.
Cutting Edge: Immunological Consequences and Trafficking of Human Regulatory Macrophages Administered to Renal Transplant Recipients
Authors: Hutchinson James A. , Riquelme Paloma , Sawitzki Birgit , Tomiuk Stefan , Miqueu Patrick , Zuhayra Maaz , Oberg Hans H. , Pascher Andreas , Lützen Ulf , Janßen Uwe , Broichhausen Christiane , Renders Lutz , Thaiss Friedrich , Scheuermann Ernst , Henze Eberhard , Volk Hans-Dieter , Chatenoud Lucienne , Lechler Robert I. , Wood Kathryn J. , Kabelitz Dieter , Schlitt Hans J. , Geissler Edward K. , Fändrich Fred
Published: July 2011

Regulatory macrophages (M regs) were administered to two living-donor renal transplant recipients. Both patients were minimized to low-dose tacrolimus monotherapy within 24 wk of transplantation and subsequently maintained excellent graft function. After central venous administration, most M regs remained viable and were seen to traffic from the pulmonary vasculature via the blood to liver, spleen, and bone marrow. By 1 y posttransplantation, both patients displayed patterns of peripheral blood gene expression converging upon the IOT-RISET signature. Furthermore, both patients maintained levels of peripheral blood FOXP3 and TOAG-1 mRNA expression within the range consistent with nonrejection. It is concluded that M regs warrant further study as a potential immune-conditioning therapy for use in solid-organ transplantation. The results of this work are being used to inform the design of The ONE Study, a multinational clinical trial of immunomodulatory cell therapy in renal transplantation.
Cutting Edge: Distinct Waves of BCL6 Expression during T Follicular Helper Cell Development
Authors: Baumjohann Dirk , Okada Takaharu , Ansel K. Mark
Published: July 2011

T follicular helper (TFH) cells are central to the development and regulation of T cell-dependent humoral immune responses. The transcriptional repressor BCL6 is required for TFH responses, but the kinetics of BCL6 protein expression in activated CD4+ T cells have not been established. We measured BCL6 expression during TFH cell development at the single-cell level using intracellular staining and YFP-BCL6 fusion protein reporter mice. BCL6 was immediately upregulated in all dividing T cells during dendritic cell–T cell interactions. A second wave of early BCL6 expression coincided with the induction of CXCR5, resulting in a distinct and stable TFH cell population. Cognate B cells were not required for the induction of BCL6, but supported the expansion of TFH cells. These data suggest that BCL6 participates in very early events in TFH cell development, and that repeated encounters with APCs reinforce BCL6 expression, thereby establishing the TFH cell phenotype.
AID Binds Cooperatively with UNG and Msh2-Msh6 to Ig Switch Regions Dependent upon the AID C Terminus
Authors: Ranjit Sanjay , Khair Lyne , Linehan Erin K. , Ucher Anna J. , Chakrabarti Mrinmay , Schrader Carol E. , Stavnezer Janet
Published: July 2011

Activation-induced cytidine deaminase (AID) is induced in B cells during an immune response and is essential for both class-switch recombination (CSR) and somatic hypermutation of Ab genes. The C-terminal 10 aa of AID are required for CSR but not for somatic hypermutation, although their role in CSR is unknown. Using retroviral transduction into mouse splenic B cells, we show that the C terminus is not required for switch (S) region double-strand breaks (DSBs) and therefore functions downstream of DSBs. Using chromatin immunoprecipitation, we show that AID binds cooperatively with UNG and the mismatch repair proteins Msh2-Msh6 to Ig Sμ and Sγ3 regions, and this depends on the C terminus and the deaminase activity of AID. We also show that mismatch repair does not contribute to the efficiency of CSR in the absence of the AID C terminus. Although it has been demonstrated that both UNG and Msh2-Msh6 are important for introduction of S region DSBs, our data suggest that the ability of AID to recruit these proteins is important for DSB resolution, perhaps by directing the S region DSBs toward accurate and efficient CSR via nonhomologous end joining.
The Multiple Shark Ig H Chain Genes Rearrange and Hypermutate Autonomously
Authors: Zhu Catherine , Feng Wendy , Weedon Jeremy , Hua Pauline , Stefanov Dimitre , Ohta Yuko , Flajnik Martin F. , Hsu Ellen
Published: July 2011

Sharks and skates are representatives of the earliest vertebrates with an immune system based on V(D)J rearrangement. They possess a unique Ig gene organization consisting of 15 to >50 individual IgM loci, each with one VH, two DH, one JH, and one set of constant region exons. The present study attempts to understand how multiple Ig genes are regulated with respect to rearrangement initiation and to targeting during somatic hypermutation. The linkage of three single-copy IgH genes was determined, and single-cell genomic PCR studies in a neonatal animal were used to examine any relationship between relative gene position and likelihood of rearrangement. Our results show that one to three IgH genes are activated independently of linkage or allelic position and the data best fit with a probability model based on the hypothesis that V(D)J rearrangement occurs as a sequence of trials within the B cell. In the neonatal cell set, two closely related IgH, G2A, and G2B, rearranged at similar frequencies, and their membrane forms were expressed at similar levels, like in other young animals. However, older animals displayed a bias in favor of the G2A isotype, which suggests that although rearrangement at G2A and G2B was randomly initiated during primary repertoire generation, the two very similar IgM sequences appear to be differentially expressed with age and exposure to Ag. We performed genomic single-cell PCR on B cells from an immunized individual to study activation-induced cytidine deaminase targeting and found that hypermutation, like V(D)J rearrangement, occurred independently among the many shark IgH.
Phylogenomics-Based Reconstruction of Protozoan Species Tree
Authors: Ocaña Kary A.C.S. , Dávila Alberto M.R.
Published: July 2011

We have developed a semi-automatic methodology to reconstruct the phylogenetic species tree in Protozoa, integrating different phylogenetic algorithms and programs, and demonstrating the utility of a supermatrix approach to construct phylogenomics-based trees using 31 universal orthologs (UO). The species tree obtained was formed by three major clades that were related to three groups of data: i) Species containing at least 80% of UO (25/31) in the concatenated multiple alignment or supermatrix, this clade was called C1, ii) Species containing between 50%–79% (15–24/31) of UO called C2, and iii) Species containing less than 50% (1–14/31) of UO called C3. C1 was composed by only protozoan species, C2 was composed by species related to Protozoa, and C3 was composed by some species of C1 (Protozoa) and C2 (related to Protozoa). Our phylogenomics-based methodology using a supermatrix approach proved to be reliable with protozoan genome data and using at least 25 UO, suggesting that (a) the more UO used the better, (b) using the entire UO sequence or just a conserved block of it for the supermatrix produced similar phylogenomic trees.
Las elecciones europeas de 2009 en la prensa aragonesa
Authors: Zurutuza Muñoz Cristina , García-Ortega Carmela
Published: July 2011

Este artículo estudia los comicios al Parlamento Europeo de 2009, hito legislativo en el proceso de consolidación de la Unión Europea. En concreto, analiza y compara las coberturas periodísticas que los diarios de pago aragoneses otorgaron a la campaña electoral. Para ello se aplica un análisis de contenido cuantitativo a todos los artículos publicados durante los 15 días de campaña en Heraldo de Aragón, El Periódico de Aragón (ambos editados en Zaragoza), Diario del Altoaragón (editado en Huesca) y Diario de Teruel (editado en Teruel). Este análisis se centra especialmente en los protagonistas políticos de la cobertura con el objetivo de descubrir de quién informa la prensa regional para determinar si la cobertura de estas elecciones supranacionales se realiza en clave europea, nacional o aragonesa. La hipótesis de partida es que la prensa aragonesa se ocupa más de los líderes políticos a nivel nacional, aunque no se presenten a las elecciones, que de los candidatos que encabezan las listas de los partidos que concurren a estos comicios. Los resultados de esta investigación confirman esta hipótesis, ya que la cobertura de la campaña se definió en términos nacionales y estuvo protagonizada, sobre todo, por José-Luis Rodríguez-Zapatero y Mariano Rajoy.
La comunicación de la responsabilidad en los medios sociales
Authors: Ros Diego Vicente José , Castelló Martínez Araceli
Published: July 2011

Plataformas sociales como Facebook o Twitter se han convertido en canales imprescindibles en las estrategias empresariales. La comunicación de la Responsabilidad Social Empresarial se enfrenta a nuevos retos en estos espacios con una filosofía 2.0, en los que la empresa puede interactuar con el usuario, generar una comunidad de marca, incrementar su notoriedad y reforzar su posicionamiento. El objetivo de la presente investigación es analizar el uso que hacen las empresas de los principales medios sociales en el ejercicio de la comunicación de la responsabilidad. Para ello se estudia la presencia corporativa en las plataformas sociales mediante case studies y se mide la reputación online de una muestra de marcas seleccionadas. Los resultados muestran el empleo de estos espacios por parte de las empresas como canales de comunicación empresarial y publicitaria, si bien los programas de Responsabilidad Social Corporativa  no tienen una presencia destacada. Pese a las posibilidades de interacción y diálogo que ofrecen estos espacios, los medios sociales son canales todavía poco utilizados para la comunicación de la responsabilidad.
Presence of S. aureus and Enterococcus spp. in goat´s cheese and their antibiotic resistance
Authors: Poľáková Lucia , Dudrikova Eva , Gallo Juraj
Published: July 2011

The aim of this study was to isolate strains of Staphylococcus spp. and Enterococcus spp. from artisanal goat`s cheese during 30 days of ripening, and to determine their antibiotic resistance. Of the total received isolates, 53 (72.60 %) isolates were confirmed  as Staphylococcus spp., from which was only 5.66% (n = 3) detected as S. aureus; and 91 (82.72 %) isolates were confirmed as Enterococcus spp. by multiplex PCR. Antibiotic resistance was tested by disc diffusion method. The 69.81% (n = 37) of staphylococci and 56.04% (n = 51) Enterococcus spp. as resistant were detected to one and more antibiotic drugs. Staphylococci were resistant to penicillin 69.81%, ampicillin 49.06%, oxacillin 39.62%, erythromycin 20.75%, and gentamycin 16.68 %. The highest resistance of enterococci was to cephalothin 42.86% and clindamycin 23.08%.
Nutritional status of subjects with dominant plant food consumption
Authors: Kudlackova Marica , Valachovičová Martina , Babinská Katarí­na , Blaží­ček Pavel , Spoustová Viera , Pauková Viera
Published: July 2011

In three groups of apparently healthy subjects – vegetarians (plant food, dairy products, eggs), semi-vegetarians (as vegetarians with addition of white meat consumption) and non-vegetarians (control group on traditional mixed diet) were analyzed the dietary questionnaires of consumption frequency  and measured the values of lipid profile, insulin resistance, homocysteine with determinants (vitamins B6, B9, B12) and plasma antioxidative vitamins (C,E, beta-carotene). Vegetarians and semi-vegetarians consumed the significantly reduced amount of cholesterol, saturated fatty acids, methionine, lysine, vitamin B12 and on the other hand, they have the significantly higher daily intake of polyunsaturated fatty acids, linoleic acid, alpha-linolenic acid, fiber, plant proteins, arginine, glycine, serine, alanine, folic acid (vitamin B9), vitamin B6, vitamins C,E and beta-carotene. Alternative nutrition groups vs. non-vegetarians have the significantly reduced concentrations of total and LDL-cholesterol, triacylglycerols, insulin as well as values of atherogenic index and insulin resistance. The vegetarian (but not semi-vegetarian) value of homocysteine is significantly increased as a consequence of the significantly reduced and low concentration of vitamin B12. Other two determinants of homocysteine degradation were significantly increased in serum of alternative nutrition groups. The both vegetarian groups have the significantly higher plasma concentrations of antioxidative vitamins and these values are in range of effective free radical disease reduction. The results  of favourable values of cardiovascular risk markers and antioxidants document a beneficial effect of vegetarian nutrition in prevention of degenerative age-related diseases.