Voice-Controlled In-Vehicle Systems: Effects of Voice-Recognition Accuracy in the Presence of Background Noise

This paper presents initial findings from a driving simulator studyThis paper presents initial findings from a driving simulator studycomparing user responses to a noise-robust voice-controlled system while drivingto a noise-sensitive one in the presence of background noise. Twenty participantsinteracted with both noise-sensitive and noise-robust simulated voice-controlledinfotainment systems while driving under three background noise conditions (nonoise, music, and children). While both systems were viewed as useful andsatisfying, user acceptance was affected by background noise with the noisesensitivesystem, but not the noise-robust one. There was also no evidence that useracceptance was calibrated by having background noise as a context for varyinglevels of accuracy. No significant differences were observed between the twosystems in driving performance metrics analyzed (average speed, speed variability,and standard deviation of lane position), but the use of either system affecteddriving performance compared to baseline driving. A larger sample size at the endof this study along with the analysis of a larger set of performance metrics willprovide further insights

The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-β

INTRODUCTION: Transforming growth factor-β (TGF-β) is a potent suppressor of mammary epithelial cell (MEC) proliferation and is thus an inhibitor of mammary tumor formation. Malignant MECs typically evolve resistance to TGF-β-mediated growth arrest, enhancing their proliferation, invasion, and metastasis when stimulated by TGF-β. Recent findings suggest that therapeutics designed to antagonize TGF-β signaling may alleviate breast cancer progression, thereby improving the prognosis and treatment of breast cancer patients. We identified the cysteine protease inhibitor cystatin C (CystC) as a novel TGF-β type II receptor antagonist that inhibits TGF-β binding and signaling in normal and cancer cells. We hypothesized that the oncogenic activities of TGF-β, particularly its stimulation of mammary epithelial–mesenchymal transition (EMT), can be prevented by CystC. METHOD: Retroviral infection was used to constitutively express CystC or a CystC mutant impaired in its ability to inhibit cathepsin protease activity (namely Δ14CystC) in murine NMuMG MECs and in normal rat kidney (NRK) fibroblasts. The effect of recombinant CystC administration or CystC expression on TGF-β stimulation of NMuMG cell EMT in vitro was determined with immunofluorescence to monitor rearrangements of actin cytoskeletal architecture and E-cadherin expression. Soft-agar growth assays were performed to determine the effectiveness of CystC in preventing TGF-β stimulation of morphological transformation and anchorage-independent growth in NRK fibroblasts. Matrigel invasion assays were performed to determine the ability of CystC to inhibit NMuMG and NRK motility stimulated by TGF-β. RESULTS: CystC and Δ14CystC both inhibited NMuMG cell EMT and invasion stimulated by TGF-β by preventing actin cytoskeletal rearrangements and E-cadherin downregulation. Moreover, both CystC molecules completely antagonized TGF-β-mediated morphological transformation and anchorage-independent growth of NRK cells, and inhibited their invasion through synthetic basement membranes. Both CystC and Δ14CystC also inhibited TGF-β signaling in two tumorigenic human breast cancer cell lines. CONCLUSION: Our findings show that TGF-β stimulation of initiating metastatic events, including decreased cell polarization, reduced cell–cell contact, and elevated cell invasion and migration, are prevented by CystC treatment. Our findings also suggest that the future development of CystC or its peptide mimetics hold the potential to improve the therapeutic response of human breast cancers regulated by TGF-β

Towards the Human Colorectal Cancer Microbiome

Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

The effects of noise-robustness of in-car voice-controlled systems on user perceptions and driving behaviour

In-car voice-controlled infotainment systems are becoming increasingly common in automobiles, but the effects on users when their accuracy degrades in the presence of background noise has not been examined. This thesis compares use of both noise-sensitive and noise-robust simulated voice-controlled infotainment systems under three background noise conditions. It was found that the sensitive system was perceived to be less useful and satisfying even when it performed identically to the robust system. No differences were observed between the systems in several driving performance metrics (with the exception of brake response), but the use of either system impaired driving performance compared to baseline. Glances and subjective workload demonstrated advantages to the robust system. Increased heart rate was observed with the robust system. The results demonstrate that noise robustness is a key factor in user acceptance, and may mitigate visual distraction generated by voice-controlled systems; however, the effects on driving performance are inconclusive.M.A.S

CystC and Δ14CystC antagonize E-cadherin downregulation stimulated by TGF-β in NMuMG cells

<p><b>Copyright information:</b></p><p>Taken from "The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-β"</p><p>Breast Cancer Research 2005;7(5):R844-R853.</p><p>Published online 23 Aug 2005</p><p>PMCID:PMC1242164.</p><p>Copyright © 2005 Sokol et al.; licensee BioMed Central Ltd.</p> Control, CystC-expressing, and Δ14CystC-expressing NMuMG cells were incubated in the absence or presence of transforming growth factor-β1 (TGF-β1; 5 ng/ml) for 36 hours, whereupon alterations in E-cadherin expression was monitored by immunoprecipitation and subsequent immunoblotting with anti-E-cadherin antibodies. The representative immunoblot depicts the downregulation of E-cadherin expression induced by TGF-β in NMuMG cells. The lower panel shows the alterations in E-cadherin expression (means ± SEM) induced by TGF-β relative to their untreated counterparts observed in three independent experiments. TGF-β significantly downregulated E-cadherin expression in NMuMG cells (*< 0.05; Student's -test). NMuMG cells were stimulated with TGF-β1 (5 ng/ml) for 36 hours in the presence of glutathione S-transferase (GST) fusion proteins (10 μg/ml) as indicated. E-cadherin expression was monitored by indirect immunofluorescence with anti-E-cadherin antibodies. Shown are representative images from a single experiment that was repeated once with identical results

CystC and Δ14CystC inhibit TGF-β signaling in human MDA-MB-231 breast cancer cells

<p><b>Copyright information:</b></p><p>Taken from "The use of cystatin C to inhibit epithelial–mesenchymal transition and morphological transformation stimulated by transforming growth factor-β"</p><p>Breast Cancer Research 2005;7(5):R844-R853.</p><p>Published online 23 Aug 2005</p><p>PMCID:PMC1242164.</p><p>Copyright © 2005 Sokol et al.; licensee BioMed Central Ltd.</p> Control, CystC-expressing, or Δ14CystC-expressing MDA-MB-231 cells were transiently transfected with p3TP-luciferase and pCMV-β-Gal cDNAs, and were subsequently stimulated with increasing concentrations of transforming growth factor-β1 (TGF-β1; from 0 to 5 ng/ml) for 24 hours. Afterward, luciferase and β-Gal activities contained in detergent-solubilized cell extracts were measured. Values are luciferase activities (means ± SEM) observed in two independent experiments normalized to maximal reporter gene expression in TGF-β-stimulated cells expressing green fluorescent protein. CystC and Δ14CystC both significantly inhibit reporter gene expression stimulated by TGF-β (*< 0.05; Student's -test). MDA-MB-231 cells were transiently transfected with p3TP-luciferase and pCMV-β-Gal cDNAs. Afterward, the transfectants were treated with 25 μg/ml recombinant glutathione S-transferase (GST; G), CystC (C), or Δ14CystC (D) and immediately stimulated with TGF-β1 (1 ng/ml) for 24 hours before determination of the luciferase and β-Gal activities contained in detergent-solubilized cell extracts. Values are luciferase activities (means ± SEM) observed in four independent experiments normalized to maximal reporter gene expression stimulated by TGF-β in GST-treated cells. MDA-MB-231 cells were treated with 25 μg/ml recombinant GST (G), CystC (C), or Δ14CystC (D) for 2 hours before their stimulation with TGF-β (1 ng/ml) for 30 min. Afterward, the activation status of Smad2 was determined by immunoblot analysis with phospho-specific Smad2 antibodies. Differences in protein loading were monitored by reprobing stripped membranes with antibodies against extracellular signal-related kinase 1. Data are from a representative experiment that was repeated once with similar results