bluuebunny/crossref_metadata_2025 huggingface dataset:
All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells
Authors: Bolis Marco , Paroni Gabriela , Fratelli Maddalena , Vallerga Arianna , Guarrera Luca , Zanetti Adriana , Kurosaki Mami , Garattini Silvio Ken , Gianni’ Maurizio , Lupi Monica , Pattini Linda , Barzago Maria Monica , Terao Mineko , Garattini Enrico
Published: May 2020

All-trans retinoic acid (ATRA), a recognized differentiating agent, has significant potential in the personalized/stratified treatment of breast cancer. The present study reports on the molecular mechanisms underlying the anti-tumor activity of ATRA in breast cancer. The work is based on transcriptomic experiments performed on ATRA-treated breast cancer cell-lines, short-term tissue cultures of patient-derived mammary-tumors and a xenograft model. ATRA upregulates gene networks involved in interferon-responses, immune-modulation and antigen-presentation in retinoid-sensitive cells and tumors characterized by poor immunogenicity. ATRA-dependent upregulation of these gene networks is caused by a viral mimicry process, involving the activation of endogenous retroviruses. ATRA induces a non-canonical type of viral mimicry, which results in increased expression of the IRF1 (Interferon Responsive Factor 1) transcription factor and the DTX3L (Deltex-E3-Ubiquitin-Ligase-3L) downstream effector. Functional knockdown studies indicate that IRF1 and DTX3L are part of a negative feedback loop controlling ATRA-dependent growth inhibition of breast cancer cells. The study is of relevance from a clinical/therapeutic perspective. In fact, ATRA stimulates processes controlling the sensitivity to immuno-modulatory drugs, such as immune-checkpoint-inhibitors. This suggests that ATRA and immunotherapeutic agents represent rational combinations for the personalized treatment of breast cancer. Remarkably, ATRA-sensitivity seems to be relatively high in immune-cold mammary tumors, which are generally resistant to immunotherapy.
Adhesion and Migration Response to Radiation Therapy of Mammary Epithelial and Adenocarcinoma Cells Interacting with Different Stiffness Substrates
Authors: Panzetta Valeria , La Verde Giuseppe , Pugliese Mariagabriella , Artiola Valeria , Arrichiello Cecilia , Muto Paolo , La Commara Marco , Netti Paolo A. , Fusco Sabato
Published: May 2020

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of their motility. In order to elucidate the role of extracellular matrix stiffness as a driving force in cancer cell motility/invasion and the effects of ionizing radiations on these processes, we evaluated adhesion and migration as biophysical properties of two different mammary cell lines, over a range of pathophysiological stiffness (1–13 kPa) in a control condition and after the exposure to two different X-ray doses (2 and 10 Gy, photon beams). We concluded that the microenvironment mimicking the normal mechanics of healthy tissue has a radioprotective role on both cell lines, preventing cell motility and invasion. Supraphysiological extracellular matrix stiffness promoted tumor cell motility instead, but also had a normalizing effect on the response to radiation of tumor cells, lowering their migratory capability. This work lays the foundation for exploiting the extracellular matrix-mediated mechanism underlying the response of healthy and tumor cells to radiation treatments and opens new frontiers in the diagnostic and therapeutic use of radiotherapy.
Inducing Angiogenesis, a Key Step in Cancer Vascularization, and Treatment Approaches
Authors: Saman Harman , Raza Syed Shadab , Uddin Shahab , Rasul Kakil
Published: May 2020

Angiogenesis is a term that describes the formation of new blood and lymphatic vessels from a pre-existing vasculature. This allows tumour cells to acquire sustenance in the form of nutrients and oxygen and the ability to evacuate metabolic waste. As one of the hallmarks of cancer, angiogenesis has been studied extensively in animal and human models to enable better understanding of cancer biology and the development of new anti-cancer treatments. Angiogenesis plays a crucial role in the process of tumour genesis, because solid tumour need a blood supply if they are to grow beyond a few millimeters in size. On the other hand, there is growing evidence that some solid tumour exploit existing normal blood supply and do not require a new vessel formation to grow and to undergo metastasis. This review of the literature will present the current understanding of this intricate process and the latest advances in the use of angiogenesis-targeting therapies in the fight against cancer.
CD34+CD38−CD123+ Leukemic Stem Cell Frequency Predicts Outcome in Older Acute Myeloid Leukemia Patients Treated by Intensive Chemotherapy but Not Hypomethylating Agents
Authors: Vergez François , Nicolau-Travers Marie-Laure , Bertoli Sarah , Rieu Jean-Baptiste , Tavitian Suzanne , Bories Pierre , Luquet Isabelle , De Mas Véronique , Largeaud Laetitia , Sarry Audrey , Huguet Françoise , Delabesse Eric , Bérard Emilie , Récher Christian
Published: May 2020

The prognostic impact of immunophenotypic CD34+CD38−CD123+ leukemic stem cell (iLSC) frequency at diagnosis has been demonstrated in younger patients treated by intensive chemotherapy, however, this is less clear in older patients. Furthermore, the impact of iLSC in patients treated by hypomethylating agents is unknown. In this single-center study, we prospectively assessed the CD34+CD38−CD123+ iLSC frequency at diagnosis in acute myeloid leukemia (AML) patients aged 60 years or older. In a cohort of 444 patients, the median percentage of iLSC at diagnosis was 4.3%. Significant differences were found between treatment groups with a lower median in the intensive chemotherapy group (0.6%) compared to hypomethylating agents (8.0%) or supportive care (11.1%) (p <0.0001). In the intensive chemotherapy group, the median overall survival was 34.5 months in patients with iLSC ≤0.10% and 14.6 months in patients with >0.10% (p = 0.031). In the multivariate analyses of this group, iLSC frequency was significantly and independently associated with the incidence of relapse, event-free, relapse-free, and overall survival. However, iLSC frequency had no prognostic impact on patients treated by hypomethylating agents. Thus, the iLSC frequency at diagnosis is an independent prognostic factor in older acute myeloid patients treated by intensive chemotherapy but not hypomethylating agents.
The Extracellular Matrix Influences Ovarian Carcinoma Cells’ Sensitivity to Cisplatinum: A First Step towards Personalized Medicine
Authors: Balduit Andrea , Agostinis Chiara , Mangogna Alessandro , Maggi Veronica , Zito Gabriella , Romano Federico , Romano Andrea , Ceccherini Rita , Grassi Gabriele , Bonin Serena , Bonazza Deborah , Zanconati Fabrizio , Ricci Giuseppe , Bulla Roberta
Published: May 2020

The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients’ responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells’ phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients’ responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients.
Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy
Authors: Blankenstein Stephanie A. , Aarts Maureen J. B. , van den Berkmortel Franchette W. P. J. , Boers-Sonderen Marye J. , van den Eertwegh Alfons J. M. , Franken Margreet G. , de Groot Jan Willem B. , Haanen John B. A. G. , Hospers Geke A. P. , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn S. , Suijkerbuijk Karijn P. M. , ten Tije Albert J. , van der Veldt Astrid A. M. , Vreugdenhil Gerard , Wouters Michel W. J. M. , van Akkooi Alexander C. J.
Published: May 2020

Opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapeutics over the past decade. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage IIIC and IV melanoma, who have previously been treated with immunotherapy or targeted therapy. Data was extracted from the Dutch Melanoma Treatment Registry (DMTR) on 154 patients obtaining disease control to systemic therapy and undergoing subsequent surgery. Disease control was defined as a complete response (CR), which was seen in 3.2% of patients; a partial response (PR), seen in 46.1% of patients; or stable disease (SD), seen in 44.2% of patients. At a median follow-up of 10.0 months (interquartile range 4–22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression-free survival (PFS) was 9.0 months (95% CI 6.3–11.7). A CR or PR at first follow-up after surgery was associated with both a better OS and PFS compared to stable or progressive disease (p < 0.001). We conclude that selected patients can benefit from surgery after achieving disease control with systemic therapy.
Influence of Different Birnessite Interlayer Alkali Cations on Catalytic Oxidation of Soot and Light Hydrocarbons
Authors: Jakubek Tomasz , Hudy Camillo , Stelmachowski Paweł , Nowicka Ewa , Golunski Stan , Kotarba Andrzej
Published: May 2020

A series of layered birnessite (AMn4O8) catalysts containing different alkali cations (A = H+, Li+, Na+, K+, Rb+, or Cs+) was synthesized. The materials were thoroughly characterized using X-ray diffraction, X-ray fluorescence, X-ray photoelectron spectroscopy, Raman spectroscopy, specific surface area analysis, work function, thermogravimetry/differential scanning calorimetry, and transmission electron microscopy. The catalytic activity in soot combustion in different reaction modes was investigated (tight contact, loose contact, loose contact with NO addition). The activity in the oxidation of light hydrocarbons was evaluated by tests with methane and propane. The obtained results revealed that alkali-promoted manganese oxides are highly catalytically active in oxidative reactions. In soot combustion, the reaction temperature window was shifted by 195 °C, 205 °C, and 90 °C in tight, loose + NO, and loose contact conditions against uncatalyzed oxidation, respectively. The catalysts were similarly active in hydrocarbon combustion, achieving a 40% methane conversion at 600 °C and a total propane conversion at ~450 °C. It was illustrated that the difference in activity between tight and loose contacts can be successfully bridged in the presence of NO due to its facile transformation into NO2 over birnessite. The particular activity of birnessite with H+ cations paves the road for the further development of the active phase, aiming at alternative catalytic systems for efficient soot, light hydrocarbons, and volatile organic compounds removal in the conditions present in combustion engine exhaust gases.
Influence of Indoleamine-2,3-Dioxygenase and Its Metabolite Kynurenine on γδ T Cell Cytotoxicity against Ductal Pancreatic Adenocarcinoma Cells
Authors: Jonescheit Hannah , Oberg Hans-Heinrich , Gonnermann Daniel , Hermes Martin , Sulaj Vjola , Peters Christian , Kabelitz Dieter , Wesch Daniela
Published: May 2020

Background: Pancreatic ductal adenocarcinoma (PDAC) is a malignant gastrointestinal disease. The enzyme indoleamine-2,3-dioxgenase (IDO) is often overexpressed in PDAC and its downstream metabolite kynurenine has been reported to inhibit T cell activation and proliferation. Since γδ T cells are of high interest for T cell-based immunotherapy against PDAC, we studied the impact of IDO and kynurenine on γδ T cell cytotoxicity against PDAC cells. Methods: IDO expression was determined in PDAC cells by flow cytometry and Western blot analysis. PDAC cells were cocultured with γδ T cells in medium or were stimulated with phosphorylated antigens or bispecific antibody in the presence or absence of IDO inhibitors. Additionally, γδ T cells were treated with recombinant kynurenine. Read-out assays included degranulation, cytotoxicity and cytokine measurement as well as cell cycle analysis. Results: Since IDO overexpression was variable in PDAC, IDO inhibitors improved γδ T cell cytotoxicity only against some but not all PDAC cells. γδ T cell degranulation and cytotoxicity were significantly decreased after their treatment with recombinant kynurenine. Conclusions: Bispecific antibody drastically enhanced γδ T cell cytotoxicity against all PDAC cells, which can be further enhanced by IDO inhibitors against several PDAC cells, suggesting a striking heterogeneity in PDAC escape mechanisms towards γδ T cell-mediated anti-tumor response.
p62 is Negatively Implicated in the TRAF6-BECN1 Signaling Axis for Autophagy Activation and Cancer Progression by Toll-Like Receptor 4 (TLR4)
Authors: Kim Mi-Jeong , Min Yoon , Im Ji Seon , Son Juhee , Lee Joo Sang , Lee Ki-Young
Published: May 2020

Toll-like receptors (TLRs) induce the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and autophagy through the TNF (Tumor necrosis factor) receptor-associated factor 6 (TRAF6)-evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) and TRAF6-BECN1 signaling axes, respectively. Having shown that p62 negatively regulates Toll-like receptor 4 (TLR4)-mediated signaling via TRAF6-ECSIT signaling axis, we herein investigated whether p62 is functionally implicated in the TRAF6-BECN1 signaling axis, thereby regulating cancer cell migration and invasion. p62 interacted with TRAF6 and BECN1, to interrupt the functional associations required for TRAF6-BECN1 complex formation, leading to inhibitions of BECN1 ubiquitination and autophagy activation. Importantly, p62-deficient cancer cells, such as p62-knockdown (p62KD) SK-HEP-1, p62KD MDA-MB-231, and p62-knockout (p62KO) A549 cells, showed increased activation of autophagy induced by TLR4 stimulation, suggesting that p62 negatively regulates autophagy activation. Moreover, these p62-deficient cancer cells exhibited marked increases in cell migration and invasion in response to TLR4 stimulation. Collectively, these results suggest that p62 is negatively implicated in the TRAF6-BECN1 signaling axis, thereby inhibiting cancer cell migration and invasion regulated by autophagy activation in response to TLR4 stimulation.
The Bioinformatic and In Vitro Studies of Clostridioides Difficile Aminopeptidase M24 Revealed the Immunoreactive KKGIK Peptide
Authors: Pacyga Katarzyna , Razim Agnieszka , Martirosian Gayane , Aptekorz Małgorzata , Szuba Andrzej , Gamian Andrzej , Myc Andrzej , Górska Sabina
Published: May 2020

Clostridioides difficile (CD) is a Gram-positive pathogen responsible for CD-associated disease (CDAD), which is characterized by symptoms ranging from mild diarrhea to pseudomembranous colitis. This work is an attempt to respond to the need of novel methods for CD infection (CDI) prevention, since the number of CDI cases is still rising. A bioinformatics approach was applied to design twenty-one peptides consisting of in silico predicted linear B-cell and T-cell epitopes of aminopeptidase M24 from CD. These peptides were mapped for epitopes exploiting PEPSCAN procedure and using sera obtained from CD infected patients, umbilical cord blood, and healthy volunteers. Two new CD epitopes, 131KKGIK135 and 184KGTSTHVIT192, were identified and characterized. Immunoreactivity of the synthetic biotinylated 131KKGIK135 epitope was significantly higher compared to 184KGTSTHVIT192 epitope in Enzyme-Linked Immunosorbent Assay (ELISA) with umbilical cord blood and CDI patients’ sera. Hereafter, the conjugate of bovine serum albumin and epitope 131KKGIK135 was evaluated in vitro on lung epithelial cell line. In vitro, a significant induction of IL-6 by conjugate was observed, thereby we postulate that this new 131KKGIK135 epitope possesses immunostimulating properties suggesting possibility of its use in a vaccine against Clostridioides difficile.
Tunable Hierarchical Nanostructures on Micro-Conical Arrays of Laser Textured TC4 Substrate by Hydrothermal Treatment for Enhanced Anti-Icing Property
Authors: Liu Mengyao , Zhou Rui , Chen Zhekun , Yan Huangping , Cui Jingqin , Liu Wanshan , Pan Jia Hong , Hong Minghui
Published: May 2020

In this work, an anti-icing structured surface was fabricated by combining laser ablation with hydrothermal treatment. A micro-patterned surface on a Ti alloy (TC4) substrate was easily fabricated by a highly effective nanosecond pulsed laser ablation. It was observed that titania (TiO2) nanostructures were formed by hydrothermal treatment in aqueous alkali on the laser ablated TC4 substrate to obtain the micro/nano-hierarchical structures. The growth mechanism of the tunable nanoarrays was discussed by the adjustment of hydrothermal temperature. The as-prepared samples exhibited excellent superhydrophobicity with contact angles greater than 160°. It was found that optimized hydrothermal treatment on laser-processed TC4 substrates could further enhance surface anti-icing property. The results showed that the delay time (DT) had been extended by achieving over 90 min for the water droplets to freeze on the as-prepared structured surfaces, providing great potential in various anti-icing applications.
The Surface Morphology of a Ti–6Al–4V Fiber-Lasered Nitride Layer
Authors: Guo Jinchang , Shi Yu , Geng Peibiao , Zhang Gang , Zhu Ming
Published: May 2020

A fiber laser was used to nitride Ti–6Al–4V titanium alloy the effect of the process parameters on the surface morphology was studied. The surface chemical composition of the nitride layer and the phase of black powder on the surface were analyzed, the two-dimensional and three-dimensional surface topography of the nitride layer surface were measured, and the cross-section microstructure of the nitride layer was photographed. The effects of laser power, laser scanning speed, nozzle distance, and nitrogen flow rate on the surface morphology were studied. The experiments show that the laser power mainly affects the surface oxidation, the laser scanning speed mainly affects the surface roughness, and the nozzle distance has a great influence on the surface morphology. The gas flow rate, however, had a slight effect on the surface morphology. A large heat input and a high nitrogen flow rate caused an increase in TiN and TiO2 black powders. Surface oxidation did not affect the formation of a continuous TiN layer nor surface roughness. Finally, the critical energy density leading to increased surface roughness was calculated.
X-ray Induced Hydroxyl Radical Generation by GdYVO4:Eu3+ Nanoparticles in Aqueous Solution: Main Mechanisms
Authors: Maksimchuk Pavel , Yefimova Svetlana , Omielaieva Valeriia , Hubenko Kateryna , Klochkov Vladimir , Opolonin Oleksandr , Malyukin Yuri
Published: May 2020

We report on strong X-ray-induced hydroxyl radical (. O H ) generation in an aqueous solution containing UV light pre-treated GdYVO4:Eu3+ nanoparticles (L-GdYVO). The methods of optical spectroscopy were used to detect . O H in the solutions. The complex nature of the mechanism of . O H generation has been revealed and discussed. The experimental data obtained indicate that the mechanism of . O H generation is associated with two main processes: (i) direct . O H generation with the participation of thermalized h+ formed at X-ray irradiation, and (ii) X-ray-facilitated jumps of h+ formed in the nanoparticles’ (NPs’) valence band at UV light pre-treatment and trapped in local levels formed by random scattering potential. At the same time, for GdYVO4:Eu3+ nanoparticles, which were not exposed to UV light before the X-ray irradiation (D-GdYVO), a strong radioprotective effect ascribed to the electron-donation properties of V4+ ions was observed. Thus, depending on the pre-treatment condition, we can change the redox properties of GdYVO4:Eu3+ NPs in an opposite direction, which makes this nanomaterial a unique theranostic agent for radiation therapy (RT) enhancement, allowing the problem of radiation therapy (RT)-resistant hypoxic tumours to be overcome.
Life History Divergence in Livebearing Fishes in Response to Predation: Is There a Microevolution to Macroevolution Barrier?
Authors: Belk Mark C. , Ingley Spencer J. , Johnson Jerald B.
Published: May 2020

A central problem in evolutionary biology is to determine whether adaptive phenotypic variation within species (microevolution) ultimately gives rise to new species (macroevolution). Predation environment can select for trait divergence among populations within species. The implied hypothesis is that the selection resulting from predation environment that creates population divergence within species would continue across the speciation boundary such that patterns of divergence after speciation would be a magnified accumulation of the trait variation observed before speciation. In this paper, we test for congruence in the mechanisms of microevolution and macroevolution by comparing the patterns of life history divergence among three closely related species of the livebearer genus Brachyrhaphis (Poeciliidae), namely B. rhabdophora, B. roseni, and B. terrabensis. Within B. rhabdophora, populations occur in either predator or predator-free environments, and have been considered to be at a nascent stage of speciation. Sister species B. roseni and B. terrabensis are segregated into predator and predator-free environments, respectively, and represent a post-speciation comparison. Male and female size at maturity, clutch size, and offspring size (and to a lesser extent reproductive allocation) all diverged according to predation environment and differences were amplified through evolutionary time, i.e., across the speciation boundary. Variation observed among nascent species differentiated by predation environment is a good predictor of variation among established species differentiated by predation environment. We found no evidence for different processes or different levels of selection acting across the speciation boundary, suggesting that macroevolution in these species can be understood as an accumulation of micro-evolutionary changes.
Same Diet, Different Strategies: Variability of Individual Feeding Habits across Three Populations of Ambrosi’s Cave Salamander (Hydromantes ambrosii)
Authors: Lunghi Enrico , Cianferoni Fabio , Ceccolini Filippo , Zhao Yahui , Manenti Raoul , Corti Claudia , Ficetola Gentile Francesco , Mancinelli Giorgio
Published: May 2020

European cave salamanders of the genus Hydromantes are a group of eight species endemic to Italy and south-eastern France. Knowledge on the trophic niche of European Hydromantes is poor, and the few available studies only partially investigate their feeding habits. We performed an in-depth study on the trophic niche of the Ambrosi’s cave salamander (H. ambrosii), assessing the potential divergences among three different populations. All the populations had a similar diet composition, showing a wider trophic niche in fall compared to spring. In only one population, “true specialists” were present; however, in all three populations, generalist individuals always represented the larger proportion. Interspecific and intraspecific competition did not play an important role in determining individual dietary specialisation in H. ambrosii; contrarily, the characteristics of the surrounding environment seemed to be an important factor. The best body conditions were observed in the population located in the site where the non-arboreal vegetation cover was the highest. Besides providing new information on the trophic niche of H. ambrosii, we here showed that studies encompassing both intrinsic and extrinsic factors at the population level are needed to fully understand the trophic dynamics occurring among European cave salamanders.
Feeding Strategies of Co-occurring Newt Species across Different Conditions of Syntopy: A Test of the “Within-Population Niche Variation” Hypothesis
Authors: Mirabasso Jennifer , Bissattini Alessandra M. , Bologna Marco A. , Luiselli Luca , Stellati Luca , Vignoli Leonardo
Published: May 2020

Intraspecific trait variation in generalist animals is widespread in nature, yet its effects on community ecology are not well understood. Newts are considered opportunistic feeders that may co-occur in different syntopic conditions and represent an excellent model for studying the role of individual feeding specialization in shaping the population dietary strategy. Here, we investigated the diet of three newt species from central Italy occurring in artificial habitats in different coexistence conditions to test the predictions of the niche width (NW) variation hypotheses. Population NW did not vary among species and between presence and absence of coexisting species. An overall positive relationship between individual specialization and population NW was observed. However, this pattern was disrupted by the condition of syntopy with newt populations showing an individual NW variation invariant with population NW in presence of coexisting species, whereas it was larger in populations occurring alone. The observed pattern of newt behavior was not consistent with any of the proposed scenarios. We found a consistent pattern with the degree of individual specialization being (1) size-dependent (specialized individuals increasing within larger sized species) and (2) assemblage-complexity-dependent (specialized individuals increasing in syntopic populations in comparison to singly populations).
CCNE1 Amplification as a Predictive Biomarker of Chemotherapy Resistance in Epithelial Ovarian Cancer
Authors: Gorski Justin W. , Ueland Frederick R. , Kolesar Jill M.
Published: May 2020

Ovarian cancer is the most-deadly gynecologic malignancy, with greater than 14,000 women expected to succumb to the disease this year in the United States alone. In the front-line setting, patients are treated with a platinum and taxane doublet. Although 40–60% of patients achieve complete clinical response to first-line chemotherapy, 25% are inherently platinum-resistant or refractory with a median overall survival of about one year. More than 80% of women afflicted with ovarian cancer will recur. Many attempts have been made to understand the mechanism of platinum and taxane based chemotherapy resistance. However, despite decades of research, few predictive markers of chemotherapy resistance have been identified. Here, we review the current understanding of one of the most common genetic alterations in epithelial ovarian cancer, CCNE1 (cyclin E1) amplification, and its role as a potential predictive marker of cytotoxic chemotherapy resistance. CCNE1 amplification has been identified as a primary oncogenic driver in a subset of high grade serous ovarian cancer that have an unmet clinical need. Understanding the interplay between cyclin E1 amplification and other common ovarian cancer genetic alterations provides the basis for chemotherapeutic resistance in CCNE1 amplified disease. Exploration of the effect of cyclin E1 amplification on the cellular machinery that causes dysregulated proliferation in cancer cells has allowed investigators to explore promising targeted therapies that provide the basis for emerging clinical trials.
The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns
Authors: Caparrós-Martín Jose A. , Flynn Stephanie , Reen F. Jerry , Woods David F. , Agudelo-Romero Patricia , Ranganathan Sarath C. , Stick Stephen M. , O’Gara Fergal
Published: May 2020

Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.
Playing with Complex Systems? The Potential to Gain Geographical System Competence through Digital Gaming
Authors: Lux Joelle-Denise , Budke Alexandra
Published: May 2020

The current socio-ecological challenges and phenomena that are major topics of geography education, like climate change and migration, are highly complex. Maturity in these contexts requires a networked way of thinking, and a systemic competence that is difficult to develop in geography classes alone. Digital games that simulate complex systems which include the pressing issues of today’s challenges may be a useful supplement to foster systems thinking. In this study, we develop a framework to assess the complexity of in-game systems. A subsequent analysis of a selection of current commercial strategy and simulation games shows how system complexity is designed differently in the various games. Based on these results, we make recommendations for the selection and use of different games in formal and informal learning contexts.
Combined Color Semantics and Deep Learning for the Automatic Detection of Dolphin Dorsal Fins
Authors: Renò Vito , Losapio Gianvito , Forenza Flavio , Politi Tiziano , Stella Ettore , Fanizza Carmelo , Hartman Karin , Carlucci Roberto , Dimauro Giovanni , Maglietta Rosalia
Published: May 2020

Photo-identification is a widely used non-invasive technique in biological studies for understanding if a specimen has been seen multiple times only relying on specific unique visual characteristics. This information is essential to infer knowledge about the spatial distribution, site fidelity, abundance or habitat use of a species. Today there is a large demand for algorithms that can help domain experts in the analysis of large image datasets. For this reason, it is straightforward that the problem of identify and crop the relevant portion of an image is not negligible in any photo-identification pipeline. This paper approaches the problem of automatically cropping cetaceans images with a hybrid technique based on domain analysis and deep learning. Domain knowledge is applied for proposing relevant regions with the aim of highlighting the dorsal fins, then a binary classification of fin vs. no-fin is performed by a convolutional neural network. Results obtained on real images demonstrate the feasibility of the proposed approach in the automated process of large datasets of Risso’s dolphins photos, enabling its use on more complex large scale studies. Moreover, the results of this study suggest to extend this methodology to biological investigations of different species.
Energy Modelling as a Trigger for Energy Communities: A Joint Socio-Technical Perspective
Authors: Bukovszki Viktor , Magyari Ábel , Braun Marina Kristina , Párdi Kitti , Reith András
Published: May 2020

Mainstreaming energy communities has been one of the main challenges in the low-carbon transition of cities. In this sense, urban building energy modelling (UBEM) has an untapped role in enabling energy communities, as simulations on urban models provide evidence-based decision support to reduce risks, engage, motivate and guide actors, assert wider policy goals and regulatory requirements. This accelerating role and the potential of UBEM is not sufficiently understood, as research into energy community focuses on its barriers and impacts, while the research of UBEM is mainly technologically oriented. This review takes a sociotechnical approach to explore whether UBEM is a technological trigger for energy communities, furthering the conceptual framework of transition management. factors influencing energy community progression in different use-cases and stages of their lifecycle are compiled to assess the affordances of distinct capabilities of prevalent UBEM tools. The study provides a guide for energy community planners to UBEM. It matches different tool capabilities to the various stages of the project lifecycle for the different use-cases, equipping them with the means to accelerate the low-carbon transition of cities from the bottom-up. Finally, the study defines a development trajectory oriented towards application in urban sustainability to a rather new UBEM field.
Less Information, Similar Performance: Comparing Machine Learning-Based Time Series of Wind Power Generation to Renewables.ninja
Authors: Baumgartner Johann , Gruber Katharina , Simoes Sofia G. , Saint-Drenan Yves-Marie , Schmidt Johannes
Published: May 2020

Driven by climatic processes, wind power generation is inherently variable. Long-term simulated wind power time series are therefore an essential component for understanding the temporal availability of wind power and its integration into future renewable energy systems. In the recent past, mainly power curve-based models such as Renewables.ninja (RN) have been used for deriving synthetic time series for wind power generation, despite their need for accurate location information and bias correction, as well as their insufficient replication of extreme events and short-term power ramps. In this paper, we assessed how time series generated by machine learning models (MLMs) compare to RN in terms of their ability to replicate the characteristics of observed nationally aggregated wind power generation for Germany. Hence, we applied neural networks to one wind speed input dataset derived from MERRA2 reanalysis with no location information and two with additional location information. The resulting time series and RN time series were compared with actual generation. All MLM time series feature an equal or even better time series quality than RN, depending on the characteristics considered. We conclude that MLM models show a similar performance to RN, even when information on turbine locations and turbine types is unavailable.
Altered Grey Wolf Optimization and Taguchi Method with FEA for Six-Phase Copper Squirrel Cage Rotor Induction Motor Design
Authors: Lin Chih-Hong
Published: May 2020

This paper presents an altered grey wolf optimization, the Taguchi method, and finite element analysis (FEA) with two-phase multi-objective optimization for the design of a six-phase copper squirrel cage rotor induction motor (SCSCRIM). The multi-objective optimization design with high-performance property aims to achieve lower starting current, lower losses, lower input power, higher efficiency, higher output torque, and higher power factor. The multi-objective optimization design with high-performance property using the altered grey wolf optimization, the Taguchi method, and FEA in the first-phase program is used for minimizing the starting current, stator iron loss, stator copper loss, and input power. The multi-objective optimization design with high-performance property using the altered grey wolf optimization, the Taguchi method, and FEA in the second-phase program is used for maximizing the efficiency, output torque, and power factor. Finally, the proposed skill with higher performances is evaluated and verified via a two-phase program design and some performance tests.
Use of Analytic Hierarchy Process for Wind Farm Installation Region Prioritization–Case Study
Authors: Lemos Bulhões Rômulo , Souza de Santana Eudemário , Álisson Bandeira Santos Alex
Published: May 2020

Electricity generation via renewable sources is emerging as a possible solution to meet the growing demand for electricity worldwide. Additionally, the need to produce clean energy, with little or no pollutants or greenhouse gas emission is paramount. Due to these factors, wind farms are noticeably increasing in number, especially in Brazil. However, the vast size of the country and the poor quality of its infrastructure are among several factors that make it difficult for effective decision-making to accelerate the growth of this segment in Brazil. With the purpose of assisting government agencies, regulatory agencies and other institutions in this area, the use of a multi-criteria selection method called the analytic hierarchy process is proposed here to assist in decision-making and to select priority regions for implementing wind farms. This work focuses on a case study of the state of Bahia, in which 27 territories were selected for an installation priority evaluation. Computational tools were used to hierarchize these chosen territories, including Matlab, for the construction of the computational algorithm. The results indicate the priority pf the regions according to the established criteria, which allows installation locations to be mapped—these could serve as a basis for regional investment.
A Case Study of LightStay (2010–2017)—Hilton’s Corporate Responsibility Management System
Authors: Zientara Piotr , Bohdanowicz-Godfrey Paulina , Whitely Claire , Maciejewski Grzegorz
Published: May 2020

This paper focuses on Hilton’s proprietary sustainability performance measurement system (SPMS) called LightStay (2010–2017). It draws on the case-study method and relies on three principal sources of information: in-house documents, a questionnaire completed by users of LightStay and interviews conducted with external experts. Specifically, the paper traces the system’s evolution and highlights its distinctive features, exploring the challenges and trade-offs related to the design and workings of an SPMS in a hotel multinational. The study shows, among other things, how LightStay, using an internationally approved methodology of data collection, calculation, metrics and benchmarking, compares a hotel’s predicted and actual environmental performance. It concludes by arguing that LightStay is a holistic platform that not only integrates precise measurement of the firm’s environmental effects with its business operations and strategic goals but also acts as a repository of sustainability knowledge and a facilitator of organisational learning. Its value and originality lie in providing unique insights into the workings of a proprietary SPMS at a nonanonymised hotel company.
Decision Support System to Implement Units of Alternative Biowaste Treatment for Producing Bioenergy and Boosting Local Bioeconomy
Authors: Vlachokostas Christos , Achillas Charisios , Agnantiaris Ioannis , Michailidou Alexandra V. , Pallas Christos , Feleki Eleni , Moussiopoulos Nicolas
Published: May 2020

Lately, the model of circular economy has gained worldwide interest. Within its concept, waste is viewed as a beneficial resource that needs to be re-introduced in the supply chains, which also requires the use of raw materials, energy, and water to be minimized. Undeniably, a strong link exists between the bioeconomy, circular economy, bioproducts, and bioenergy. In this light, in order to promote a circular economy, a range of alternative options and technologies for biowaste exploitation are currently available. In this paper, we propose a generic methodological scheme for the development of small, medium, or large-scale units of alternative biowaste treatment, with an emphasis on the production of bioenergy and other bioproducts. With the use of multi-criteria decision analysis, the model simultaneously considers environmental, economic, and social criteria to support robust decision-making. In order to validate the methodology, the latter was demonstrated in a real-world case study for the development of a facility in the region of Serres, Greece. Based on the proposed methodological scheme, the optimal location of the facility was selected, based on its excellent assessment in criteria related to environmental performance, financial considerations, and local acceptance. Moreover, anaerobic digestion of agricultural residues, together with farming and livestock wastes, was recommended in order to produce bioenergy and bioproducts.
Comparative Numerical Analysis on Vertical Wind Turbine Rotor Pattern of Bach and Benesh Type
Authors: Scheaua Fanel Dorel
Published: May 2020

In this work, 3D models in classic configuration of Bach and Benesh rotor type, as well as models with modified blade pattern geometry were analyzed from the air circulation point of view inside the rotor enclosure in order to identify the operating parameters differences according to rotor geometric modified configuration. Constructive design aspects are presented, as well as results obtained from the virtual model analysis in terms of circulation velocity and pressure values which enhance rotor operation related to torque and power coefficients. The rotors design pattern is made according to previous results obtained by different researchers who have performed numerical analysis on virtual models and tests on the experimental rotor models using the wind tunnel. The constructive solutions are describing two-bladed rotor models, in four new designed constructive variants and analyzed using ANSYS CFX. The air velocity specific values, static and total pressure recorded at the rotor blade level are highlighted, that influence the obtaining of rotor shaft torque and power. Also torque coefficient (CT) and power coefficient (CP) values according with specific values of tip speed ratio (TSR) are presented for each analyzed case. The analysis results show higher power coefficient values for analyzed Bach V2 and Benesh V2 rotor modified models compared to the classic Bach and Benesh models for 0.3 TSR of 0.11–012 CP, 0.4 TSR of 0.18 CP (Benesh V2 model) and 0.27 CP at 0.6 TSR (Bach V2). The resulted values confirm that Benesh V2 model offers higher CP up to 5% at TSR 0.3, 2% at TSR 0.6 and 3% at TSR 0.4 compared to the Benesh classical model. The Bach V2 model offers 4% higher CP compared to the classic Bach model at TSR 0.6. Based on these results it is intended the further analytical and experimental research in order to obtain optimal rotor pattern.
Nucleate Pool Boiling Heat Transfer from High-Flux Tube with Dielectric Fluid HFE-7200
Authors: Kumar Abhishek , Hung Kuo-Shu , Wang Chi-Chuan
Published: May 2020

In the present experimental study, nucleate pool boiling heat transfer measurements of two high-flux tubes (sample A and sample B) were conducted at atmospheric pressure with HFE-7200 as the working fluid. Both high-flux tubes were made from a sintered Cu-Ni (high-flux) alloy powder. The porous high-flux surface was coated inside the test tube and it is tested within the heat flux ranging from 2.6 to 86 kW/m2. The major difference between sample A and sample B was the coating thickness, where sample B (0.6 mm) was much larger than that of sample A (0.07 mm). Both tubes showed about three times enhancement in heat transfer coefficient (HTC) when compared to plain tube. Even though sample B contained a higher HTC than sample A, it also revealed a faster level-off phenomenon regarding the HTC vs. wall superheat. The major parameter which characterizes the boiling performance of high-flux tube was the ratio of coating thickness to pore diameter which also yielded different trends upon HTC vs. wall superheat amid sample A and B. It was found that the porous based Nishikawa correlation can well predict the performance of sample A but not sample B. This is because the ratio of coating thickness to pore diameter is far outside the applicable range of the Nishikawa correlation. Hence, a modified Nishikawa correlation is proposed. The predicted capability of the proposed modified Nishikawa correlation against sample A and sample for HTC was within ±28% deviation. The standard mean deviation of the Nishikawa correlation with experimental data for sample A and sample B was 0.302 (12.48%) and 5.64 (73%), respectively.
In Vitro Characterisation of the Antioxidative Properties of Whey Protein Hydrolysates Generated under pH- and Non pH-Controlled Conditions
Authors: Kleekayai Thanyaporn , Le Gouic Aurélien V. , Deracinois Barbara , Cudennec Benoit , FitzGerald Richard J.
Published: May 2020

Bovine whey protein concentrate (WPC) was hydrolysed under pH-stat (ST) and non pH-controlled (free-fall, FF) conditions using Debitrase (DBT) and FlavorPro Whey (FPW). The resultant whey protein hydrolysates (WPHs) were assessed for the impact of hydrolysis conditions on the physicochemical and the in vitro antioxidant and intracellular reactive oxygen species (ROS) generation in oxidatively stressed HepG2 cells. Enzyme and hydrolysis condition dependent differences in the physicochemical properties of the hydrolysates were observed, however, the extent of hydrolysis was similar under ST and FF conditions. Significantly higher (p < 0.05) in vitro and cellular antioxidant activities were observed for the DBT compared to the FPW–WPHs. The WPHs generated under ST conditions displayed significantly higher (p < 0.05) oxygen radical absorbance capacity (ORAC) and Trolox equivalent antioxidant capacity (TEAC) values compared to the FF-WPHs. The impact of hydrolysis conditions was more pronounced in the in vitro compared to the cellular antioxidant assay. WPH peptide profiles (LC-MS/MS) were also enzyme and hydrolysis conditions dependent as illustrated in the case of β-lactoglobulin. Therefore, variation in the profiles of the peptides released may explain the observed differences in the antioxidant activity. Targeted generation of antioxidant hydrolysates needs to consider the hydrolysis conditions and the antioxidant assessment method employed.