bluuebunny/crossref_metadata_2025 huggingface dataset:
Measures of Outcome in Metastatic Breast Cancer: Insights From a Real-World Scenario
Authors: Bonotto Marta , Gerratana Lorenzo , Poletto Elena , Driol Pamela , Giangreco Manuela , Russo Stefania , Minisini Alessandro M. , Andreetta Claudia , Mansutti Mauro , Pisa Federica E. , Fasola Gianpiero , Puglisi Fabio
Published: May 2014

No gold standard treatment exists for metastatic breast cancer (MBC). Clinical decision making is based on knowledge of prognostic and predictive factors that are extrapolated from clinical trials and, sometimes, are not reliably transferable to a real-world scenario. Moreover, misalignment between endpoints used in drug development and measures of outcome in clinical practice has been noted. The roles of overall survival (OS) and progression-free survival (PFS) as primary endpoints in the context of clinical trials are the subjects of lively debate. Information about these parameters in routine clinical practice is potentially useful to design new studies and/or to interpret the results of clinical research. This study analyzed the impact of patient and tumor characteristics on the major measures of outcome across different lines of treatment in a cohort of 472 patients treated for MBC. OS, PFS, and postprogression survival (PPS) were analyzed. The study showed how biological and clinical characteristics may have different prognostic value across different lines of therapy for MBC. After first-line treatment, the median PPS of luminal A, luminal B, and human epidermal growth factor receptor 2 (HER2)-positive groups was longer than 12 months. The choice of OS as a primary endpoint for clinical trials could not be appropriate with these subtypes. In contrast, OS could be an appropriate endpoint when PPS is expected to be low (e.g., triple-negative subtype after the first line; other subtypes after the third line). The potential implications of these findings are clinical and methodological.
Simulating hydration of cement paste based on a kinetics model modified by nanoindentation modulus
Authors: Wang Wei , Yao Wu , Liang Kang
Published: May 2014

This paper presents a kinetics model that describes the hydration of cement paste. The kinetics model extends an earlier version by linking the diffusion coefficients in the model and the nanoindentation modulus of calcium silicate hydrate gel that occurs owing to the relationship between the diffusivity and porosity of calcium silicate hydrate gel and the relation of the porosity of calcium silicate hydrate gel to its indentation modulus. Using the modified model, this paper predicts the hydration degree of cement paste at different curing temperatures, different water to cement ratios and different curing conditions. The agreement between model predictions and experimental results demonstrates that the modified model is quite effective, especially for the study of the effects of temperature, water to cement ratio and curing conditions on the hydration kinetics of cement paste.
Refurbishment of South Bridge, Oundle, Northamptonshire, UK
Authors: Price Raymond D. , Grindley Sara , Grindley David , Jichi Mohamad
Published: May 2014

Oundle is a picturesque and historic market town in north Northamptonshire that lies on the banks of the River Nene. South Bridge lies on the south western outskirts of the town and formed an important transport link around the western side. It is a seven-span stone arch structure dating back to medieval times and is a scheduled monument and grade II listed. Following the discovery of a leak from a water main, concern was expressed regarding the structural integrity of parts of the bridge and it was decided to close the bridge to traffic for reasons of public safety. This paper describes the original leakage incident and the subsequent procedures that were adopted to reopen the bridge. Assessment of the bridge condition, stakeholder engagement, refurbishment options, works procurement, site works and subsequent monitoring are described.
Assessment of the consolidated breakout response of partially embedded subsea pipelines
Authors: CHATTERJEE S. , GOURVENEC S. , WHITE D.J.
Published: May 2014

The changing soil strength due to consolidation around a subsea pipeline can alter the lateral breakout resistance. Results of elasto-plastic coupled consolidation finite-element analyses are presented that quantify the effect of consolidation on the undrained breakout resistance and trajectory of partially embedded seabed pipelines. Breakout resistance is presented in terms of failure envelopes in vertical–horizontal load space, which also allow the trajectory of the pipe during breakout to be determined by normality. Observed responses for consolidated undrained breakout are described by simple algebraic expressions as a function of initial pipe embedment, pipe self-weight (and consequent consolidation pressure) and breakout load path. Consolidation and the associated enhancement of the shear strength of the surrounding soil can have a significant effect on the breakout response. The assumption in current practice of unconsolidated undrained soil behaviour may lead to underestimation of pipeline breakout resistance and inaccurate prediction of the trajectory of the pipe during breakout.
EMDR as a Therapeutic Treatment for Complex Regional Pain Syndrome: A Case Report
Authors: Hughes Megan
Published: May 2014

Complex regional pain syndrome (CRPS) is characterized by ongoing pain, swelling, and stiffness following an acute injury. CRPS is difficult to diagnose, significantly impacts functioning, and is frequently incurable. Current treatments are pharmacotherapy, surgery, and physiotherapy. This case report describes the use of eye movement desensitization and reprocessing (EMDR) in the psychotherapeutic treatment of a woman diagnosed with CRPS in 2009 as a result of injuries sustained during an assault in 2004. This article reports on EMDR treatment provided 1–2 years after her diagnosis. At initial assessment, the client was debilitated and suicidal, unable to work or care for her children, and dependent on her family for financial support because of CRPS. Two phases of 7 EMDR sessions were provided; the first focused on past traumatic experiences; the second addressed her pain with Grant’s (2009) EMDR chronic pain protocol. At the end of treatment, the client reported decreased pain, decreased substance dependence, improved mood and outlook, and was able to resume part-time work. Results were maintained at 8-month follow-up and suggest that EMDR was helpful for this client in reducing the symptoms associated with CRPS.
Vitamin D Status and 5‐Year Changes in Periodontal Disease Measures Among Postmenopausal Women: The Buffalo OsteoPerio Study
Authors: Millen Amy E. , Andrews Christopher A. , LaMonte Michael J. , Hovey Kathleen M. , Swanson Mya , Genco Robert J. , Wactawski‐Wende Jean
Published: May 2014

Background: Vitamin D is hypothesized to prevent periodontal disease progression through its immune‐modulating properties and its role in maintaining systemic calcium concentrations. The authors investigated associations between plasma 25‐hydroxyvitamin D [25(OH)D] (collected 1997 to 2000) and the 5‐year change in periodontal disease measures from baseline (1997 to 2000) to follow‐up (2002 to 2005) among 655 postmenopausal women in a Women's Health Initiative Observational Study ancillary study. Exploratory analyses were conducted in 628 women who also had 25(OH)D measures at follow‐up.

Methods: Four continuous measures of the 5‐year change in periodontal disease were assessed using alveolar crest height (ACH), clinical attachment level (CAL), probing depth (PD), and percentage of gingival sites that bled on assessment. Linear regression was used to estimate β‐coefficients, standard errors, and P values corresponding to change in periodontal disease (a 1‐mm change in ACH, CAL, or PD or a 1‐unit change in the percentage of gingival sites that bled) for a 10‐nmol/L difference in 25(OH)D. Models were adjusted for age, education, dental visit frequency, smoking, diabetes status, current medications affecting bone health, baseline measures of periodontal disease, body mass index, and recreational physical activity.

Results: No statistically significant associations were observed between baseline 25(OH)D and change in periodontal disease measures, overall or in a subset (n = 442) of women with stable 25(OH)D concentrations [25(OH)D change <20 nmol/L from baseline to follow‐up]. Results also did not vary significantly in analyses that were stratified by baseline periodontal disease status.

Conclusions: No association between baseline 25(OH)D and the subsequent 5‐year change in periodontal disease measures was observed. Vitamin D status may not influence periodontal disease progression. More studies are needed to confirm these results.
Crestal Bone Level Changes Around Immediately Placed Implants: A Systematic Review and Meta‐Analyses With at Least 12 Months’ Follow‐Up After Functional Loading
Authors: Kinaia Bassam M. , Shah Maanas , Neely Anthony L. , Goodis Harold E.
Published: May 2014

Background: Immediate implant placement (IIP) is a successful treatment and has the advantages of reducing time and increasing patient satisfaction. However, achieving predictable esthetic results with IIP presents a challenge because of naturally occurring bone loss postextraction. Therefore, the focused question of this systematic review is: What is the effect of IIP on crestal bone level (CBL) changes after at least 12 months of functional loading?

Methods: Extensive literature review of the Cochrane and MEDLINE electronic databases and a manual search up to November 2012 identified eligible studies. Two reviewers independently assessed the study data and methodologic quality using data extraction and assessment forms.

Results: Electronic and manual searches identified 648 relevant publications. A total of 57 articles satisfied the inclusion criteria. Sixteen studies had test and control groups; therefore, meta‐analyses could be performed. The results demonstrated better CBL preservation around IIP compared with implant placement in healed/native bone at 12 months [CBL difference of −0.242 (95% confidence interval [CI], −0.403 to −0.080; P = 0.003)]. Similarly, platform switching around IIP showed better results compared with non–platform switching (CBL difference of −0.770 [95% CI, −1.153 to −0.387; P <0.001]). There was no difference in mean CBL changes with regard to one‐stage or two‐stage IIP protocol (−0.017 [95% CI, −0.249 to 0.216; P = 0.85]) or the use of immediate or delayed immediate implant loading (0.002 [95% CI, −0.269 to 0.272; P = 0.99]).

Conclusions: Meta‐analyses showed less CBL loss around IIP compared with implant placement in healed bone. Platform‐switched implants showed greater crestal bone preservation than non–platform‐switched implants. There was no significant difference in CBL with one‐ versus two‐stage placement or use of immediate versus delayed IIP loading. Although there were statistically significant differences favoring IIP, the small differences may not be clinically relevant. Although IIP showed favorable outcomes for CBL changes, these results should be interpreted with caution because of high heterogeneity among studies.
Detection and Quantification of Periodontal Pathogens in Smokers and Never‐Smokers With Chronic Periodontitis by Real‐Time Polymerase Chain Reaction
Authors: Guglielmetti Mariana R. , Rosa Ecinele F. , Lourenção Daniele S. , Inoue Gislene , Gomes Elaine F. , De Micheli Giorgio , Mendes Fausto Medeiros , Hirata Rosário D.C. , Hirata Mario H. , Pannuti Claudio M.
Published: May 2014

Background: The purpose of the present investigation is to compare the presence and number of periodontal pathogens in the subgingival microbiota of smokers versus never‐smokers with chronic periodontitis and matched probing depths (PDs) using real‐time polymerase chain reaction (RT‐PCR).

Methods: Forty current smokers and 40 never‐smokers, matched for age, sex, and mean PD of sampling site, were included in this investigation. A full‐mouth periodontal examination was performed, and a pooled subgingival plaque sample was collected from the deepest site in each quadrant of each participant. To confirm smoking status, expired carbon monoxide (CO) concentrations were measured with a CO monitor. The presence and quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola were determined using RT‐PCR.

Results: Smokers had greater overall mean PD (P = 0.001) and attachment loss (P = 0.006) and fewer bleeding on probing sites (P = 0.001). An association was observed between smoking status and the presence of A. actinomycetemcomitans (P <0.001). The counts of A. actinomycetemcomitans (P <0.001), P. gingivalis (P = 0.042), and T. forsythia (P <0.001) were significantly higher in smokers.

Conclusions: Smokers showed significantly greater amounts of P. gingivalis, A. actinomycetemcomitans, and T. forsythia than never‐smokers. There was a significant association between smoking and the presence of A. actinomycetemcomitans.
Corrosion properties of Zn-Ni-P alloys in neutral model medium
Authors: Bachvarov Vassil , Peshova Miglena , Vitkova Stefana , Boshkov Nikolai
Published: May 2014

The presented work reports on the peculiarities of the anodic behavior, corrosion resistance and protective ability of electrodeposited Zn-Ni-P alloys with a different composition in a model corrosion medium of 5% NaCl. Three characteristic coating types have been investigated using experimental methods such as potentiodynamic polarization (PD) technique and polarization resistance (Rp) measurements. In addition, X-ray diffraction (XRD) analysis as well as scanning electron microscopy (SEM) coupled with an Energy-dispersive X-ray (EDAX) device were applied to determine the differences in the chemical composition and surface morphology which appeared as a result of the corrosion treatment. The data obtained are compared to those of electrodeposited pure Zn coatings with identical experimental conditions demonstrating the enhanced protective characteristics of the ternary alloys during the test period in the model medium. The influence of the chemical and phase composition of the alloys on its corrosion resistance and protective ability is also commented and discussed.
Career Attitudes of First-Year Veterinary Students Before and After a Required Course on Veterinary Careers
Authors: Fish Richard E. , Griffith Emily H.
Published: May 2014

Careers in Veterinary Medicine is a required, one-credit-hour course at the North Carolina State University College of Veterinary Medicine (NCSU-CVM), which meets once weekly during veterinary students' first semester. Lectures in this course are presented by one or more veterinarians representing diverse career areas. A voluntary, anonymous survey was distributed before the first class meeting in 2011 (PRE) and at the end of the semester (POST) to assess if students' career interests changed during the semester. The survey collected basic demographic data and students' preferences (on a Likert scale) for 17 veterinary career paths. Out of 63 students, 36 (57%) in the POST survey said that their career interests had changed during the semester, and 17 of the 26 students (65%) who gave a reason credited the careers course as one factor in reconsidering their career choice. Only 3 of the 17 career paths had statistically significant PRE/POST survey differences in Likert response frequency (equine practice, pathology, and wildlife medicine), but both informal discussions with students and responses to open-ended survey questions indicated that many students valued the introduction to unfamiliar veterinary career areas. Careers in Veterinary Medicine is a vital component of recent career-planning initiatives in the college, which will be especially important to veterinary students as they face continued changes in the profession, such as the increased debt load of the new graduate and the threat of veterinary workforce oversupply.
Collaborative Quiz-Based Teaching Strategy in Histology
Authors: Li Enzhong , Guo Yuping
Published: May 2014

In the present article we introduce a teaching strategy used in a histology course with first-year students in the first term of their studies at the Faculty of Veterinary Medicine at Huanghuai University, China. Forty students were randomly divided into two sections (n=20/section). Students in the first section were taught using a collaborative quiz-based strategy (the experimental section), and students in the second section were taught using a traditional teaching strategy (the control section). To assess achievement of learning, a final examination was carried out at the end of the course. To determine students' attitudes toward the teaching strategy used, a questionnaire was conducted at the end of the term. Results showed that students preferred the collaborative quiz-based teaching strategy. The final-examination scores of students in the experimental section were significantly higher than those of students in the control section (p<.05), which indicates that the collaborative quiz-based strategy results in better performance on examinations compared to the traditional histology course.
Using lexical variables to identify language ideologies in a policy corpus
Authors: Fitzsimmons-Doolan Shannon
Published: May 2014

Though theorised as important objects of inquiry, language ideologies – beliefs about the roles of language in society – are difficult to identify from texts because of their covert nature. Language ideologies of institutions are thought to have particular power with respect to subsequent policy development at micro- and macro levels. This study applies an inductive, corpus-based approach to identify language ideologies in a corpus of language policy texts using lexical items as variables. A corpus of more than one-million words of educational language policy texts from the 2010 Arizona Department of Education website was explored using collocate and factor analysis. The resulting solution accounted for 47.48 percent of the variance investigated. Five language ideology factors were identified and interpreted using quantitative and qualitative techniques: ‘written language as measurably communicative’, ‘language acquisition as systematically metalinguistic and monolingual’, ‘academic language as standard and informational’, ‘language acquisition as a process of decoding meaning’ and ‘nativeness of language skills as marking group variation’. The findings (a) present likely ideological stances of the Department of Education in a state where educational language policy development has been robust in recent years, and (b) validate the somewhat novel methodological approach used in this study.
Using regressions to explore deviations between corpus data and a standard/target: two suggestions
Authors: Gries Stefan Th. , Deshors Sandra C.
Published: May 2014

The main goal of this study is to develop more appropriate ways to study variation between corpus data that instantiate a linguistic standard or target on the one hand, and corpus data that are compared to that standard, or that represent speakers that may aspire to approximate the target (such as second- or foreign-language learners). Using the example of SLA/FLA research, we first, briefly, discuss a highly influential model, Granger's (1996) Contrastive Interlanguage Analysis (CIA), and the extent to which much current research fails to exploit this model to its full potential. Then, we outline a few methodological suggestions that, if followed, can elevate corpus-based analysis in SLA/FLA to a new level of precision and predictive accuracy. Specifically, we propose that, and exemplify how, the inclusion of statistical interactions in regressions on corpus data can highlight important differences between native speakers (NS) and learners/non-native speakers (NNS) with different native linguistic (L1) backgrounds. Secondly, we develop a two-step regression procedure that answers one of the most important questions in SLA/FLA research – ‘What would a native speaker do?’ – and, thus, allows us to study systematic deviations between NS and NNS at an unprecedented degree of granularity. Both methods are explained and exemplified in detail on the basis of over 5,000 uses of may and can produced by NSs of English and French and Chinese learners of English.
The Eternal Return of Teaching in the Time of the Corporation
Authors: Thompson Greg , Cook Ian
Published: May 2014

This article addresses the new conditions under which teachers are making the choice to teach. Our core contention is that the reorganisation of schools according to the logic of the corporation, as described in Deleuze's ‘Postscript’, is changing the flows and forces on the primary surface of ‘the classroom’. These changes block the usual movements of teaching to discipline, normalise and individualise, which was the role of the school as precursor to the factory. Blocked from repeating, or returning, teaching as it has always been done, teachers must actively re-will to teach; teachers cannot use order words to name themselves and direct flows and forces as they have usually been done. While many choices to teach will be undertaken, the most popular being that of choosing to teach toward the corporation, the repetition of teaching toward enclosed spaces becomes less compelling. Like Nietzsche's Zarathustra, teachers, who have the courage to actively choose, face a new dawn in which teaching cannot be what it once was. In that moment they must choose to repeat that choice an infinite number of times, the choice of eternal return, and it is from here that new times might begin.
An Isoflavone from Dipteryx alata Vogel is Active against the in Vitro Neuromuscular Paralysis of Bothrops jararacussu Snake Venom and Bothropstoxin I, and Prevents Venom-Induced Myonecrosis
Authors: Ferraz Miriéle , Yoshida Edson , Tavares Renata , Cogo José , Cintra Adélia , Dal Belo Cháriston , Franco Luiz , Dos Santos Márcio , Resende Flávia , Varanda Eliana , Hyslop Stephen , Puebla Pilar , San Feliciano Arturo , Oshima-Franco Yoko
Published: May 2014

Snakebite is a neglected disease and serious health problem in Brazil, with most bites being caused by snakes of the genus Bothrops. Although serum therapy is the primary treatment for systemic envenomation, it is generally ineffective in neutralizing the local effects of these venoms. In this work, we examined the ability of 7,8,3'-trihydroxy-4'-methoxyisoflavone (TM), an isoflavone from Dipteryx alata, to neutralize the neurotoxicity (in mouse phrenic nerve-diaphragm preparations) and myotoxicity (assessed by light microscopy) of Bothrops jararacussu snake venom in vitro. The toxicity of TM was assessed using the Salmonella microsome assay (Ames test). Incubation with TM alone (200 μg/mL) did not alter the muscle twitch tension whereas incubation with venom (40 μg/mL) caused irreversible paralysis. Preincubation of TM (200 μg/mL) with venom attenuated the venom-induced neuromuscular blockade by 84% ± 5% (mean ± SEM; n = 4). The neuromuscular blockade caused by bothropstoxin-I (BthTX-I), the major myotoxic PLA2 of this venom, was also attenuated by TM. Histological analysis of diaphragm muscle incubated with TM showed that most fibers were preserved (only 9.2% ± 1.7% were damaged; n = 4) compared to venom alone (50.3% ± 5.4% of fibers damaged; n = 3), and preincubation of TM with venom significantly attenuated the venom-induced damage (only 17% ± 3.4% of fibers damaged; n = 3; p < 0.05 compared to venom alone). TM showed no mutagenicity in the Ames test using Salmonella strains TA98 and TA97a with (+S9) and without (−S9) metabolic activation. These findings indicate that TM is a potentially useful compound for antagonizing the neuromuscular effects (neurotoxicity and myotoxicity) of B. jararacussu venom.
Interdépendance macro-économique des pays européens et propagation des chocs conjoncturels d'activité
Authors: Tavera Christophe , Rondeau Fabien
Published: May 2014

Cet article analyse le rôle du commerce international de biens en tant que canal de transmission des chocs macro-économiques conjoncturels entre les pays européens. Les interdépendances des conjonctures européennes sont modélisées à partir d’un processus VAR contraint. Les fonctions de réponses font apparaître que la capacité de diffusion des chocs conjoncturels d’un pays est clairement reliée aux parts commerciales de ce pays avec les autres pays partenaires. La construction d’un indicateur de diffusion des chocs conforte l’idée du rôle prépondérant des grandes économies telles que la France et l’Allemagne. Enfin, la synchronisation des mouvements conjoncturels des PIB européens devrait s’accroître si l’Union Monétaire conduit à une augmentation des échanges commerciaux intra-européens.
Les effets macroéconomiques de trois méthodes pures pour équilibrer le régime de retraite français
Authors: Brun Amandine
Published: May 2014

This study deals with the macroeconomic effects of population aging. We examine the effects of the various policies designed to ensure the equilibrium of the pay-as-you-go retirement pension system threatened by demographic trends. Policies include increased contributions, reduced replacement rate, and longer working period. Effects are assessed for an open economy and a closed economy. The study highlights the issues of inter-generation equity raised by each adjustment to the pension system. By examining utility shifts across generations, it attempts to rank these measures according to various criteria.
Premières simulations de la directive européenne sur les quotas d'émission avec le modèle GEMINI-E3
Authors: Viguier Laurent , Vielle Marc , Bernard Alain
Published: May 2014

The article assesses the European Directive on CO2 emission quotas using the GEMINI-E3 model. After summarizing the Directive and briefly describing the model, we present and analyze scenarios for different potential allocation rules. While the European quota mechanism creates a single market for eligible firms, it can also cause distortions vis-à-vis other economic sectors in each country. The arrangement does yield a single carbon price for all eligible firms, but a different carbon price for other sectors — with variations from country to country. The resulting excess costs can be significant.
Approche graphique du fonctionnement des contingents tarifaires : effets sur laccès au marché dimportation et le bien-être économique des exportateurs
Authors: Matthews Alan , Laroche-Dupraz Cathie
Published: May 2014

L’article étudie l’économie des contingents tarifaires sous l’hypothèse d’un grand pays importateur et en considérant que plusieurs offres d’exportation, aux niveaux de compétitivité distincts, se concurrencent sur le marché d’importation. Onze situations théoriques sont identifiées selon le niveau de contrainte imposé par le contingent sur les importations, la façon dont le quota est alloué aux exportateurs potentiels et les compétitivités relatives des offres en présence. Une représentation graphique est développée pour analyser chacune de ces situations et discuter des effets du contingent tarifaire en termes d’accès au marché d’importation, d’une part, et de bien-être économique pour les exportateurs qui bénéficient de cet instrument, d’autre part.
Radial variation in wood specific gravity of tropical tree species differing in growth–mortality strategies
Authors: Osazuwa‐Peters Oyomoare L. , Wright S. Joseph , Zanne Amy E.
Published: May 2014

•Premise of the study:Wood specific gravity (WSG) mediates an interspecific trade‐off between growth and mortality and is a key measure for estimating carbon stocks. Most studies use species mean values to represent WSG, despite variation at different levels of biological organization. We examined sources of variation in WSG across four nested scales (segments within cores, cores within trees, trees within species, and species), compared the pattern of radial variation in WSG among species differing in growth strategies, and investigated the effect of WSG radial variation on aboveground biomass estimates.

•Methods:We took two perpendicular cores from six individuals each of 20 tropical tree species representing a broad range of mean WSGs and growth–mortality strategies in a lowland tropical moist forest in Panama. Cores were divided into 1‐cm segments, and WSG was determined for each segment.

•Key results:The bulk of the total variance in WSG was dominated by interspecies variation (88%), whereas variation due to measurement error, segments within cores, and cores within trees (8%) was minimal. Radial variation in WSG, defined as change in WSG with increasing distance from the pith, was significant in 17 of the 20 species and included significant monotonic increases in 6 species and nonmonotonic patterns in 11 species. Radial variation in WSG resulted in a small but significant bias in aboveground biomass estimates.

•Conclusions:Radial variation in WSG is related to a species’ growth strategy and, though minimal compared with interspecific variation in WSG, can cause a downward bias when not incorporated into aboveground biomass estimates.
Du paysagement diffus à la condensation économique du paysage (1) : la valorisation de fragments urbains pétersbourgeois
Authors: Mager Christophe
Published: May 2014

Où est le paysage dans la ville, quand le paysage est partout ? Qu’est-ce qui fait paysage quand des « hommes sans qualités » – au sens de Robert Musil – se retrouvent projetés dans une ville inconnue (Saint-Pétersbourg) ? Qu’est-ce qui fait paysage quand un géographe (Laurent Matthey) et un économiste (Christophe Mager) se posent la question au gré de leurs pratiques de ville, toujours un peu imprégnées d’un savoir disciplinaire ? Ces questions qui relèvent de l’ontologie (de quoi parle le paysage ?), de l’épistémologie (comment penser le paysage ?) et de la politique (que fait-on collectivement quand on produit de la valeur paysagère). Nous avons néanmoins cherché à y répondre pratiquement : 1) en recourant à un principe méthodologique qui tient tout autant du transect paysager (il s’agissait de traverser la ville) que de la dérive situationniste (il s’agissait de traverser la ville dans tous les sens), 2) en usant d’une médiation technique (un téléphone portable dit intelligent) susceptible d’introduire un double effet de cadrage et de mise à distance et, 3) en définissant quelques contraintes formelles élémentaires (un dialogue réflexif et critique ancré dans des savoirs disciplinaires et des sensibilités distincts ; un jeu de rôle puisque le géographe radicalisera le côté impressionniste de ses notations, tandis que l’économiste accentuera l’appréhension de la réalité au travers de catégories aprioriques).
Du paysagement diffus à la condensation économique du paysage (2) : la valeur de l’ordinaire
Authors: Matthey Laurent
Published: May 2014

Où est le paysage dans la ville, quand le paysage est partout ? Qu’est-ce qui fait paysage quand des « hommes sans qualités » – au sens de Robert Musil – se retrouvent projetés dans une ville inconnue (Saint-Pétersbourg) ? Qu’est-ce qui fait paysage quand un géographe (Laurent Matthey) et un économiste (Christophe Mager) se posent la question au gré de leurs pratiques de ville, toujours un peu imprégnées d’un savoir disciplinaire ? Ces questions qui relèvent de l’ontologie (de quoi parle le paysage ?), de l’épistémologie (comment penser le paysage ?) et de la politique (que fait-on collectivement quand on produit de la valeur paysagère). Nous avons néanmoins cherché à y répondre pratiquement : 1) en recourant à un principe méthodologique qui tient tout autant du transect paysager (il s’agissait de traverser la ville) que de la dérive situationniste (il s’agissait de traverser la ville dans tous les sens), 2) en usant d’une médiation technique (un téléphone portable dit intelligent) susceptible d’introduire un double effet de cadrage et de mise à distance et, 3) en définissant quelques contraintes formelles élémentaires (un dialogue réflexif et critique ancré dans des savoirs disciplinaires et des sensibilités distincts ; un jeu de rôle puisque le géographe radicalisera le côté impressionniste de ses notations, tandis que l’économiste accentuera l’appréhension de la réalité au travers de catégories aprioriques).
Confronting the Productivity Challenge in the High Cost Economy
Authors: Ford Jerad A. , Steen John , Verreynne Martie-Louise , Farrell Bradley , Marion Gerald , Naicker Seelan
Published: May 2014

This chapter reports research findings into the productivity challenge facing the Australian oil and gas industry. This industry has been experiencing cost overruns indicating a productivity decline that puts future projects and investment at risk. Using world-class survey methodologies developed by the Centre for Business Research at Cambridge University and adapted for the oil and gas industry, an evidence-based view on business decisions and conditions is provided and linked to performance. While many of the productivity challenges facing the Australian oil and gas industry are beyond immediate managerial control, this research shows that key productivity drivers are in the realm of the firm to influence. The research reported in this chapter shows that improvements in innovation, collaboration, and deeper competitive capabilities are the best levers to lift business productivity and to build a growth pathway for the future for this industry.
Simulating an Incentive Framework for Scientific Production by Means of Adaptive Agents
Authors: Franklin Gabriel , Bonates Tibérius O.
Published: May 2014

This chapter describes an agent-based simulation of an incentive mechanism for scientific production. In the proposed framework, a central agency is responsible for devising and enforcing a policy consisting of performance-based incentives in an attempt to induce a global positive behavior of a group of researchers, in terms of number and type of scientific publications. The macro-level incentive mechanism triggers micro-level actions that, once intensified by social interactions, lead to certain patterns of behavior from individual agents (researchers). Positive reinforcement from receiving incentives (as well as negative reinforcement from not receiving them) shape the behavior of agents in the course of the simulation. The authors show, by means of computational experiments, that a policy devised to act at the individual level might induce a single global behavior that can, depending on the values of certain parameters, be distinct from the original target and have an overall negative effect. The agent-based simulation provides an objective way of assessing the quantitative effect that different policies might induce on the behavior of individual researchers when it comes to their preferences regarding scientific publications.
Towards a Multi-Agent-Based Tool for the Analysis of the Social Production and Management Processes in an Urban Ecosystem
Authors: Santos Flávia , Rodrigues Thiago , Donancio Henrique , Santos Iverton , Adamatti Diana F. , Dimuro Graçaliz P. , Dimuro Glenda , Jerez Esteban De Manuel
Published: May 2014

The SJVG-MAS Project addresses, in an interdisciplinary approach, the development of MAS-based tools for the simulation of the social production and management processes observed in urban ecosystems, adopting as case study the social vegetable garden project conducted at the San Jerónimo Park (Seville/Spain), headed by the confederation “Ecologistas en Acción.” The authors aim at the analysis of the current reality of the SJVG project, allowing discussions on the adopted social management processes, and also for investigating how possible changes in the social organization (e.g., roles assumed by the agents in the organization, actions, behaviors, (in)formal interaction/communication protocols, regulation norms), especially from the point of view of the agent's participation in the decision making processes, may transform this reality, from the social, environmental and economic point of view, then contributing for the sustainability of the project. The MAS was conceived as a multi-dimensional BDI-like agent social system, involving the development of five components: the agents' population, the system's organization, the system's environment, the set of interactions executed among agents playing organizational roles (e.g., communication protocols for reaching agreements) and the normative policy structure (internal regulation established by SJVG community). The aim of this chapter is to discuss the problems faced and to present the solution found for the modeling of SJVG social organization using JaCAMo framework. The chapter shows the integration of the considered dimensions, discussing the adopted methodology, which may be applied in several other contexts.
Increased Peripheral IL-4 Leads to an Expanded Virtual Memory CD8+ Population
Authors: Kurzweil Vanessa , LaRoche Ami , Oliver Paula M.
Published: May 2014

Memory-phenotype CD8+ T cells can arise even in the absence of overt Ag stimulation. Virtual memory (VM) CD8+ T cells are CD8+ T cells that develop a memory phenotype in the periphery of wild-type mice in an IL-15–dependent manner. Innate CD8+ T cells, in contrast, are memory-phenotype CD8+ T cells that develop in the thymus in response to elevated thymic IL-4. It is not clear whether VM cells and innate CD8+ T cells represent two independent T cell lineages or whether they arise through similar processes. In this study, we use mice deficient in Nedd4-family interacting protein 1 to show that overproduction of IL-4 in the periphery leads to an expanded VM population. Nedd4-family interacting protein 1−/− CD4+ T cells produce large amounts of IL-4 due to a defect in JunB degradation. This IL-4 induces a memory-like phenotype in peripheral CD8+ T cells that includes elevated expression of CD44, CD122, and Eomesodermin and decreased expression of CD49d. Thus, our data show that excess peripheral IL-4 is sufficient to cause an increase in the VM population. Our results suggest that VM and innate CD8+ T cells may be more similar than previously appreciated.
Steady-State Antigen Scavenging, Cross-Presentation, and CD8+ T Cell Priming: A New Role for Lymphatic Endothelial Cells
Authors: Hirosue Sachiko , Vokali Efthymia , Raghavan Vidya R. , Rincon-Restrepo Marcela , Lund Amanda W. , Corthésy-Henrioud Patricia , Capotosti Francesca , Halin Winter Cornelia , Hugues Stéphanie , Swartz Melody A.
Published: May 2014

Until recently, the known roles of lymphatic endothelial cells (LECs) in immune modulation were limited to directing immune cell trafficking and passively transporting peripheral Ags to lymph nodes. Recent studies demonstrated that LECs can directly suppress dendritic cell maturation and present peripheral tissue and tumor Ags for autoreactive T cell deletion. We asked whether LECs play a constitutive role in T cell deletion under homeostatic conditions. In this study, we demonstrate that murine LECs under noninflamed conditions actively scavenge and cross-present foreign exogenous Ags to cognate CD8+ T cells. This cross-presentation was sensitive to inhibitors of lysosomal acidification and endoplasmic reticulum–golgi transport and was TAP1 dependent. Furthermore, LECs upregulated MHC class I and the PD-1 ligand PD-L1, but not the costimulatory molecules CD40, CD80, or CD86, upon Ag-specific interactions with CD8+ T cells. Finally, Ag-specific CD8+ T cells that were activated by LECs underwent proliferation, with early-generation apoptosis and dysfunctionally activated phenotypes that could not be reversed by exogenous IL-2. These findings help to establish LECs as APCs that are capable of scavenging and cross-presenting exogenous Ags, in turn causing dysfunctional activation of CD8+ T cells under homeostatic conditions. Thus, we suggest that steady-state lymphatic drainage may contribute to peripheral tolerance by delivering self-Ags to lymph node–resident leukocytes, as well as by providing constant exposure of draining peripheral Ags to LECs, which maintain tolerogenic cross-presentation of such Ags.
S100A4 and Uric Acid Promote Mesenchymal Stromal Cell Induction of IL-10+/IDO+ Lymphocytes
Authors: Eisenbacher Judith Luiza , Schrezenmeier Hubert , Jahrsdörfer Bernd , Kaltenmeier Christof , Rojewski Markus Thomas , Yildiz Tatjana , Beyer Thamara , Erle Alexander , Wiegmann Denis Sebastian , Grassl Stefan , Hang Regina , Körper Sixten , Wiesneth Markus , Lotze Michael T. , Lotfi Ramin
Published: May 2014

Simple stress or necrotic cell death with subsequent release of damage-associated molecular patterns (DAMPs) is a characteristic feature of most advanced tumors. DAMPs within the tumor microenvironment stimulate tumor-associated cells, including dendritic cells and mesenchymal stromal cells (MSCs). The presence of tumor-infiltrating MSCs is associated with tumor progression and metastasis. Oxidized necrotic material loses its stimulatory capacity for MSCs. As a DAMP, S100A4 is sensitive to oxidation whereas uric acid (UA) acts primarily as an antioxidant. We tested these two biologic moieties separately and in combination for their activity on MSCs. Similar to necrotic tumor material, S100A4 and UA both dose-dependently induced chemotaxis of MSCs with synergistic effects when combined. Substituting for UA, alternative antioxidants (vitamin C, DTT, and N-acetylcysteine) also enhanced the chemotactic activity of S100A4 in a synergistic manner. This emphasizes the reducing potential of UA being, at least in part, responsible for the observed synergy. With regard to MSC proliferation, both S100A4 and UA inhibited MSCs without altering survival or inducing differentiation toward adipo-, osteo-, or chondrocytes. In the presence of S100A4 or UA, MSCs gained an immunosuppressive capability and stably induced IL-10– and IDO-expressing lymphocytes that maintained their phenotype following proliferation. We have thus demonstrated that both S100A4 and UA act as DAMPs and, as such, may play a critical role in promoting some aspects of MSC-associated immunoregulation. Our findings have implications for therapeutic approaches targeting the tumor microenvironment and addressing the immunosuppressive nature of unscheduled cell death within the tumor microenvironment.
KIR/HLA Interactions Negatively Affect Rituximab- but Not GA101 (Obinutuzumab)-Induced Antibody-Dependent Cellular Cytotoxicity
Authors: Terszowski Grzegorz , Klein Christian , Stern Martin
Published: May 2014

Ab-dependent cellular cytotoxicity (ADCC) mediated by NK cells is regulated by inhibitory killer cell Ig–like receptors (KIRs), which interact with target cell HLA class I. We analyzed how KIR/HLA interactions influence ADCC induced by rituximab and by GA101, a novel type II CD20 Ab glycoengineered for increased FcgRIII binding and ADCC capacity. We found that KIR/HLA interactions strongly and selectively inhibit rituximab-induced in vitro ADCC toward target cells expressing cognate HLA KIR ligands. NK cells of donors carrying all three ligands to inhibitory KIR showed weak activation and target cell depletion capacity when incubated with rituximab and KIR-ligand matched target B cells. In contrast, NK cells from individuals missing one or more KIR ligands activated more strongly and depleted KIR ligand–matched target B cells more efficiently in the presence of rituximab. NK cells expressing a KIR for which the ligand was absent were the main effectors of ADCC in these donors. Notably, the influence of KIR/HLA interactions on NK cell activation was synergistic with the effect of the V158F FCGR3A single nucleotide polymorphism. In contrast, GA101 induced activation of NK cells irrespective of inhibitory KIR expression, and efficiency of target cell depletion was not negatively affected by KIR/HLA interactions. These data show that modification of the Fc fragment to enhance ADCC can be an effective strategy to augment the efficacy of therapeutic mAbs by recruiting NK cells irrespective of their inhibitory KIR expression.
Critical Role for the NLRP3 Inflammasome during Acute Lung Injury
Authors: Grailer Jamison J. , Canning Bethany A. , Kalbitz Miriam , Haggadone Mikel D. , Dhond Rasika M. , Andjelkovic Anuska V. , Zetoune Firas S. , Ward Peter A.
Published: May 2014

The inflammasome is a key factor in innate immunity and senses soluble pathogen and danger-associated molecular patterns as well as biological crystals (urate, cholesterol, etc.), resulting in expression of IL-1β and IL-18. Using a standard model of acute lung injury (ALI) in mice featuring airway instillation of LPS, ALI was dependent on availability of NLRP3 as well as caspase-1, which are known features of the NLRP3 inflammasome. The appearance of IL-1β, a product of NLRP3 inflammasome activation, was detected in bronchoalveolar lavage fluids (BALF) in a macrophage- and neutrophil-dependent manner. Neutrophil-derived extracellular histones appeared in the BALF during ALI and directly activated the NLRP3 inflammasome. Ab-mediated neutralization of histones significantly reduced IL-1β levels in BALF during ALI. Inflammasome activation by extracellular histones in LPS-primed macrophages required NLRP3 and caspase-1 as well as extrusion of K+, increased intracellular Ca2+ concentration, and generation of reactive oxygen species. NLRP3 and caspase-1 were also required for full extracellular histone presence during ALI, suggesting a positive feedback mechanism. Extracellular histone and IL-1β levels in BALF were also elevated in C5a-induced and IgG immune complex ALI models, suggesting a common inflammatory mechanism. These data indicate an interaction between extracellular histones and the NLRP3 inflammasome, resulting in ALI. Such findings suggest novel targets for treatment of ALI, for which there is currently no known efficacious drug.
Myeloid Glycosylation Defects Lead to a Spontaneous Common Variable Immunodeficiency-like Condition with Associated Hemolytic Anemia and Antilymphocyte Autoimmunity
Authors: Ryan Sean O. , Abbott Derek W. , Cobb Brian A.
Published: May 2014

Common variable immunodeficiency (CVID), the most frequent symptomatic primary immune deficiency in humans, is a heterogeneous group of immunologic disorders estimated to affect 1:10,000–1:50,000. Although a clear disease etiology remains elusive, a common characteristic of CVID is deficient IgG Ab production in response to infection or vaccination. Patients often also exhibit autoimmune cytopenias with symptoms of abnormal T cell function, including reductions in naive T cells, which correlate with clinical severity. In this study, we discovered that targeted alterations in the glycome of the myeloid lineage lead to spontaneous immunodeficiency characteristic of both humoral and T cell dysfunction regularly found in human CVID. Mice carrying a myeloid-specific knockout of the Mgat2 gene encoding UDP-GlcNAc:α-6-d-mannoside β-1,2-N-acetylglucosaminyltransferase II enzyme exhibit deficiencies in IgG responses to both protein and polysaccharide conjugate vaccines. Interestingly, the immunodeficiency is associated with decreased T cell activity because of a persistent autoimmune-mediated depletion of naive T cells, which is induced by changes in erythrocyte surface glycosylation. The N-glycosylation dependent autoepitopes that emerge on erythrocytes lead to autoimmune hemolytic anemia, and the causative auto-IgM cross-reacts with naive T cells despite the lack of glycan change on T cells. These findings demonstrate that alterations in erythrocyte glycosylation trigger the development of autoantibodies directed at both erythrocytes and naive T cells, revealing a possible mechanistic link between the induction of autoimmune hemolytic anemia, the reduction in naive T cells, and poor Ab responses to vaccine in severe CVID patients.
Stability and bifurcation of equilibria for the axisymmetric averaged mean curvature flow
Authors: LeCrone Jeremy
Published: May 2014

We study the
averaged mean curvature flow
, also called the
volume preserving mean curvature flow
, in the particular setting of axisymmetric surfaces embedded in

\mathbb R^3

satisfying periodic boundary conditions. We establish analytic well-posedness of the flow within the space of little-Hölder continuous surfaces, given rough initial data. We also establish dynamic properties of equilibria, including stability, instability, and bifurcation behavior of cylinders, where the radius acts as a bifurcation parameter.