Fault-Tolerant Multiport Converter for Hybrid Distribution Systems: Configuration, Control Principles and Fault Analysis

Multiport converters (MCs) are widely adopted in many applications, from renewable energy sources and storage integration to automotive applications and distribution systems. They are used in order to interface different energy sources, storage devices and loads with one single, simple converter topology in contrast to the traditional approach, which can require different solutions made by two-port converters. MCs allow for a reduction in the number of components and cascaded conversion stages with respect to an equivalent system of two-port converters, resulting in reduced complexity, dimensions and costs, as well as in improved reliability and enhanced efficiency. Nevertheless, some aspects related to the design of MCs are still worth further discussion when MCs are applied to hybrid AC/DC distribution systems. First, most converters are developed for one specific application and are not modular in structure. Furthermore, many of the proposed solutions are not equally suitable for AC and DC applications and they can introduce significant issues in hybrid distribution systems, with earthing management being particularly critical. Even though most available solutions offer satisfying steady-state and dynamic performances, fault behavior is often not considered and the possibility of maintaining controllability during faults is overlooked. Building on these three aspects, in this paper, a new MC for hybrid distribution systems is presented. An innovative circuit topology integrating three-phase AC ports and three-wire DC ports and characterized by a unique connection between the AC neutral wire and the DC midpoint neutral wire is presented. Its control principles and properties during external faults are highlighted, and extensive numerical simulations support the presented discussion

To branch or to expand?

Oscillating protein signals control the branching and expansion of blood vessels

Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes

BACKGROUND: Different approaches have been developed to dissect the interplay between transcription factors (TFs) and their cis-acting sequences on DNA in order to identify TF target genes. Here we used a combination of computational and experimental approaches to identify novel direct targets of TFAP2A, a key TF for a variety of physiological and pathological cellular processes. Gene expression profiles of HeLa cells either silenced for TFAP2A by RNA interference or not were previously compared and a set of differentially expressed genes was revealed. RESULTS: The regulatory regions of 494 TFAP2A-modulated genes were analyzed for the presence of TFAP2A binding sites, employing the canonical TFAP2A Positional Weight Matrix (PWM) reported in Jaspar http://jaspar.genereg.net/. 264 genes containing at least 2 high score TFAP2A binding sites were identified, showing a central role in "Cellular Movement" and "Cellular Development". In an attempt to identify TFs that could cooperate with TFAP2A, a statistically significant enrichment for SP1 binding sites was found for TFAP2A-activated but not repressed genes. The direct binding of TFAP2A or SP1 to a random subset of TFAP2A-modulated genes was demonstrated by Chromatin ImmunoPrecipitation (ChIP) assay and the TFAP2A-driven regulation of DCBLD2/ESDN/CLCP1 gene studied in details. CONCLUSIONS: We proved that our computational approaches applied to microarray selected genes are valid tools to identify functional TF binding sites in gene regulatory regions as confirmed by experimental validations. In addition, we demonstrated a fine-tuned regulation of DCBLD2/ESDN transcription by TFAP2A

Flow cytometric analysis of DNA content in human ovarian cancers.

A total of 155 samples from 101 patients with ovarian cancer were investigated using flow cytometry to evaluate the DNA index and the percentage of cells in the various cell cycle phases. Thirty-four samples were DNA diploid tumours, while the other 121 were DNA aneuploid tumours. The DNA index was very stable in different sites and over time in the same patient. Tumour stage and ploidy were significantly associated: stages III and IV tumour stage were more likely to be DNA aneuploid. Patients with residual tumour size at first surgery greater than 2 cm had a significantly larger number of DNA aneuploid than DNA diploid tumours. The DNA index was also related to the degree of differentiation of the tumours. The percentage of cells in the S phase of the cell cycle was significantly higher in DNA aneuploid and in poorly differentiated tumours than DNA diploid and well differentiated tumours. Multivariate analysis using the Cox model showed that the DNA index and the percentage of cells in S phase were not independent prognostic variables in this study. Prospectively collected data should be accumulated before assigning the DNA index an important role as a biological prognostic factor in ovarian cancer

Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells

Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunostimulatory DCs express high levels of costimulatory molecules, produce pro-inflammatory cytokines, and stimulate T cell proliferation, whereas tolerogenic DCs express low levels of costimulatory molecules, produce immunomodulatory cytokines and impair T cell proliferation. Relevant to the increasing use of immune checkpoint blockade in cancer treatment, signals generated from inhibitory checkpoint molecules on DC surface may also contribute to the inhibitory properties of tolerogenic DCs. Yet, our knowledge on the expression of inhibitory molecules on human DC subsets is fragmentary. Therefore, in this study, we investigated the expression of three immune checkpoints on peripheral blood DC subsets, in basal conditions and upon exposure to pro-inflammatory and anti-inflammatory stimuli, by using a flow cytometric panel that allows a direct comparison of the activatory/inhibitory phenotype of DC-lineage and inflammatory DC subsets. We demonstrated that functionally distinct DC subsets are characterized by differential expression of activatory and inhibitory molecules, and that cDC1s in particular are endowed with a unique immune checkpoint repertoire characterized by high TIM-3 expression, scarce PD-L1 expression and lack of ILT2. Notably, this unique cDC1 repertoire was subverted in a group of patients with myelodysplastic syndromes included in the study. Applied to the characterization of DCs in the tumor microenvironment, this panel has the potential to provide valuable information to be used for investigating the role of DC subsets in cancer, guiding DC-targeting treatments, and possibly identifying predictive biomarkers for clinical response to cancer immunotherapy

The noradrenergic component in tapentadol action counteracts \u3bc-opioid receptor-mediated adverse effects on adult neurogenesis

Opiates were the first drugs shown to negatively impact neurogenesis in the adult mammalian hippocampus. Literature data also suggest that norepinephrine is a positive modulator of hippocampal neurogenesis in vitro and in vivo. On the basis of these observations, we investigated whether tapentadol, a novel central analgesic combining \u3bc-opioid receptor (MOR) agonism with norepinephrine reuptake inhibition (NRI), may produce less inhibition of hippocampal neurogenesis compared with morphine. When tested in vitro, morphine inhibited neuronal differentiation, neurite outgrowth, and survival of adult mouse hippocampal neural progenitors and their progeny, via MOR interaction. By contrast, tapentadol was devoid of these adverse effects on cell survival and reduced neurite outgrowth and the number of newly generated neurons only at nanomolar concentrations where the MOR component is predominant. On the contrary, at higher (micromolar) concentrations, tapentadol elicited proneurogenic and antiapoptotic effects via activation of \u3b22 and \u3b12 adrenergic receptors, respectively. Altogether, these data suggest that the noradrenergic component in tapentadol has the potential to counteract the adverse MOR-mediated effects on hippocampal neurogenesis. As a proof of concept, we showed that reboxetine, an NRI antidepressant, counteracted both antineurogenic and apoptotic effects of morphine in vitro. In line with these observations, chronic tapentadol treatment did not negatively affect hippocampal neurogenesis in vivo. In light of the increasing long-term use of opiates in chronic pain, in principle, the tapentadol combined mechanism of action may result in less or no reduction in adult neurogenesis compared with classic opiates

Modeling of Non-Small Cell Lung Cancer Volume Changes during CT-Based Image Guided Radiotherapy: Patterns Observed and Clinical Implications

Background. To characterize the lung tumor volume response during conventional and hypofractionated radiotherapy (RT) based on diagnostic quality CT images prior to each treatment fraction. Methods. Out of 26 consecutive patients who had received CT-on-rails IGRT to the lung from 2004 to 2008, 18 were selected because they had lung lesions that could be easily distinguished. The time course of the tumor volume for each patient was individually analyzed using a computer program. Results. The model fits of group L (conventional fractionation) patients were very close to experimental data, with a median Δ% (average percent difference between data and fit) of 5.1% (range 3.5–10.2%). The fits obtained in group S (hypofractionation) patients were generally good, with a median Δ% of 7.2% (range 3.7–23.9%) for the best fitting model. Four types of tumor responses were observed—Type A: “high� kill and “slow� dying rate; Type B: “high� kill and “fast� dying rate; Type C: “low� kill and “slow� dying rate; and Type D: “low� kill and “fast� dying rate. Conclusions. The models used in this study performed well in fitting the available dataset. The models provided useful insights into the possible underlying mechanisms responsible for the RT tumor volume response