512 research outputs found
The Influence of the Aspect Ratio on the Lateral Response of the Sheathed Cold Formed Steel Walls
The influence of the aspect ratio on the lateral response of cold formed steel walls is analyzed by three design methodologies. In particular the prediction provided by the AISI Lateral Design, that is at the moment the main document for the design of CFS buildings under horizontal loads, is compared with the results obtained by applying the principles of mechanics and with those provided by non-linear finite element models. This paper presents and discusses in terms of strength and stiffness the validity of the different design methodologies in case of non-conventional wall aspect ratios comparing the numerical results with available experimental data
Highly purified extracellular vesicles from human cardiomyocytes demonstrate preferential uptake by human endothelial cells
Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types. Here we established a robust technique for the production and isolation of EVs harvested from an enriched (>97% purity) population of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) with size exclusion chromatography. Utilizing an advanced fluorescence labelling strategy, we then investigated the interplay of the CM-EVs with the three major cellular components of the myocardium (fibroblasts, cardiomyocytes and endothelial cells) and identified that cardiac endothelial cells show preferential uptake of these EVs. Overall, our findings provide a great opportunity to overcome the translational hurdles associated with the isolation of intact, non-aggregated human iPSC-CM EVs at high purity. Furthermore, understanding in detail the interaction of the secreted EVs with their surrounding cells in the heart may open promising new avenues in the field of EV engineering for targeted delivery in cardiac regeneration
Five-Factor Model personality profiles of drug users
<p>Abstract</p> <p>Background</p> <p>Personality traits are considered risk factors for drug use, and, in turn, the psychoactive substances impact individuals' traits. Furthermore, there is increasing interest in developing treatment approaches that match an individual's personality profile. To advance our knowledge of the role of individual differences in drug use, the present study compares the personality profile of tobacco, marijuana, cocaine, and heroin users and non-users using the wide spectrum Five-Factor Model (FFM) of personality in a diverse community sample.</p> <p>Method</p> <p>Participants (<it>N </it>= 1,102; mean age = 57) were part of the Epidemiologic Catchment Area (ECA) program in Baltimore, MD, USA. The sample was drawn from a community with a wide range of socio-economic conditions. Personality traits were assessed with the Revised NEO Personality Inventory (NEO-PI-R), and psychoactive substance use was assessed with systematic interview.</p> <p>Results</p> <p>Compared to never smokers, current cigarette smokers score lower on Conscientiousness and higher on Neuroticism. Similar, but more extreme, is the profile of cocaine/heroin users, which score very high on Neuroticism, especially Vulnerability, and very low on Conscientiousness, particularly Competence, Achievement-Striving, and Deliberation. By contrast, marijuana users score high on Openness to Experience, average on Neuroticism, but low on Agreeableness and Conscientiousness.</p> <p>Conclusion</p> <p>In addition to confirming high levels of negative affect and impulsive traits, this study highlights the links between drug use and low Conscientiousness. These links provide insight into the etiology of drug use and have implications for public health interventions.</p
Seismic Design Method for CFS Diagonal Strap-Braced Stud Walls: Experimental Validation
The search for innovative methods to ensure high structural, technological and environmental performance is an important issue in the development of new constructions. Among the several available building systems, constructions involving the structural use of Cold-Formed Steel (CFS) profiles represent an efficient and reliable solution. In an effort to characterize the seismic response of CFS structures and to support the spreading of these systems, a theoretical and experimental research has been carried out at University of Naples Federico II within the Italian research project RELUIS-DPC 2010-2013. It focused on the "all steel design" solution, in which CFS diagonal strap-braced stud walls are the main lateral resisting system. In order to overcome the lack of information in the current European codes, a critical analysis of the requirements for these systems provided by the AISI S213-2007 has been carried out by comparing them with those given by Eurocodes for hot-rolled X-braced steel frames (tension-only). On the basis of the design hypothesis outlined from this analysis, a case study has been developed with the aim to define an extended experimental campaign involving 12 tests on full-scale CFS diagonal strap-braced stud walls. Finally, on the basis of experimental results, the assumed design prescriptions and requirements, such as the force modification factor and the capacity design rules, have been verified
The Five Factor Model of personality and evaluation of drug consumption risk
The problem of evaluating an individual's risk of drug consumption and misuse
is highly important. An online survey methodology was employed to collect data
including Big Five personality traits (NEO-FFI-R), impulsivity (BIS-11),
sensation seeking (ImpSS), and demographic information. The data set contained
information on the consumption of 18 central nervous system psychoactive drugs.
Correlation analysis demonstrated the existence of groups of drugs with
strongly correlated consumption patterns. Three correlation pleiades were
identified, named by the central drug in the pleiade: ecstasy, heroin, and
benzodiazepines pleiades. An exhaustive search was performed to select the most
effective subset of input features and data mining methods to classify users
and non-users for each drug and pleiad. A number of classification methods were
employed (decision tree, random forest, -nearest neighbors, linear
discriminant analysis, Gaussian mixture, probability density function
estimation, logistic regression and na{\"i}ve Bayes) and the most effective
classifier was selected for each drug. The quality of classification was
surprisingly high with sensitivity and specificity (evaluated by leave-one-out
cross-validation) being greater than 70\% for almost all classification tasks.
The best results with sensitivity and specificity being greater than 75\% were
achieved for cannabis, crack, ecstasy, legal highs, LSD, and volatile substance
abuse (VSA).Comment: Significantly extended report with 67 pages, 27 tables, 21 figure
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Molecular testing for the clinical diagnosis of fibrolamellar carcinoma.
Fibrolamellar carcinoma has a distinctive morphology and immunophenotype, including cytokeratin 7 and CD68 co-expression. Despite the distinct findings, accurate diagnosis of fibrolamellar carcinoma continues to be a challenge. Recently, fibrolamellar carcinomas were found to harbor a characteristic somatic gene fusion, DNAJB1-PRKACA. A break-apart fluorescence in situ hybridization (FISH) assay was designed to detect this fusion event and to examine its diagnostic performance in a large, multicenter, multinational study. Cases initially classified as fibrolamellar carcinoma based on histological features were reviewed from 124 patients. Upon central review, 104 of the 124 cases were classified histologically as typical of fibrolamellar carcinoma, 12 cases as 'possible fibrolamellar carcinoma' and 8 cases as 'unlikely to be fibrolamellar carcinoma'. PRKACA FISH was positive for rearrangement in 102 of 103 (99%) typical fibrolamellar carcinomas, 9 of 12 'possible fibrolamellar carcinomas' and 0 of 8 cases 'unlikely to be fibrolamellar carcinomas'. Within the morphologically typical group of fibrolamellar carcinomas, two tumors with unusual FISH patterns were also identified. Both cases had the fusion gene DNAJB1-PRKACA, but one also had amplification of the fusion gene and one had heterozygous deletion of the normal PRKACA locus. In addition, 88 conventional hepatocellular carcinomas were evaluated with PRKACA FISH and all were negative. These findings demonstrate that FISH for the PRKACA rearrangement is a clinically useful tool to confirm the diagnosis of fibrolamellar carcinoma, with high sensitivity and specificity. A diagnosis of fibrolamellar carcinoma is more accurate when based on morphology plus confirmatory testing than when based on morphology alone
Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis
Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies. Copyright (c) 2006 S. Karger AG, Basel
Expression Patterns of TNFα, MAdCAM1, and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease.
Pathogenesis of cutaneous extraintestinal manifestations [EIM] in inflammatory bowel disease [IBD] remains elusive. Efficacy of anti-TNF agents suggests TNF-dependent mechanisms. The role of other biologics, such as anti-integrins or JAK-inhibitors, is not yet clear.
We performed immunohistochemistry for TNFα, NFκB, STAT1/STAT3, MAdCAM1, CD20/68, caspase 3/9, IFNγ, and Hsp-27/70 on 240 intestinal [55 controls, 185 IBD] and 64 skin biopsies [11 controls, 18 erythema nodosum [EN], 13 pyoderma gangenosum [PG], 22 psoriasis]. A semiquantitative score [0-100%] was used for evaluation.
TNFα was upregulated in intestinal biopsies from active Crohn`s disease [CD] vs controls [36.2 vs 12.1, p < 0.001], but not ulcerative colitis [UC: 17.9]. NFκB, however, was upregulated in intestinal biopsies from both active CD and UC [43.2 and 34.5 vs 21.8, p < 0.001 and p = 0.017, respectively]. TNFα and NFκB were overexpressed in skin biopsies from EN, PG, and psoriasis. No MAdCAM1 overexpression was seen in skin tissues, whereas it was upregulated in active UC vs controls [57.5 vs 35.4, p = 0.003]. STAT3 was overexpressed in the intestinal mucosa of active and non-active IBD, and a similar upregulation was seen in skin biopsies from EN [84.7 vs 22.3, p < 0.001] and PG [60.5 vs 22.3, p = 0.011], but not in psoriasis. Caspase 3 and CD68 overexpression in skin biopsies distinguished EN/PG from psoriasis and controls.
Upregulation of TNFα/NFκB in EN and PG is compatible with the efficacy of anti-TNF in EIM management. Data on overexpressed STAT3, but not MAdCAM1, support a rationale for JAK-inhibitors in EN and PG, while questioning the role of vedolizumab
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