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This article mainly introduces a discharge circuit structure based on a coupled split inductor (CSI) and its parameter design method to solve the current equalization problem caused by parallel solid-state switches. This article first introduces the working principle of the power conditioning module (PCM) discharge circuit based on the CSI and analyzes the benefits of using this inductor to improve the current equalization of parallel solid-state switches. Then, this article introduces the overall parameter design method of the PCM and proposes a method for allocating overall parameters to unit components, which is calculated by an example. Next, this article analyzes the relationship between the coupled coefficient of the CSI and the delay turn-on voltage of the switch tube and the degree of discharge current distortion, optimizes the coupled coefficient, and proposes a structural parameter design method for the CSI based on this coefficient. Finally, this article applies the above circuit structure and its parameter design method and CSI design method to engineering prototype design. The practice proves that the structure and parameter design methods proposed in this article are effective.

Pre-COVID-19 pandemic, patients who attended the emergency department (ED) for upper respiratory tract infection (URTI) were more likely to receive antibiotics if they expected them. These expectations could have changed with the change in health-seeking behaviour during the pandemic. We assessed the factors associated with antibiotics expectation and receipt for uncomplicated URTI patients in four Singapore EDs during the COVID-19 pandemic.

The spiral inductor is one of the components in the pulse power supply of large laser fusion facility, which plays the role of limiting discharge current and protecting system components. Strong electromagnetic stress and high temperature rise caused by large current greatly limit the current capacity of the spiral inductor and increase the possibility of inductor damage. Taking the 100-kA pulse current as the design goal, based on the particle swarm optimization (PSO) algorithm and the elliptic integral Bartky’s transformation method, a new numerical calculation method for calculating the inductance value of the spiral inductor is established, which can quickly determine the inductance structure parameters that meet the circuit parameter requirements and have the minimum volume and ensure that the temperature rise of the inductor metal coil is within the allowable range. Through the electromagnetic structure coupling simulation, the electromagnetic stress distribution of the inductor is obtained. It is found that the maximum electromagnetic stress appears on the innermost coil. By increasing the radial thickness of the inner insulation frame of the coil, the stress distribution on the inner coil can be reduced and the mechanical strength of the inductor can be satisfied. Experimental results show that the spiral inductor can withstand 171-kA current and 622-kJ energy, and it can meet the requirements of the most serious fault caused by one capacitor internal insulation breakdown.

Deep learning is a novel machine learning technique that has been shown to be as effective as human graders in detecting diabetic retinopathy from fundus photographs. We used a cost-minimisation analysis to evaluate the potential savings of two deep learning approaches as compared with the current human assessment: a semi-automated deep learning model as a triage filter before secondary human assessment; and a fully automated deep learning model without human assessment.

Abstract Efficient clustering in dynamic spatial databases is currently an open problem with many potential applications. Most traditional spatial clustering algorithms are inadequate because they do not have an efficient support for incremental clustering.In this paper, we propose DClust , a novel clustering technique for dynamic spatial databases. DClust is able to provide multi-resolution view of the clusters, generate arbitrary shapes clusters in the presence of noise, generate clusters that are insensitive to ordering of input data and support incremental clustering efficiently. DClust utilizes the density criterion that captures arbitrary cluster shapes and sizes to select a number of representative points, and builds the Minimum Spanning Tree (MST) of these representative points, called R-MST. After the initial clustering, a summary of the cluster structure is built. This summary enables quick localization of the effect of data updates on the current set of clusters. Our experimental results show that DClust outperforms existing spatial clustering methods such as DBSCAN, C2P, DENCLUE, Incremental DBSCAN and BIRCH in terms of clustering time and accuracy of clusters found.

Highly saturated (HS) soybean oil (SBO), which contained 23.3% palmitic acid (C16:0) and 20.0% stearic acid (C18:0), was interesterified at 70°C in preparation for the processing of a trans-free margarine. High-performance liquid chromatography analysis of the triacylglycerides and analysis of the sn-2 fatty acid composition showed no further change after 10 min of interesterification. The interesterified HS SBO had a slip melting point of 34.5°C, compared with 9.5°C in the non-interesterified HS SBO, and increased melting and crystallization temperatures were found using differential scanning calorimetry. Analysis of solid-fat content by nuclear magnetic resonance revealed the presence of only a small amount of solids above 33°C. A 50:50 blend of interesterified HS SBO and SBO with a typical fatty acid composition was used to make the margarine. Compared to commercial soft-tub margarine, the maximal peak force on the texture analyzer of this blended margarine was about 2.3 times greater, the hardness about 2.6 times greater, and adhesiveness about 1.5 times greater. There were small but statistically significant differences (a=0.05) in the sensory properties of spreadability, graininess, and waxiness between the commercial and blended margarines at 4.5°C and, except for graininess, at 11.5°C. These very small differences suggest a potential use for HS SBO in margarine products.

Allogeneic bone marrow transplant (BMT) is the only curative method for a number of monogenic blood disorders, including various forms of hemoglobinopathies and severe combined immunodeficiencies. Aside from the significant hurdle of finding an identical HLA-matched related donor, allogeneic BMT recipients require chronic immunosuppression to mitigate the significant risk of GVHD and are at greater risk for graft failure. Autologous gene modified HSPC potentially provide a much safer alternative to allogeneic BMT and abrogate the need for finding HLA-matched donors. Here, we report the development of a highly efficient process for generating gene modified human HSPC at clinical-scale (>150 x 10^6 cells for 2x10^6/kg) using clinical-grade equipment.

Allogeneic bone marrow transplant (BMT) is the only curative method for a number of monogenic blood disorders, including various forms of hemoglobinopathies and severe combined immunodeficiencies. Aside from the significant hurdle of finding an identical HLA-matched related donor, allogeneic BMT recipients require chronic immunosuppression to mitigate the significant risk of GVHD and are at greater risk for graft failure. Autologous gene modified HSPC potentially provide a much safer alternative to allogeneic BMT and abrogate the need for finding HLA-matched donors. Here, we report the development of a highly efficient process for generating gene modified human HSPC at clinical-scale (>150 x 10^6 cells for 2x10^6/kg) using clinical-grade equipment.Healthy donors were administered Neupogen® (10mg/kg/day) for 4-5 consecutive days and then apheresed. Enrichment of CD34+ cells was performed with the Miltenyi CliniMACS® system. Genome editing was achieved via the introduction of mRNA encoding two engineered zinc finger nucleases (ZFN) using a scalable electroporation device. Cells were harvested and cryo-preserved with a controlled-rate freezer. Cell recovery and viability, gene modification efficiency, stem cell pluripotency and engraftment potential were evaluated by in vitro assays and in a humanized NSG mouse model.Enrichment of CD34+ cells from mobilized leukopak products was highly efficient with the Miltenyi CliniMACS® system (median recovery = 327 million CD34+ cells per 10L mobilized leukopak). The positively selected fractions were >98% CD34+ by FACS analysis. Two large scale electroporation devices (BTX AgilePulse Max® and MaxCyte GT®) were evaluated. Each device is capable of electroporating up to 300 million cells. The optimal transfection conditions for both devices were first identified by using a GFP mRNA to evaluate transfection efficiency by flow cytometry, which resulted in the identification of conditions (voltage and duration) that yielded gene transfer efficiencies of >90%. Compatibility of this protocol with driving endogenous gene modification was evaluated using mRNA encoding ZFNs that target various endogenous gene loci. Highly efficient levels of genome editing were observed in CD34+ HSPC each transfected with a different pair of ZFNs (median = 53%, 43%, 45% and 42% modified alleles at four distinct disease-relevant loci). At the optimal mRNA dose for each ZFN pair, cell viability post electroporation was >80%, comparable to untransfected controls. Process suitability was evaluated by in vitro colony forming cell assay. No significant differences in colony formation were observed between gene modified and untransfected control samples. The capacity of electroporated HSPC to engraft and support multi-lineage development of human hematopoietic cells was evaluated in NSG mice, and no differences were observed between the ZFN-treated and untransfected control cells. In addition, high levels of gene modification (19-28%) were detected in bulk human cells from the blood and tissues of engrafted mice, and in various sorted cell types (bone marrow CD34 and differentiated B and T cells).We have developed a scalable process capable of deriving >300 million gene-modified CD34+ HSPC. This process supports high levels of ZFN-driven genome editing, is well tolerated, and causes no discernable defect in the hematopoietic potential of these cells to develop into multiple cell lineages, with high gene editing levels maintained in the differentiated progeny of the HSPC. These results support the use of gene modified autologus HSPC for the treatment of monogenic blood disorders.Lee: Sangamo BioSciences: Employment. Truong:Sangamo BioSciences: Employment. Wood:Sangamo BioSciences: Employment. Ya-Li:Sangamo BioSciences: Employment. Kim:Sangamo BioSciences: Employment. Zhou:Sangamo BioSciences: Employment. Wang:Sangamo BioSciences: Employment. Reik:Sangamo BioSciences: Employment. Urnov:Sangamo BioSciences: Employment. Holmes:Sangamo BioSciences: Employment. Ando:Sangamo BioSciences: Employment. Giedlin:Sangamo BioSciences: Employment.