bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Video Transmission Using Residue Octree Cubes
Authors: Enache Adrian , Boiangiu Costin-Anton
Published: July 2014

This paper proposes a method of transmitting video streaming data based on downsampling-upsampling pyramidal decomposition. By implementing an octal tree decomposition of the frame cubes, prior to transforming them into hypercubes, the algorithm manages to increase the granularity of the transmitted data. In this sense, the communication relies on a series of smaller hypercubes, as opposed to a single hypercube containing the entire, undivided frames form a sequence. This translates into increased adaptability to the variations of the transmitting channel’s bandwidth.
Economics of Harmful Invasive Species: A Review
Authors: Marbuah George , Gren Ing-Marie , McKie Brendan
Published: July 2014

The purpose of this study is to review theoretical and empirical findings in economics with respect to the challenging question of how to manage invasive species. The review revealed a relatively large body of literature on the assessment of damage costs of invasive species; single species and groups of species at different geographical scales. However, the estimated damage costs show large variation, from less than 1 million USD to costs corresponding to 12% of gross domestic product, depending on the methods employed, geographical scale, and scope with respect to inclusion of different species. Decisions regarding optimal management strategies, when to act in the invasion chain and which policy to choose, have received much less attention in earlier years, but have been subject to increasing research during the last decade. More difficult, but also more relevant policy issues have been raised, which concern the targeting in time and space of strategies under conditions of uncertainty. In particular, the weighting of costs and benefits from early detection and mitigation against the uncertain avoidance of damage with later control, when the precision in targeting species is typically greater is identified as a key challenge. The role of improved monitoring for detecting species and their spread and damage has been emphasized, but questions remain on how to achieve this in practice. This is in contrast to the relatively large body of literature on policies for mitigating dispersal by trade, which is regarded as one of the most important vectors for the spread of invasive species. On the other hand, the literature on how to mitigate established species, by control or adaptation, is much more scant. Studies evaluating causes for success or failure of policies against invasive in practice are in principal non-existing.
Outlook for the Next Generation’s Precision Forestry in Finland
Authors: Holopainen Markus , Vastaranta Mikko , Hyyppä Juha
Published: July 2014

During the past decade in forest mapping and monitoring applications, the ability to acquire spatially accurate, 3D remote-sensing information by means of laser scanning, digital stereo imagery and radar imagery has been a major turning point. These 3D data sets that use single- or multi-temporal point clouds enable a wide range of applications when combined with other geoinformation and logging machine-measured data. New technologies enable precision forestry, which can be defined as a method to accurately determine characteristics of forests and treatments at stand, sub-stand or individual tree level. In precision forestry, even individual tree-level assessments can be used for simulation and optimization models of the forest management decision support system. At the moment, the forest industry in Finland is looking forward to next generation’s forest inventory techniques to improve the current wood procurement practices. Our vision is that in the future, the data solution for detailed forest management and wood procurement will be to use multi-source and -sensor information. In this communication, we review our recent findings and describe our future vision in precision forestry research in Finland.
Compton Composites Late in the Early Universe
Authors: Mayer Frederick , Reitz John
Published: July 2014

Beginning roughly two hundred years after the big-bang, a tresino phase transition generated Compton-scale composite particles and converted most of the ordinary plasma baryons into new forms of dark matter. Our model consists of ordinary electrons and protons that have been bound into mostly undetectable forms. This picture provides an explanation of the composition and history of ordinary to dark matter conversion starting with, and maintaining, a critical density Universe. The tresino phase transition started the conversion of ordinary matter plasma into tresino-proton pairs prior to the the recombination era. We derive the appropriate Saha–Boltzmann equilibrium to determine the plasma composition throughout the phase transition and later. The baryon population is shown to be quickly modified from ordinary matter plasma prior to the transition to a small amount of ordinary matter and a much larger amount of dark matter after the transition. We describe the tresino phase transition and the origin, quantity and evolution of the dark matter as it takes place from late in the early Universe until the present.
Diagnostic Reasoning across the Medical Education Continuum
Authors: Smith C. , Hill William , Francovich Chris , Morris Magdalena , Robbins Bruce , Robins Lynne , Turner Andrew
Published: July 2014

We aimed to study linguistic and non-linguistic elements of diagnostic reasoning across the continuum of medical education. We performed semi-structured interviews of premedical students, first year medical students, third year medical students, second year internal medicine residents, and experienced faculty (ten each) as they diagnosed three common causes of dyspnea. A second observer recorded emotional tone. All interviews were digitally recorded and blinded transcripts were created. Propositional analysis and concept mapping were performed. Grounded theory was used to identify salient categories and transcripts were scored with these categories. Transcripts were then unblinded. Systematic differences in propositional structure, number of concept connections, distribution of grounded theory categories, episodic and semantic memories, and emotional tone were identified. Summary concept maps were created and grounded theory concepts were explored for each learning level. We identified three major findings: (1) The “apprentice effect” in novices (high stress and low narrative competence); (2) logistic concept growth in intermediates; and (3) a cognitive state transition (between analytical and intuitive approaches) in experts. These findings warrant further study and comparison.
A Disease Marker for Aspirin-Induced Chronic Urticaria
Authors: Hsieh Chia-Wei , Lee Jeen-Wei , Liao En-Chih , Tsai Jaw-Ji
Published: July 2014

There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T) and rs2251746 (–66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T) were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p < 0.05), and the percentages of histamine release were 31.3% ± 7.4% vs. −24.0% ± 17.5%, (p < 0.05) respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (–344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU.
SOTB Implementation of a Field Programmable Gate Array with Fine-Grained Vt Programmability
Authors: Hioki Masakazu , Ma Chao , Kawanami Takashi , Ogasahara Yasuhiro , Nakagawa Tadashi , Sekigawa Toshihiro , Tsutsumi Toshiyuki , Koike Hanpei
Published: July 2014

Field programmable gate arrays (FPGAs) are one of the most widespread reconfigurable devices in which various functions can be implemented by storing circuit connection information and logic values into configuration memories. One of the most important issues in the modern FPGA is the reduction of its static leakage power consumption. Flex Power FPGA, which has been proposed to overcome this problem, uses a body biasing technique to implement the fine-grained threshold voltage (Vt) programmability in the FPGA. A low-Vt state can be assigned only to the component circuits along the critical path of the application design mapped on the FPGA, so that the static leakage power consumption can be reduced drastically. Flex Power FPGA is an important application target for the SOTB (silicon on thin buried oxide) device, which features a wide-range body biasing ability and the high sensitivity of Vt variation by body biasing, resulting in a drastic subthreshold leakage current reduction caused by static leakage power. In this paper, the Flex Power FPGA test chip is fabricated in SOTB technology, and the functional test and performance evaluation of a mapped 32-bit binary counter circuit are performed successfully. As a result, a three orders of magnitude static leakage reduction with a bias range of 2.1 V demonstrates the excellent Vt controllability of the SOTB transistors, and the 1.2 V bias difference achieves a 50× leakage reduction without degrading speed.
Continuous Ethanol Production with a Membrane Bioreactor at High Acetic Acid Concentrations
Authors: Ylitervo Päivi , Franzén Carl , Taherzadeh Mohammad
Published: July 2014

The release of inhibitory concentrations of acetic acid from lignocellulosic raw materials during hydrolysis is one of the main concerns for 2nd generation ethanol production. The undissociated form of acetic acid can enter the cell by diffusion through the plasma membrane and trigger several toxic effects, such as uncoupling and lowered intracellular pH. The effect of acetic acid on the ethanol production was investigated in continuous cultivations by adding medium containing 2.5 to 20.0 g·L−1 acetic acid at pH 5.0, at a dilution rate of 0.5 h−1. The cultivations were performed at both high (~25 g·L−1) and very high (100–200 g·L−1) yeast concentration by retaining the yeast cells inside the reactor by a cross-flow membrane in a membrane bioreactor. The yeast was able to steadily produce ethanol from 25 g·L−1 sucrose, at volumetric rates of 5–6 g·L−1·h−1 at acetic acid concentrations up to 15.0 g·L−1. However, the yeast continued to produce ethanol also at a concentration of 20 g·L−1 acetic acid but at a declining rate. The study thereby demonstrates the great potential of the membrane bioreactor for improving the robustness of the ethanol production based on lignocellulosic raw materials.
QM/MM Studies of Contemporary and Novel Membrane Raft Fluorescent Probes
Authors: Blake Hannah , Robinson David
Published: July 2014

We have studied a number of contemporary and novel membrane probes, selected for their structural similarity to membrane raft components, in order to properly anchor themselves within a sphingolipid/cholesterol rich region. A QM/MM approach was adopted in order to understand the structural and electrostatic influences of fluorescence emission shifts of the probes in different lipid and solvation environments. The proposed modifications to the membrane probes have shown encouraging data relating not only to emission shifts within the membrane, but also their ability to anchor within a membrane raft domain and the stability to internalization within a membrane system.
Jasmonic Acid Effect on the Fatty Acid and Terpenoid Indole Alkaloid Accumulation in Cell Suspension Cultures of Catharanthus roseus
Authors: Goldhaber-Pasillas Guitele , Mustafa Natali , Verpoorte Robert
Published: July 2014

The stress response after jasmonic acid (JA) treatment was studied in cell suspension cultures of Catharanthus roseus. The effect of JA on the primary and secondary metabolism was based on changes in profiles of fatty acids (FA) and terpenoid indole alkaloids (TIA). According to multivariate data analyses (MVDA), three major time events were observed and characterized according to the variations of specific FA and TIA: after 0–30 min of induction FA such as C18:1, C20:0, C22:0 and C24:0 were highly induced by JA; 90–360 min after treatment was characterized by variations of C14:0 and C15:0; and 1440 min after induction JA had the largest effect on both group of metabolites were C18:1, C18:2, C18:3, C16:0, C20:0, C22:0, C24:0, catharanthine, tabersonine-like 1, serpentine, tabersonine and ajmalicine-like had the most significant variations. These results unambiguously demonstrate the profound effect of JA particularly on the accumulation of its own precursor, C18:3 and the accumulation of TIA, which can be considered as late stress response events to JA since they occurred only after 1440 min. These observations show that the early events in the JA response do not involve the de novo biosynthesis of neither its own precursor nor TIA, but is due to an already present biochemical system.
The Natural Product Citral Can Cause Significant Damage to the Hyphal Cell Walls of Magnaporthe grisea
Authors: Li Rong-Yu , Wu Xiao-Mao , Yin Xian-Hui , Liang Jing-Nan , Li Ming
Published: July 2014

In order to find a natural alternative to the synthetic fungicides currently used against the devastating rice blast fungus, Magnaporthe grisea, this study explored the antifungal potential of citral and its mechanism of action. It was found that citral not only inhibited hyphal growth of M. grisea, but also caused a series of marked hyphal morphological and structural alterations. Specifically, citral was tested for antifungal activity against M. grisea in vitro and was found to significantly inhibit colony development and mycelial growth with IC50 and IC90 values of 40.71 and 203.75 μg/mL, respectively. Furthermore, citral reduced spore germination and germ tube length in a concentration-dependent manner. Following exposure to citral, the hyphal cell surface became wrinkled with folds and cell breakage that were observed under scanning electron microscopy (SEM). There was damage to hyphal cell walls and membrane structures, loss of villous-like material outside of the cell wall, thinning of the cell wall, and discontinuities formed in the cell membrane following treatment based on transmission electron microscopy (TEM). This increase in chitinase activity both supports the morphological changes seen in the hyphae, and also suggests a mechanism of action. In conclusion, citral has strong antifungal properties, and treatment with this compound is capable of causing significant damage to the hyphal cell walls of M. grisea.
Photoswitchable precision glycooligomers and their lectin binding
Authors: Ponader Daniela , Igde Sinaida , Wehle Marko , Märker Katharina , Santer Mark , Bléger David , Hartmann Laura
Published: July 2014

The synthesis of photoswitchable glycooligomers is presented by applying solid-phase polymer synthesis and functional building blocks. The obtained glycoligands are monodisperse and present azobenzene moieties as well as sugar ligands at defined positions within the oligomeric backbone and side chains, respectively. We show that the combination of molecular precision together with the photoswitchable properties of the azobenzene unit allows for the photosensitive control of glycoligand binding to protein receptors. These stimuli-sensitive glycoligands promote the understanding of multivalent binding and will be further developed as novel biosensors.
Sacred, Secular, and Ecological Discourses: the Sethusamudram Project
Authors: Feagans Carl T.
Published: July 2014

The nature of discourse in public culture has changed significantly if not noticeably in just the past few decades. The Sethusamudram Shipping Canal Project (SSCP) intended to create a commercial shipping lane between India and Sri Lanka demonstrates the nature of this change in discourse, which seems focused around the convergence of traditional news media and public commentary through the medium of the Internet which increases the reach of news as well as the speed with which that news arrives to its audience. Just two decades earlier, at a time when the Internet was very young, many of the same political parties and government agencies involved with the SSCP were also involved in the Babri Mosque controversy which culminated in the deaths of perhaps 2000 people as well as the destruction of an historical site, the mosque itself. While many factors are likely to have contributed, the SSCP controversy, in which thousands of concerned Hindus mobilized in protests, resulted in little if no injury or damage to property. This was, perhaps, due in part to the nature of the public discourse.
The Language of Threat in our Political Discourse
Authors: Boynton G. R. , Richardson, Jr. Glenn W.
Published: July 2014

This chapter is a report about negotiating the boundaries of appropriate political discourse via Twitter. The instance looked at in depth is the communication about the shooting of Representative Giffords in 2011. The first month over 400,000 messages referred to Giffords and substantially more referred to the controversy about the campaign rhetoric of targets and reloading. The authors tracked the communication in 6 ongoing collections of streams of messages and 2 that resulted from the shooting and controversy. One stream was about how “terrorist” was used in characterizing the shooter. The major controversy was about the use of targeting or gun references in campaign rhetoric. Palin released a video using the phrase “blood libel” leading to opposing interpretations of the appropriate use of the term. The authors look in less depth at the controversy in early 2012 about Rush Limbaugh's characterization of a student who testified to a committee of the House of Representatives. That controversy reinforced points found in the communication about the Giffords shooting. It also reminds us that the boundaries of appropriate political rhetoric are continuously negotiated in a free speech society and that there is now a new domain for the negotiation in the new media.
The Experiences of Women Working in the Computer Games Industry
Authors: Prescott Julie , Bogg Jan
Published: July 2014

This chapter provides a unique understanding of women working in the computer games industry. In depth interviews were undertaken with seven female game workers based in the UK. The women were interviewed as part of a larger study focusing on women in this male dominated industry. The issues detailed in this chapter focus on the industry as a viable career for women, the experience of being a woman working in games and the working environment; including work life balance issues, experiences of discrimination and experiences of sexism. The research discussed is related to attracting and retaining women in games development. The issues are of relevance to employers, professional bodies, policy makers and researchers of the games industry and the wider ICT and SET industries. Recommendations from the findings and future research directions are provided.
Women's Participation in the Australian Digital Content Industry
Authors: Geneve Anitza
Published: July 2014

There is a need to understand the phenomenon of women's under-representation in the Australian Digital Content Industry (DCI) workforce. This chapter presents the findings from an Australian case study where both women working in the industry and industry stakeholders were interviewed for their insight into the influences on women's participation. The rich empirical data and findings from the case study are interpreted using the Acts of Agency theory—an original theory by the author of this chapter. As the chapter reveals there are five ‘Acts of Agency' (containing 10 agent-driven mechanisms) identified as influencing women's participation. Agent-driven mechanisms recognise the causal effect of people themselves; that is, the role individuals play in their participation.
Professional Socialization in STEM Academia and its Gendered Impact on Creativity and Innovation
Authors: Warmuth Gloria-Sophia , Hanappi-Egger Edeltraud
Published: July 2014

The chapter focuses on internal professionalization processes in STEM academia and their impact on creativity and innovation capacity. The discussion looks at how internal structures and value systems in STEM academia are used to shape the professional self-understanding of members. Exemplified by a higher education institution in the field of science, engineering, technology and math we show how gendered exclusion and inclusion is established structurally. Restrictive and rigid professional scripts and role expectations are identified as the main obstacles to greater potentials for creativity and innovation.
Lessons from the STEM Sector
Authors: Pugh Vachon M.C.
Published: July 2014

The purpose of this chapter is to examine possible causes such as lack of interest, lack of skill/ability, and anticipated work/family conflict (WFC), in addition to analyzing successful recruitment tactics that have brought more women into various other male dominated fields in an attempt to solve this problem. Results of the literature review show that the main contributing factors for the lack of women within the sector are lack of confidence in skills and abilities, lack of female industry role models, and lack of available mentorship and community outreach programs for interested women. This chapter takes this information into consideration and makes possible suggestions for the industry on how to remedy this problem.
A Framework for Addressing Gender Imbalance in the Game Industry through Outreach
Authors: McGill Monica M. , Decker Adrienne , Settle Amber
Published: July 2014

Though the lack of diversity in the game industry workforce has received a great deal of attention recently, few initiatives have been implemented to address it. In particular, gender composition in the game industry workforce and among students studying games at post-secondary institutions is highly imbalanced, with an approximate 9 to 1 ratio of male to female students. This chapter considers three key aspects: 1) the current demographics of the game industry, 2) the effects of gender imbalance on the game industry and one of its current pipelines, and 3) a potential framework to address the imbalance. The proposed outreach strategy is informed by a discussion of established frameworks for initiating change in related fields. The chapter concludes with suggestions for future research to address the gender imbalance in the game industry and its pipeline.
Female Game Workers: Career Development, and Aspirations
Authors: Prescott Julie , Bogg Jan
Published: July 2014

Understanding the career factors that influence women's career aspirations in male-dominated occupations is important for increasing women's progression within these occupations. This chapter assesses the impact of career influencers on career aspirations of women working in the male-dominated computer games industry. An online questionnaire obtained international data from 450 women working in the computer games industry. A structural equation model was employed to investigate the influencers. Findings suggest that to increase women's career development and career aspirations within the computer games industry, self-efficacy, attitudes towards career barriers, work-life balance attitudes, person-environment fit and job satisfaction are crucial.
Lymph Node Stromal Cells Negatively Regulate Antigen-Specific CD4+ T Cell Responses
Authors: Abe Jun , Shichino Shigeyuki , Ueha Satoshi , Hashimoto Shin-ichi , Tomura Michio , Inagaki Yutaka , Stein Jens V. , Matsushima Kouji
Published: July 2014

Lymph node (LN) stromal cells (LNSCs) form the functional structure of LNs and play an important role in lymphocyte survival and the maintenance of immune tolerance. Despite their broad spectrum of function, little is known about LNSC responses during microbial infection. In this study, we demonstrate that LNSC subsets display distinct kinetics following vaccinia virus infection. In particular, compared with the expansion of other LNSC subsets and the total LN cell population, the expansion of fibroblastic reticular cells (FRCs) was delayed and sustained by noncirculating progenitor cells. Notably, newly generated FRCs were preferentially located in perivascular areas. Viral clearance in reactive LNs preceded the onset of FRC expansion, raising the possibility that viral infection in LNs may have a negative impact on the differentiation of FRCs. We also found that MHC class II expression was upregulated in all LNSC subsets until day 10 postinfection. Genetic ablation of radioresistant stromal cell–mediated Ag presentation resulted in slower contraction of Ag-specific CD4+ T cells. We propose that activated LNSCs acquire enhanced Ag-presentation capacity, serving as an extrinsic brake system for CD4+ T cell responses. Disrupted function and homeostasis of LNSCs may contribute to immune deregulation in the context of chronic viral infection, autoimmunity, and graft-versus-host disease.
Antigen Targeting to CD11b+ Dendritic Cells in Association with TLR4/TRIF Signaling Promotes Strong CD8+ T Cell Responses
Authors: Dadaglio Gilles , Fayolle Catherine , Zhang Xiaoming , Ryffel Bernard , Oberkampf Marine , Felix Tristan , Hervas-Stubbs Sandra , Osicka Radim , Sebo Peter , Ladant Daniel , Leclerc Claude
Published: July 2014

Deciphering the mechanisms that allow the induction of strong immune responses is crucial to developing efficient vaccines against infectious diseases and cancer. Based on the discovery that the adenylate cyclase from Bordetella pertussis binds to the CD11b/CD18 integrin, we developed a highly efficient detoxified adenylate cyclase-based vector (CyaA) capable of delivering a large variety of Ags to the APC. This vector allows the induction of protective and therapeutic immunity against viral and tumoral challenges as well as against transplanted tumors in the absence of any added adjuvant. Two therapeutic vaccine candidates against human papilloma viruses and melanoma have been developed recently, based on the CyaA vector, and are currently in clinical trials. We took advantage of one of these highly purified vaccines, produced under good manufacturing practice–like conditions, to decipher the mechanisms by which CyaA induces immune responses. In this study, we demonstrate that CyaA binds both human and mouse CD11b+ dendritic cells (DCs) and induces their maturation, as shown by the upregulation of costimulatory and MHC molecules and the production of proinflammatory cytokines. Importantly, we show that DCs sense CyaA through the TLR4/Toll/IL-1R domain–containing adapter-inducing IFN-β pathway, independent of the presence of LPS. These findings show that CyaA possesses the intrinsic ability to not only target DCs but also to activate them, leading to the induction of strong immune responses. Overall, this study demonstrates that Ag delivery to CD11b+ DCs in association with TLR4/Toll/IL-1R domain–containing adapter-inducing IFN-β activation is an efficient strategy to promote strong specific CD8+ T cell responses.
Fcγ Receptor Dependency of Agonistic CD40 Antibody in Lymphoma Therapy Can Be Overcome through Antibody Multimerization
Authors: White Ann L. , Dou Lang , Chan H. T. Claude , Field Vikki L. , Mockridge C. Ian , Moss Kane , Williams Emily L. , Booth Steven G. , French Ruth R. , Potter Elizabeth A. , Butts Cherié , Al-Shamkhani Aymen , Cragg Mark S. , Verbeek J. Sjef , Johnson Peter W. M. , Glennie Martin J. , Beers Stephen A.
Published: July 2014

Immunomodulatory mAbs, led by the anti-CTLA4 mAb ipilimumab, are an exciting new class of drugs capable of promoting anticancer immunity and providing durable control of some tumors. Close analysis of a number of agents has revealed a critical yet variable role for Fcγ receptors in their efficacy. In this article, we reveal that agonistic anti-CD40 mAbs have an absolute requirement for cross-linking by inhibitory FcγRIIB when used systemically to treat established BCL1 syngeneic lymphoma, and therapy is lost when using a mouse IgG2a mAb not cross-linked by FcγRIIB. Furthermore, in FcγRIIB-deficient mice the lymphoma itself can provide FcγRIIB to cross-link anti-CD40 on neighboring cells, and only when this is blocked does therapy fail. The dependence on FcγRIIB for immunostimulatory activity was not absolute, however, because when anti-CD40 mAbs were administered systemically with the TLR3 agonist polyinosinic:polycytidylic acid or were given subcutaneously, activatory FcγR could also provide cross-linking. Using this mechanistic insight, we designed multimeric forms of anti-CD40 mAb with intrinsic FcγR-independent activity that were highly effective in the treatment of lymphoma-bearing mice. In conclusion, FcγR-independent anti-CD40 activation is a viable strategy in vivo. These findings have important translational implications, as humans, unlike mice, do not have IgG that binds strongly to FcγRIIB; therefore FcγR-independent derivatives represent an attractive therapeutic option.
Lnk/Sh2b3 Controls the Production and Function of Dendritic Cells and Regulates the Induction of IFN-γ–Producing T Cells
Authors: Mori Taizo , Iwasaki Yukiko , Seki Yoichi , Iseki Masanori , Katayama Hiroko , Yamamoto Kazuhiko , Takatsu Kiyoshi , Takaki Satoshi
Published: July 2014

Dendritic cells (DCs) are proficient APCs that play crucial roles in the immune responses to various Ags and pathogens and polarize Th cell immune responses. Lnk/SH2B adaptor protein 3 (Sh2b3) is an intracellular adaptor protein that regulates B lymphopoiesis, megakaryopoiesis, and expansion of hematopoietic stem cells by constraining cytokine signals. Recent genome-wide association studies have revealed a link between polymorphism in this adaptor protein and autoimmune diseases, including type 1 diabetes and celiac disease. We found that Lnk/Sh2b3 was also expressed in DCs and investigated its role in the production and function of DC lineage cells. In Lnk−/− mice, DC numbers were increased in the spleen and lymph nodes, and growth responses of bone marrow–derived DCs to GM-CSF were augmented. Mature DCs from Lnk−/− mice were hypersensitive and showed enhanced responses to IL-15 and GM-CSF. Compared to normal DCs, Lnk−/− DCs had enhanced abilities to support the differentiation of IFN-γ–producing Th1 cells from naive CD4+ T cells. This was due to their elevated expression of IL-12Rβ1 and increased production of IFN-γ. Lnk−/− DCs supported the appearance of IFN-γ–producing T cells even under conditions in which normal DCs supported induction of regulatory T cells. These results indicated that Lnk/Sh2b3 plays a regulatory role in the expansion of DCs and might influence inflammatory immune responses in peripheral lymphoid tissues.
Recombinant Human IgA1 and IgA2 Autoantibodies to Type VII Collagen Induce Subepidermal Blistering Ex Vivo
Authors: Recke Andreas , Trog Luisa M. , Pas Hendri H. , Vorobyev Artem , Abadpour Aida , Jonkman Marcel F. , van Zandbergen Ger , Kauderer Claudia , Zillikens Detlef , Vidarsson Gestur , Ludwig Ralf J.
Published: July 2014

Subepidermal autoimmune blistering dermatoses (AIBD) are prototypic autoantibody-mediated diseases. In epidermolysis bullosa acquisita (EBA), an autoimmune disease with severe and chronic skin blistering, autoantibodies are directed against type VII collagen. IgG is the predominant autoantibody isotype of EBA, the pathogenicity of which has been demonstrated in a variety of in vivo and ex vivo disease models. In contrast, there is not much evidence for the pathogenicity of IgA, which may appear as the only autoantibody isotype in some EBA patients. To investigate the pathogenic potential of IgA autoantibodies, we generated chimeric V gene–matched human IgA1, IgA2, and control IgG1 autoantibodies directed against type VII collagen. Immobilized immune complexes containing the rIgA1 and rIgA2 autoantibodies induced the dose-dependent release of reactive oxygen species from neutrophil granulocytes, a precondition for blister formation. Moreover, both rIgA1 and rIgA2 induced leukocyte-dependent dermal–epidermal separation in cryosections of human skin. In contrast with rIgG1, neither rIgA1 nor rIgA2 was capable of inducing complement deposition at the dermal–epidermal junction. Because complement activation is a prerequisite for blister induction, this lack of function compared with IgG1 may be compensated for by the stronger activation of neutrophil granulocytes by both IgA1 and IgA2. For IgG-mediated AIBD, immunoadsorption therapy is a convenient treatment modality for the removal of pathogenic autoantibodies, particularly in treatment-resistant cases. The results of this study show the pathogenic potential of IgA autoantibodies and support the development of adsorber matrices for IgA-mediated AIBD.
The Differential Regulation of Human ACT1 Isoforms by Hsp90 in IL-17 Signaling
Authors: Wu Ling , Wang Chenhui , Boisson Bertrand , Misra Saurav , Rayman Patricia , Finke James H. , Puel Anne , Casanova Jean-Laurent , Li Xiaoxia
Published: July 2014

IL-17 is a proinflammatory cytokine implicated in the pathogenesis of autoimmune diseases including psoriasis. ACT1 is an essential adaptor molecule in the IL-17 signaling pathway. A missense single nucleotide polymorphism (rs33980500; SNP-D10N) that resulted in the substitution of an asparagine for an aspartic acid at position 10 of ACT1 (ACT1-D10N) is associated with psoriasis susceptibility. Due to alternative splicing in humans, SNP-D10N encodes two mutated ACT1 proteins, ACT1-D10N and ACT1-D19N. Although both ACT1 isoforms are Hsp90 client proteins, the nine additional amino acids in ACT1-D19N provide an additional Hsp90 binding site that is absent in ACT1-D10N. Therefore, whereas ACT1-D10N is a dead protein that is unable to transduce IL-17 signals for gene expression, ACT1-D19N is fully responsive to IL-17. Intriguingly, the two ACT1 isoforms are differentially expressed in ACT1D10N/D10N fibroblasts and T cells. Fibroblasts express both isoforms equally, enabling ACT1-D19N to compensate for the loss of ACT1-D10N function. ACT1D10N/D10N T cells, however, express predominantly ACT1-D10N. Lacking this compensatory mechanism, ACT1D10N/D10N T cells behave like ACT1-deficient T cells, exhibiting a dysregulated and hyperactive Th17 phenotype with overproduction of IL-22 and IL-17. The hyperactive Th17 response combined with fully responsive fibroblasts likely synergized to contribute to psoriasis susceptibility in SNP-D10N patients.
Cowpox Virus Protein CPXV012 Eludes CTLs by Blocking ATP Binding to TAP
Authors: Luteijn Rutger D. , Hoelen Hanneke , Kruse Elisabeth , van Leeuwen Wouter F. , Grootens Jennine , Horst Daniëlle , Koorengevel Martijn , Drijfhout Jan W. , Kremmer Elisabeth , Früh Klaus , Neefjes Jacques J. , Killian Antoinette , Lebbink Robert Jan , Ressing Maaike E. , Wiertz Emmanuel J. H. J.
Published: July 2014

CD8+ CTLs detect virus-infected cells through recognition of virus-derived peptides presented at the cell surface by MHC class I molecules. The cowpox virus protein CPXV012 deprives the endoplasmic reticulum (ER) lumen of peptides for loading onto newly synthesized MHC class I molecules by inhibiting the transporter associated with Ag processing (TAP). This evasion strategy allows the virus to avoid detection by the immune system. In this article, we show that CPXV012, a 9-kDa type II transmembrane protein, prevents peptide transport by inhibiting ATP binding to TAP. We identified a segment within the ER-luminal domain of CPXV012 that imposes the block in peptide transport by TAP. Biophysical studies show that this domain has a strong affinity for phospholipids that are also abundant in the ER membrane. We discuss these findings in an evolutionary context and show that a frameshift deletion in the CPXV012 gene in an ancestral cowpox virus created the current form of CPXV012 that is capable of inhibiting TAP. In conclusion, our findings indicate that the ER-luminal domain of CPXV012 inserts into the ER membrane, where it interacts with TAP. CPXV012 presumably induces a conformational arrest that precludes ATP binding to TAP and, thus, activity of TAP, thereby preventing the presentation of viral peptides to CTLs.
The church and the secular: The effect of the post-secular on Christianity
Authors: Beyers Jaco
Published: July 2014

Paradigms determine relationships. During the Enlightenment period Emile Durkheim proposed a relationship between the sacred and the profane. Religion, which is concerned with the sacred, was defined in terms of being different from the profane. The profane came to denote the secular. The organic character of religion caused some scholars to predict the end of the church at the hand of modernisation and rationalisation. Some scholars instead envisaged a new form and function of the church. Some scholars anticipated the growth of Christianity. Reality shows that Christianity has not died out but seems to be growing. The new era we are currently in (identified as the postmodern) has been described as the post-secular age where a process of re-sacralisation takes place. How will the post-secular influence the church? What will the relationship between the church and the secular be like under a new paradigm? This article suggests that within a postmodern paradigm, the post-secular will emphasise the place of the individual in the church. Fragmentation of society will also be the result of the post-secular. Religiosity in future will have to contend with fundamentalism and civil religion.
Relationship of angiogenic and apoptotic activities in soft-tissue sarcoma
Authors: Win Thin Thin , Jaafar Hasnan , Yusuf Yusri
Published: July 2014

Introduction: Angiogenesis and apoptosis play an essential role in tumor development and progression. Previous studies on apoptosis and angiogenesis of soft-tissue sarcoma (STS) were done separately. This is the first study of the relationship between apoptotic and angiogenic activity. Correlation of expression of anti-apoptotic protein (Bcl-2) and pro-apoptotic protein (Bax) in the tumor cells (TCs) with their expression in endothelial cell (EC) of the tumor blood vessels in STS were also carried out. Materials and Methods: 101 cases of STS; consisting liposarcoma, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma and malignant peripheral nerve sheath tumor; were collected and immunohistochemical reaction of vascular endothelial growth factor (VEGF), Bcl-2 and Bax were examined. Results: Higher Bax expression in TCs (54.5%) was seen compared to Bcl-2 expression (44.6%). There was a significant association between Bcl-2 and Bax in TCs with ECs. Significant association was also seen between histological types of STS with Bcl-2 expression; however not with Bax expression. There was an association between VEGF and Bax with high VEGF expression and weak Bax expression. However, VEGF expression was not associated with Bcl-2 expression and histological types. Conclusion: This study supports the role of ECs of tumor blood vessels and apoptosis of TCs in tumor management. Increased angiogenesis may inhibit apoptosis of TCs and lead to tumor growth. Therefore, inhibition of ECs survival or activation of ECs death is promising prospect for tumor therapy. Immunohistochemical antibodies in this study might be potential useful marker for the prognosis of STS.
Nitrogen application rate, timing and history effects on nitrous oxide emissions from corn (Zea maysL.)
Authors: Roy Amal K. , Wagner-Riddle Claudia , Deen Bill , Lauzon John , Bruulsema Tom
Published: July 2014

Roy, A. K., Wagner-Riddle, C., Deen, B., Lauzon, J. and Bruulsema, T. 2014. Nitrogen application rate, timing and history effects on nitrous oxide emissions from corn (Zea mays L.). Can. J. Soil Sci. 94: 563–573. Nitrous oxide (N2O) emissions resulting from application of nitrogen (N) fertilizer contribute to the greenhouse gas footprint of corn production. In eastern Canada, corn is a major crop with most N fertilizer applied pre- or at planting. This timing of application results in a lack of synchrony of soil N supply and crop N demand. Matching the amount and timing of application to crop uptake has been suggested as a mitigation measure to reduce N losses, and is an integral part of the 4R Nutrient Stewardship program. This study examined the effect of timing, rate and history of urea-ammonium nitrate application on N2O emissions in corn in 2011 and 2012 at Elora, ON, Canada. Treatments were three N rates (30, 145 and 218 kg N ha−1); two timings (N injected in mid-row at planting and at the 8th leaf stage, V8); two histories (short-term: applying N rate treatments on plots that had received 145 kg N ha−1in the previous year, and long-term: applying the same N rate to a given plot over the duration of the trial). N2O emissions were measured using static chambers. History of N application did not have an effect on N2O emissions or grain yield. In both years, cumulative N2O emissions during the growing season and corn yields increased significantly with increasing N application rates. In 2011, cumulative N2O emissions were significantly lower when N was applied as side-dress at V8 (0.88 kg N ha−1) compared with planting (2.12 kg N ha−1), with no significant impact on corn grain yield (average 9.1 Mg ha−1). In contrast, in 2012, limited rainfall reduced both N2O emissions and corn grain yield, and neither N2O emission (average 0.17 kg N ha−1) nor grain yield (average 6.7 Mg ha−1) was affected by timing of N application. Applying N as side-dress at V8 instead of at planting and using the recommended N rate were shown to be effective N2O emission mitigation practices without affecting corn yield during a typical wet spring in Ontario.
A feedback loop links brownification and anoxia in a temperate, shallow lake
Authors: Brothers S. , Köhler J. , Attermeyer K. , Grossart H. P. , Mehner T. , Meyer N. , Scharnweber K. , Hilt S.
Published: July 2014

This study examines a natural, rapid, fivefold increase in dissolved organic carbon (DOC) concentrations in a temperate shallow lake, describing the processes by which increased DOC resulted in anoxic conditions and altered existing carbon cycling pathways. High precipitation for two consecutive years led to rising water levels and the flooding of adjacent degraded peatlands. Leaching from the flooded soils provided an initial increase in DOC concentrations (from a 2010 mean of 12 ± 1 mg L−1 to a maximum concentration of 53 mg L−1 by June 2012). Increasing water levels, DOC, and phytoplankton concentrations reduced light reaching the sediment surface, eliminating most benthic primary production and promoting anoxia in the hypolimnion. From January to June 2012 there was a sudden increase in total phosphorus (from 57 µg L−1 to 216 µg L−1), DOC (from 24.6 mg L−1 to 53 mg L−1), and iron (from 0.12 mg L−1 to 1.07 mg L−1) concentrations, without any further large fluxes in water levels. We suggest that anoxic conditions at the sediment surface and flooded soils produced a dramatic release of these chemicals that exacerbated brownification and eutrophication, creating anoxic conditions that persisted roughly 6 months below a water depth of 1 m and extended periodically to the water surface. This brownification‐anoxia feedback loop resulted in a near‐complete loss of macroinvertebrate and fish populations, and increased surface carbon dioxide (CO2) emissions by an order of magnitude relative to previous years.
Numerical simulations of larval transport into a rip‐channeled surf zone
Authors: Fujimura Atsushi G. , Reniers Ad J. H. M. , Paris Claire B. , Shanks Alan L. , MacMahan Jamie H. , Morgan Steven G.
Published: July 2014

Competent larvae of intertidal invertebrates have to migrate toward shore for settlement; however, their migration through the surf zone is not understood. We investigated larval transport mechanisms at a rip‐channeled beach. Because tracking larvae in the surf zone is infeasible, we used a three‐dimensional biophysical model to simulate the processes. The coupled model consists of a physical module for currents and waves, and a biological module for adding larval traits and behaviors as well as Stokes drift to Lagrangian particles. Model calculations were performed with and without onshore wind forcing. Without wind, wave‐driven onshore streaming occurs in the bottom boundary layer outside the surf zone. With onshore wind, onshore currents occur near the surface. In the surf zone, offshore‐directed rip currents and compensating onshore‐directed currents over shoals are formed in both no‐wind and wind cases. In the biological module, neutral, negative, and positive buoyant particles were released offshore. Additionally, particles either sank in the presence of turbulence or not. Two scenarios achieved successful onshore migration: Negatively buoyant larvae without wind forcing sink in the turbulent bottom boundary layer and are carried onshore by streaming; positively buoyant larvae drift toward shore in wind‐driven surface currents to the surf zone, then sink in the turbulent surf zone and remain near the bottom while transported shoreward. In both cases, the larval concentration is highest in the rip channel, consistent with field data. This successful result is only obtained if turbulence‐dependent sinking behavior and Stokes drift are included in the transport of larvae.
Mass‐specific light absorption coefficients of natural aquatic particles in the near‐infrared spectral region
Authors: Röttgers Rüdiger , Dupouy Cecile , Taylor Bettina B. , Bracher Astrid , Woźniak Slawomir B.
Published: July 2014

The extent of light absorption in the near‐infrared spectral region (NIR; 700–900 nm) of natural suspended particles was investigated by determining the absorption and mass‐specific absorption coefficients of samples from different environments: river, coastal waters, tropical lagoon, and oceanic waters. Large amounts of sample were collected onto glass‐fiber filters and measured inside the integrating sphere of a spectrophotometer. The absorption coefficient of particle suspension was also determined for visible wavelengths with a point‐source integrating cavity absorption meter. Measurable nonzero particulate absorption in the NIR was determined in all samples, even in algal cultures. It was highest in the river samples (e.g., 1.7 m−1 at 850 nm), reaching values similar to the NIR absorption of pure water—a strong NIR absorber. Lowest values were in oligotrophic waters and in algal cultures. Ratios of absorption at 750 nm to absorption at 442 and 672 nm varied between 2% to 30% and 3% to 80%, respectively. Mass‐specific absorption in the NIR at 850 nm was also highest in the river (0.012 m2 g−1) and lowest in oligotrophic waters (0.002–0.003 m2 g−1). The observed NIR absorption can partly be explained by absorption of minerogenic particles, whereas the contribution of organic detritus to the NIR absorption is still mostly unknown.