Quasi two-level PWM operation of a nine-arm modular multilevel converter for six-phase medium-voltage motor drives

This paper proposes a hybrid converter for medium-voltage six-phase machine drive systems that mixes the operation of a traditional two-level voltage-source inverter and the modular multilevel converter (MMC) to enable operation over a wide frequency range. Topologically, the proposed converter consists of nine arms resembling two sets of three-phase MMCs with three common arms, yielding a nine-arm MMC with a 25% reduction in the number of employed arms compared to a traditional dual three-phase MMC. The multilevel property of a standard MMC is emulated in the proposed converter, however on a two-level basis, resulting in a stepped two-level output voltage waveform. The proposed converter has a reduced footprint with advantages of small voltage steps, modular structure, and ease of scalability. Further, it is able to drive high-power six-phase machines within low operating frequencies at the rated torque. The operating principle of the converter is elaborated, and its modulation scheme is discussed. The features of the proposed converter are verified through simulations and experimentally

Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC

Insulin-like growth factor binding protein-1 (IGFBP-1), secreted by fetal liver, is a key regulator of IGF-I bioavailability and fetal growth. IGFBP-1 phosphorylation decreases IGF-I bioavailability and diminishes its growth-promoting effects. Growth-restricted fetuses have decreased levels of circulating essential amino acids. We recently showed that IGFBP-1 hyperphosphorylation (pSer101/119/169) in response to leucine deprivation is regulated via activation of the amino acid response (AAR) in HepG2 cells. Here we investigated nutrient-sensitive protein kinases CK2/PKC/PKA in mediating IGFBP-1 phosphorylation in leucine deprivation. We demonstrated that leucine deprivation stimulated CK2 activity (enzymatic assay) and induced IGFBP-1 phosphorylation (immunoblotting/MRM-MS). Inhibition (pharmacological/siRNA) of CK2/PKC, but not PKA, prevented IGFBP-1 hyperphosphorylation in leucine deprivation. PKC inhibition also prevented leucine deprivation-stimulated CK2 activity. Functionally, leucine deprivation decreased IGF-I-induced-IGF-1R autophosphorylation when CK2/PKC were not inhibited. Our data strongly support that PKC promotes leucine deprivation-induced IGFBP-1 hyperphosphorylation via CK2 activation, mechanistically linking decreased amino acid availability and reduced fetal growth

A modular multilevel converter with DHB energy balancing channels for medium-voltage adjustable-speed drives

This paper presents a modular multilevel converter (MMC) configuration that utilises energy exchange between submodules (SMs) of upper and lower arms, for energy rebalancing. The configuration is applicable to mediumvoltage high-power variable-speed drives with any number of motor phases, where the traditional MMC topology experiences challenging shortcomings. With the out-of-phase alternation of the fundamental ripple power in upper and lower arms, the proposed MMC configuration decouples this ripple power by employing dual half-bridge modules linking opposite SMs in upper and lower arms of the same MMC-leg. This counter-balances arm ripple-power through bidirectional power transfer between opposite SMs, resulting in a reduction in the SM capacitance and the MMC system stored energy. The proposed MMC configuration solves the problem of wide SM capacitor voltage fluctuation, especially at low operating frequencies, where the SM capacitor voltage ripple profile is almost constant, independent of the operating frequency. Therefore, the configuration is able to drive multi-megawatt machines from stand-still to the rated speed, at rated torque. The operation of the proposed converter topology is elucidated in detail, and its effectiveness is verified through simulation and experimentation

State-of-the-art in product service-systems

A Product Service-System (PSS) is an integrated combination of products and services. This western concept embraces a service-led competitive strategy, environmental sustainability, and the basis to differentiate from competitors who simply offer lower priced products. This paper aims to report the state-of-the-art of PSS research by presenting a clinical review of literature currently available on this topic. The literature is classified and the major outcomes of each study are addressed and analysed. On this basis, this paper defines the PSS concept, reports on its origin and features, gives examples of applications along with potential benefits and barriers to adoption, summarises available tools and methodologies, and identifies future research challenges

Soft Tissue Pathology Detected By Ultrasound Seem To Be Risk Factors for Painful Flare in Osteoarthritic Knee

BACKGROUND: To our knowledge, the importance of US findings, pain (brief pain inventory (BPI)) and disability in osteoarthritic knee (OA) pain patients remain uncertain. AIM: The objectives are to evaluate the correlation of US findings, pain (brief pain inventory (BPI)) and disability in OA pain patients. MATERIALS AND METHODS: Eighty - three patients with OA knee were divided into two groups. The first group was OA as symptomatic knee group and the second group was an asymptomatic control group. The maximum sagittal height of synovial fluid in 12 scans at 0, 30, 60 and 90 degrees flexion knee in 3 major recesses were measured. RESULTS: There were a significant positive correlation between BPI Pain severity index, or BPI function interference index and a maximum height of effusion at 30-degree flexion angle in a supra-patellar recess in painful symptomatic knees. But, there was a significant negative correlation between BPI Pain severity index, and BPI function interference index and cartilage thickness in painful symptomatic knees. CONCLUSION: The increase of maximum height of synovial effusion at different angles of knee and decrease of cartilage thickness associated with pain and disability in OA pain patients and are being predictors for pain severity and disability in OA pain patients

Cost engineering for manufacturing: current and future research

The article aims to identify the scientific challenges and point out future research directions on Cost Engineering. The research areas covered in this article include Design Cost; Manufacturing Cost; Operating Cost; Life Cycle Cost; Risk and Uncertainty management and Affordability Engineering. Collected information at the Academic Forum on Cost Engineering held at Cranfield University in 2008 and further literature review findings are presented. The forum set the scope of the Cost Engineering research, a brainstorming was held on the forum and literatures were further reviewed to understand the current and future practices in cost engineering. The main benefits of the article include coverage of the current research on cost engineering from different perspectives and the future research areas on Cost Engineering

MISCAST : MIssense variant to protein StruCture Analysis web SuiTe

Human genome sequencing efforts have greatly expanded, and a plethora of missense variants identified both in patients and in the general population is now publicly accessible. Interpretation of the molecular-level effect of missense variants, however, remains challenging and requires a particular investigation of amino acid substitutions in the context of protein structure and function. Answers to questions like 'Is a variant perturbing a site involved in key macromolecular interactions and/or cellular signaling?', or 'Is a variant changing an amino acid located at the protein core or part of a cluster of known pathogenic mutations in 3D?' are crucial. Motivated by these needs, we developed MISCAST (missense variant to protein structure analysis web suite; http://miscast.broadinstitute.org/). MISCAST is an interactive and user-friendly web server to visualize and analyze missense variants in protein sequence and structure space. Additionally, a comprehensive set of protein structural and functional features have been aggregated in MISCAST from multiple databases, and displayed on structures alongside the variants to provide users with the biological context of the variant location in an integrated platform. We further made the annotated data and protein structures readily downloadable from MISCAST to foster advanced offline analysis of missense variants by a wide biological community.Peer reviewe

Exploring stakeholders’ ecosystem services perceptions across Massachusetts Bays using deliberative valuation

Deliberative methods to assess ecosystem services values formalize community members’ and stakeholders’ involvement in decision-making related to natural resources management. This paper presents the methodological design and the application of a deliberative multicriteria evaluation (DMCE) method that combines the advantages of deliberation with structured decision-making to assess community-based values of four coastal ecosystem services (valued by indicators such as Total Nitrogen, Blue Carbon, Scallop Landings, Fish Abundance) and explore the spatial variability of group values along the Massachusetts coastline. We implemented four virtual deliberative workshops consisting of stakeholders from four Massachusetts Bays (MassBays) estuarine categorizations to collect quantitative and qualitative data. Quantitative data came from individual survey results and group preferences, while qualitative data were derived through the analysis of video recordings and transcripts of deliberations. Compared to previous studies, we combined quantitative and qualitative data by using applied thematic and co-occurrence analysis to identify themes of discussion during the deliberative process. Our results show that coastal stakeholders place a particular emphasis on access to clean water and services that directly support human wellbeing and provide direct economic benefits. Differences in the quantitative and qualitative results of these deliberative tasks between groups provide insight into the need for localized policymaking instead of solely regional or statewide management. Environmental managers and policymakers will utilize these insights to address local values and priorities as they work towards implementing habitat restoration efforts

Comprehensive characterization of amino acid positions in protein structures reveals molecular effect of missense variants

Interpretation of the colossal number of genetic variants identified from sequencing applications is one of the major bottlenecks in clinical genetics, with the inference of the effect of amino acid-substituting missense variations on protein structure and function being especially challenging. Here we characterize the three-dimensional (3D) amino acid positions affected in pathogenic and population variants from 1,330 disease-associated genes using over 14,000 experimentally solved human protein structures. By measuring the statistical burden of variations (i.e., point mutations) from all genes on 40 3D protein features, accounting for the structural, chemical, and functional context of the variations' positions, we identify features that are generally associated with pathogenic and population missense variants. We then perform the same amino acid-level analysis individually for 24 protein functional classes, which reveals unique characteristics of the positions of the altered amino acids: We observe up to 46% divergence of the class-specific features from the general characteristics obtained by the analysis on all genes, which is consistent with the structural diversity of essential regions across different protein classes. We demonstrate that the function-specific 3D features of the variants match the readouts of mutagenesis experiments for BRCA1 and PTEN, and positively correlate with an independent set of clinically interpreted pathogenic and benign missense variants. Finally, we make our results available through a web server to foster accessibility and downstream research. Our findings represent a crucial step toward translational genetics, from highlighting the impact of mutations on protein structure to rationalizing the variants' pathogenicity in terms of the perturbed molecular mechanisms.Peer reviewe

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD