69 research outputs found
What a pity, Pepper! How warmth in robot's language impacts reactions to errors during a collaborative task
Hoffmann L, Derksen M, Kopp S. What a pity, Pepper! How warmth in robot's language impacts reactions to errors during a collaborative task. In: HRI '20 Companion. ACM; 2020
Information, social interactions and health seeking behavior
This thesis examines the underlying cause of social stigma towards people living with HIV, and the extent to which it discourages HIV testing and treatment. We use a discrete choice model to describe a personâs decision to seek treatment for HIV (antiretroviral therapy or ART), and estimate the social cost of seeking treatment using administrative health records from southern Malawi. We show that seeking ART at a clinic where many other community members are present carries a significant cost, even after taking into account clinic quality and location. We investigate the theoretical effects of policy interventions designed to reduce stigma and other barriers to care, and demonstrate important complementarities between such policies. We next evaluate a cluster-randomized information experiment in Zomba, Malawi designed to correct a common misconception: most do not know that ART drugs have a public benefit, that is, the medication prevents HIV transmission between sexual partners. We microfound HIV stigma as sexual discrimination between sexual partners, and model the decision to seek an HIV test (and then, if required, medical treatment) as a signal of infection. We show, theoretically and empirically, that the randomized information intervention reduces this type of stigma and significantly increases the rate of HIV testing. The results demonstrate that social stigma is an important barrier to HIV testing and treatment, that stigma can be due to rational behavior by a misinformed public, and that providing new information can be an effective way to mitigate its effects
Repetitive desiccation events weaken a salt marsh mutualism
1. Salt marshes suffered largeâscale degradation in recent decades. Extreme events such as hot and dry spells contributed significantly to this, and are predicted to increase not only in intensity, but also in frequency under future climate scenarios. Such repetitive extreme events may generate cumulative effects on ecosystem resilience. It is therefore important to elucidate how marsh vegetation responds to repetitive stress, and whether changes in key species interactions can modulate vegetation resilience.2. In this study, we investigated how moderate but repetitive desiccation events, caused by the combined effects of drought and high temperatures, affect cordgrass (<i>Spartina alterniflora</i>), the dominant habitatâforming grass in southeastern US salt marshes. In a 4âmonth field experiment, we simulated four consecutive desiccation events by periodically excluding tidal flooding and rainfall, while raising temperature. We crossed this desiccation treatment with the presence/absence of ribbed mussels (<i>Geukensia demissa</i>) â a mutualist of cordgrass known to enhance its desiccation resilience â and with grazing pressure by the marsh periwinkle (<i>Littoraria irrorate</i>) that is known to suppress cordgrassâ desiccation resilience. 3. We found that each subsequent desiccation event deteriorated sediment porewater conditions, resulting in high salinity (53 ppt), low pHâlevels (3.7) and increased porewater Al and Fe concentrations (â800 ÎŒmol/L and â1,500 ÎŒmol/L) upon rewetting. No effects on porewater chemistry were found as a result of snail grazing, while ribbed mussels strongly mitigated desiccation effects almost to control levels and increased cordgrass biomass by approximately 128%. Importantly, although cordgrass generally appeared healthy aboveâground at the end of the experiment, we found clear negative responses of the repetitive desiccation treatment on cordgrass belowâground biomass, on proline (osmolyte) levels in shoots and on the number of tillers (â40%), regardless of mussel and/or snail presence.4. <i>Synthesis</i>. Even though the mutualism with mussels strongly mitigated chemical effects in the sediment porewater throughout the experiment, mussels could not buffer the adverse ecophysiological effects observed in cordgrass tissue. Our results therefore suggest that although mussels may alleviate desiccation stress, the predicted increased frequency and intensity of hot dry spells may eventually affect saltmarsh resilience by stressing the mutualism beyond its buffering capacity
Variability and change in the Canadian cryosphere
Abstract
During the International Polar Year (IPY), comprehensive observational research programs were undertaken to increase our understanding of the Canadian polar cryosphere response to a changing climate. Cryospheric components considered were snow, permafrost, sea ice, freshwater ice, glaciers and ice shelves. Enhancement of conventional observing systems and retrieval algorithms for satellite measurements facilitated development of a snapshot of current cryospheric conditions, providing a baseline against which future change can be assessed. Key findings include: 1. surface air temperatures across the Canadian Arctic exhibit a warming trend in all seasons over the past 40 years. A consistent pan-cryospheric response to these warming temperatures is evident through the analysis of multi-decadal datasets; 2. in recent years (including the IPY period) a higher rate of change was observed compared to previous decades including warming permafrost, reduction in snow cover extent and duration, reduction in summer sea ice extent, increased mass loss from glaciers, and thinning and break-up of the remaining Canadian ice shelves. These changes illustrate both a reduction in the spatial extent and mass of the cryosphere and an increase in the temporal persistence of melt related parameters. The observed changes in the cryosphere have important implications for human activity including the close ties of northerners to the land, access to northern regions for natural resource development, and the integrity of northern infrastructure
Glycogen Synthase Kinase-3 regulates multiple myeloma cell growth and bortezomib-induced cell death
BACKGROUND:
Glycogen Synthase Kinase-3 (GSK-3) \u3b1 and \u3b2 are two serine-threonine kinases controlling insulin, Wnt/\u3b2-catenin, NF-\u3baB signaling and other cancer-associated transduction pathways. Recent evidence suggests that GSK-3 could function as growth-promoting kinases, especially in malignant cells. In this study, we have investigated GSK-3\u3b1 and GSK-3\u3b2 function in multiple myeloma (MM).
METHODS:
GSK-3 \u3b1 and \u3b2 expression and cellular localization were investigated by Western blot (WB) and immunofluorescence analysis in a panel of MM cell lines and in freshly isolated plasma cells from patients. MM cell growth, viability and sensitivity to bortezomib was assessed upon treatment with GSK-3 specific inhibitors or transfection with siRNAs against GSK-3 \u3b1 and \u3b2 isoforms. Survival signaling pathways were studied with WB analysis.
RESULTS:
GSK-3\u3b1 and GSK-3\u3b2 were differently expressed and phosphorylated in MM cells. Inhibition of GSK-3 with the ATP-competitive, small chemical compounds SB216763 and SB415286 caused MM cell growth arrest and apoptosis through the activation of the intrinsic pathway. Importantly, the two inhibitors augmented the bortezomib-induced MM cell cytotoxicity. RNA interference experiments showed that the two GSK-3 isoforms have distinct roles: GSK-3\u3b2 knock down decreased MM cell viability, while GSK-3\u3b1 knock down was associated with a higher rate of bortezomib-induced cytotoxicity. GSK-3 inhibition caused accumulation of \u3b2-catenin and nuclear phospho-ERK1, 2. Moreover, GSK-3 inhibition and GSK-3\u3b1 knockdown enhanced bortezomib-induced AKT and MCL-1 protein degradation. Interestingly, bortezomib caused a reduction of GSK-3 serine phosphorylation and its nuclear accumulation with a mechanism that resulted partly dependent on GSK-3 itself.
CONCLUSIONS:
These data suggest that in MM cells GSK-3\u3b1 and \u3b2 i) play distinct roles in cell survival and ii) modulate the sensitivity to proteasome inhibitors
Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis.
The expression of the transcription factor SOX4 is increased in many human cancers, however, the pro-oncogenic capacity of SOX4 can vary greatly depending on the type of tumor. Both the contextual nature and the mechanisms underlying the pro-oncogenic SOX4 response remain unexplored. Here, we demonstrate that in mammary tumorigenesis, the SOX4 transcriptional network is dictated by the epigenome and is enriched for pro-angiogenic processes. We show that SOX4 directly regulates endothelin-1 (ET-1) expression and can thereby promote tumor-induced angiogenesis both in vitro and in vivo. Furthermore, in breast tumors, SOX4 expression correlates with blood vessel density and size, and predicts poor-prognosis in patients with breast cancer. Our data provide novel mechanistic insights into context-dependent SOX4 target gene selection, and uncover a novel pro-oncogenic role for this transcription factor in promoting tumor-induced angiogenesis. These findings establish a key role for SOX4 in promoting metastasis through exploiting diverse pro-tumorigenic pathways
The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study
AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4âweeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4âweeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, PÂ =Â 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, Pâ<â0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, PÂ =Â 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, PÂ =Â 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease
Rapid autopsies to enhance metastatic research: the UPTIDER post-mortem tissue donation program
Research on metastatic cancer has been hampered by limited sample availability. Here we present the breast cancer post-mortem tissue donation program UPTIDER and show how it enabled sampling of a median of 31 (range: 5-90) metastases and 5-8 liquids per patient from its first 20 patients. In a dedicated experiment, we show the mild impact of increasing time after death on RNA quality, transcriptional profiles and immunohistochemical staining in tumor tissue samples. We show that this impact can be counteracted by organ cooling. We successfully generated ex vivo models from tissue and liquid biopsies from distinct histological subtypes of breast cancer. We anticipate these and future findings of UPTIDER to elucidate mechanisms of disease progression and treatment resistance and to provide tools for the exploration of precision medicine strategies in the metastatic setting
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