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Due to the increased penetration of wind energy into the electrical power systems in recent years, the turbine controls are actively occupied in the research. This paper presents a nonlinear backstepping strategy to control the generators and the grid sides of a Wind Farm System (WFS) based Direct Drive Synchronous Generator (DDSG). The control objectives such as Tracking the Maximum Power (TMP) from the WFS, pitch control, regulation of dc-link voltage, and reactive and active power generation at varying wind velocity are included. To validate the proposed control strategy, simulation results for 6-MW-DDSG based Wind Farm System are carried out by MATLAB-Simulink. Performance comparison and evaluation with Vector Oriented Control (VOC) are provided under a wide range of functioning conditions, three-phase voltage dips, and the probable occurrence of uncertainties. The proposed control strategy offers remarkable characteristics such as excellent dynamic and steady state performance under varying wind speed and robustness to parametric variations in the WFS and under severe faults of grid voltage. [ABSTRACT FROM AUTHOR]

• Establish the MPPT with optimal speed ratio combined with hidden layer recurrent neural network (HLRNN) to obtain faster convergence. • Optimize the PI controller gains by using a hidden layer recurrent neural network. • Investigate the active power behavior in the presence of unbalanced grid faults. • Amelioration of the response time of the produced power compared with some other existing neural network schemes. This paper suggests the Hidden Layer Recurrent Neural Network (HLRNN) for controlling a wind power generation system based on a dual-fed induction generator. The generator's stator is connected directly to the electrical grid, while the rotor is linked through bidirectional converters. A PI controller-based Indirect Vector Control (IVC) scheme has been established to pilot the system. The PI regulator allows linear systems to perform well, but when subjected to physical variation conditions, the system's response becomes unstable, making the PI controller insufficient. This paper aims to ensure the PI controller gains self-adaptation regardless of the severity of the circumstances. The effectiveness of the proposed control is demonstrated by taking into account critical conditions such as wind speed changes, generator parameter variations, and asymmetrical faults in the grid. Furthermore, it is confirmed by the enhanced performance and the reduced oscillations during a voltage dip. The simulation results, achieved using MATLAB/Simulink, demonstrate that the response time is reduced to 1.8 (m s), the static error is minimized to 0.16%, and the overshoot is improved to 0.24% when compared to the IVC based on the PI controller and some existing neural network schemes. [ABSTRACT FROM AUTHOR]

As the penetration of the Wind Energy Generation System (WEGS) into the modern power systems is extensively increased, an efficient control strategy of a WEGS plays an essential role in wind power utilization. This study presents Sliding Mode Control (SMC) design for the Variable Speed Wind Farm Systems (VS-WFS) based on Permanent Magnet Synchronous Generator (PMSG) and interconnected to the electric network. The proposed control laws are used to regulate both grid-side and generator converters. The generator side converters are used to track the maximum wind power. The function of the grid side inverter is to transfer the total extracted wind power from DC-link to the electric network and regulate the DC-link voltage. A SMC scheme is developed in the sense of Lyapunov stability theorem for the VS-WFS. Besides, the effectiveness of the proposed SMC scheme is demonstrated by comparison with a traditional Proportional Integral (PI) control strategy for fault conditions as well as for normal working conditions. Simulation results with Matlab/Simulink environment are presented to support the theoretical considerations demonstrating the potential contributions of both control strategies. The proposed SMC scheme can provide excellent control performance than the traditional PI strategy. [ABSTRACT FROM AUTHOR]

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples. From our analysis, a 13-gene signature panel, in both test and validation datasets, could identify treatment-resistant or progressed melanoma cases with an accuracy and sensitivity of over 70%. The dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a BRAF/MEK treatment-resistant landscape, with resistant cases showing a >2-fold risk of expression of these genes. Furthermore, we utilized a combination of functional enrichment- and gene expression-derived scores to model and identify pathways, such as HMOX1-mediated mitochondrial stress response, as potential key drivers of the emergence of a BRAF/MEK inhibitor-resistant state in melanoma cells. Overall, our results highlight the utility of these genes in predicting treatment outcomes and the underlying mechanisms that can be targeted to reduce the development of resistance to BRAF/MEK targeted therapy. [ABSTRACT FROM AUTHOR]

With the increased penetration of wind energy on modern power systems all over the world, the Wind Farm Systems (WFS) are today required to participate actively in electric network operation by an appropriate generation control strategy. This paper presents a comparative study of two control strategies for wind farm based on Permanent Magnet Synchronous Generator (PMSG) and interconnected to the distribution network. The 4 MW wind farm consists of 2 PMSGs based on 2 MW generators connected to a common DC-bus system. Each PMSG of the WFS is connected to the DC-bus through a rectifier, but the DC-bus is connected to the grid through only one inverter system. The proposed control laws are based on a sliding mode algorithm and classical Proportional Integral (PI) controllers to regulate both generator and grid-side converters. The control strategy combines a pitch control scheme and Maximum Power Point Tracking (MPPT) to maximize the total generated power of WFS. Furthermore, the aim of the control strategy is to maximize the extracted power with the lowest possible impact in the power network voltage and frequency for fault conditions as well as for normal working conditions. Finally, simulation results with Matlab/Simulink environment confirm that the proposed strategy has excellent performance. [ABSTRACT FROM AUTHOR]

This paper presents a Variable Structure Sliding Mode Control (VS-SMC) scheme and Direct Torque Control (DTC) for Wind Farm (WF) based on the Permanent Magnet Synchronous Generator (PMSG). The WF consists of a 3 PMSGs which are connected to a common dc bus system with rectifier. The dc-bus is connected to the electrical network using only one inverter system, a grid-side filter as well as the transformer. The efficiency of the WF can be greatly improved using an appropriate control approach. So, the control strategy uses the technique of DTC to regulate the speeds of PMSGs for Maximum Power Point Tracking (MPPT) mode. Besides, by employing VS-SMC the grid-side inverter is controlled to inject the generated power into the electrical network, to regulate DC-link voltage and to achieve Unity Power Factor. The used control strategies provide an optimal control solution for WF systems based on the PMSG. [ABSTRACT FROM AUTHOR]

We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage caused by a low dose of irradiation, ICAD cells acquire a tumorigenic phenotype. Colon epithelial cells derived from ICAD mice showed a significant resistance to death induced by the colon carcinogen dimethylhydrazine in vitro and in mice. Such resistance was associated with a decrease in PARP-1 activation. In an animal model of dimethylhydrazine-induced colon tumorigenesis, ICAD−/− mice developed significantly higher numbers of tumors with markedly larger sizes than the wild-type counterparts. Interestingly, the phenotype of the ICAD−/− mice was not associated with a significant increase in the precancerous aberrant crypt foci suggesting a potential link to tumor progression rather than initiation. More importantly, ICAD deficiency was associated with severe genomic instability as assessed by array comparative genomic hybridization. Such genomic instability consisted most prominently of amplifications but with sizable deletions as compared to the wild-type counterparts affecting several cancer-related genes including RAF-1, GSN, LMO3, and Fzd6 independently of p53. Altogether, our results present a viable case for the involvement of ICAD deficiency in colon carcinogenesis and show that apoptosis and genomic instability may comprise the means by which such deficiency may contribute to the process of increasing susceptibility to carcinogen-induced tumorigenesis. [ABSTRACT FROM AUTHOR]

When developing any product, one of the factors that determine its price is the volume of the product. In this paper, the effect of various geometrical forms on the performance of a segmented TEGs with the same leg volume was performed. For this purpose, a numerical study was performed using the finite element method (FEM) for different geometrical shapes by considering 3 following forms: Rectangular-leg, Pinleg, and Cone-leg. In each region, Bismuth Telluride was deposited on the cold side while Lead Telluride was placed on the hot side. Two cases were studied. In the 1st case, the 2 regions' the same length, for n and p types, which constitute the leg was taken. While in the 2nd case, all forms of the same volume were evaluated by taking a variable leg length and a fixed cross-sectional area of the hot side. The optimal ratios of the Bismuth Telluride lengths in p2 - type and n2 - type regions for the Rect-leg, Pin-leg, and Coneleg were studied. The obtained results showed that the Rectangular-leg model in the 1st case presents the highest output power and efficiency with about 0.3019 watt and 12.47 % with leg length values of (p2 - type andn2 - type) 1 and 4.5 mm, respectively. Based on the simulation results, we conclude that the leg form and the length ratio influence the performance of the segmented TEGs. The findings indicate that the Rect-leg model presents the best performance. [ABSTRACT FROM AUTHOR]

Aging modifies risk in all cancers, but age is used as a clinical staging criterion uniquely in thyroid cancer (TC). The molecular drivers of age-dependent TC onset and aggressiveness remain poorly understood. We applied an integrative, multi-omics data analysis approach to characterize these signatures. Our analysis reveals that aging, independent of BRAFV600E mutational status, drives a significant accumulation of aggressiveness-related markers and poorer survival outcomes, most noticeably at age 55 and over. We identified that chromosomal alterations in loci 1p/1q as aging-associated drivers of aggressiveness, and that depleted infiltration with tumor surveillant CD8+T and follicular helper T cells, dysregulation of proteostasis- and senescence-related processes, and ERK1/2 signaling cascade are key features of the aging thyroid and TC onset/progression and aggressiveness in aging patients but not in young individuals. A panel of 23 genes, including those related to cell division such as CENPF, ERCC6L, and the kinases MELK and NEK2, were identified and rigorously characterized as aging-dependent and aggressiveness-specific markers. These genes effectively stratified patients into aggressive clusters with distinct phenotypic enrichment and genomic/transcriptomic profiles. This panel also showed excellent performance in predicting metastasis stage, BRAFV600E, TERT promoter mutation, and survival outcomes and was superior to the American Thyroid Association (ATA) methodology in predicting aggressiveness risk. Our analysis established clinically relevant biomarkers for TC aggressiveness factoring in aging as an important component. [ABSTRACT FROM AUTHOR]

This paper presents a novel structure which aims to significantly reduce the mutual coupling between two planar patch antennas, radiating in the same frequency band of 7.5 GHz with the help of a novel absorber. The design is printed on a lossy FR-4 dielectric substrate (εr = 4.4, tanδ = 0.02) with an overall size of 60 × 40 × 1.5 mm3. The new absorbing unit cell consists of two complementary rectangular spiral resonators (CRSR) having three turns in each and coupled by a rectangular slot. This absorbing unit cell is etched on the backed plane of the ground of both patch antennas. Mutual coupling among both electromagnetic radiators has been reduced by 40 dB in the case of simulations, and 35 dB in the case of measurements at the resonant frequency of 7.5 GHz. Optimum measured directivity is more than 6 dBi after including the proposed slot coupled CRSR, whereas it is about 3.4 dBi before integrating the absorbing structure. So, there is 56.6% increase in the gain using the CRSR technique. [ABSTRACT FROM AUTHOR]

Simple Summary: Some thyroid tumors elected for surveillance remain indolent, while others progress. The mechanism responsible for this difference is poorly understood, making it challenging to devise patient surveillance plans. Early prediction is important for tailoring treatment and follow-up in high-risk patients. The aim of our study was to identify predictive markers for progression. We leveraged a highly sensitive test that accurately predicts which thyroid nodules are more likely to develop lymph node metastasis, thereby improving care and outcomes for cancer patients. Papillary thyroid carcinomas (PTCs) account for most endocrine tumors; however, screening and diagnosing the recurrence of PTC remains a clinical challenge. Using microRNA sequencing (miR-seq) to explore miRNA expression profiles in PTC tissues and adjacent normal tissues, we aimed to determine which miRNAs may be associated with PTC recurrence and metastasis. Public databases such as TCGA and GEO were utilized for data sourcing and external validation, respectively, and miR-seq results were validated using quantitative real-time PCR (qRT-PCR). We found miR-145 to be significantly downregulated in tumor tissues and blood. Deregulation was significantly related to clinicopathological features of PTC patients including tumor size, lymph node metastasis, TNM stage, and recurrence. In silico data analysis showed that miR-145 can negatively regulate multiple genes in the TC signaling pathway and was associated with cell apoptosis, proliferation, stem cell differentiation, angiogenesis, and metastasis. Taken together, the current study suggests that miR-145 may be a biomarker for PTC recurrence. Further mechanistic studies are required to uncover its cellular roles in this regard. [ABSTRACT FROM AUTHOR]

Abstract: Post-transcriptional modification of proteins is crucial for balancing protein structure and function in many biological processes. The addition of polymers of adenosine diphosphate (ADP)-ribose (PAR), which are synthesized by PAR polymerases (PARPs) from nicotinamide adenine dinucleotide (NAD), is one such distinctive post-translational modification. PARP-1, the best characterized of the 17-member PARP family, is considered a key isoform responsible for poly(ADP-ribosyl)ation of several nuclear proteins. ADP-ribose polymers add a highly negative charge to their target proteins, resulting in a modification of their activities and functions. PARPs not only participate in regulating cell survival and cell death programs, but are also involved in other biological functions with which novel members of the PARP family have been shown to be involved. Among such functions are transcription regulation, telomere cohesion and mitotic spindle formation during cell division, and intracellular energy metabolism. Recent work from our laboratory and others has highlighted the novel role of PARP-1 in regulating the intracellular trafficking of key cellular proteins such as p53 and nuclear factor-kappa B (NF-κB). Recent literature has revealed that ADP-ribosylation reactions may play important roles in cellular trafficking during inflammation, cell death, and DNA repair. This review will summarize recent findings and concepts linking the role of PARP enzymes and their poly-ADP-ribosylation activity in the regulation of intracellular transport processes. A special focus is placed on the proposed molecular mechanisms involved in such transport processes as the functional significance of PARylation of p53, NF-κB, and high-mobility group protein box 1. [Copyright &y& Elsevier]

Cordycepin has been shown to interfere with a myriad of molecular processes from RNA elongation to kinase activity, and prevents numerous inflammatory processes in animal models. Here we show in a mouse model of LPS-induced acute lung injury that cordycepin prevents airway neutrophilia via a robust blockade of expression of several inflammatory genes, including the adhesion molecule ICAM-1 and VCAM-1, the cytokine/chemokine MCP-1, MIP-1α, MIP-2 and KC, and the chemokine receptor CXCR2. Such a blockade appears to be related to a severe reduction in TNF-α expression. Interestingly, in an in vitro system of A549 epithelial cell inflammation, cordycepin effectively blocked LPS-induced, but not TNF-α-induced, VCAM-1 expression. Such effects correlated with a marked reduction in p65-NF-κB activation as assessed by its phosphorylation at serine-536 but without an apparent effect on its nuclear translocation. The effects of cordycepin on the expression of VCAM-1 and ICAM-1, and of NF-κB activation and nuclear translocation upon TNF-α stimulation resembled the effects achieved upon poly(ADP-ribose) polymerase (PARP) inhibition, suggesting that cordycepin may function as a PARP inhibitor. Indeed, cordycepin blocked H2O2- induced PARP activation in A549 cells. In a cell-free system, cordycepin inhibited PARP-1 activity at nanomolar concentrations. Similar to PARP inhibitors, cordycepin significantly induced killing of breast cancer susceptibility gene (BRCA1)-deficient MCF-7 cells, supporting its therapeutic use for the treatment of BRCA-deficient breast cancers. With added antiinflammatory characteristics, therapies that include cordycepin may prevent potential inflammation triggered by traditional chemotherapeutic drugs. Cordycepin, to the best of our knowledge, represents the first natural product possessing PARP inhibitory traits. [ABSTRACT FROM AUTHOR]

The DNA binding activity of NF-κB is critical for VCAM-1 expression during inflammation. DNA-dependent protein kinase (DNA-PK) is thought to be involved in NF-κB activation. Here we show that DNA-PK is required for VCAM-1 expression in response to TNF. The phosphorylation and subsequent degradation of I-κBα as well as the serine 536 phosphorylation and nuclear translocation of p65 NF-κB were insufficient for VCAM-1 expression in response to TNF. The requirement for p50 NF-κB in TNF-induced VCAM-1 expression may be associated with its interaction with and phosphorylation by DNA-PK, which appears to be dominant over the requirement for p65 NF-κB activation. p50 NF-κB binding to its consensus sequence increased its susceptibility to phosphorylation by DNA-PK. Additionally, DNA-PK activity appeared to increase the association between p50/p50 and p50/p65 NF-κB dimers upon binding to DNA and after binding of p50 NF-κB to the VCAM-1 promoter. Analyses of the p50 NF-κB protein sequence revealed that both serine 20 and serine 227 at the amino terminus of the protein are putative sites for phosphorylation by DNA-PK. Mutation of serine 20 completely eliminated phosphorylation of p50 NF-κB by DNA-PK, suggesting that serine 20 is the only site in p50 NF-κB for phosphorylation by DNA-PK. Re-establishing wild-type p50 NF-κB, but not its serine 20/alanine mutant, in p50 NF-κB-/- fibroblasts reversed VCAM-1 expression after TNF treatment, demonstrating the importance of the serine 20 phosphorylation site in the induction of VCAM-1 expression. Together, these results elucidate a novel mechanism for the involvement of DNA-PK in the positive regulation of p50 NF-κB to drive VCAM-1 expression. [ABSTRACT FROM AUTHOR]

Radon natural is the main cause of lung cancer in non-smokers. Therefore, the study of the behavior of radon and its descendants in indoor air is of the highest importance, in order to limit the risk of radiation dose due to inhalation of radon by members of the public. This article focuses to study the effects of meteorological parameters on the concentration and distribution of radon in a traditional hammam by both numerical simulations and experiments. The results of the numerical simulations are qualitative and show that the concentration and distribution of radon decrease when the ventilation rate increase, as well as, when the temperature increases, however, it increases with the increase in relative humidity. The results obtained by the numerical simulations were in agreement with those obtained experimentally with a maximum deviation of 7%. Numerical simulations allow a better estimate of the distribution of radon in indoor air. [ABSTRACT FROM AUTHOR]

The high operating temperature of solid oxide fuel cells, can cause serious damage such as cathode delamination or cracking of the SOFC layers, which cause a decrease in the performance of the latter, a rigorous nondestructive inspection is necessary, in particular that their prices are high. In this paper we have treated thermal control by pulsed infrared thermography of the solid oxide fuel cells electrodes, using 3D finite elements method. The thermal images obtained were processed, and a quantitative analysis was performed to obtain information concerning cracks in electrolyte supported and anode supported planar cells, and cathode delamination in electrolyte supported and cathode supported cells. The results obtained as the temperature distribution in the fuel cells, with and without defects, shows the difference between the flawed and the unflawed cells. The thermal response informs us about the presence of the defects, and in addition it informed us about their depths. • The pulsed infrared thermography technique was applied to the oxide fuel cells damages detection. • The technique is based on an instantaneous pulse light excitation. • The results obtained in term of damages detection show the effectiveness of the technique used. [ABSTRACT FROM AUTHOR]

Targeting membrane proteins could improve the efficacy of T cell–based immunotherapies. To facilitate the identification of T cell targets, we developed a hybrid genetic screening system where the Sleeping Beauty (SB) transposon and single guide RNA cassette are nested in an adeno-associated virus (AAV). SB-mediated genomic integration of the single guide RNA cassette enables efficient gene editing in primary murine T cells as well as a screen readout. We performed in vivo AAV–SB-CRISPR screens for membrane protein targets in CD8+ T cells in mouse models of glioblastoma (GBM). We validated screen hits by demonstrating that adoptive transfer of CD8+ T cells with Pdia3, Mgat5, Emp1 or Lag3 gene editing enhances the survival of GBM-bearing mice in both syngeneic and T-cell receptor transgenic models. Transcriptome profiling, single cell sequencing, cytokine assays and T cell signaling analysis showed that Pdia3 editing in T cells enhances effector functions. Engineered PDIA3 mutant EGFRvIII chimeric antigen T cells are more potent in antigen-specific killing of human GBM cells. A hybrid AAV–transposon CRISPR approach enables large-scale in vivo screens in T cells and identifies potential targets for immunotherapy. [ABSTRACT FROM AUTHOR]

This paper investigates a robust controller for the wind energy conversion system (WECS) based on permanent magnet synchronous generator (PMSG) with parametric uncertainties. A robust nonlinear controller is developed for PMSG wind turbine (PMSG-WT) using integral-type terminal sliding mode control (ITTSMC) to ensure maximum aerodynamic power for the system and enhance its performance. The proposed control technique: (i) ensures the convergence of the state variables of the system in finite-time; (ii) reduces the chattering problem in the sliding mode control (SMC); (iii) increases the robustness of the PMSG-WT in the presence of uncertainties. The simulation results for the proposed controller efficiency are performed using the MATLAB/Simulink environment. Besides, a comparative study considers the performance of the suggested control technique with backstepping and SMC techniques. The performance of the ITTSMC method is checked using different situations such as varying wind conditions, parametric uncertainties, and random noise. [Display omitted] • Integral-type terminal sliding mode control (ITTSMC) is proposed for the PMSG-WT. • Finite-time control of the WECS based on PMSG are obtained using the ITTSMC. • Parametric uncertainties and random noise effect are handled by the ITTSMC. • Simulation results are given to verify the effectiveness of proposed ITTSMC approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite some successes of selective anti-BRAFV600E inhibitors, resistance remains a major challenge. The aim of our study is to determine the role of nuclear BRAFV600E and its newly identified partner, HMOX1, in melanoma aggressiveness and drug resistance. We identified the mechanism by which drug resistance is developed via the nuclear localization of BRAFV600E and its partner HMOX1 in melanoma tissues and cell lines. According to our studies, the outcomes of our manuscript have a direct clinical impact on establishing novel prognostic markers and therapeutic intervention strategies in metastatic melanoma. This study provides new information on the ability to selectively classify patients with cytosolic BRAF for selective BRAF inhibitors and offers an alternative treatment to patients with nuclear BRAFV600E and high HMOX1 expressions. Background: Previously, we have demonstrated that nuclear BRAFV600E is associated with melanoma aggressiveness and vemurafenib resistance. However, the underlying mechanisms of how nuclear localization of BRAFV600E promotes cell aggressiveness have not yet been investigated. Despite therapeutic advancements targeting cutaneous melanoma, unknown cellular processes prevent effective treatment for this malignancy, prompting an urgent need to identify new biological targets. This study aims to explore the association of inducible heme oxygenase 1 (HMOX-1) with nuclear BRAFV600E in promoting melanoma aggressiveness. Methods: Proteomics analysis was performed to identify the interacting partner(s) of nuclear BRAFV600E. Immunohistochemistry was applied to evaluate the levels of HMOX-1 and nuclear BRAFV600E expression in melanoma and adjacent healthy tissues. Immunofluorescence assessed the nuclear localization of BRAFV600E in vemurafenib-resistant A375R melanoma cells. Further study of HMOX-1 knockdown or BRAFV600E overexpression in melanoma cells suggested a role for HMOX-1 in the regulation of cell proliferation in vivo and in vitro. Finally, Western blot analysis was performed to confirm the pathway by which HMOX-1 mediates Akt signaling. Results: Proteomics results showed that HMOX-1 protein expression was 10-fold higher in resistant A375R cells compared to parental counterpart cells. In vitro and in vivo results illustrate that nuclear BRAFV600E promotes HMOX-1 overexpression, whereas HMOX-1 reduction represses melanoma cell proliferation and tumor growth. Mechanistic studies revealed that HMOX-1 was associated with nuclear BRAFV600E localization, thus promoting melanoma proliferation via a persistent activation of the AKT pathway. Conclusions: Our results highlight a previously unknown mechanism in which the nuclear BRAFV600E/HMOX-1/AKT axis plays an essential role in melanoma cell proliferation. Targeting HMOX-1 could be a novel method for treating melanoma patients who develop BRAF inhibitor resistance. [ABSTRACT FROM AUTHOR]

Minocycline protects against asthma independently of its antibiotic function and was recently reported as a potent poly-(ADP-ribose) polymerase (PARP) inhibitor. In an animal model of asthma, a single administration of minocycline conferred excellent protection against ovalbumin-induced airway eosinophilia, mucus hypersecretion, and Th2 cytokine production (IL-4/IL-5/IL-12(p70)/IL-13/GM-CSF) and a partial protection against airway hyperresponsiveness. These effects correlated with pronounced reduction in lung and sera allergen-specific IgE. A reduction in poly(ADP-ribose) immunoreactivity in the lungs of minocycline-treated/ovalbumin-challenged mice correlated with decreased oxidative DNA damage. The effect of minocycline on PARP may be indirect, as the drug failed to efficiently block direct PARP activation in lungs of N-methyl-N'-nitro-N-nitroso-guanidine-treated mice or H2O2-treated cells. Minocycline blocked allergen-specific IgE production in B cells potentially by modulating T cell receptor (TCR)-linked IL-4 production at the mRNA level but not through a modulation of the IL-4-JAK-STAT-6 axis, IL-2 production, or NFAT1 activation. Restoration of IL-4, ex vivo, rescued IgE production by minocycline-treated/ovalbumin-stimulated B cells. IL-4 blockade correlated with a preferential inhibition of the NF-κB activation arm of TCR but not GSK3, Src, p38 MAPK, or ERK1/2. Interestingly, the drug promoted a slightly higher Src and ERK1/2 phosphorylation. Inhibition of NF-κB was linked to a complete blockade of TCR-stimulated GATA-3 expression, a pivotal transcription factor for IL-4 expression. Minocycline also reduced TNF-α-mediated NF-κB activation and expression of dependent genes. These results show a potentially broad effect of minocycline but that it may block IgE production in part by modulating TCR function, particularly by inhibiting the signaling pathway, leading to NF-κB activation, GATA-3 expression, and subsequent IL-4 production. [ABSTRACT FROM AUTHOR]

Simple Summary: The three-tiered American Thyroid Association (ATA) risk stratification helps clinicians tailor decisions regarding follow-up modalities and the need for postoperative radioactive iodine (RAI) ablation and radiotherapy. However, a significant number of well-differentiated thyroid cancers (DTC) progress after treatment. Current follow-up modalities have also been proposed to detect disease relapse and recurrence but have failed to be sufficiently sensitive or specific to detect, monitor, or determine progression. Therefore, we assessed the predictive accuracy of the microRNA-based risk score in DTC with and without postoperative RAI. We confirm the prognostic role of triad biomarkers (miR-2f04, miR-221, and miR-222) with higher sensitivity and specificity for predicting disease progression than the ATA risk score. Compared to indolent tumors, a higher risk score was found in progressive samples and was associated with shorter survival. Consequently, our prognostic microRNA signature and nomogram provide a clinically practical and reliable ancillary measure to determine the prognosis of DTC patients. To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues (p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86–3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC. [ABSTRACT FROM AUTHOR]

In this paper, we propose a comparative study of linear and nonlinear algorithms designed for grid-side control of the power flow in a wind energy conversion system. We performed several simulations and experiments with step and variable power scenarios for different values of the DC-link capacity with the DC storage element being the key element of the grid-side converter. The linear control was designed on the basis of the internal model control theory where an active damping was added to avoid steady state errors. Nonlinear controls were built using first and second order sliding mode controls with theoretical considerations to ensure accuracy and stability. We observed that the first order sliding mode control was the most efficient algorithm for controlling the DC-link voltage but that the chattering degraded the quality of the energy injected into the grid as well as the efficiency of the grid-side converter. The linear control caused overshoots on the DC-link voltage; however, this algorithm had better performance on the grid side due to its smoother control. Finally, the second order sliding mode control did not prove to be more robust than the other two algorithms. This can be explained by the fact that this control is theoretically more sensitive to converter losses. [ABSTRACT FROM AUTHOR]

The product development process consists of all the steps required to transform a product from concept to market availability. The volume used to make a product is one of the most important factors affecting the final price of a product and has to be taken into account in the design stage. In this context, a study based on the finite element method was carried out using different geometrical shapes of the same volume by considering the five following shapes: rectangle, I-leg, X-leg, trap-leg, and Y-leg. To achieve this, two cases were examined. In the first case, all five shapes of the same volume (47.915 mm3) were studied by considering an identical length of X-leg (6 mm) and the variable cross-sectional area of the hot ceramic junction. The results obtained show that the rectangular leg model generates the highest efficiency and output power with 5.482% and 0.041 W respectively. In the second case, all shapes of identical volume (47.915 mm3) were analyzed by condensing a variable leg length and a fixed cross-sectional area of the hot ceramic junction of X-leg. The results also show that the rectangular leg model generates the highest output power, which is approximately 0.114 W. In addition, in order to optimize the best model found, the length of the legs allowing to obtain the optimal internal resistance and thermal conductivity has been determined. The findings indicate that the rectangular leg model with a leg length of 6 mm gives the best performance. • Difference of the internal temperature distribution with the variable leg geometry. • Internal resistance and thermal conductivity is influenced by the geometry of leg. • Diverse variable leg geometry with the same leg volumehave an effect on performance of (TEG). [ABSTRACT FROM AUTHOR]