Handbook of life design : from practice to theory and from theory to practice

Our lives and careers are becoming ever more unpredictable. The "life-design paradigm" described in detail in this ground-breaking handbook helps counselors and others meet people's increasing need to develop and manage their own lives and careers. Life-design interventions, suited to a wide variety of cultural settings, help individuals become actors in their own lives and careers by activating, stimulating, and developing their personal resources. This handbook first addresses life-design theory, then shows how to apply life designing to different age groups and with more at-risk people, and looks at how to train life-design counselors

The octagon, the hendecagon and the approximation of pi: the geometric design of the clypeus in the enclosure of Imperial cult in Tarraco

The ancient temple dedicated to the Roman Emperor Augustus on the hilltop of Tarraco (today’s Tarragona), was the main element of the sacred precinct of the Imperial cult. It was a two hectare square, bordered by a portico with an attic decorated with a sequence of clypeus (i.e. monumental shields) made with marble plates from the Luni-Carrara’s quarries. This contribution presents the results of the analysis of a three-dimensional photogrammetric survey of one of these clipeus, partially restored and exhibited at the National Archaeological Museum of Tarragona. The perimeter ring was bounded by a sequence of meanders inscribed in a polygon of 11 sides, a hendecagon. Moreover, a closer geometric analysis suggests that the relationship between the outer meander rim and the oval pearl ring that delimited the divinity of Jupiter Ammon can be accurately determined by the diagonals of an octagon inscribed in the perimeter of the clypeus. This double evidence suggests a combined layout, in the same design, of an octagon and a hendecagon. Hypothetically, this could be achieved by combining the octagon with the approximation to Pi used in antiquity: 22/7 of the circle’s diameter. This method allows the drawing of a hendecagon with a clearly higher precision than with other ancient methods. Even the modelling of the motifs that separate the different decorative stripes corroborates the geometric scheme that we propose.

An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules.

OBJECTIVES: To investigate the frequency of interim analyses, stopping rules, and data safety and monitoring boards (DSMBs) in protocols of randomized controlled trials (RCTs); to examine these features across different reasons for trial discontinuation; and to identify discrepancies in reporting between protocols and publications. STUDY DESIGN AND SETTING: We used data from a cohort of RCT protocols approved between 2000 and 2003 by six research ethics committees in Switzerland, Germany, and Canada. RESULTS: Of 894 RCT protocols, 289 prespecified interim analyses (32.3%), 153 stopping rules (17.1%), and 257 DSMBs (28.7%). Overall, 249 of 894 RCTs (27.9%) were prematurely discontinued; mostly due to reasons such as poor recruitment, administrative reasons, or unexpected harm. Forty-six of 249 RCTs (18.4%) were discontinued due to early benefit or futility; of those, 37 (80.4%) were stopped outside a formal interim analysis or stopping rule. Of 515 published RCTs, there were discrepancies between protocols and publications for interim analyses (21.1%), stopping rules (14.4%), and DSMBs (19.6%). CONCLUSION: Two-thirds of RCT protocols did not consider interim analyses, stopping rules, or DSMBs. Most RCTs discontinued for early benefit or futility were stopped without a prespecified mechanism. When assessing trial manuscripts, journals should require access to the protocol.

Structure-Based, Rational Design of T Cell Receptors.

Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = ∼1 - 5 μM. Beyond the affinity threshold at K D < 1 μM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.

Design of flywheel generator for a diesel hybrid working machine

The aim of this work is to design a flywheel generator for a diesel hybrid working machine. In this work we perform detailed design of a generator. Mobile machines are commonly used in industry: road building machines, three harvesting machines, boring machines, trucks and other equipment. These machines work with a hydraulic drive system. This system provides good service property and high technical level. Manufacturers of mobile machines tend to satisfy all requirements of customers and modernized drive system. In this work also a description of the frequency inverter is present. Power electronics system is one of the basic parts for structures perform in the project.

Early Modern Persian, Urdu, and English Historiography and the Imagination of Islamic India under British Rule

This paper analyses the early modern transformations of South Asian literary cultures through the production of historiography in Persian, English, and Urdu. In the 18th-19th centuries, South Asian communities experienced and participated in a major restructuring of the languages of the subcontinent. Urdu and English were institutionalized as governmental languages and utilized in new literary productions as Persian was gradually marginalized from the centre of literary and governmental polities. Three interrelated colonial policies reshaped the historical consciousness of South Asia and Britain: the production of new Persian histories commissioned under British patronage, the initiation of Urdu historiography through the translation of Persian and English histories, and the construction of the British history of India written in English. This article explores the historical and social dynamics of these events and situates the origins and evolution of the colonial historiographical project. Major works discussed are the Tārīkh-i Bangālah of Salīm Allāh Munshī (fl. 1763), James Mill's (1773-1836) The History of British India first published in 1817, Mīr Sher ʿAlī Afsos' the Ārāʾish-i mahfil, as well as the production of original Urdu histories such as Muḥammad Zakāʾ-Allāh's (1832-1910) the Tārīkh-i Hindustān.

Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies.

We have designed and validated a novel generic platform for production of tetravalent IgG1-like chimeric bispecific Abs. The VH-CH1-hinge domains of mAb2 are fused through a peptidic linker to the N terminus of mAb1 H chain, and paired mutations at the CH1-CL interface mAb1 are introduced that force the correct pairing of the two different free L chains. Two different sets of these CH1-CL interface mutations, called CR3 and MUT4, were designed and tested, and prototypic bispecific Abs directed against CD5 and HLA-DR were produced (CD5xDR). Two different hinge sequences between mAb1 and mAb2 were also tested in the CD5xDR-CR3 or -MUT4 background, leading to bispecific Ab (BsAbs) with a more rigid or flexible structure. All four Abs produced bound with good specificity and affinity to CD5 and HLA-DR present either on the same target or on different cells. Indeed, the BsAbs were able to efficiently redirect killing of HLA-DR(+) leukemic cells by human CD5(+) cytokine-induced killer T cells. Finally, all BsAbs had a functional Fc, as shown by their capacity to activate human complement and NK cells and to mediate phagocytosis. CD5xDR-CR3 was chosen as the best format because it had overall the highest functional activity and was very stable in vitro in both neutral buffer and in serum. In vivo, CD5xDR-CR3 was shown to have significant therapeutic activity in a xenograft model of human leukemia.

From breaking the rule to making the rules : the adoption, entrenchment and diffusion of gender quotas in France

Once a country allergic to any type of preferential treatment or quota measure for women, France has become a country that applies gender quotas to regulate women's presence and representation in politics, the business sector, public bodies, public administration, and even some civil society organizations. While research has concentrated on the adoption of electoral gender quotas in many countries and their international diffusion, few studies focus on explaining the successful diffusion of gender quotas from politics to other domains in the same country. This paper proposes to fill this gap by studying the particularly puzzling case of a country that at one point strongly opposed the adoption of gender quotas in politics, but, in less than a decade, transformed into one of the few countries applying gender quotas across several policy domains. This paper argues that the legal entrenchment of the parity principle, the institutionalization of parity in several successive women's policy agencies, and key players in these newly created agencies are mainly responsible for this unexpected development. The diffusion of gender quotas in France thus offers an illuminating example of under which conditions women's policy agencies can act autonomously to diffuse and impose a new tool for gender equality

Design of highly focused fields that remain unpolarized on axis

Research on the properties of highly focused fields mainly involved fully polarized light, whereas partially polarized waves received less attention. The aim of this Letter is to provide an appropriate framework, for designing some features of the focused field, when dealing with incoming partially polarized beams. In particular, in this Letter, we describe how to get an unpolarized field on the axis of a high numerical aperture objective lens. Some numerical results that corroborate theoretical predictions are provided.

Self-rule Index for Local Authorities (Release 1.0)

Local autonomy is a highly valued feature of good governance. The continuous attempts of many European countries to strengthen the autonomy of local government show the importance given to decentralisation and far-reaching competences at the lowest units of a state. Measuring and comparing local autonomy, however, has proven to be a difficult task. Not only are there diverging ideas about the core elements of local autonomy, there are also considerable difficulties to apply specific concepts to different countries. This project suggests a comprehensive methodology to measure local autonomy. It analyses 39 European countries and reports changes between 1990 and 2014. A network of experts on local government assessed the autonomy of local government of their respective countries on the basis of a common code book. The eleven variables measured are located on seven imensions and can be combined to a "Local Autonomy Index" (LAI). The data show an increase of local autonomy between 1990 and 2005, especially in the new Central and Eastern European countries. Countries with a particularly high degree of local autonomy are Switzerland, the Nordic countries, Germany and Poland.

Exploring new criteria to design materials for online education

Peer-reviewed

User-Centered Design Gymkhana

The User-centered design (UCD) Gymkhana is a tool for human-computer interaction practitioners to demonstrate through a game the key user-centered design methods and how they interrelate in the design process.The target audiences are other organizational departments unfamiliar with UCD but whose work is related to the definition, cretaion, and update of a product service.

Creating a research network for a successful e-portfolio design and implementation

The presence of e-portfolios in educational centres, companies and administrations has emergedstrongly during the last years by creating very different practices coming from different objectives and purposes. This situation has led researchers and practitioners to design and implement e-portfolios with little reference to previous knowledge of them; consequently, developments are disparate with many of the processes and dimensions used both in development and use being unnecessary complex. In order to minimize the inconveniences, unify these developmental processes and improve the resultsof implementation and use of e-portfolios, it seemed necessary to create a network of researchers, teachers and trainers coming from different universities and institutions of different kinds who are interested in the investigation and the practice of e-portfolios in Spain. Therefore, The Network on e-portfoliowas created in 2006, funded by the Spanish Ministry of Education and led by the UniversitatOberta de Catalunya. Besides the goals associatedwith the creation of this network and which wewanted to share with other European researchers and experts of other continents, we will also present in this paper some data concerned with the first study carried out on the use of e-portfolios in our country that shows where we are and which trends are the most important for the near future.