338 research outputs found

    Designing nanomaterials with desired mechanical properties by constraining the evolution of their grain shapes

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    Grain shapes are acknowledged to impact nanomaterials' overall properties. Research works on this issue include grain-elongation and grain-strain measurements and their impacts on nanomaterials' mechanical properties. This paper proposes a stochastic model for grain strain undergoing severe plastic deformation. Most models deal with equivalent radii assuming that nanomaterials' grains are spherical. These models neglect true grain shapes. This paper also proposes a theoretical approach of extending existing models by considering grain shape distribution during stochastic design and modelling of nanomaterials' constituent structures and mechanical properties. This is achieved by introducing grain 'form'. Example 'forms' for 2-D and 3-D grains are proposed. From the definitions of form, strain and Hall-Petch-Relationship to Reversed-Hall-Petch-Relationship, data obtained for nanomaterials' grain size and conventional materials' properties are sufficient for analysis. Proposed extended models are solved simultaneously and tested with grain growth data. It is shown that the nature of form evolution depends on form choice and dimensional space. Long-run results reveal that grain boundary migration process causes grains to become spherical, grain rotation coalescence makes them deviate away from becoming spherical and they initially deviate away from becoming spherical before converging into spherical ones due to the TOTAL process. Percentage deviations from spherical grains depend on dimensional space and form: 0% minimum and 100% maximum deviations were observed. It is shown that the plots for grain shape functions lie above the spherical (control) value of 1 in 2-D grains for all considered grain growth mechanisms. Some plots lie above the spherical value, and others approach the spherical value before deviating below it when dealing with 3-D grains. The physical interpretations of these variations are explained from elementary principles about the different grain growth mechanisms. It is observed that materials whose grains deviate further away from the spherical ones have more enhanced properties, while materials with spherical grains have lesser properties. It is observed that there exist critical states beyond which Hall-Petch Relationship changes to Reversed Hall-Petch Relationship. It can be concluded that if grain shapes in nanomaterials are constrained in the way they evolve, then nanomaterials with desired properties can be designed

    To respond or not to respond - a personal perspective of intestinal tolerance

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    For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

    Descriptive epidemiology of stigma against depression in a general population sample in Alberta

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    <p>Abstract</p> <p>Background</p> <p>Mental health illnesses, such as depression, are responsible for a growing disease burden worldwide. Unfortunately, effective treatment is often impeded by stigmatizing attitudes of other individuals, which have been found to lead to a number of negative consequences including reduced help-seeking behavior and increased social distance. Despite the high prevalence of depression in Canada, little research has been conducted to examine stigma against depression in the Canadian general population. Such information is crucial to understanding the current state of stigmatizing attitudes in the Canadian communities, and framing future stigma reduction initiatives. The objectives of this study were to estimate the percentages of various stigmatizing attitudes toward depression in a general population sample and to compare the percentages by demographics and socioeconomic characteristics.</p> <p>Methods</p> <p>We conducted a cross-sectional telephone survey in Alberta, Canada, between February and June 2006. Random digit dialing was used to recruit participants who were aged 18-74 years old (n = 3047). Participants were presented a case vignette describing a depressed individual, and responded to a 9-item Personal Stigma questionnaire. The percentages of stigmatizing attitudes were estimated and compared by demographic and socioeconomic variables.</p> <p>Results</p> <p>Among the participants, 45.9% endorsed that depressed individuals were unpredictable and 21.9% held the view that people with depression were dangerous. Significant differences in stigmatizing attitudes were found by gender, age, education, and immigration status. A greater proportion of men than women held stigmatizing views on each stigma item. No consistent trend emerged by age in stigma against depression. Participants with higher levels of education reported less stigmatizing attitudes than those with less education. Participants who were not born in Canada were more likely to hold stigmatizing attitudes than those who were born in Canada.</p> <p>Conclusion</p> <p>In the general population, stigmatizing attitudes towards depression differ by demographic characteristics. Men, those with less education and immigrants should be the targets of stigma reduction campaigns.</p

    Estimation of the severity of breathlessness in the emergency department: a dyspnea score

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    BACKGROUND: Dyspnea is a frequent complaint in emergency departments (ED). It has a significant amount of subjective and affective components, therefore the dyspnea scores, based on the patients' rating, can be ambiguous. Our purpose was to develop and validate a simple scoring system to evaluate the severity of dyspnea in emergency care, based on objectively measured parameters. METHODS: We performed a double center, prospective, observational study including 350 patients who were admitted in EDs with dyspnea. We evaluated the patients' subjective feeling about dyspnea and applied our Dyspnea Severity Score (DSS), rating the dyspnea in 7 Dimensions from 0 to 3 points. The DSS was validated using the deterioration of pH, base-excess and lactate levels in the blood gas samples (Objective Classification Scale (OCS) 9 points and 13 points groups). RESULTS: All of the Dimensions correlated closely with the OCS values and with the subjective feeling of the dyspnea. Using multiple linear regression analysis we were able to decrease the numbers of Dimensions from seven to four without causing a significant change in the determination coefficient in any OCS groups. This reduced DSS values (exercise tolerance, cooperation, cyanosis, SpO2 value) showed high sensitivity and specificity to predict the values of OCS groups (the ranges: AUC 0.77-0.99, sensitivity 65-100%, specificity 64-99%). There was a close correlation between the subjective dyspnea scores and the OCS point values (p /=7 points without correction factors) can be useful at the triage or in pre-hospital care

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

    Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease

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    International audiencePURPOSE: Increased type I interferon is considered relevant to the pathology of a number of monogenic and complex disorders spanning pediatric rheumatology, neurology, and dermatology. However, no test exists in routine clinical practice to identify enhanced interferon signaling, thus limiting the ability to diagnose and monitor treatment of these diseases. Here, we set out to investigate the use of an assay measuring the expression of a panel of interferon-stimulated genes (ISGs) in children affected by a range of inflammatory diseases. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted between 2011 and 2016 at the University of Manchester, UK, and the Institut Imagine, Paris, France. RNA PAXgene blood samples and clinical data were collected from controls and symptomatic patients with a genetically confirmed or clinically well-defined inflammatory phenotype. The expression of six ISGs was measured by quantitative polymerase chain reaction, and the median fold change was used to calculate an interferon score (IS) for each subject compared to a previously derived panel of 29 controls (where +2 SD of the control data, an IS of \textgreater2.466, is considered as abnormal). Results were correlated with genetic and clinical data. RESULTS: Nine hundred ninety-two samples were analyzed from 630 individuals comprising symptomatic patients across 24 inflammatory genotypes/phenotypes, unaffected heterozygous carriers, and controls. A consistent upregulation of ISG expression was seen in 13 monogenic conditions (455 samples, 265 patients; median IS 10.73, interquartile range (IQR) 5.90-18.41), juvenile systemic lupus erythematosus (78 samples, 55 patients; median IS 10.60, IQR 3.99-17.27), and juvenile dermatomyositis (101 samples, 59 patients; median IS 9.02, IQR 2.51-21.73) compared to controls (78 samples, 65 subjects; median IS 0.688, IQR 0.427-1.196), heterozygous mutation carriers (89 samples, 76 subjects; median IS 0.862, IQR 0.493-1.942), and individuals with non-molecularly defined autoinflammation (89 samples, 69 patients; median IS 1.07, IQR 0.491-3.74). CONCLUSIONS AND RELEVANCE: An assessment of six ISGs can be used to define a spectrum of inflammatory diseases related to enhanced type I interferon signaling. If future studies demonstrate that the IS is a reactive biomarker, this measure may prove useful both in the diagnosis and the assessment of treatment efficacy

    Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation

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    Background: Anoikis resistance is one of the abilities acquired along tumor progression. This characteristic is associated with metastasis development, since tumorigenic cells must survive independently of cell-matrix interactions in this process. in our laboratory, it was developed a murine melanocyte malignant transformation model associated with a sustained stressful condition. After subjecting melan-a melanocytes to 1, 2, 3 and 4 cycles of anchorage impediment, anoikis resistant cells were established and named 1C, 2C, 3C and 4C, respectively. These cells showed altered morphology and PMA independent cell growth, but were not tumorigenic, corresponding to pre-malignant cells. After limiting dilution of 4C pre-malignant cells, melanoma cell lines with different characteristics were obtained. Previous data from our group showed that increased Timp1 expression correlated with anoikis-resistant phenotype. Timp1 was shown to confer anchorage-independent growth capability to melan-a melanocytes and render melanoma cells more aggressive when injected into mice. However, the mechanisms involved in anoikis regulation by Timp1 in tumorigenic cells are not clear yet.Methods: the beta 1-integrin and Timp1 expression were evaluated by Western blotting and CD63 protein expression by flow cytometry using specific antibodies. To analyze the interaction among Timp1, CD63 and beta 1-integrin, immunoprecipitation assays were performed, anoikis resistance capability was evaluated in the presence or not of the PI3-K inhibitors, Wortmannin and LY294002. Relative expression of TIMP1 and CD63 in human metastatic melanoma cells was analyzed by real time PCR.Results: Differential association among Timp1, CD63 and beta 1-integrins was observed in melan-a melanocytes, 4C pre-malignant melanocytes and 4C11- and 4C11+ melanoma cells. Timp1 present in conditioned medium of melanoma cells rendered melan-a melanocytes anoikis-resistant through PI3-K signaling pathway independently of Akt activation. in human melanoma cell lines, in which TIMP1 and beta-1 integrin were also found to be interacting, TIMP1 and CD63 levels together was shown to correlate significantly with colony formation capacity.Conclusions: Our results show that Timp1 is assembled in a supramolecular complex containing CD63 and beta 1-integrins along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway, independently of Akt phosphorylation. in addition, our data point TIMP1, mainly together with CD63, as a potential biomarker of melanoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilLudwig Inst Canc Res, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Microbiol Immunol & Parasitol Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, São Paulo, BrazilFAPESP: 2011/12306-1FAPESP: 2010/18715-8CAPES: 2867/10Web of Scienc
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