Enriching Discourse on Public Domains

Studying microvascular responses to iontophoresis of vasoconstricting drugs contributes to a better understanding of the regulatory mechanisms of cutaneous vessels, but measuring these responses with laser-Doppler flowmetry at basal blood flow conditions is technically challenging. This study aimed to investigate whether the measurement of cutaneous vasoconstrictor responses to noradrenaline (NA) and phenylephrine (PE), delivered by iontophoresis, is facilitated by predilatation of the microvascular bed using local heating. We used different drug delivery rates (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x 0.04 mA) to investigate whether predilatation affects the local drug dynamics by an increased removal of drugs from the skin. In a predilatated vascular bed, iontophoresis of NA and PE resulted in a significant decrease in perfusion from the thermal plateau (p andlt; 0.001). The decrease was 25-33%, depending on drug delivery rate. In unheated skin, a significant vasoconstriction was observed (p andlt; 0.001), with 17% and 14% decrease from baseline for NA and PE, respectively. These results indicate that predilatating the cutaneous vascular bed by local heating facilitates measurement of vasoconstriction with laser-Doppler flowmetry and does not seem to significantly affect the result by an increased removal of drugs from the skin.Original Publication: Joakim Henricson, Yashma Baiat and Folke Sjöberg, Local Heating as a Predilatation Method for Measurement of Vasoconstrictor Responses with Laser-Doppler Flowmetry, 2011, MICROCIRCULATION, (18), 3, 214-220. http://dx.doi.org/10.1111/j.1549-8719.2010.00079.x Copyright: Wiley http://eu.wiley.com/WileyCDA/Brand/id-35.html</p

Är att en citatmarkör?

Artikel i konferensrapport.I artikeln presenteras en studie av hur konnektiven att används i citatkontext i svenska ungdomssamtal. Materialet utgörs av svenska samtal inspelade i Helsingfors, på finskdominerade orter i Finland (s.k. svenska språköar) och i Göteborg. En genomgående frågeställning är den regionala variationen, där skillnaden ter sig klarast mellan de finlandssvenska och de göteborgssvenska samtalen. I de göteborgssvenska samtalen verkar att ha bevarat sin funktion som subjunktion och förekommer i första hand framför indirekta citat, medan att i de finlandssvenska samtalen i högsta grad även förknippas med direkta citat

The Role of Suppressor of Fused in Development and Tumorigenesis in the Mouse

Embryonic development is a process that involves a number of evolutionarily wellconserved signaling cascades, including the hedgehog pathway. Mutations in components of this pathway have been identified in certain developmental disorders, and in many different kinds of cancers. In fact, the most common cancer in the Western World, basal cell carcinoma (BCC) of the skin, is due to mutations that cause aberrantly activated hedgehog signaling. This thesis focuses on a protein known as Suppressor of fused (Sufu), which is an essential tumor suppressor within the hedgehog pathway. In PAPER I, we made the surprising observation that Sufu actually plays a fundamental role in the mammalian hedgehog signaling pathway, in contrast to its role in fruit flies and even zebrafish. In these organisms, Sufu plays an insignificant part in normal hedgehog signaling, since its absence only results in minor phenotypic changes. However, in the mouse, we showed that loss of Sufu leads to embryonic death in midgestation with the embryos exhibiting severe cephalic defects and an open neural tube. We also demonstrated that the Sufu loss-of-function phenotype was due to ligandindependent activation of the hedgehog signaling pathway. In humans, Gorlin syndrome is a rare developmental disorder that in the majority of cases is due to inactivating mutations in the gene that encodes the hedgehog receptor, PTCH1. This leads to overactivated hedgehog signaling, since PTCH1 is no longer able to inhibit the signal transducer, Smoothened (SMO). Gorlin syndrome involves an array of different developmental defects, but it also leads to increased tumor susceptibility, especially in the form of multiple BCCs. In PAPER I we discovered that mice, heterozygous for the Sufu gene, develop features of Gorlin syndrome, including a skin phenotype with BCC-like attributes, in addition to developmental aberrations in the form of jaw keratocysts. In addition, we showed that the extent of epidermal skin changes correlated with increased hedgehog pathway activation. The BCC-like lesions in Sufu+/- mice are reminiscent of basaloid follicular hamartomas (BFH), which are more benign lesions than BCCs. In PAPER II, the aim was to investigate whether the Sufu+/- skin lesions would develop into full-blown BCCs if Trp53 was knocked out simultaneously. Trp53 is a well-known tumor suppressor gene that can enhance hedgehog-driven tumors, and is often mutated in sporadic BCCs, sometimes in combination with PTCH1 mutations. We showed that Sufu+/- mice on a Trp53 null background develop medulloblastomas and rhabdomyosarcomas, which is consistent with previous reports. Surprisingly, however, the Sufu+/- skin phenotype was not altered in the absence of Trp53, and showed no changes in latency, multiplicity, cellular phenotype or proliferative capacity during the lifespan of the mice. This finding suggests a differential, tissue-specific sensitivity to Sufu and Trp53 gene loss, possibly linked to developmental phase and proliferative potential in specific tissues. In PAPER III, we studied developmental and differentiation processes in the absence of Sufu, using embryonic stem cells (ESCs) derived from Sufu-/- preimplantation embryos. Sufu-/- ESCs were found to express typical pluripotency markers, but the activity of the hedgehog pathway was increased only modestly compared to wild-type ESCs, as indicated by Gli1 target gene expression. The Sufu-/- ESCs formed embryoid bodies in vitro, which, in later stages, were smaller than their wild-type counterparts, suggesting a deficiency in proliferation. To test the differentiation capacity of the Sufu-/- ESCs in vivo, the cells were injected subcutaneously into nude mice to form teratomas. Teratomas from Sufu-/- ESCs developed at efficiencies and latencies equivalent to teratomas from wild-type ESCs, yet in stark contrast to wild-type, Sufu-/- teratomas were dominated by neuroectodermal tissues and were deficient in the mesodermal derivatives, cartilage and bone. These findings call attention to the central role played by Sufu in the hedgehog signaling pathway, and propose a function for Sufu in ectodermal-mesodermal cell fate decision. In a PRELIMINARY STUDY, we have generated conditional Sufu mutant mice with the aim of deleting Sufu in specific tissues at specific time-points. These studies are ongoing, and experiments to create mice with complete loss of Sufu in the K5 (basal cell) compartment of the skin have been initiated. In summary, the studies in this thesis highlight an essential role for Sufu in the hedgehog signaling pathway during development and tumorigenesis in mammals

Integrating Exception Handling in Machine Development

In modern batch plants, alarm floods overwhelming the operator is a common problem of ever increasing severity. As plant hardware increase in complexity and performance, measures such as downtime and meantime between failures, increase in importance and the need for a well-functioning exception handling routine therefore grows critical. In order to minimize downtime and hence boost production efficiency, it is important that faulty or unexpected behaviour is noted early and diagnosed accurately. If it is, the machine or its operator can deal with it fast and accurately, perhaps even while production continues. If it is not, however, it basically means two bad things, the first being unnecessary production stops and the second a flooded alarm list. The alarm list is the screen on which all exceptions are listed and which is meant to tell the process operator what is wrong and what he should do about it. If no care is taken about it, the list will be flooded since one key exception will cause several others, leaving the operator with the quite unpleasant task of identifying what went wrong and how he should fix it. This master's thesis, carried out at Tetra Pak in Lund, Sweden, presents a well-structured exception handling method and a way of linking it to a workflow. It uses advantages of reusability, modularisation and linking to almost any structural model such as a Function Means Tree (used in WCE) or a UML-model. The linking has several advantages minimizing the work and improving evolutionary possibilities. Examples are being made for illustrational purposes but no implementational efforts or issues are addressed. A well-defined structure for information flow is also suggested to provide modular thinking that, for example, prepares the possibility to collect data for statistical analysis and such

The translation of an incubator: the case of the Lighthouse in Bubulo, Uganda

This article reviews a social entrepreneurial initiative to set up a solar-powered incubator in Bubulo, Uganda, initiated by a group of Sweden-based entrepreneurship students. Using an Actor-Network Theory-informed approach, it addresses the question of how the original aims of the initiative shifted as it moved from Sweden to Uganda, securing new allies and resources. In the tracing of this movement from northern Europe to central Africa, concepts from Actor-Network Theory, such as ‘translation’ and ‘drift’, are drawn upon. Thus, the text deals with spatial aspects of social entrepreneurial projects, heeding the call from Steyaert and Dey, who list ‘spatializing’ as one of ‘nine verbs that can keep the social entrepreneurship research agenda “dangerous”’. The text thus engages in the debate on the merits of business incubation in low-income countries–a topic currently high on the international development policy agenda. The study, it is argued, prompts scholars and policy-makers to shift perspectives when evaluating what this type of initiatives achieve. Rather than ‘creating’ entrepreneurship, projects like the Lighthouse are better seen as efforts to ‘mobilize’ existing activities. Moreover, the article also raises the issue of whether the classic incubator-as-we-know-it is a suitable model for the generation of economic activity in low-income countries

Tracks for change, flexibility, interdisciplinarity and creativity in engineering education

This paper describes the early stages of the developments of Tracks, an initiative to create,implement and evaluate a new educational model where the structure of the education isdeveloped to give students the opportunity to create multi- and interdisciplinary competencies,meet their expectations and need for a more individualized study plan and shorten the leadtimes for changing the education to embrace new technologies. The new education model isbased on the creation of tracks with different themes lying between existing programs notbelonging to a specific department or school. The idea is to create individual and flexible studyopportunities by introducing Track-courses within the themes. These courses address specificchallenges that may be broad societal and profound research-driven. Tracks also include largeinvestments in Chalmers learning environment. The paper focuses on Tracks as a largechange initiative, strategies to manage the complexity of this change as well as developmentphilosophy and working methods in the early phases of the initiative. Change at universitieshas been discussed previously, but this is a unique opportunity to study how large change maybe managed over time, including both the content of the education and the learningenvironments. Through action research, where interventions may be done to influence theinitiative, it is possible to develop practical contributions for other universities in need of similardevelopment. The research has been conducted over approximately a year and includes datafrom interviews and action research, where the authors are the main people working with thisinitiative. The close contact with the data gives a unique understanding of how differentactivities within the initiative influence the outcome. Thus, this paper will contribute to theunderstanding of how large institutional change initiatives are facilitated by a flexible and agileapproach contrasting the traditional and somewhat slower university culture

Pseudo-cleft constructions in Swedish talk-in-interaction : Turn projection and discourse organization

In this study we present an interactional linguistic analysis of pseudoclefts in Swedish based on audio and video recordings of everyday and institutional conversations, resulting in a collection of 100 instances. There is variation in the degree to which pseudo-cleft constructions are syntactically integrated: from fully integrated biclausal constructions (cleft clause + copula verb + main clause) to non-copular variants and further to variants in which the cleft-clause is followed by an indeterminate stretch of discourse. The construction's functional properties have to do with projecting actions and generating discourse events, e.g. showing that the initial part has an important turn-projecting function by disclosing the speaker's stance towards the issue at hand. Pseudo-cleft constructions are recurrently employed for marking discourse shifts, e.g. from a positive to a negative stance. Prosodic organization brings unity to the overall construction of clefts and visual cues can be used to convey significant processing activity by the speaker during the production of a pseudocleft. Our data from institutional interaction shows that pseudoclefts are heavily used by the expert rather than lay participant, thus contributing to the creation of institutional roles and social order. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).Peer reviewe

10-year survival of total ankle arthroplasties: A report on 780 cases from the Swedish Ankle Register

Background and purpose There is an ongoing need to review large series of total ankle replacements (TARs) for monitoring of changes in practice and their outcome. 4 national registries, including the Swedish Ankle Register, have previously reported their 5-year results. We now present an extended series with a longer follow-up, and with a 10-year survival analysis. Patients and methods Records of uncemented 3-component TARs were retrospectively reviewed, determining risk factors such as age, sex, and diagnosis. Prosthetic survival rates were calculated with exchange or removal of components as endpoint-excluding incidental exchange of the polyethylene meniscus. Results Of the 780 prostheses implanted since 1993, 168 (22%) had been revised by June 15, 2010. The overall survival rate fell from 0.81 (95% CI: 0.79-0.83) at 5 years to 0.69 (95% CI: 0.67-0.71) at 10 years. The survival rate was higher, although not statistically significantly so, during the latter part of the period investigated. Excluding the STAR prosthesis, the survival rate for all the remaining designs was 0.78 at 10 years. Women below the age of 60 with osteoarthritis were at a higher risk of revision, but age did not influence the outcome in men or women with rheumatoid arthritis. Revisions due to technical mistakes at the index surgery and instability were undertaken earlier than revisions for other reasons. Interpretation The results have slowly improved during the 18-year period investigated. However, we do not believe that the survival rates of ankle replacements in the near future will approach those of hip and knee replacements-even though improved instrumentation and design of the prostheses, together with better patient selection, will presumably give better results