bluuebunny/crossref_metadata_2025 huggingface dataset:
An ecological approach to promoting population mental health and well-being — A response to the challenge of climate change
Authors: Nurse Jo , Basher Damian , Bone Angie , Bird William
Published: January 2010

Climate change can be viewed as human-induced change to climate and depletion of natural systems. It potentially the biggest global health threat of the 21st century.1 It is predicted to have wide-ranging impacts upon human mental health and well-being, through changes and challenges to people’s environment, socioeconomic structures and physical security. Even the most conservative estimates of the health impacts are extremely alarming. Increasingly, the causes of poor human health and environmental damage are related. This implies that there are common solutions. For example, there are co-benefits to human health and biodiversity from mitigating and adapting to climate change (e.g. promoting active transport and reducing car use reduces CO2 emissions, benefits our environment and reduces morbidity and mortality associated with a sedentary lifestyle). This article outlines how climate change impacts upon mental health and well-being. It introduces ecological concepts, applies these to public health and outlines their implications in transforming the way that we prioritize and deliver public health in order to promote both environmental and human health. Evidence, from psychology and neuroscience, suggests that the perception of being disconnected from our inner selves, from each other and from our environment has contributed to poor mental and physical health. We argue that we must transform the way we understand mental health and well-being and integrate it into action against climate change. We describe a Public Health Framework for Developing Well-Being, based on the principles of ecological public health.
The high-performance link
Authors: Pflueger Dane
Published: January 2010

Sustainable organizations are successful ones, argues Dane Pflueger, PhD Candidate in Department of Accounting at the London School of Economics and Political Science
Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells
Authors: Moosmann Andreas , Bigalke Iris , Tischer Johanna , Schirrmann Leah , Kasten Julitta , Tippmer Stefanie , Leeping Marina , Prevalšek Dušan , Jaeger Gundula , Ledderose Georg , Mautner Josef , Hammerschmidt Wolfgang , Schendel Dolores J. , Kolb Hans-Jochem
Published: January 2010

Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available in urgent clinical situations, we developed a rapid protocol for their isolation by overnight stimulation of donor blood cells with peptides derived from 11 EBV antigens, interferon-γ surface capture, and immunomagnetic separation. Six patients with PTLD received 1 transfusion of EBV-specific T cells. No response was seen in 3 patients who had late-stage disease with multiorgan dysfunction at the time of T-cell transfer. In 3 patients who received T cells at an earlier stage of disease, we observed complete and stable remission of PTLD. Two patients have remained free from EBV-associated disease for more than 2 years. CD8+ T cells specific for EBV early antigens rapidly expanded after T-cell transfer, temporarily constituted greater than 20% of all peripheral blood lymphocytes, and were maintained throughout the observation period. Thus, a rapid and sustained reconstitution of a protective EBV-specific T-cell memory occurred after the infusion of small numbers of directly isolated EBV-specific T cells.
Biana: a software framework for compiling biological interactions and analyzing networks
Authors: Garcia-Garcia Javier , Guney Emre , Aragues Ramon , Planas-Iglesias Joan , Oliva Baldo
Published: January 2010

Background

The analysis and usage of biological data is hindered by the spread of information across multiple repositories and the difficulties posed by different nomenclature systems and storage formats. In particular, there is an important need for data unification in the study and use of protein-protein interactions. Without good integration strategies, it is difficult to analyze the whole set of available data and its properties.

Results

We introduce BIANA (Biologic Interactions and Network Analysis), a tool for biological information integration and network management. BIANA is a Python framework designed to achieve two major goals: i) the integration of multiple sources of biological information, including biological entities and their relationships, and ii) the management of biological information as a network where entities are nodes and relationships are edges. Moreover, BIANA uses properties of proteins and genes to infer latent biomolecular relationships by transferring edges to entities sharing similar properties. BIANA is also provided as a plugin for Cytoscape, which allows users to visualize and interactively manage the data. A web interface to BIANA providing basic functionalities is also available. The software can be downloaded under GNU GPL license from http://sbi.imim.es/web/BIANA.php.

Conclusions

BIANA's approach to data unification solves many of the nomenclature issues common to systems dealing with biological data. BIANA can easily be extended to handle new specific data repositories and new specific data types. The unification protocol allows BIANA to be a flexible tool suitable for different user requirements: non-expert users can use a suggested unification protocol while expert users can define their own specific unification rules.
A variational Bayes algorithm for fast and accurate multiple locus genome-wide association analysis
Authors: Logsdon Benjamin A , Hoffman Gabriel E , Mezey Jason G
Published: January 2010

Background

The success achieved by genome-wide association (GWA) studies in the identification of candidate loci for complex diseases has been accompanied by an inability to explain the bulk of heritability. Here, we describe the algorithm V-Bay, a variational Bayes algorithm for multiple locus GWA analysis, which is designed to identify weaker associations that may contribute to this missing heritability.

Results

V-Bay provides a novel solution to the computational scaling constraints of most multiple locus methods and can complete a simultaneous analysis of a million genetic markers in a few hours, when using a desktop. Using a range of simulated genetic and GWA experimental scenarios, we demonstrate that V-Bay is highly accurate, and reliably identifies associations that are too weak to be discovered by single-marker testing approaches. V-Bay can also outperform a multiple locus analysis method based on the lasso, which has similar scaling properties for large numbers of genetic markers. For demonstration purposes, we also use V-Bay to confirm associations with gene expression in cell lines derived from the Phase II individuals of HapMap.

Conclusions

V-Bay is a versatile, fast, and accurate multiple locus GWA analysis tool for the practitioner interested in identifying weaker associations without high false positive rates.
Lineage-specific co-evolution of the Egf receptor/ligand signaling system
Authors: Laisney Juliette AGC , Braasch Ingo , Walter Ronald B , Meierjohann Svenja , Schartl Manfred
Published: January 2010

Background

The epidermal growth factor receptor (Egfr) with its numerous ligands has fundamental roles in development, cell differentiation and physiology. Dysfunction of the receptor-ligand system contributes to many human malignancies. Consistent with such various tasks, the Egfr gene family has expanded during vertebrate evolution as a consequence of several rounds of whole genome duplication. Of particular interest is the effect of the fish-specific whole genome duplication (FSGD) on the ligand-receptor system, as it has supplied this largest group of vertebrates with additional opportunities for sub- and/or neofunctionalization in this signaling system.

Results

We identified the predicted components of the Egf receptor-ligand signaling system in teleost fishes (medaka, platyfish, stickleback, pufferfishes and zebrafish). We found two duplicated egfr genes, egfra and egfrb, in all available teleost genomes. Surprisingly only one copy for each of the seven Egfr ligands could be identified in most fishes, with zebrafish hbegf being the only exception. Special focus was put on medaka, for which we more closely investigated all Egf receptors and Egfr ligands. The different expression patterns of egfra, egfrb and their ligands in medaka tissues and embryo stages suggest differences in role and function. Preferential co-expression of different subsets of Egfr ligands corroborates the possible subfunctionalization and specialization of the two receptors in adult tissues. Bioinformatic analyses of the ligand-receptor interface between Egfr and its ligands show a very weak evolutionary conservation within this region. Using in vitro analyses of medaka Egfra, we could show that this receptor is only activated by medaka ligands, but not by human EGF. Altogether, our data suggest a lineage-specific Egfr/Egfr ligand co-evolution.

Conclusions

Our data indicate that medaka Egfr signaling occurs via its two copies, Egfra and Egfrb, each of them being preferentially coexpressed with different subsets of Egfr ligands. This fish-specific occurrence of Egf receptor specialization offers unique opportunities to study the functions of different Egf receptor-ligand combinations and their biological outputs in vertebrates. Furthermore, our results strongly support the use of homologous ligands in future studies, as sufficient cross-specificity is very unlikely for this ligand/receptor system.
The chitobiose transporter, chbC, is required for chitin utilization in Borrelia burgdorferi
Authors: Rhodes Ryan G , Atoyan Janet A , Nelson David R
Published: January 2010

Background

The bacterium Borrelia burgdorferi, the causative agent of Lyme disease, is a limited-genome organism that must obtain many of its biochemical building blocks, including N-acetylglucosamine (GlcNAc), from its tick or vertebrate host. GlcNAc can be imported into the cell as a monomer or dimer (chitobiose), and the annotation for several B. burgdorferi genes suggests that this organism may be able to degrade and utilize chitin, a polymer of GlcNAc. We investigated the ability of B. burgdorferi to utilize chitin in the absence of free GlcNAc, and we attempted to identify genes involved in the process. We also examined the role of RpoS, one of two alternative sigma factors present in B. burgdorferi, in the regulation of chitin utilization.

Results

Using fluorescent chitinase substrates, we demonstrated an inherent chitinase activity in rabbit serum, a component of the B. burgdorferi growth medium (BSK-II). After inactivating this activity by boiling, we showed that wild-type cells can utilize chitotriose, chitohexose or coarse chitin flakes in the presence of boiled serum and in the absence of free GlcNAc. Further, we replaced the serum component of BSK-II with a lipid extract and still observed growth on chitin substrates without free GlcNAc. In an attempt to knockout B. burgdorferi chitinase activity, we generated mutations in two genes (bb0002 and bb0620) predicted to encode enzymes that could potentially cleave the β-(1,4)-glycosidic linkages found in chitin. While these mutations had no effect on the ability to utilize chitin, a mutation in the gene encoding the chitobiose transporter (bbb04, chbC) did block utilization of chitin substrates by B. burgdorferi. Finally, we provide evidence that chitin utilization in an rpoS mutant is delayed compared to wild-type cells, indicating that RpoS may be involved in the regulation of chitin degradation by this organism.

Conclusions

The data collected in this study demonstrate that B. burgdorferi can utilize chitin as a source of GlcNAc in the absence of free GlcNAc, and suggest that chitin is cleaved into dimers before being imported across the cytoplasmic membrane via the chitobiose transporter. In addition, our data suggest that the enzyme(s) involved in chitin degradation are at least partially regulated by the alternative sigma factor RpoS.
CXCR4/SDF1 mediate hypoxia induced chondrosarcoma cell invasion through ERK signaling and increased MMP1 expression
Authors: Sun Xiaojuan , Wei Lei , Chen Qian , Terek Richard M
Published: January 2010

Background

Chondrosarcoma is a disease that does not respond to conventional cytotoxic chemotherapy and expression of MMP1 is a marker for a poor prognosis. The mechanism of increased MMP1 expression in chondrosarcoma is not completely known. Our goal is to identify molecular pathways that could serve as therapeutic targets. Chondrosarcoma become hypoxic as they grow, are capable of eliciting an angiogenic response, and typically metastasize to the lungs. The present study determined the effect of hypoxia and specifically HIF-1a on expression of CXCR4 and MMP1 and their role in chondrosarcoma cell invasion.

Results

CXCR4 and its ligand, SDF1, are upregulated in primary chondrosarcoma tumors compared to normal articular cartilage, and CXCR4 was upregulated in chondrosarcoma cell line JJ compared to normal chondrocytes. Hypoxia and specifically HIF-1a increased CXCR4 and MMP1 expression in JJ cell line and chondrosarcoma invasionin vitro. The hypoxia mediated increase in MMP1 expression and chondrosarcoma invasion could be inhibited by siRNA directed at HIF-1a or CXCR4, the CXCR4 inhibitor AMD3100, as well as with ERK inhibitor U0126 and ERK siRNA.

Conclusions

Chondrosarcoma cell invasion is increased by hypoxia induced expression of CXCR4 and MMP1 and is mediated by HIF-1a and ERK. Both invasion and MMP1 can be inhibited with CXCR4 blockade, suggesting that CXCR4/SDF1 signaling may be a therapeutic target for chondrosarcoma.
S100A8 and S100A9 in experimental osteoarthritis
Authors: Zreiqat Hala , Belluoccio Daniele , Smith Margaret M , Wilson Richard , Rowley Lynn A , Jones Katie , Ramaswamy Yogambha , Vogl Thomas , Roth Johannes , Bateman John F , Little Christopher B
Published: January 2010

Introduction

The objective was to evaluate the changes in S100A8 S100A9, and their complex (S100A8/S100A9) in cartilage during the onset of osteoarthritis (OA) as opposed to inflammatory arthritis.

Methods

S100A8 and S100A9 protein localization were determined in antigen-induced inflammatory arthritis in mice, mouse femoral head cartilage explants stimulated with interleukin-1 (IL-1), and in surgically-induced OA in mice. Microarray expression profiling of all S100 proteins in cartilage was evaluated at different times after initiation of degradation in femoral head explant cultures stimulated with IL-1 and surgically-induced OA. The effect of S100A8, S100A9 or the complex on the expression of aggrecan (Acan), collagen II (Col2a1), disintegrin and metalloproteases with thrombospondin motifs (Adamts1, Adamts 4 &Adamts 5), matrix metalloproteases (Mmp1, Mmp3, Mmp13 &Mmp14) and tissue inhibitors of metalloproteinases (Timp1, Timp2 &Timp3), by primary adult ovine articular chondrocytes was determined using real time quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

Stimulation with IL-1 increased chondrocyte S100a8 and S100a9 mRNA and protein levels. There was increased chondrocyte mRNA expression of S100a8 and S100a9 in early but not late mouse OA. However, loss of the S100A8 staining in chondrocytes occurred as mouse OA progressed, in contrast to the positive reactivity for both S100A8 and S100A9 in chondrocytes in inflammatory arthritis in mice. Homodimeric S100A8 and S100A9, but not the heterodimeric complex, significantly upregulated chondrocyte Adamts1, Adamts4 and Adamts 5, Mmp1, Mmp3 and Mmp13 gene expression, while collagen II and aggrecan mRNAs were significantly decreased.

Conclusions

Chondrocyte derived S100A8 and S100A9 may have a sustained role in cartilage degradation in inflammatory arthritis. In contrast, while these proteins may have a role in initiating early cartilage degradation in OA by upregulating MMPs and aggrecanases, their reduced expression in late stages of OA suggests they do not have an ongoing role in cartilage degradation in this non-inflammatory arthropathy.
PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-κB-independent manner
Authors: Sousa Lirlândia P , Lopes Fernando , Silva Douglas M , Tavares Luciana P , Vieira Angélica T , Rezende Bárbara M , Carmo Aline F , Russo Remo C , Garcia Cristiana C , Bonjardim Cláudio A , Alessandri Ana L , Rossi Adriano G , Pinho Vanessa , Teixeira Mauro M
Published: January 2010

PDE4 inhibition is effective at resolving neutrophilic inflammation after LPS-challenge by promoting caspase-3-dependent apoptosis of inflammatory cells in the pleural cavity.

PDE4 inhibitors are effective anti-inflammatory drugs whose effects and putative mechanisms on resolution of inflammation and neutrophil apoptosis in vivo are still unclear. Here, we examined the effects of specific PDE4 inhibition on the resolution of neutrophilic inflammation in the pleural cavity of LPS-challenged mice. LPS induced neutrophil recruitment that was increased at 4 h, peaked at 8–24 h, and declined thereafter. Such an event in the pleural cavity was preceded by increased levels of KC and MIP-2 at 1 and 2 h. Treatment with the PDE4 inhibitor rolipram, at 4 h after LPS administration, decreased the number of neutrophils and increased the percentage of apoptotic cells in the pleural cavity in a PKA-dependent manner. Conversely, delayed treatment with a CXCR2 antagonist failed to prevent neutrophil recruitment. Forskolin and db-cAMP also decreased the number of neutrophils and increased apoptosis in the pleural cavity. The proapoptotic effect of rolipram was associated with decreased levels of the prosurvival protein Mcl-1 and increased caspase-3 cleavage. The pan-caspase inhibitor zVAD-fmk prevented rolipram-induced resolution of inflammation. LPS resulted in a time-dependent activation of Akt, which was blocked by treatment with rolipram or PI3K and Akt inhibitors, and PI3K and Akt inhibitors also enhanced apoptosis and promoted neutrophil clearance. Although LPS induced NF-κB activation, which was blocked by rolipram, NF-κB inhibitors did not promote resolution of neutrophil accumulation in this model. In conclusion, our data show that PDE4 inhibition resolves neutrophilic inflammation by promoting caspase-dependent apoptosis of inflammatory cells by targeting a PKA/PI3K/Akt-dependent survival pathway.
Pivotal Advance: Nonfunctional lung effectors exhibit decreased calcium mobilization associated with reduced expression of ORAI1
Authors: Arimilli Subhashini , Sharma Sharad K , Yammani Rama , Reid Sean D , Parks Griffith D , Alexander-Miller Martha A
Published: January 2010

A previously unknown mechanism for the active negative regulation of function in effector T cells is described.

CD8+ T cells play a critical role in the clearance of respiratory pathogens. Thus, it is surprising that functional inactivation of lung effectors has been observed in many models of viral infection. Currently, the molecular defect responsible for the shut-off of function in these cells is unknown. In the present study, we addressed this question using a model of respiratory infection with the paramyxovirus SV5. Nonfunctional cells were found to exhibit decreases in SOCE, resulting in reduced NFAT1 activation. Notably, function could be restored by the provision of increased levels of extracellular calcium. The reduced ability to mobilize calcium was associated with reduced expression of ORAI1, the CRAC channel subunit. These findings reveal a previously unknown mechanism for the negative regulation of function in effector T cells.
TNF-α, IL-6, and IL-1 expression is inhibited by GAS6 in monocytes/macrophages
Authors: Alciato Federica , Sainaghi Pier Paolo , Sola Daniele , Castello Luigi , Avanzi Gian Carlo
Published: January 2010

Gas6 is able to inhibit pro-inflammatory cytokine secretion by macrophages acting on Mer receptor; the pathway involved is mediated by PI3K, Akt, GSK3β, and NFκB.

GAS6 protein has been described to be involved in immune modulation in vitro and in vivo. Some of these effects are probably mediated through the involvement of monocytes/macrophages. To understand the role of GAS6 in modulating the immune response, we evaluated the effect on cytokine secretion by monocytes/macrophages and the molecular pathways involved. GAS6 inhibits TNF-α and IL-6 secretion by LPS-stimulated U937 cells and monocytes/machrophages. We evidenced that among GAS6 receptors, only Mer (but not Axl or Tyro3) is expressed on differentiated U937 cells, and its activation is responsible for the reduction of cytokine expression. In immunoblot analysis, Mer was activated after GAS6 stimulation, giving rise to an increased phosphorylation of Akt. We also observed GSK3β phosphorylation and consequent inhibition of NF-κB nuclear translocation. Therefore, GAS6 modulates macrophage cytokine secretion, triggering an “anti-inflammatory pathway” involving PI3K/Akt/GSK3β and NF-κB.
Induction of neutrophil degranulation by S100A9 via a MAPK-dependent mechanism
Authors: Simard Jean-Christophe , Girard Denis , Tessier Philippe A
Published: January 2010

S100A9 induces degranulation in human neutrophils.

S100A9 is a proinflammatory protein, expressed abundantly in the cytosol of neutrophils and monocytes. High extracellular S100A9 concentrations have been correlated with chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease, as well as with phagocyte extravasation. This study tested the hypothesis that S100A9 induces degranulation in human neutrophils. S100A9 was found to up-regulate the surface expression of CD35 and CD66b, proteins contained in secretory vesicles and specific/gelatinase granules, respectively. In addition, gelatinase and albumin, stored, respectively, in specific/gelatinase granules and secretory vesicles, were detected in the supernatants of neutrophils stimulated with S100A9. In contrast, stimulation with S100A9 had no effect on CD63 expression or MPO secretion, two proteins contained in azurophilic granules. S100A9 induced the phosphorylation of the MAPKs, ERK1/2, p38, and JNK. Inhibition of p38 and JNK but not ERK1/2, with specific inhibitors (SB203580, JNKII, and PD98059, respectively), blocked neutrophil degranulation induced by S100A9. Taken together, these results support the hypothesis and clearly indicate that S100A9 induces the degranulation of secretory and specific/gelatinase granules but not of azurophilic granules in a process involving p38 and JNK and further support its classification as a DAMP.
Reading Anishinaabe Identities: Meaning and Metaphor in Nindoodem Pictographs
Authors: Bohaker Heidi
Published: January 2010

Anishinaabe peoples of the Great Lakes region consistently signed treaties, petitions, and other paper documents from the seventeenth through the nineteenth centuries with pictographic representations of their nindoodem (clan) identities. Close study of these pictographs reveals a wealth of information about Anishinaabe cultural and political priorities, their struggles to maintain control of land in specific locations, and their extensive ecological knowledge, opening rich interpretative doors for future research. Perhaps most important, the pictographs, in contrast to ever-changing European names for “Indian nations” that give an impression of near constant ethnogenesis, provide evidence of political continuity over time.
The Pragmatics of Language Learning: Graphic Pluralism on Martha's Vineyard, 1660-1720
Authors: Bragdon Kathleen J.
Published: January 2010

This paper discusses the development of vernacular literacy among Massachusett and Wampanoag speakers of southern New England in the seventeenth and eighteenth centuries. While other research focuses on the role of Protestant missionaries in the conversion of native people of the region to Christianity, or treats the adoption of literacy as a sign of cultural transformation, it is argued here that the adoption and spread of native-language literacy in southern New England was one element of a pragmatic strategy that reflected and responded to the natives' multilingual new world. The diaspora of native readers and writers, the production of native documents, and their curation within certain families also demonstrate the way native people made vernacular literacy their own.
Writing as Resistance: Maya Graphic Pluralism and Indigenous Elite Strategies for Survival in Colonial Yucatan, 1550-1750
Authors: Chuchiak John F.
Published: January 2010

This paper offers a revisionist viewpoint on the nature of colonial Maya literacy, showing that the colonial Yucatec Maya elite utilized both the traditional hieroglyphic script and the new alphabetic writing skills taught by the Franciscan friars. By adapting and utilizing both styles of writing, the colonial Maya elite created a system of graphic pluralism that enabled the Maya nobility to better defend their elite interests in a manner consistent with both pre-Columbian and colonial forms of writing, address, religion, and government administration.
MY FATHER, CYNTHIA CONROY
Authors: Gould Janice
Published: January 2010

This personal essay discusses the life and death of the author's father, who late in life changed genders to become a “trans-woman.” The essay deals with the author's conflicted feelings about this transformation.
SETTLER HOMONATIONALISM
Authors: Morgensen Scott Lauria
Published: January 2010

Settlement conditions the formation of modern queer subjects and politics in the United States. This essay newly interprets the settler formation of U.S. queer modernities by inspiration of Jasbir Puar's critique of homonationalism. Puar argues that homonationalism produces U.S. queers as regulatory over the racialized and sexualized populations targeted within the imperial biopolitics of the war on terror. I explain homonationalism as a quality of U.S. queer modernities having formed within a colonial biopolitics, in which the terrorizing sexual colonization of Native peoples produces modern sexuality as a function of settlement. This essay reinterprets historical accounts at the intersections of queer, Native, and colonial studies to show how a colonial biopolitics of modern sexuality relationally produces Native and settler sexual subjects. Modern queer projects enact this biopolitics when their normatively non-Native and settler form distances Native people from sexual modernity, even as they seek modern sexual freedoms in the settler state. Homonationalism arises here, as one effect of settlement's naturalization and defense in U.S. queer modernities, and as one means by which the continued colonization of Native peoples and land shapes the imperial projections of the United States and its subjects. Settler homonationalism may be destabilized by marking and challenging its historical formation and holding queer projects accountable to Native struggles for decolonization.
PUO'WINUE'L PRAYERS
Authors: Cruz Louis Esme , Driskill Qwo-Li
Published: January 2010

In the formative years of the developing cultural relations between the Mi'kmaq of the Maritime Provinces of Canada and European Judeo-Christian missionaries, Father Chrestien Le Clercq systematized Mi'kmaq written language in order to convert the Original People. More recently, collaborations between scholars such as Mi'kmaq Hieroglyphic Prayers: Readings in North America's First Indigenous Script, by Murdena Marshall and David L. Schmidt, have begun to translate and reinterpret this script using contemporary decolonial methodologies that privilege Indigenous survival. In “Puo'winue'l Prayers: Readings from North America's First Transtextual Script,” I continue this conversation while engaging the script from a multiracial, visual-textual, Two-Spirit perspective.
A design principle underlying the synchronization of oscillations in cellular systems
Authors: Kim Jeong-Rae , Shin Dongkwan , Jung Sung Hoon , Heslop-Harrison Pat , Cho Kwang-Hyun
Published: January 2010

Biological oscillations are found ubiquitously in cells and are widely variable, with periods varying from milliseconds to months, and scales involving subcellular components to large groups of organisms. Interestingly, independent oscillators from different cells often show synchronization that is not the consequence of an external regulator. What is the underlying design principle of such synchronized oscillations, and can modeling show that the complex consequences arise from simple molecular or other interactions between oscillators? When biological oscillators are coupled with each other, we found that synchronization is induced when they are connected together through a positive feedback loop. Increasing the coupling strength of two independent oscillators shows a threshold beyond which synchronization occurs within a few cycles, and a second threshold where oscillation stops. The positive feedback loop can be composed of either double-positive (PP) or double-negative (NN) interactions between a node of each of the two oscillating networks. The different coupling structures have contrasting characteristics. In particular, PP coupling is advantageous with respect to stability of period and amplitude, when local oscillators are coupled with a short time delay, whereas NN coupling is advantageous for a long time delay. In addition, PP coupling results in more robust synchronized oscillations with respect to amplitude excursions but not period, with applied noise disturbances compared to NN coupling. However, PP coupling can induce a large fluctuation in the amplitude and period of the resulting synchronized oscillation depending on the coupling strength, whereas NN coupling ensures almost constant amplitude and period irrespective of the coupling strength. Intriguingly, we have also observed that artificial evolution of random digital oscillator circuits also follows this design principle. We conclude that a different coupling strategy might have been selected according to different evolutionary requirements.
A finite element application in the analysis and design of point-supported composite conoidal shell roofs: Suggesting selection guidelines
Authors: Das H S , Chakravorty D
Published: January 2010

In the present paper, a finite element code is applied to study the bending behaviour of point-supported composite conoidal shells. These doubly curved surfaces may look similar to single curved conical shells, but the non-developable conoids present much stiffer surfaces. Laminated composites offer a high strength-to-weight ratio, and composite conoidal shells can cover large column-free areas. These shells on point supports have wide applications in car parks and theatres. Research reports are available regarding the static and dynamic behaviour of composite and isotropic conoidal shells, but with different combinations of simply supported, clamped, and free boundary conditions. Reports on corner-point-supported isotropic rhombic plates and doubly curved shells also exist, but data on the bending behaviour of conoidal shells supported at discrete points only are missing. Hence, in the present paper, three different point-supported boundary conditions are considered with four different laminations, the relative performance of different shell options is studied in detail, and suitable approaches are proposed to choosing the best shell option among many in a practical situation.
Understanding the effect of non-conventional laser beam geometry on material processing by finite-element modelling
Authors: Sheikh M A , Li L
Published: January 2010

The temperature distribution inside the material is of prime importance in laser material processing. Optimization of laser processes requires control over this temperature distribution in order to achieve the desired outcomes by manipulating heating/cooling rates and thermal gradients. So far, most of the laser material processing has been carried out by using circular and rectangular beam geometries with variations in laser power, spot size, and scanning speed. However, variations in these parameters are often limited by other processing conditions and it is not always possible to change, e.g. the scanning speed or laser power. One possible method of varying the temperature distribution, and hence the heating/cooling rates and thermal gradients, is to modify the geometry of laser beams. It has been shown that non-conventional laser beam geometries can be effectively employed for laser processes such as surface heating, transformation hardening, forming, melting of metallic materials, and laser cutting. This article presents a review of non-conventional laser beam geometries that can be utilized to improve and/or optimize many laser material processes. Some examples of laser material processing that have been previously studied in detail are briefly discussed.
The dynamics of a parallel-misaligned and unbalanced rotor system under the action of non-linear oil film forces
Authors: Li M , He L
Published: January 2010

A mathematical model of a parallel-misaligned rotor system with mass eccentricity that is supported on journal bearings is discussed and its dynamic behaviours are analysed under the action of non-linear oil forces in the present work. First, some assumptions are introduced, such as the long bearing model, small parallel misalignment between rotors and tiny eccentricity of discs, the misaligned displacement constraint between two rotors is taken into account, and the motion equations are deduced by the Lagrange method of undetermined multiplier. Then, the rotor orbits, Poincaré maps, and bifurcation diagrams of the system are studied by a numerical method; the results show that there exists some unrevealed motions and phenomena in the parallel-misaligned and unbalanced rotor system such as period 2, 3, 6, and 7 motions besides chaotic oscillations and so on.
On the mechanical properties of a treated betelnut fibre-reinforced polyester composite
Authors: Yousif B F , Nirmal U
Published: January 2010

The present work is an attempt to investigate the mechanical properties of a treated betelnut fibre-reinforced polyester composite. Tensile, flexural, compression, and hardness tests were carried out. As a result of reinforcing the polyester with the treated betelnut fibre mats, the tensile, flexural, compression, and hardness properties of the composite were enhanced by about 141 per cent, 28 per cent, 85 per cent, and 6 per cent when compared to neat polyester. The high roughness of the outer layer of the treated betelnut fibre and the presence of trichomes were the main reasons for the high enhancement of mechanical properties of the composites. Scanning electron microscopy observation showed low fibre pullout during the mechanical test. The failure mechanism was dominated by fibre breakage and slight debonding during the tensile tests.
Microtechnologies in implant and restorative dentistry: A stroll through a digital dental landscape
Authors: Dawood A , Purkayastha S , Patel S , MacKillop F , Tanner S
Published: January 2010

This is an explanatory article introducing the combination of various technologies used in implant and restorative dentistry. The aim of the article is to provide an overview of some of the techniques supporting the restorative treatment plan at various stages to provide contemporary, state-of-the-art bridgework based on dental implants. It is a discussion of the way existing technologies used in fields of engineering and medicine are brought together to form a complete process.
Validation of a diagnostic method for estimating the compression condition of direct injection diesel engines
Authors: Lamaris V T , Hountalas D T
Published: January 2010

The compression stroke is an important index for engine operation because in-cylinder conditions at the end of compression have a major effect on its overall performance and efficiency. It is widely recognized that the compression stroke is strongly affected, beyond heat losses, by the initial pressure at inlet valve closure, the compression ratio (CR), and the blow-by rate. However, when a compression degradation is detected (i.e. decrease in peak compression pressure), it is very difficult to directly define the actual cause for this. In the present work, an advanced diagnostic technique is used to estimate the compression condition of a direct injection diesel engine and determine the actual cause for a reduction in peak compression pressure. To validate the proposed technique, a detailed experimental investigation was conducted on a single-cylinder test engine installed in the author's laboratory. At first, measurements were taken during the engine's normal operation (i.e. firing and motoring conditions). Then, ‘virtual’ faults have been created on the engine (i.e. reduced CR, cylinder mass leakage increase, and inlet chocking), aiming to reduce the peak compression pressure. The diagnostic technique is applied for each test case to estimate the cylinder compression condition and to detect the actual parameter that causes a decrease in peak compression pressure. The diagnosis results reveal that the technique can determine correctly the actual parameter responsible for compression deterioration in each case. This is accomplished even in cases where a combination of faults exists. The results obtained are extremely valuable, because the proposed diagnostic technique can be applied to any type of diesel engine and mainly to large-scale diesel engines (i.e. marine or stationary applications), where the application of non-catastrophic methods (i.e. without modifications or interventions to the engine cylinder) for estimating the cylinder compression conditions is extremely important.
Written Medicine Information from English-Speaking Countries—How Does It Compare?
Authors: Luk Alice , Tasker Natalie , Theo Raynor David K , Aslani Parisa
Published: January 2010

Background:

There has been an increasing drive from consumers for more information to be available about their medicines. However, the layout and presentation of such written information is variable, and the poor format and design discourages people from reading the documents.

Objective:

To identify, collate, and evaluate different formats of written medicine information (WMI).

Methods:

Three researchers evaluated 157 samples of WMI for 10 prescription and 3 over-the-counter medicines from 6 English-speaking countries compared with the United States Keystone Consensus Criterion 8 (USKCC8) and the Ten Key Principles (TKP) of Consumer Medicine Information. Readability was measured using Flesch-Kincaid Grade Level (FKGL) and Fog tests. Compliance (%) with the criteria was computed and examined using the median test.

Results:

Overall median compliance with USKCC8 was 70%, and 74% to TKP. New Zealand leaflets achieved the highest compliance with USKCC8 (83%, Interquartile range (IQR) 70–89%), with US leaflets the lowest (55%. IQR 45–70%). Australian and New Zealand leaflets showed the highest compliance with TKP (90%, IQR 80–100% and 87–97%, respectively), while UK leaflets demonstrated the lowest (60%, IQR 52–71%). Overall median reading grades for the leaflets were 10 (Flesch-Kincaid Grade Level) and 11 (Fog).

Conclusions:

Compliance with USKCC8 and TKP varied greatly between countries, with readability grades exceeding the recommended range. International examples of WMI show wide variation in compliance with guidelines on recommended format and presentation. These examples of WMI require high literacy to read. Future WMI development should use more recommended formats and increase comprehensibility.
The Role of Health Literacy and Written Medicine Information in Nonsteroidal Antiinflammatory Drug Risk Awareness
Authors: Miller Michael J , Schmitt Michael R , Allison Jeroan J , Cobaugh Daniel J , Ray Midge N , Saag Kenneth G
Published: January 2010

Background:

Despite widespread use of prescription nonsteroidal antiinflammatory drugs (NSAIDs), patients are commonly unaware of their risks. Pharmacies regularly distribute written medicine information (WMI) describing the risks and benefits of NSAID therapy at the time of dispensing.

Objective:

To clarify the relationship among common sociodemographic factors, education, health literacy, reading of WMI routinefy distributed at pharmacies, and NSAID risk awareness.

Methods:

Generalized linear latent and mixed models (GLLAMM) ordered logistic regression and confirmatory path analysis were used to evaluate multivariable relationships in a cross-sectional dataset of 382 patients in the second phase of the Alabama NSAID Patient Safety Study.

Results:

The majority of the analytical sample was female (72.0%) with 38.7% African American, 38.1% age 65 years or older, and 43.3% reporting at least some college education. Health literacy was positively associated with reading of WMI (p = 0.001) and NSAID risk awareness (p = 0.025), while age was negatively associated with reading WMI (p = 0.001) and NSAID risk awareness (p = 0.005). Medicaid/uninsured status was negatively associated with risk awareness (p = 0.013). Reading of WMI was not associated with NSAID risk awareness (p = 0.659). The final path model demonstrated excellent fit.

Conclusions:

The lack of relationship between reading of WMI and NSAID risk awareness questions the current strategy of distribution of patient-targeted print education materials at pharmacies. To maximize limited resources, future research should identify more effective strategies to deliver risk information to patients and ensure its retention, especially in high-risk groups such as the elderly, the indigent, and those with inadequate health literacy.
Diabetes: Intensive Insulin Protocol Implementation and Outcomes in the Medical and Surgical Wards at a Veterans Affairs Medical Center
Authors: Chen Helen J , Steinke Douglas T , Karounos Dennis G , Lane Matthew T , Matson Adrienne W
Published: January 2010

Background:

Hyperglycemia is an important marker for clinical outcomes and mortality in hospitalized patients. New national standards have been established emphasizing the importance of improving inpatient glycemic control in individuals with diabetes or new-onset hyperglycemia. Implementation of these new standards is complex and requires a multidisciplinary team approach. A basal-bolus insulin regimen approach has been shown to improve inpatient glycemic control. Few studies have been published regarding basal-bolus insulin protocol outcomes in the non–intensive care unit (ICU) setting.

Objective:

To evaluate the efficacy of a basal-bolus insulin protocol on inpatient glycemic control in a non-ICU setting, as measured by mean blood glucose and number of hypoglycemic episodes per patient admission.

Methods:

A retrospective, observational, single-center study was conducted to compare blood glucose control pre- (October 2006–March 2007) and postprotocol (November 2007–January 2008) implementation. Inclusion criteria consisted of patient admission to a medical or surgical ward for at least 72 hours, with a diagnosis of diabetes, or presentation with 2 blood glucose readings greater than 180 mg/dL. Patients admitted to the ICU or those not admitted to a medical or surgical ward were excluded.

Results:

Following protocol implementation, the mean ± SD blood glucose level increased from 174 ± 88 mg/dL to 188 ± 95 mg/dL (p < 0.001) and the hypoglycemic incidents significantly decreased, from 1.11 to 0.51 events per patient admission (p < 0.0025).

Conclusions:

In this pilot study, implementation of a basal-bolus insulin protocol significantly reduced hypoglycemic events; however, mean blood glucose values increased. These results suggest that a basal-bolus insulin protocol can reduce hypoglycemia; however, factors such as protocol compliance, barriers in overcoming the use of the traditional sliding scale insulin regimens, staff education, and change of work-flow habits can influence the overall efficacy and impact of a basal-bolus insulin protocol on inpatient gtycemic control.
Stability of Cyclophosphamide in Extemporaneous Oral Suspensions
Authors: Kennedy Rachel , Groepper Daniel , Tagen Michael , Christensen Robbin , Navid Fariba , Gajjar Amar , Stewart Clinton F
Published: January 2010

Background:

Cyclophosphamide, an alkylating agent, is widely used for the treatment of many adult and pediatric malignancies. The stability of cyclophosphamide in aqueous- and methylcellulose-based oral suspending vehicles is currently unknown.

Objective:

To develop and validate a stability-indicating high-performance liquid chromatography (HPLC) method to measure cyclophosphamide concentrations in simple syrup and Ora-Plus, and assess the 56-day chemical stability and physical appearance of cyclophosphamide in these suspensions at both room temperature (22 °C) and 4 °C.

Methods:

The intravenous formulation of cyclophosphamide was diluted to 20 mg/mL in NaCI 0.9%, compounded 1:1 with either suspending vehicle, and stored in the dark in 3-mL amber polypropylene oral syringes at 4 °C and 22 °C. Aliquots from each syringe were obtained on days 0.3, 7, 14, 21, 28, 35, 42, 49, and 56 and assayed using the validated stability-indicating HPLC-UV method. A C18 analytical column was used to separate cyclophosphamide from the internal standard, ifosfamide, with a mobile phase of 21% acetonitrile in 79% sodium phosphate buffer. The suspension was examined for odor change, visually examined under normal fluorescent light for color change, and examined under a light microscope for evidence of microbial growth.

Results:

Samples of cyclophosphamide in both simple syrup and Ora-Plus were stable when kept at 4 °C for at least 56 days. At room temperature, cyclophosphamide in simple syrup and Ora-Plus had a shell life of 8 and 3 days, respectively. No changes in color or odor or evidence of microbial growth were observed.

Conclusions:

Cyclophosphamide can be extemporaneously prepared in simple syrup or Ora-Plus and stored for at least 2 months under refrigeration without significant degradation.
BAMBI (Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor) Reveals the Involvement of the Transforming Growth Factor-β Family in Pain Modulation
Authors: Tramullas Mónica , Lantero Aquilino , Díaz Álvaro , Morchón Néstor , Merino David , Villar Ana , Buscher Dirk , Merino Ramón , Hurlé Juan M. , Izpisúa-Belmonte Juan Carlos , Hurlé María A.
Published: January 2010

Transforming growth factors-β (TGF-βs) signal through type I and type II serine–threonine kinase receptor complexes. During ligand binding, type II receptors recruit and phosphorylate type I receptors, triggering downstream signaling. BAMBI [bone morphogenetic protein (BMP) and activin membrane-bound inhibitor] is a transmembrane pseudoreceptor structurally similar to type I receptors but lacks the intracellular kinase domain. BAMBI modulates negatively pan-TGF-β family signaling; therefore, it can be used as an instrument for unraveling the roles of these cytokines in the adult CNS.BAMBIis expressed in regions of the CNS involved in pain transmission and modulation. The lack ofBAMBIin mutant mice resulted in increased levels of TGF-β signaling activity, which was associated with attenuation of acute pain behaviors, regardless of the modality of the stimuli (thermal, mechanical, chemical/inflammatory). The nociceptive hyposensitivity exhibited byBAMBI−/−mice was reversed by the opioid antagonist naloxone. Moreover, in a model of chronic neuropathic pain, the allodynic responses ofBAMBI−/−mice also appeared attenuated through a mechanism involving δ-opioid receptor signaling. Basal mRNA and protein levels of precursor proteins of the endogenous opioid peptidesproopiomelanocortin(POMC) andproenkephalin(PENK) appeared increased in the spinal cords ofBAMBI−/−. Transcript levels of TGF-βs and their intracellular effectors correlated directly with genes encoding opioid peptides, whereasBAMBIcorrelated inversely. Furthermore, incubation of spinal cord explants with activin A or BMP-7 increasedPOMCand/orPENKmRNA levels. Our findings identify TGF-β family members as modulators of acute and chronic pain perception through the transcriptional regulation of genes encoding the endogenous opioids.