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Thermal control of semiconductor devices in the submodules (SMs) is a key factor for the safe and reliable operation of modular multilevel converters (MMCs). During normal operation, significant thermal differences can arise among SMs due to the manufacturing tolerance and aging effect of capacitors, which can affect the lifespan of semiconductor devices and even lead to equipment failure. To address the problem, this paper presents a method for achieving thermal balancing among SMs with different capacitances by adjusting their switching principle. Firstly, the relationship between the degree of capacitance degradation and the junction temperature difference among SMs is revealed. Then, by setting data windows to capture the dynamic losses of power devices, which can reflect the trend of junction temperature. The switching principle of thermal balance among SMs is studied based on the trend of junction temperature in power devices. The thermal balancing method has advantages including not requiring high-precision temperature sensors and eliminating the reliance on capacitance monitoring technology. Finally, the simulation and experimentation results demonstrate that the proposed method can effectively achieve balanced junction temperatures of power devices among different SMs.

The friction consolidation method successfully reinforced aluminum 7075 alloy (AA7075) with high-volume fractions (12 and 24 vol%) of titanium diboride (TiB2) by high pressure and severe plastic deformation at elevated temperatures. The consolidated AMCs have a uniform dispersion of submicron- and micron-sized TiB2 particles in the AA7075 matrix, with significant refinement of the matrix grain size and the particles. The addition of TiB2 significantly increases hardness by up to 50 %, Young’s modulus by up to 62 %, and ultimate tensile strength by up to 28 % to 672 MPa, while reducing ductility by 80 %. Wear resistance of 7075/24 vol% TiB2 improves seven-fold compared to baseline, making it comparable to that of carburized steels. Microstructure-based finite element modeling provided a theoretical strength limit of ∼730 MPa for the composites and indicated that high triaxiality in conjunction with severe equivalent plastic strain in a narrow area between the TiB2 particles led to early fracture initiations, limiting the ductility.

The voltage source converter (VSC) based HVDC (high voltage direct current system) offers the possibility to integrate other renewable energy sources (RES) into the electrical grid, and allows power flow reversal capability. These appealing features of VSC technology led to the further development of multi-terminal direct current (MTDC) systems. MTDC grids provide the possibility of interconnection between conventional power systems and other large-scale offshore sources like wind and solar systems. The modular multilevel converter (MMC) has become a popular technology in the development of the VSC-MTDC system due to its salient features such as modularity and scalability. Although, the employment of MMC converter in the MTDC system improves the overall system performance. However, there are some technical challenges related to its operation, control, modeling and protection that need to be addressed. This paper mainly provides a comprehensive review and investigation of the control and protection of the MMC-based MTDC system. In addition, the issues and challenges associated with the development of the MMC-MTDC system have been discussed in this paper. It majorly covers the control schemes that provide the AC system support and state-of-the-art relaying algorithm/ dc fault detection and location algorithms. Different types of dc fault detection and location algorithms presented in the literature have been reviewed, such as local measurement-based, communication-based, traveling wave-based and artificial intelligence-based. Characteristics of the protection techniques are compared and analyzed in terms of various scenarios such as implementation in CBs, system configuration, selectivity, and robustness. Finally, future challenges and issues regarding the development of the MTDC system have been discussed in detail.

The integration of renewable energy sources in Medium-/High-voltage DC grids has called up continuous research to develop DC-DC conversion systems. This paper presents a hybrid modular multilevel DC-DC converter topology which successfully overcomes the issue of capacitors voltage imbalance during DC-DC conversion. In the proposed topology, single MMC leg is employed with half-bridge submodules in the upper arm and full-bridge submodules in the lower arm along with soft-switched high-voltage valves. The proposed hybrid modular multilevel converter has inherited arm energy equalization with the help of the parallel connectivity of involved arms’ capacitors. During the equalization period, the series-connected upper arm capacitors are connected in parallel to the series-connected lower arm capacitors to transfer the energy between the involved arms which results in operating with balanced capacitors voltages. The proposed modular DC-DC converter is a bidirectional converter which allows power flow from high-voltage side to low-voltage side and vice versa, i.e., it can be operated successfully as a DC transformer. The operational concept of the proposed configuration, control strategy, and parameters design are presented. Simulation results are presented along with experimental results of a scaled-down prototype to validate the proposed approach. Simulation and experimental results show the viability of the suggested approach.

Modular multilevel converter (MMC), which is highly modular, easy to be expanded, and has good output voltage waveform, is especially suitable for medium and high voltage power system applications. The MMC bridge arm inductance fault and the independent sub-module fault have the greatest influence on the transmission quality of transmission systems. However, there is few research on fault diagnosis and location for multiple sub-modules(SM) in a single arm at present. A deep bidirectional Long Short Term Memory (Bid-LSTM) network is proposed in this paper, which is used to diagnose and locate the faults of different sub-modules. which can deal well with the prediction problem with sequence dependence. In addition, because the Bid-LSTM model contains many hyperparameters, which seriously affects the prediction performance of BiD-LSTM, an optimal fruit fly optimization (FOA) algorithm based on the composite chaotic mapping of 3-dimensional Logistic-Sine (3d-CCFOA), which searches the optimal value of related hyperparameters to ensure the accuracy of classification. 3d-CCFOA has good chaos characteristics, which enables FOA to avoid falling into local optimal solution effectively and obtains an effective global optimal solution. Then, the MMC simulation system of RT-TAB is used to simulate the open circuit faults of different independent sub-modules of one bridge arm and collect relevant fault data. The analysis process and experimental results adequately indicate that this method can effectively and accurately diagnose and locate the faults of independent sub-modules. Meanwhile, this method also provides a reference diagnosis strategy for multi-bridge arm fault diagnosis and multi-sub-module location.

Modular multilevel converter (MMC) topology has received widespread attention in flexible DC transmission, power quality control, and other fields because of its high modularity and malleability characteristics, and has become one of the most promising topologies. However, owing to the characteristics of the MMC itself, the fluctuation of the capacitor voltage of the MMC sub-module is inversely proportional to the MMC working frequency. One of the main technical challenges for MMC is effectively suppressing the fluctuation of the capacitor voltage of the MMC sub-module when working at low frequencies. This study first analyzes the reasons for the fluctuation of the MMC sub-module capacitor voltage at low frequency. Then, based on the results of this analysis, we propose a suppression control strategy for the capacitor voltage fluctuation of the MMC sub-module in variable-frequency working situations. Finally, an MMC module was built using the MATLAB/Simulink environment for simulation verification, and a five-level MMC physical experimental platform was built for experimental verification. The simulation and experimental results demonstrate that the proposed suppression control strategy for the MMC sub-module capacitor voltage effectively suppresses the fluctuation of the capacitor voltage under variable-frequency working situations.

Modular multi-level converter (MMC)-based multi-terminal dc (MTDC) grid (abbreviated as MMC-MTDC) is promising in the integration and transmission of bulk renewable energy. This paper analyzes the transient characteristic of large-scale power systems with the MMC-MTDC. First, the transient stability-electromagnetic transient (TS-EMT) model of the system is established. The corresponding simulation flowchart is also presented, where the MMC-MTDC grid dynamics are calculated by EMT simulation and the ac grid is simulated by the TS program. Second, based on the mathematical model of the MMC-MTDC grid, the transient characteristics during various faults are analyzed. Third, it analyzes the influences of the controller parameters on the transient characteristics. Test results on the North-China power system with Zhangbei MTDC verifies the correctness of the transient characteristic analyses.

The United Kingdom (UK) construction industry is world renowned for its volatile boom and bust cycle, its inefficiencies, heavy environmental impact and recurring budget and programme overruns. The Construction 2025 Strategy was published by the UK Government and industry leaders with a vision of changing the industry for the better using four key targets i.e., reduction in construction projects duration, operational cost, level of greenhouse gas emissions, and import/export trade gap. This paper investigates whether a greater uptake in modern methods of construction (MMC) could help us achieve these targets. Key insights and findings from the existing literature on MMCs cost, time, greenhouse gas emissions and trade factors were analysed with strong indications of MMCs benefit to the targets. By using snowball sampling a quantitative survey was conducted on 134 professional working in the Architectural, Engineering and Construction sectors of UK with 23 questions on the four key targets. Cronbach’s Alpha and Pearson correlation analysis techniques were employed in conjunction with factor ranking to determine the internal validity, factor links and most important factors. The results showed that the majority of respondents believed that MMC could help us achieve the construction 2025 targets, with a similarity index ranking revealing that MMC would be of the most benefit to the greenhouse gas emissions and trade targets, however, all factors ranked tightly together. This body of research will benefit the UK Government, construction associations and industrial key stakeholders in their pursuit of reaching the reduction targets, and with only three years until the deadline, there is a strong chance they will promote MMC in the industry.

Monoclonal antibodies (mAbs) continue to dominate the biopharmaceutical industry. Certain mAbs are prone to fragmentation and clipping and in these cases, adequate removal of these species is critical during manufacturing. Fragments can be generated during fermentation, purification, storage, formulation, and administration. Their addition to the acidic charge-variant of the purified mAb has been reported to decrease stability and potency of the final product. However, contrary to mAb aggregation, manufacturers have not given much attention to removal of fragments and clipped species and as a result most conventional mAb platforms offer at best limited capabilities for their removal. In this study, we propose a novel purification platform that uses multimodal chromatography and achieves complete removal of a range of mAb fragments and clipped products (25-120 kDa). The utility of the platform has been successfully demonstrated for 2 IgG1s and 2 IgG4s. Further, adequate removal of the various host cell impurities such as host cell proteins (<10 ppm) and host cell DNA (<5 ppb) has been achieved. Finally, the platform was able to deliver adequate removal of high molecular weight impurities (<1 %) and a 30 % clearance of the acidic charge variant. The proposed single step has been shown to deliver what the polishing chromatography and intermediate purification chromatography steps deliver in a traditional mAb platform., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anurag Singh Rathore, PhD reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. Vineela Peruri reports financial support was provided by Council of Scientific & Industrial Research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

On the present work the objective is to manufacture a AA2014+10 vol-% Intermetallic (NbAl3 or FeAl2 ) metal matrix composites. Since Powder Metallurgy route was chosen, the powder mixtures of metallic powders which forms AA2014 alloy and intermetallic powders were obtained by mechanical alloying. Powder mixtures were cold die pressing and green samples were hot extruded. As result of this intermetallic addition, mechanical properties of AA2014 alloy are improved and a tensile strength of 516 MPa on AA2014+NbAl3 and 465MPa on AA2014+FeAl2 within an elongation close to 2% on both metal matrix composite materials are reached.El objeto del presente trabajo es la obtención de los materiales compuestos AA2014 +10 vol-% NbAl3 o FeAl2. Para ello se realizó la mezcla inicial de los polvos metálicos que constituyen la aleación AA2014 y de los polvos de estos intermetálicos seguido de su aleación. Las mezclas obtenidas se compactaron en frío y los compactos en verde se extruyeron en caliente. Como resultado de la adición de los intermetálicos se mejoran las propiedades mecánicas de la aleación AA2014, alcanzándose resistencias a tracción de 516 MPa para el AA2014+NbAl3 y de 465MPa para el AA2014+FeAl2, con un alargamiento próximo al 2.0% en ambos materiales compuestos de matriz metálica.

This paper suggests a methodology for the identification, classification, and evaluation of various types of interactions that may occur in an HVDC link based on modular multi-level converters (MMC). The methodology incorporates the most suitable analytic tools for the frequency-domain study of each interaction category. To do so, a detailed nonlinear model of an MMC-based HVDC link that consists of master and slave MMCs, AC grids, and the DC transmission system is derived. Then, it is linearized to obtain a multi-input multi-output (MIMO) linear model that represents the dynamics of the complete MMC-based HVDC link. Based on the control loops of interest, interactions are classified as (1) state variable interactions, (2) disturbance interactions, (3) control loop interactions, and (4) overall system interactions. Then, through the application examples, the mentioned four categories of interactions are studied in frequency domain via the relevant analytic tools. The results obtained from the frequency-domain analysis are validated by time-domain simulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Thebaine is an alkaloid and can be found in poppy seeds in relatively high concentrations. Acute toxicity of thebaine is fairly high, but not much is known about chronic toxicity. To investigate the genotoxicity of thebaine, cytokinesis-block micronucleus test and comet assay were conducted in TK6 cells. In addition, effects of putative thebaine metabolites were analysed using metabolically active HepG2 cells and TK6 cells with S9 mix. FDA test and trypan blue test were used together with the frequency of mitotic and apoptotic cells to assess potential cytotoxicity of thebaine treatment. Micronucleus induction was observed after high doses (150 and 500 μM) of thebaine without metabolic activation in the presence of slight to moderate cytotoxicity. No effects were observed in the comet assay or after metabolic activation up to the highest dose of 500 μM. A potential protective effect on micronucleus induction after thebaine treatment was investigated via co-treatment with MMC and BaP in TK6 cells. Only after co-treatment with MMC, a reduction of micronucleus frequency was found. Overall, this study shows a potential of thebaine to induce genotoxic effects at high concentrations. The observation of cytotoxicity at these concentrations supports the hypothesis that genotoxicity may be caused by cytotoxic effects. Further studies will need to elucidate whether these effects are directly genotoxic or indeed result from cytotoxicity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mast cell-deficient mice are helpful for understanding the roles of mast cells in vivo. To date, a dozen mouse models for mast cell deficiency have been reported. However, mice with a specific depletion of all populations of mast cells have not been reported. We generated knock-in mice, termed Mcpt5/Cma1 DTR mice, expressing human diphtheria toxin A (DT) receptor under the endogenous promoter of Mcpt5 (also known as Cma1), which encodes mouse mast cell protease-5. Flow cytometry and histological analysis showed that intraperitoneal injection of DT induced almost complete depletion of mast cells in heterozygote Mcpt5/Cma1 DTR/+ mice. The deletion rates of mast cells in peritoneal cavity, mesentery, abdominal skin, ear skin, and glandular stomach were 99.9%, 100%, 98.7%, 97.7%, and 100%, respectively. Passive cutaneous anaphylaxis reaction also revealed mast cell deficiency in ear skin after DT treatment. Other than mast cells, a small percentage of marginal zone B cells in Mcpt5/Cma1 DTR/+ mice were killed by DT treatment. In conclusion, the Mcpt5/Cma1 DTR/+ mouse model is valuable for achieving conditional depletion of all populations of mast cells without inducing a marked reduction in other cells., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed., Objective: We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure., Design, Setting, and Participants: A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients., Results and Limitations: Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study., Conclusions: EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Two-dimensional liquid chromatography requires orthogonal columns and/or separation principles in the first and second separation dimension. It is sometimes not straightforward to achieve. Chiral columns could expand the toolbox for 2D-LC, but are rarely exploited for this purpose, not least due to missing understanding of retention principles under non-chiral application conditions. To gain more insight, in this study Chiralpak ZWIX(+) and ZWIX(-), based on zwitterionic quinine and quinidine carbamate selectors, were carefully characterized by molecular dynamics simulations, lipophilicity/hydrophilicity measurements of selectors, pH-dependent ζ-potential determinations, and chromatographic characterization in RPLC and HILIC modes combined with unsupervised principal component analysis to extract classification of these columns in comparison to a number of commercial benchmarks (RP, HILIC and mixed-mode columns). The results showed that these chiral columns can be classified as mixed-mode chromatography phases with balanced lipophilic-hydrophilic surface character, excess of negative net charge due to sulfonic acid groups (in spite of weakly basic quinuclidine and quinoline rings), and multimodal applicability (RP, HILIC and polar organic elution modes). Orthogonality mapping in comparison to a number of modern HILIC and mixed-mode columns revealed that Poroshell HILIC-Z (with a zwitterionic ligand on 2.7 μm core-shell particles) can be beneficially combined as second dimension with the ZWIX column for comprehensive LC × LC. The online hyphenation of this 2D-LC system with complementary detection modalities including UV (DAD for chromophoric substances), charged aerosol detection (for universal detection and calibration of non-volatile analytes) and high-resolution mass spectrometry (ESI-QTOF-MS/MS for identification) provided an advanced method for comprehensive impurity profiling, applicable for instance for amino acid pharmaceutical products., (Copyright © 2019 Elsevier B.V. All rights reserved.)

While reversed-phase (RP) liquid chromatography can separate a wide range of analytes, for strongly acidic compounds such as environmentally relevant dialkyl phosphates (DAPs), this remains a challenge because they have low affinity for standard RP columns or they exhibit inferior peak shapes. Mixed-mode chromatographic (MMC) columns, which contain both RP and ion-exchange functionalities, can address these resolution problems. However, using current MMC separation approaches, analyte peaks are relatively broad as compared to conventional RP chromatography. Herein we present an enhanced MMC-based UHPLC/ESI-MS method for the analysis of DAPs. In contrast to commonly available MMC-based methods, we applied the MMC Luna ® Omega PS C18 column that was conditioned by 0.1% formic acid and equilibrated with the initial mobile phase before sample injection. This conditioning step tremendously improved the retention and separation of the DAPs, especially for those with high water solubility and shorter carbon chain lengths. Using water/methanol (95 v/5 v) and ammonium acetate in methanol as the mobile phases, nine DAPs could be baseline resolved with very sharp peaks, including the shorter-chain dimethyl phosphate, diethyl phosphate and bis(2-chloroethyl) phosphate. Other columns were examined to facilitate method optimization, and to identify stationary phases with the ability to separate DAPs as well as to elucidate the retention and separation mechanisms. With this novel UHPLC and post-column dication ion-pairing ESI-MS/MS method, instrumental detection limits as low as 0.01 ng/mL level were achieved. Representing other strongly acidic analytes, the short-chain perfluoroalkyl acid, perfluorobutyl sulfonic acid could also be analyzed with this method., (Copyright © 2018 Elsevier B.V. All rights reserved.)

During development of the CNS, stem and progenitor cell proliferation, cell fate designation, and patterning decisions are tightly regulated by interdependent networks of key transcriptional regulators. In a genetic approach we analyzed divergent functionality of the PAI and RED sub-domains of the Pax6 Paired domain (PD) during progenitor zone formation, motor and interneuron development, and peripheral connectivity at distinct levels within the neural tube: within the hindbrain, mutation of the PAI sub-domain severely affected patterning of the p3 and pMN domains and establishment of the corresponding motor neurons. Exit point designation of hypoglossal axons was disturbed in embryos harboring either mutations in the PD sub-domains or containing a functional Pax6 Null allele. At brachial spinal levels, we propose a selective involvement of the PAI sub-domain during patterning of ventral p2 and pMN domains, critically disturbing generation of specific motor neuron subtypes and increasing V2 interneuron numbers. Our findings present a novel aspect of how Pax6 not only utilizes its modular structure to perform distinct functions via its paired and homeodomain. Individual sub-domains can exert distinct functions, generating a new level of complexity for transcriptional regulation by one single transcription factor not only in dorso-ventral, but also rostro-caudal neural tube patterning., (Copyright © 2016. Published by Elsevier Inc.)

Introduction: The drugs and protocols used for hyperthermic intraperitoneal chemotherapy (HIPEC) vary among institutions. Here we show the efficacy of the 3-drug combination of mitomycin C (MMC), 5-fluorouracil (5FU), and oxaliplatin (OHP) in an in vitro simulation of HIPEC and the safety of HIPEC with these drugs during a Phase I study of patients at high risk of developing colorectal peritoneal metastasis., Methods: To simulate HIPEC, we used HCT116 and WiDr cells to assess the growth inhibitory efficacy of MMC 2 μg/mL, 5FU 200 μg/mL, and OHP 40 μg/mL as single drugs or their combination after an exposure time of 30 min at 37 or 42 °C. In addition, nine patients underwent surgical resection of tumors and HIPEC with MMC, 5FU, and an escalating dose of OHP (90/110/130 mg/m²). Dose-limiting toxicity was monitored., Results: In the simulation, the 3-drug combination showed marked tumor-suppressive effects compared with those from ten times higher dose of OHP 400 μg/mL, with significant augmentation under hyperthermic conditions. No dose-limiting toxicity occurred in the clinical study. Dose escalation was completed at the final level of OHP., Conclusions: The MMC-5FU-OHP combination showed marked growth inhibition against colorectal cancer cells under hyperthermic conditions in vitro. In the phase I study, the recommended dose of OHP was determined as 130 mg/m² when used with MMC and 5FU; HIPEC using MMC-5FU-OHP appears to be safe and feasible for patients at high risk of colorectal peritoneal metastasis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Methylmalonic aciduria (MMA) is one of the most frequent organic acidurias, a class of diseases caused by enzymatic defects mainly involved in the catabolism of branched-chain amino acids. Recently, mild MMA and C4-dicarboxylyl-carnitine (C4DC-C) accumulation have been reported in patients carrying mutation in genes encoding the α-subunit (SUCLG1) and the β-subunit (SUCLA2) of the ADP-forming succinyl-CoA synthetase (SCS). We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify in dried blood spot the two isobaric compounds of C4DC-C, succinyl-carnitine and methylmalonyl-carnitine, to allow the differential diagnosis between classical MMA and SCS-related defects. This method, with an easy liquid-phase extraction and derivatization procedure, has been validated to demonstrate the specificity, linearity, recovery, lowest limit of quantification (LLOQ), accuracy and precision for quantitative determination of blood succinyl-carnitine and methylmalonyl-carnitine. The assay was linear over a concentration range of 0.025-10 μmol/L and achieved the LLOQ of 0.025 μmol/L for both metabolites. The average slope, intercept, and coefficient of linear regression (r(2)) were respectively: 0.3389 (95% confidence interval 0.2888-0.3889), 0.0113 (95% confidence interval -0.0157 to 0.0384), 0.9995 (95% confidence interval 0.9990-1.0000) for succinyl-carnitine and 0.5699 (95% confidence interval 0.5263-0.6134), 0.0319 (95% confidence interval -0.0038 to 0.0677), 0.9997 (95% confidence interval 0.9995-1.0000) for methylmalonyl-carnitine. Within-day and between-day coefficients of variation (CV) were 1.94% and 3.19% for succinyl-carnitine and 3.21%, and 2.56 for methylmalonyl-carnitine. This method is accurate and provides a new tool to differentiate patients with classical methylmalonic acidemia from those with SCS-related defects., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This mini-review aims to compare the differences in the kinetics of the induction of micronucleated polychromatic erythrocytes (MN-PCE) and cytotoxicity by distinct antineoplastic and genotoxic agents in murine peripheral blood in vivo and to correlate these kinetics with the underlying processes. Comparisons were carried out using our previously obtained data with nominal doses causing similar levels of cytotoxicity, as measured in terms reduction of PCE. The aneuploidogens caused the most rapid induction of MN-PCEs and had the highest rates of cytotoxicity and genotoxicity. The promutagens cyclophosphamide and dimethylnitrosamine showed the most delayed responses and had the lowest genotoxic and cytotoxic efficiencies. DNA crosslinking agents had a similar delay of 4-5 h, greater than those of aneuploidogens, but differed in their cytotoxic and genotoxic efficiencies. Methylnitrosourea and 5-aza-cytidine caused greater delays than crosslinking agents. These delays can be due to the methylnitrosourea-mediated induction of formation of mono alkyl adducts which are interpreted as mismatches during DNA duplication, whereas 5-aza-cytidine requires incorporation into the DNA to induce breakage. This review allows us to conclude that the requirement for metabolic activation and the mechanisms of DNA breakage and of micronucleus induction are the main factors that affect the time of maximal MN-PCE induction., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Urothelial carcinoma (UC) of the bladder is the second most common cancer of the genitourinary system. Clinical UC treatment usually involves transurethral resection of the bladder tumor followed by adjuvant intravesical immunotherapy or chemotherapy to prevent recurrence. Intravesical chemotherapy induces fewer side effects than immunotherapy but is less effective at preventing tumor recurrence. Improvement to intravesical chemotherapy is, therefore, needed., Methods and Materials: Cellular effects of mitomycin C (MMC) and hydrostatic pressure on UC BFTC905 cells were assessed. The viability of the UC cells was determined using cellular proliferation assay. Changes in apoptotic function were evaluated by caspase 3/7 activities, expression of FasL, and loss of mitochondrial membrane potential., Results: Reduced cell viability was associated with increasing hydrostatic pressure. Caspase 3/7 activities were increased following treatment of the UC cells with MMC or hydrostatic pressure. In combination with 10 kPa hydrostatic pressure, MMC treatment induced increasing FasL expression. The mitochondria of UC cells displayed increasingly impaired membrane potentials following a combined treatment with 10 μg/ml MMC and 10 kPa hydrostatic pressure., Conclusions: Both MMC and hydrostatic pressure can induce apoptosis in UC cells through an extrinsic pathway. Hydrostatic pressure specifically increases MMC-induced apoptosis and might minimize the side effects of the chemotherapy by reducing the concentration of the chemical agent. This study provides a new and alternative approach for treatment of patients with UC following transurethral resection of the bladder tumor., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: We aimed to review patients with a solitary kidney and ipsilateral vesicoureteral reflux (VUR) who underwent endoscopic correction of VUR (ECVUR) and to evaluate the prevalence of obstruction in this group of patients., Materials and Methods: We retrospectively reviewed the files of all patients who underwent ECVUR at our center between January 2000 and June 2011. Only patients with a solitary kidney and ipsilateral VUR were included., Results: Thirteen patients met our criteria. Two patients (15.38%) developed obstruction post-ECVUR. Both patients developed anuria in the first 24 h after surgery and required intervention. Two patients (15.38%) had increasing hydroureteronephrosis that was discovered on follow-up ultrasound, with no symptoms or signs of obstruction. Both were managed conservatively., Conclusion: Our results showed a higher percentage of obstruction post-ECVUR in patients with a solitary kidney (15.38%), who required immediate intervention. Thus, we recommend giving clear instructions to parents of patients with VUR and a solitary kidney post-ECVUR before discharge from the hospital regarding decreased urine output and loin pain. We recommend a follow-up ultrasound to rule out obstruction and detect new-onset hydronephrosis., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo., (Copyright © 2013 Elsevier Inc. All rights reserved.)