Multilevel converters are very widely used for industrial applications as it has various advantages like less distortion and high efficiency. Multilevel converters reduced the need of high rating switches in the converter. High value of output voltage and high value of current can be obtained whenever required by application. It produces multiple levels in output voltage and output current. We used Voltage feedback for the control of the output voltage. Usually PI controller is used for the control of output voltage in order to reduce total harmonic distortion. We replaced PI controller with artificial neural network (ANN) to reduce THD. Learning algorithm in closed loop is implemented and reduction in THD is achieved.

M. Shaminur Rahman1, Md Firoz Ahmed2*, Md Shariful Islam3, Mohammad Moniruzzaman4* 1. Department of Microbiology, Jashore University of Science and Technology, Jashore-7408, Bangladesh.2. Department of Microbiology, Jahangirnagar University, Bangladesh3. Department of Geography, Virginia Polytechnic Institute and State University, VA, USA4. Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, FL, USA * Corresponding authors. Email: m.monir@miami.edu, firoz@juniv.edu

Mariline Poupauda,b, Margot Galièrea,c, Isabelle Dieuzy-Labayed, Nicolas Antoine-Moussiauxb, Marisa Peyreaa UMR ASTRE, Univ Montpellier, CIRAD, INRAE, 34980 Montpellier, France.b Fundamental and Applied Research for Animals and Health (FARAH), University of Liège, 4000 Liège, Belgium.c Association vétérinaires éleveurs du millavois (AVEM), 12100 Millau, France.d World Organisation for Animal Health (OIE), 75017 Paris, France.Corresponding author: Mariline Poupaud. E-mail:mpoupaud@protonmail.com

Background and Purpose: Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes that has limited treatment options. NLRP3-initiated pyroptosis is tightly implicated in DN progression. Mitochondrial ROS (mtROS) are a critical trigger of NLRP3 activation. Syringaresinol, a natural plant-derived polyphenolic compound, possesses strong antioxidant properties. However, whether syringaresinol provides renoprotection in DN remains unclear. Experimental Approach: The renoprotection effects of syringaresinol were investigated in streptozotocin-induced wild-type and Nrf2-KO mice. The underlying mechanism of syringaresinol on DN was assessed in diabetic renal tissues and high glucose-stimulated primary renal tubular epithelial cells as well as glomerular mesangial cells HBZY-1. Key Results: Syringaresinol treatment ameliorated renal structural and functional changes in streptozotocin-induced diabetic mice, including renal hypertrophy, fibrosis, mesangial expansion, glomerular basement membrane thickening, podocyte foot process effacement and albuminuria. Mechanistically, syringaresinol prevented the NLRP3/Caspase-1/GSDMD pyroptosis pathway and promoted Nrf2 expression and nuclear transfer in both diabetic renal tissues and high glucose-stimulated primary renal tubular epithelial cells as well as HBZY-1 cells. After that, the nuclear-transferred Nrf2 upregulated the antioxidant genes HO-1 and MnSOD, thereby effectively improving mitochondrial dysfunction and decreasing excess cytosolic ROS and mtROS. Most importantly, knockout of Nrf2 abolished the syringaresinol-mediated renoprotection and antioxidant effects and subsequent mtROS overproduction, resulting in the activation of NLRP3/Caspase-1/GSDMD signaling. Conclusion and Implications: Syringaresinol attenuated diabetic renal lesions by preventing the NLRP3/Caspase-1/GSDMD pyroptosis pathway in an Nrf2-dependent manner. This suggests that syringaresinol may represent promising therapeutic options for DN.

Background and Purpose: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of BLA astrocytes in DNP pathogenesis and provide new insights into DNP therapeutic strategies. Experimental Approach: A streptozotocin-induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate the activity of astrocytes. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety-like behaviors were detected by open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA. Key Results: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and anxiety-like behavior in DNP rats. Contrastively, temporary activation of BLA astrocytes induced allodynia without anxious behavior in naive rats. In addition, we found that koumine alleviates mechanical allodynia and anxiety-like behavior in DNP rats, inhibits the activation of BLA astrocytes and suppresses the inflammatory response. Furthermore, persistent activation of BLA astrocytes by chemogenetic mimics chronic pain, and koumine can alleviate its pain hypersensitivity and anxiety-like behavior. Conclusion and Implications: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocytes activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. Koumine ameliorated DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.

Background and Purpose: Cancer stem cells (CSCs) are a type of cancer cell owning the characteristic of self-renew and differentiation.We hypothesize that the stemness properties in CD44v6+ hepatocellular carcinoma cells (HCC) is promoted via the Met/cjun/Nanog signaling pathway, thus, serves as a valuable target for HCC therapy. Experimental Approach: We use lentiviral shMet and selective Met inhibitor PHA665752 to explore the function of Met/cjun/Nanog axi in CD44v6+ cells. The orthotopic liver xenograft tumor model was used to detect self-renewal ability of CD44v6+ cells. Furthermore, a luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were carried out to find the exact binding site of cjun in the Nanog promoter. Key Results: In this study, we demonstrated that CD44v6+ CSCs not only facilitate the properties of cancer stemness, but also represent the high expression of the HGF/MET signal pathway. Inhibiting the activation of Met in CD44v6+ HCC cells in vidvo and in vitro significantly decrease the expression of cjun and Nanog. Furthermore, we found a binding site of cjun in 1700bp before the transcription start site of Nanog. Conclusion and Implications: The stemness properties of CD44v6+ cells is promoted by the Met/cjun/Nanog signaling pathway. And the cjun is binding in 1700bp before the transcription start site of Nanog. KEYWORDS：Hepatocellular Carcinoma, Cancer Stem Cells, HGF/MET, CD44v6, cjun

A document by Aviti T. Mushi. Click on the document to view its contents.

Climate change alters global mean surface temperatures and precipitation regimes. This changes the composition and diversity of grasslands worldwide. To date, there are no assessments of plant functional trait responses to experimentally controlled atmospheric drought (separate from soil drought). We examined whether soil and atmospheric drought result in changes to Poa secunda functional traits in monoculture and 8-species grass communities. We focused on SLA, leaf area, stomatal density, root:shoot ratio, and fine root:coarse root ratios. Leaf area and overall growth were higher with increased watering and higher atmospheric moisture in most cases. However, root:shoot ratio significantly increased in atmospheric drought combined with drought watering. Plant energy allocation strategy (measured using PCA) differed when P. secunda was grown in combination soil and atmospheric drought conditions. Our results indicate that methods focused purely on soil water inputs, such as rainout shelters, may be imprecisely predicting drought effects.

The objective of this study was to identify if delayed routine pessary reviews during the covid-19 pandemic (as per the guidance from Royal College of Obstetrics and Gynaecology and British Society of Urogynaecology) led to an increase in complication rates. A retrospective comparative cohort study was conducted in NHS Tayside, Scotland involving 300 patients (150 pre-pandemic and 150 during the covid-19 pandemic). Their notes were reviewed to identify age, care provider, pessary type, length of pessary usage, review date, timeframe from previous review, bleeding/infection/ulceration, removal issues, pessary replacement and outcome. Exclusion criteria was applied: Patients with no pessary insitu at review, reviews at 8 months (pre-pandemic) and reviews at

The conflicting selection pressures of advertising to conspecifics and inadvertently advertising to predators has direct fitness consequences. It is unclear, however, how signalling prey species balance costs and benefits of those vital tasks over their lifetime. To address this, we quantified how a prey species with a conspicuous courtship song, the bush-cricket Tettigonia viridissima (Orthoptera: Tettigoniidae), adjusts its singing behaviour in response to increasing threat levels of bat predation and how those adjustments change in the course of its lifetime. We show that young males favour predator avoidance over mating by acoustically hiding from predators for a longer time, while old males prioritize mating opportunities over predator avoidance. Thus, males of different ages trade-off differently the risk of losing mating opportunities against the risk of falling prey to bats. This illustrates that prey species balance the costs and the benefits of reproduction and survival throughout their lifetime. Our results highlight the flexibility of vital behaviours and demonstrate how they are balanced over a lifetime to maximize fitness.

By-products of bioethanol production, such as vinasse can be transformed by biotechnological processes into valuable compounds. In this work, the economic feasibility of producing poly(hydroxyalcanoate)s (PHAs) from vinasse and diverse microorganisms was studied employing a superstructure whose objective function is the maximization of the Net Present Value (NPV). The model was run employing data reported in the literature about PHAs productivities obtained by using different bacteria strains and vinasse as carbon source. Thus, comparison of different scenarios is shown from techno-economic and environmental aspects. Mathematical model estimated that PHA production cost was 2.27 - 3.02 USD and the investment resulted 9- 13 million dollars. The energy consumption was also calculated and it was 13.8 - 21 MJ/Kg PHA. The model returned NPV negative values in those scenarios with low accumulation and low yield of PHAs, indicating that benefits are not being obtained and, therefore, would not meet the expectations for an investment project. Positive NPV values were obtained, being the highest one 35.09 million dollars. Results evidenced that microorganism selection, concentration of the pretreated vinasse, and inorganic salts in the culture media would be the most relevant factors to take into account when designing a PHA production plant.

"AI & Drug Discovery" mode has significantly promoted drug development and achieved excellent performance, especially with the rapid development of deep learning, making remarkable contributions to protecting human physiological health. However, due to the "black-box" characteristic of the deep learning model, the decision route and predicted results in different research stages assisted by deep models are usually unexplainable, limiting their application in practice and more in-depth research of drug discovery. Focusing on the drug molecules, we propose an explainable fragment-based molecular property attribution technique for analyzing the influence of particular molecule fragments on properties and the relationship between the molecular properties in this paper. Quantitative experiments on 42 benchmark property tasks demonstrate that 325 attribution fragments, which account for 90% of the overall attribution results obtained by the proposed method, have positive relevance to the corresponding property tasks. More impressively, most of the attribution results randomly selected are consistent with the existing mechanism explanations. The discovery mentioned above provides a reference standard for assisting researchers in developing more specific and practical drug molecule studies, such as synthesizing molecular with the targeted property using a fragment obtained from the attribution method.Corresponding author(s) Email:   brooksong@zju.edu.cn  

A 69-year-old woman with mechanical aortic valve presented with decompensated heart failure. Emergent echocardiogram and fluoroscopy demonstrated acute aortic regurgitation due to a dysfunctional mechanical aortic valve and non-obstructive coronary disease. An emergent valve replacement was performed confirming fixed-open valve with pathology demonstrating obstructive pannus formation without thrombosis or vegetation.

We wish to describe the omission of adverse event reporting on finerenone in a recently published trial. We suspect that this case illustrates the tip of an iceberg of underreporting of adverse events in clinical trials. We propose as a requirement in clinical trials, to have routine direct reporting by patients for safety monitoring.

A 28-year-old male with a childhood history of osteopetrosis treated with a stem cell transplantation (SCT) presented with chronic fatigue, malaise, and abdominal pain. CT imaging identified a left lung nodule with osseous, hepatic, and splenic metastases, and diffuse lymphadenopathy. Hepatic biopsy demonstrated metastatic pulmonary adenocarcinoma, ALK-mutated. He received alectinib with an excellent radiographic response maintained a year later. Recipients of a SCT have an increased risk of secondary solid cancer (SSC) and a cumulative incidence of 10-15% by 15-years. Awareness and screening for SSCs are essential for an earlier diagnosis and the possibility of improved outcomes.

A document by Chinnaraji Annamalai. Click on the document to view its contents.

Background T-cell lymphoblastic lymphoma (T-LBL) is an aggressive neoplasm closely related to T-cell acute lymphoblastic leukaemia (T-ALL). Despite their similarities, and contrary to T-ALL, studies on pediatric T-LBL are scarce and, therefore, its molecular landscape has not been fully elucidated yet. Procedure To characterize the genetic and molecular heterogeneity of paediatric T-LBL, 33 patients were analyzed using an integrated approach, including targeted next generation sequencing, RNA-sequencing transcriptome analysis and copy-number arrays. Results Copy number and mutational analyses allowed the detection of recurrent homozygous deletions of 9p/CDKN2A (78%), trisomy 20 (19%) and gains of 17q24-q25 (16%), as well as frequent mutations of NOTCH1 (62%), followed by BCL11B (23%), WT1 (19%) and FBXW7, PHF6 and RPL10 genes (15%, respectively). This genetic profile did not differ to that described in T-ALL in terms of mutation incidence and global genomic complexity level but unveiled virtually exclusive 17q25 gains and trisomy 20 in T-LBL. Additionally, we identified novel gene fusions in paediatric T-LBL including NOTCH1-IKZF2, RNGTT-SNAP91 and DDX3X-MLLT10, the latter being the only one previously described in T-ALL. Moreover, clinical correlations highlighted the presence of Notch pathway alterations as a factor related to favorable outcome. Conclusions In summary, the genomic landscape of paediatric T-LBL is similar to that observed in T-ALL and Notch signaling pathway deregulation remains the cornerstone in its pathogenesis, including not only mutations but fusion genes targeting NOTCH1.

BACKGROUND: Rhabdomyosarcoma (RMS) is an aggressive malignancy, and 20% of children present with metastases at diagnosis. Patients presenting with disseminated disease very occasionally have no clear evidence of a primary tumor mass. Since these patients have rarely been investigated, we report on a series of patients with RMS and unknown primary tumor site registered in the MTS 2008 protocol (October 2008 - December 2016) coordinated by the European pediatric Soft tissue sarcoma Study Group. METHODS: Patients were administered 9 cycles of induction chemotherapy, and 48 weeks of maintenance chemotherapy. Surgery and/or radiotherapy was planned after the first assessment of tumor response, and implemented after six cycles of chemotherapy. If feasible, radiotherapy to all sites of metastasis was recommended. RESULTS: We identified 10 patients with RMS and unknown primary site, most of them adolescents (median age 15.8 years, range 4.6-20.4). Nine had fusion-positive alveolar RMS. Multiple organ involvement was identified in 7 patients, 2 only had bone marrow disease, and 1 only had leptomeningeal dissemination. All patients were given chemotherapy, 4 were irradiated, and none had surgery. Three patients underwent allogeneic bone marrow transplantation. At the time of this analysis, only 2 patients are alive in complete remission: 1 had received radiotherapy; and 1 had a bone marrow transplant. CONCLUSIONS: RMS with unknown primary tumor occurs mainly in adolescents and is typically fusion-positive alveolar. Radiotherapy may be important, but survival is poor and patients should be offered enrollment in investigational trials.

The adaptive significance of polyploidy has been extensively debated and chromosome level genome assemblies of non-model polyploids can provide insight into this topic. The Australian grass, Bothriochloa decipiens, belongs to the BCD clade, a group with a complex history of hybridization and polyploidy. We sequenced, assembled and annotated a chromosomal level genome reference of Bothriochloa decipiens using linked read sequencing and proximity ligation scaffolding. Comparative analysis revealed that the species is a diploidized allotetraploid. We grouped the 20 major scaffolds, representing the 20 chromosomes, into the two subgenomes of the parental species using unique repeat signatures. We found evidence of biased fractionation as well as differences in the activity of TEs between the subgenomes prior to hybridization. Genes retained as duplicates were enriched for biological functions such as transcription and response to external stimuli such as drought, supporting theories of biased duplicate gene retention following WGD events. This is a widespread species with the ability to establish well on many soil types easily, making it useful for ecological restoration of Australian grasslands. This reference genome is a valuable resource for future population genomic research involving Australian grasses which may be helpful in decision making during the ecological restoration processes.

Background: Coronary artery bypass grafting (CABG) may be performed with or without cardiopulmonary bypass (CPB). The Society of Thoracic Surgeons (STS) provides a preoperative risk assessment tool for CABG and reports postoperative outcomes from a database that is updated quarterly. This manuscript aimed to analyze the preoperative risk and postoperative outcomes in a subset of CABG patients with ejection fraction < 40% utilizing a pump-assisted beating-heart technique. These study results were compared to the STS risk calculator and database. Methods: A single-center observational study of 108 patients undergoing pump-assisted direct coronary artery bypass (PAD-CAB) surgery with an ejection fraction < 40% were examined. All patients were evaluated preoperatively with the STS risk assessment calculator. Postoperative outcomes were compared with the expected outcomes using the Wilcoxon signed-rank test and the area under the receiver operating characteristic curve (AUC). Results: The STS-predicted rates for mortality (3.3% vs 2.7%, P = 0.11) and composite morbidity or mortality (21.4% vs 7.4%, P < .001) were higher than the observed. STS showed poor discriminatory power for mortality (AUC = 0.48), reoperation (AUC = 0.48), morbidity (AUC = 0.51) and prolonged length of stay (AUC = 0.62). Discussion: PAD-CAB results compare favorably to the STS database predicted outcomes for CABG. However, comparison of the study group to STS is problematic because specific STS risk calculator definitions are subjective, and database outcomes do not consider the technique of PAD-CAB. Further refinements in these areas are necessary.

This is an invited commentary and does not need a commentary.

By taking Sugeno-derivative into account, firstly, we investigate the existence of solutions to the initial value problems (IVP) of first-order differential equations with respect to non-additive measure (more precisely, distorted Lebesgue measure). It particularly occurs in the mathematical modeling of biology. We begin by expressing the differential equation in terms of ordinary derivative and the derivative with respect to the distorted Lebesgue measure. Then, by using the fixed point theorem on cones, we construct an operator and prove the existence of positive increasing solutions on cones in semi-order Banach spaces. In addition, we also use Picard’s-Lindel\”of theorem to prove the existence and uniqueness of the solution of the equation. Second, we investigate the existence of a solution to the boundary value problem (BVP) on cones with integral boundary conditions of a mix-order differential equation with respect to non-additive measures. Moreover, the Krasnoselskii fixed point theorem is also applied to both BVP and IVP and obtains at least one positive increasing solution. Examples with graphs are provided to validate the results.

Determining an optimal protein configuration for the employment of protein binding analysis as completed by Temperature based Replica Exchange Molecular Dynamics (T-REMD) is an important process in the accurate depiction of a protein’s behavior in different solvent environments, especially when determining a protein’s top binding sites for use in protein-ligand and protein-protein docking studies. However, the completion of this analysis, which pushes out top binding sites through configurational changes, is an polynomial-state computational problem that can take multiple hours to compute, even on the fastest supercomputers. In this study, we aim to determine if graph cutting provide approximated solutions the MaxCut problem can be used as a method to provide similar results to T-REMD in the determination of top binding sites of Surfactant Protein A (SP-A) for binding analysis. Additionally, we utilize a quantum-hybrid algorithm within Iff Technology’s Polar+ package using an actual quantum processor unit (QPU), an implementation of Polar+ using an emulated QPU, or Quantum Abstract Machine (QAM), on a large scale classical computing device, and an implementation of a classical MaxCut algorithm on a supercomputer in order to determine the types of advantages that can be gained through using a quantum computing device for this problem, or even using quantum algorithms on a classical device. This study found that Polar+ provides a dramatic speedup over a classical implementation of a MaxCut approximation algorithm or the use of GROMACS T-REMD, and produces viable results, in both its QPU and QAM implementations. However, the lack of direct configurational changes carried out onto the structure of SP-A after the use of graph cutting methods produces different final binding results than those produced by GROMACS T-REMD. Thus, further work needs to be completed into translating quantum-based probabilities into configurational changes based on a variety of noise conditions to better determine the accuracy advantage that quantum algorithms and quantum devices can provide in the near future.

Introduction: Left bundle branch pacing (LBBP) is a developing method of native conduction pacing, but cases of injury to the septal perforator arteries during implantation have been reported. Knowing the distance between the His bundle and the first septal perforator artery can help operators implant LBBP leads more safely Methods: Using previously performed coronary CT angiography (CCTA) studies, the distance between the His bundle and the first septal perforator was measured. Results: A total of 50 CCTA studies were included. The mean distance from the His bundle to the first septal perforator (His-SP) along the line connecting the His bundle to the RV apex (His-RV apex) was 27.17 ± 7.7 mm with a range of 13.0 to 44.7 mm. The distance was greater than 2.0 cm in 90% of patients. To standardize this distance among patients with varying cardiac structures, the ratio between the His-SP distance and the His-RV Apex distance was also measured. The mean His-SP:His-RV Apex was 0.302 and the median was 0.298. 86% of patients had a ratio of greater than 0.20. Conclusion: Using this information, operators can aim to implant LBBP leads within 2.0 cm of the His bundle or 20% of the distance between the His bundle and the RV apex with minimal risk of causing vascular injury.