bluuebunny/crossref_metadata_2025 huggingface dataset:
Dengue Pathogenesis: A Disease Driven by the Host Response
Authors: Martina Byron E.E.
Published: September 2014

Dengue viruses cause mild disease in the majority of infected individuals. In most cases, the disease is characterised by fever, headache, pain behind the eyes, muscle ache, joint pains, vomiting and diarrhoea. In a low percentage of patients, bleeding and loss of plasma (haemorrhage and plasma leakage) may occur. The hyper-permeability syndrome results in plasma leakage and, if the compensatory mechanisms of the body fail to control the plasma leakage or if medical intervention is late, shock may set in. Profound shock will subsequently lead to acidic blood (metabolic acidosis) and development of disseminated intravascular coagulation (DIC). During DIC multiple micro thromboses occur, leading to organ failure. The mechanisms governing pathogenesis of these forms of severe disease are not clear. High amounts of virus in the blood are believed to cause vascular fragility which, together with infection of endothelial cells and high levels of cytokines and other soluble mediators, may result in bleeding. In the absence of a correlation between the amount of virus in the blood and disease severity, it is likely that response to infection is an important cause of disease. The aberrant immune response to infection is believed to result in a cytokine storm, defined as an imbalance between cytokines driving an inflammation (pro-inflammatory) and those silencing an inflammation (anti-inflammatory). Several lines of evidence indicate that displacement of viral genotype and host genetic background are key factors driving the production of a cytokine storm. Several cytokines are known to induce apoptosis, a form of cell suicide (cause of haemorrhage), and/or affect adherens junctions (cause permeability) in vitro. Whether these cytokines may have such effects in vivo remains to be established.
Park Rangers’ Behaviors and Their Effects on Tourists and Tibetan Macaques (Macaca thibetana) at Mt. Huangshan, China
Authors: Usui Rie , Sheeran Lori , Li Jin-hua , Sun Lixing , Wang Xi , Pritchard Alexander , DuVall-Lash Alexander , Wagner R.
Published: September 2014

Previous studies have reported the negative impacts of tourism on nonhuman primates (NHPs) and tourists and advocated the improvement of tourism management, yet what constitutes good quality management remains unclear. We explored whether rates of macaque aggression and self-directed behaviors (SDBs) differed under the supervision of two park ranger teams at the Valley of the Wild Monkeys (VWM) in Mt. Huangshan, Anhui Province, China. The two ranger teams provisioned and managed a group of macaques on an alternating monthly basis. Monkey, tourist and ranger behaviors were collected from August 16–September 30, 2012. Macaque aggression and SDB rates did not differ significantly under the management of the two teams. Overall, there was little intervention in tourist-macaque interactions by park rangers, and even when rangers discouraged tourists’ undesirable behaviors, tourist interactions with monkeys persisted. Furthermore, only one or sometimes two park rangers managed monkeys and tourists, and rangers established dominance over the monkeys to control them. In order to effectively manage tourists and monkeys by a single park ranger, we recommend that rangers: (1) prohibit tourists from feeding; (2) move around the viewing platform more frequently; and (3) limit the number of tourists each visiting session.
Distributed Control of Heat Conduction in Thermal Inductive Materials with 2D Geometrical Isomorphism
Authors: Chou Chia-Yu , Hong Boe-Shong , Chiang Pei-Ju , Wang Wen-Teng , Chen Liang-Kuang , Lee Chia-Yen
Published: September 2014

In a previous study we provided analytical and experimental evidence that some materials are able to store entropy-flow, of which the heat-conduction behaves as standing waves in a bounded region small enough in practice. In this paper we continue to develop distributed control of heat conduction in these thermal-inductive materials. The control objective is to achieve subtle temperature distribution in space and simultaneously to suppress its transient overshoots in time. This technology concerns safe and accurate heating/cooling treatments in medical operations, polymer processing, and other prevailing modern day practices. Serving for distributed feedback, spatiotemporal H ∞ /μ control is developed by expansion of the conventional 1D-H ∞ /μ control to a 2D version. Therein 2D geometrical isomorphism is constructed with the Laplace-Galerkin transform, which extends the small-gain theorem into the mode-frequency domain, wherein 2D transfer-function controllers are synthesized with graphical methods. Finally, 2D digital-signal processing is programmed to implement 2D transfer-function controllers, possibly of spatial fraction-orders, into DSP-engine embedded microcontrollers.
Extraction, Preliminary Characterization and Evaluation of in Vitro Antitumor and Antioxidant Activities of Polysaccharides from Mentha piperita
Authors: Liu Xin , Sun Zhen-Liang , Jia Ai-Rong , Shi Ya-Ping , Li Rui-Hong , Yang Pei-Ming
Published: September 2014

This study describes the extraction, preliminary characterization and evaluation of the in vitro antitumor and antioxidant activities of polysaccharides extracted from Mentha piperita (MPP). The optimal parameters for the extraction of MPP were obtained by Box-Behnken experimental design and response surface methodology (RSM) at the ratio of water to raw material of 20, extraction time of 1.5 h and extraction temperature at 80 °C. Chemical composition analysis showed that MPP was mainly composed of glucuronic acid, galacturonic acid, glucose, galactose and arabinose, and the molecular weight of its two major fractions were estimated to be about 2.843 and 1.139 kDa, respectively. In vitro bioactivity experiments showed that MPP not only inhibited the growth of A549 cells but possessed potent inhibitory action against DNA topoisomerase I (topo I), and an appreciative antioxidant action as well. These results indicate that MPP may be useful for developing safe natural health products.
Ectopic Expression of CsCTR1, a Cucumber CTR-Like Gene, Attenuates Constitutive Ethylene Signaling in an Arabidopsis ctr1-1 Mutant and Expression Pattern Analysis of CsCTR1 in Cucumber (Cucumis sativus)
Authors: Bie Beibei , Sun Jin , Pan Junsong , He Huanle , Cai Run
Published: September 2014

The gaseous plant hormone ethylene regulates many aspects of plant growth, development and responses to the environment. Constitutive triple response 1 (CTR1) is a central regulator involved in the ethylene signal transduction pathway. To obtain a better understanding of this particular pathway in cucumber, the cDNA-encoding CTR1 (designated CsCTR1) was isolated from cucumber. A sequence alignment and phylogenetic analyses revealed that CsCTR1 has a high degree of homology with other plant CTR1 proteins. The ectopic expression of CsCTR1 in the Arabidopsis ctr1-1 mutant attenuates constitutive ethylene signaling of this mutant, suggesting that CsCTR1 indeed performs its function as negative regulator of the ethylene signaling pathway. CsCTR1 is constitutively expressed in all of the examined cucumber organs, including roots, stems, leaves, shoot apices, mature male and female flowers, as well as young fruits. CsCTR1 expression gradually declined during male flower development and increased during female flower development. Additionally, our results indicate that CsCTR1 can be induced in the roots, leaves and shoot apices by external ethylene. In conclusion, this study provides a basis for further studies on the role of CTR1 in the biological processes of cucumber and on the molecular mechanism of the cucumber ethylene signaling pathway.
Carrier Screening: Past, Present, and Future
Authors: Bajaj Komal , Gross Susan
Published: September 2014

To date, preconceptual and prenatal patients have been offered gene-by-gene, disorder-by-disorder carrier screening. Newer techniques allow screening of many disorders at one time. The goal of this review is to provide an overview of the current practice and future direction of carrier screening within the preconceptual/prenatal setting.
Carbon Nanotubes as Supports for Inulinase Immobilization
Authors: Garlet Tais , Weber Caroline , Klaic Rodrigo , Foletto Edson , Jahn Sergio , Mazutti Marcio , Kuhn Raquel
Published: September 2014

The commercial inulinase obtained from Aspergillus niger was non-covalently immobilized on multiwalled carbon nanotubes (MWNT-COOH). The immobilization conditions for the carbon nanotubes were defined by the central composite rotational design (CCRD). The effects of enzyme concentration (0.8%–1.7% v/v) and adsorbent:adsorbate ratio (1:460–1:175) on the enzyme immobilization were studied. The adsorbent:adsorbate ratio variable has positive effect and the enzyme concentration has a negative effect on the inulinase immobilization (U/g) response at the 90% significance level. These results show that the lower the enzyme concentration and the higher the adsorbent:adsorbate ratio, better is the immobilization. According to the results, it is possible to observe that the carbon nanotubes present an effective inulinase adsorption. Fast adsorption in about six minutes and a loading capacity of 51,047 U/g support using a 1.3% (v/v) inulinase concentration and a 1:460 adsorbent:adsorbate ratio was observed. The effects of temperature on the immobilized enzyme activity were evaluated, showing better activity at 50 °C. The immobilized enzyme maintained 100% of its activity during five weeks at room temperature. The immobilization strategy with MWNT-COOH was defined by the experimental design, showing that inulinase immobilization is a promising biotechnological application of carbon nanotubes.
The Content of Phenolic Compounds in Leaf Tissues of White (Aesculus hippocastanum L.) and Red Horse Chestnut (Aesculus carea H.) Colonized by the Horse Chestnut Leaf Miner (Cameraria ohridella Deschka & Dimić)
Authors: Oszmiański Jan , Kalisz Stanisław , Aneta Wojdyło
Published: September 2014

Normally, plant phenolics are secondary metabolites involved in the defense mechanisms of plants against fungal pathogens. Therefore, in this study we attempted to quantify and characterize phenolic compounds in leaves of white and red horse chestnut with leaf miner larvae before and after Cameraria ohridella attack. A total of 17 phenolic compounds belonging to the hydroxycinnamic acid, flavan-3-ols and flavonol groups were identified and quantified in white and red horse chestnut leaf extracts. Significantly decreased concentrations of some phenolic compounds, especially of flavan-3-ols, were observed in infected leaves compared to the non-infected ones. Additionally, a higher content of polyphenolic compounds especially (−)-epicatechin and procyanidins in leaves of red-flowering than in white-flowering horse chestnut may explain their greater resistance to C. ohridella insects.
A Novel Angle Computation and Calibration Algorithm of Bio-Inspired Sky-Light Polarization Navigation Sensor
Authors: Xian Zhiwen , Hu Xiaoping , Lian Junxiang , Zhang Lilian , Cao Juliang , Wang Yujie , Ma Tao
Published: September 2014

Navigation plays a vital role in our daily life. As traditional and commonly used navigation technologies, Inertial Navigation System (INS) and Global Navigation Satellite System (GNSS) can provide accurate location information, but suffer from the accumulative error of inertial sensors and cannot be used in a satellite denied environment. The remarkable navigation ability of animals shows that the pattern of the polarization sky can be used for navigation. A bio-inspired POLarization Navigation Sensor (POLNS) is constructed to detect the polarization of skylight. Contrary to the previous approach, we utilize all the outputs of POLNS to compute input polarization angle, based on Least Squares, which provides optimal angle estimation. In addition, a new sensor calibration algorithm is presented, in which the installation angle errors and sensor biases are taken into consideration. Derivation and implementation of our calibration algorithm are discussed in detail. To evaluate the performance of our algorithms, simulation and real data test are done to compare our algorithms with several exiting algorithms. Comparison results indicate that our algorithms are superior to the others and are more feasible and effective in practice.
Theoretical Prediction of Experimental Jump and Pull-In Dynamics in a MEMS Sensor
Authors: Ruzziconi Laura , Ramini Abdallah , Younis Mohammad , Lenci Stefano
Published: September 2014

The present research study deals with an electrically actuated MEMS device. An experimental investigation is performed, via frequency sweeps in a neighbourhood of the first natural frequency. Resonant behavior is explored, with special attention devoted to jump and pull-in dynamics. A theoretical single degree-of-freedom spring-mass model is derived. Classical numerical simulations are observed to properly predict the main nonlinear features. Nevertheless, some discrepancies arise, which are particularly visible in the resonant branch. They mainly concern the practical range of existence of each attractor and the final outcome after its disappearance. These differences are likely due to disturbances, which are unavoidable in practice, but have not been included in the model. To take disturbances into account, in addition to the classical local investigations, we consider the global dynamics and explore the robustness of the obtained results by performing a dynamical integrity analysis. Our aim is that of developing an applicable confident estimate of the system response. Integrity profiles and integrity charts are built to detect the parameter range where reliability is practically strong and where it becomes weak. Integrity curves exactly follow the experimental data. They inform about the practical range of actuality. We discuss the combined use of integrity charts in the engineering design. Although we refer to a particular case-study, the approach is very general.
Genomics: A potential panacea for the perennial problem
Authors: McClure Kendra A. , Sawler Jason , Gardner Kyle M. , Money Daniel , Myles Sean
Published: September 2014

Perennial crops represent important fresh and processed food sources worldwide, but advancements in breeding perennials are often impeded due to their very nature. The perennial crops we rely on most for food take several years to reach production maturity and require large spaces to grow, which make breeding new cultivars costly compared with most annual crops. Because breeding perennials is inefficient and expensive, they are often grown in monocultures consisting of small numbers of elite cultivars that are vegetatively propagated for decades or even centuries. This practice puts many perennial crops at risk for calamity since they remain stationary in the face of evolving pest and disease pressures. Although there is tremendous genetic diversity available to them, perennial crop breeders often struggle to generate commercially successful cultivars in a timely and cost‐effective manner because of the high costs of breeding. Moreover, consumers often expect the same cultivars to be available indefinitely, and there is often little or no incentive for growers and retailers to take the risk of adopting new cultivars. While genomics studies linking DNA variants to commercially important traits have been performed in diverse perennial crops, the translation of these studies into accelerated breeding of improved cultivars has been limited. Here we explain the “perennial problem” in detail and demonstrate how modern genomics tools can significantly improve the cost effectiveness of breeding perennial crops and thereby prevent crucial food sources from succumbing to the perils of perpetual propagation.
A cool experimental approach to explain elevational treelines, but can it explain them?
Authors: Bader Maaike Y. , Loranger Hannah , Zotz Gerhard
Published: September 2014

At alpine treeline, trees give way to low‐stature alpine vegetation. The main reason may be that tree canopies warm up less in the sun and experience lower average temperatures than alpine vegetation. Low growth temperatures limit tissue formation more than carbon gain, but whether this mechanism universally determines potential treeline elevations is the subject of debate. To study low‐temperature limitation in two contrasting treeline tree species, Fajardo and Piper (American Journal of Botany 101: 788–795) grew potted seedlings at ground level or suspended at tree‐canopy height (2 m), introducing a promising experimental method for studying the effects of alpine‐vegetation and tree‐canopy microclimates on tree growth. On the basis of this experiment, the authors concluded that lower temperatures at 2 m caused carbon limitation in one of the species and that treeline‐forming mechanisms may thus be taxon‐dependent. Here we contest that this important conclusion can be drawn based on the presented experiment, because of confounding effects of extreme root‐zone temperature fluctuations and potential drought conditions. To interpret the results of this elegant experiment without logistically challenging technical modifications and to better understand how low temperature leads to treeline formation, studies on effects of fluctuating vs. stable temperatures are badly needed. Other treeline research priorities are interactions between temperature and other climatic factors and differences in microclimate between tree canopies with contrasting morphology and physiology. In spite of our criticism of this particular study, we agree that the development of a universal treeline theory should include continuing explorations of taxon‐specific treeline‐forming mechanisms.
Measuring Peritoneal Absorption with the Prolonged Peritoneal Equilibration Test from 4 to 8 Hours Using Various Glucose Concentrations
Authors: Teixidó–Planas Josep , Troya–Saborido Maria Isabel , Pedreira–Robles Guillermo , Del-Rio–Lafuente Milagros , Romero–Gonzalez Ramon , Bonet–Sol Josep
Published: September 2014

Background

Peritoneal fluid flows such as small-pore ultrafiltration and free water transport can now be calculated by means of the modified peritoneal equilibration test (PET). To calculate peritoneal fluid absorption, volume markers have been used, but that method is not easily applicable in clinical practice. Alternatively, absorption can be estimated using the personal dialysis capacity test. However, a method of measuring overall peritoneal absorption together with the PET is lacking. The aim of the present study was to assess whether overall peritoneal absorption was different when measured from the 4th to 8th hour in a prolonged PET using three different glucose solutions.

Methods

The study enrolled 32 stable peritoneal dialysis (PD) patients from a tertiary university hospital, who underwent three 8-hour prolonged PETs with 1.36%, 2.27%, and 3.86% glucose solution. The PETs were performed in random order over a period of less than 1 month. During the prolonged PET, the peritoneal volume was emptied and reinfused at 60 and 240 minutes and drained at 480 minutes. Peritoneal absorption was calculated as the volume difference between the 4th and the 8th hour.

Results

The dialysate-to-plasma ratio (D/P) of urea, the D/P creatinine, and the mass transfer area coefficient (MTC) of creatinine at 240 minutes were not significantly different with the three glucose solutions. The end-to-initial (D/D0) glucose, MTC urea, and MTC glucose were significantly different. All water transport parameters were significantly different, except for the 4- to 8-hour absorption volumes and rates. The peritoneal absorption rates were, for 1.36% solution, 1.03 ± 0.58 mL/min [95% confidence interval (CI): 0.83 to 1.24 mL/min]; for 2.27% solution, 0.86 ± 0.71 mL/min (95% CI: 0.61 to 1.11 mL/min); and for 3.86% solution, 1.05 ± 0.78 mL/min (95% CI: 0.77 to 1.33 mL/min). Peritoneal absorption volumes and rates from the 4th to the 8th hour showed good correlations for the various solutions.

Conclusions

Using any glucose solution, the prolonged PET with voiding and reinfusion at the 4th hour could be a practical method for calculating overall peritoneal absorption from the 4th to the 8th hour in PD patients.
Spreadable media: Creating value and meaning in a networked culture
Authors: Stein Louisa Ellen
Published: September 2014

Online Roundtable on Spreadable Media, by Henry Jenkins, Sam Ford, and Joshua Green, with participants Paul Booth, Kristina Busse, Melissa Click, Sam Ford, Henry Jenkins, Xiaochang Li, and Sharon Ross. Section 1 first published as "Spreadable Media: Creating Value and Meaning in a Networked Culture," by Louisa Stein, Cinema Journal 53 (3): 152–77. Copyright 2014 by The University of Texas Press. All rights reserved.
L’étudiant déficient visuel dans l’enseignement supérieur : ses rapports à l’institution, ses relations avec les enseignants et ses pairs
Authors: Carrière Véronique
Published: September 2014

Cette recherche s’intéresse à l’inclusion des étudiants déficients visuels dans l’enseignement supérieur depuis la loi 2005 sur l’égalité des chances. Plus spécifiquement, nous nous intéressons aux rapports de ces étudiants avec l’institution, leurs pairs et les enseignants. Les résultats nous indiquent que si cette loi, par le biais des chargés d’accueil du service des étudiants en situation de handicap, facilite les rapports avec l’institution, les représentations sociales liées au handicap peuvent influer sur les relations entre les individus. En effet, ces représentations, imprégnées par des stéréotypes, peuvent constituer une difficulté dans les relations entre les étudiants déficients visuels, leurs pairs et les enseignants. De ce fait, les freins à la communication peuvent entraîner des difficultés à demander les adaptations requises pour accéder aux ressources pédagogiques.
La question de l’égalité des parcours en faculté de médecine : les conditions d’entrée à l’université des nouvelles carabines
Authors: Avenel Céline
Published: September 2014

Au cours de ces vingt dernières années, les études de médecine ont connu une féminisation massive de ces effectifs d’étudiant-e-s du premier au dernier cycle. Les filles sont devenues largement majoritaires (64 %) parmi les étudiants de première année en 2002 (Hérault et Labarthe, 2003). Cette féminisation massive actuelle représente donc une véritable « bascule» historique. Nous proposons une lecture socio-sexuée de cette féminisation, évolution majeure du système universitaire français, au regard de la combinaison de deux principes : celui de l’égalité des parcours en médecine et celui de l’égalité des sexes. Quelles peuvent être les incidences d’un mouvement d’une telle ampleur en termes de trajectoires des futur-e-s étudiant-e-s de médecine ? Cette féminisation participe-t-elle à une égalité d’accès aux études de médecine, en termes d’origines sociales ?
La responsabilité sociale des universités en France : un concept en émergence ?
Authors: Annoot Emmanuelle
Published: September 2014

Des réformes récentes ont renforcé les liens entre les universités et leur territoire en France. Les collectivités et les associations jouent un rôle considérable pour accompagner ces politiques de développement des établissements. Les universités autonomes sont ainsi confirmées comme des acteurs économiques, sociaux et culturels majeurs dans leur environnement. Ces orientations modifient la place de l’université dans la société. La responsabilité sociale des universités commence à être évoquée quand l’institution répond aux besoins des habitants d’un territoire en matière de vie sociale et de culture. En particulier, l’accès aux études supérieures, la fidélisation des diplômés constituent des enjeux locaux qui valorisent le rôle de service public des universités. Reste à étudier les effets de l’autonomie des établissements sur la démocratisation de l’accès à la connaissance au cœur de ces nouvelles formes de régulation entre échelons européen, national et local.
La responsabilité sociale de l’enseignement supérieur au Brésil
Authors: Tassigny Monica Mota , Annoot Emmanuelle
Published: September 2014

Dans un monde globalisé, la responsabilité sociale des universités tend à s’étendre au-delà de leurs propres frontières. Dans un entretien accordé à Emmanuelle Annoot, Monica M. Tassigny, Professeur Dr. à l’Université de Fortaleza UNIFOR (Brésil), expose les possibilités d’articulations entre l’université et la collectivité, soulignant ainsi le rôle de la responsabilité sociale universitaire brésilienne et plus particulièrement, celui de l’Université de Fortaleza.
Une méthode pour approcher les présentations de soi dans les communications : l’analyse des adresses
Authors: Dutoit Martine
Published: September 2014

Un grand nombre de recherches, ayant d’autres objets que la présentation de soi, notamment des recherches en éducation et formation, utilisent de fait comme matériau des informations obtenues en situation de présentation de soi, ce qui pose d’emblée la question de l’influence de cette situation de communication sur les énoncés recueillis par le chercheur. Bien souvent, ce dernier croit avoir accès à une parole personnelle et privée, alors qu’il s’agit d’une parole adressée. Difficile dans ces conditions de ne pas mettre en rapport les contenus du discours et les adressages du discours avant d’en faire une utilisation pour la recherche. L’objet de cet article est d’exposer et d’explorer une approche méthodologique et ses résultats pour l’analyse des présentations de soi en groupe dans une situation de communication. La situation de référence est une situation de communication publique de personnes étiquetées (patients de la psychiatrie) visant à changer les représentations de leurs destinataires sur leur groupe d’appartenance. Il a été choisi, notamment, de privilégier l’analyse des « adresses» du discours.
Distorsions dans les interactions entre adultes et enfants
Authors: M’Badi Miehakanda
Published: September 2014

Cette approche des interactions adultes-enfants se situe dans le cadre des théories des actes de langage, avec pour objet l’observation éthologique et l’analyse pragmatique des pratiques langagières parcourues par des distorsions interactionnelles.
L’écriture comme analyseur des tensions identitaires dans une formation professionnalisante à l’université
Authors: Guillemot Valérie , Vial Michel
Published: September 2014

Cet article rend compte d’une recherche en sciences de l’éducation, à l’occasion de laquelle le traitement d’un corpus de données met en évidence la tension d’un remaniement identitaire accéléré par le dispositif de professionnalisation que constitue une formation diplômante professionnalisante en sciences de l’éducation à l’Université. À partir du postulat que l’écrit joue un rôle d’accélérateur d’un changement en cours, cet article questionne la place spécifique des productions écrites, commandes ou non, dans l’expression de ces tensions et dans le remaniement identitaire de son auteur.
Alpha-1 Antitrypsin Augmentation Therapy Corrects Accelerated Neutrophil Apoptosis in Deficient Individuals
Authors: Hurley Killian , Lacey Noreen , O’Dwyer Ciara A. , Bergin David A. , McElvaney Oliver J. , O’Brien M. Emmet , McElvaney Oisín F. , Reeves Emer P. , McElvaney Noel G.
Published: September 2014

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by neutrophil-driven lung destruction and early emphysema in a low AAT, and high neutrophil elastase environment in the lungs of affected individuals. In this study, we examined peripheral blood neutrophil apoptosis and showed it to be accelerated in individuals with AATD by a mechanism involving endoplasmic reticulum stress and aberrant TNF-α signaling. We reveal that neutrophil apoptosis in individuals homozygous for the Z allele (PiZZ) is increased nearly 2-fold compared with healthy controls and is associated with activation of the external death pathway. We demonstrate that in AATD, misfolded AAT protein accumulates in the endoplasmic reticulum of neutrophils, leading to endoplasmic reticulum stress and the expression of proapoptotic signals, including TNF-α, resulting in increased apoptosis and defective bacterial killing. In addition, treatment of AATD individuals with AAT augmentation therapy decreased neutrophil ADAM-17 activity and apoptosis in vivo and increased bacterial killing by treated cells. In summary, this study demonstrates that AAT can regulate neutrophil apoptosis by a previously unidentified and novel mechanism and highlights the role of AAT augmentation therapy in ameliorating inflammation in AATD.
Autoimmune Predisposition in Down Syndrome May Result from a Partial Central Tolerance Failure due to Insufficient Intrathymic Expression of AIRE and Peripheral Antigens
Authors: Giménez-Barcons Mireia , Casteràs Anna , Armengol Maria del Pilar , Porta Eduard , Correa Paula A. , Marín Ana , Pujol-Borrell Ricardo , Colobran Roger
Published: September 2014

Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals.
Imipramine Exploits Histone Deacetylase 11 To Increase the IL-12/IL-10 Ratio in Macrophages Infected with Antimony-Resistant Leishmania donovani and Clears Organ Parasites in Experimental Infection
Authors: Mukherjee Sandip , Mukherjee Budhaditya , Mukhopadhyay Rupkatha , Naskar Kshudiram , Sundar Shyam , Dujardin Jean-Claude , Roy Syamal
Published: September 2014

The efflux of antimony through multidrug resistance protein (MDR)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant Leishmania donovani (SbRLD). Previously we showed that MDR-1 upregulation in SbRLD infection is IL-10–dependent. Imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits IL-10 production from SbRLD-infected macrophages (SbRLD-Mϕs) and favors accumulation of surrogates of antimonials. It inhibits IL-10–driven nuclear translocation of c-Fos/c-Jun, critical for enhanced MDR-1 expression. The drug upregulates histone deacetylase 11, which inhibits acetylation of IL-10 promoter, leading to a decrease in IL-10 production from SbRLD-Mϕs. It abrogates SbRLD-mediated p50/c-Rel binding to IL-10 promoter and preferentially recruits p65/RelB to IL-12 p35 and p40 promoters, causing a decrease in IL-10 and overproduction of IL-12 in SbRLD-Mϕs. Histone deacetylase 11 per se does not influence IL-12 promoter activity. Instead, a imipramine-mediated decreased IL-10 level allows optimal IL-12 production in SbRLD-Mϕs. Furthermore, exogenous rIL-12 inhibits intracellular SbRLD replication, which can be mimicked by the presence of Ab to IL-10. This observation indicated that reciprocity exists between IL-10 and IL-12 and that imipramine tips the balance toward an increased IL-12/IL-10 ratio in SbRLD-Mϕs. Oral treatment of infected BALB/c mice with imipramine in combination with sodium stibogluconate cleared organ SbRLD parasites and caused an expansion of the antileishmanial T cell repertoire where sodium stibogluconate alone had no effect. Our study deciphers a detailed molecular mechanism of imipramine-mediated regulation of IL-10/IL-12 reciprocity and its impact on SbRLD clearance from infected hosts.
Fc-Optimized NKG2D–Fc Constructs Induce NK Cell Antibody-Dependent Cellular Cytotoxicity against Breast Cancer Cells Independently of HER2/neu Expression Status
Authors: Raab Stefanie , Steinbacher Julia , Schmiedel Benjamin J. , Kousis Philaretos C. , Steinle Alexander , Jung Gundram , Grosse-Hovest Ludger , Salih Helmut R.
Published: September 2014

The ability of NK cells to mediate Ab-dependent cellular cytotoxicity (ADCC) largely contributes to the clinical success of antitumor Abs, including trastuzumab, which is approved for the treatment of breast cancer with HER2/neu overexpression. Notably, only ∼25% of breast cancer patients overexpress HER2/neu. Moreover, HER2/neu is expressed on healthy cells, and trastuzumab application is associated with side effects. In contrast, the ligands of the activating immunoreceptor NKG2D (NKG2DL) are selectively expressed on malignant cells. In this study, we took advantage of the tumor-associated expression of NKG2DL by using them as target Ags for NKG2D-IgG1 fusion proteins optimized by amino acid exchange S239D/I332E in their Fc part. Compared to constructs with wild-type Fc parts, fusion proteins carrying the S239D/I332E modification (NKG2D–Fc–ADCC) mediated highly enhanced degranulation, ADCC, and IFN-γ production of NK cells in response to breast cancer cells. NKG2D–Fc–ADCC substantially enhanced NK reactivity also against HER2/neu-low targets that were unaffected by trastuzumab, as both compounds mediated their immunostimulatory effects in strict dependence of target Ag expression levels. Thus, in line with the hierarchically organized potential of the various activating receptors governing NK reactivity and due to its highly increased affinity to CD16, NKG2D–Fc–ADCC potently enhances NK cell reactivity despite the inevitable reduction of activating signals upon binding to NKG2DL. Due to the tumor-restricted expression of NKG2DL, NKG2D–Fc–ADCC may constitute an attractive means for immunotherapy especially of HER2/neu-low or -negative breast cancer.
Therapeutic Activity of High-Dose Intratumoral IFN-β Requires Direct Effect on the Tumor Vasculature
Authors: Spaapen Robbert M. , Leung Michael Y. K. , Fuertes Mercedes B. , Kline Justin P. , Zhang Long , Zheng Yan , Fu Yang-Xin , Luo Xixi , Cohen Kenneth S. , Gajewski Thomas F.
Published: September 2014

Endogenous type I IFN production after innate immune recognition of tumor cells is critical for generating natural adaptive immune responses against tumors in vivo. We recently have reported that targeting low doses of IFN-β to the tumor microenvironment using tumor-specific mAbs can facilitate antitumor immunity, which could be augmented further with PD-L1/PD-1 blockade. However, sustained high doses of type I IFNs in the tumor microenvironment, which are potently therapeutic alone, may function through distinct mechanisms. In the current report, we demonstrate that high-dose intratumoral type I IFNs indeed exerted a profound therapeutic effect in the murine B16 model, which unexpectedly did not increase T cell responses. Moreover, bone marrow chimeras revealed a role for type I IFN signaling on nonhematopoietic cells, and most of the therapeutic effect was retained in mice deficient in T, B, and NK cells. Rather, the tumor vasculature was ablated with high-dose intratumoral IFN-β, and conditional deletion of IFN-α/βR in Tie2-positive vascular endothelial cells eliminated most of the antitumor activity. Therefore, the major component of the antitumor activity of sustained high doses of type I IFNs occurs through a direct antiangiogenic effect. Our data help resolve conditions under which distinct antitumor mechanisms of type I IFNs are operational in vivo.
Aging Delays Resolution of Acute Inflammation in Mice: Reprogramming the Host Response with Novel Nano-Proresolving Medicines
Authors: Arnardottir Hildur H. , Dalli Jesmond , Colas Romain A. , Shinohara Masakazu , Serhan Charles N.
Published: September 2014

Aging is associated with an overt inflammatory phenotype and physiological decline. Specialized proresolving lipid mediators (SPMs) are endogenous autacoids that actively promote resolution of inflammation. In this study, we investigated resolution of acute inflammation in aging and the roles of SPMs. Using a self-resolving peritonitis and resolution indices coupled with lipid mediator metabololipidomics, we found that aged mice had both delayed resolution and reduced SPMs. The SPM precursor docosahexaenoic acid accelerated resolution via increased SPMs and promoted human monocyte reprogramming. In aged mice, novel nano-proresolving medicines carrying aspirin-triggered resolvins D1 and D3 reduced inflammation by promoting efferocytosis. These findings provide evidence for age-dependent resolution pathways in acute inflammation and novel means to activate resolution.
The microRNA Biogenesis Machinery Modulates Lineage Commitment during αβ T Cell Development
Authors: Rupp Levi J. , Brady Brenna L. , Carpenter Andrea C. , De Obaldia Maria Elena , Bhandoola Avinash , Bosselut Remy , Muljo Stefan A. , Bassing Craig H.
Published: September 2014

Differentiation of CD4+ helper and CD8+ cytotoxic αβ T cells from CD4+CD8+ thymocytes involves upregulation of lineage-specifying transcription factors and transcriptional silencing of CD8 or CD4 coreceptors, respectively, in MHC class II or I (MHCII or I)–restricted thymocytes. In this study, we demonstrate that inactivation of the Dicer RNA endonuclease in murine thymocytes impairs initiation of Cd4 and Cd8 silencing, leading to development of positively selected MHCI- and MHCII-restricted mature CD4+CD8+ thymocytes. Expression of the antiapoptotic BCL2 protein or inactivation of the p53 proapoptotic protein rescues these thymocytes from apoptosis, increasing their frequency and permitting accumulation of CD4+CD8+ αβ T cells in the periphery. Dicer-deficient MHCI-restricted αβ T cells fail to normally silence Cd4 and display impaired induction of the CD8 lineage–specifying transcription factor Runx3, whereas Dicer-deficient MHCII-restricted αβ T cells show impaired Cd8 silencing and impaired induction of the CD4 lineage–specifying transcription factor Thpok. Finally, we show that the Drosha RNA endonuclease, which functions upstream of Dicer in microRNA biogenesis, also regulates Cd4 and Cd8 silencing. Our data demonstrate a previously dismissed function for the microRNA biogenesis machinery in regulating expression of lineage-specifying transcription factors and silencing of Cd4 and Cd8 during αβ T cell differentiation.
CD8+ T Cells Prevent Antigen-Induced Antibody-Dependent Enhancement of Dengue Disease in Mice
Authors: Zellweger Raphaël M. , Eddy William E. , Tang William W. , Miller Robyn , Shresta Sujan
Published: September 2014

Dengue virus (DENV) causes pathologies ranging from the febrile illness dengue fever to the potentially lethal severe dengue disease. A major risk factor for developing severe dengue disease is the presence of subprotective DENV-reactive Abs from a previous infection (or from an immune mother), which can induce Ab-dependent enhancement of infection (ADE). However, infection in the presence of subprotective anti–DENV Abs does not always result in severe disease, suggesting that other factors influence disease severity. In this study we investigated how CD8+ T cell responses influence the outcome of Ab-mediated severe dengue disease. Mice were primed with aluminum hydroxide–adjuvanted UV-inactivated DENV prior to challenge with DENV. Priming failed to induce robust CD8+ T cell responses, and it induced nonneutralizing Ab responses that increased disease severity upon infection. Transfer of exogenous DENV-activated CD8+ T cells into primed mice prior to infection prevented Ab-dependent enhancement and dramatically reduced viral load. Our results suggest that in the presence of subprotective anti–DENV Abs, efficient CD8+ T cell responses reduce the risk of Ab-mediated severe dengue disease.
SAP-Regulated T Cell–APC Adhesion and Ligation-Dependent and -Independent Ly108–CD3ζ Interactions
Authors: Chu Coco , Wang Yifeng , Zhang Xu , Ni Xinya , Cao Junxia , Xu Wan , Dong Zhongjun , Yuan Pengfei , Wei Wensheng , Ma Yuanwu , Zhang Lianfeng , Wu Longyan , Qi Hai
Published: September 2014

The germinal center response requires cooperation between Ag-specific T and B lymphocytes, which takes the form of long-lasting cell–cell conjugation in vivo. Signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) is required for stable cognate T–B cell conjugation, whereas SLAM family transmembrane (TM) receptor Ly108 may negatively regulate this process. We show that, other than phosphotyrosine-binding, SAP does not harbor motifs that recruit additional signaling intermediates to stabilize T–B adhesion. Ly108 dampens T cell adhesion to not only Ag-presenting B cells, but also dendritic cells by inhibiting CD3ζ phosphorylation through two levels of regulated Ly108–CD3ζ interactions. Constitutively associated with Src homology 2 domain–containing tyrosine phosphatase-1 even in SAP-competent cells, Ly108 is codistributed with the CD3 complex within a length scale of 100–200 nm on quiescent cells and can reduce CD3ζ phosphorylation in the absence of overt TCR stimulation or Ly108 ligation. When Ly108 is engaged in trans during cell–cell interactions, Ly108–CD3ζ interactions are promoted in a manner that uniquely depends on Ly108 TM domain, leading to more efficient CD3ζ dephosphorylation. Whereas replacement of the Ly108 TM domain still allows the constitutive, colocalization-dependent inhibition of CD3ζ phosphorylation, it abrogates the ligation-dependent Ly108–CD3ζ interactions and CD3ζ dephosphorylation, and it abolishes the suppression on Ag-triggered T–B adhesion. These results offer new insights into how SAP and Ly108 antagonistically modulate the strength of proximal TCR signaling and thereby control cognate T cell–APC interactions.
Asymptotic morphisms and superselection theory in the scaling limit
Authors: Conti Roberto , Morsella Gerardo
Published: September 2014

Given a local Haag–Kastler net of von Neumann algebras and one of its scaling limit states, we introduce a variant of the notion of asymptotic morphism by Connes and Higson, and we show that the unitary equivalence classes of (localized) morphisms of the scaling limit theory of the original net are in bijection with classes of suitable pairs of such asymptotic morphisms. In the process, we also show that the quasi-local C*-algebras of two nets are isomorphic under very general hypotheses, and we construct an extension of the scaling algebra whose representation on the scaling limit Hilbert space contains the local von Neumann algebras. We also study the relation between our asymptotic morphisms and superselection sectors preserved in the scaling limit.
Theoretical and Experimental Investigation of Magneto-Rheological Damper based Semi-Active Suspension Systems
Authors: Shojaei Alisina , Metered H. , Shojaei Siamak , Oyadiji S. Olutunde
Published: September 2014

Semi-active vehicle suspension systems with Magneto-Rheological (MR) dampers have recently received an increasing attention. Satisfactory performance of these systems is highly dependent on the adopted control method. This paper offers theoretical and experimental investigation of the control of vehicle suspension systems using a quarter car suspension equipped with a MR damper. To achieve the best performance, a control method made of two nested controllers is used. Fuzzy logic, skyhook and On-Off control techniques are studied as system controllers in conjunction with a Heaviside step function as the damper controller. For the theoretical study, the modified Bouc-Wen model of MR dampers is used to calculate the damping force and a mathematical model of the semi-active quarter car suspension is derived and used in the simulation. To prove the applicability of the proposed fuzzy logic controller in a real suspension system, a two degrees of freedom quarter car test rig is designed and used. To quantify the effectiveness of the system under bump and random road disturbance, various performance criteria are evaluated based on the dynamic response of the quarter car suspension system in time and frequency domains,. Simulation and experimental results from the system with the fuzzy logic controllers are compared to the results from the system with skyhook controller, On-Off controller, a passive MR damper and a conventional passive damper.
Phytoplankton blooms on the western shelf of Tasmania: evidence of a highly productive ecosystem
Authors: Kämpf J.
Published: September 2014

Abstract. Analyses of >10 years of satellite-derived ocean-color data reveal the existence of a highly productive ecosystem on the west Tasmanian shelf. A closer event-based analysis indicates that the nutrient supply for this system has two different dynamical origins: (a) wind-driven coastal upwelling and (b) river plumes. During austral summer months, the west Tasmanian shelf forms a previously unknown upwelling center of the "Great South Australian Coastal Upwelling System", presumably injecting nutrient-rich water into western Bass Strait. Surprisingly, river discharges render the study region productive during other seasons of the year, except when nutrient-poor water of the South Australian Current reaches the region. Overall, the west Tasmanian shelf is more phytoplankton-productive than the long-known coastal upwelling along the Bonney Coast. The existence of phytoplankton blooms during the off-upwelling-season may explain the wintertime spawing aggregations of the blue grenadier (Macruronus novaezelandiae) and the associated regionally high abundance of Australian fur seals (Arctocephalus pusillus doriferus).
EDUCAÇÃO A DISTÂNCIA (EAD) E O USO DAS TECNOLOGIAS DE INFORMAÇÃO E COMUNICAÇÃO (TICS), BASEADA EM AMBIENTES VIRTUAIS DE APRENDIZAGEM (AVA) Algumas Reflexões sobre a Importância da Tutoria On-Line
Authors: Paese Cláudia Regina
Published: September 2014

O artigo trata da educação à distância (EAD), baseada na utilização de tecnologias de informação e comunicação (TICs) on-line. Analisamos, especificamente, os ambientes virtuais de aprendizagem (AVAs), que demandam a orientação de um tutor. Seu objetivo é discutir e analisar as estratégias metodológicas da EAD frente ao uso de tecnologias de informação e comunicação (TICs). Tais estratégias são mediadas pedagogicamente pelo trabalho dos tutores on-line, "uma nova prática" fundamental para o processo de efetivação da aprendizagem dos estudantes nessa modalidade. Este estudo iniciou-se após minha entrada no grupo de pesquisa “Ciência, Tecnologia e Inovação Tecnológica – INTEC” da UFMT, que estuda a relação entre tecnologia e sociedade, mediada pelas inovações.
O LÚDICO COMO FACILITADOR DA APRENDIZAGEM NA SALA DE AULA
Authors: Mendes Silva Ana Regina
Published: September 2014

Através de uma abordagem construtivista o trabalho apresentado para esse artigo buscou na ludicidade a construção do conhecimento do educando. O suporte para encaminhar a analise dos resultados e conclusão deste estudo baseou-se  em alguns autores que defendem essa teoria, o trabalho visando relatar os dados obtidos  através da  pesquisa. O trabalho visa relatar os dados obtidos através de uma pesquisa desenvolvida em uma Escola Estadual da periferia na cidade de Jataí –Go, onde foi realizada a inserção do lúdico em duas (2), turmas do oitavo ano do ensino fundamental, sobre o conteúdo: Sistema Renal. Através desta, pôde-se comprovar que o lúdico se usada corretamente como uma ferramenta poderá ser significativo para a aquisição e apreensão do conhecimento.