Predictive Optimal Switching Sequence Direct Power Control for Grid-Connected Power Converters

© 1982-2012 IEEE. Grid-connected power converters play a key role in several applications such as the integration of renewable energy sources and motor drives. For this reason, the development of high performance control strategies for this particular class of power converters has increasingly attracted the interest of both academic and industry researchers. This paper presents the predictive optimal switching sequence (OSS) direct power control (DPC) (OSS-DPC) algorithm for grid-connected converters. The OSS-DPC method belongs to the predictive-DPC family and provides the desired power references by calculating globally OSSs. To address computational and implementation issues, an efficient control algorithm, named reduced OSS-DPC, is introduced. The implementation of the proposed control strategy in a standard DSP is evaluated on a two-level power converter prototype working as a STATCOM. Experimental results show the algorithm's potential to provide high performance during both transient and steady states

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Surface Feature-Guided Mapping of Cerebral Metabolic Changes in Cognitively Normal and Mildly Impaired Elderly

Purpose: The aim of this study was to investigate the longitudinal positron emission tomography (PET) metabolic changes in the elderly. Procedures: Nineteen nondemented subjects (mean Mini-Mental Status Examination 29.4±0.7 SD) underwent two detailed neuropsychological evaluations and resting 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET scan (interval 21.7±3.7 months), baseline structural 3T magnetic resonance (MR) imaging, and apolipoprotein E4 genotyping. Cortical PET metabolic changes were analyzed in 3-D using the cortical pattern matching technique. Results: Baseline vs. follow-up whole-group comparison revealed significant metabolic decline bilaterally in the posterior temporal, parietal, and occipital lobes and the left lateral frontal cortex. The declining group demonstrated 10–15 % decline in bilateral posterior cingulate/precuneus, posterior temporal, parietal, and occipital cortices. The cognitively stable group showed 2.5–5% similarly distributed decline. ApoE4-positive individuals underwent 5–15 % metabolic decline in the posterior association cortices. Conclusions: Using 3-D surface-based MR-guided FDG-PET mapping, significant metaboli

The effect of timing and frequency of push notifications on usage of a smartphone-based stress management intervention: An exploratory trial

Push notifications offer a promising strategy for enhancing engagement with smartphone-based health interventions. Intelligent sensor-driven machine learning models may improve the timeliness of notifications by adapting delivery to a user's current context (e.g. location). This exploratory mixed-methods study examined the potential impact of timing and frequency on notification response and usage of Healthy Mind, a smartphone-based stress management intervention. 77 participants were randomised to use one of three versions of Healthy Mind that provided: intelligent notifications; daily notifications within pre-defined time frames; or occasional notifications within pre-defined time frames. Notification response and Healthy Mind usage were automatically recorded. Telephone interviews explored participants' experiences of using Healthy Mind. Participants in the intelligent and daily conditions viewed (d = .47, .44 respectively) and actioned (d = .50, .43 respectively) more notifications compared to the occasional group. Notification group had no meaningful effects on percentage of notifications viewed or usage of Healthy Mind. No meaningful differences were indicated between the intelligent and non-intelligent groups. Our findings suggest that frequent notifications may encourage greater exposure to intervention content without deterring engagement, but adaptive tailoring of notification timing does not always enhance their use. Hypotheses generated from this study require testing in future work. Trial registration number: ISRCTN67177737 © 2017 Morrison et al

Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models

Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols

Gain in cellular organization of inflammatory breast cancer: A 3D in vitro model that mimics the in vivo metastasis

<p>Abstract</p> <p>Background</p> <p>The initial step of metastasis in carcinomas, often referred to as the epithelial-mesenchymal transition (EMT), occurs via the loss of adherens junctions (e.g. cadherins) by the tumor embolus. This leads to a subsequent loss of cell polarity and cellular differentiation and organization, enabling cells of the embolus to become motile and invasive. However highly malignant inflammatory breast cancer (IBC) over-expresses E-cadherin. The human xenograft model of IBC (MARY-X), like IBC, displays the signature phenotype of an exaggerated degree of lymphovascular invasion (LVI) <it>in situ </it>by tumor emboli. An intact E-cadherin/α, β-catenin axis mediates the tight, compact clump of cells found both <it>in vitro </it>and <it>in vivo </it>as spheroids and tumor emboli, respectively.</p> <p>Methods</p> <p>Using electron microscopy and focused ion beam milling to acquire <it>in situ </it>sections, we performed ultrastructural analysis of both an IBC and non-IBC, E-cadherin positive cell line to determine if retention of this adhesion molecule contributed to cellular organization.</p> <p>Results</p> <p>Here we report through ultrastructural analysis that IBC exhibits a high degree of cellular organization with polar elements such as apical/lateral positioning of E-cadherin, apical surface microvilli, and tortuous lumen-like (canalis) structures. In contrast, agarose-induced spheroids of MCF-7, a weakly invasive E-cadherin positive breast carcinoma cell line, do not exhibit ultrastructural polar features.</p> <p>Conclusions</p> <p>This study has determined that the highly metastatic IBC with an exaggerated malignant phenotype challenges conventional wisdom in that instead of displaying a loss of cellular organization, IBC acquires a highly structured architecture.</p> <p>These findings suggest that the metastatic efficiency might be linked to the formation and maintenance of these architectural features. The comparative architectural features of both the spheroid and embolus of MARY-X provide an <it>in vitro </it>model with tractable <it>in vivo </it>applications.</p

Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds

BACKGROUND: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation. METHODS: Modulation of glycolytic gene expression was evaluated by PCR arrays in tumour cells and primary cultures growing under hypoxia, in spheroids and after PCFT silencing. Inhibitors of lactate dehydrogenase (LDH-A) were tested in vitro and in vivo. LDH-A expression was determined in tissue microarrays of radically resected malignant pleural mesothelioma (MPM, N = 33) and diffuse peritoneal mesothelioma (DMPM, N = 56) patients. RESULTS: Overexpression of hypoxia marker CAIX was associated with low PCFT expression and decreased MPM cell growth inhibition by pemetrexed. Through integration of PCR arrays in hypoxic cells and spheroids and following PCFT silencing, we identified the upregulation of LDH-A, which correlated with shorter survival of MPM and DMPM patients. Novel LDH-A inhibitors enhanced spheroid disintegration and displayed synergistic effects with pemetrexed in MPM and gemcitabine in DMPM cells. Studies with bioluminescent hypoxic orthotopic and subcutaneous DMPM athymic-mice models revealed the marked antitumour activity of the LDH-A inhibitor NHI-Glc-2, alone or combined with gemcitabine. CONCLUSIONS: This study provides novel insights into hypoxia/PCFT-dependent chemoresistance, unravelling the potential prognostic value of LDH-A, and demonstrating the preclinical activity of LDH-A inhibitors

In Vitro Neutralisation of Rotavirus Infection by Two Broadly Specific Recombinant Monovalent Llama-Derived Antibody Fragments

Rotavirus is the main cause of viral gastroenteritis in young children. Therefore, the development of inexpensive antiviral products for the prevention and/or treatment of rotavirus disease remains a priority. Previously we have shown that a recombinant monovalent antibody fragment (referred to as Anti-Rotavirus Proteins or ARP1) derived from a heavy chain antibody of a llama immunised with rotavirus was able to neutralise rotavirus infection in a mouse model system. In the present work we investigated the specificity and neutralising activity of two llama antibody fragments, ARP1 and ARP3, against 13 cell culture adapted rotavirus strains of diverse genotypes. In addition, immunocapture electron microscopy (IEM) was performed to determine binding of ARP1 to clinical isolates and cell culture adapted strains. ARP1 and ARP3 were able to neutralise a broad variety of rotavirus serotypes/genotypes in vitro, and in addition, IEM showed specific binding to a variety of cell adapted strains as well as strains from clinical specimens. These results indicated that these molecules could potentially be used as immunoprophylactic and/or immunotherapeutic products for the prevention and/or treatment of infection of a broad range of clinically relevant rotavirus strains

Biomarkers in anal cancer: from biological understanding to stratified treatment

Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities. Understanding the biology of ASCC promises to allow a more personalised approach to treatment, with the development and validation of a range of biomarkers and associated techniques that are the focus of this review