bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXPLORING THE DIVERSITY OF GREEN BUILDINGS
Authors: Bornais Crystal 
Published: October 2012

INTRODUCTION 25 years of experience in sustainable architecture and 10 years of experience in designing LEED-certified buildings and providing LEED consulting to projects has allowed our firm, Prairie Architects Inc., to collect a great deal of experience on green buildings. Through the years, we have come to realize the great diversity of what it means to be a green building and the multitude of avenues that can be followed in order to pursue that end goal. Factors such as building type, location, and owner representation can have a dramatic impact on what sustainability opportunities are available to a project. This article examines the process of determining the path to a green building through three case studies of recently constructed projects in Manitoba, Canada. Through each case study we will reflect on the challenges encountered as well as highlight the successes and opportunities that were found.
Des inégalités garantes de la protection des Calanques ?
Authors: Deldrève Valérie , Hérat Arlette 
Published: October 2012

Le futur Parc national des calanques, aux portes d’une agglomération de près de deux millions d’habitants, est porteur de nombreux enjeux liés à la proximité de la ville. Ceux-ci sont mis en débat dans des arènes instituées par le GIP, et dans celles plus spontanées qu’animent des collectifs de résidents — usagers locaux, dont les pratiques et la nécessaire implication sont reconnues par la nouvelle loi sur les parcs (2006). L’objectif de notre article est de montrer comment au nom de la protection de la nature sont finalement renforcées des formes plurielles d’inégalités environnementales. Ni la dimension périurbaine du parc national, ni sa mission d’accueil n’ont permis de faire valoir des préoccupations en termes d’égalité d’accès ou d’ouverture au public. L’occultation de cette périurbanité, voire son assimilation à ses seuls impacts négatifs sur le milieu naturel (sur ou mal-fréquentation, pollutions), ainsi que la délégitimation des usages du plus grand nombre (« non-traditionnels » et « moins méritants ») l’explique en grande partie. Afin de compléter notre réponse et de mieux mettre en exergue l’articulation entre ville et nature dans le projet de parc, nous focalisons ensuite sur l’exemple du quartier de la Cayolle, porte d’accès viaire de la calanque habitée de Sormiou (cabanons). Les interactions entre politique de préservation et stratégie de requalification urbaine y sont patentes. Mais l’évitement des questions qu’elles posent en termes d’inégalités n’a pas permis au parc en constitution d’être un catalyseur de développement social pour le quartier.
The B10 Idd9.3 Locus Mediates Accumulation of Functionally Superior CD137+ Regulatory T Cells in the Nonobese Diabetic Type 1 Diabetes Model
Authors: Kachapati Kritika , Adams David E. , Wu Yuehong , Steward Charles A. , Rainbow Daniel B. , Wicker Linda S. , Mittler Robert S. , Ridgway William M. 
Published: October 2012

Abstract
CD137 is a T cell costimulatory molecule encoded by the prime candidate gene (designated Tnfrsf9) in NOD.B10 Idd9.3 congenic mice protected from type 1 diabetes (T1D). NOD T cells show decreased CD137-mediated T cell signaling compared with NOD.B10 Idd9.3 T cells, but it has been unclear how this decreased CD137 T cell signaling could mediate susceptibility to T1D. We and others have shown that a subset of regulatory T cells (Tregs) constitutively expresses CD137 (whereas effector T cells do not, and only express CD137 briefly after activation). In this study, we show that the B10 Idd9.3 region intrinsically contributes to accumulation of CD137+ Tregs with age. NOD.B10 Idd9.3 mice showed significantly increased percentages and numbers of CD137+ peripheral Tregs compared with NOD mice. Moreover, Tregs expressing the B10 Idd9.3 region preferentially accumulated in mixed bone marrow chimeric mice reconstituted with allotypically marked NOD and NOD.B10 Idd9.3 bone marrow. We demonstrate a possible significance of increased numbers of CD137+ Tregs by showing functional superiority of FACS-purified CD137+ Tregs in vitro compared with CD137− Tregs in T cell-suppression assays. Increased functional suppression was also associated with increased production of the alternatively spliced CD137 isoform, soluble CD137, which has been shown to suppress T cell proliferation. We show for the first time, to our knowledge, that CD137+ Tregs are the primary cellular source of soluble CD137. NOD.B10 Idd9.3 mice showed significantly increased serum soluble CD137 compared with NOD mice with age, consistent with their increased numbers of CD137+ Tregs with age. These studies demonstrate the importance of CD137+ Tregs in T1D and offer a new hypothesis for how the NOD Idd9.3 region could act to increase T1D susceptibility.
TLR15 Is Unique to Avian and Reptilian Lineages and Recognizes a Yeast-Derived Agonist
Authors: Boyd Amy C. , Peroval Marylene Y. , Hammond John A. , Prickett Michael D. , Young John R. , Smith Adrian L. 
Published: October 2012

Abstract
The TLRs represent a family of pattern recognition receptors critical in the induction of vertebrate immune responses. Between 10 and 13 different TLR genes can be identified in each vertebrate species, with many represented as orthologous genes in different species. The agonist specificity of orthologous TLR is also highly conserved. In contrast, TLR15 can only be identified in avian and reptilian genomes, suggesting that this receptor arose ∼320 million years ago after divergence of the bird/reptile and mammalian lineages. Transfection of a constitutively active form of chicken TLR15 led to NF-κB activation in HEK293 cells and induced cytokine mRNA upregulation in chicken cell lines. Full-length TLR15 mediated NF-κB induction in response to lysates from yeast, but not those derived from viral or bacterial pathogens, or a panel of well-characterized TLR agonists. TLR15 responses were induced by whole-cell lysates derived from Candida albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe, but not zymosan preparations from S. cerevisiae. The ability of yeast lysate to activate TLR15-dependent NF-κB pathways (in transfection assays) or stimulate IL-1β mRNA upregulation in chicken macrophages was abrogated by heat inactivation or pre-exposure of the lysate to PMSF. Identification of yeast as an agonist source for TLR15 provides a functional framework for consideration of this TLR within the context of pattern recognition receptor evolution and may impact on the development of novel adjuvants.
p16INK4a Exerts an Anti-Inflammatory Effect through Accelerated IRAK1 Degradation in Macrophages
Authors: Murakami Yousuke , Mizoguchi Fumitaka , Saito Tetsuya , Miyasaka Nobuyuki , Kohsaka Hitoshi 
Published: October 2012

Abstract
Induction of cyclin-dependent kinase (CDK) inhibitor gene p16INK4a into the synovial tissues suppresses rheumatoid arthritis in animal models. In vitro studies have shown that the cell-cycle inhibitor p16INK4a also exerts anti-inflammatory effects on rheumatoid synovial fibroblasts (RSF) in CDK activity-dependent and -independent manners. The present study was conducted to discern how p16INK4a modulates macrophages, which are the major source of inflammatory cytokines in inflamed synovial tissues. We found that p16INK4a suppresses LPS-induced production of IL-6 but not of TNF-α from macrophages. This inhibition did not depend on CDK4/6 activity and was not observed in RSF. p16INK4a gene transfer accelerated LPS-triggered IL-1R–associated kinase 1 (IRAK1) degradation in macrophages but not in RSF. The degradation inhibited the AP-1 pathway without affecting the NF-κB pathway. Treatment with a proteosome inhibitor prevented the acceleration of IRAK1 degradation and downregulation of the AP-1 pathway. THP-1 macrophages with forced IRAK1 expression were resistant to the p16INK4a-induced IL-6 suppression. Senescent macrophages with physiological expression of p16INK4a upregulated IL-6 production when p16INK4a was targeted by specific small interfering RNA. These findings indicate that p16INK4a promotes ubiquitin-dependent IRAK1 degradation, impairs AP-1 activation, and suppresses IL-6 production. Thus, p16INK4a senescence gene upregulation inhibits inflammatory cytokine production in macrophages in a different way than in RSF.
IL-17 Receptor Adaptor Protein Act1/CIKS Plays an Evolutionarily Conserved Role in Antiviral Signaling
Authors: Ryzhakov Grigory , Blazek Katrina , Lai Cheryl Chuk-ke , Udalova Irina A. 
Published: October 2012

Abstract
Double-stranded RNA-induced antiviral gene expression in mammalian cells requires activation of IFN regulatory factor 3 (IRF3). In this study, we show that the IL-17R adaptor protein Act1/CIKS is involved in this process. Small interfering RNA-mediated knockdown of Act1 in primary human skin fibroblasts specifically attenuates expression of IFN-β and IFN-stimulated antiviral genes induced by a synthetic viral mimic, polyinosinic-polycytidylic acid. Ectopic expression of Act1 potentiates the IRF3-driven expression of a synthetic reporter construct as well as the induction of antiviral genes. We demonstrate that this effect is dependent on the ability of Act1 to functionally and physically interact with IκB kinase ε (IKKε), a known IRF3 kinase, and IRF3: 1) Act1 binds IKKε and IRF3; 2) Act1-induced IRF3 activation can be blocked specifically by coexpression of a catalytically inactive mutant of IKKε; and 3) mutants of IRF3, either lacking the C terminus or mutated at the key phosphorylation sites, important for its activation by IKKε, do not support Act1-dependent IRF3 activation. We also show that a zebrafish Act1 protein is able to trigger antiviral gene expression in human cells, which suggests an evolutionarily conserved function of vertebrate Act1 in the host defense against viruses. On the whole, our study demonstrates that Act1 is a component of antiviral signaling.
NK Cell Lytic Granules Are Highly Motile at the Immunological Synapse and Require F-Actin for Post-Degranulation Persistence
Authors: Mace Emily M. , Wu Winona W. , Ho Tina , Mann Shaina S. , Hsu Hsiang-Ting , Orange Jordan S. 
Published: October 2012

Abstract
The formation of a dynamic, actin-rich immunological synapse (IS) and the polarization of cytolytic granules toward target cells are essential to the cytotoxic function of NK cells. Following polarization, lytic granules navigate through the pervasive actin network at the IS to degranulate and secrete their toxic contents onto target cells. We examined lytic granule motility and persistence at the cell cortex of activated human NK cells, using high-resolution total internal reflection microscopy and highly quantitative analysis techniques. We illustrate that lytic granules are dynamic and observe substantial motility at the plane of the cell cortex prior to, but not after, degranulation. We also show that there is no significant change in granule motility in the presence of Latrunculin A (which induces actin depolymerization), when added after granule polarization, but that there is a significant decrease in lytic granule persistence subsequent to degranulation. Thus, we show that lytic granules are highly dynamic at the cytolytic human NK cell IS prior to degranulation and that the persistence of granules at the cortex following exocytosis requires the integrity of the synaptic actin network.
Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity
Authors: Kellner Christian , Maurer Tina , Hallack Daniela , Repp Roland , van de Winkel Jan G. J. , Parren Paul W. H. I. , Valerius Thomas , Humpe Andreas , Gramatzki Martin , Peipp Matthias 
Published: October 2012

Abstract
Induced self expression of the NKp30 ligand B7-H6 facilitates NK cell-mediated elimination of stressed cells. A fusion protein consisting of the ectodomain of B7-H6 and the CD20 single-chain fragment variable 7D8 was generated to mimic an induced self phenotype required for NK cell-mediated target cell elimination. B7-H6:7D8 had bifunctional properties as reflected by its ability to simultaneously bind to the CD20 Ag and to the NKp30 receptor. B7-H6:7D8 bound by CD20+ lymphoma cells activated human NK cells and triggered degranulation. Consequently, the immunoligand B7-H6:7D8 induced killing of lymphoma-derived cell lines as well as fresh tumor cells from chronic lymphocytic leukemia or lymphoma patients. B7-H6:7D8 was active at nanomolar concentrations in a strictly Ag-specific manner and required interaction with both CD20 and NKp30. Remarkably, NK cell cytotoxicity was further augmented by concomitant activation of Fcγ receptor IIIa or NK group 2 member D. Thus, B7-H6:7D8 acted synergistically with the CD20 Ab rituximab and the immunoligand ULBP2:7D8, which was similarly designed as B7-H6:7D8 but engaging the NK group 2 member D receptor. In conclusion, to our knowledge, B7-H6:7D8 represents the first Ab-based molecule stimulating NKp30-mediated NK cell cytotoxicity for therapeutic purposes and provides proof of concept that Ag-specific NKp30 engagement may represent an innovative strategy to enhance antitumoral NK cell cytotoxicity.
Highly Restricted Usage of Ig H Chain VH14 Family Gene Segments in Slp65-Deficient Pre-B Cell Leukemia in Mice
Authors: Ta Van B. T. , de Bruijn Marjolein J. W. , Matheson Louise , Zoller Markus , Bach Martina P. , Wardemann Hedda , Jumaa Hassan , Corcoran Anne , Hendriks Rudi W. 
Published: October 2012

Abstract
Mice deficient for the adapter protein Slp65 (also known as Blnk), a key component in precursor-BCR (pre-BCR) signaling, spontaneously develop pre-B cell leukemia. In these leukemias, proliferation is thought to be driven by constitutive Jak3/Stat5 signaling, mostly due to autocrine production of IL-7, together with high surface expression of the pre-BCR. In this study, we investigated whether particular IgH specificities would predispose Slp65-deficient pre-B cells to malignant transformation. Whereas VH-D-JH junctions were diverse, we found highly restricted Ig VH gene usage: 55 out of 60 (∼92%) leukemias used a VH14/SM7-family gene, mainly VH14-1 and VH14-2. When combined with surrogate or conventional L chains, these VH14 IgH chains did not provide increased proliferative signals or exhibit enhanced poly- or autoreactivity. We therefore conclude that pre-BCR specificity per se did not contribute to oncogenic transformation. Remarkably, in a high proportion of Slp65-deficient leukemias, the nonexpressed IgH allele also harbored a VH14-family rearrangement (10 out of 50) or was in the germline configuration (10 out of 50). VH14-1 and VH14-2 gene regions differed from their neighboring VH genes in that they showed active H3K4me3 histone modification marks and germline transcription at the pro-B cell stage in Rag1-deficient mice. Taken together, these findings demonstrate that in Slp65-deficient mice, malignant transformation is largely limited to particular pre-B cells that originate from pro-B cells that had restricted IgH VH region accessibility at the time of VH-to D-JH recombination.
Trogocytosis Results in Sustained Intracellular Signaling in CD4+ T Cells
Authors: Osborne Douglas G. , Wetzel Scott A. 
Published: October 2012

Abstract
CD4+ T cells capture membrane and membrane-bound molecules from APCs directly from the immunological synapse in a process termed trogocytosis. The function and biological consequences of trogocytosis are largely unknown. In this study, we examine the biological significance of this phenomenon on the trogocytosis-positive T cell. We used murine fibroblasts expressing GFP-tagged I-Ek molecules loaded with a covalently attached antigenic peptide (moth cytochrome c 88–103) to present Ag to primary TCR transgenic T cells. Using a combination of high-resolution light microscopy and flow cytometry, we show that the trogocytosed molecules are retained on the surface of the T cell in association with the TCR and elevated phosphorylated ZAP-70, phosphorylated tyrosine, and phosphorylated ERK 1/2. Through the use of the Src inhibitor PP2, we demonstrate that trogocytosed molecules directly sustain TCR signaling. In addition, after removal of APC, trogocytosis-positive cells preferentially survive in culture over several days. These novel findings suggest that trogocytosed molecules continue to engage their receptors on the T cell surface and sustain intracellular signaling leading to selective survival of these cells.
The Tumor Suppressor CYLD Controls the Function of Murine Regulatory T Cells
Authors: Reissig Sonja , Hövelmeyer Nadine , Weigmann Benno , Nikolaev Alexei , Kalt Bettina , Wunderlich Thomas F. , Hahn Matthias , Neurath Marcus F. , Waisman Ari 
Published: October 2012

Abstract
CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2. We have previously described a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8). In this study, we demonstrate that CYLD plays a critical role in Treg development and function. T cells of CYLDex7/8 mice had a hyperactive phenotype manifested by increased production of inflammatory cytokines and constitutive activation of the NF-κB pathway. Furthermore, the amount of Foxp3+ regulatory T cells in these mice was markedly enhanced in thymus and peripheral organs. Importantly, these regulatory T cells displayed decreased expression levels of CD25 and CTLA-4 associated with impaired suppressive capacity. Hence, our data emphasize an essential role of CYLD in maintaining T cell homeostasis as well as normal T regulatory cell function, thereby controlling abnormal T cell responses.
Thymidine Phosphorylase Gene Expression in Stage III Colorectal Cancer
Authors: Lindskog Elinor B. , Wettergren Yvonne , Odin Elisabeth , Gustavsson Bengt , Derwinger Kristoffer 
Published: October 2012

Background The thymidine phosphorylase (TP) enzyme has several tumor-promoting functions. The aim of this study was to explore TP gene expression in relation to clinical and histopathological data obtained from patients with stage III colorectal cancer. Methods and Results TP gene expression was analyzed by real-time quantitative PCR in tumor and mucosa samples from 254 patients. TP gene expression in tumors correlated with lymph node staging, with higher expression relating to a higher number of positive nodes and a worse N-stage. Higher TP expression was also associated with a worse histological tumor grade. Patients with rectal cancer had significantly higher TP expression in mucosa and tumors compared with patients having colon cancer. Conclusion Higher intratumoral TP expression appears to be related to a worse N stage, and thus, with a worse prognosis. TP gene expression measured in a preoperative biopsy could be of interest in preoperative staging.
Low Educational Status, Smoking, and Multidisciplinary Team Experience Predict Hospital Length of Stay after Bariatric Surgery
Authors: Marchini Julio F.M. , Souza Fernanda L.N. , Schmidt Andre , Cunha Selma F.C. , Salgado Wilson , Marchini Julio S. , Nonino Carla B. , Ceneviva Reginaldo , Santos Jose E.D. 
Published: October 2012

Objective The objective of the present study was to identify new risk factors associated with longer hospitalization following bariatric surgery. Methods Patient clinical, social, and biochemical data in addition to multidisciplinary team experience were analyzed in a cohort that included all patients undergoing bariatric surgery at our hospital. The primary outcome was length of hospital stay (LOS). Mortality was recorded to validate the obesity surgery mortality risk score (OS-MRS). Results This study included 299 sequential patients, 41 ± 10 years of age, and BMI of 50 ± 8 kg/m2 who underwent bariatric surgery. Two thirds (196) of patients were hypertensive, a third (86) were diabetic and a third (91) were current or former smokers. Overall, LOS was 8 ± 5 days. The predictors of a longer LOS were smoking ( P < 0.05) and less multidisciplinary team experience ( P < 0.05). Looking at only the last three years of data, LOS was 6 ± 5 days, and the predictors of a longer LOS were low educational attainment ( P < 0.02) and smoking ( P < 0.01) but not team experience. The global mortality was 2.6%, with the OS-MRS identifying a high-risk group. Conclusion Excluding the initial learning phase, longer LOS independent predictors were patient low educational attainment and smoking. These predictors can help guide care to reduce complications.
Two‐stage Kalman filter‐based actuator/surface fault identification and reconfigurable control applied to F‐16 fighter dynamics
Authors: Hajiyev Chingiz 
Published: October 2012

SUMMARYIn this study, an active fault‐tolerant control technique with reconfiguration against actuator/surface failures is presented. A two‐stage Kalman filter is designed in order to identify the control distribution matrix elements that correspond to the faulty actuator/surface; thus, the control reconfiguration is carried out using this identified control distribution matrix. The actuator/surface fault identification problem is solved through two jointly operating Kalman filters: the first one is for the estimation of the control distribution matrix elements that correspond to the faulty actuator/surface, and the second one is for the estimation of the state variables of the aircraft model.A structure for the active fault‐tolerant aircraft flight control system with reconfiguration against actuator/surface failures is presented. A control reconfiguration action is taken in order to keep the performance of the impaired aircraft the same as that of the unimpaired aircraft.In simulations, the nonlinear flight dynamics of an AFTI/F‐16 fighter model is considered, and the performance of the proposed actuator/surface failure identification and reconfigurable control schemes are examined for this model. Copyright © 2012 John Wiley & Sons, Ltd.
Biomimetic Membrane System Composed of a Composite Interpenetrating Hydrogel Film and a Lipid Bilayer
Authors: Stidder Barry , Alcaraz Jean‐Pierre , Liguori Lavinia , Khalef Nawel , Bakri Aziz , Watkins Erik B. , Cinquin Philippe , Martin Donald K. 
Published: October 2012

AbstractA simple way to form an interpenetrating hydrogel (IPH) by combining a layer‐by‐layer polyelectrolyte membrane with agarose is reported. The formed IPH membrane is more robust and easily manipulated compared to a polyelectrolyte membrane with the same number of layers. The IPH has good diffusion characteristics and retains the advantageous surface charge from the polyectrolyte composition that facilitates the adsorption of a stable lipid bilayer. The stable adsorption of a lipid bilayer on the IPH creates a biomimetic membrane system that is optimized for utilization in a diffusion chamber.