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Stimuli-SoS: a model-based approach to derive stimuli generators for simulations of systems-of-systems software architectures
No full textAbstract\ud
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Background\ud
Systems-of-systems (SoS) are alliances of independent and interoperable software-intensive systems. SoS often support critical domains, being required to exhibit a reliable operation, specially because people’s safety relies on their services. In this direction, simulations enable the validation of different operational scenarios in a controlled environment, allowing a benchmarking of its response as well as revealing possible breaches that could lead to failures. However, simulations are traditionally manual, demanding a high level of human intervention, being costly and error-prone. A stimuli generator could aid in by continuously providing data to trigger a SoS simulation and maintaining its operation.\ud
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Methods\ud
We established a model-based approach termed Stimuli-SoS to support the creation of stimuli generators to be used in SoS simulations. Stimuli-SoS uses software architecture descriptions for automating the creation of such generators. Specifically, this approach transforms SoSADL, a formal architectural description language for SoS, into dynamic models expressed in DEVS, a simulation formalism. We carried out a case study in which Stimuli-SoS was used to automatically produce stimuli generators for a simulation of a flood monitoring SoS.\ud
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Results\ud
We run simulations of a SoS architectural configuration with 69 constituent systems, i.e., 42 sensors, 9 crowdsourcing systems, and 18 drones. Stimuli generators were automatically generated for each type of constituent. These stimuli generators were capable of receiving the input data from the database and generating the expected stimuli for the constituents, allowing to simulate constituent systems interoperations into the flood monitoring SoS. Using Stimuli-SoS, we simulated 38 days of flood monitoring in little more than 6 h. Stimuli generators correctly forwarded data to the simulation, which was able to reproduce 29 flood alerts triggered by the SoS during a flooding event. In particular, Stimuli-SoS is almost 65 times more productive than a manual approach to producing data for the same type of simulation.\ud
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Conclusions\ud
Our approach succeeded in automatically deriving a functional stimuli generator that can reproduce environmental conditions for simulating a SoS. In particular, we presented new contributions regarding productivity and automation for the use of a model-based approach in SoS engineering.Núcleo de Informação e Coordenção do br NIC.br for the waiver received
Use of artificial primary teeth for endodontic laboratory research: experiments related to canal length determination
No full textAbstract\ud
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Background\ud
Due to the scarcity of exfoliated/extracted human primary teeth with complete roots, artificial teeth were developed as an alternative to be used for educational and laboratory research purposes. This study aimed to assess the feasibility of using artificial primary teeth for conducting laboratory research through an experiment related to canal length determination, comparing artificial teeth with natural teeth.\ud
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Methods\ud
Thirty anterior and 21 posterior artificial teeth, and the same number of natural primary teeth were selected. After preparing the access cavity, the root canal length was determined by two examiners twice using three different methods: radiography and two electronic apex locators. Then, the actual root canal length was measured by inserting a K-file up to the apical foramen (reference standard). Accuracy was calculated using Bland-Altman analysis and intraclass correlation coefficient (ICC). The inter- and intra-examiner reproducibility was also calculated using the ICC.\ud
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Results\ud
The methods using the electronic apex locators showed better accuracy in both artificial and natural teeth. Trends observed with artificial primary teeth were similar to those observed with natural teeth, except for the results in artificial anterior teeth.\ud
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Conclusions\ud
The model of artificial teeth might be a good alternative for educational purposes; however, improvements are necessary to employ these teeth for research purposes when considering experiments for canal length determination.This research was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa no Estado de São Paulo (FAPESP)
Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin
No full textAbstract\ud
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Background\ud
Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders.\ud
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Method\ud
A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment.\ud
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Results\ud
Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719).\ud
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Conclusions\ud
Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.Thanks to Capes (Commission for the Improvement of Higher Education Personnel) for the scholarship during the study for Barbosa ME
Thromboelastometry analysis of thrombocytopenic dengue patients: a cross-sectional study
No full textAbstract\ud
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Background\ud
Dengue virus infection (DVI) is a prevalent and potentially fatal viral disease associated with coagulopathy. So far, the coagulation profile of DVI patients with thrombocytopenia has not been assessed through a viscoelastic test such as rotational thromboelastometry. We aimed to describe the prevalence and characteristics of coagulation abnormalities in dengue fever outpatients with thrombocytopenia, addressed by both rotational thromboelastometry and conventional coagulation tests.\ud
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Methods\ud
This was a cross-sectional study conducted between April 6th and May 5th 2015 in São Paulo, Brazil during a dengue outbreak. Thromboelastometry (ROTEM®) and the conventional coagulation tests prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), platelet count and fibrinogen levels were performed in 53 patients with DVI and thrombocytopenia.\ud
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Results\ud
Despite a median interquartile range (IQR) platelet count of 77 (63–88) x 109/L in DVI patients, conventional coagulation tests and plasma fibrinogen levels were within the normal range. Subjects demonstrated hypocoagulability in 71.7% (38/53) in INTEM and 54.7% (29/53) in EXTEM DVI patients. FIBTEM analyses detected only 5.7% (3/53) with hypocoagulability among this population. The median (IQR) clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) on INTEM were, respectively, 177 (160–207) sec, 144 (108–178) sec and 48 (42–52) mm. On EXTEM, median (IQR) CT, CFT and MCF were, respectively, 69 (65–78) sec, 148 (126–198) sec and 49 (44–55) mm. Median (IQR) MCF on FIBTEM was 15 (13–18) mm.\ud
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Conclusion\ud
Thromboelastometry impairment is highly prevalent in DVI patients with thrombocytopenia, particularly in INTEM and EXTEM analyses, while standard coagulation tests are normal in this setting. Clinical implications remain to be established
Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway
No full textAbstract\ud
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Background\ud
Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFβ pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients.\ud
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Methods\ud
After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFβ isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay.\ud
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Results\ud
There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFβ1 and TGFβ3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue.\ud
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Conclusions\ud
Cancer cachexia promotes the development of AT fibrosis, in association with altered TGFβ signaling, compromising AT organization and function.This work was supported mainly by São Paulo Research Foundation\ud
(FAPESP; 2012/50079-0) and CAPES. The contents of this work are solely the\ud
responsibility of the authors and do not necessarily represent the official\ud
views of FAPESP
Oral β-hydroxybutyrate increases ketonemia, decreases visceral adipocyte volume and improves serum lipid profile in Wistar rats
No full textAbstract
Background
Ketosis can be induced in humans and in animals by fasting or dietary interventions, such as ketogenic diets. However, the increasing interest on the ketogenic state has motivated the development of alternative approaches to rapidly increase ketonemia using less drastic interventions. Here, it was tested whether oral intake of a β-hydroxybutyrate (βHB) mineral salt mixture could increase ketonemia in Wistar rats without any other dietary changes, thereby being a useful model to study ketones effects alone on metabolism.
Methods
βHB salts were orally administered to provoke elevation in the ketonemia. Effects of this intervention were tested acutely (by gavage) and chronically (4 weeks in drinking water). Acutely, a concomitant glucose overload was used to suppress endogenous ketogenesis and verify whether βHB salts were really absorbed or not. Long-term administration allowed to weekly evaluate the impact on ketonemia, blood glucose and, after 4 weeks, on body weight, visceral fat mass, lipid blood profile, serum lipolysis products and adiponectinemia.
Results
βHB salts increased ketonemia in acute and long-term administrations, improved blood lipid profile by raising HDL-cholesterol concentration and decreasing LDL/HDL ratio, while reduced visceral adipocyte volume. Mean ketonemia correlated positively with HDLc and negatively with adipocyte volume and serum lipolysis products.
Conclusions
Oral βHB can rapidly increase ketonemia and, therefore, be used as an acute and long-term animal model of ketosis. Long-term treatment points to important beneficial effects of ketone bodies in serum lipid concentrations and visceral fat mass. These results may help to explain the metabolic adaptations following ketogenic diets, such as a better body fat control and a serum lipid profile improvement
Tapping the biotechnological potential of insect microbial symbionts: new insecticidal porphyrins
No full textAbstract\ud
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Background\ud
The demand for sustainable agricultural practices and the limited progress toward newer and safer chemicals for use in pest control maintain the impetus for research and identification of new natural molecules. Natural molecules are preferable to synthetic organic molecules because they are biodegradable, have low toxicity, are often selective and can be applied at low concentrations. Microbes are one source of natural insecticides, and microbial insect symbionts have attracted attention as a source of new bioactive molecules because these microbes are exposed to various selection pressures in their association with insects. Analytical techniques must be used to isolate and characterize new compounds, and sensitive analytical tools such as mass spectrometry and high-resolution chromatography are required to identify the least-abundant molecules.\ud
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Results\ud
We used classical fermentation techniques combined with tandem mass spectrometry to prospect for insecticidal substances produced by the ant symbiont Streptomyces caniferus. Crude extracts from this bacterium showed low biological activity (less than 10% mortality) against the larval stage of the fall armyworm Spodoptera frugiperda. Because of the complexity of the crude extract, we used fractionation-guided bioassays to investigate if the low toxicity was related to the relative abundance of the active molecule, leading to the isolation of porphyrins as active molecules. Porphyrins are a class of photoactive molecules with a broad range of bioactivity, including insecticidal. The active fraction, containing a mixture of porphyrins, induced up to 100% larval mortality (LD50 = 37.7 μg.cm−2). Tandem mass-spectrometry analyses provided structural information for two new porphyrin structures. Data on the availability of porphyrins in 67 other crude extracts of ant ectosymbionts were also obtained with ion-monitoring experiments.\ud
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Conclusions\ud
Insect-associated bacterial symbionts are a rich source of bioactive compounds. Exploring microbial diversity through mass-spectrometry analyses is a useful approach for isolating and identifying new compounds. Our results showed high insecticidal activity of porphyrin compounds. Applications of different experiments in mass spectrometry allowed the characterization of two new porphyrins.We thank the Fundação de Amparo à Pesquisa do Estado de São Paulo\ud
(FAPESP) for providing a fellowship to AFCM (Process 2014/21584–3) and a\ud
research grant to FLC (Process 2011/50877–0)
Cognitive flexibility training intervention among children with autism: a longitudinal study
No full textAbstract\ud
Autism is defined by persistent deficits in social communication and social interaction in multiple contexts as well as restricted and repetitive patterns of behavior. There are also reported difficulties in the dynamic activation and modification of cognitive processes in response to changes in tasks’ demands. Such difficulties are believed to be due to poor flexible cognition. This research aimed to assess and intervene in cognitive flexibility in subjects with autism.\ud
Ten subjects diagnosed with autism by psychiatrists, aged 5 years to 13 years and 5 months, were assessed in non-verbal intelligence through Raven’s Progressive Matrices in pretest. They were also assessed in cognitive flexibility through Wisconsin Card Sorting Test (WCST) and in patterns of social interactions, behaviors, and communication through Autism Diagnostic Interview-Revised (ADI-R). An intervention program of 14 to 21 sessions was established to enhance cognitive flexibility. In posttest, they were assessed in WCST and ADI-R.\ud
All measures of cognitive flexibility improved in posttest except for failure to maintain set. Among the measures improved in posttest, perseverative errors and responses improved in posttest with statistical significance as well as categories completed. Total scores on ADI-R were lower in posttest as well as scores on communication abilities.\ud
The qualitative improvement showed by the individuals of this research concerning cognitive flexibility and also patterns of restricted behavior, social interaction, and communication abilities suggests that individuals with autism can benefit from the development of strategies for the enhancement of cognitive flexibility. Nevertheless, more research is suggested with a larger sample among subjects on the autism spectrum.The first author thanks the National Council of Technological and Scientific\ud
Development in Brazil for the post-doctoral research fellowship during the\ud
fisrt year of research (CNPQ - Process: 150739/2012-5)
Report on the development of putative functional SSR and SNP markers in passion fruits
No full textAbstract\ud
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Background\ud
Passionflowers Passiflora edulis and Passiflora alata are diploid, outcrossing and understudied fruit bearing species. In Brazil, passion fruit cultivation began relatively recently and has earned the country an outstanding position as the world’s top producer of passion fruit. The fruit’s main economic value lies in the production of juice, an essential exotic ingredient in juice blends. Currently, crop improvement strategies, including those for underexploited tropical species, tend to incorporate molecular genetic approaches. In this study, we examined a set of P. edulis transcripts expressed in response to infection by Xanthomonas axonopodis, (the passion fruit’s main bacterial pathogen that attacks the vines), aiming at the development of putative functional markers, i.e. SSRs (simple sequence repeats) and SNPs (single nucleotide polymorphisms).\ud
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Results\ud
A total of 210 microsatellites were found in 998 sequences, and trinucleotide repeats were found to be the most frequent (31.4%). Of the sequences selected for designing primers, 80.9% could be used to develop SSR markers, and 60.6% SNP markers for P. alata. SNPs were all biallelic and found within 15 gene fragments of P. alata. Overall, gene fragments generated 10,003 bp. SNP frequency was estimated as one SNP every 294 bp. Polymorphism rates revealed by SSR and SNP loci were 29.4 and 53.6%, respectively.\ud
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Conclusions\ud
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Passiflora edulis transcripts were useful for the development of putative functional markers for P. alata, suggesting a certain level of sequence conservation between these cultivated species. The markers developed herein could be used for genetic mapping purposes and also in diversity studies.ZPC and CFM received scholarships from CNPq (Conselho Nacional de Desen‑\ud
volvimento Científco e Tecnológico, Brazil) and FAPESP (Fundação de Amparo\ud
à Pesquisado Estado de São Paulo, Brazil), respectively. This study is part of a\ud
research project granted by FAPESP
The effects of 17 alpha-estradiol to inhibit inflammation in vitro
No full textAbstract\ud
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Background\ud
17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown.\ud
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Methods\ud
To begin to address this, we analyzed the ability of 17 α-E2 and 17 β-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ERα (ERKO) male and female mice. Additionally, we further probed if there were sex differences with respect to the effects of E2s using primary pre-adipocyte cells from C57BL/6J male and female mice. Also, we probed mechanistically the effects of E2s in fully differentiated 3T3-L1 cells.\ud
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Results\ud
Both E2s decreased LPS-induced markers of inflammation Tnf-α and Il-6, and increased the anti-inflammatory markers Il-4 and IL-6 receptor (Il-6ra) in MEF cells. To begin to understand the mechanisms by which both E2’s mediate their anti-inflammatory effects, we probed the role of ERα using two methods. First, we used MEF cells from ERKO mice and found reductions in ERα diminished the ability of 17 α-E2 to suppress Tnf-α in female but not in male cells, demonstrating a sexual dimorphism in regard to the role of ERα to mediate 17 α-E2’s effects. Second, we selectively reduced the expression of ERα in 3T3-L1 cells using siRNA and found reductions in ERα diminished the ability of both E2s to suppress Tnf-α and Il-6 expression. Lastly, to determine the mechanisms by which E2s reduce inflammation, we explored the role of NFκB-p65 and found both E2s decreased NFκB-p65 expression.\ud
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Conclusions\ud
In conclusion, we demonstrate for the first time that 17 α-E2, as well as 17 β-E2, suppresses inflammation through their effects on ERα and NFκB-p65