1,937 research outputs found

    Tensin1 expression and function in chronic obstructive pulmonary disease

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    open access articleChronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFβ1. TGFβ1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs

    The Serums Tool-Chain:Ensuring Security and Privacy of Medical Data in Smart Patient-Centric Healthcare Systems

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    Digital technology is permeating all aspects of human society and life. This leads to humans becoming highly dependent on digital devices, including upon digital: assistance, intelligence, and decisions. A major concern of this digital dependence is the lack of human oversight or intervention in many of the ways humans use this technology. This dependence and reliance on digital technology raises concerns in how humans trust such systems, and how to ensure digital technology behaves appropriately. This works considers recent developments and projects that combine digital technology and artificial intelligence with human society. The focus is on critical scenarios where failure of digital technology can lead to significant harm or even death. We explore how to build trust for users of digital technology in such scenarios and considering many different challenges for digital technology. The approaches applied and proposed here address user trust along many dimensions and aim to build collaborative and empowering use of digital technologies in critical aspects of human society

    Methodology for estimating the ground heat absorption rate of Ground Heat Exchangers

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    In Ground Source Heat Pump systems, the heat exchange rate is an important factor with regard to the initial cost of the system. When the Ground Heat Exchanger (GHE) is installed in a lithology with high thermal properties in the presence of groundwater, the heat exchange rates are larger than in the cases with poor thermal response of the ground and no groundwater. This research, hence, focuses on a methodology of measuring and analyzing the thermal properties of the lithologies encountered in an area, which can be used for the prediction of heat injection rates of a GHE, depending on its characteristics, the installation area ground properties and groundwater flow. A tool was created with the use of FlexPDE software, and a study case was chosen in order to validate the results. Twenty-two, 100 m in depth, boreholes located in Lefkosia (Cyprus) were tested through simulation for their geothermal performance over time. Subsequently the estimated heat load for the boreholes, after 24 h of operation in cooling mode, was used with the help of Geographic Information System software for the compilation of a heat load per meter depth map that can be transferred to the ground by a GHE. A review of similar studies and Geographical Information System applications referring to other countries is also presented and their results are compared to the results of this study. The step by step procedure presented in this paper can be used by engineers handling geothermal projects as a useful guide for sizing GHEs and calculating the heat injection rates of any area

    Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor

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    The Notch receptor signalling pathway plays an important role in breast development, regulation of stem cells and differentiation of luminal progenitor cells. The pathway also plays a significant role in breast cancer development and progression. However, which of the Notch receptors that regulate breast cancer stem cells is unknown. We assessed stem cell activity in breast cancer cell lines and nine primary human tumour samples. In vitro and in vivo breast cancer stem cell activity was enriched using selection of anoikis resistant cells or cells expressing the membrane phenotype ESA(+)/CD44(+)/CD24(low). We compared the activation of Notch receptors in the breast cancer stem cell-enriched population to luminally differentiated cells and studied the effects of pathway inhibition, both in vitro and in vivo. We find that Notch4 signalling activity is 8-fold higher in the breast cancer stem cell-enriched cells compared to the differentiated cells while Notch1 activation is 4-fold lower in breast cancer stem cells. Furthermore, pharmacological or genetic Notch inhibition markedly reduced breast cancer stem cell activity in vitro, and significantly reduced tumour formation in vivo. Importantly, cells with Notch4 knock-down using specific shRNA formed fewer mammosphere colonies than Notch1 knock-down cells. In vivo Notch1 knock-down, like pharmacological inhibition, reduced the number and size of tumours but Notch4 knock-down suppressed tumour initiation completely. Our findings indicate that Notch4-targeted therapies will be more effective than targeting Notch1 in suppressing breast cancer recurrence initiated by breast cancer stem cells

    Atenolol versus losartan in children and young adults with Marfan's syndrome

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    BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

    The Effects of COVID-19 on the Placenta During Pregnancy.

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    Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission
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