2,007 research outputs found

    Exploring two methods of usability testing: concurrent versus retrospective think-aloud protocols

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    Think-aloud protocols are commonly used for the usability testing of instructional documents, Web sites and interfaces. This paper addresses the benefits and drawbacks of two think-aloud variations: the traditional concurrent think-aloud method and the less familiar retrospective think-aloud protocols. It also offers an outline of a long-term research project designed to empirically investigate the value of both variants. The results of a first comparative study indicate that, although the two methods have distinct differences, they do seem to produce a similar outcome. A more detailed description of the results will be offered during the presentation

    Analyzing the interaction between facilitator and participants in two variants of the think-aloud method.

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    This paper focuses on the interaction between test participants and test facilitator in two variants of the think-aloud method. In a first, explorative study, we analyzed think-aloud transcripts from two usability tests: a concurrent think-aloud test and a constructive interaction test. The results of our analysis show that while the participants in both studies never explicitly addressed the facilitator, the think-aloud participants showed more signs of awareness of the facilitator than the participants in the constructive interaction test. This finding may have practical implications for the validity of the two methods

    Rho/MRTF Pathway Signaling and Small-Molecule Inhibitor Development in Systemic Sclerosis and Metastatic Melanoma

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    Rho GTPases regulate multiple biological functions; most notably, they stimulate formation of F-actin stress fiber formations. Through their modulation of the actin cytoskeleton Rho GTPases also activate gene transcription through myocardin-related transcription factors (MRTF) and the serum response factor (SRF). Recent evidence suggests MRTF/SRF-regulated gene transcription represent a novel target for the treatment of systemic sclerosis and melanoma. The work of this thesis details mechanisms of Rho GTPase and MRTF/SRF activation in these diseases, and provides in vitro and in vivo efficacy studies for a small-molecule inhibitor of the MRTF pathway developed in our lab, CCG-203971. Tissue fibrosis disorders, including systemic sclerosis are characterized by activated myofibroblasts within the affected tissue. These myofibroblasts are stimulated by multiple microenvironment factors. Transforming growth factor beta (TGF-beta) signaling involves cross talk between multiple mediators including Rho GTPase. However, the mechanism by which TGF-beta activates Rho GTPase and subsequent MRTF/SRF-regulated transcription is poorly understood. Based on the evidence here we outline a mechanism where TGF-beta stimulates expression of connective tissue growth factor (CTGF) and endothelin-1 (ET-1), which then mediate the activation of the Rho/MRTF pathway. MRTF/SRF transcription is a convergent mechanism downstream of multiple receptors that stimulate fibrosis. We tested our MRTF pathway inhibitor, CCG-203971 in models of systemic sclerosis and showed inhibition of multiple markers of fibrosis in vitro, as well as efficacy in a mouse model of dermal fibrosis in vivo. Melanoma is the most deadly form of skin cancer, with the majority of deaths attributed to metastasis. Rho GTPases have been implicated in cancer metastasis for many years, however recently it has been shown that MRTF/SRF-regulated gene transcription is essential for melanoma metastasis. Here we show that in highly invasive and metastatic melanoma cells, overexpression of RhoC leading to constitutively active MRTF. CCG-203971 treatment in these cells reduced cellular migration and invasion in vitro and blocked lung colonization in a mouse model of melanoma metastasis in vivo.PhDPharmacologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111506/1/haak_1.pd

    Minister van mynwese En van beplanning om 'n instituut van beplanning Formeel af te kondig by die Potchefstroomse Universiteit vir C.H.O. Op 8 September 1965

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    Dit is vir my ’n voorreg en ’n plesier om vanmiddag ’n paar gedagtes by hierdie belangrike byeenkoms uit te spreek. Alhoewel die Departement van Beplanning sopas slegs sy eerste verjaarsdag gevier het, is die verbintenis van sekere afdelings van my Departement met hierdie Universiteit heel- wat ouer en is dit ook nie die eerste keer dat ek hier optree nie. Ek voel dus baie tuis in hierdie omgewing omdat ons ou vriende is maar veral omdat hierdie Universiteit met die instelling van die beplanningskursus ’n landsdiens verrig. 

    Revisiting the Meteor 1925-1927 hydrographic dataset reveals centennial full-depth changes in the Atlantic Ocean

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    The hydrographic data set of the German Atlantic Expedition (GAE) 1925-1927 is compared with the contemporary profiling float and ship-based hydrography to reveal full-depth changes in the Atlantic Ocean between 19°N and 64°S. The volume-mean warming over the last 80 years amounts to 0.119 ± 0.067°C, accompanied by an increase in salinity of 0.014 ± 0.010. A clear vertical structure of these changes is observed: on average, the ocean has warmed by 0.272 ± 0.093°C and became saltier by 0.030 ± 0.014 down to about 2000 m, but cooled and freshened slightly in the deeper layers. These changes can be traced throughout the whole hydrographic survey, indicating the basin-wide character of the observed changes on a centennial timescale. The observed warming is consistent with climate model simulations over the 20th century, suggesting an attribution to anthropogenic forcing. Comparison with the pre-GAE cruises reveals no discernible warming between the 1870s and 1906/1911. © 2013 American Geophysical Union. All Rights Reserved

    Regulator of G protein signaling 2 inhibits Gαq-dependent uveal melanoma cell growth

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    Activating mutations in Gαq/11 are a major driver of uveal melanoma (UM), the most common intraocular cancer in adults. While progress has recently been made in targeting Gαq/11 for UM therapy, the crucial role for these proteins in normal physiology and their high structural similarity with many other important GTPase proteins renders this approach challenging. The aim of the current study was to validate whether a key regulator of Gq signaling, regulator of G protein signaling 2 (RGS2), can inhibit Gαq-mediated UM cell growth. We used two UM cell lines, 92.1 and Mel-202, which both contain the most common activating mutation GαqQ209L and developed stable cell lines with doxycycline-inducible RGS2 protein expression. Using cell viability assays, we showed that RGS2 could inhibit cell growth in both of these UM cell lines. We also found that this effect was independent of the canonical GTPase-activating protein activity of RGS2 but was dependent on the association between RGS2 and Gαq. Furthermore, RGS2 induction resulted in only partial reduction in cell growth as compared to siRNA-mediated Gαq knockdown, perhaps because RGS2 was only able to reduce mitogen-activated protein kinase signaling downstream of phospholipase Cβ, while leaving activation of the Hippo signaling mediators yes-associated protein 1/TAZ, the other major pathway downstream of Gαq, unaffected. Taken together, our data indicate that RGS2 can inhibit UM cancer cell growth by associating with GαqQ209L as a partial effector antagonist

    Types of problems elicited by verbal protocols for blind and sighted participants

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    Verbal protocols are often used in user-based studies of interactive technologies. This study investigated whether different types of problems are revealed by concurrent and retrospective verbal protocols (CVP and RVP) for blind and sighted participants. Eight blind and eight sighted participants undertook both CVP and RVP on four websites. Overall, interactivity problems were significantly more frequent in comparison to content or information architecture problems. In addition, RVP revealed significantly more interactivity problems than CVP for both user groups. Finally, blind participants encountered significantly more interactivity problems than sighted participants. The findings have implications for which protocol is appropriate, depending on the purpose of a particular study and the user groups involved

    Arctic-North Atlantic interactions and multidecadal variability of the meridional overturning circulation

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    Analyses of a 500-yr control integration with the non-flux-adjusted coupled atmosphere–sea ice–oceanmodel ECHAM5/Max-Planck-Institute Ocean Model (MPI-OM) show pronounced multidecadal fluctuations of the Atlantic overturning circulation and the associated meridional heat transport. The period of the oscillations is about 70–80 yr. The low-frequency variability of the meridional overturning circulation (MOC) contributes substantially to sea surface temperature and sea ice fluctuations in the North Atlantic.The strength of the overturning circulation is related to the convective activity in the deep-water formation regions, most notably the Labrador Sea, and the time-varying control on the freshwater export from the Arctic to the convection sites modulates the overturning circulation. The variability is sustained by an interplay between the storage and release of freshwater from the central Arctic and circulation changes in the Nordic Seas that are caused by variations in the Atlantic heat and salt transport. The relatively highresolution in the deep-water formation region and the Arctic Ocean suggests that a better representation of convective and frontal processes not only leads to an improvement in the mean state but also introduces new mechanisms determining multidecadal variability in large-scale ocean circulation
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