A noticeboard in "both worlds" unsurprising interfaces supporting easy bi-cultural content publication

We describe the design of a digital noticeboard to support communication within a remote Aboriginal community whose aspiration is to live in "both worlds", nurturing and extending their Aboriginal culture and actively participating in Western society and economy. Three bi-cultural aspects have emerged and are presented here: the need for a bi-lingual noticeboard to span both oral and written language traditions, the tension between perfunctory information exchange and social, embodied protocols of telling in person and the different ways in which time is represented in both cultures. The design approach, developed iteratively through consultation, demonstration and testing led to an "unsurprising interface", aimed at maximizing use and appropriation across cultures by unifying visual, text and spoken contents in both passive and interactive displays in a modeless manner.

Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis

The mechanism by which human leukocyte antigen B27 (HLA-B27) contributes to ankylosing spondylitis (AS) remains unclear. Genetic studies demonstrate that association with and interaction between polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) and HLA-B27 influence the risk of AS. It has been hypothesised that ERAP1-mediated HLA-B27 misfolding increases endoplasmic reticulum (ER) stress, driving an interleukin (IL) 23-dependent, pro-inflammatory immune response. We tested the hypothesis that AS-risk ERAP1 variants increase ER-stress and concomitant pro-inflammatory cytokine production in HLA-B27 + but not HLA-B27-AS patients or controls. Forty-nine AS cases and 22 healthy controls were grouped according to HLA-B27 status and AS-associated ERAP1 rs30187 genotypes: HLA-B27 + ERAP1 risk, HLA-B27 + ERAP1 protective, HLA-B27-ERAP1 risk and HLA-B27-ERAP1 protective. Expression levels of ER-stress markers GRP78 (8 kDa glucose-regulated protein), CHOP (C/EBP-homologous protein) and inflammatory cytokines were determined in peripheral blood mononuclear cell and ileal biopsies. We found no differences in ER-stress gene expression between HLA-B27 + and HLA-B27-cases or healthy controls, or between cases or controls stratified by carriage of ERAP1 risk or protective alleles in the presence or absence of HLA-B27. No differences were observed between expression of IL17A or TNF (tumour necrosis factor) in HLA-B27 + ERAP1 risk, HLA-B27 + ERAP1 protective and HLA-B27-ERAP1 protective cases. These data demonstrate that aberrant ERAP1 activity and HLA-B27 carriage does not alter ER-stress levels in AS, suggesting that ERAP1 and HLA-B27 may influence disease susceptibility through other mechanisms. © 2015 Macmillan Publishers Limited.

Genetic analysis of chromosomal regions 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility

Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system (CNS) affecting 0.1-0.2% of Northern European descent population. MS is considered to be a multifactorial disease, both environment and genetics play a role in its pathogenesis. Despite several decades of intense research, the etiological and pathogenic mechanisms underlying MS remain still largely unknown and no curative treatment exists. The genetic architecture underlying MS is complex with multiple genes involved. The strongest and the best characterized predisposing genetic factors for MS are located, as in other immune-mediated diseases, in the major histocompatibility complex (MHC) on chromosome 6. In humans MHC is called human leukocyte antigen (HLA). Alleles of the HLA locus have been found to associate strongly with MS and remained for many years the only consistently replicable genetic associations. However, recently other genes located outside the MHC region have been proposed as strong candidates for susceptibility to MS in several studies. In this thesis a new genetic locus located on chromosome 7q32, interferon regulatory factor 5 (IRF5), was identified in the susceptibility to MS. In particular, we found that common variation of the gene was associated with the disease in three different populations, Spanish, Swedish and Finnish. We also suggested a possible functional role for one of the risk alleles with impact on the expression of the IRF5 locus. Previous studies have pointed out a possible role played by chromosome 2q33 in the susceptibility to MS and other autoimmune disorders. The work described here also investigated the involvement of this chromosomal region in MS predisposition. After the detection of genetic association with 2q33 (article-1), we extended our analysis through fine-scale single nucleotide polymorphism (SNP) mapping to define further the contribution of this genomic area to disease pathogenesis (article-4). We found a trend (p=0.04) for association to MS with an intronic SNP located in the inducible T-cell co-stimulator (ICOS) gene, an important player in the co-stimulatory pathway of the immune system. Expression analysis of ICOS revealed a novel, previously uncharacterized, alternatively spliced isoform, lacking the extracellular domain that is needed for ligand binding. The stability of the newly-identified transcript variant and its subcellular localization were analyzed. These studies indicated that the novel isoform is stable and shows different subcellular localization as compared to full-length ICOS. The novel isoform might have a regulatory function, but further studies are required to elucidate its function. Chromosome 19q13 has been previously suggested as one of the genomic areas involved in MS predisposition. In several populations, suggestive linkage signals between MS predisposition and 19q13 have been obtained. Here, we analysed the role of allelic variation in 19q13 by family based association analysis in 782 MS families collected from Finland. In this dataset, we were not able to detect any statistically significant associations, although several previously suggested markers were included to the analysis. Replication of the previous findings on the basis of linkage disequilibrium between marker allele and disease/risk allele appears notoriously difficult because of limitations such as allelic heterogeneity. Re-sequencing based approaches may be required for elucidating the role of chromosome 19q13 with MS. This thesis has resulted in the identification of a new MS susceptibility locus (IRF5) previously associated with other inflammatory or autoimmune disorders, such as SLE. IRF5 is one of the mediators of interferons biological function. In addition to providing new insight in the possible pathogenetic pathway of the disease, this finding suggests that there might be common mechanisms between different immune-mediated disorders. Furthermore the work presented here has uncovered a novel isoform of ICOS, which may play a role in regulatory mechanisms of ICOS, an important mediator of lymphocyte activation. Further work is required to uncover its functions and possible involvement of the ICOS locus in MS susceptibility.

Bi-cultural content publication on a digital noticeboard: A design and cultural differences case study

We present our observations of Aboriginal Australian practices around a custom digital noticeboard and compare our insights to related research on cultural differences, literacy and ICT4D. The digital noticeboard was created, upon a request by the community Elders, to foster communication across the community. The initial design, informed by discussions and consultations, aimed at supporting the local Aboriginal language and English, both in written and spoken form, at supporting the oral tradition, and at accommodating for different perceptions and representations of time. This paper presents observations about the first encounters with the digital noticeboard by those members of the community that took part in its conceptualization. Such observations reinforce existing knowledge on such cultural phenomena as collectivism and time perception, issues related to literacy, moderation and censorship. We contribute to framing such knowledge within a concrete case study and draw implication for design of tools for bi-cultural content publication.

The Messaging Kettle: It’s IoTea time

We demonstrate a working prototype of a Messaging Kettle designed to facilitate asynchronous communication and enable a sense of presence between adult children and their older parents living abroad. Our goal is to offer a human centred critique of the Internet of Things, which has largely been conceived without consideration of the people who will use the things, and rather has traditionally moved from a technology oriented perspective. In the case of smart homes this approach has produced a wide array of projects focused on monitoring the habits of the elderly, recognizing anomalies and alerting the caregivers. In contrast we propose to focus on engagement and reciprocity, building on the rituals associated to habitually used and cherished objects. We conclude revisiting the technology oriented framework for the Internet of Things to include our observations on people’s perspective on smart communicating objects.

Towards an analysis framework of technology habituation by older users

Smart everyday objects could support the wellbeing, independent living and social connectedness of ageing people, but their successful adoption depends upon them fitting with their skills, values and goals. Many technologies fail in this respect. Our work is aimed at designs that engage older people by building on their individual affective attachment to habituated objects and leveraging, from a participatory design perspective, the creative process through which people continuously adapt their homes and tools to their own lifestyle. We contribute a novel analytic framework based on an analysis of related research on appropriation and habituated objects. It identifies steps in appropriation from inspection to performance and habituation. We test this framework with the preliminary testing of an augmented habituated object, a messaging kettle. While only used in one home so far, its daily use has provoked many thoughts, scenarios and projections about use by friends, both practical, utopian and dystopian.

The internet of playful things

This one-day workshop brings together researchers and practitioners to share knowledge and practices on how people can connect and interact with the Internet of Things in a playful way. Open to participants with a diverse range of interests and expertise, and by exploring novel ways to playfully connect people through their everyday objects and activities, the workshop will facilitate discussion across a range of HCI discipline areas. The outcomes from the workshop will include an archive of participants' initial position papers along with the materials created during the workshop. The result will be a road map to support the development of a Model of Playful Connectedness, focusing on how best to design and make playful networks of things, identifying the challenges that need to be addressed in order to do so.

Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa

Purpose: Mutations in IDH3B, an enzyme participating in the Krebs cycle, have recently been found to cause autosomal recessive retinitis pigmentosa (arRP). The MDH1 gene maps within the RP28 arRP linkage interval and encodes cytoplasmic malate dehydrogenase, an enzyme functionally related to IDH3B. As a proof of concept for candidate gene screening to be routinely performed by ultra high throughput sequencing (UHTs), we analyzed MDH1 in a patient from each of the two families described so far to show linkage between arRP and RP28. Methods: With genomic long-range PCR, we amplified all introns and exons of the MDH1 gene (23.4 kb). PCR products were then sequenced by short-read UHTs with no further processing. Computer-based mapping of the reads and mutation detection were performed by three independent software packages. Results: Despite the intrinsic complexity of human genome sequences, reads were easily mapped and analyzed, and all algorithms used provided the same results. The two patients were homozygous for all DNA variants identified in the region, which confirms previous linkage and homozygosity mapping results, but had different haplotypes, indicating genetic or allelic heterogeneity. None of the DNA changes detected could be associated with the disease. Conclusions: The MDH1 gene is not the cause of RP28-linked arRP. Our experimental strategy shows that long-range genomic PCR followed by UHTs provides an excellent system to perform a thorough screening of candidate genes for hereditary retinal degeneration.

Ultra high throughput sequencing excludes MDH1 as candidate gene for RP28-linked retinitis pigmentosa

Purpose: Mutations in IDH3B, an enzyme participating in the Krebs cycle, have recently been found to cause autosomal recessive retinitis pigmentosa (arRP). The MDH1 gene maps within the RP28 arRP linkage interval and encodes cytoplasmic malate dehydrogenase, an enzyme functionally related to IDH3B. As a proof of concept for candidate gene screening to be routinely performed by ultra high throughput sequencing (UHTs), we analyzed MDH1 in a patient from each of the two families described so far to show linkage between arRP and RP28. Methods: With genomic long-range PCR, we amplified all introns and exons of the MDH1 gene (23.4 kb). PCR products were then sequenced by short-read UHTs with no further processing. Computer-based mapping of the reads and mutation detection were performed by three independent software packages. Results: Despite the intrinsic complexity of human genome sequences, reads were easily mapped and analyzed, and all algorithms used provided the same results. The two patients were homozygous for all DNA variants identified in the region, which confirms previous linkage and homozygosity mapping results, but had different haplotypes, indicating genetic or allelic heterogeneity. None of the DNA changes detected could be associated with the disease.

Limiting two-Higgs-doublet models

We update the constraints on two-Higgs-doublet models (2HDMs) focusing on the parameter space relevant to explain the present muon g - 2 anomaly, Delta alpha(mu), in four different types of models, type I, II, ``lepton specific'' (or X) and ``flipped'' (or Y). We show that the strong constraints provided by the electroweak precision data on the mass of the pseudoscalar Higgs, whose contribution may account for Delta alpha(mu), are evaded in regions where the charged scalar is degenerate with the heavy neutral one and the mixing angles alpha and beta satisfy the Standard Model limit beta - alpha approximate to pi/2. We combine theoretical constraints from vacuum stability and perturbativity with direct and indirect bounds arising from collider and B physics. Possible future constraints from the electron g - 2 are also considered. If the 126 GeV resonance discovered at the LHC is interpreted as the light CP-even Higgs boson of the 2HDM, we find that only models of type X can satisfy all the considered theoretical and experimental constraints.

Peptide delta-Turn: Literature Survey and Recent Progress

Among the various types of a-peptide folding motifs, delta-turn, which requires a central cis-amide disposition, has been one of the least extensively investigated. In particular, this main-chain reversal topology has been studied in-depth neither in linear/cyclic peptides nor in proteins. This Minireview article assembles and critically analyzes relevant data from a literature survey on the d-turn conformation in those compounds. Unpublished results from recent conformational energy calculations and a preliminary solution-state analysis on a small model peptide, currently ongoing in our laboratories, are also briefly outlined.

Sapientia, 2000, Vol. LV, nº 207 (número completo)

Contenido: Il Dio dei filosofi e il Dio dei teologi in Guglielmo di Ockham / Alessandro Ghisalberti – La Trinidad divina y la deificación del hombre por el nacimiento del hijo en el alma, según los escritos del maestro Eckhart / Brian J. Farrelly – Suárez y Descartes sobre la noción de verdades eternas y su relación con Dios / Bernardo Cantens – Interacción mente-cuerpo y libre arbitrio en Descarles / Enrique Chávez-Arvizo – Razón y verdad : Hobbes y el Aquinate / María L. Lukac de Stier – Pascal y la crisis de la razón / Francisco Leocata – La contribución de Jacques Maritain a la teología natural / Juan J. Álvarez – Ontología de lo social / Abelardo Pithod – Réflexions sur une introduction à la métaphysique / Yves Floucat – El conocimiento divino del ente futuro contingente / Gabriel Delgado – Insegnamento sociale cristiano : magistero e scienze umane / Enrique Colom – Aquinas on Aristotle and creation : use or misuse? / Timothy L. Smith – La verdad, raíz de la libertad / Gustavo Eloy Ponferrada – Besoin de Dieu et désir de Dieu : l’illusion d’une mort / Michel Mahé – El ser a merced de la afectividad / Mario Enrique Sacchi – Notas y comentarios -- Bibliografía

Prudentia Iuris, 1997, n° 44 (número completo)

Contenido: Semblanza del Doctor Jorge Joaquín Llambías / Guillermo A. Borda – El derecho a la identidad personal / José Luis Mozos – La mediación / Susana I. Cures – Bioética / Rubén Oscar Revello – La hipoteca cambiaria y de títulos-valores / Joaquín Rams Albesa – El Derecho Internacional Privado en las relaciones Mercosur-Unión Europea Nafta / Siegbert Rippe – La Convención Universal sobre derechos de los niños y adolescentes en la Constitución Nacional Argentina / Nora D’Alessandro Halty – Los acreedores en el proceso sucesorio / Claudia Schmidt Hott – Autonomía de la voluntad : problemática actual / María Cármen Gómez Laplaza – Actuación dañosa de los grupos / Ricardo de Ángel Yagüez – La legítima en el Derecho Romano / Alfredo Di Pietro

Criminalização das ocupações de propriedades rurais por movimentos sociais : reflexões à luz dos princípios de direito penal mínimo

Analisa a pretensão da criminalização primária das ocupações de propriedades públicas e privadas por movimentos sociais, tendo como marco teórico o pensamento de Alessandro Baratta sobre os limites de intervenção penal estatal, especialmente os princípios da “proporcionalidade abstrata” e da “articulação autônoma dos conflitos e das necessidades reais”.

The role of the terms of trade in the trade channel of transmission of oil price shocks

This paper highlights the role of the terms of trade in the trade channel of propagation of oil price shocks both empirically and theoretically. Empirically, I show that oil price shocks have a large, persistent and statistically significant impact on the US terms of trade. Theoretically, I add oil in the model by Corsetti and Pesenti (2005) and analyse under what conditions the terms of trade plays a relevant role in the international transmission of oil price shocks. With nominal price rigidities and full exchange rate pass-through positive oil price shocks depreciate the currency of the oil importing country. The subsequent negative wealth effect adds to the recessive effect of the supply channel and may trongly reduce the consumption in the oil importing country economy. Without exchange rate pass-through oil shocks transmit to the economy only through the supply channel. The model suggests that a change in the exchange rate pass-through might contribute to explain the evidence of a weaker impact of oil price shocks on the macroeconomic activity in recent times.