Interleaved Half-Bridge Submodules with Sensorless Leg Current Balancing in Modular Multilevel Converters

A new state observer-based current balancing method for Modular Multilevel Converters with Interleaved half-bridge Sub-Modules (ISM-MMC) is presented in this paper. The developed observer allows estimating currents through interleaved half-bridge legs in each submodule of ISM-MMC basing only on arm current and submodule’s capacitor voltage measurements. Then, the interleaved current balancing control uses the estimated currents to reduce the interleaved currents imbalance caused by upstream control actions. This technique minimizes the number of required current sensors in ISM-MMC, thereby reducing the converter's cost, weight, and volume. Capabilities of the proposed interleaved currents sensorless balancing control has been tested against standard parameter tolerances of the composing passive elements. The feasibility of the proposed method is verified by extensive simulation and experimental tests.

Interleaved Half-Bridge Submodules with Sensorless Leg Current Balancing in Modular Multilevel Converters

A new state observer-based current balancing method for Modular Multilevel Converters with Interleaved half-bridge Sub-Modules (ISM-MMC) is presented in this paper. The developed observer allows estimating currents through interleaved half-bridge legs in each submodule of ISM-MMC basing only on arm current and submodule’s capacitor voltage measurements. Then, the interleaved current balancing control uses the estimated currents to reduce the interleaved currents imbalance caused by upstream control actions. This technique minimizes the number of required current sensors in ISM-MMC, thereby reducing the converter's cost, weight, and volume. Capabilities of the proposed interleaved currents sensorless balancing control has been tested against standard parameter tolerances of the composing passive elements. The feasibility of the proposed method is verified by extensive simulation and experimental tests.

P–528 rDNA methylation of human oocytes of women undergoing intracytoplasmic sperm injection (ICSI) increases with maternal age

Study question Is there a correlation between the age of women undergoing ICSI and methylation pattern of rDNA core promoter and upstream control element in immature human oocytes? Summary answer Methylation levels of the upstream control element and the rDNA core promoter in immature human oocytes increase with age of women undergoing ICSI. What is known already Methylation of ribosomal DNA (rDNA) in germ cells regulates temporary and spatially highly coordinated nucleolar activity, cellular metabolism, and thus developmental potential of the early embryo. Alterations of methylation pattern may therefore cause dysregulation of genes and signal cascades resulting in limited fertility. It has been shown that the methylation of sperm rDNA increases with the donor’s age. The positive correlation between sperm rDNA methylation and age has been conserved among mammals during evolution including humans and mice. In contrast to sperm, little is known about the methylome of human oocytes and its role in human reproduction. Study design, size, duration Consecutive women undergoing ICSI because of male subfertility were included. Patients with endometriosis, polycystic ovary syndrome, ovarian, uterine or breast cancer, as well as patients with an anti-Mullerian hormone level <1ng/ml were excluded. Immature oocytes (germinal vesicle; GV) collected during oocyte pick-up at the Fertility Centre Dortmund between 2018 and 2020 were examined. Participants/materials, setting, methods Cumulus-free GV oocytes which were not usable for ICSI were rinsed in phosphate buffer and stored at –20 °C until further investigation. Multiplex-PCR followed by singleplex-PCRs were carried out on the rDNA core promoter and upstream control element. Methylation levels were quantified by bisulphite pyrosequencing. Two oppositely imprinted genes (hPEG3 and hGTL2) were used as controls to ensure correct amplification and bisulphite conversion. Spearman’s-rank-order-correlation and Mann-Whitney-U-Test were used for statistical analysis. Main results and the role of chance For each GV oocyte, nine different Cytosine-phosphate-Guanine dinucleotides (CpGs) were quantified by bisulphite pyrosequencing for the rDNA core promoter and 26 different CpGs for the upstream control element (UCE). 120 human single oocytes from 60 women were analyzed. Connected statistical analysis was used if one patient had more than one oocyte. The age of the included women ranged from 26 to 40 years (mean±SD 33.5±3.2). Only oocytes which showed a correct methylation pattern for at least one imprinting control gene (hPEG3 and hGTL2) were considered for analysis. Mean methylation level ranged from 2–31% (mean±SD 8.7±5.5) of the analyzed CpGs for the rDNA core promoter and from 3–36% (mean±SD 11.4±7.1) CpGs for UCE. Spearman’s correlation analysis revealed that the methylation levels of the human oocyte rDNA core promoter and rDNA UCE significantly increased with the age of the donor (p < 0.05). Correlation coefficient for rDNA core promoter was r = 0.22 and for upstream control element r = 0.21. It is also interesting to note that different oocytes from the same donors can display enormous methylation variation. Regarding clinical parameters, no correlation was observed between the methylation pattern of the rDNA core promoter or UCE and the body mass index or smoking status, respectively. Limitations, reasons for caution Limitations of this study include difficulties in extrapolating the findings to the general population, because no data of women not undergoing ICSI are available. Only GV-oocytes were analyzed. Additional research is needed to clarify the effect of different methylation pattern with increasing female age and its role in human reproduction. Wider implications of the findings: We propose that the increase of rDNA methylation in male and female germ cells with advanced age directly or indirectly influences the regulation of nucleolar activity, cellular metabolism, and thus the developmental potential of the early embryo. This age-dependent epigenetic effect may result in decreased human fertility. Trial registration number NCT03565107

Impact of Minor Irrigation on Agricultural Production: An Inter-Crop Analysis in Odisha

The study examined the impact of minor irrigation on agricultural production and evaluated the gap between IPC and IPU in the Keonjhar district of Odisha. For this rationale, data were collected from 210 farm households through the primary survey. In support of the analysis, the Cobb Douglas model and factor analysis were used. The results revealed that the input use efficiency had a positive and significant impact on paddy production the most in all the MIPs regions compared to the other crops. However, the study indicated that insufficient water availability was the major cause behind the gap between irrigation potential created and utilised. Thus, minor irrigation played a crucial role in enhancing agricultural production in hilly regions. With the enthusiastic participation of planners, effective working of Pani Panchayats, canals, and upstream control, NGOs' involvement can achieve selfsufficiency in agricultural production by encouraging minor irrigation projects in the hilly province.

Bivariate Entropy Analysis of Electrocardiographic RR–QT Time Series

QT interval variability (QTV) and heart rate variability (HRV) are both accepted biomarkers for cardiovascular events. QTV characterizes the variations in ventricular depolarization and repolarization. It is a predominant element of HRV. However, QTV is also believed to accept direct inputs from upstream control system. How QTV varies along with HRV is yet to be elucidated. We studied the dynamic relationship of QTV and HRV during different physiological conditions from resting, to cycling, and to recovering. We applied several entropy-based measures to examine their bivariate relationships, including cross sample entropy (XSampEn), cross fuzzy entropy (XFuzzyEn), cross conditional entropy (XCE), and joint distribution entropy (JDistEn). Results showed no statistically significant differences in XSampEn, XFuzzyEn, and XCE across different physiological states. Interestingly, JDistEn demonstrated significant decreases during cycling as compared with that during the resting state. Besides, JDistEn also showed a progressively recovering trend from cycling to the first 3 min during recovering, and further to the second 3 min during recovering. It appeared to be fully recovered to its level in the resting state during the second 3 min during the recovering phase. The results suggest that there is certain nonlinear temporal relationship between QTV and HRV, and that the JDistEn could help unravel this nuanced property.

LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning

Signaling from lysosomes controls cellular clearance and energy metabolism. Lysosomal malfunction has been implicated in several pathologies, including neurodegeneration, cancer, infection, immunodeficiency, and obesity. Interestingly, many functions are dependent on the organelle position. Lysosomal motility requires the integration of extracellular and intracellular signals that converge on a competition between motor proteins that ultimately control lysosomal movement on microtubules. Here, we identify a novel upstream control mechanism of Arl8b-dependent lysosomal movement toward the periphery of the cell. We show that the C-terminal domain of lyspersin, a subunit of BLOC-1–related complex (BORC), is essential and sufficient for BORC-dependent recruitment of Arl8b to lysosomes. In addition, we establish lyspersin as the linker between BORC and late endosomal/lysosomal adaptor and mitogen activated protein kinase and mechanistic target of rapamycin activator (LAMTOR) complexes and show that epidermal growth factor stimulation decreases LAMTOR/BORC association, thereby promoting BORC- and Arl8b-dependent lysosomal centrifugal transport.

Membrane tension controls adhesion positioning at the leading edge of cells

Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II–independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions. As membrane tension decreases, protrusion resumes and buckling disappears, until the next cycle. We propose that the mechanical signal of membrane tension exerts upstream control in mechanotransduction by periodically compressing and relaxing the lamellipodium, leading to the positioning of adhesions at the leading edge of cells.

Responses of Skeletal Muscle Hypertrophy in Wistar Rats to Different Resistance Exercise Models

This study aimed to compare the effects of three different resistance exercise models on the quadriceps muscle cross-sectional area, as well as on mTOR phosphorylation and other pivotal molecules involved in the upstream regulation of mTOR. Twenty-four male Wistar rats were divided into untrained (control), endurance resistance training, strength resistance training, and hypertrophy resistance training (HRT) groups (n=6). After 12 weeks of training, the red portion of the quadriceps was removed for histological and Western blot analyses. The results showed that the quadriceps weight and cross-sectional areas in the exercised groups were higher than those of the untrained rats. However, the HRT group presented better results than the other two experimental groups. This same pattern was observed for mTOR phosphorylation and for the most pivotal molecules involved in the upstream control of mTOR (increase of PKB, 14-3-3, ERK, p38 MAPK, and 4E-BP1 phosphorylation, and reduction of tuberin, sestrin 2, REDD1, and phospho AMPK). In summary, our study showed that HRT leads to high levels of mTOR phosphorylation as well as of other proteins involved in the upstream regulation of mTOR.