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based on the characteristics that the magnitude of active-current vector in the rectifier stage is zero when the zero-voltage vector is used in the inverter stage, a novel Discontinuous Pulse Width Modulation (DPWM) strategy for the indirect matrix converter is proposed in this paper to reduce the common-mode voltage (CMV). In this DPWM strategy, the reference current vector in the rectifier stage is synthesized by two adjacent active-current vectors, and the reference voltage vector in the inverter stage is synthesized by two adjacent active-voltage vectors and one zero-voltage vector. When the inverter stage utilizes one zero-voltage vector, the active-current vector with zero magnitude among the two adjacent active-current vectors, which produce smaller CMV, is selected to apply in the rectifier stage. The DPWM strategy reduces the peak magnitude of common-mode voltage by 42.3% while maintaining the advantages of the traditional DPWM modulation strategy such as less hard switching times in a carrier period, wide voltage transfer ratio, and input/output performance. Finally, the effectiveness of the modulation strategy is verified by simulation and experiments.

Due to the second order harmonic in the phase voltage, the voltage peak value is much higher than the amplitude of its fundamental component in the 6/4 variable flux reluctance machines (VFRMs). Conventionally, the amplitude of the fundamental component in the phase voltage is used to calculate the voltage constraint in flux-weakening control, which results in a large voltage margin and reduces the DC link voltage utilization. To deal with this problem in the VFRMs, the flux-weakening control considering the second order harmonic of the phase voltage is proposed in this paper. In this method, the voltage peak value is used to calculate the current operating points, by using which the maximum voltage utilization in flux-weakening region can be achieved. It shows by using the proposed method a wider the constant torque region owing to the lower voltage margin in the VFRMs, which exhibits higher power output in flux-weakening region. Finally, the method is verified by the test results in the VFRM.

Matrix converter (MC) rotating vector (RV) has the natural advantage for common-mode voltage (CMV) minimization. However, the application of RV in direct torque control (DTC) strategy for motor drive system is limited, mainly due to the extensive torque ripple and current distortion. To improve the steady state torque and current performance of the traditional RV-based DTC, a novel RV- based DTC method is proposed in this paper. According to the analysis of the angle offset between stator flux and the candidate voltage vector, the vector plane is divided into 12 sectors, and virtual vector synthesized by two adjacent rotating vectors is employed to fill in the blank sectors. Based on this, a 12 sector- switching table combined with a novel mapping table of rotating vectors are established to fulfill the proposed RV-DTC method. Experiments are carried out to verify the proposed method. The results show that compared with the traditional RV-DTC, steady state torque and current performances are evidently improved with the proposed RV-DTC at approximate switching frequency, while zero CMV is reserved.

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here we report that the deletion ofPTPMT1,a mitochondria-based phosphatase, critically alters mitochondrial fuel selection – the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced.PTPMT1knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly,PTPMT1deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that PTPMT1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.

The concept of open-current vector for sparse matrix converter is put forward along with its application constraints in this article. Based on the open-current vector, an improved space vector modulation (SVM) strategy is proposed to reduce the peak magnitude of common-mode voltage (CMV) by 42.3% without sacrificing the performance of input and output waveforms and the voltage transfer ratio (VTR). First, the application constraints and common-mode equivalent circuit of the open-current vector in the rectifier stage of the sparse matrix converter are analyzed. After that, in accordance with the principle of minimum switching action and two adjacent active vector synthesis, the improved SVM strategy used a suitable open-current vector instead of the active-current vector in the rectifier stage when the zero-voltage vector is used in the inverter stage, which contributes to CMV reduction. The improved SVM strategy not only reduces the peak magnitude of the CMV, but also ensures that the performance of input and output waveforms and the VTR are the same with those of traditional SVM. Finally, the effectiveness of the improved SVM strategy is verified by simulation and experiments.

Effective strategies to improve charge separation in semiconductor particles are critical for improving the photodegradation of organic pollutants at levels sufficient for environmental applications. Herein, Bi

In the control of variable flux reluctance machine (VFRM) excited by zero-sequence current, neglecting the zero-sequence resistive voltage drop would cause a large calculation deviation of the stator voltage, which can saturate the inverter and influence the switching from constant torque region to flux-weakening region. To solve with this problem, a flux-weakening control method considering the zero-sequence resistive voltage drop for VFRM is proposed. Firstly, the relationship between dq -axis voltages, zero-sequence voltage and the maximum voltage is presented. Secondly, based on the deduced voltage constraint, the calculation of optimal reference currents in flux-weakening region is presented by using Lagrange multiplier method. Since the zero-sequence voltage is considered, the calculation accuracy of the stator voltage and the utilization rate of DC link voltage are improved, which improves the output power capability. Finally, the proposed method is verified by the experimental results.

A novel direct torque control (DTC) is proposed for a matrix converter (MC)-fed permanent magnet synchronous motor (PMSM) drive system in order to minimize common-mode voltage. Rotating vectors are utilized due to the fact that they produce zero common-mode voltage. As the distribution of rotating vectors varies with the input voltage phase, the DTC switching table has to vary for numerous different values of input voltage phase, which will lead to a highly complicated control structure. The merit of the proposed MC–DTC method is that it provides a feasible and fairly simple way to establish a multidimensional switching table for rotating vectors. To fulfill that, six specific values of input voltage phase are selected to approximately represent the whole range of (0, 2π), and the corresponding six switching tables are combined as the multidimensional switching table. Experiments are carried out, and the results show that adequate dynamic and steady-state performance and considerable common-mode voltage reduction are achieved by using the proposed MC–DTC.

A parallel four-quadrant sensing method utilizing a specially designed gold nanodot array is created for sensing virus-like particles with a sub-diffraction limit size (∼100 nm) in a wide-field image. Direct label-free sensing of viruses using multiple four-quadrant sensing channels in parallel in a wide-field view enables the possibility of high-throughput onsite screening of viruses.

A novel direct torque control (DTC) using rotating sector switching table is proposed for a matrix converter (MC) fed permanent magnet synchronous motor (PMSM) system in order to minimise common-mode voltage of the system, exploiting MC rotating vector's advantage of generating zero common-mode voltage. To overcome the difficulty that the angle between adjacent rotating vectors varies according to the phase of input voltage, the rotating vectors are classified into two groups, and each group of vectors have identical rotating direction and fixed angle between adjacent vectors. Rotating sectors of the vector plane are then established, and concise switching table is put forward for the MC-DTC. Experiments are carried out on a 1.6 kW prototype. The results demonstrate considerable common-mode voltage reduction and adequate dynamic performance of the proposed MC-DTC.

Extensively modulating gene expression to achieve optimal flux is a critical step in metabolic engineering. Gene expression is usually modulated at the transcriptional level by controlling the strength of a promoter. However, this type of modulation is often hampered by its inability to fully sample the complete continuum of transcriptional control. In Escherichia coli, this limitation can be solved by constructing promoters with a wide range of strengths. In this study, a highly efficient method was developed to modulate a particular chromosomal gene of E. coli at a wide range of expression levels. This was achieved by combining highly efficient single-stranded oligonucleotide-mediated recombination and a stringent counter selection system kil. Using this strategy, a chromosomal library, with a range from 0.3% to 388% relative to the wild lac promoter, was easily obtained. The strength of our chromosomal promoter library was approximately 5–60 times wider in range than those of libraries reported before.

The ability to identify virus particles is important for research and clinical applications. Because of the optical diffraction limit, conventional optical microscopes are generally not suitable for virus particle detection, and higher resolution instruments such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are required. In this paper, we propose a new method for identifying virus particles based on polarization parametric indirect microscopic imaging (PIMI) and deep learning techniques. By introducing an abrupt change of refractivity at the virus particle using antibody-conjugated gold nanoparticles (AuNPs), the strength of the photon scattering signal can be magnified. After acquiring the PIMI images, a deep learning method was applied to identify discriminating features and classify the virus particles, using electron microscopy (EM) images as the ground truth. Experimental results confirm that gold-virus particles can be identified in PIMI images with a high level of confidence.

The polarization parametric indirect microscopic imaging (PIMI) method, which employs a polarization-modulated incidence illumination and fitting the far-field variation of polarization states of scattered photons, is capable of direct identification of subdiffraction-scale structures and substances, such as virus particles. However, in the present strategy, the optical elements that collect the scattered photons are nearly fixed above the sample, making the collected information relatively limited, as the side-scattering photons are not fully utilized. To address this problem, we propose a multiperspective PIMI imaging method to maximize the collection of scattering photons from different spatial directions, which can obtain more information of optical anisotropy among particles. As a proof-of-concept study, virus detection using such a method is performed theoretically and experimentally. Results reveal that the virus particles can be detected and determined more distinctly thanks to the set of PIMI images from different spatial angles, showing notable superiority to the previous scheme, where only a plane PIMI image is derived from a fixed spatial direction. With the capability of acquiring more characteristics of the samples, the proposed multiperspective PIMI method can be applied in many fields, such as morphological characterization and biosensing.

BackgroundBrucella is an important pathogen causing Brucellosis. Vaccine strains obtained by a single knockout cannot combine low virulence and immunogenicity. Our study modified the SD sequence and spacer sequence of the RBS of Brucella to affect its protein expression. We altered the RBS of LPS-associated genes to reduce LPS-associated protein expression while retaining LPS integrity.ResultsWe first established an evaluation system based on the reporter gene red fluorescent protein mCherry. The mCherry expression could be changed by altering the Shine Dalgarno sequence and spacer sequence of RBS. After optimizing the Shine Dalgarno sequence, mCherry expression was increased 4-fold in E. coli and decreased by 1/4 in Brucella. The mCherry expression was increased 1.5-fold in E. coli and decreased to 1/2 in Brucella when the length of the spacer sequence was 0. When the spacer sequence was NA (N = 4, 8, 12nt) or NG (N = 4, 8, 12nt), mCherry expression was reduced in both E. coli and Brucella. Accordingly, two mutant strains were constructed in an attempt to decrease the expression of LptA and LpxO, Brucella LPS-related genes, by 1/4. Silver staining experiments of LPS SDS-PAGE revealed an alteration in the composition of LPS in the two mutant strains. Polymyxin B experiments revealed that both mutant strains were more sensitive to Polymyxin B resistance.Conclusion: In Brucella, the expression of the target gene could be affected by changing the length or the composition of the RBS sequence. The LPS gene remained unchanged while reducing the expression of its associated protein, achieving the original goal of reducing bacterial virulence while retaining immunogenicity. It is a promising strategy to improve the safety and efficacy of vaccines.

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

Seamless modification of the Escherichia coli genome using positive selection / negative selection is widely used in metabolic engineering and functional genome analysis. Some excellent negative selection systems have been reported, of which tetA-sacB and inducible toxins system are prominent. To expand the existing negative selection toolkit, we constructed a new negative selection marker system based on kil gene of lambda prophage. The selection stringency of kil was measured and compared with the most widely used counter-selection gene, sacB, at the lacI, ack, and dbpa loci using different E. coli strains. At all these loci of tested strains, the selection stringency of kil significantly exceeds that of sacB by 2- to 28-fold. When dsDNA fragments were employed for recombination, the efficiency for isolating the correct recombinant of kil was significantly higher than that of sacB. This new negative selection system does not require special media or extended incubation time. However, our system cannot be used in host strains containing temperature-sensitive kil gene. A Red system providing plasmid without kil gene is recommended for use together with our system. Our counter-selection system is expected to be an addition to the engineering arsenal of E. coli.

The PI3K/AKT/mTOR signaling pathway is constitutively active in PTEN-deficient cancer cells, and its targeted inhibition has significant anti-tumor effects. However, the efficacy of targeted therapies is often limited due to drug resistance. The relevant signaling pathways in PTEN-deficient cancer cells treated with the PI3K/mTOR inhibitor BEZ235 were screened using a phosphokinase array, and further validated following treatment with multiple PI3K/AKT/mTOR inhibitors or AKT knockdown. The correlation between PTEN expression levels and STAT3 kinase phosphorylation in the tissue microarrays of gastric cancer patients was analyzed by immunohistochemistry. Cell proliferation and clonogenic assays were performed on the suitably treated PTEN-deficient cancer cells. Cytokine arrays, small molecule inhibition and knockdown assays were performed to identify related factors. PTEN-deficient tumor xenografts were established in nude mice that were treated with PI3K/AKT/mTOR and/or STAT3 inhibitors. PTEN deficiency was positively correlated with low STAT3 activity. PI3K/mTOR inhibitors increased the expression and secretion of macrophage migration inhibitory factor (MIF) and activated the JAK1/STAT3 signaling pathway. Both cancer cells and in vivo tumor xenografts showed that the combined inhibition of PI3K/AKT/mTOR and STAT3 activity enhanced the inhibitory effect of BEZ235 on the proliferation of PTEN-deficient cancer cells. Our findings provide a scientific basis for a novel treatment strategy in cancer patients with PTEN deficiency.

The high-grade glioma is characterized by cell heterogeneity, gene mutations, and poor prognosis. The deletions and mutations of the tumor suppressor gene PTEN (5%-40%) in glioma patients are associated with worse survival and therapeutic resistance. Characterization of unique prognosis molecular signatures by PTEN status in glioma is still unclear. This study established a novel risk model, screened optimal prognostic signatures, and calculated the risk score for the individual glioma patients with different PTEN status. Screening results revealed fourteen independent prognostic gene signatures in PTEN-wt and three in the -50PTEN-mut subgroup. Moreover, we verified risk score as an independent prognostic factor significantly correlated with tumor malignancy. Due to the higher malignancy of the PTEN-mut gliomas, we explored the independent prognostic signatures (CLCF1, AEBP1, and OS9) for a potential therapeutic target in PTEN-mut glioma. We further separated IDH wild-type glioma patients into GBM and LGG to verify the therapeutic target along with PTEN status, notably, the above screened therapeutic targets are also significant prognostic genes in both IDH-wt/PTEN-mut GBM and LGG patients. We further identified the small molecule compound (+)-JQ1 binds to all three targets, indicating a potential therapy for PTEN-mut glioma. In sum, gene signatures and risk scores in the novel risk model facilitate glioma diagnosis, prognosis prediction, and treatment.

Tanshinone I, one of the components of Salvia miltiorrhiza Bunge, exhibits anti-tumor ability and induces autophagy. But the mechanisms are not fully understood. This study aims to investigate whether AMP-activated protein kinase dependent pathway is involved in the autophagic signaling regulation and its relationship with tumor suppression. Breast cancer cells (MDA-MB-231, MCF-7) and hepatocellular carcinoma cells (HepG2) were treated with Tanshinone I or vehicle. Acridine orange dyeing and transmission electron microscopy were employed to evaluate autophagic cells. MTT and Cell Counting Kit-8 assays were used to detect the effect of Tanshinone I combined with autophagy inhibitors on cell proliferation. Western blot was used to detect the expression levels of Beclin1 and LC3-I/II, as well as the phosphorylation of AMPKα and ULK1. Our results showed that Tanshinone I suppressed proliferation of HepG2, MDA-MB-231 and MCF-7 cancer cell lines. LC3-II and P62 were induced by Tanshinone I in all three cancer cell lines. But autophagic flux analysis showed that Tanshinone I treatment induced autophagy only in MDA-MB-231, which was also proved by transmission electron microscopy. Tanshinone I upregulated the phosphorylation of AMPKα and its downstream ULK1. AMP-activated protein kinase inhibitor compound C attenuated Beclin 1 and LC3-II expression induced by Tanshinone I in HepG2. In MDA-MB-231, compound C surprisingly induced LC3-II upregulation which is independent of AMPKα activation. Under this circumstance, treatment of Tanshinone I combined with compound C significantly inhibited MDA-MB-231 proliferation, compared with Tanshinone I treatment alone. This study demonstrates that Tanshinone I could induce cancer cell death and regulate autophagy signaling in breast cancer and hepatic carcinoma cells. Activation of AMPKα was found to be involved in autophagic signaling regulation by Tanshinone I.

In order to increase fundamental voltage transfer ratio for ultrasparse matrix converter, a novel multimode space vector overmodulation strategy is proposed. First, the relationship among voltage transfer ratio (VTR), the output voltage harmonic distortion rate under three inverter modulation methods and the input current harmonic distortion rate under two rectifier modulation methods is analyzed. After that, according to minimum principle of output voltage and input current harmonics, the three overmodulation modes are divided: the output voltage minimum-phase-error, input current minimum-magnitude-error (MME), and output voltage MME overmodulation strategies are realized in overmodulation mode I, II, and III, respectively. The proposed multimode overmodulation strategy not only extends the maximum VTR to 1.05, but also reduces the output low-frequency harmonic voltage components of the overmodulation mode I and mode II. In addition, the harmonic components of output voltage and input current in overmodulation mode are analyzed by double Fourier integral transform method. Finally, the effectiveness of the proposed multimode overmodulation strategy and the correctness of harmonic analysis method are verified by experiments.

In order to further improve the voltage transfer ratio (VTR) of indirect matrix converter (IMC), a novel space vector overmodulation strategy by modifying the modulation in rectifier stage is proposed. This strategy increases the VTR to 1.05 and achieves no magnitude error between the fundamental output voltage and the reference output voltage. Based on the conventional overmodulation region I and II, the overmodulation region III is added. The main low frequency harmonic component of input and output current is analyzed. Finally, the validity of the novel overmodulation strategy and the correctness of the input and output low frequency harmonic characteristics are verified by experiments.

The isolated dual active bridge (DAB) dc-dc converter with conventional dual-phase-shift (DPS) modulation exhibits large variations of currents under a small change of phase shift ratio at light load and larger peak current and reactive power at non-heavy load. To solve this problem, this paper proposes a novel dual phase shift (NDPS) modulation method based on two degrees of freedom under non-heavy load conditions. By redefining the constraints of two inner phase shift ratios and one outer phase shift ratio, NDPS modulation achieves a wider phase shift adjustment range at non-heavy load, and basically eliminates reactive power. By establishing mathematical models of transmission power, the paper introduces and analyzes the operating principle of the NDPS modulation in detail, and provides the operation mode analysis of the converter. Finally, the effectiveness of the proposed method is verified by experimental result.

In hybrid excited switched flux permanent magnet (HESFPM) machines, the d-axis flux-linkage can be adjusted by both the dc field current (if) and the d-axis current (id). Thus, in the flux-weakening region, the high output power can be obtained by changing the field excitation of HESFPM machine with the limitation of converter constraint. In this paper, a current distributer for the armature and field currents accounting for the winding resistance and magnetic saturation is developed to obtain the maximum output power of HESFPM machine. It shows that by taking the winding resistance and magnetic saturation into consideration the maximum output power is higher than that without accounting for the winding resistance and magnetic saturation. The experiment results on a prototype machine are presented for verification.

In this paper, based on the characteristics of six space vector modulation methods, a variety of Space Vector Over-modulation strategies with voltage transfer ratio of 1.05 for indirect matrix converter is proposed. Firstly, the six space vector modulation methods are combined by adjusting the phase of the input current vector and the amplitude and phase of the output voltage vector. Secondly, the limit input current and output voltage vector characteristics, the limit fundamental voltage amplitude and the main low-frequency harmonic components of the input and output under the six modulation methods are analyzed in detail. According to the limit characteristics of the six modulation methods and the principle of limit vector superposition, multiple space vector over-modulation strategies based on single-mode, double-mode and multi-mode are proposed. Finally, the characteristics of the six space vector modulation methods are verified by experiments.