bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in the Phenotype, Cytokine Gene Expression Profiles, and In Vivo Alloreactivity of T Cells Mobilized with Plerixafor Compared with G-CSF
Authors: Lundqvist Andreas , Smith Aleah L. , Takahashi Yoshiyuki , Wong Susan , Bahceci Erkut , Cook Lisa , Ramos Catalina , Tawab Abdul , McCoy J. Philip , Read Elizabeth J. , Khuu Hanh M. , Bolan Charles D. , Joo Jungnam , Geller Nancy , Leitman Susan F. , Calandra Gary , Dunbar Cynthia , Kurlander Roger , Childs Richard W.
Published: November 2013

Plerixafor (Mozobil) is a CXCR4 antagonist that rapidly mobilizes CD34+ cells into circulation. Recently, plerixafor has been used as a single agent to mobilize peripheral blood stem cells for allogeneic hematopoietic cell transplantation. Although G-CSF mobilization is known to alter the phenotype and cytokine polarization of transplanted T cells, the effects of plerixafor mobilization on T cells have not been well characterized. In this study, we show that alterations in the T cell phenotype and cytokine gene expression profiles characteristic of G-CSF mobilization do not occur after mobilization with plerixafor. Compared with nonmobilized T cells, plerixafor-mobilized T cells had similar phenotype, mixed lymphocyte reactivity, and Foxp3 gene expression levels in CD4+ T cells, and did not undergo a change in expression levels of 84 genes associated with Th1/Th2/Th3 pathways. In contrast with plerixafor, G-CSF mobilization decreased CD62L expression on both CD4 and CD8+ T cells and altered expression levels of 16 cytokine-associated genes in CD3+ T cells. To assess the clinical relevance of these findings, we explored a murine model of graft-versus-host disease in which transplant recipients received plerixafor or G-CSF mobilized allograft from MHC-matched, minor histocompatibility–mismatched donors; recipients of plerixafor mobilized peripheral blood stem cells had a significantly higher incidence of skin graft-versus-host disease compared with mice receiving G-CSF mobilized transplants (100 versus 50%, respectively, p = 0.02). These preclinical data show plerixafor, in contrast with G-CSF, does not alter the phenotype and cytokine polarization of T cells, which raises the possibility that T cell–mediated immune sequelae of allogeneic transplantation in humans may differ when donor allografts are mobilized with plerixafor compared with G-CSF.
Double Positive Thymocytes Select Mucosal-Associated Invariant T Cells
Authors: Seach Natalie , Guerri Lucia , Le Bourhis Lionel , Mburu Yvonne , Cui Yue , Bessoles Stéphanie , Soudais Claire , Lantz Olivier
Published: November 2013

NKT and mucosal-associated invariant T (MAIT) cells express semi-invariant TCR and restriction by nonclassical MHC class Ib molecules. Despite common features, the respective development of NKT and MAIT subsets is distinct. NKTs proliferate extensively and acquire effector properties prior to thymic export. MAIT cells exit the thymus as naive cells and acquire an effector/memory phenotype in a process requiring both commensal flora and B cells. During thymic development, NKTs are selected by CD1d-expressing cortical thymocytes; however, the hematopoietic cell type responsible for MAIT cell selection remains unresolved. Using reaggregated thymic organ culture and bone marrow chimeras, we demonstrate that positive selection of mouse iVα19 transgenic and Vβ6 transgenic MAIT cell progenitors requires MHC-related 1–expressing CD4+CD8+ double positive thymocytes, whereas thymic B cells, macrophages, and dendritic cell subsets are dispensable. Preincubation of double positive thymocytes with exogenous bacterial ligand increases MHC-related 1 surface expression and enhances mature MAIT cell activation in the in vitro cocultures. The revelation of a common cell type for the selection of both NKT and MAIT subsets raises questions about the mechanisms underlying acquisition of their specific features.
Essential Functions for ID Proteins at Multiple Checkpoints in Invariant NKT Cell Development
Authors: Verykokakis Mihalis , Krishnamoorthy Veena , Iavarone Antonio , Lasorella Anna , Sigvardsson Mikael , Kee Barbara L.
Published: November 2013

Invariant NKT (iNKT) cells display characteristics of both adaptive and innate lymphoid cells (ILCs). Like other ILCs, iNKT cells constitutively express ID proteins, which antagonize the E protein transcription factors that are essential for adaptive lymphocyte development. However, unlike ILCs, ID2 is not essential for thymic iNKT cell development. In this study, we demonstrated that ID2 and ID3 redundantly promoted iNKT cell lineage specification involving the induction of the signature transcription factor PLZF and that ID3 was critical for development of TBET-dependent NKT1 cells. In contrast, both ID2 and ID3 limited iNKT cell numbers by enforcing the postselection checkpoint in conventional thymocytes. Therefore, iNKT cells show both adaptive and innate-like requirements for ID proteins at distinct checkpoints during iNKT cell development.
Coupled IL-2–Dependent Extracellular Feedbacks Govern Two Distinct Consecutive Phases of CD4 T Cell Activation
Authors: Waysbort Nir , Russ Dor , Chain Benjamin M. , Friedman Nir
Published: November 2013

T cells integrate cell-specific Ag receptor signaling with shared signals mediated by secreted cytokines, which often involve regulatory feedback loops. IL-2 signaling, for example, reduces the synthesis of IL-2 and increases the synthesis of IL-2Rα-chain, whereas both genes require TCR signaling for their activation. The ways by which T cells dynamically integrate these private and public signals during activation are not well understood. We combined robotics, multiparameter flow cytometry, and real-time quantitative PCR to analyze T cell activation at high temporal resolution over several days. Two distinct temporal phases of T cell activation were evident. First, Ag-dependent signals activated low IL-2Rα and high IL-2 production, independent of IL-2 signaling. Subsequently, secreted IL-2 acted as a shared resource driving high IL-2Rα expression, reduced IL-2 synthesis, and cell proliferation. This transition was independent of continued TCR signaling. Our data allowed the determination of the parameters of the IL-2–mediated extracellular positive and negative feedback circuits and demonstrated that the two loops are coupled and become activated at a similar level of IL-2 signaling. We propose that temporal separation of private and shared signals allows T cells to first integrate Ag-specific responses and subsequently share information leading to collective decision making.
Two Types of TNF-α Exist in Teleost Fish: Phylogeny, Expression, and Bioactivity Analysis of Type-II TNF-α3 in Rainbow Trout Oncorhynchus mykiss
Authors: Hong Suhee , Li Ronggai , Xu Qiaoqing , Secombes Chris J. , Wang Tiehui
Published: November 2013

TNF-α is a cytokine involved in systemic inflammation and regulation of immune cells. It is produced chiefly by activated macrophages as a membrane or secreted form. In rainbow trout, two TNF-α molecules were described previously. In this article, we report a third TNF-α (TNF-α3) that has only low identities to known trout molecules. Phylogenetic tree and synteny analyses of trout and other fish species suggest that two types (named I and II) of TNF-α exist in teleost fish. The fish type-II TNF-α has a short stalk that may impact on its enzymatic release or restrict it to a membrane-bound form. The constitutive expression of trout TNF-α3 was generally lower than the other two genes in tissues and cell lines, with the exception of the macrophage RTS-11 cell line, in which expression was higher. Expression of all three TNF-α isoforms could be modulated by crude LPS, peptidoglycan, polyinosinic:polycytidylic acid, and rIFN-γ in cell lines and primary macrophages, as well as by bacterial and viral infections. TNF-α3 is the most responsive gene at early time points post-LPS stimulation and can be highly induced by the T cell–stimulant PHA, suggesting it is a particularly important TNF-α isoform. rTNF-α3 produced in CHO cells was bioactive in different cell lines and primary macrophages. In the latter, it induced the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-17C, and TNF-αs), negative regulators (SOCS1–3, TGF-β1b), antimicrobial peptides (cathelicidin-1 and hepcidin), and the macrophage growth factor IL-34, verifying its key role in the inflammatory cytokine network and macrophage biology of fish.
The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer
Authors: Mimura Kousaku , Shiraishi Kensuke , Mueller Anja , Izawa Shinichiro , Kua Ley-Fang , So Jimmy , Yong Wei-Peng , Fujii Hideki , Seliger Barbara , Kiessling Rolf , Kono Koji
Published: November 2013

Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag–specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.
Optineurin Insufficiency Impairs IRF3 but Not NF-κB Activation in Immune Cells
Authors: Munitic Ivana , Giardino Torchia Maria Letizia , Meena Netra Pal , Zhu Guozhi , Li Caiyi C. , Ashwell Jonathan D.
Published: November 2013

Optineurin is a widely expressed polyubiquitin-binding protein that has been implicated in regulating cell signaling via its NF-κB essential modulator–homologous C-terminal ubiquitin (Ub)-binding region. Its functions are controversial, with in vitro studies finding that optineurin suppressed TNF-mediated NF-κB activation and virus-induced activation of IFN regulatory factor 3 (IRF3), whereas bone marrow–derived macrophages (BMDMs) from mice carrying an optineurin Ub-binding point mutation had normal TLR-mediated NF-κB activation and diminished IRF3 activation. We have generated a mouse model in which the entire Ub-binding C-terminal region is deleted (Optn470T). Akin to C-terminal optineurin mutations found in patients with certain neurodegenerative diseases, Optn470T was expressed at substantially lower levels than the native protein, allowing assessment not only of the lack of Ub binding, but also of protein insufficiency. Embryonic lethality with incomplete penetrance was observed for 129 × C57BL/6 Optn470T/470T mice, but after further backcrossing to C57BL/6, offspring viability was restored. Moreover, the mice that survived were indistinguishable from wild type littermates and had normal immune cell distributions. Activation of NF-κB in Optn470T BMDM and BM-derived dendritic cells with TNF or via TLR4, T cells via the TCR, and B cells with LPS or anti-CD40 was normal. In contrast, optineurin and/or its Ub-binding function was necessary for optimal TANK binding kinase 1 and IRF3 activation, and both Optn470T BMDMs and bone marrow–derived dendritic cells had diminished IFN-β production upon LPS stimulation. Importantly, Optn470T mice produced less IFN-β upon LPS challenge. Therefore, endogenous optineurin is dispensable for NF-κB activation but necessary for optimal IRF3 activation in immune cells.
AID and Caspase 8 Shape the Germinal Center Response through Apoptosis
Authors: Boulianne Bryant , Rojas Olga L. , Haddad Dania , Zaheen Ahmad , Kapelnikov Anat , Nguyen Thanh , Li Conglei , Hakem Razq , Gommerman Jennifer L. , Martin Alberto
Published: November 2013

Germinal centers (GCs) are clusters of activated B cells that form in secondary lymphoid organs during a T-dependent immune response. B cells enter GCs and become rapidly proliferating centroblasts that express the enzyme activation-induced deaminase (AID) to undergo somatic hypermutation and class-switch recombination. Centroblasts then mature into centrocytes to undergo clonal selection. Within the GC, the highest affinity B cell clones are selected to mature into memory or plasma cells while lower affinity clones undergo apoptosis. We reported previously that murine Aicda−/− GC B cells have enhanced viability and accumulate in GCs. We now show that murine Aicda−/− GC B cells accumulate as centrocytes and inefficiently generate plasma cells. The reduced rate of plasma cell formation was not due to an absence of AID-induced DNA lesions. In addition, we show that the deletion of caspase 8 specifically in murine GC-B cells results in larger GCs and a delay in affinity maturation, demonstrating the importance of apoptosis in GC homeostasis and clonal selection.
α2β1 Integrin Regulates Th17 Cell Activity and Its Neutralization Decreases the Severity of Collagen-Induced Arthritis
Authors: El Azreq Mohammed-Amine , Boisvert Marc , Cesaro Annabelle , Pagé Nathalie , Loubaki Lionel , Allaeys Isabelle , Chakir Jamila , Poubelle Patrice E. , Tessier Philippe A. , Aoudjit Fawzi
Published: November 2013

Th17 cells play a critical role in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms by which these cells regulate the development of RA are not fully understood. We have recently shown that α2β1 integrin, the receptor of type I collagen, is the major collagen-binding integrin expressed by human Th17 cells. In this study, we examined the role of α2β1 integrin in Th17-mediated destructive arthritis in the murine model of collagen-induced arthritis (CIA). We found that α2β1 integrin is expressed on synovial Th17 cells from CIA mice and its neutralization with a specific mAb significantly reduced inflammation and cartilage degradation, and protected the mice from bone erosion. Blockade of α2β1 integrin led to a decrease in the number of Th17 cells in the joints and to a reduction of IL-17 levels in CIA mice. This was associated with an inhibition of receptor activator of NF-κB ligand levels and osteoclast numbers, and reduction of bone loss. We further show that α2β1 integrin is expressed on synovial Th17 cells from RA patients, and that its ligation with collagen costimulated the production of IL-17 by polarized human Th17 cells by enhancing the expression of retinoic acid receptor–related orphan receptor C through ERK and PI3K/AKT. Our findings provide the first evidence, to our knowledge, that α2β1 integrin is an important pathway in Th17 cell activation in the pathogenesis of CIA, suggesting that its blockade can be beneficial for the treatment of RA and other Th17-associated autoimmune diseases.
Cutting Edge: Leukotriene C4 Activates Mouse Platelets in Plasma Exclusively through the Type 2 Cysteinyl Leukotriene Receptor
Authors: Cummings Hannah E. , Liu Tao , Feng Chunli , Laidlaw Tanya M. , Conley Pamela B. , Kanaoka Yoshihide , Boyce Joshua A.
Published: November 2013

Leukotriene C4 (LTC4) and its extracellular metabolites, LTD4 and LTE4, mediate airway inflammation. They signal through three specific receptors (type 1 cys-LT receptor [CysLT1R], CysLT2R, and GPR99) with overlapping ligand preferences. In this article, we demonstrate that LTC4, but not LTD4 or LTE4, activates mouse platelets exclusively through CysLT2R. Platelets expressed CysLT1R and CysLT2R proteins. LTC4 induced surface expression of CD62P by wild-type mouse platelets in platelet-rich plasma (PRP) and caused their secretion of thromboxane A2 and CXCL4. LTC4 was fully active on PRP from mice lacking either CysLT1R or GPR99, but completely inactive on PRP from CysLT2R-null (Cysltr2−/−) mice. LTC4/CysLT2R signaling required an autocrine ADP-mediated response through P2Y12 receptors. LTC4 potentiated airway inflammation in a platelet- and CysLT2R-dependent manner. Thus, CysLT2R on platelets recognizes LTC4 with unexpected selectivity. Nascent LTC4 may activate platelets at a synapse with granulocytes before it is converted to LTD4, promoting mediator generation and the formation of leukocyte–platelet complexes that facilitate inflammation.
TAM Receptors Affect Adult Brain Neurogenesis by Negative Regulation of Microglial Cell Activation
Authors: Ji Rui , Tian Shifu , Lu Helen J. , Lu Qingjun , Zheng Yan , Wang Xiaomin , Ding Jixiang , Li Qiutang , Lu Qingxian
Published: November 2013

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3−/−Axl−/−Mertk−/− triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl−/−Mertk−/− double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.
Information, communication, travel behavior and accessibility
Authors: Wee Bert van , Geurs Karst , Chorus Caspar
Published: November 2013

Over the past two decades many papers have been published on the impact of Information and Communication Technologies (ICT) on travel behavior, but the literature focusing on the impact of ICT on accessibility is relatively scarce. In this paper we give an overview of the impact of ICT on four components of accessibility as distinguished by Geurs and van Wee (2004): (1) the land-use component, (2) the transportation component, (3) the temporal component, and (4) the individual component. Conclusions are that first much more literature exists on the potential impacts of ICT on travel behavior than on its impact on accessibility. Second, we argue that ICT potentially has an impact on all four components of the concept of accessibility. Literature exists on the direct impacts but fails to incorporate impacts due to the interactions between the accessibility components. Third, there seems to be a major challenge in developing accessibility measures and indicators that include ICT, including those that measure the utility of accessibility. Fourth, in the area of ICT’s impact on travel behavior, many research gaps exist. Examples are the impact of ICT on overall activity and trip patterns, the impact of ICT on activities and trips at the household and social-network level, ICT as a means of avoiding congestion or mitigating its effects, and the role of the phenomenon of self-selection in the context of ICT use. Finally, a major challenge is to develop models for activities, including ICT-impacts, which combine high levels of behavioral realism with (econometric) tractability.
A multidimensional decisions modeling framework for built space supply
Authors: Farooq Bilal , Miller Eric J. , Haider Murtaza
Published: November 2013

The spatial and temporal distribution of built space supply plays an important role in shaping urban form and thus the general travel pattern in an urban area. Within an integrated framework, we are interested in modeling the decisions of a builder in terms of when, where, what type, and how much built space to build. We present a multidimensional discrete-continuous model formulation for the built space supply decisions that are based on expected profit maximization. The framework is applied to estimate a model for supply of new office space in the greater Toronto area (GTA) for the 1986 to 2006 period. To our knowledge, this work is the first that models the where, when, how much, and what type of office space to build in a single econometric framework at a fairly disaggregate spatial zoning system. The results indicate risk taker behavior on the builders’ part, while market conditions and supply of resources (labor, construction cost, etc.) are also found to be important factors in decision making.
Stylised Worlds: Colour Separation Overlay in BBC Television Plays of the 1970s
Authors: Panos Leah
Published: November 2013

This essay aims to understand and interrogate the use of Colour Separation Overlay (CSO) as a mode of experimental production and aesthetic innovation in television drama in the 1970s. It sets out to do this by describing, accounting for and evaluating CSO as a production technique, considering the role of key production personnel, and analysing four specific BBC productions. Deploying methodologies of archival research, practitioner interview, and close textual analysis, the essay also delivers a significant reassessment of the role of the producer and designer in the conceptualisation and realisation of small-screen dramatic fiction.
‘I Want My MTS’: The Development of US Stereo Television
Authors: Lyons James
Published: November 2013

This article examines the development of stereo television broadcasting in America, in the wake of the Federal Communications Commission (FCC) ruling on Multichannel Television Sound (MTS) in 1984. It makes the case for understanding stereo broadcasting as a landmark special effect, playing a pivotal role in fashioning the medium's transformation over the last twenty-five years, helping to usher in an era of ‘home cinema’ and significantly enhancing the experiential and aesthetic coordinates of television programming.
‘And All is Real.’ Historical Spaces and Special F/X in HBO's Rome
Authors: Elliott Andrew B.R.
Published: November 2013

This essay explores the use of special effects in HBO's Rome. Looking at depictions of the classical past, it argues that special effects were traditionally used in the cinema to heighten verisimilitude by a sense of spectacle, whose cost put them out of reach of early historical television. With the increase in budgets and the greater affordability of special effects, however, this paper suggests that Rome signals a new kind of classical world on television, wherein special effects not only enhance verisimilitude by a kind of spectacle but also serve a narrative function.
Sanctuary: A Paradigm for Television in the Age of the Internet
Authors: Beeler Stan
Published: November 2013

This article considers the science fiction series Sanctuary (2008–11) as a paradigm for new genre fiction methodologies in both production methods and aesthetics. This series was first presented as a series of short webisodes in order to gauge public interest in the subject material as well as production techniques. It relies heavily upon a combination of green screen technology and CGI sets. The contemporary special effects technology is placed in historical context through a comparison with the use of optical printers. The article discusses new developments in acting techniques designed to compensate for green screen sets. Sanctuary's Steampunk aesthetics are also considered in relation to its reliance upon computerised special effects.
Visual Effects and Visceral Affect: ‘Tele-Affectivity’ and the Intensified Intimacy of Contemporary Television
Authors: Smit Alexia
Published: November 2013

This article considers television special effects which reveal the human body in visceral, affecting detail. Building on John Caldwell's work on ‘televisuality,’ this paper uses the term ‘tele-affectivity’ to describe the self-conscious foregrounding of the body as site of affect in three television dramas Grey's Anatomy, House and Fringe.
Factors driving mercury variability in the Arctic atmosphere and ocean over the past 30 years
Authors: Fisher Jenny A. , Jacob Daniel J. , Soerensen Anne L. , Amos Helen M. , Corbitt Elizabeth S. , Streets David G. , Wang Qiaoqiao , Yantosca Robert M. , Sunderland Elsie M.
Published: November 2013

Long‐term observations at Arctic sites (Alert and Zeppelin) show large interannual variability (IAV) in atmospheric mercury (Hg), implying a strong sensitivity of Hg to environmental factors and potentially to climate change. We use the GEOS‐Chem global biogeochemical Hg model to interpret these observations and identify the principal drivers of spring and summer IAV in the Arctic atmosphere and surface ocean from 1979–2008. The model has moderate skill in simulating the observed atmospheric IAV at the two sites (r ~ 0.4) and successfully reproduces a long‐term shift at Alert in the timing of the spring minimum from May to April (r = 0.7). Principal component analysis indicates that much of the IAV in the model can be explained by a single climate mode with high temperatures, low sea ice fraction, low cloudiness, and shallow boundary layer. This mode drives decreased bromine‐driven deposition in spring and increased ocean evasion in summer. In the Arctic surface ocean, we find that the IAV for modeled total Hg is dominated by the meltwater flux of Hg previously deposited to sea ice, which is largest in years with high solar radiation (clear skies) and cold spring air temperature. Climate change in the Arctic is projected to result in increased cloudiness and strong warming in spring, which may thus lead to decreased Hg inputs to the Arctic Ocean. The effect of climate change on Hg discharges from Arctic rivers remains a major source of uncertainty.
Quantitative description of induced seismic activity before and after the 2011 Tohoku‐Oki earthquake by nonstationary ETAS models
Authors: Kumazawa Takao , Ogata Yosihiko
Published: November 2013

The epidemic‐type aftershock sequence (ETAS) model is extended for application to nonstationary seismic activity, including transient swarm activity or seismicity anomalies, in a seismogenic region. The time‐dependent rates of both background seismicity and aftershock productivity in the ETAS model are optimally estimated from hypocenter data. These rates can provide quantitative evidence for abrupt or gradual changes in shear stress and/or fault strength due to aseismic transient causes such as triggering by remote earthquakes, slow slips, or fluid intrusions within the region. This extended model is applied to data sets from several seismic events including swarms that were induced by the M9.0 Tohoku‐Oki earthquake of 2011.
Change of apparent segmentation of the San Andreas fault around Parkfield from space geodetic observations across multiple periods
Authors: Barbot Sylvain , Agram Piyush , De Michele Marcello
Published: November 2013

Sequences of earthquakes are commonly represented as a succession of periods of interseismic stress accumulation followed by coseismic and postseismic phases of stress release. Because the recurrence time of large earthquakes is often greater than the available span of space geodetic data, it has been challenging to monitor the evolution of interseismic loading in its entire duration. Here we analyze large data sets of surface deformation at different key episodes around the Cholame, Parkfield and creeping segments of the San Andreas Fault that show evidence of significant deceleration of fault slip during the interseismic period. We compare the average fault slip rates before and after the 2004 Mw6 Parkfield earthquake, in the 1986–2004 and 2006–2012 periods, respectively, avoiding 2 years of postseismic deformation after 2004. Using a combination of GPS data from the Plate Boundary Observatory, the Southern California Earthquake Center Crustal Motion Map and the Bay Area Velocity Unification networks and interferometric synthetic aperture radar from the Advanced Land Observing Satellite (ALOS) and Envisat satellites, we show that the area of coupling at the transition between the Parkfield and Cholame segments appears larger later in the interseismic period than it does earlier on. While strong plate coupling is uniform across the Parkfield and Cholame segments in the 1986–2004 period, creep occurs south of the 2004 epicenter after 2006, making segmentation of the San Andreas Fault south of Parkfield more clearly apparent. These observations indicate that analyses of surface deformation late in the earthquake cycle may overestimate the area of plate coupling. A fault surface creeping much below plate rate may in some case be a region that does not promote earthquake nucleation but rather just be at a slower stage of its evolution. Our analysis also shows signs of large variation of slip velocity above and below plate rate in the creeping segment indicating that cycles of weakening and hardening can also be at play in dominantly aseismic areas.
On the dynamics of the seasonal variation in the South China Sea throughflow transport
Authors: Yang Jiayan , Lin Xiaopei , Wu Dexing
Published: November 2013

The Luzon Strait transport (LST) of water mass from the Pacific Ocean to the South China Sea (SCS) varies significantly with seasons. The mechanisms for this large variability are still not well understood. The steady‐state island rule, which is derived from a steady‐state model, is not applicable to seasonal time scale variations in a large basin like the Pacific Ocean. In this paper, we will use a theoretical model that is based on the circulation integral around the Philippines. The model relates the LST variability to changes in the boundary currents along the east coast of the Philippines, including the North Equatorial Current (NEC) Bifurcation Latitude (NECBL), the transports of Kuroshio and Mindanao Currents (KC and MC), and to the local wind‐stress forcing. Our result shows that a northward shift of the NECBL, a weakening of the KC or a strengthening of the MC would enhance the LST into the SCS. This relationship between the LST and the NEC‐KC‐MC is consistent with observations. The analytical result is tested by a set of idealized numerical simulations.
Subtropical‐polar jet interactions in Southern Plains dust storms
Authors: Kaplan Michael L. , Vellore Ramesh K. , Lewis John M. , Underwood S. Jeffrey , Pauley Patricia M. , Martin Jonathan E. , Rabin Robert M. , Krishnan R.
Published: November 2013

The origin of two separate Southern High Plains dust storms, which occurred over a 2 day period in February 2007, is traced to an interaction between the subtropical jet (STJ) and the polar jet (PJ). A large‐scale thermal wind imbalance resulting from the confluence of these two jets led to a series of mesoscale circulations that ultimately produced the dust storms. Understanding the connectivity between the dust storms with differing geometries is central to the present investigation. The study rests on the interpretation of analyses from upper air and surface observations complemented by imagery from satellites, the 32 km gridded data set from the North American Regional Reanalysis, and a fine‐resolution (6 km grid) simulation from the Weather Research and Forecasting model. Principal assertions from the present study are (1) scale interaction is fundamental to the creation of an environment conducive to dust storm development, (2) low to middle tropospheric mass adjustment is the primary response to a large‐scale imbalance, (3) the mesoscale mass adjustment is associated with circulations about a highly accelerative jet streak resulting from the merger of the PJ and STJ, (4) the structure of the jet streak resulting from this merger governs the evolution of the geometry of the dust plumes, with plumes that initially had a straight‐line orientation developing a semicircular geometry, and (5) it is concluded that improvements in dust storm prediction will depend on an augmentation to the upper air network in concert with a flow‐dependent data assimilation strategy.
On the equilibrium profile of river beds
Authors: Bolla Pittaluga M. , Luchi R. , Seminara G.
Published: November 2013

Despite the wide spectrum of perturbations of flow and sediment transport experienced by rivers as a result of hydrologic variations, the paradigm of morphodynamic equilibrium has long been present in the geomorphological literature where it is traditionally associated with the semiempirical notion of formative discharge, whereby the unsteady forcing is taken as morphologically equivalent to some effective steady forcing. Here we investigate the mechanisms responsible for maintaining a quasi‐equilibrium bed profile of a river reach sufficiently short to have no significant tributary inputs. More importantly, we assume the channel banks to be fixed, hence, the case we have in mind is that of rivers protected by levees which cannot respond to hydrologic forcing by changing their width like natural rivers. Employing a 1‐D model of river morphodynamics, we first determine the equilibrium profile of the river reach for given steady forcing conditions and discuss the capability of this approach for interpreting bed profiles observed in the field by applying it to the terminal reach of the Magra River, Italy. Field observations turn out to be reasonably well fitted by the equilibrium profile associated with a steady effective discharge, which however differs from the typical formative discharge (mean annual flood) for natural channels with erodible banks. Finally, we clarify how fluctuations of the hydrodynamic forcing associated with the recorded historical sequence of hydrologic events of variable intensities have acted to maintain the river equilibrium.
Nutritional status in parasitized and nonparasitized children from two districts of buenos aires, Argentina
Authors: Orden Alicia B. , Apezteguía María C. , Ciarmela María L. , Molina Nora B. , Pezzani Betina C. , Rosa Diana , Minvielle Marta C.
Published: November 2013

The Program for the Control of Intestinal Parasites and Nutrition was designed to intervene in small communities to prevent and control the effects of parasitic infections on children's health. Objectives: To analyze the association between nutritional status and parasitic infection in suburban and rural children from Buenos Aires, Argentina. Methods: Nutritional status was assessed by anthropometric (weight, height, BMI, skinfolds, upper arm circumference, muscle, and fat upper arm areas) and biochemical (Hb, Ca, Mg, Zn, and Cu) indicators. Parasitological analysis were made on both serial stool and perianal swab samples. A total of 708 children aged 3–11 were measured. The biochemical analysis included 217 blood samples and the parasitological study included 284 samples. Results: Anthropometric status was similar in both settings with low rates of underweight and stunting (<6%), and high rates of overweight (∼17%) and obesity (∼12%). Ca deficiency was significantly higher in suburban children where 80% of them were hypocalcemic. Around 70% of fecal samples contained parasites. Among infected children, the most prevalent species were Blastocystis hominis and Enterobius vermicularis (∼43%) followed by Giardia lamblia (∼17%). Differences in parasitological status between districts were not significant. In the suburban district parasitized children were lighter, shorter, and had a lower upper arm circumference than their non‐infected peers. No differences in anthropometric status were seen among infected and uninfected rural children. Conclusions: The results suggest an association between intestinal parasites and physical growth in suburban children. Rural children seem to be protected against the effects of parasitic infection. Am. J. Hum. Biol. 26:73–79, 2014. © 2013 Wiley Periodicals, Inc.
The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens
Authors: Oleinick Arthur
Published: November 2013

Background

OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens.

Methods

JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992–2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case‐control study of EPA's Toxic Release Inventory 1988–2009 data compared carcinogen and non‐carcinogens' releases.

Results

The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569–459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non‐carcinogens.

Discussion

The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. Am. J. Ind. Med. 57:138–152, 2014. © 2013 Wiley Periodicals, Inc.
Novel hypoglycemic injury mechanism: N‐methyl‐D‐aspartate receptor–mediated white matter damage
Authors: Yang Xin , Hamner Margaret A. , Brown Angus M. , Evans Richard D. , Ye Zu‐Cheng , Chen Shengdi , Ransom Bruce R.
Published: November 2013

Objective

Hypoglycemia is a common adverse event and can injure central nervous system (CNS) white matter (WM). We determined whether glutamate receptors were involved in hypoglycemic WM injury.

Methods

Mouse optic nerves (MON), CNS WM tracts, were maintained at 37°C with oxygenated artificial cerebrospinal fluid (ACSF) containing 10mM glucose. Aglycemia was produced by switching to 0 glucose ACSF. Supramaximal compound action potentials (CAPs) were elicited using suction electrodes, and axon function was quantified as the area under the CAP. Amino acid release was measured using high‐performance liquid chromatography. Extracellular lactate concentration ([lactate−]o) was measured using an enzyme electrode.

Results

About 50% of MON axons were injured after 60 minutes of aglycemia (90% after 90 minutes); injury extent was not affected by animal age. Blockade of N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptors improved recovery after 90 minutes of aglycemia by 250%. Aglycemic injury was increased by reducing [Mg2+]o or increasing [glycine]o, and decreased by lowering pHo, expected results for NMDA receptor‐mediated injury. pHo increased during aglycemia due to a drop in [lactate−]o. Aglycemic injury was dramatically reduced in the absence of [Ca2+]o. Extracellular aspartate, a selective NMDA receptor agonist, increased during aglycemia ([glutamate]o fell).

Interpretation

Aglycemia injured WM by a unique excitotoxic mechanism involving NMDA receptors (located primarily on oligodendrocytes). During WM aglycemia, the selective NMDA agonist aspartate is released, probably from astrocytes. Injury is mediated by Ca2+ influx through aspartate‐activated NMDA receptors made permeable by an accompanying alkaline shift in pHo caused by a fall in [lactate−]o. These insights have important clinical implications. Ann Neurol 2014;75:492–507
Metallothioneins as dynamic markers for brain disease in lysosomal disorders
Authors: Cesani Martina , Cavalca Eleonora , Macco Romina , Leoncini Giuseppe , Terreni Maria Rosa , Lorioli Laura , Furlan Roberto , Comi Giancarlo , Doglioni Claudio , Zacchetti Daniele , Sessa Maria , Scherzer Clemens R. , Biffi Alessandra
Published: November 2013

Objective

To facilitate development of novel disease‐modifying therapies for lysosomal storage disorder (LSDs) characterized by nervous system involvement such as metachromatic leukodystrophy (MLD), molecular markers for monitoring disease progression and therapeutic response are needed. To this end, we sought to identify blood transcripts associated with the progression of MLD.

Methods

Genome‐wide expression analysis was performed in primary T lymphocytes of 24 patients with MLD compared to 24 age‐ and sex‐matched healthy controls. Genes associated with MLD were identified, confirmed on a quantitative polymerase chain reaction platform, and replicated in an independent patient cohort. mRNA and protein expression of the prioritized gene family of metallothioneins was evaluated in postmortem patient brains and in mouse models representing 6 other LSDs. Metallothionein expression during disease progression and in response to specific treatment was evaluated in 1 of the tested LSD mouse models. Finally, a set of in vitro studies was planned to dissect the biological functions exerted by this class of molecules.

Results

Metallothionein genes were significantly overexpressed in T lymphocytes and brain of patients with MLD and generally marked nervous tissue damage in the LSDs here evaluated. Overexpression of metallothioneins correlated with measures of disease progression in mice and patients, whereas their levels decreased in mice upon therapeutic treatment. In vitro studies indicated that metallothionein expression is regulated in response to oxidative stress and inflammation, which are biochemical hallmarks of lysosomal storage diseases.

Interpretation

Metallothioneins are potential markers of neurologic disease processes and treatment response in LSDs.Ann Neurol 2014;75:127–137
Self‐welding 1‐butene/ethylene copolymers from metallocene catalysts: Structure, morphology, and mechanical properties
Authors: Marega Carla , Spataro Stefano , Fassone Elisa , Camurati Isabella , Marigo Antonio
Published: November 2013

Samples of random copolymers consisting of 1‐butene modified with a low ethylene content (4, 5, 8% by weight) produced with metallocene catalysts were studied to elucidate the polymorphic behavior of this new class of materials and to characterize them from a structural, morphological, and mechanical point of view. The samples cooled down from the melt are in amorphous phase and crystallize in a mixture of form I and I′ or in pure form I′ with aging time, according to the C2 content. Infrared and nuclear magnetic resonance spectroscopy, X‐ray diffraction and microscopic techniques were used to follow the changes of the material with aging time and to correlate the structural and morphological behavior with the peculiar mechanical properties that differentiate the samples with increasing C2 content. The presence, in the aged samples with higher C2 content, of the pure form I′ induces the peculiar ability to self‐welding and these copolymers combine high flexibility with good elasticity and ductility and can be processed directly or used as modifying agents in polymers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40119.
Small diameter tubular structure design using solvent‐free textile techniques
Authors: Chrzanowska Olga , Struszczyk Marcin Henryk , Krucinska Izabella
Published: November 2013

The aim of research was to elaborate the non‐biodegradable (made of polypropylene (PP)) and resorbable (made of polylactide (PLA)) tubular fibrous structures for the reconstruction of the vascular vessels. For the mentioned structures design, nonconventional manufacturing techniques such as melt blown, melt electrospinning, and melt electroblowing were used. Three techniques were chosen as methods allowing on the fibrous structures manufacture containing fibers in nano‐ or submicro‐size diameter. Other advantages of free‐solvent technique use is the reduction in the clinical adverse events associated with solvent resided in the fibrous structure during the fabrication. The tubular fibrous structures of PP and PLA using above‐mentioned techniques were designed. In first stage, the analysis of the processing parameters influence on the nonbiodegradable and biodegradable tubular structures fiber diameter was performed. Subsequently, the validation step was the analysis of the influence of processing parameters on PP and PLA structural properties for each manufacturing techniques was investigated. The research results confirmed the ability of the tubular structures manufacture with various fiber diameter depending on the applied technique and processing parameters. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40147.
Miniemulsion polymerization of fluorinated siloxane‐acrylate latex and the application as waterborne textile finishing agent
Authors: Guo Longhai , Jiang Sijiu , Qiu Teng , Zhang Shengwen , He Lifan , Tan Jie , Li Xiaoyu
Published: November 2013

Fluorinated siloxane–acrylate polymer latex was synthesized via miniemulsion polymerization, which was carried out by pseudo one‐step method. In the synthesis protocol, the monomers of octamethylclotetrasiloxane (D4), tetravinyltetramethylcyclotetrasiloxane (D4v), methyl methylacrylate, butyl acrylate, N‐methylol acrylamide, and dodecafluoroheptyl methacrylate (DFMA) were first mixed and homogenized into a miniemulsion, which was stabilized by dedecybenzene sulfonic acid. The ring‐opening polymerization of cyclosiloxane was then steadily performed under miniemulsion conditions and followed by the postaddition of radical initiators to initiate the polymerization of acrylate and DFMA monomers. The influences on the emulsion properties by acrylic monomer with different addition protocol were investigated in this work. In addition, the synthesized latexes were characterized by using dynamic laser scattering, transmission electron microscope, differential scanning calorimetry, and Fourier transform infrared spectroscopy. These results indicated that the introduction of D4v in the latex can successfully suppress the phase separation between the thermodynamically incompatible components for the formation of uniform hybrid latex particles. The further application of the as‐synthesized latex was investigated as a new kind of waterborne textile finishing agent. Moreover, the influences of the content of D4v and DFMA on the finishing properties, especially for the softness, the water repellence, and the antimoisture properties, were systematically studied in this work. With a proper design on the content of the D4v and DFMA, stable textile finishing emulsion was prepared, which can endow the fabric both desirable softness and excellent water resistances. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40161.