Phosphonate and quinoxaline cavitands for molecular recognition and sensing

In the last decade, phosphonate and quinoxaline cavitand have been extensively studied, highlighting their outstanding recognition properties. Their successful applications in material science and sensing open the way to new potential applications, such as border security, environmental monitoring and chiral recognition. The present thesis explores the recognition properties of phosphonate and quinoxaline cavitands towards new targets, for molecular recognition and sensing applications. Chapter 2 highlights the enantioselective behavior of phosphonate cavitands towards chiral guests in the solid state and in solution. Phosphonate cavitands were exploited for the molecular recognition of L-lactic acid (chapter 3), a widespread natural molecule which offer multiple potential applications, and a human sweat marker used for the detection of human presence (chapter 4). The second part is devoted to sensing applications of quinoxaline cavitands. Chapter 5 describes the use of QxCav for the preconcentration of drugs precursors, while chapter 6 reports the design, synthesis and grafting of a rigidified EtQxBox on a silicon wafer.

In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction

Studies were performed to investigate the UDP-glucuronosyltransferase enzyme( s) responsible for the human liver microsomal N2-glucuronidation of the anticonvulsant drug lamotrigine ( LTG) and the mechanistic basis for the LTG-valproic acid ( VPA) interaction in vivo. LTG N2-glucuronidation by microsomes from five livers exhibited atypical kinetics, best described by a model comprising the expressions for the Hill ( 1869 +/- 1286 mu M, n = 0.65 +/- 0.16) and Michaelis-Menten ( Km 2234 +/- 774 mu M) equations. The UGT1A4 inhibitor hecogenin abolished the Michaelis-Menten component, without affecting the Hill component. LTG N2-glucuronidation by recombinant UGT1A4 exhibited Michaelis-Menten kinetics, with a K-m of 1558 mu M. Although recombinant UGT2B7 exhibited only low activity toward LTG, inhibition by zidovudine and fluconazole and activation by bovine serum albumin ( BSA) ( 2%) strongly suggested that this enzyme was responsible for the Hill component of microsomal LTG N2-glucuronidation. VPA ( 10 mM) abolished the Hill component of microsomal LTG N2-glucuronidation, without affecting the Michaelis-Menten component or UGT1A4-catalyzed LTG metabolism. K-i values for inhibition of the Hill component of LTG N2-glucuronidation by VPA were 2465 +/- 370 mu M and 387 +/- 12 mu M in the absence and presence, respectively, of BSA ( 2%). Consistent with published data for the effect of fluconazole on zidovudine glucuronidation by human liver microsomal UGT2B7, the Ki value generated in the presence of BSA predicted the magnitude of the LTG-VPA interaction reported in vivo. These data indicate that UGT2B7 and UGT1A4 are responsible for the Hill and Michaelis-Menten components, respectively, of microsomal LTG N2-glucuronidation, and the LTG-VPA interaction in vivo arises from inhibition of UGT2B7.

Multiple receptors for calcitonin gene-related peptide and amylin on guinea-pig ileum and vas deferens

1. The responses of the electrically stimulated guinea-pig ileum and vas deferens to human and rat calcitonin gene-related peptide (CGRP) and amylin were investigated. 2. The inhibition of contraction of the ileum produced by human alpha CGRP was antagonized by human alpha CGRP8-37 (apparent pA2 estimated at 7.15 +/- 0.23) > human alpha CGRP19-37 (apparent pA2 estimated as 6.67 +/- 0.33) > [Tyr0]-human alpha CGRP28-37. The amylin antagonist, AC187, was three fold less potent than CGRP8-37 in antagonizing human alpha CGRP. 3. Both human beta- and rat alpha CGRP inhibited contractions of the ileum, but this was less sensitive to inhibition by CGRP8-37 than the effect of human alpha CGRP. However, CGRP19-37 was twenty times more effective in inhibiting the response to rat alpha CGRP (apparent pA2 estimated as 8.0 +/- 0.1) compared to human alpha CGRP. 4. Rat amylin inhibited contractions in about 10% of ileal preparations; this effect was not antagonized by any CGRP fragment. Human amylin had no action on this preparation. 5. Both human and rat alpha CGRP inhibited electrically stimulated contractions of the vas deferens, which were not antagonized by 3 microM CGRP8-37 or 10 microM AC187. 6. Rat amylin inhibited the stimulated contractions of the vas deferens (EC50 = 77 +/- 9 nM); human amylin was less potent (EC50 = 213 +/- 22 nM). The response to rat amylin was antagonized by 10 microM CGRP8-37 (EC50 = 242 +/- 25 nM) and 10 microM AC187 (EC50 = 610 +/- 22 nM). 7. It is concluded that human alpha CGRP relaxes the guinea-pig ileum via CGRP1-like receptors, but that human beta CGRP and rat alpha CGRP may use additional receptors. These are distinct CGRP2-like and amylin receptors on guinea-pig vas deferens.

Nurturing health-related online support groups:exploring the experience of patient moderators

The aim of this study was to examine the views of moderators across a diverse and geographically broad range of online support groups about their moderator experiences and to explore both the personal benefits as well as challenges involved. Thirty-three patient moderators completed an online questionnaire which included a series of open-ended questions. Thematic analysis identified three themes: emergence, empowerment, nurturing. Several moderators declared their own diagnosis and for some, being able to share personal insights motivated them to establish the group and in turn offered validation. They felt empowered by helping others and learned more about the condition through accessing the "communal brain". Some felt the group aided patients' access to health services and their ability to communicate with health professionals while others worried about them becoming over-dependent. Moderators described needing to nurture their group to ensure it offered a safe space for members. Clear rules of engagement, trust, organisation skills, compassion and kindness were considered essential. Patient moderated online support groups can be successfully developed and facilitated and can be empowering for both the group member and moderator alike.© 2013 Elsevier Ltd. All rights reserved.

Network learning:Exploring learning by interorganizational networks

The importance of interorganizational networks in supporting or hindering the achievement of organizational objectives is now widely acknowledged. Network research is directed at understanding network processes and structures, and their impact upon performance. A key process is learning. The concepts of individual, group and organizational learning are long established. This article argues that learning might also usefully be regarded as occurring at a fourth system level, the interorganizational network. The concept of network learning - learning by a group of organizations as a group - is presented, and differentiated from other types of learning, notably interorganizational learning (learning in interorganizational contexts). Four cases of network learning are identified and analysed to provide insights into network learning processes and outcomes. It is proposed that 'network learning episode' offers a suitable unit of analysis for the empirical research needed to develop our understanding of this potentially important concept.

Nanofabrication towards biophotonics

This thesis explores methods for fabrication of nanohole arrays, and their integration into a benchtop system for use as sensors or anti-counterfeit labels. Chapter 1 gives an introduction to plasmonics and more specifically nanohole arrays and how they have potential as label free sensors compared to the current biosensors on the market. Various fabrication methods are explored, including Focused Ion Beam, Electron Beam Lithography, Nanoimprint lithography, Template stripping and Phase Shift Lithography. Focused Ion Beam was chosen to fabricate the nanohole arrays due to its suitability for rapid prototyping and it’s relatively low cost. In chapter 2 the fabrication of nanohole arrays using FIB is described, and the samples characterised. The fabricated nanohole arrays are tested as bulk refractive index sensors, before a bioassay using whole molecule human IgG antibodies and antigen is developed and performed on the senor. In chapter 3 the fabricated sensors are integrated into a custom built system, capable of real time, multiplexed detection of biomolecules. Here, scFv antibodies of two biomolecules relevant to the detection of pancreatic cancer (C1q and C3) are attached to the nanohole arrays, and detection of their complementary proteins is demonstrated both in buffer (10 nM detection of C1q Ag) and human serum. Chapter 4 explores arrays of anisotropic (elliptical) nanoholes and shows how the shape anisotropy induces polarisation sensitive transmission spectra, in both simulations and fabricated arrays. The potential use of such samples as visible and NIR tag for anti-counterfeiting applications is demonstrated. Finally, chapter 5 gives a summary of the work completed and discusses potential future work in this area.

Utilizing ICT to prevent loneliness and social isolation of the elderly. A literature review

Ageing of the population is a worldwide phenomenon. Numerous ICT-based solutions have been developed for elderly care but mainly connected to the physiological and nursing aspects in services for the elderly. Social work is a profession that should pay attention to the comprehensive wellbeing and social needs of the elderly. Many people experience loneliness and depression in their old age, either as a result of living alone or due to a lack of close family ties and reduced connections with their culture of origin, which results in an inability to participate actively in community activities (Singh & Misra, 2009). Participation in society would enhance the quality of life. With the development of information technology, the use of technology in social work practice has risen dramatically. The aim of this literature review is to map out the state of the art of knowledge about the usage of ICT in elderly care and to figure out research-based knowledge about the usability of ICT for the prevention of loneliness and social isolation of elderly people. The data for the current research comes from the core collection of the Web of Science and the data searching was performed using Boolean? The searching resulted in 216 published English articles. After going through the topics and abstracts, 34 articles were selected for the data analysis that is based on a multi approach framework. The analysis of the research approach is categorized according to some aspects of using ICT by older adults from the adoption of ICT to the impact of usage, and the social services for them. This literature review focused on the function of communication by excluding the applications that mainly relate to physical nursing. The results show that the so-called ‘digital divide’ still exists, but the older adults have the willingness to learn and utilise ICT in daily life, especially for communication. The data shows that the usage of ICT can prevent the loneliness and social isolation of older adults, and they are eager for technical support in using ICT. The results of data analysis on theoretical frames and concepts show that this research field applies different theoretical frames from various scientific fields, while a social work approach is lacking. However, a synergic frame of applied theories will be suggested from the perspective of social work.

On a first-name basis: Englishization and naming in Flanders

Following and contributing to the ongoing shift from more structuralist, system-oriented to more pragmatic, socio-cultural oriented anglicism research, this paper verifies to what extent the global spread of English affects naming patterns in Flanders. To this end, a diachronic database of first names is constructed, containing the top 75 most popular boy and girl names from 2005 until 2014. In a first step, the etymological background of these names is documented and the evolution in popularity of the English names in the database is tracked. Results reveal no notable surge in the preference for English names. This paper complements these database-driven results with an experimental study, aiming to show how associations through referents are in this case more telling than associations through phonological form (here based on etymology). Focusing on the socio-cultural background of first names in general and of Anglo-American pop culture in particular, the second part of the study specifically reports on results from a survey where participants are asked to name the first three celebrities that leap to mind when hearing a certain first name (e.g. Lana, triggering the response Del Rey). Very clear associations are found between certain first names and specific celebrities from Anglo-American pop culture. Linking back to marketing research and the social turn in onomastics, we will discuss how these celebrities might function as referees, and how social stereotypes surrounding these referees are metonymically attached to their first names. Similar to the country-of-origin-effect in marketing, these metonymical links could very well be the reason why parents select specific “celebrity names”. Although further attitudinal research is needed, this paper supports the importance of including socio-cultural parameters when conducting onomastic research.

Systemizers are better code-breakers: self-reported systemizing predicts code-breaking performance in expert hackers and naïve participants

Studies on hacking have typically focused on motivational aspects and general personality traits of the individuals who engage in hacking; little systematic research has been conducted on predispositions that may be associated not only with the choice to pursue a hacking career but also with performance in either naïve or expert populations. Here, we test the hypotheses that two traits that are typically enhanced in autism spectrum disorders—attention to detail and systemizing—may be positively related to both the choice of pursuing a career in information security and skilled performance in a prototypical hacking task (i.e., crypto-analysis or code-breaking). A group of naïve participants and of ethical hackers completed the Autism Spectrum Quotient, including an attention to detail scale, and the Systemizing Quotient (Baron-Cohen et al., 2001, 2003). They were also tested with behavioral tasks involving code-breaking and a control task involving security X-ray image interpretation. Hackers reported significantly higher systemizing and attention to detail than non-hackers. We found a positive relation between self-reported systemizing (but not attention to detail) and code-breaking skills in both hackers and non-hackers, whereas attention to detail (but not systemizing) was related with performance in the X-ray screening task in both groups, as previously reported with naïve participants (Rusconi et al., 2015). We discuss the theoretical and translational implications of our findings.

Isomérisation du lactose en lactulose en solution modèle de lactose et dans du perméat de lactosérum par électro-activation supportée par échange ionique sur résine

L’isomérisation alcaline du lactose en lactulose a été effectuée électro-chimiquement à l’aide d’un réacteur d’électro-activation en combinaison avec des résines échangeuses d’anions de polystyrène de trois types; à savoir Lewatit VP-OC-1065 faible-acide, Lewatit MP-64 moyenne-acide et Lewatit Monoplus M500 forte-acide. Les paramètres opératoires qui ont fait l’objet de cette étude ont été étudiés sur trois blocs expérimentaux pour optimiser le système. Dans le Premier bloc, les paramètres étudiés sont : (1) ratio lactose-5%(p/v) : résine échangeuse d’anions (1:0.5, 1:1 et 1:2), (2) intensité du champ électrique : 50 mA, 100 mA et 200 mA et (3) type de résines : faible, moyenne et forte. Dans le Deuxième bloc, les paramètres mis à l’étude comprenaient : (1) l’intensité du champ électrique : 300 mA, 450 mA et 550 mA, (2) le débit de la solution traitée : 25 ml / min, 50 ml/ min et 100 ml/min et (3) la surface active de la membrane adjacente au compartiment cathodique : 0.78 cm2, 7.06 cm2 et 18.1 cm2. Le Troisième bloc expérimental a été effectué sur la base de la distance entre la membrane et l’électrode : 3.1 cm, 5.6 cm et 9 cm. Le même modèle expérimental a était également réalisé avec du perméat du lactosérum d’une concentration de 7% (p/v). Les résultats obtenus ont révélé que le meilleur rendement de l’isomérisation du lactose en lactulose était obtenu après 30 minutes d’électroactivation en utilisant une solution modèle de lactose-5% avec une valeur d’environ 20.1%. Les conditions opératoires qui ont permis d’avoir ce taux de conversion sont une intensité du courant de 550 mA, un débit de la solution de 25 ml/min, une surface active de la membrane de 7.06 cm2 et une distance de 9 cm entre la cathode et la membrane qui lui y est adjacente. En utilisant le perméat de lactosérum-7%, un taux de conversion de lactose en lactulose de 8.34% a était obtenu avec une intensité du courant de 200 mA, un débit de 120 ml/min, une surface active de de 18.1cm2 et une distance de 9 cm entre la membrane et l’électrode dans le compartiment cathodique. Les analyses de variance ont indiqué un effet catalytique significatif du type de la résine. En effet, la résine-forte a permis d’avoir les plus hauts rendements de la réaction d’isomérisation par électro-activation. La résistance électrique globale du système d’électroactivation dépendait de la valeur de l’intensité du courant. Le produit final était d’une grande pureté, car il ne présentait que quelques traces de galactose (< 4%).

Skeletal maturity and socio-economic status in portuguese children and youths: the Madeira growth study

Skeletal maturity is used to evaluate biological maturity status. Information about the association between socio-economic status (SES) and skeletal maturity is limited in Portugal. Aims: The aim of this study is to document the skeletal maturity of youths in Madeira and to evaluate variation in maturity associated with SES. Subjects and methods: The study involved 507 subjects (256 boys and 251 girls) from the Madeira Growth Study, a mixed-longitudinal study of five cohorts (8, 10, 12, 14 and 16 years of age) followed at yearly intervals over 3 years (1996–1998). A total of 1493 observations were made. Skeletal age was estimated from radiographs of the hand and wrist using the Tanner–Whitehouse 2 method (TW2). Social class rankings were based on Graffar’s (1956) method. Five social rankings were subsequently grouped into three SES categories: high, average and low. Results: Median for the radius, ulna and short finger bones (RUS scores) in the total sample of boys and girls increased curvilinearly across age whereas median for the 7 (without pisiform) carpal bones (Carpal scores) increased almost linearly. The 20-bone maturity scores demonstrated distinctive trends by gender: the medians for boys increased almost linearly while the medians for girls increased curvilinearly. SES differences were minimal. Only among children aged 10–11 years were high SES boys and girls advanced in skeletal maturity. Madeira adolescents were advanced in skeletal maturity compared with Belgian reference values. Conclusion: The data suggests population variation in TW2 estimates of skeletal maturation. Skeletal maturity was not related to SES in youths from Madeira.