13 research outputs found

    Design for subjective wellbeing: towards a design framework for constructing narrative

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    We explore the role that interaction with products and services can play in the narratives that we develop about ourselves. We propose a four-level model, which seeks to explain this and use it as the basis for analyzing eight immersion studies. In each, we investigate the role that products and services play in shaping narratives, which in turn reflect our self-identity. We also look at archetypes – the various ideals that we can have about ourselves – and at how the alignment of narratives with these enhances our wellbeing. The model offers the potential to link narrative to design features and to identify new market opportunities. However, we recognize there may be challenges in enabling people to articulate narrative and identify their ideal archetype

    Narrative and design for wellbeing: a user-centered approach

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    The narratives that we have about our lives can affect our wellbeing. The Products and services that we own or use can play a role in these narratives (Jordan, Bardill, Herd and Grimaldi 2020) – the car that says "I am a success", the toy that says "I am a good parent" or the customer-care that lets me know that "I am not important.” In an exploratory study, 41 undergraduate students described experiences with two different products or services – one that enabled and one that failed to enable a desired narrative. These 82 case studies were analysed to explore concepts relevant to narrative in the context of product and service use. We identify six different ways in which a product or service can enable a narrative, evaluate Jung’s archetypes as a means of narrative classification, and explore the roles of products and users in enabling stories. The implications for user research and design are explored

    Identification of non-dot/icm suppressors of the Legionella pneumophila △dotL lethality phenotype

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    Legionella pneumophila, a causative agent of bacterial pneumonia, survives inside phagocytic cells by avoiding rapid targeting to the lysosome. This bacterium utilizes a type IVB secretion system, encoded by the dot/icm genes, to replicate inside host cells. DotL, a critical component of the Dot/Icm secretion apparatus, functions as the type IV coupling protein. In contrast to most dot/icm genes, which are dispensable for growth on bacteriological media, dotL is required for the viability of wild-type L. pneumophila. Previously we reported that ΔdotL lethality could be suppressed by inactivation of the Dot/Icm complex via mutations in other dot/icm genes. Here we report the isolation of non-dot/icm suppressors of this phenotype. These ΔdotL suppressors include insertions that disrupt the function of the L. pneumophila homologs of cpxR, djlA, lysS, and two novel open reading frames, lpg0742 and lpg1594, that we have named ldsA and ldsB for lethality of ΔdotL suppressor. In addition to suppressing ΔdotL lethality, inactivation of these genes in a wild-type strain background causes a range of defects in L. pneumophila virulence traits, including intracellular growth, implicating these factors in the proper function of the Dot/Icm complex. Consistent with previous data showing a role for the cpx system in regulating expression of several dot/icm genes, the cpxR insertion mutant produced decreased levels of three Dot/Icm proteins, DotA, IcmV, and IcmW. The remaining four suppressors did not affect the steady-state levels of any Dot/Icm protein and are likely to represent the first identified factors necessary for assembly and/or activation of the Dot/Icm secretion complex

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Narrativa e design para o bem-estar: uma abordagem centrada no usuário

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    The narratives that we have about our lives can affect our wellbeing. The Products and services that we own or use can play a role in these narratives (Jordan, Bardill, Herd and Grimaldi, 2020) – the car that says "I am a success", the toy that says "I am a good parent" or the customer-care that lets me know that "I am not important.” In an exploratory study, 41 undergraduate students described experiences with two different products or services – one that enabled and one that failed to enable a desired narrative. These 82 case studies were analysed to explore concepts relevant to narrative in the context of product and service use. We identify six different ways in which a product or service can enable a narrative, evaluate Jung’s archetypes as a means of narrative classification, and explore the roles of products and users in enabling stories. The implications for user research and design are explored.Las narrativas que tenemos acerca de nuestras vidas pueden afectar nuestro bienestar. Los productos y servicios que poseemos pueden desempeñar un papel en estas narrativas (Jordan, Bardill, Herd y Grimaldi, 2020) – el auto que dice "Soy exitoso ", el juguete que dice "Soy un buen padre" o el servicio al cliente que me deja saber que "Yo no soy importante.” En un estudio exploratorio, 41 estudiantes de pregrado describieron experiencias con dos productos o servicios diferentes – uno que permitía una narrativa deseada y otro que no la permitía. Estos 82 estudios de caso se analizaron para explorar conceptos pertinentes para la narrativa dentro del contexto del uso de productos y servicios. Identificamos seis maneras diferentes en las que un producto o servicio puede permitir una narrativa, evaluamos los arquetipos de Jung como una manera de clasificar narrativas, y exploramos los papeles de productos y usuarios para permitir relatos. Se exploran las implicaciones de lo anterior para la investigación sobre usuarios y diseño.Les récits dont nous disposons sur nos vies peuvent affecter notre bien-être. Les produits et services que nous possédons peuvent jouer un rôle dans ces récits (Jordan, Bardill, Herd et Grimaldi, 2020) : la voiture qui dit “J’ai réussi socialement”, le jouet qui dit “Je suis un bon père”, ou le service à la clientèle qui me fait savoir que “Je ne suis pas important”. Dans une étude exploratoire, on a demandé à 41 étudiants du premier cycle universitaire de décrire des expériences avec deux produits ou services différents : l’un permettant un récit désiré, l’autre ne le permettant pas. On a analysé ces 82 études de cas pour explorer les concepts pertinents pour le récit dans le contexte de l’utilisation de produits et de services. On a identifié six façons différentes dont un produit ou un service peut permettre un récit ; on a évalué les archétypes de Jung comme un moyen de classer les récits ; puis on a exploré les rôles des produits et des utilisateurs pour permettre des histoires ; enfin, on a examiné les implications de ces résultats pour la recherche sur les utilisateurs et le design.Le narrative che circondano le nostre vite possono incidere nel nostro benessere. I prodotti e i servizi che abbiamo giocano un ruolo nelle narrative (Jordan, Bardill, Herd y Grimaldi, 2020) – la macchina che porta lo slogan “sono una persona di successo”, il giocattolo “Sono un buon papá” oppure il servizio che fa sapere ai clienti “io non sono importante”. Uno studio di esplorazione fatto sulle percezioni di quarantuno studenti universitari descrive l’esperienza con due prodotti o servizi diversi, il primo con una narrativa desiderata e l’altro, invece, no. Gli ottantadue studi di casi si analizzano per esplorare concetti pertinenti per le narrative in riferimento all’uso dei prodotti e i servizi. Si sono identificati sei modi diversi in cui in prodotto oppure un servizio permette una narrativa specifica, abbiamo valutato gli archetipi di Jung come un modo adeguato per classificare i narrativi e abbiamo anche esplorato i ruoli dei prodotti e degli utenti per la creazione di racconti. Finalmente, se n’esplorano anche le implicazioni per la ricerca su utenti e design.As nossas narrativas sobre nossas vidas podem afetar nosso bem-estar. Os produtos e serviços que possuímos podem ter um papel nestas narrativas (Jordan, Bardill, Herd e Grimaldi, 2020) - o carro que diz “Sou bem sucedido”, o brinquedo que diz “Sou um bom pai”, ou o serviço ao cliente que me faz sentir que “Não sou importante”. Em um estudo exploratório, 41 estudantes de graduação descreveram experiências com dois produtos ou serviços diferentes - um permitindo uma narrativa desejada e outro que não permitindo-a. Estes 82 estudos de caso foram analisados para explorar conceitos relevantes à narrativa dentro do contexto do uso de produtos e serviços. Foram identificadas seis maneiras diferentes nas que um produto ou serviço pode propiciar uma narrativa, foram avaliados arquétipos junguianos como forma de classificar narrativas, e foram explorados os papéis dos produtos e usuários para propiciar histórias. As implicações do acima exposto foram exploradas visando pesquisar usuários e projetos

    Requirements of Hsp104p activity and Sis1p binding for propagation of the [RNQ+] prion

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    The formation and maintenance of prions in the yeast Saccharomyces cerevisiae is highly regulated by the cellular chaperone machinery. The most important player in this regulation is Hsp104p, which is required for the maintenance of all known prions. The requirements for other chaperones, such as members of the Hsp40 or Hsp70 families, vary with each individual prion. [RNQ+] cells do not have a phenotype that is amenable to genetic screens to identify cellular factors important in prion propagation. Therefore, we used a chimeric construct that reports the [RNQ+] status of cells to perform a screen for mutants that are unable to maintain [RNQ+]. We found eight separate mutations in Hsp104p that caused [RNQ+] cells to become [rnq−]. These mutations also caused the loss of the [PSI+] prion. The expression of one of these mutants, Hsp104p-E190K, showed differential loss of the [RNQ+] and [PSI+] prions in the presence of wild type Hsp104p. Hsp104p-E190K inefficiently propagated [RNQ+] and was unable to maintain [PSI+]. The mutant was unable to act on other in vivo substrates, as strains carrying it were not thermotolerant. Purified recombinant Hsp104p-E190K showed a reduced level of ATP hydrolysis as compared to wild type protein. This is likely the cause of both prion loss and lack of in vivo function. Furthermore, it suggests that [RNQ+] requires less Hsp104p activity to maintain transmissible protein aggregates than Sup35p. Additionally, we show that the L94A mutation in Rnq1p, which reduces its interaction with Sis1p, prevents Rnq1p from maintaining a prion and inducing [PSI+]

    The Spontaneous Appearance Rate of the Yeast Prion [PSI+] and Its Implications for the Evolution of the Evolvability Properties of the [PSI+] System

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    Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects of natural selection on modifiers of [PSI+] appearance have been the subject of much debate. It seems likely that [PSI+] would be at least mildly deleterious in most environments, but this may be counteracted by its evolvability properties on rare occasions. Indirect selection on modifiers of [PSI+] is predicted to depend primarily on the spontaneous [PSI+] appearance rate, but this critical parameter has not previously been adequately measured. Here we measure this epimutation rate accurately and precisely as 5.8 × 10−7 per generation, using a fluctuation test. We also determine that genetic “mimics” of [PSI+] account for up to 80% of all phenotypes involving general nonsense suppression. Using previously developed mathematical models, we can now infer that even in the absence of opportunities for adaptation, modifiers of [PSI+] are only weakly deleterious relative to genetic drift. If we assume that the spontaneous [PSI+] appearance rate is at its evolutionary optimum, then opportunities for adaptation are inferred to be rare, such that the [PSI+] system is favored only very weakly overall. But when we account for the observed increase in the [PSI+] appearance rate in response to stress, we infer much higher overall selection in favor of [PSI+] modifiers, suggesting that [PSI+]-forming ability may be a consequence of selection for evolvability

    Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice

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    Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent of viral spread and replication typically require the sacrifice of infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used a strain KOS HSV-1 recombinant that expresses firefly (Photinus pyralis) and Renilla (Renilla reniformis) luciferase reporter proteins and monitored infection with a cooled charge-coupled device camera. Viral infection in mouse footpads, peritoneal cavity, brain, and eyes could be detected by bioluminescence imaging of firefly luciferase. The activity of Renilla luciferase could be imaged after direct administration of substrate to infected eyes but not following the systemic delivery of substrate. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated directly with input titers of recombinant virus used for infection. Treatment of infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced dose-dependent decreases in firefly luciferase activity that correlated with changes in viral titers. These data demonstrate that bioluminescence imaging can be used for noninvasive, real-time monitoring of HSV-1 infection and therapy in living mice
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