This paper proposes a discrete-time fuzzy fractional-order sliding-mode control (Fuzzy-FOSMC) dual loop current controller for a three-phase LCL-type grid-connected converter (GCC) with reduced ...order. Conventional sliding-mode control (SMC) has been widely used in GCC due to its robustness to disturbances. However, the chattering in SMC may reduce the tracking performance of the controller, and even lead to system instability. To solve this problem, a Fuzzy-FOSMC controller is proposed in this paper. The introduced fractional-order term can suppress the chattering, and the fractional-order of FOSMC is further adjusted by the fuzzy controller to improve the overall system performance. In addition, the inner loop is implemented by a Fuzzy-FOSMC controller to ensure the tracking of the converter-side current, making the LCL-GCC converter behave like a controllable current source converter with a capacitive-inductive filter, the grid current control problem falls from a third-order to a reduced order system, which solves some difficulties on the design of most controller types. The stability of the two-stage PV system is analyzed. Finally, the effectiveness of the proposed controller is verified by experiments.
•A FOSMC controller is proposed for converter-side current tracking control, which makes the converter to behave like a current source inverter with a CL filter. Compared with existing methods, it exhibits great advantages in current convergence speed, steady-state tracking error, robustness to filter parameter variations and dc-bus voltage changes.•To increase the system robustness, based on the fixed parameters of the FOSMC, a fuzzy controller is designed to adjust the fractional order of FOSMC, which could greatly suppress the chattering in conventional SMC.•By establishing the small signal model of the PV LCL grid connected inverter, the matrix of the overall linear state equation of the PV system including MPPT is obtained, and the stability analysis of the PV system is realized.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Future smart grid (SG) has been considered a complex and advanced power system, where energy consumers are connected not only to the traditional energy retailers (e.g., the utility companies), but ...also to some local energy networks for bidirectional energy trading opportunities. This paper aims to investigate a hybrid energy trading market that is comprised of an external utility company and a local trading market managed by a local trading center (LTC). The existence of local energy market provides new opportunities for the energy consumers and the distributed energy sellers to perform the local energy trading in a cooperative manner such that they all can benefit. This paper first quantifies the respective benefits of the energy consumers and the sellers from the local trading and then investigates how they can optimize their benefits by controlling their energy scheduling in response to the LTC's pricing. Two different types of the LTC are considered: 1) the nonprofit-oriented LTC, which solely aims at benefiting the energy consumers and the sellers; and 2) the profit-oriented LTC, which aims at maximizing its own profit while guaranteeing the required benefit for each consumer and seller. For each type of the LTC, the optimal trading problem is formulated and the associated algorithm is further proposed to efficiently find the LTC's optimal price, as well as the optimal energy scheduling for each consumer and seller. Numerical results are provided to validate the benefits of the hybrid energy trading market and the performance of the proposed algorithms.
The Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the Ascomycota. The present work provides an overview of all validly published, currently used ...basidiomycete genera to date in a single document. An outline of all genera of Basidiomycota is provided, which includes 1928 currently used genera names, with 1263 synonyms, which are distributed in 241 families, 68 orders, 18 classes and four subphyla. We provide brief notes for each accepted genus including information on classification, number of accepted species, type species, life mode, habitat, distribution, and sequence information. Furthermore, three phylogenetic analyses with combined LSU, SSU, 5.8s, rpb1, rpb2, and ef1 datasets for the subphyla Agaricomycotina, Pucciniomycotina and Ustilaginomycotina are conducted, respectively. Divergence time estimates are provided to the family level with 632 species from 62 orders, 168 families and 605 genera. Our study indicates that the divergence times of the subphyla in Basidiomycota are 406–430 Mya, classes are 211–383 Mya, and orders are 99–323 Mya, which are largely consistent with previous studies. In this study, all phylogenetically supported families were dated, with the families of Agaricomycotina diverging from 27–178 Mya, Pucciniomycotina from 85–222 Mya, and Ustilaginomycotina from 79–177 Mya. Divergence times as additional criterion in ranking provide additional evidence to resolve taxonomic problems in the Basidiomycota taxonomic system, and also provide a better understanding of their phylogeny and evolution.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Human papillomavirus (HPV)–mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV‐negative OPC and can be successfully treated with ...surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB).
Methods
The NCDB was reviewed for primary HPV‐mediated OPC in 2010‐2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT).
Results
There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple‐modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R2 = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R2 = 0.89). Hospitals in the top treatment volume quartile (quartile 1 Q1; n = 29) had a lower rate of positive margins (16.3%) than bottom‐quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use.
Conclusions
The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient‐, geographic‐, and hospital‐specific factors. Lower hospital volume remains independently associated with increased triple‐modality therapy after adjustments for positive margins, ENE, and pathologic staging.
There is significant national treatment variability for human papillomavirus–mediated oropharyngeal cancer, and the utilization of both surgery with chemoradiation and upfront surgical approaches overall is decreasing. In addition to disease‐specific variables, numerous patient‐ and hospital‐specific variables play an important role in the upfront treatment strategy and the receipt of adjuvant chemoradiation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Species delimitation is one of the most fundamental processes in biology. Biodiversity undertakings, for instance, require explicit species concepts and criteria for species delimitation in order to ...be relevant and translatable. However, a perfect species concept does not exist for Fungi. Here, we review the species concepts commonly used in Basidiomycota, the second largest phylum of Fungi that contains some of the best known species of mushrooms, rusts, smuts, and jelly fungi. In general, best practice is to delimitate species, publish new taxa, and conduct taxonomic revisions based on as many independent lines of evidence as possible, that is, by applying a so-called unifying (or integrative) conceptual framework. However, the types of data used vary considerably from group to group. For this reason we discuss the different classes of Basidiomycota, and for each provide: (i) a general introduction with difficulties faced in species recognition, (ii) species concepts and methods for species delimitation, and (iii) community recommendations and conclusions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Genome editing of allogeneic T cells can provide "off-the-shelf" alternatives to autologous chimeric antigen receptor (CAR) T cell therapies. Disruption of T cell receptor α chain (TRAC) to prevent ...graft-versus-host disease (GVHD) and removal of CD52 (cluster of differentiation 52) for a survival advantage in the presence of alemtuzumab have previously been investigated using transcription activator-like effector nuclease (TALEN)-mediated knockout. Here, we deployed next-generation CRISPR-Cas9 editing and linked CAR expression to multiplexed DNA editing of TRAC and CD52 through incorporation of self-duplicating CRISPR guide RNA expression cassettes within the 3' long terminal repeat of a CAR19 lentiviral vector. Three cell banks of TT52CAR19 T cells were generated and cryopreserved. A phase 1, open-label, non-randomized clinical trial was conducted and treated six children with relapsed/refractory CD19-positive B cell acute lymphoblastic leukemia (B-ALL) (NCT04557436). Lymphodepletion included fludarabine, cyclophosphamide, and alemtuzumab and was followed by a single infusion of 0.8 × 10
to 2.0 × 10
CAR19 T cells per kilogram with no immediate toxicities. Four of six patients infused with TT52CAR19 T cells exhibited cell expansion, achieved flow cytometric remission, and then proceeded to receive allogeneic stem cell transplantation. Two patients required biological intervention for grade II cytokine release syndrome, one patient developed transient grade IV neurotoxicity, and one patient developed skin GVHD, which resolved after transplant conditioning. Other complications were within expectations, and primary safety objectives were met. This study provides a demonstration of the feasibility, safety, and therapeutic potential of CRISPR-engineered immunotherapy.
Abstract
As most of treatment options do not work very well for metastatic cancer. Patients with metastatic cancer have a greatly lower survival rate compared with patients with local cancer. ...Metastasis remains a life-threat to cancer patients and an unmet medical need. The RBP Hu antigen R (HuR) is overexpressed in virtually all malignancies tested, including breast cancer. Cytoplasmic HuR accumulation correlates with high-grade malignancy, poor distant disease-free survival and serves as a prognostic factor for poor clinical outcome in breast cancer. HuR promotes tumorigenesis by promoting mRNA stability and translation of proteins implicated in proliferation, survival, angiogenesis, invasion, and metastasis. We found that silencing of HuR inhibited cell invasion in vitro in breast cancer. Using RIP-seq (ribonucleoprotein immunoprecipitation-sequencing), a transcription factor FOXQ1, which is recently revealed to implicate in breast cancer invasion and metastasis processes, is found to be a direct HuR target. Furthermore, exogenous introduction of FOXQ1 can rescue cell invasive ability inhibited by HuR knockout. Taken together, HuR-FOXQ1 signaling axis is a potential target for blocking breast cancer metastasis. RNA-binding proteins had previously been considered “undruggable” due to lack of a well-defined binding pocket for target RNAs. Using high throughput screening followed by structure-based rational design and lead optimization, we have identified small molecules that inhibit HuR-mRNA interaction at nM to sub-µM potency. Our lead compound, KH-3, potently inhibits breast cancer cell growth and decreases cell invasion in vitro similar to HuR knockout, as well as increasing the expression of epithelial marker E-cadherin. FOXQ1 overexpression abolishes the effect of KH-3 on blocking metastasis in breast cancer cells, demonstrating that the HuR inhibitor KH-3 inhibits cell metastasis by blocking FOXQ1 function. Moreover, KH-3 treatment disrupts HuR-FOXQ1 interaction in RNP-IP and FOXQ1 3′-UTR luciferase reporter assays. In vivo efficacy studies show that KH-3 not only exhibits potent antitumor efficacy in orthotopic xenograft models of breast cancer, but also efficiently blocks lung metastasis in experimental metastatic cancer model. In conclusion, we identified a potent and specific small molecule disrupter of HuR-FOXQ1 interaction for potential novel anti-metastatic therapy of breast cancer with HuR overexpression.
Citation Format: Xiaoqing Wu, Gulhumay Gardashova, Lan Lan, Yu Zhan, Jiajun Liu, Dan A. Dixon, Jeffrey Aubé, Danny R. Welch, Liang Xu. Blocking breast cancer metastasis by targeting HuR-FOXQ1 signaling axis abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 867.
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