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Electronic power converters are extensively applied in microgrids to interface distributed energy resources to the grid. Besides the primary active-power control, electronic converters support increasingly advanced and flexible control capabilities. While the former is typically bound to local needs (e.g., maximum power extraction from renewables), additional degrees of freedom can be exploited to support microgrid operation. This article proposes a control algorithm that allows the optimal provision of reactive power, negative-sequence, and zero-sequence currents by distributed converters. The resulting operation shows enhanced power quality at the point of common coupling (PCC) and limited conversion losses, which are taken into account in the optimization algorithm. Three modes of operation are discussed, that is, i) power loss minimization; ii) balanced currents at the PCC; iii) zero reactive power flow at the PCC. An algorithm based on the primal-dual method is proposed to solve the optimization problem. Results based on experimental measurements are discussed to prove the effectiveness of the proposal.

A flexible power electronic converter embedding a rapid control prototyping platform suitable to be applied in research test setups and teaching laboratories is proposed and described in this paper. The electronic system is composed of three subsystems, namely, i) three half-bridge power boards, ii) a dc-link capacitor bank with a half-bridge power module for active dc-link control, iii) an interfacing board, called motherboard, to couple the power modules with a control unit, iv) a digital control unit with rapid control prototyping functionalities for controlling power electronic circuits. Power modules integrate sensors with related conditioning circuits, driving circuits for power switches, and protection circuits. Conversion circuits exploit GaN electronic switches for optimal performance. The architecture and implementation of the system are described in detail in this manuscript. Main applications are in the implementation of conversion circuits for supplying arbitrary ac or dc voltages or currents, testing of new control algorithms for power electronic converters, testing of systems of electronic converters in, for example, smart nanogrids or renewable energy applications, training of undergraduate and graduate students.

This manuscript describes the operation of a droop-based controller for three-phase converters in the case of the absence of a neutral connection to the grid. The controller is capable of output power tracking and smooth transitions into the islanded operation. While independent per-phase control of the converter output power is possible if a neutral connection is present, its absence implies additional constraints to be considered. Focusing on this latter case, the controller described herein allows the independent control of the active power at the output of each phase of the converter and a smooth transition to the islanded operation. These features are paramount in future smart power systems, such as smart microgrids, for implementing demand–response, power-flow management, and uninterrupted power operation.

Background CD34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be “memorized” by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord‐blood–derived CD34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal‐cell–derived factor 1 alpha and reduced protein and mRNA expression of the C‐X‐C chemokine receptor type 4 (CXCR4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR4 promoter revealed a significant increase in DNA methylation density in high‐glucose CD34+ stem cells that negatively correlated with mRNA expression (Pearson r=−0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR4 promoter. Notably, alteration of CXCR4 DNA methylation, as well as transcriptional and functional defects, persisted in high‐glucose CD34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD34+ stem cells “memorize” the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR4 receptor expression and migration.

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Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (N4BP2L1), pleckstrin homology domain-containing family A member 4 (PLEKHA4), and brain-enriched guanylate kinase-associated protein (BEGAIN) that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of PLEKHA4 in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified N4BP2L1 and BEGAIN as potential biomarkers of HER2-positive breast cancer. Furthermore, low BEGAIN expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed N4BP2L1 as a promising diagnostic protein biomarker in breast cancer. In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.

Long non-coding RNAs (lncRNAs) regulate gene expression through different molecular mechanisms, including DNA binding via the formation of RNA:DNA:DNA triple helices (TPXs). Despite the increasing amount of experimental evidence, TPXs investigation remains challenging. Here we present 3plex, a software able to predict TPX interactions in silico. Given an RNA sequence and a set of DNA sequences, 3plex integrates 1) Hoogsteen pairing rules that describe the biochemical interactions between RNA and DNA nucleotides, 2) RNA secondary structure prediction and 3) determination of the TPX thermal stability derived from a collection of TPX experimental evidences. We systematically collected and uniformly re-analysed published experimental lncRNA binding sites on human and mouse genomes. We used these data to evaluate 3plex performance and showed that its specific features allow a reliable identification of TPX interactions. We compared 3plex with the other available software and obtained comparable or even better accuracy at a fraction of the computation time. Interestingly, by inspecting collected data with 3plex we found that TPXs tend to be shorter and more degenerated than previously expected and that the majority of analysed lncRNAs can directly bind to the genome by TPX formation. Those results suggest that an important fraction of lncRNAs can exert its biological function through this mechanism. The software is available at https://github.com/molinerisLab/3plex.

DNMT3B-dependent DNA methylation provides epigenetic priming at epiblast stage by methylating enhancers of ectodermal genes to ensure proper differentiation toward mesoendoderm tissues.

Background. Urban planning is a key tool to promote health in cities. The COVID-19 emergency accelerated several social, environmental, and digital challenges, stressing the importance of some issues regarding housing, urban mobility, green areas, and health service networks, urban health policies, and actions. These issues were the subject of an intensive residential course (the 57th) held in Erice, Sicily, in June 2021 in the “International School of Epidemiology and Preventive Medicine G. D’Alessandro”, and the main findings are described here. Methods. Lectures presented the topics, subsequently developed them, and argued them in parallel practical sessions using the World Café technique, since it is well suited for the interaction of participants and the involvement of groups. Results. The World Café provides new insights into how to improve the livability and health of urban spaces, and a set of strategies and actions were proposed for each topic. Discussion and Conclusions. All attendees agreed on the importance of participation in the planning processes, but also on the need for strong political support to ensure the resources needed and a full integration of health with other local policies. A multidisciplinary approach to developing systemic operational capacities and health literacy is considered pivotal to raising awareness and participation.

In patients with acute ischemic stroke, hemorrhagic transformation (HT) of infarcted tissue frequently occurs after reperfusion treatment. We aimed to assess whether HT and its severity influences the start of secondary prevention therapy and increases the risk of stroke recurrence. In this retrospective dual-center study, we recruited ischemic stroke patients treated with thrombolysis, thrombectomy or both. Our primary outcome was the time between revascularization and the start of any secondary prevention therapy. The secondary outcome was ischemic stroke recurrence within three months. We compared patients with vs. without HT and no (n = 653), minor (n = 158) and major (n = 51) HT patients using propensity score matching. The delay in the start of antithrombotics or anticoagulants was median 24 h in no HT, 26 h in minor HT and 39 h in major HT. No and minor HT patients had similar rates of any stroke recurrence (3.4% (all ischemic) vs. 2.5% (1.6% ischemic plus 0.9% hemorrhagic)). Major HT patients had a higher stroke recurrence at 7.8% (3.9% ischemic, 3.9% hemorrhagic), but this difference did not reach significance. A total of 22% of major HT patients did not start any antithrombotic treatment during the three-month follow-up. In conclusion, the presence of HT influences the timing of secondary prevention in ischemic stroke patients undergoing reperfusion treatments. Minor HT did not delay the start of antithrombotics or anticoagulants compared to no HT, with no significant difference in safety outcomes. Major HT patients remain a clinical challenge with both a delayed or lacking start of treatment. In this group, we did not see a higher rate of ischemic recurrence; however, this may have been censored by elevated early mortality. While not reaching statistical significance, hemorrhagic recurrence was somewhat more common in this group, warranting further study using larger datasets.

Introduction: We sought to verify the predicting role of a favorable profile on computed tomography perfusion (CTP) in the outcome of patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) undergoing effective mechanical thrombectomy (MT). Methods: We retrospectively enrolled 25 patients with AIS due to LVO and with a CTP study showing the presence of ischemic penumbra who underwent effective MT, regardless of the time of onset. The controls were 25 AIS patients with overlapping demographics and clinical and computed tomography angiography features at admission who had undergone successful MT within 6 h from onset and without a previous CTP study. The outcome measure was the modified Rankin Scale (mRS) score at 90 days. Results: Sixty-four percent of the study patients had an mRS score of 0–1 at 90 days versus 12% of the control patients (p < 0.001). Patients of the study group had a more favorable distribution of disability scores (median mRS [IQR] score of 0 [0–2] vs. 2 [2–3]). Multivariate analysis showed that the selection of patients based on a favorable CTP study was strongly associated (p < 0.001) with a better neurological outcome. Conclusions: In our small-sized and retrospective study, the presence of ischemic penumbra was associated with a better clinical outcome in patients with AIS due to LVO after MT. In the future, a larger and controlled study with similar criteria of enrollment is needed to further validate the role of CTP in patient selection for MT, regardless of the time from the onset of symptoms.

Smad7 has been identified as a negative regulator of the transforming growth factor TGF-β pathway by direct interaction with the TGF-β type I receptor (TβR-I). Although Smad7 has also been shown to play TGF-β unrelated functions in the cytoplasm and in the nucleus, a comprehensive analysis of its nuclear function has not yet been performed. Here, we show that in ESCs Smad7 is mainly nuclear and acts as a general transcription factor regulating several genes unrelated to the TGF-β pathway. Loss of Smad7 results in the downregulation of several key stemness master regulators, including Pou5f1 and Zfp42, and in the upregulation of developmental genes, with consequent loss of the stem phenotype. Integrative analysis of genome-wide mapping data for Smad7 and ESC self-renewal and pluripotency transcriptional regulators revealed that Smad7 co-occupies promoters of highly expressed key stemness regulators genes, by binding to a specific consensus response element NCGGAAMM. Altogether, our data establishes Smad7 as a new, integral component of the regulatory circuitry that controls ESC identity.

miR-29b2 and miR-29c play a suppressive role in breast cancer progression. C1orf132 (also named MIR29B2CHG) is the host gene for generating both microRNAs. However, the region also expresses longer transcripts with unknown functions. We employed bioinformatics and experimental approaches to decipher C1orf132 expression and function in breast cancer tissues. We also used the CRISPR/Cas9 technique to excise a predicted C1orf132 distal promoter and followed the behavior of the edited cells by real-time PCR, flow cytometry, migration assay, and RNA-seq techniques. We observed that C1orf132 long transcript is significantly downregulated in triple-negative breast cancer. We also identified a promoter for the longer transcripts of C1orf132 whose functionality was demonstrated by transfecting MCF7 cells with a C1orf132 promoter-GFP construct. Knocking-out the promoter by means of CRISPR/Cas9 revealed no alterations in the expression of the neighboring genes CD46 and CD34, while the expression of miR-29c was reduced by half. Furthermore, the promoter knockout elevated the migration ability of the edited cells. RNA sequencing revealed many up- and downregulated genes involved in various cellular pathways, including epithelial to mesenchymal transition and mammary gland development pathways. Altogether, we are reporting here the existence of an additional/distal promoter with an enhancer effect on miR-29 generation and an inhibitory effect on cell migration.

BACKGROUND:Next generation sequencing methods are widely adopted for a large amount of scientific purposes, from pure research to health-related studies. The decreasing costs per analysis led to big amounts of generated data and to the subsequent improvement of software for the respective analyses. As a consequence, many approaches have been developed to chain different software in order to obtain reliable and reproducible workflows. However, the large range of applications for NGS approaches entails the challenge to manage many different workflows without losing reliability. METHODS:We here present a high-throughput sequencing pipeline (HaTSPiL), a Python-powered CLI tool designed to handle different approaches for data analysis with a high level of reliability. The software relies on the barcoding of filenames using a human readable naming convention that contains any information regarding the sample needed by the software to automatically choose different workflows and parameters. HaTSPiL is highly modular and customisable, allowing the users to extend its features for any specific need. CONCLUSIONS:HaTSPiL is licensed as Free Software under the MIT license and it is available at https://github.com/dodomorandi/hatspil.