CXCR3 biased signaling, heteromerization and decoy properties

Le récepteur de chimiokine CXCR3 est un récepteur couplé à la protéine G (RCPG) exprimé, entre autre, sur les cellules T activées lors d’une réponse immune. CXCR3 est activé par trois ligands inductibles par l’interféron-γ (CXCL9, 10, 11) et, plus récemment, il a été découvert que CXCL4 liait CXCR3. Nous savons que CXCR3 joue un rôle dans la chimiotaxie des leucocytes, mais peu d’attention a été portée sur la signalisation biaisée induite par ces quatre ligands. Alors que l’homodimérisation entre récepteurs de chimiokine est un concept grandement observé, l’hétéromérisation entre deux récepteurs reste un domaine de recherche active. La signalisation biaisée et l’hétéromérisation ont été testées grâce à la technique de bioluminescene resonance energy transfer (BRET) dans des cellules HEK293E. Nous présentons une caractérisation pharmacologique des quatre ligands de CXCR3 et démontrons l’hétéromérisation de CXCR3 avec CXCR4 et avec CXCR7. Nos résultats suggèrent que les ligands de CXCR3 n’agissent pas de manière redondante.

Predicting the profile of nutrients available for absorption: from nutrient requirement to animal response and environmental impact

Current feed evaluation systems for dairy cattle aim to match nutrient requirements with nutrient intake at pre-defined production levels. These systems were not developed to address, and are not suitable to predict, the responses to dietary changes in terms of production level and product composition, excretion of nutrients to the environment, and nutrition related disorders. The change from a requirement to a response system to meet the needs of various stakeholders requires prediction of the profile of absorbed nutrients and its subsequent utilisation for various purposes. This contribution examines the challenges to predicting the profile of nutrients available for absorption in dairy cattle and provides guidelines for further improved prediction with regard to animal production responses and environmental pollution. The profile of nutrients available for absorption comprises volatile fatty acids, long-chain fatty acids, amino acids and glucose. Thus the importance of processes in the reticulo-rumen is obvious. Much research into rumen fermentation is aimed at determination of substrate degradation rates. Quantitative knowledge on rates of passage of nutrients out of the rumen is rather limited compared with that on degradation rates, and thus should be an important theme in future research. Current systems largely ignore microbial metabolic variation, and extant mechanistic models of rumen fermentation give only limited attention to explicit representation of microbial metabolic activity. Recent molecular techniques indicate that knowledge on the presence and activity of various microbial species is far from complete. Such techniques may give a wealth of information, but to include such findings in systems predicting the nutrient profile requires close collaboration between molecular scientists and mathematical modellers on interpreting and evaluating quantitative data. Protozoal metabolism is of particular interest here given the paucity of quantitative data. Empirical models lack the biological basis necessary to evaluate mitigation strategies to reduce excretion of waste, including nitrogen, phosphorus and methane. Such models may have little predictive value when comparing various feeding strategies. Examples include the Intergovernmental Panel on Climate Change (IPCC) Tier II models to quantify methane emissions and current protein evaluation systems to evaluate low protein diets to reduce nitrogen losses to the environment. Nutrient based mechanistic models can address such issues. Since environmental issues generally attract more funding from governmental offices, further development of nutrient based models may well take place within an environmental framework.

Motivations for innovation in the built environment: new directions for research

Innovation in the built environment involves multiple actors with diverse motivations. Policy-makers find it difficult to promote changes that require cooperation from these numerous and dispersed actors and to align their sometimes divergent interests. Established research traditions on the economics and management of innovation pay only limited attention to stakeholder choices, engagement and motivation. This paper reviews the insights that emerge as research in these traditions comes into contact with work on innovation from sociological and political perspectives. It contributes by highlighting growing areas of research on user involvement in complex innovation, collective action, distributed innovation and transition management. To differing extents, these provide approaches to incorporate the motivations of different actors into theoretical understanding. These indicate new directions for research that promise to enrich understanding of innovation.

Unpacking the mechanism by which corporate responsibility impacts stakeholder relationships

Most research on corporate responsibility (CR) has investigated CR from the perspective of organizations, often focusing on how organizations define, manage and implement CR to gain benefits or competitive advantage. The benefits of CR for organizations are, however, often said to be achieved through increased support of stakeholders. Despite this, limited attention has been given to understanding CR from the perspective of stakeholders and, in particular, the mechanism by which CR drives stakeholder support. This study addresses this deficit. Building on advances in the application of psychological theories to the field of management, the research develops and empirically tests a theoretical model of how CR-related experiences and beliefs drive stakeholder trust and positive intent. The research is conducted with customers (n = 708) and employees (n = 359) of a service organization in the UK that introduced a range of CR-related activities into their business. The findings contribute to literature by empirically demonstrating (a) the impact of CR-related experiences on the development of beliefs about, and trust towards, the organization; (b) the importance of ‘others-related’ CR experiences even in the presence of ‘self-related’ CR experiences; and (c) the role of beliefs as partial mediators in how experiences of CR, both ‘self-related’ and ‘others-related’, translate into trust and positive intent.

Chickpea (Cicer arietinum) and other plant-derived protease inhibitor concentrates inhibit breast and prostate cancer cell proliferation in vitro

The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is currently showing great promise as a novel cancer chemopreventive agent. In contrast to the wealth of research conducted on this compound, the anticancer effects of protease inhibitors isolated from other leguminous sources have received limited attention. In the current study, 7 protease inhibitor concentrates (PICs) were isolated from various leguminous sources (including soybean) and characterized. The effects of PICs on the proliferation of breast and prostate cancer cells were investigated in vitro. Chickpea PIC significantly inhibited the viability of MDA-MB-231 breast cancer and PC-3 and LNCaP prostate cancer cells at all concentrations tested (25-400 μg/ml). In addition, kidney bean (200, 400 μg/ml), soybean (50, 100 μg/ml), and mungbean (100, 200 μg/ml) PICs inhibited LNCaP cell viability. These findings suggest that leguminous PICs may possess similar anticancer properties to that of soybean BBI and deserve further study as possible chemopreventive agents.

How culture and government shape entrepreneurial innovation: the case of Korean and UK online gaming firms

This paper examines institutional sources of product innovation with reference to the online gaming sector of Korea and the UK. It examines the combined impact of formal and informal institutions and their interaction with multiple case studies. Despite the growing importance of innovative products in contemporary entertainment (including interactive games), the ‘informal’ source of innovation has attracted limited attention. By closely looking at the idea exploration, generation and selection process (where creativity plays a major role), we intend to find out how values and public policy affect product innovation. This study shows that the value of Korean and UK online gaming firms (regardless of their different socio-economic contexts) plays an important role in generating product innovation. An additional point is that Korean firms are likely to take advantage of government policy support to overcome inadequate institutional settings in conjunction with the initial conditions of online game development.

Research data management and openness: the role of data sharing in developing institutional policies and practices

Purpose: To investigate the relationship between research data management (RDM) and data sharing in the formulation of RDM policies and development of practices in higher education institutions (HEIs). Design/methodology/approach: Two strands of work were undertaken sequentially: firstly, content analysis of 37 RDM policies from UK HEIs; secondly, two detailed case studies of institutions with different approaches to RDM based on semi-structured interviews with staff involved in the development of RDM policy and services. The data are interpreted using insights from Actor Network Theory. Findings: RDM policy formation and service development has created a complex set of networks within and beyond institutions involving different professional groups with widely varying priorities shaping activities. Data sharing is considered an important activity in the policies and services of HEIs studied, but its prominence can in most cases be attributed to the positions adopted by large research funders. Research limitations/implications: The case studies, as research based on qualitative data, cannot be assumed to be universally applicable but do illustrate a variety of issues and challenges experienced more generally, particularly in the UK. Practical implications: The research may help to inform development of policy and practice in RDM in HEIs and funder organisations. Originality/value: This paper makes an early contribution to the RDM literature on the specific topic of the relationship between RDM policy and services, and openness – a topic which to date has received limited attention.

Antecedents of travellers' electronic word-of-mouth communication

Electronic word-of-mouth (eWOM) is recognised as a means of interpersonal communication and a powerful marketing tool. However, previous studies have focussed on related motivations, and limited attention has been given to understanding the antecedents of eWOM communication behaviour in the travel industry. This study proposes a full and partial mediation model, which brings together for the first time three key antecedents: adoption of electronic communication technology, consumer dis/satisfaction with travel consumption experience, and subjective norm. The model aims to understand the impact of these antecedents on travellers' attitude towards eWOM communication and intention to use eWOM communication media. The data were collected from international travellers (n = 524), and structural equation modelling is used to test the conceptual framework. The findings of the study suggest that overall attitude towards eWOM communication partially mediates the impact of the traveller's adoption of electronic communication technology and subjective norm, and fully mediates the impact of consumer dis/satisfaction with travel consumption experience on travellers' intention to use eWOM communication media.

Symbolic consumption of tourism destination brands

Electronic word-of-mouth (eWOM) is recognised as a means of interpersonal communication and a powerful marketing tool. However, previous studies have focussed on related motivations, and limited attention has been given to understanding the antecedents of eWOM communication behaviour in the travel industry. This study proposes a full and partial mediation model, which brings together for the first time three key antecedents: adoption of electronic communication technology, consumer dis/satisfaction with travel consumption experience, and subjective norm. The model aims to understand the impact of these antecedents on travellers' attitude towards eWOM communication and intention to use eWOM communication media. The data were collected from international travellers (n = 524), and structural equation modelling is used to test the conceptual framework. The findings of the study suggest that overall attitude towards eWOM communication partially mediates the impact of the traveller's adoption of electronic communication technology and subjective norm, and fully mediates the impact of consumer dis/satisfaction with travel consumption experience on travellers' intention to use eWOM communication media.

EVOLUTIONARY BIOLOGY IN BIODIVERSITY SCIENCE, CONSERVATION, AND POLICY: A CALL TO ACTION

Evolutionary biologists have long endeavored to document how many species exist on Earth, to understand the processes by which biodiversity waxes and wanes, to document and interpret spatial patterns of biodiversity, and to infer evolutionary relationships. Despite the great potential of this knowledge to improve biodiversity science, conservation, and policy, evolutionary biologists have generally devoted limited attention to these broader implications. Likewise, many workers in biodiversity science have underappreciated the fundamental relevance of evolutionary biology. The aim of this article is to summarize and illustrate some ways in which evolutionary biology is directly relevant We do so in the context of four broad areas: (1) discovering and documenting biodiversity, (2) understanding the causes of diversification, (3) evaluating evolutionary responses to human disturbances, and (4) implications for ecological communities, ecosystems, and humans We also introduce bioGENESIS, a new project within DIVERSITAS launched to explore the potential practical contributions of evolutionary biology In addition to fostering the integration of evolutionary thinking into biodiversity science, bioGENESIS provides practical recommendations to policy makers for incorporating evolutionary perspectives into biodiversity agendas and conservation. We solicit your involvement in developing innovative ways of using evolutionary biology to better comprehend and stem the loss of biodiversity.

Investor disagreement: the modern approach

Disagreement between economists is a well know fact. However, it took a long time for this concept to be incorporated in economic models. In this survey, we review the consequences and insights provided by recent models. Since disagreement between market agents can be generated through different hypotheses, the main differences between them are highlighted. Finally, this work concludes with a short review of nowcasting using google trends, emphasizing advances connecting both literatures.

Engaging environments: Tacit knowledge sharing on the shop floor

Purpose: The purpose of this paper is to identify factors that facilitate tacit knowledge sharing in unstructured work environments, such as those found in automated production lines. Design/methodology/approach: The study is based on a qualitative approach, and it draws data from a four-month field study at a blown-molded glass factory. Data collection techniques included interviews, informal conversations and on-site observations, and data were interpreted using content analysis. Findings: The results indicated that sharing of tacit knowledge is facilitated by an engaging environment. An engaging environment is supported by shared language and knowledge, which are developed through intense communication and a strong sense of collegiality and a social climate that is dominated by openness and trust. Other factors that contribute to the creation of an engaging environment include managerial efforts to provide appropriate work conditions and to communicate company goals, and HRM practices such as the provision of formal training, on-the-job training and incentives. Practical implications: This paper clarifies the scope of managerial actions that impact knowledge creation and sharing among blue-collar workers. Originality/value: Despite the acknowledgement of the importance of blue-collar workers' knowledge, both the knowledge management and operations management literatures have devoted limited attention to it. Studies related to knowledge management in unstructured working environments are also not abundant. © Emerald Group Publishing Limited.

Determinants of cognitive performance among community dwelling older adults in an impoverished sub-district of Sao Paulo in Brazil

Determinants of cognitive performance in old age have received limited attention in Latin America. We investigated the association of socio-demographic and health-related variables with cognitive performance in a sample of older adults with limited educational experience living in a poor subdistrict of the city of Sao Paulo. This was a cross-sectional population-based study which included a sample of 384 seniors 65 years and older. Cognition was assessed by the Mini-Mental State Examination (MMSE) and the Brief Cognitive Screening Battery (BCSB) (episodic memory test with 10 pictures, verbal fluency (VF), Clock Drawing Test (CDT)). Results indicated that age, sex, schooling, depressive symptoms, and systolic blood pressure (SBP) level had a significant impact on the cognitive performance of the sample. Therefore, pharmacological and psychosocial interventions with a focus on improving mood and controlling hypertension may have beneficial effects on cognition among seniors with similar socio-demographic characteristics. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Some issues concerning the dynamic response and damage of composite laminates subjected to low velocity impact

Abstract. This thesis presents a discussion on a few specific topics regarding the low velocity impact behaviour of laminated composites. These topics were chosen because of their significance as well as the relatively limited attention received so far by the scientific community. The first issue considered is the comparison between the effects induced by a low velocity impact and by a quasi-static indentation experimental test. An analysis of both test conditions is presented, based on the results of experiments carried out on carbon fibre laminates and on numerical computations by a finite element model. It is shown that both quasi-static and dynamic tests led to qualitatively similar failure patterns; three characteristic contact force thresholds, corresponding to the main steps of damage progression, were identified and found to be equal for impact and indentation. On the other hand, an equal energy absorption resulted in a larger delaminated area in quasi-static than in dynamic tests, while the maximum displacement of the impactor (or indentor) was higher in the case of impact, suggesting a probably more severe fibre damage than in indentation. Secondly, the effect of different specimen dimensions and boundary conditions on its impact response was examined. Experimental testing showed that the relationships of delaminated area with two significant impact parameters, the absorbed energy and the maximum contact force, did not depend on the in-plane dimensions and on the support condition of the coupons. The possibility of predicting, by means of a simplified numerical computation, the occurrence of delaminations during a specific impact event is also discussed. A study about the compressive behaviour of impact damaged laminates is also presented. Unlike most of the contributions available about this subject, the results of compression after impact tests on thin laminates are described in which the global specimen buckling was not prevented. Two different quasi-isotropic stacking sequences, as well as two specimen geometries, were considered. It is shown that in the case of rectangular coupons the lay-up can significantly affect the damage induced by impact. Different buckling shapes were observed in laminates with different stacking sequences, in agreement with the results of numerical analysis. In addition, the experiments showed that impact damage can alter the buckling mode of the laminates in certain situations, whereas it did not affect the compressive strength in every case, depending on the buckling shape. Some considerations about the significance of the test method employed are also proposed. Finally, a comprehensive study is presented regarding the influence of pre-existing in-plane loads on the impact response of laminates. Impact events in several conditions, including both tensile and compressive preloads, both uniaxial and biaxial, were analysed by means of numerical finite element simulations; the case of laminates impacted in postbuckling conditions was also considered. The study focused on how the effect of preload varies with the span-to-thickness ratio of the specimen, which was found to be a key parameter. It is shown that a tensile preload has the strongest effect on the peak stresses at low span-to-thickness ratios, leading to a reduction of the minimum impact energy required to initiate damage, whereas this effect tends to disappear as the span-to-thickness ratio increases. On the other hand, a compression preload exhibits the most detrimental effects at medium span-to-thickness ratios, at which the laminate compressive strength and the critical instability load are close to each other, while the influence of preload can be negligible for thin plates or even beneficial for very thick plates. The possibility to obtain a better explanation of the experimental results described in the literature, in view of the present findings, is highlighted. Throughout the thesis the capabilities and limitations of the finite element model, which was implemented in an in-house program, are discussed. The program did not include any damage model of the material. It is shown that, although this kind of analysis can yield accurate results as long as damage has little effect on the overall mechanical properties of a laminate, it can be helpful in explaining some phenomena and also in distinguishing between what can be modelled without taking into account the material degradation and what requires an appropriate simulation of damage. Sommario. Questa tesi presenta una discussione su alcune tematiche specifiche riguardanti il comportamento dei compositi laminati soggetti ad impatto a bassa velocità. Tali tematiche sono state scelte per la loro importanza, oltre che per l’attenzione relativamente limitata ricevuta finora dalla comunità scientifica. La prima delle problematiche considerate è il confronto fra gli effetti prodotti da una prova sperimentale di impatto a bassa velocità e da una prova di indentazione quasi statica. Viene presentata un’analisi di entrambe le condizioni di prova, basata sui risultati di esperimenti condotti su laminati in fibra di carbonio e su calcoli numerici svolti con un modello ad elementi finiti. È mostrato che sia le prove quasi statiche sia quelle dinamiche portano a un danneggiamento con caratteristiche qualitativamente simili; tre valori di soglia caratteristici della forza di contatto, corrispondenti alle fasi principali di progressione del danno, sono stati individuati e stimati uguali per impatto e indentazione. D’altro canto lo stesso assorbimento di energia ha portato ad un’area delaminata maggiore nelle prove statiche rispetto a quelle dinamiche, mentre il massimo spostamento dell’impattatore (o indentatore) è risultato maggiore nel caso dell’impatto, indicando la probabilità di un danneggiamento delle fibre più severo rispetto al caso dell’indentazione. In secondo luogo è stato esaminato l’effetto di diverse dimensioni del provino e diverse condizioni al contorno sulla sua risposta all’impatto. Le prove sperimentali hanno mostrato che le relazioni fra l’area delaminata e due parametri di impatto significativi, l’energia assorbita e la massima forza di contatto, non dipendono dalle dimensioni nel piano dei provini e dalle loro condizioni di supporto. Viene anche discussa la possibilità di prevedere, per mezzo di un calcolo numerico semplificato, il verificarsi di delaminazioni durante un determinato caso di impatto. È presentato anche uno studio sul comportamento a compressione di laminati danneggiati da impatto. Diversamente della maggior parte della letteratura disponibile su questo argomento, vengono qui descritti i risultati di prove di compressione dopo impatto su laminati sottili durante le quali l’instabilità elastica globale dei provini non è stata impedita. Sono state considerate due differenti sequenze di laminazione quasi isotrope, oltre a due geometrie per i provini. Viene mostrato come nel caso di provini rettangolari la sequenza di laminazione possa influenzare sensibilmente il danno prodotto dall’impatto. Due diversi tipi di deformate in condizioni di instabilità sono stati osservati per laminati con diversa laminazione, in accordo con i risultati dell’analisi numerica. Gli esperimenti hanno mostrato inoltre che in certe situazioni il danno da impatto può alterare la deformata che il laminato assume in seguito ad instabilità; d’altra parte tale danno non ha sempre influenzato la resistenza a compressione, a seconda della deformata. Vengono proposte anche alcune considerazioni sulla significatività del metodo di prova utilizzato. Infine viene presentato uno studio esaustivo riguardo all’influenza di carichi membranali preesistenti sulla risposta all’impatto dei laminati. Sono stati analizzati con simulazioni numeriche ad elementi finiti casi di impatto in diverse condizioni di precarico, sia di trazione sia di compressione, sia monoassiali sia biassiali; è stato preso in considerazione anche il caso di laminati impattati in condizioni di postbuckling. Lo studio si è concentrato in particolare sulla dipendenza degli effetti del precarico dal rapporto larghezza-spessore del provino, che si è rivelato un parametro fondamentale. Viene illustrato che un precarico di trazione ha l’effetto più marcato sulle massime tensioni per bassi rapporti larghezza-spessore, portando ad una riduzione della minima energia di impatto necessaria per innescare il danneggiamento, mentre questo effetto tende a scomparire all’aumentare di tale rapporto. Il precarico di compressione evidenzia invece gli effetti più deleteri a rapporti larghezza-spessore intermedi, ai quali la resistenza a compressione del laminato e il suo carico critico di instabilità sono paragonabili, mentre l’influenza del precarico può essere trascurabile per piastre sottili o addirittura benefica per piastre molto spesse. Viene evidenziata la possibilità di trovare una spiegazione più soddisfacente dei risultati sperimentali riportati in letteratura, alla luce del presente contributo. Nel corso della tesi vengono anche discussi le potenzialità ed i limiti del modello ad elementi finiti utilizzato, che è stato implementato in un programma scritto in proprio. Il programma non comprende alcuna modellazione del danneggiamento del materiale. Viene però spiegato come, nonostante questo tipo di analisi possa portare a risultati accurati soltanto finché il danno ha scarsi effetti sulle proprietà meccaniche d’insieme del laminato, esso possa essere utile per spiegare alcuni fenomeni, oltre che per distinguere fra ciò che si può riprodurre senza tenere conto del degrado del materiale e ciò che invece richiede una simulazione adeguata del danneggiamento.

Antennal courtship and functional morphology of tyloids in the parasitoid wasp Syrphoctonus tarsatorius (Hymenoptera: Ichneumonidae: Diplazontinae)

Courtship behaviour and associated morphological characters are believed to evolve under diversifying sexual selection. In Hymenoptera, sexually dimorphic antennal structures, the 'tyloids', show a large variability. Although crucial for functional interpretation, the link between tyloid morphology and courtship behaviour has gained only limited attention. Here, we investigate antennal morphology and antennal courtship in the parasitoid wasp Syrphoctonus tarsatorius (Hymenoptera: Ichneumonidae: Diplazontinae). We confirm the glandular nature of the tyloids by light and scanning electron microscopy. Moreover, we report a new form of antennation during courtship, antennal double-coiling, which links morphology and behaviour by bringing the tyloids in direct contact with the antennae of the female, thus probably facilitating the transfer of a contact pheromone. We show that a change in haemolymph pressure is the activator of the antennal movement and that it can be reproduced in the laboratory using amputated antennae. Investigations of antennal structure and movement in three additional hymenopteran species suggest that the number and location of tyloids coincide with the modality of antennal coiling. Our method for simulating antennal movement will enable retrieving information about courtship behaviour from museum specimens, thus leading to a better understanding of the evolution of courtship behaviour in Hymenoptera.