bluuebunny/crossref_metadata_2025 huggingface dataset:
Procalcitonin Is a Specific Marker for Detecting Bacterial Infection in Patients with Rheumatoid Arthritis
Authors: SATO HIROE , TANABE NAOHITO , MURASAWA AKIRA , OTAKI YASUHIRO , SAKAI TAKEHITO , SUGAYA TOSHIAKI , ITO SATOSHI , OTANI HIROSHI , ABE ASAMI , ISHIKAWA HAJIME , NAKAZONO KIYOSHI , KURODA TAKESHI , NAKANO MASAAKI , NARITA ICHIEI
Published: July 2012

Objective.

Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by many complications, and serious infections are associated with many of the advanced therapeutics used to treat it. We assessed serum procalcitonin (PCT) levels to distinguish bacterial infection from other complications in patients with RA.

Methods.

One hundred eighteen patients experiencing an RA flare, noninfectious complication of RA or its treatment, nonbacterial infection, or bacterial infection were studied. Serum PCT concentrations were determined with a chemiluminescent enzyme immunoassay.

Results.

All patients experiencing an RA flare showed negative PCT levels (≤ 0.1 ng/ml; n = 18). The PCT level was higher in the bacterial infection group (25.8% had levels ≥ 0.5 ng/ml) than in the other 3 groups (0.0–4.3% had levels ≥ 0.5 ng/ml) and the difference was significant among groups (p = 0.003). Conversely, no statistically significant difference was observed among the groups with C-reactive protein (CRP) concentration ≥ 0.3 mg/dl (p = 0.513), white blood cell (WBC) count > 8500/mm3 (p = 0.053), or erythrocyte sedimentation rate (ESR) > 15 mm/h (p = 0.328). The OR of high PCT level (≥ 0.5 ng/ml) for detection of bacterial infection was 19.13 (95% CI 2.44–149.78, p = 0.005). Specificity and positive likelihood ratio of PCT ≥ 0.5 ng/ml were highest (98.2% and 14.33, respectively) for detection of bacterial infection, although the sensitivity was low (25.8%).

Conclusion.

Serum PCT level is a more specific marker for detection of bacterial infection than either CRP, ESR, or WBC count in patients with RA. High PCT levels (≥ 0.5 ng/ml) strongly suggest bacterial infection. However, PCT < 0.5 ng/ml, even if < 0.2 ng/ml, does not rule out bacterial infection and physicians should treat appropriately.
Ultrasound in the Assessment of Pulmonary Fibrosis in Connective Tissue Disorders: Correlation with High-Resolution Computed Tomography
Authors: TARDELLA MARIKA , GUTIERREZ MARWIN , SALAFFI FAUSTO , CAROTTI MARINA , ARIANI ALARICO , BERTOLAZZI CHIARA , FILIPPUCCI EMILIO , GRASSI WALTER
Published: July 2012

Objective.

To investigate the correlation between ultrasound (US) B-lines and high-resolution computed tomography (HRCT) findings in the assessment of pulmonary fibrosis (PF) in patients with connective tissue disorders (CTD).

Methods.

Thirty-four patients with a diagnosis of CTD were included. Each patient underwent clinical examination, pulmonary function test (PFT), chest HRCT, and lung US by an experienced radiologist or rheumatologist. A second rheumatologist carried out US examinations to assess interobserver agreement. In each patient, US B-line lung assessment including 50 intercostal spaces (IS) was performed. For the anterior and lateral chest, the IS were the second to the fifth along the parasternal, mid-clavicular, anterior axillary, and medial axillary lines (the left fifth IS of the anterior and lateral chest was not performed because of the presence of the heart, which limits lung visualization). For the posterior chest, the IS assessed were the seventh to the eighth along the posterior-axillary and subscapular lines. The second to eighth IS were assessed in the paravertebral line. In each IS, the number of US B-lines under the transducer was recorded, summed, and graded according to the following semiquantitative scoring: grade 0 = normal (< 10 B-lines); grade 1 = mild (11 to 20 B-lines); grade 2 = moderate (21 to 50 B-lines); and grade 3 = marked (> 50 B-lines).

Results.

A total of 1700 IS in 34 patients were assessed. A significant linear correlation was found between the US score and the HRCT score (p < 0.001; correlation coefficient ρ = 0.875). A positive correlation was found between US B-line assessments and values of DLCO (p = 0.014). Both κ values and overall percentages of interobserver agreement showed excellent agreement.

Conclusion.

Our study demonstrates that US B-line assessment may be a useful and reliable additional imaging method in the evaluation of PF in patients with CTD.
Defining the Minimally Important Change for the SpondyloArthritis Research Consortium of Canada Spine and Sacroiliac Joint Magnetic Resonance Imaging Indices for Ankylosing Spondylitis
Authors: MAKSYMOWYCH WALTER P. , LAMBERT ROBERT G. , BROWN L. STEVEN , PANGAN AILEEN L.
Published: July 2012

Objective.

To define the minimally important change (MIC) in the SpondyloArthritis Research Consortium of Canada (SPARCC) spine and sacroiliac (SI) joint magnetic resonance imaging (MRI) indices in patients with ankylosing spondylitis.

Methods.

MRI scans were performed during a placebo-controlled trial of adalimumab (no. NCT00195819). Two independent readers, blinded to treatment and sequence, determined SPARCC scores for the spine and SI joints and a global evaluation of change (GEC; “much worse,” “worse,” “no change,” “better,” or “much better”; categories other than “no change” were pooled together as “change”) between baseline–Week 12, baseline–Week 52, and Weeks 12–52. Mean absolute changes in SPARCC scores (95% CI) were calculated for each interval, treatment group, and GEC. Receiver-operating characteristic (ROC) curves were used to identify the MIC. Relationships of MIC to clinical responses were examined.

Results.

Reader agreement on GEC evaluations was > 70%. Changes in SPARCC scores were generally comparable between time intervals and treatment groups for “change” and “no change” categories and were combined for each category; change in score was significantly associated with GEC of “change” (area under ROC curves: spine 0.839; SI joints 0.960). ROC curves peaked at values of 5.0 for the spine and 2.5 for SI joints. Placebo-treated patients achieving > 2.5 unit improvement in SI joint score had significantly better clinical responses than placebo-treated patients who did not achieve such improvement. MRI and clinical responses were uncoupled in adalimumab-treated patients.

Conclusion.

We propose that changes of 5.0 for the spine and 2.5 for SI joints define the MIC for the SPARCC MRI indices.
Pour une nouvelle dynamique collective de santé publique
Authors: Van Roekeghem Frédéric
Published: July 2012

Résumé Près de trois ans après l’instauration du contrat d’amélioration des pratiques individuelles, la mise en œuvre d’un complément de rémunération sur objectifs des médecins traitants a démontré son intérêt en santé publique, tout particulièrement pour la prise en charge des patients souffrant de pathologies chroniques. La généralisation de cette approche dans le cadre de la convention médicale ouvre la voie à une nouvelle dynamique, fondée sur la modernisation des cabinets de médecine de ville et la diversification des modes de rémunération des médecins traitants, qui tend à favoriser la diffusion des recommandations de bonne pratique professionnelle et les programmes de prévention. Son extension aux pratiques pluridisciplinaires et à certaines spécialités médicales est d’ores et déjà engagée.
Performance, apprentissage et santé des étudiants
Authors: Marra Donata
Published: July 2012

Résumé Dans une société où les indices de performance se multiplient et où le culte de la réussite individuelle ne laisse pas de place à l’échec, devenir ou rester performant dans ses études peut être à l’origine de consommation de psychostimulants. Bien que le phénomène reste limité chez les étudiants, la « cosméto-neurologie » avec recours à des molécules dopantes sur le plan cognitif est source de débats : pour certains évolution normale et attendue de la médecine et de ses bénéfices, pour d’autres évolution dont les répercussions sur le fonctionnement cérébral sont d’autant plus inquiétantes qu’elles sont difficiles à évaluer. Devenir de l’équité, pressions pour rester performant... les questions éthiques sont nombreuses. Il est urgent de proposer des interventions permettant aux étudiants de développer des méthodes d’apprentissage efficaces et de leur enseigner les bienfaits et l’utilité des interactions entre réussite et mode de vie : apprendre à apprendre avec plaisir et efficacité...
Le dopage et ses conséquences en termes de santé individuelle et de santé publique
Authors: Duclos Martine
Published: July 2012

Résumé Les données scientifiques montrent que le dopage hormonal peut augmenter les performances sportives, sachant que les doses utilisées dans les études sont bien inférieures à celles qui peuvent être utilisées par les sportifs. Toutes les analyses s’accordent aussi pour montrer que ce dopage se fait aux dépens de la santé du sportif. De plus, l’accès à des produits via Internet peut conduire à l’usage « tout public » de produits dopants. Ainsi, le dopage dépasse le cadre du seul sport de haut niveau et devient aujourd’hui un problème de santé publique.
Pharmacopée de la performance : mythe ou réalité ?
Authors: Tutin Corinne
Published: July 2012

Résumé Le succès du Prozac, puis du Viagra, a souvent été considéré comme emblématique d’une société à la recherche de la performance. Davantage que de surconsommation du médicament, notre société est plutôt victime de mésusage de celui-ci, soulignent cependant certains acteurs qui plaident pour un usage raisonné de la pharmacopée. Retour sur des réussites commerciales qui ont fait couler beaucoup d’encre à l’époque et continuent aujourd’hui d’interroger sociologues et professionnels de santé.
Quantum Confinement Modeling and Simulation for Quantum Well Solar Cells
Authors: Fara Laurentiu , Mitroi Mihai Razvan
Published: July 2012

In this chapter, the authors present the modelling and simulation of the multi-layered quantum well solar cells as well as the simulated results of this model. The quantum confinement of a semiconductor induces new energy levels, located in the band gap, as well as resonant levels located in the conduction and valence bands. These levels allow supplementary absorption in the visible and near infrared range. The quantum efficiency of the supplementary absorption is calculated within the infinite rectangular quantum well approximation. As the absorption excites carriers in the gap of each layer, even a small absorption significantly increases the photocurrent (by photoassisted tunneling) and, therefore, the cell efficiency. The results of the simulation are presented for the internal quantum efficiency of the transitions between the resonant levels of GaAs, as well as the internal quantum efficiency of the transitions between the confinement levels for GaAs and AlxGa1-xAs. New directions for the research of quantum well solar cells are indicated.
Organic Solar Cells Modeling and Simulation
Authors: Mitroi Mihai Razvan , Fara Laurentiu , Moraru Andrei Galbeaza
Published: July 2012

Modelling and simulation of organic (polymer, dye sensitized, and nanotube) solar cells is discussed. High J-V theoretical curves, the calculation of key parameters, and also the relative influence of different parameters on the cell operation, are evidenced and analyzed. On this basis, the authors obtain information on the optimization of the solar cell design and manufacturing.
Super High Efficiency Multi-Junction Solar Cells and Concentrator Solar Cells
Authors: Yamaguchi Masafumi
Published: July 2012

While single-junction solar cells may be capable of attaining AM1.5 efficiencies of up to 29%, Multi-Junction (MJ, Tandem) III-V compound solar cells appear capable of realistic efficiencies of up to 50% and are promising for space and terrestrial applications. In fact, the InGaP/GaAs/Ge triple-junction solar cells have been widely used in space since 1997. In addition, industrialization of concentrator solar cell modules using III-V compound MJ solar cells have been announced by some companies. This chapter presents principles and key issues for realizing high-efficiency MJ solar cells, issues relating to development and manufacturing, and applications for space and terrestrial uses.
Chronic Activation of the Kinase IKKβ Impairs T Cell Function and Survival
Authors: Krishna Sruti , Xie Danli , Gorentla Balachandra , Shin Jinwook , Gao Jimin , Zhong Xiao-Ping
Published: July 2012

Activation of the transcription factor NF-κB is critical for cytokine production and T cell survival after TCR engagement. The effects of persistent NF-κB activity on T cell function and survival are poorly understood. In this study, using a murine model that expresses a constitutively active form of inhibitor of NF-κB kinase β (caIKKβ) in a T cell-specific manner, we demonstrate that chronic inhibitor of NF-κB kinase β signaling promotes T cell apoptosis, attenuates responsiveness to TCR-mediated stimulation in vitro, and impairs T cell responses to bacterial infection in vivo. caIKKβ T cells showed increased Fas ligand expression and caspase-8 activation, and blocking Fas/Fas ligand interactions enhanced cell survival. T cell unresponsiveness was associated with defects in TCR proximal signaling and elevated levels of B lymphocyte-induced maturation protein 1, a transcriptional repressor that promotes T cell exhaustion. caIKKβ T cells also showed a defect in IL-2 production, and addition of exogenous IL-2 enhanced their survival and proliferation. Conditional deletion of B lymphocyte-induced maturation protein 1 partially rescued the sensitivity of caIKKβ T cells to TCR triggering. Furthermore, adoptively transferred caIKKβ T cells showed diminished expansion and increased contraction in response to infection with Listeria monocytogenes expressing a cognate Ag. Despite their functional defects, caIKKβ T cells readily produced proinflammatory cytokines, and mice developed autoimmunity. In contrast to NF-κB’s critical role in T cell activation and survival, our study demonstrates that persistent IKK–NF-κB signaling is sufficient to impair both T cell function and survival.
Targeting Stat3 Induces Senescence in Tumor Cells and Elicits Prophylactic and Therapeutic Immune Responses against Breast Cancer Growth Mediated by NK Cells and CD4+ T Cells
Authors: Tkach Mercedes , Coria Lorena , Rosemblit Cinthia , Rivas Martín A. , Proietti Cecilia J. , Díaz Flaqué María Celeste , Beguelin Wendy , Frahm Isabel , Charreau Eduardo H. , Cassataro Juliana , Elizalde Patricia V. , Schillaci Roxana
Published: July 2012

Aberrant Stat3 activation and signaling contribute to malignant transformation by promoting cell cycle progression, inhibiting apoptosis, and mediating tumor immune evasion. Stat3 inhibition in tumor cells induces the expression of chemokines and proinflammatory cytokines, so we proposed to apply Stat3-inhibited breast cancer cells as a source of immunogens to induce an antitumor immune response. Studies were performed in two murine breast cancer models in which Stat3 is activated: progestin-dependent C4HD cells and 4T1 cells. We immunized BALB/c mice with irradiated cancer cells previously transfected with a dominant-negative Stat3 vector (Stat3Y705F) in either a prophylactic or a therapeutic manner. Prophylactic administration of breast cancer cells transfected with Stat3Y705F (Stat3Y705F-breast cancer cells) inhibited primary tumor growth compared with administration of empty vector-transfected cells in both models. In the 4T1 model, 50% of the challenged mice were tumor free, and the incidence of metastasis decreased by 90%. In vivo assays of C4HD tumors showed that the antitumor immune response involves the participation of CD4+ T cells and cytotoxic NK cells. Therapeutic immunization with Stat3Y705F-breast cancer cells inhibited tumor growth, promoted tumor cell differentiation, and decreased metastasis. Furthermore, inhibition of Stat3 activation in breast cancer cells induced cellular senescence, contributing to their immunogenic phenotype. In this work, we provide preclinical proof of concept that ablating Stat3 signaling in breast cancer cells results in an effective immunotherapy against breast cancer growth and metastasis. Moreover, our findings showing that Stat3 inactivation results in induction of a cellular senescence program disclose a potential mechanism for immunotherapy research.
Transgenic Overexpression of G5PR That Is Normally Augmented in Centrocytes Impairs the Enrichment of High-Affinity Antigen-Specific B Cells, Increases Peritoneal B-1a Cells, and Induces Autoimmunity in Aged Female Mice
Authors: Kitabatake Masahiro , Toda Teppei , Kuwahara Kazuhiko , Igarashi Hideya , Ohtsuji Mareki , Tsurui Hiromichi , Hirose Sachiko , Sakaguchi Nobuo
Published: July 2012

To investigate signals that control B cell selection, we examined expression of G5PR, a regulatory subunit of the serine/threonine protein phosphatase 2A, which suppresses JNK phosphorylation. G5PR is upregulated in activated B cells, in Ki67-negative centrocytes at germinal centers (GCs), and in purified B220+Fas+GL7+ mature GC B cells following Ag immunization. G5PR rescues transformed B cells from BCR-mediated activation-induced cell death by suppression of late-phase JNK activation. In G5PR-transgenic (G5PRTg) mice, G5PR overexpression leads to an augmented generation of GC B cells via an increase in non-Ag–specific B cells and a consequent reduction in the proportion of Ag-specific B cells and high-affinity Ab production after immunization with nitrophenyl-conjugated chicken γ-globulin. G5PR overexpression impaired the affinity–maturation of Ag-specific B cells, presumably by diluting the numbers of high-affinity B cells. However, aged nonimmunized female G5PRTg mice showed an increase in the numbers of peritoneal B-1a cells and the generation of autoantibodies. G5PR overexpression did not affect the proliferation of B-1a and B-2 cells but rescued B-1a cells from activation-induced cell death in vitro. G5PR might play a pivotal role in B cell selection not only for B-2 cells but also for B-1 cells in peripheral lymphoid organs.
A Protective Role for Human IL-10–Expressing CD4+ T Cells in Colitis
Authors: Ranatunga Dilini C. , Ramakrishnan Amritha , Uprety Priyanka , Wang Fengying , Zhang Hao , Margolick Joseph B. , Brayton Cory , Bream Jay H.
Published: July 2012

IL-10 is an immunoregulatory cytokine expressed by numerous cell types. Studies in mice confirm that different IL-10–expressing cell subsets contribute differentially to disease phenotypes. However, little is known about the relationship between cell- or tissue-specific IL-10 expression and disease susceptibility in humans. In this study, we used the previously described human (h)IL10BAC transgenic model to examine the role of hIL-10 in maintaining intestinal homeostasis. Genomically controlled hIL-10 expression rescued Il10−/− mice from Helicobacter-induced colitis and was associated with control of proinflammatory cytokine expression and Th17 cell accumulation in gut tissues. Resistance to colitis was associated with an accumulation of hIL-10–expressing CD4+Foxp3+ regulatory T cells specifically within the lamina propria but not other secondary lymphoid tissues. Cotransfer of CD4+CD45RBlo cells from Il10−/−/hIL10BAC mice rescued Rag1−/− mice from colitis, further suggesting that CD4+ T cells represent a protective source of hIL-10 in the colon. In concordance with an enhanced capacity to express IL-10, CD4+CD44+ T cells isolated from the lamina propria exhibited lower levels of the repressive histone mark H3K27Me3 and higher levels of the permissive histone mark acetylated histone H3 in both the human and mouse IL10 locus compared with the spleen. These results provide experimental evidence verifying the importance of T cell-derived hIL-10 expression in controlling inflammation within the colonic mucosa. We also provide molecular evidence suggesting the tissue microenvironment influences IL-10 expression patterns and chromatin structure in the human (and mouse) IL10 locus.
Chronic Alcohol Consumption Impairs Distribution and Compromises Circulation of B Cells in B16BL6 Melanoma-Bearing Mice
Authors: Zhang Hui , Zhu Zhaohui , Meadows Gary G.
Published: July 2012

Accumulating research indicates that B cells are involved in anti-tumor immunity. Chronic alcohol consumption is associated with decreased survival of cancer patients. The effect of alcohol consumption on B cells in tumor-bearing hosts is unknown. Results in melanoma-bearing mice showed that chronic alcohol consumption did not alter the percentage and number of B cells in bone marrow, spleen, and lymph nodes but dramatically decreased B cells in the peripheral blood. Alcohol consumption did not alter the development of B cells in the bone marrow and did not affect follicular B cells in the spleen; however, it increased T1 B cells and decreased marginal zone B cells in the spleen. Alcohol consumption also decreased mature B cells in the blood. It did not alter the chemotactic capacity of plasma to facilitate migration of splenocytes or the chemotactic response of splenocytes to CXCL13 and CCL21. However, the response of splenocytes to sphingosine-1-phosphate was impaired in alcohol-consuming, melanoma-bearing mice. The expression of sphingosine-1-phosphate receptor-1 (S1PR1) and sphingosine-1-phosphate lyase-1 (SPL1) in splenocytes was downregulated. Taken together, these results indicate that chronic alcohol consumption decreases peripheral blood B cells by compromising B cell egress from the spleen. The downregulation of S1PR1 and SPL1 expression in alcohol-consuming, melanoma-bearing mice could be associated with compromised egress of B cells from the spleen.
Transcription Factor Zinc Finger and BTB Domain 1 Is Essential for Lymphocyte Development
Authors: Punwani Divya , Simon Karen , Choi Youngnim , Dutra Amalia , Gonzalez-Espinosa Diana , Pak Evgenia , Naradikian Martin , Song Chang-Hwa , Zhang Jenny , Bodine David M. , Puck Jennifer M.
Published: July 2012

Absent T lymphocytes were unexpectedly found in homozygotes of a transgenic mouse from an unrelated project. T cell development did not progress beyond double-negative stage 1 thymocytes, resulting in a hypocellular, vestigial thymus. B cells were present, but NK cell number and B cell isotype switching were reduced. Transplantation of wild-type hematopoietic cells corrected the defect, which was traced to a deletion involving five contiguous genes at the transgene insertion site on chromosome 12C3. Complementation using bacterial artificial chromosome transgenesis implicated zinc finger BTB-POZ domain protein 1 (Zbtb1) in the immunodeficiency, confirming its role in T cell development and suggesting involvement in B and NK cell differentiation. Targeted disruption of Zbtb1 recapitulated the T−B+NK− SCID phenotype of the original transgenic animal. Knockouts for Zbtb1 had expanded populations of bone marrow hematopoietic stem cells and also multipotent and early lymphoid lineages, suggesting a differentiation bottleneck for common lymphoid progenitors. Expression of mRNA encoding Zbtb1, a predicted transcription repressor, was greatest in hematopoietic stem cells, thymocytes, and pre-B cells, highlighting its essential role in lymphoid development.
The Peptide-Receptive Transition State of MHC Class I Molecules: Insight from Structure and Molecular Dynamics
Authors: Mage Michael G. , Dolan Michael A. , Wang Rui , Boyd Lisa F. , Revilleza Maria Jamela , Robinson Howard , Natarajan Kannan , Myers Nancy B. , Hansen Ted H. , Margulies David H.
Published: July 2012

MHC class I (MHC-I) proteins of the adaptive immune system require antigenic peptides for maintenance of mature conformation and immune function via specific recognition by MHC-I–restricted CD8+ T lymphocytes. New MHC-I molecules in the endoplasmic reticulum are held by chaperones in a peptide-receptive (PR) transition state pending release by tightly binding peptides. In this study, we show, by crystallographic, docking, and molecular dynamics methods, dramatic movement of a hinged unit containing a conserved 310 helix that flips from an exposed “open” position in the PR transition state to a “closed” position with buried hydrophobic side chains in the peptide-loaded mature molecule. Crystallography of hinged unit residues 46–53 of murine H-2Ld MHC-I H chain, complexed with mAb 64-3-7, demonstrates solvent exposure of these residues in the PR conformation. Docking and molecular dynamics predict how this segment moves to help form the A and B pockets crucial for the tight peptide binding needed for stability of the mature peptide-loaded conformation, chaperone dissociation, and Ag presentation.
Cutting Edge: Cell-Extrinsic Immune Regulation by CTLA-4 Expressed on Conventional T Cells
Authors: Wang Chun Jing , Kenefeck Rupert , Wardzinski Lukasz , Attridge Kesley , Manzotti Claire , Schmidt Emily M. , Qureshi Omar S. , Sansom David M. , Walker Lucy S. K.
Published: July 2012

The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an ongoing paradox in the field. Although CTLA-4 expressed on conventional T cells (Tconv) can mediate inhibitory function, it is unclear why this fails to manifest as an intrinsic effect. In this study, we show that Tconv-expressed CTLA-4 can function in a cell-extrinsic manner in vivo. CTLA-4+/+ T cells, from DO11/rag−/− mice that lack regulatory T cells, were able to regulate the response of CTLA-4−/− T cells in cotransfer experiments. This observation provides a potential resolution to the above paradox and suggests CTLA-4 function on both Tconv and regulatory T cells can be achieved through cell-extrinsic mechanisms.
Cutting Edge: In the Absence of TGF-β Signaling in T Cells, Fewer CD103+ Regulatory T Cells Develop, but Exuberant IFN-γ Production Renders Mice More Susceptible to Helminth Infection
Authors: Reynolds Lisa A. , Maizels Rick M.
Published: July 2012

Multiple factors control susceptibility of C57BL/6 mice to infection with the helminth Heligmosomoides polygyrus, including TGF-β signaling, which inhibits immunity in vivo. However, mice expressing a T cell-specific dominant-negative TGF-β receptor II (TGF-βRII DN) show dampened Th2 immunity and diminished resistance to infection. Interestingly, H. polygyrus-infected TGF-βRII DN mice show greater frequencies of CD4+Foxp3+Helios+ Tregs than infected wild-type mice, but levels of CD103 are greatly reduced on both these cells and on the CD4+Foxp3+Helios– population. Although Th9 and Th17 levels are comparable between infected TGF-βRII DN and wild-type mice, the former develop exaggerated CD4+ and CD8+ T cell IFN-γ responses. Increased susceptibility conferred by TGF-βRII DN expression was lost in IFN-γ–deficient mice, although they remained unable to completely clear infection. Hence, overexpression of IFN-γ negatively modulates immunity, and the presence of Helios+ Tregs may maintain susceptibility on the C57BL/6 background.
NLRP1-Dependent Pyroptosis Leads to Acute Lung Injury and Morbidity in Mice
Authors: Kovarova Martina , Hesker Pamela R. , Jania Leigh , Nguyen MyTrang , Snouwaert John N. , Xiang Zhidan , Lommatzsch Stephen E. , Huang Max T. , Ting Jenny P.-Y. , Koller Beverly H.
Published: July 2012

Acute inflammation in response to both exogenous and endogenous danger signals can lead to the assembly of cytoplasmic inflammasomes that stimulate the activation of caspase-1. Subsequently, caspase-1 facilitates the maturation and release of cytokines and also, under some circumstances, the induction of cell death by pyroptosis. Using a mouse line lacking expression of NLRP1, we show that assembly of this inflammasome in cells is triggered by a toxin from anthrax and that it initiates caspase-1 activation and release of IL-1β. Furthermore, NLRP1 inflammasome activation also leads to cell death, which escalates over 3 d following exposure to the toxin and culminates in acute lung injury and death of the mice. We show that these events are not dependent on production of IL-1β by the inflammasome but are dependent on caspase-1 expression. In contrast, muramyl dipeptide-mediated inflammasome formation is not dependent on NLRP1 but NLRP3. Taken together, our findings show that assembly of the NLRP1 inflammasome is sufficient to initiate pyroptosis, which subsequently leads to a self-amplifying cascade of cell injury within the lung from which the lung cannot recover, eventually resulting in catastrophic consequences for the organism.
Investigation of Backward-Facing-Step Flow Field for Dynamic Interface Application
Authors: Nacakli Yavuz , Landman Drew , Doane Stargel
Published: July 2012

A research program to investigate helicopter downwash and frigate airwake interaction has been initiated using a statistically robust experimental program featuring design of experiments. Engineering analysis of the helicopter/frigate interface is complicated by the fact that two flow
fields become inherently coupled as a separation distance decreases. The work presented was performed in the Old Dominion University 7 × 8 ft Low-Speed Wind Tunnel using a simplified 1/50-scale frigate waterline model and traverse-mounted powered rotor with thrust measurement capability.
Particle image velocimetry velocity surveys were acquired with rotor thrust coefficient measurements at coincident locations to help understand the underlying flow physics.
Application of Computational Fluid Dynamics/Computational Structural Dynamics Coupling for Analysis of Rotorcraft Airloads and Blade Loads in Maneuvering Flight
Authors: Bhagwat Mahendra J. , Ormiston Robert A. , Saberi Hossein A. , Xin Hong
Published: July 2012

This paper presents coupled calculations of both the airloads and structural loads for the UH-60A main rotor during the UTTAS pull-up maneuver performed under the NASA/Army UH-60A Airloads Program. These calculations were performed using OVERFLOW-2, a computational fluid dynamics (CFD)
solver, coupled to the Rotorcraft Comprehensive Analysis System (RCAS), a rotorcraft comprehensive analysis. For time-varying maneuvers, the two codes were tightly coupled and exchanged airloads and structural deflections at every time step. The coupled solution methodology gives improved
airload prediction because of the ability to model three-dimensional transonic effects on the advancing blade, stall events on the retreating blade, as well as the aeroelastic deformations. Correlation with data for both the airloads and structural loads is reasonably good. Control load predictions
also show good correlation with data, which is a substantial improvement over conventional analyses. A quasisteady loosely coupled approximate solution was also examined and was found to give good airload and structural load predictions, for this relatively slow maneuver.
Considering Ethnicity and Gender Effects in Disgust Propensity and Spider and Snake Phobia: Comparing Asian Americans and European Americans
Authors: Vernon Laura L. , Hirai Michiyo
Published: July 2012

This study examined ethnic and gender differences and ethnicity by gender interactions in disgust propensity, spider and snake phobic distress, and their interrelationships. A main effect for ethnicity was found, with Asian Americans (n = 219) reporting more disgust propensity and phobic distress than European Americans (n = 581). Gender effects were modified by ethnicity by gender interactions, with European American males reporting the least disgust propensity and distress, and gender differences present only for European Americans. For both ethnic groups, phobic distress scores were strongly correlated with animal and non-animal disgust propensity. In hierarchical regression analyses, animal disgust propensity was uniquely related to spider and snake distress scores among both ethnic groups, although non-animal disgust propensity was only a significant individual predictor among European Americans. The results suggest that models of animal phobia and disgust propensity based on European American samples cannot be uniformly applied to Asian Americans. Ethnicity and gender, and their interaction, may influence the intensity of disgust propensity and animal phobic distress and their relationships with one another.
Testing the Stroop Effect in a Nonclinical Sample: Hypervigilance or Difficulty to Disengage?
Authors: Peach Natalie , Jovev Martina , Foster Alexander , Jackson Henry
Published: July 2012

Traditional interpretations of the bias have suggested that anxious people are hypervigilant to threat; that is, their attention orients more quickly towards threatening stimuli. Recent research has questioned the validity of this interpretation, suggesting that difficulty disengaging attention from threat might play a role in the attentional bias. A limited number of experimental paradigms have differentiated between hypervigilance and difficulty disengaging. In this study, 169 undergraduate students completed an emotional Stroop task to investigate the presence of an attentional bias to threat, and a lexical decision task to differentiate between hypervigilance and difficulty disengaging. Hypotheses regarding the emotional Stroop task were partially supported; Stroop effects were found in some, but not all, of the threat-types investigated. Lexical decision task results lent support for the hypervigilance hypothesis. Anxiety levels did not predict the extent of the attentional bias. Results are discussed in relation to future directions for attentional bias research.
Individual Variation in Behavioral Economic Indices of the Relative Value of Alcohol: Incremental Validity in Relation to Impulsivity, Craving, and Intellectual Functioning
Authors: Acker John , Amlung Michael , Stojek Monika , Murphy James G. , MacKillop James
Published: July 2012

There is increasing interest in the role of individual variation in behavioral economic indices of the relative value of alcohol in relation to alcohol use and misuse. The aim of the present study was to investigate the importance of behavioral economic indices of demand for alcohol generated from an alcohol purchase task (APT), a task that measures estimated alcohol consumption and price sensitivity above and beyond established risk variables, including dimensions of impulsivity and craving for alcohol. In addition, the study examined the APT indices in relation to intellectual functioning. Hierarchical regressions revealed that the behavioral economic index of Omax and intellectual functioning were significantly and uniquely associated with weekly alcohol consumption. In contrast, Intensity, and craving for alcohol were uniquely associated with alcohol misuse. These results provide further support for the importance of behavioral economic indices of demand in relation to both alcohol use and alcohol misuse. Parallels to previous studies, limitations, and important future directions are discussed.
Did I Forget to Lock the Door? The Link between Prospective Memory Failures and Doubt in the Compulsion to Check
Authors: Cuttler Carrie , Taylor Steven
Published: July 2012

Previous research has demonstrated links between prospective memory failures and checking compulsions. The findings suggest that experiences with prospective memory failures may contribute to the intrusive doubts that tasks were not completed that instigate checking compulsions. However, the link between prospective memory and intrusive doubts has yet to be empirically investigated. Accordingly, the present study focused on examining whether prospective memory failures are related to doubting, as well as whether doubting mediates the relationship between prospective memory and checking compulsions. Undergraduate students completed self-report measures of checking compulsions, doubting, prospective memory and retrospective memory. Participants also completed objective tests of prospective memory and retrospective memory. Prospective memory failures and excessive doubting showed consistent correlations. Two of three objective tests of prospective memory and one of two measures of confidence in performance on prospective memory tests showed significant correlations with checking. Tests of mediation showed that the links between checking compulsions, objective prospective memory test failures and confidence in prospective memory performance were mediated by doubting. The results thereby supported the hypothesis that experiences with prospective memory failures contribute to the intrusive doubts that instigate checking.
Difficulty Disengaging from Threat in Anxiety: Preliminary Evidence for Delayed Response Execution
Authors: Matlow Ryan B. , Gard David E. , Berg David J.
Published: July 2012

High anxiety is associated with an attentional bias for threatening information that appears to be the result of difficulty disengaging attention from such stimuli. However, it is yet unknown whether difficulty disengaging, often detected using the probe detection task, results from delayed shifting of visual attention or from interference in executing a behavioral response. The present study tested this distinction by measuring reaction times and eye movements of 30 high trait anxious (HTA) and 28 low trait anxious (LTA) individuals during completion of a probe detection task involving 500 ms presentation of threatening, positive, and neutral images. Difficulty disengaging was detected in the HTA group only for both positive and threatening images. Eye movement results did not show that HTA individuals experience delays in shifting visual attention away from an affective stimulus, thus providing preliminary evidence that difficulty disengaging in the probe detection task is likely a result of delays in decision-making and/or manual response execution.
The effects of cognitive and affective priming on law of contagion appraisals
Authors: Adams T. G. , Cisler J. M. , Brady R. E. , Lohr J. M.
Published: July 2012

The law of contagion is the magical belief that contagion can spread in an absolute fashion despite minimal contact, extreme lapses in time, and many degrees of removal. Research suggests that two broad mechanisms may underlie inflated law of contagion beliefs and appraisals. These include cognitive (attention, informational) and affective (disgust). The present study tested the effects of cognitive-informational (script that described the spreading nature of germs) and affective (disgust odorant) priming on law of contagion appraisals using the chain of contagion task. Results showed that disgust priming had a non-significant impact on law of contagion appraisals while cognitive-informational priming caused participants to appraise contagion as being able to spread in a more virulent fashion. These data are consistent with previous research and support the idea that appraisals related to the law of contagion can be affected by informational manipulations. Results are discussed in relation to contamination fears in OCD.
Is “Cootie” in the Eye of the Beholder? An Experimental Attempt to Modify Implicit Associations Tied to Contamination Fears
Authors: Green Jennifer S. , Teachman Bethany A.
Published: July 2012

To examine the causal link between implicit associations and fear reduction, a conditioning paradigm was used in an attempt to modify contamination-related implicit associations for individuals high in contamination fear. Individuals (N = 81) were assigned to a Positive, Neutral, or No Training condition. In the Positive training condition, individuals clicked on images of potential contaminants that were followed by images of the individual's smiling face or by an approach-related word. Positive training was hypothesized to result in decreased behavioral avoidance and emotional vulnerability ratings during subsequent behavioral avoidance tasks. In the Neutral training control condition, the images of potential contaminants were followed by an equal mix of the individual's smiling, disgusted, and fearful faces or an avoidance-related word. The No Training condition served as an additional control group. Contrary to expectations, training did not shift implicit associations, nor did it affect avoidance or emotional vulnerability ratings. These results raise questions about the most appropriate form and dosage of training for this population – we conclude with suggestions for researchers to learn from these null findings when developing new training programs.
Anxiety-Related Biases in Visual Orienting and Spatial Motor Response Selection Independently Assessed by a Probe-Classification Task
Authors: Schrooten Martien G.S. , Smulders Fren T.Y. , Mogg Karin , Bradley Brendan P.
Published: July 2012

This dot-probe study assessed anxiety-related biases in visual attentional orienting and spatial motor response selection (motor attention) in high- and low-trait-anxious adults, and whether anxiety-related biases depend on response speed. Emotional-neutral word pairs appeared for 14 or 500 ms, with one word of each pair replaced by a probe. Visual attention bias to emotional words was reflected by faster responses to probes replacing emotional words (spatial correspondence between probe and word positions). Response selection bias was reflected by faster responses when emotional word position (top/bottom screen) spatially corresponded to response position (upper/lower response key). Results revealed anxiety-related bias in visual attention for physical-threat words. In distributional analyses, this bias was associated with slower responses in the 14 ms condition (first task half). Results also revealed anxiety-related effects of spatial correspondence between emotional word and response, which are discussed in terms of increased bias in motor attention towards emotional stimuli in anxiety.
Role of Inhibition in Exposure Therapy
Authors: Craske Michelle G. , Liao Betty , Brown Lily , Vervliet Bram
Published: July 2012

While many researchers have largely focused on principles of systematic desensitization and habituation in explaining fear extinction, these processes have mixed evidence at best. In particular, these models do not account for spontaneous recovery or reinstatement of fear, nor do they explain the context dependency of extinction or rapid reacquisition. This may in part account for the significant number of patients who fail to respond to our available treatments which rely on these principles in designing exposure sessions. However, recent research is converging to suggest that an inhibitory model of fear reduction, in which the original feared association (CS-US) remains but is inhibited by a newly formed association (CS-noUS) representing safety, holds promise in explaining the long-term attenuation of fear and anxiety. This paper reviews research in a number of areas, including neuroimaging, psychophysiology, and psychopharmacology that all provide support for the inhibition model of anxiety. Limitations to this body of research are discussed, along with recommendations for future research and suggestions for improving exposure therapy for fear and anxiety disorders. Clinical implications discussed in this paper include incorporating random and variable practice in exposure sessions, multiple contexts, and pharmacological aides, among others.
Assessing large-scale weekly cycles in meteorological variables: a review
Authors: Sanchez-Lorenzo A. , Laux P. , Hendricks Franssen H.-J. , Calbó J. , Vogl S. , Georgoulias A. K. , Quaas J.
Published: July 2012

Abstract. Several studies have claimed to have found significant weekly cycles of meteorological variables appearing over large domains, which can hardly be related to urban effects exclusively. Nevertheless, there is still an ongoing scientific debate whether these large-scale weekly cycles exist or not, and some other studies fail to reproduce them with statistical significance. In addition to the lack of the positive proof for the existence of these cycles, their possible physical explanations have been controversially discussed during the last years. In this work we review the main results about this topic published during the recent two decades, including a summary of the existence or non-existence of significant weekly weather cycles across different regions of the world, mainly over the US, Europe and Asia. In addition, some shortcomings of common statistical methods for analyzing weekly cycles are listed. Finally, a brief summary of supposed causes of the weekly cycles, focusing on the aerosol-cloud-radiation interactions and their impact on meteorological variables as a result of the weekly cycles of anthropogenic activities, and possible directions for future research, is presented.
Volcanic SO2 and SiF4 visualization using 2-D thermal emission spectroscopy – Part 2: Wind propagation and emission fluxes
Authors: Krueger A. , Stremme W. , Harig R. , Grutter M.
Published: July 2012

Abstract. The technique for measuring two-dimensional (2-D) plumes of volcanic gases with thermal emission spectroscopy was described in Part 1 by Stremme et al. (2012). In that paper the instrumental aspects as well as retrieval strategies for obtaining the slant column images of SO2 and SiF4, as well as animations of particular events observed at the Popocatépetl volcano, were presented. This work focuses on the procedures for determining the propagation speed of the gases and estimating an emission flux from the given image sequences. A 2-D column density distribution of a volcanic gas, available as time-consecutive frames, provides information of a wind-field and the average velocity at which the volcanic plume is propagating. The presented reconstruction method solves the equation of continuity as an ill-posed problem using mainly a Tikhonov-like regularization. It is observed from the available data sets that if the main direction of propagation is perpendicular to the line-of-sight, the algorithm works well for SO2 which has the strongest signals, and also for SiF4 in some favourable cases. Due to the similarity of the algorithm used here with the reconstruction methods used for profile retrievals based on optimal estimation theory, diagnostic tools like the averaging kernels can be calculated analogously and the information can be quantified as degrees of freedom. Thus, it is shown that the combination of wind-field and column distribution of the gas plume can provide the emission flux of the volcano both during day and night.
Implications of observed inconsistencies in carbonate chemistry measurements for ocean acidification studies
Authors: Hoppe C. J. M. , Langer G. , Rokitta S. D. , Wolf-Gladrow D. A. , Rost B.
Published: July 2012

Abstract. The growing field of ocean acidification research is concerned with the investigation of organism responses to increasing pCO2 values. One important approach in this context is culture work using seawater with adjusted CO2 levels. As aqueous pCO2 is difficult to measure directly in small-scale experiments, it is generally calculated from two other measured parameters of the carbonate system (often AT, CT or pH). Unfortunately, the overall uncertainties of measured and subsequently calculated values are often unknown. Especially under high pCO2, this can become a severe problem with respect to the interpretation of physiological and ecological data. In the few datasets from ocean acidification research where all three of these parameters were measured, pCO2 values calculated from AT and CT are typically about 30% lower (i.e. ~300 μatm at a target pCO2 of 1000 μatm) than those calculated from AT and pH or CT and pH. This study presents and discusses these discrepancies as well as likely consequences for the ocean acidification community. Until this problem is solved, one has to consider that calculated parameters of the carbonate system (e.g. pCO2, calcite saturation state) may not be comparable between studies, and that this may have important implications for the interpretation of CO2 perturbation experiments.