A smart active vibration control (AVC) system containing piezoelectric (PZT) actuators, jointly with a linear quadratic regulator (LQR) controller, is proposed in this article to control transverse ...deflections of a wind turbine (WT) blade. In order to apply controlling rules to the WT blade, a state-of-the-art semi-analytical solution is developed to obtain WT blade lateral displacement under external loadings. The proposed method maps the WT blade to a Euler–Bernoulli beam under the same conditions to find the blade’s vibration and dynamic responses by solving analytical vibration solutions of the Euler–Bernoulli beam. The governing equations of the beam with PZT patches are derived by integrating the PZT transducer vibration equations into the vibration equations of the Euler–Bernoulli beam structure. A finite element model of the WT blade with PZT patches is developed. Next, a unique transfer function matrix is derived by exciting the structures and achieving responses. The beam structure is projected to the blade using the transfer function matrix. The results obtained from the mapping method are compared with the counter of the blade’s finite element model. A satisfying agreement is observed between the results. The results showed that the method’s accuracy decreased as the sensors’ distance from the base of the wind turbine increased. In the designing process of the LQR controller, various weighting factors are used to tune control actions of the AVC system. LQR optimal control gain is obtained by using the state-feedback control law. The PZT actuators are located at the same distance from each other an this effort to prevent neutralizing their actuating effects. The LQR shows significant performance by diminishing the weights on the control input in the cost function. The obtained results indicate that the proposed smart control system efficiently suppresses the vibration peaks along the WT blade and the maximum flap-wise displacement belonging to the tip of the structure is successfully controlled.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose Fused Filament Fabrication (FFF) is one of the growing technologies in additive manufacturing, that can be used in a number of applications. In this method, process parameters can be ...customized and their simultaneous variation has conflicting impacts on various properties of printed parts such as dimensional accuracy (DA) and surface finish. These properties could be improved by optimizing the values of these parameters. Design/methodology/approach In this paper, four process parameters, namely, print speed, build orientation, raster width, and layer height which are referred to as “input variables” were investigated. The conflicting influence of their simultaneous variations on the DA of printed parts was investigated and predicated. To achieve this goal, a hybrid Genetic Algorithm – Artificial Neural Network (GA-ANN) model, was developed in C#.net, and three geometries, namely, U-shape, cube and cylinder were selected. To investigate the DA of printed parts, samples were printed with a central through hole. Design of Experiments (DoE), specifically the Rotational Central Composite Design method was adopted to establish the number of parts to be printed (30 for each selected geometry) and also the value of each input process parameter. The dimensions of printed parts were accurately measured by a shadowgraph and were used as an input data set for the training phase of the developed ANN to predict the behavior of process parameters. Then the predicted values were used as input to the Desirability Function tool which resulted in a mathematical model that optimizes the input process variables for selected geometries. The mean square error of 0.0528 was achieved, which is indicative of the accuracy of the developed model. Findings The results showed that print speed is the most dominant input variable compared to others, and by increasing its value, considerable variations resulted in DA. The inaccuracy increased, especially with parts of circular cross section. In addition, if there is no need to print parts in vertical position, the build orientation should be set at 0° to achieve the highest DA. Finally, optimized values of raster width and layer height improved the DA especially when the print speed was set at a high value. Originality/value By using ANN, it is possible to investigate the impact of simultaneous variations of FFF machines’ input process parameters on the DA of printed parts. By their optimization, parts of highly accurate dimensions could be printed. These findings will be of significant value to those industries that need to produce parts of high DA on FFF machines.
Biofilms are communities of microorganisms that are formed on and attached to living or nonliving surfaces and are surrounded by an extracellular polymeric material. Biofilm formation enjoys several ...advantages over the pathogens in the colonization process of medical devices and patients' organs. Unlike planktonic cells, biofilms have high intrinsic resistance to antibiotics and sanitizers, and overcoming them is a significant problematic challenge in the medical and food industries. There are no approved treatments to specifically target biofilms. Thus, it is required to study and present innovative and effective methods to combat a bacterial biofilm. In this review, several strategies have been discussed for combating bacterial biofilms to improve healthcare, food safety, and industrial process.
Bacteria are the cause of evolution of several strategies to deal with problems and challenges existing under hostile environments. One of the significant survival strategies used by bacteria is a biofilm formation. we have tried to provide a comprehensive picture of current knowledge about antibiofilm agents of different sources.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Computational chemistry provides a versatile toolbox for studying mechanistic details of catalytic reactions and holds promise to deliver practical strategies to enable the rational in silico ...catalyst design. The versatile reactivity and nontrivial electronic structure effects, common for systems based on 3d transition metals, introduce additional complexity that may represent a particular challenge to the standard computational strategies. In this review, we discuss the challenges and capabilities of modern electronic structure methods for studying the reaction mechanisms promoted by 3d transition metal molecular catalysts. Particular focus will be placed on the ways of addressing the multiconfigurational problem in electronic structure calculations and the role of expert bias in the practical utilization of the available methods. The development of density functionals designed to address transition metals is also discussed. Special emphasis is placed on the methods that account for solvation effects and the multicomponent nature of practical catalytic systems. This is followed by an overview of recent computational studies addressing the mechanistic complexity of catalytic processes by molecular catalysts based on 3d metals. Cases that involve noninnocent ligands, multicomponent reaction systems, metal–ligand and metal–metal cooperativity, as well as modeling complex catalytic systems such as metal–organic frameworks are presented. Conventionally, computational studies on catalytic mechanisms are heavily dependent on the chemical intuition and expert input of the researcher. Recent developments in advanced automated methods for reaction path analysis hold promise for eliminating such human-bias from computational catalysis studies. A brief overview of these approaches is presented in the final section of the review. The paper is closed with general concluding remarks.
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IJS, KILJ, NUK, PNG, UL, UM
Epidermal growth factor receptor (EGFR) mutations enable constitutive active downstream signaling of PI3K/AKT, KRAS/ERK and JAK/STAT pathways, and promote tumor progression by inducing uncontrolled ...proliferation, evasion of apoptosis and migration of non-small cell lung cancer (NSCLC). In addition, such EGFR mutations increase the susceptibility of patients with NSCLC to tyrosine kinase inhibitor (TKI) therapy, but treated patients will invariably relapse with resistant disease. A global understanding of underlying molecular mechanisms of EGFR signaling may improve the management of NSCLC patients.
microarray analysis was performed to identify PI3K/AKT-regulated miRNAs. Phosphoproteomic analysis and cell based assays were performed using NSCLC cell lines lentivirally transduced with anti-miR or miR overexpressing constructs.
Here, we show that 17 miRNAs including members of the miR-17~ 92 cluster are dysregulated following PI3K/AKT inhibition of EGFR mutant NSCLC cells. Bioinformatics analysis revealed that dysregulated miRNAs act in a concerted manner to enhance the activity of the EGFR signaling pathway. These findings were closely mirrored by attenuation of miR-17~ 92 family member miR-19b in NSCLC cell lines which resulted in reduced phosphorylation of ERK, AKT and STAT and effector proteins in EGFR mutant NSCLC cells. Consistent with this finding, cell cycle progression, clonogenic growth and migration were reduced and apoptosis was enhanced. Co-treatment of NSCLC cells with the tyrosine kinase inhibitor (TKI) gefitinib and anti-miR-19b construct reduced migration and clonogenic growth in a synergistic manner suggesting that EGFR and miR-19b act together to control oncogenic processes. Serine/threonine phosphatase PP2A subunit PPP2R5E and BCL2L11 encoding BIM were identified as major targets of miR-19b by target validation assays. Consistent with this finding, PP2A activity was strongly enhanced in NSCLC transduced with anti-miR-19b construct, but not in cells co-transduced with anti-miR-19b and shPPP2R5E, suggesting that PPP2R5E is a major constituent of the PP2A complex. Accordingly, enhanced proliferation by miR-19b was due to targeting PPP2R5E. In contrast, apoptosis resistance was mainly due to targeting BCL2L11.
Our results provide insight into the importance of targeting PPP2R5E and BCL2L11 by miR-19b in oncogenic processes of NSCLC. Attenuation of miR-19b expression could potentially be exploited in adjuvant therapy of EGFR mutant NSCLC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circulating miRNAs are detected in extracellular space and body fluids such as urine. Circulating RNAs can be packaged in secreted urinary extracellular vesicles (uEVs) and thus protected from ...degradation. Urinary exosome preparations might contain specific miRNAs, relevant as biomarkers in renal and bladder diseases. Major difficulties in application of uEVs into the clinical environment are the high variability and low reproducibility of uEV isolation methods. Here we used five different methods to isolate uEVs and compared the size distribution, morphology, yield, presence of exosomal protein markers and RNA content of uEVs. We present an optimized ultracentrifugation and size exclusion chromatography approach for highly reproducible isolation for 50-150 nm uEVs, corresponding to the exosomes, from 50 ml urine. We profiled the miRNA content of uEVs and total urine from the same samples with the NanoString platform and validated the data using qPCR. Our results indicate that 18 miRNAs, robustly detected in uEVs were always present in the total urine. However, 15 miRNAs could be detected only in the total urine preparations and might represent naked circulating miRNA species. This is a novel unbiased and reproducible strategy for uEVs isolation, content normalization and miRNA cargo analysis, suitable for biomarker discovery studies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose:
To clinically evaluate an iterative metal artifact reduction (IMAR) algorithm prototype in the radiation oncology clinic setting by testing for accuracy in CT number retrieval, relative ...dosimetric changes in regions affected by artifacts, and improvements in anatomical and shape conspicuity of corrected images.
Methods:
A phantom with known material inserts was scanned in the presence/absence of metal with different configurations of placement and sizes. The relative change in CT numbers from the reference data (CT with no metal) was analyzed. The CT studies were also used for dosimetric tests where dose distributions from both photon and proton beams were calculated. Dose differences and gamma analysis were calculated to quantify the relative changes between doses calculated on the different CT studies. Data from eight patients (all different treatment sites) were also used to quantify the differences between dose distributions before and after correction with IMAR, with no reference standard. A ranking experiment was also conducted to analyze the relative confidence of physicians delineating anatomy in the near vicinity of the metal implants.
Results:
IMAR corrected images proved to accurately retrieve CT numbers in the phantom study, independent of metal insert configuration, size of the metal, and acquisition energy. For plastic water, the mean difference between corrected images and reference images was −1.3 HU across all scenarios (N = 37) with a 90% confidence interval of −2.4, −0.2 HU. While deviations were relatively higher in images with more metal content, IMAR was able to effectively correct the CT numbers independent of the quantity of metal. Residual errors in the CT numbers as well as some induced by the correction algorithm were found in the IMAR corrected images. However, the dose distributions calculated on IMAR corrected images were closer to the reference data in phantom studies. Relative spatial difference in the dose distributions in the regions affected by the metal artifacts was also observed in patient data. However, in absence of a reference ground truth (CT set without metal inserts), these differences should not be interpreted as improvement/deterioration of the accuracy of calculated dose. With limited data presented, it was observed that proton dosimetry was affected more than photons as expected. Physicians were significantly more confident contouring anatomy in the regions affected by artifacts. While site specific preferences were detected, all indicated that they would consistently use IMAR corrected images.
Conclusions:
IMAR correction algorithm could be readily implemented in an existing clinical workflow upon commercial release. While residual errors still exist in IMAR corrected images, these images present with better overall conspicuity of the patient/phantom geometry and offer more accurate CT numbers for improved local dosimetry. The variety of different scenarios included herein attest to the utility of the evaluated IMAR for a wide range of radiotherapy clinical scenarios.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
MicroRNA miR-199a-5p impairs tight junction formation, leading to increased urothelial permeability in bladder pain syndrome. Now, using transcriptome analysis in urothelial TEU-2 cells, we implicate ...it in the regulation of cell cycle, cytoskeleton remodeling, TGF, and WNT signaling pathways. MiR-199a-5p is highly expressed in the smooth muscle layer of the bladder, and we altered its levels in bladder smooth muscle cells (SMCs) to validate the pathway analysis. Inhibition of miR-199a-5p with antimiR increased SMC proliferation, reduced cell size, and up-regulated miR-199a-5p targets, including WNT2. Overexpression of WNT2 protein or treating SMCs with recombinant WNT2 closely mimicked the miR-199a-5p inhibition, whereas down-regulation of WNT2 in antimiR-expressing SMCs with shRNA restored cell phenotype and proliferation rates. Overexpression of miR-199a-5p in the bladder SMCs significantly increased cell size and up-regulated SM22, SM α-actin, and SM myosin heavy chain mRNA and protein levels. These changes as well as increased expression of ACTG2, TGFB1I1, and CDKN1A were mediated by up-regulation of the smooth muscle-specific transcriptional activator myocardin at mRNA and protein levels. Myocardin-related transcription factor A downstream targets Id3 and MYL9 were also induced. Up-regulation of myocardin was accompanied by down-regulation of WNT-dependent inhibitory Krüppel-like transcription factor 4 in miR-199a-5p-overexpressing cells. In contrast, Krüppel-like transcription factor 4 was induced in antimiR-expressing cells following the activation of WNT2 signaling, leading to repression of myocardin-dependent genes. MiR-199a-5p plays a critical role in the WNT2-mediated regulation of proliferative and differentiation processes in the smooth muscle and may behave as a key modulator of smooth muscle hypertrophy, which is relevant for organ remodeling.
Background: MicroRNA miR-199a-5p, implicated in cell motility and proliferation, is highly expressed in bladder smooth muscle.
Results: MiR-199a-5p regulates WNT, cytoskeleton, and cell cycle pathways in urothelial and smooth muscle cells and promotes myocardin-driven gene expression.
Conclusion: MiR-199a-5p acts via its target WNT2 to control smooth muscle proliferation and morphology.
Significance: MiR-199a-5p is a key modulator of smooth muscle hypertrophy, relevant for bladder organ remodeling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The cervix of the uterus is a rare site for cavernous hemangiomas. Cervical hemangiomas are slow‐growing tumors with characteristic histological findings, including dilated vessels with increased ...endothelial cells. Although their pathophysiology remains unclear, hormones are believed to play an important role in the development of these vascular tumors. They may be asymptomatic due to their small size, but they can cause gynecological and obstetrical complications, including abnormal uterine bleeding and impaired fertility. Due to their small size, conservative treatment is the first line of management. Hysterectomy is considered for refractory cases or for patients who are not of childbearing age. In this study, firstly, we presented a case of a 60‐year‐old postmenopausal female without any gynecological‐related signs or symptoms with a polypoid nodule hanging over the anterior cervical wall through its stalk. The surgical biopsy revealed no signs of neoplastic changes, with the only notable finding being a benign vascular lesion representing a cavernous hemangiomatous cervical polyp. The patient underwent a total abdominal hysterectomy and bilateral salpingo‐oophorectomy and she is currently healthy without any further abnormal findings. Additionally, we provided a comprehensive review of 137 cases in the literature since 1883, detailing their characteristics, signs and symptoms, and pathology.
Synopsis
Cervical hemangiomas are rare tumors, mostly found incidentally, and some present symptomatically, especially with abnormal uterine bleeding. We presented the 138th case in the literature.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We evaluated the distribution of carbapenem and colistin resistance mechanisms of clinical E. coli and K. pneumoniae isolates from Iran.
165 non-duplicate non-consecutive isolates of K. pneumoniae ...and E. coli were collected from hospitalized patients admitted to Iran's tertiary care hospitals from September 2016 to August 2018. The isolates were cultured from different clinical specimens, including wound, urine, blood, and tracheal aspirates. Antibiotic susceptibility testing was performed by disc diffusion and microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) guideline. The presence of extended spectrum β-lactamases (ESBLs) genes, carbapenemase genes, as well as fosfomycin resistance genes, and colistin resistance genes was also examined by PCR-sequencing. The ability of biofilm formation was assessed with crystal violet staining method. The expression of colistin resistance genes were measured by quantitative reverse transcription-PCR (RT-qPCR) analysis to evaluate the association between gene upregulation and colistin resistance. Genotyping was performed using the multi-locus sequencing typing (MLST).
Colistin and tigecycline were the most effective antimicrobial agents with 90.3% and 82.4% susceptibility. Notably, 16 (9.7%) isolates showed resistance to colistin. Overall, 33 (20%), 31 (18.8%), and 95 (57.6%) isolates were categorized as strong, moderate, and weak biofilm-producer, respectively. Additionally, bla
, bla
, bla
, bla
, bla
and bla
resistance genes were detected in 98 (59.4%), 54 (32.7%), 77 (46.7%), 3 (1.8%), 17 (10.30%) and 3 (1.8%) isolates, respectively. Inactivation of mgrB gene due to nonsense mutations and insertion of IS elements was observed in 6 colistin resistant isolates. Colistin resistance was found to be linked to upregulation of pmrA-C, pmrK, phoP, and phoQ genes. Three of bla
and 3 of bla
variants were found to be carried by IncL/M and IncF plasmid, respectively. MLST revealed that bla
positive isolates were clonally related and belonged to three distinct clonal complexes, including ST147, ST15 and ST3299.
The large-scale surveillance and effective infection control measures are also urgently needed to prevent the outbreak of diverse carbapenem- and colistin-resistant isolates in the future.
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