bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory pathways involved in adipose tissue hypertrophy and the effect of Acai (Euterpe oleracea Martius) on the modulation of this process: a review
Authors: Souza Tamires Cássia de Melo , Souza Gabriel Vitor de Melo , Volp Ana Carolina Pinheiro
Published: August 2020

Adipose tissue plays an important role in chronic inflammation and the presence of bioactive compounds in food has been widely discussed as a means of prevention and treatment of various pathological conditions. The aim of this review is to promote an overview and elucidate pathways involved in the chronic inflammatory process triggered by adipose tissue hypertrophy and to discuss data related to the use of Acai in the modulation of inflammation. Initially, a narrative review was carried out on metabolic and molecular pathways involved in the process of subclinical chronic inflammation (NF-κB, AP-1, cross-talk between macrophages and adipocytes, increased LPS and Nrf2 pathway). Then, an integrative review was carried out on the effect of Acai in processes of chronic subclinical inflammation in humans. The database consulted was PubMed, in which the name of the fruit was crossed with the descriptors "inflammation" and "chronic diseases", prioritizing in vivo and in vitro studies related to the human species, carried out in the last ten years. It was observed that the immunomodulatory effects of Acai are increasingly clear, however, are not enough to classify the fruit as a tool in the treatment and prevention of metabolic diseases. To make possible more comprehensive inferences, it is necessary that future studies include assessment of the bioavailability of the bioactive compounds present, in addition to being performed using more suitable methods, with humans, containing sample size calculation, control group and placebo.
Fatores biológicos do nascimento e o excesso de peso de adolescentes: prospectando sobre o imprinting metabólico
Authors: Canuto Pollyanna Jorge , Dantas Jaqueline Costa , De Farias Camilla Ribeiro Lima , De Carvalho Danielle Franklin
Published: August 2020

Estudo transversal, de abordagem quantitativa, realizado em duas escolas municipais de Campina Grande-PB, com escolares entre 10 e 16 anos 11 meses e 29 dias, com sobrepeso ou obesidade. Os dados foram coletados através de questionário e medidas antropométricas, entre maio e agosto de 2018. A seleção da amostra foi conglomerada e estratificada por porte escolar, sendo a amostra final constituída por 71 escolares. Foram excluídos os que apresentassem limitação motora, cognitiva e pulmonar; presença de síndrome genética; realização de tratamento para emagrecer; uso de medicamentos que alterem o metabolismo; condição de puerpério, gravidez ou lactação. Para análise dos dados, utilizou-se o programa SPSS - versão 22.0, considerando o nível de significância estatística de 5%. Dos 71 escolares avaliados, a média de idade foi de 12,7 anos, maior parte com sobrepeso, maioria do sexo feminino para excesso de peso (EP) como um todo, e destaque para obesidade em meninos. Além disso, foi observado que a maioria não realizou o AME recomendado por no mínimo seis meses, e a maior parte nasceu com peso adequado para a idade gestacional. Apesar da maioria das variáveis relacionadas não apresentarem significância estatística entre os EP, compreender essa dinâmica entre estes fatores biológicos do nascimento constitui tarefa primordial de forma a complementar o quadro de componentes associados ao aumento do EP. Assim, com vistas na prevenção, importa investigar os fatores biológicos do nascimento visando entender e fornecer subsídios para intervir no meio, evitando a ocorrência de efeitos deletérios à saúde dos infantes na vida adulta.
‘Scotland's different’: Narratives of Scotland's distinctiveness in the post-Brexit-vote era
Authors: Gawlewicz Anna
Published: August 2020

While Scotland has been portrayed as an outlier in the context of Brexit, we know relatively little about how ordinary people in Scotland, including a growing migrant population, make sense of this (political and media) narrative. In order to address this gap, in this article I look at everyday narratives of Scotland's distinctiveness in the post-Brexit-vote era among the long-settled population and Polish – and to a lesser degree other European Union – migrants in the East End of Glasgow. By drawing upon scholarship on everyday nationalism and imagined communities, I explore discursive claims which romanticise Scotland as different and ‘welcoming’ of immigration and position it in binary opposition to England. How is Scotland produced as different in the context of Brexit? How are these stories used to re-imagine increasingly diverse Scottish society? In what ways are they being employed by migrant communities?
PEMBINAAN KETENTRAMAN DAN KETERTIBAN UMUM: (Studi Kasus Gelandangan dan Pengemis)
Authors: Rahmadanita Annisa
Published: August 2020

Fokus kajian ini dilatarbelakangi atas fenomena yang terjadi di wilayah perkotaan adalah hadirnya gelandangan dan pengemis. Tujuan penulisan kajian ini adalah untuk memperoleh gambaran terkait dengan pembinaan gelandangan dan pengemis dalam pemeliharaan ketentraman dan ketertiban umum. Metode penulisan yang digunakan adalah pendekatan Studi Kepustakaan (Library Research). Berdasarkan analisis dan pembahasan, maka penulis menyimpulkan bahwa pembinaan yang dapat dilakukan oleh pemerintah daerah adalah sebagai berikut: (1) pemerintah daerah perlu menyusun peraturan mengenai penertiban gelandangan dan pengemis; (2) pemerintah daerah perlu memiliki data yang konkrit dan real tentang jumlah dan kondisi gelandangan dan pengemis; (3) pemerintah daerah perlu membangun komunitas dengan masyarakat dalam mendukung penertiban dan pembinaaan gelandanagan dan pengemis. (4) pemerintah daerah perlu menyusun program pembinaan dan pendampingan secara bertahap dan berkelanjutan kepada gelandangan dan pengemis; (5) pemerintah daerah perlu mengevaluasi terkait program pembinaan dan pendampingan bagi gelandangan dan pengemis. Berdasarkan kesimpulan di atas, maka penulis memberi saran sebagai berikut: (1) pemerintah daerah perlu meningkatkan koordinasi dan kerjasama dengan baik dengan entitas yang lebih besar maupun entitas yang lebih kecil; (2) pemerintah daerah perlu memberi ruang kepada masyarakat agar dapat berpartisipasi aktif dalam penertiban gelandangan dan pengemis di daerah; (c) pemerintah daerah perlu menyusun dan mengevaluasi program pembinaan terhadap gelandangan dan pengemis di daerah.

Kata kunci: pembinaan, ketentraman dan ketertiban umum, gelandangan dan pengemis
A Review of Non-Chemical Management of Couch Grass (Elymus repens)
Authors: Ringselle Björn , De Cauwer Benny , Salonen Jukka , Soukup Josef
Published: August 2020

Couch grass (Elymus repens) is a morphologically diverse, rhizomatous, perennial grass that is a problematic weed in a wide range of crops. It is generally controlled by glyphosate or intensive tillage in the intercrop period, or selective herbicides in non-susceptible crops. The aim of this review is to determine the efficacy of non-chemical strategies for E. repens control. The review shows that indirect control measures like crop choice, subsidiary crops, and fertilizer regimes influence E. repens abundance, but usually cannot control E. repens. Defoliation (e.g., mowing) can control E. repens growth, but efficacy varies between clones, seasons, and defoliation frequencies. Tillage in the intercrop period is still the main direct non-chemical control method for E. repens and its efficacy can be increased, and negative side-effects minimized by an appropriate tillage strategy. Some new tillage implements are on the market (Kvik-up type machines) or under development (root/rhizome cutters). Alternative methods that can kill E. repens rhizomes (e.g., steaming, soil solarization, biofumigation, hot water, flooding) often have high costs or time requirements. More studies on the effect of cropping system approaches on E. repens and other perennial weeds are needed.
Levers and Obstacles of Effective Research and Innovation for Organic Food and Farming in Italy
Authors: Canali Stefano , Antichi Daniele , Cristiano Simona , Diacono Mariangela , Ferrante Valentina , Migliorini Paola , Riva Francesco , Trinchera Alessandra , Zanoli Raffaele , Colombo Luca
Published: August 2020

The objectives of this paper are to present the dynamic of organic food and farming (OFF) research and innovation, to outline challenges in deploying programs and accessing funding, and to define key actions to foster the development of tailored quality research on organic farming in Italy. The baseline starts from the main outcomes that emerged during the World Café held in the frame of the Salone Internazionale del biologico e del naturale (SANA Expo) in 2018, where the Italian OFF research community met to build a convergence on scope and modus operandi in the research endeavor. These outcomes were examined in the light of the key features of the research and innovation projects funded in Italy in the last 10 years, respectively by the Italian Ministry of Agriculture and the regional administrations through the innovation support instruments in the Rural Development Plan programming periods. In the period 2009–2018, 70 research projects for a total funding of 21.081 million € (<0.1% of the value of the sector) were launched, addressing nine different topic areas. Over a similar period (2007–2019), 53 regional innovation projects addressing organic farming were activated for a total budget of 14.299 million € (<10% of the entire available funding). The implementation of interventions in the research and the innovation areas were often scattered in terms of the topics, disciplines, and types of supply chain/network addressed. The relatively high share of multi/interdisciplinary research and innovation projects as well as the acknowledgement of the multi-actor approach as a fundamental step toward co-research and co-innovation were upshots that emerged from our analysis. The outcomes of this study can be used by competent national and the regional authorities to design their future research and innovation policies and interventions.
Genetic Diversity among Lathyrus ssp. Based on Agronomic Traits and Molecular Markers
Authors: Aci Meriem Miyassa , Lupini Antonio , Badagliacca Giuseppe , Mauceri Antonio , Lo Presti Emilio , Preiti Giovanni
Published: August 2020

Grasspea (Lathyrus sativus L.) and its relatives are considered resilient legumes due to their high ability to cope with different stresses. In this study, the genetic diversity of three Lathyrus species (L. sativus, L cicera and L. ochrus) was assessed by agronomic traits and molecular markers (Simple Sequence Repeat-SSR) in order to detect accessions useful for future breeding strategies. Phenotypic traits showed a high significant variation in which 1000 seed weight (1000 SW) and protein content appeared the most discriminant, as observed by principal component analysis (PCA). SSR analysis was able to detect forty-eight different alleles with an average of 9.6 allele per locus, and a Polymorphic Information Content (PIC) and a gene diversity of 0.745 and 0.784, respectively. Cluster analysis based on agronomic traits as well as molecular data grouped accessions by species but not by geographical origin. This result was confirmed by Principal Coordinates Analysis (PCoA) and Structure Analysis as well. Moreover, genetic structure analysis revealed a high genetic differentiation between L. ochrus and the other species. Analysis of MOlecular Variance (AMOVA) displayed a greater genetic diversity within species (77%) than among them (23%). Finally, a significant positive correlation was observed between agronomic and genetic distances (Mantel’s test). In conclusion, the variability detected within accessions in each species and the differences among species may be useful to plan next breeding programs, focusing on biomass production as well as protein content.
Cultivation of Hair Matrix Cells from Cashmere Goat Skins and Exemplified Applications
Authors: Ma Sen , Wang Lamei , Zong Bo , Wang Ying , Wang Xiaolong , Shi Yinghua , Yang Yuxin , Chen Yulin
Published: August 2020

A functional interpretation of filtered candidates and predicted regulatory pathways related to cashmere growth from sequencing trials needs available cell models, especially for hair matrix cells (HMCs), whose continual proliferation and differentiation result in rapid hair growth. To fulfill such goals, we herein obtained primary goat HMCs via a microdissection-based method; optimized the selection of the culture medium and coating substances for better cell maintenance; and exemplified their usefulness through examining the effects of calcium and all-trans retinoic acid (ATRA) on cells using immunoblotting, flow cytometry, and other techniques. As a result, we successfully acquired primary and passaged goat HMCs with typical keratinocyte morphology. Calcium-free RPMI (Roswell Park Memorial Institute) 1640 and MEM (minimum Eagle’s medium) outperformed normal DMEM/F12 (Dulbecco’s modified Eagle’s medium/Nutrient Mixture F-12) on long-term cell maintenance, whereas serum-free media K-SFM and EpiLife failed to support cell growth. HMCs differed molecularly and morphologically from their neighbor dermal papilla cells on expressions of feature genes, such as HOXC13, and on characteristic keratinocyte-like appearances versus fibroblast shapes, respectively. Higher calcium concentrations significantly stimulated the expression of the genes (e.g., KRT1 and IVL) involved in keratinocyte differentiation and, promoted cell proliferation. Moreover, 10−5 M ATRA obviously boosted goat HMC expansions and changed their cell cycle distributions compared to the controls. Our study shines a light on researches exploring the mechanisms underlying the growth of cashmere.
A Comparative Study of Intramuscular Alfaxalone- or Ketamine-Based Anesthetic Mixtures in Gray Squirrels Undergoing Gonadectomy: Clinical and Physiologic Findings
Authors: Nannarone Sara , Moretti Giulia , Bellocchi Federica , Menchetti Laura , Bufalari Antonello
Published: August 2020

The gray squirrel is one of the most common invasive species in Europe, whose presence is dangerous for the survival of the European red squirrel. To cope with this biological invasion and to safeguard biodiversity, the LIFE+U-SAVEREDS project aims to protect the red squirrel, by limiting the growth of the current population of gray squirrels and simultaneously promoting their eradication with surgical sterilization. This study compares two different anesthetic protocols, including dexmedetomidine (40 µg/kg) and midazolam (0.3 mg/kg) associated with ketamine (15 mg/kg; n = 25 squirrels) or alfaxalone (5 mg/kg; n = 22 squirrels). A blinded investigator evaluated the quality and onset of sedation, intraoperative anesthesia, and recovery, as well as the physiologic parameters for each animal. Alfaxalone provided a good quality of anesthesia with limited cardiovascular effects (p < 0.05) and good intraoperative myorelaxation. Ketamine induced complete relaxation in a shorter time (p < 0.05) and a rapid (p < 0.001) and excellent (p < 0.05) recovery. Despite the overall superiority of ketamine, alfaxalone appeared to be an adequate alternative anesthetic drug that can be administered without requiring intravascular access. It should be rapidly metabolized and excreted; however, it requires the combination of longer acting sedatives/myorelaxants to prevent a poor recovery quality.
Copper Kills Escherichia coli Persister Cells
Authors: Moreira Martins Paula Maria , Gong Ting , de Souza Alessandra A. , Wood Thomas K.
Published: August 2020

Due to their reduced metabolism, persister cells can survive most antimicrobial treatments, which usually rely on corrupting active biochemical pathways. Therefore, molecules that kill bacterial persisters should function in a metabolism-independent manner. Some anti-persister compounds have been found previously, such as the DNA-crosslinkers mitomycin C and cisplatin, but more effective and lower cost alternatives are needed. Copper alloys have been used since ancient times due to their antimicrobial properties, and they are still used in agriculture to control plant bacterial diseases. By stopping transcription with rifampicin and by treating with ampicillin to remove non-persister cells, we created a population that consists solely of Escherichia coli persister cells. Using this population of persister cells, we demonstrate that cupric compounds kill E. coli persister cells. Hence, copper ions may be used in controlling the spread of important bacterial strains that withstand treatment with conventional antimicrobials by forming persister cells.
Is Sleep Associated with the S-Klotho Anti-Aging Protein in Sedentary Middle-Aged Adults? The FIT-AGEING Study
Authors: Mochón-Benguigui Sol , Carneiro-Barrera Almudena , Castillo Manuel J. , Amaro-Gahete Francisco J.
Published: August 2020

Sleep and Klotho have both been closely related to the ageing process, both playing a substantial role in the endocrine and immune systems and, thereby, in oxidative stress and chronic inflammation. However, there are no studies elucidating the relationship between sleep and Klotho. Therefore, this study investigated the association of sleep quantity and quality with the shed form of the α-Klotho gene (S-Klotho plasma levels) in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for the present study. Objective sleep quality parameters (total sleep time (TST), wake after sleep onset (WASO), and sleep efficiency (SE)) were determined using a wrist-worn accelerometer over seven consecutive days, and the subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI; higher scores indicate worse sleep quality). The S-Klotho plasma levels were measured in the ethylenediaminetetraacetic acid plasma using a solid-phase sandwich enzyme-linked immunosorbent assay. Objective sleep parameters were associated with the S-Klotho plasma levels only after including the age, fat mass percentage, and lean mass index as covariates. A direct relationship was observed between the subjective sleep quality (inverse of PSQI scores) and the S-Klotho plasma levels in sedentary middle-aged adults. Improving sleep quantity and quality could be considered an anti-aging therapeutic approach for the prevention, slowing, and even reversal of the physiological decline and degenerative pathologies that are certainly related to the aging process.
Cigarette Smoke Extract Stimulates MMP-2 Production in Nasal Fibroblasts via ROS/PI3K, Akt, and NF-κB Signaling Pathways
Authors: Park Joo-Hoo , Shin Jae-Min , Yang Hyun-Woo , Kim Tae Hoon , Lee Seung Hoon , Lee Heung-Man , Cho Jae-Gu , Park Il-Ho
Published: August 2020

Cigarette smoke exposure has been shown to be associated with chronic rhinosinusitis and tissue remodeling. The present study aimed to investigate the effects of cigarette smoke extract (CSE) on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) production in nasal fibroblasts and to determine the underlying molecular mechanisms. Primary nasal fibroblasts from six patients were isolated and cultured. After the exposure of fibroblasts to CSE, the expression levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by real-time PCR, ELISA, and immunofluorescence staining. The enzymatic activities of MMP-2 and MMP-9 were measured by gelatin zymography. Reactive oxygen species (ROS) production was analyzed using dichloro-dihydro-fluorescein diacetate and Amplex Red assays. PI3K/Akt phosphorylation and NF-κB activation were determined by Western blotting and luciferase assay. CSE significantly increased MMP-2 expression and inhibited TIMP-2 expression but did not affect MMP-9 and TIMP-1 expression. Furthermore, CSE significantly induced ROS production. However, treatment with ROS scavengers, specific PI3K/Akt inhibitors, NF-κB inhibitor, and glucocorticosteroids significantly decreased MMP-2 expression and increased TIMP-2 expression. Our results suggest that steroids inhibit CSE-regulated MMP-2 and TIMP-2 production and activation through the ROS/ PI3K, Akt, and NF-κB signaling pathways in nasal fibroblasts. CSE may contribute to the pathogenesis of chronic rhinosinusitis by regulating MMP-2 and TIMP-2 expression.
Exploring Seminal Plasma GSTM3 as a Quality and In Vivo Fertility Biomarker in Pigs—Relationship with Sperm Morphology
Authors: Llavanera Marc , Delgado-Bermúdez Ariadna , Mateo-Otero Yentel , Padilla Lorena , Romeu Xavier , Roca Jordi , Barranco Isabel , Yeste Marc
Published: August 2020

Glutathione S-transferases Mu 3 (GSTM3) is an essential antioxidant enzyme whose presence in sperm has recently been related to sperm cryotolerance, quality and fertility. However, its role in seminal plasma (SP) as a predictor of the same sperm parameters has never been investigated. Herein, cell biology and proteomic approaches were performed to explore the presence, origin and role of SP-GSTM3 as a sperm quality and in vivo fertility biomarker. GSTM3 in SP was quantified using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit specific for Sus scrofa, whereas the presence of GSTM3 in testis, epididymis and accessory sex glands was assessed through immunoblotting analysis. Sperm quality and functionality parameters were evaluated in semen samples at 0 and 72 h of liquid-storage, whereas fertility parameters were recorded over a 12-months as farrowing rate and litter size. The presence and concentration of GSTM3 in SP was established for the first time in mammalian species, predominantly synthesized in the epididymis. The present study also evidenced a relationship between SP-GSTM3 and sperm morphology and suggested it is involved in epididymal maturation rather than in ejaculated sperm physiology. Finally, the data reported herein ruled out the role of this antioxidant enzyme as a quality and in vivo fertility biomarker of pig sperm.
Numerical Investigation on Generation and Propagation Characteristics of Offshore Tsunami Wave under Landslide
Authors: Sun Junkai , Wang Yang , Huang Cheng , Wang Wanhu , Wang Hongbing , Zhao Enjin
Published: August 2020

Tsunamis induced by the landslide will divide into a traveling wave component propagating along the coastline and an offshore wave component propagating perpendicular to the coastline. The offshore tsunami wave has the non-negligible energy and destruction in enclosed basins as fjords, reservoirs, and lakes, which are worth studying. The initial submergence condition, the falling height and sliding angle of slider, are important reference indexes of damage degree of landslide and may also matter at that of the landslide-induced tsunami. Depending on the fully coupled model, the effects of them on the production and propagation of the tsunami were considered in the study. Since the slider used was semi-elliptic, the effect of the ratio of the long axis to the short axis was also analyzed. According to the computational fluid dynamics theory, a numerical wave tank was developed by the immersed boundary (IB) method; besides, the general moving-object module of slide mass was also embedded to the numerical tanker. The results indicate that the effects of the squeezing and pushing of the slider on water produce a naturally attenuated wave at the front of the wave train, and the attenuation becomes more serious with the increase in the initial submersion range of the slider. The effects of the vertical movement of the slider cause the increase in the amplitude of the back of the wave train. As the falling height increases, the large wave height increases when the slider is initially submerged and decreases when it is not initially submerged, except for the accidental elevation of that at smaller falling heights. The results also indicate that the hazard of the subaerial landslide-induced tsunami is greater under a small or large falling angle, and that of the partial subaerial and submarine landslide-induced tsunami is greater under a small falling angle. With the increase in the ratio of the long axis to the short axis, the total induced wave energy decreases and the shape of the wave train proportionally reduces, while the wave propagation mode does not change.
Spatial Domain-Based Nonlinear Residual Feature Extraction for Identification of Image Operations
Authors: Yuan Xiaochen , Huang Tian
Published: August 2020

In this paper, a novel approach that uses a deep learning technique is proposed to detect and identify a variety of image operations. First, we propose the spatial domain-based nonlinear residual (SDNR) feature extraction method by constructing residual values from locally supported filters in the spatial domain. By applying minimum and maximum operators, diversity and nonlinearity are introduced; moreover, this construction brings nonsymmetry to the distribution of SDNR samples. Then, we propose applying a deep learning technique to the extracted SDNR features to detect and classify a variety of image operations. Many experiments have been conducted to verify the performance of the proposed approach, and the results indicate that the proposed method performs well in detecting and identifying the various common image postprocessing operations. Furthermore, comparisons between the proposed approach and the existing methods show the superiority of the proposed approach.
Weather Effects of Aerosols in the Global Forecast Model
Authors: Jeong Gill-Ran
Published: August 2020

The weather effects of aerosol types were investigated using well-posed aerosol climatology through the aerosol sensitivity test of thermodynamic and hydrometeor fields, and the weather forecast performances in July of 2017. The largest aerosol direct radiative forcing (ADRF) in July was due to dust aerosols at the surface and atmosphere, and sulfate at the top of the atmosphere (TOA), respectively. The ADRF of total aerosols had unilateral tendencies in thermodynamic and hydrometeor fields. The contribution of individual aerosols was linearly additive to those of total aerosols in the heat fluxes, heating rates, humidity, and convective precipitation. However, no such linearity existed in temperature, geopotential height, cloud liquid or ice contents, and large-scale precipitation. Dust was the most influential forcing agent in July among five aerosol types due to the largest light-absorption capacity. Such unilateral tendencies of total aerosols and a part of the linearity of individual aerosols were exerted on the weather systems. The verification of medium-range forecasts showed that aerosols alleviated the overestimation of surface shortwave (SW) downward fluxes, the negative biases of temperature and geopotential heights at TOA and surface, and the underestimation in light and moderate precipitation. In contrast, they enhanced warm biases at the mid-atmosphere and underestimation in heavy precipitations, particularly negative biases in the intertropical convergence zone (ITCZ). Weather forecast scores including current aerosol information were improved in geopotential height (GPH) of the northern hemisphere (NH); however, they got worse in the temperature and the upper atmosphere GPH of the southern hemisphere (SH), which was mostly due to black carbon (BC) aerosols in the tropical regions. The missing mechanisms such as aerosol–cloud interactions, better aerosol spectral optical properties including mixing states and aging, and the near-real-time (NRT) based aerosol loading data are worthwhile to be tried in the near future for fixing the intrinsic underestimation of precipitation in ITCZ and surface radiative fluxes in the desert and biomass burning area.
Peroxisomal Cofactor Transport
Authors: Plett Anastasija , Charton Lennart , Linka Nicole
Published: August 2020

Peroxisomes are eukaryotic organelles that are essential for growth and development. They are highly metabolically active and house many biochemical reactions, including lipid metabolism and synthesis of signaling molecules. Most of these metabolic pathways are shared with other compartments, such as Endoplasmic reticulum (ER), mitochondria, and plastids. Peroxisomes, in common with all other cellular organelles are dependent on a wide range of cofactors, such as adenosine 5′-triphosphate (ATP), Coenzyme A (CoA), and nicotinamide adenine dinucleotide (NAD). The availability of the peroxisomal cofactor pool controls peroxisome function. The levels of these cofactors available for peroxisomal metabolism is determined by the balance between synthesis, import, export, binding, and degradation. Since the final steps of cofactor synthesis are thought to be located in the cytosol, cofactors must be imported into peroxisomes. This review gives an overview about our current knowledge of the permeability of the peroxisomal membrane with the focus on ATP, CoA, and NAD. Several members of the mitochondrial carrier family are located in peroxisomes, catalyzing the transfer of these organic cofactors across the peroxisomal membrane. Most of the functions of these peroxisomal cofactor transporters are known from studies in yeast, humans, and plants. Parallels and differences between the transporters in the different organisms are discussed here.
Differential Expression of Multiple Disease-Related Protein Groups Induced by Valproic Acid in Human SH-SY5Y Neuroblastoma Cells
Authors: Hu Tsung-Ming , Chung Hsiang-Sheng , Ping Lieh-Yung , Hsu Shih-Hsin , Tsai Hsin-Yao , Chen Shaw-Ji , Cheng Min-Chih
Published: August 2020

Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer’s disease, Parkinson’s disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases.
Cerebral Hemodynamic Changes to Transcranial Doppler in Asymptomatic Patients with Fabry’s Disease
Authors: Vagli Carla , Fisicaro Francesco , Vinciguerra Luisa , Puglisi Valentina , Rodolico Margherita Stefania , Giordano Antonello , Ferri Raffaele , Lanza Giuseppe , Bella Rita
Published: August 2020

Background: Patients with Fabry’s disease (FD) may be asymptomatic or show a spectrum of clinical manifestations, including cerebrovascular disease, mainly affecting posterior circulation. Few and conflicting studies on cerebral blood flow (CBF) velocity by transcranial Doppler sonography (TCD) in asymptomatic FD (aFD) subjects have been published. Our study aims to assess TCD in aFD subjects to identify any preclinical CBF change. Methods: A total of 30 aFD subjects were consecutively recruited and compared to 28 healthy controls. Brain magnetic resonance imaging was normal in all participants. TCD was used to study blood flow velocity and indices of resistance of intracranial arteries from the middle cerebral artery (MCA), bilaterally, and from the basilar artery (BA). Cerebral vasomotor reactivity (CVR) was also evaluated from MCA. Results: No difference was found between groups for MCA parameters of CBF velocity and CVR. Compared to controls, a higher mean blood flow velocity and a lower resistance index from BA were observed in FD subjects. No correlation was found between any BA-derived TCD parameter and the level of lyso-globotriaosylceramide. Conclusions: aFD subjects show evidence of altered CBF velocity in posterior circulation. Preclinical detection of neurovascular involvement in FD might allow appropriate management and prevention of future cerebrovascular complications and disability.
Neoadjuvant Systemic Treatment of Primary Angiosarcoma
Authors: Heinhuis Kimberley M. , IJzerman Nikki S. , van der Graaf Winette T. A. , Kerst Jan Martijn , Schrage Yvonne , Beijnen Jos H. , Steeghs Neeltje , van Houdt Winan J.
Published: August 2020

Angiosarcoma is an extremely rare and aggressive malignancy. Standard of care of localized tumors includes surgery ± radiation. Despite this multimodal treatment, >50% of the angiosarcoma patients develop local or distant recurrent disease. The role of neoadjuvant systemic therapy is still controversial and we therefore performed a systematic review of the literature to define the role of neoadjuvant systemic therapy based on available evidence. We focused on the effects of neoadjuvant systemic therapy on: 1. The success of surgical resection and 2. the long-term survival. All articles published before October 2019 on Ovid Medline, Ovid Embase, Cochrane library and Scopus were evaluated. Eighteen case reports and six retrospective cohort studies were included. There were no randomized controlled trials. This literature showed a beneficial role of neoadjuvant chemotherapy on downsizing of the tumor resulting in an improvement of the resection margins, especially in patients with cardiac or cutaneous angiosarcoma. However, no definitive conclusions on survival can be drawn based on the available literature lacking any prospective randomized studies in this setting. We advise that neoadjuvant chemotherapy should be considered, since this could lead to less mutilating resections and a higher rate of free resection margins. An international angiosarcoma registry could help to develop guidelines for this rare disease.
Long-Term Treatment of Cancer-Associated Thrombosis (CAT) Beyond 6 Months in the Medical Practice: USCAT, a 432-Patient Retrospective Non-Interventional Study
Authors: Mahé Isabelle , Plaisance Ludovic , Chapelle Céline , Laporte Silvy , Planquette Benjamin , Bertoletti Laurent , Couturaud Francis , Falvo Nicolas , Falchero Lionel , Mahé Isild , Helfer Hélène , Chidiac Jean , Meyer Guy
Published: August 2020

Background: extended anticoagulant therapy beyond the initial 6 months is suggested in patients with cancer-associated thrombosis (CAT) and active cancer. Few data are available on patient management and outcomes on the period between 6 and 12 months after the venous thromboembolism (VTE) event. Objectives: our objective was to document patient management and outcomes beyond 6 months and up to 12 months in CAT patients initially treated for 6 months with tinzaparin. Methods: adult CAT patients with a cancer still alive at the end of an initial 6-month treatment period were eligible to participate in this retrospective non-interventional French multicenter study. Results: a total of 432 patients aged 66.5 ± 12.7 years were available to participate in this study. Out of the patients included in the study, the anticoagulant treatment was maintained in 348 of 422 documented patients (82.5%) while it was discontinued in 74 (17.5%) patients (before the end or at the end of the initial 6-month treatment period). Between 6 and 12 months, 24 patients (5.7%) experienced VTE recurrence, while 21 (5.1%) patients had clinically relevant bleeding, 11 patients (2.7%) had major bleeding and 96 patients (22.3%) died, mostly from cancer. VTE recurrence was more frequent in patients with lung (14.3%) and colorectal cancer (6.0%) while major bleeding was more frequent in patients with colorectal cancer (6.0%). Conclusion: clinical outcomes were consistent with previous observations and variable according to the type of cancer. Further clinical research is required to orient the management of patients with CAT beyond 6 months based on cancer-specific treatment strategies.
The State of Art of Regenerative Therapy in Cardiovascular Ischemic Disease: Biology, Signaling Pathways, and Epigenetics of Endothelial Progenitor Cells
Authors: Perrotta Fabio , Perna Angelica , Komici Klara , Nigro Ersilia , Mollica Mariano , D’Agnano Vito , De Luca Antonio , Guerra Germano
Published: August 2020

Ischemic heart disease is currently a major cause of mortality and morbidity worldwide. Nevertheless, the actual therapeutic scenario does not target myocardial cell regeneration and consequently, the progression toward the late stage of chronic heart failure is common. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that contribute to the homeostasis of the endothelial wall in acute and chronic ischemic disease. Calcium modulation and other molecular pathways (NOTCH, VEGFR, and CXCR4) contribute to EPC proliferation and differentiation. The present review provides a summary of EPC biology with a particular focus on the regulatory pathways of EPCs and describes promising applications for cardiovascular cell therapy.
Therapeutic Target Discovery Using High-Throughput Genetic Screens in Acute Myeloid Leukemia
Authors: Liu Qiao , Garcia Michelle , Wang Shaoyuan , Chen Chun-Wei
Published: August 2020

The development of high-throughput gene manipulating tools such as short hairpin RNA (shRNA) and CRISPR/Cas9 libraries has enabled robust characterization of novel functional genes contributing to the pathological states of the diseases. In acute myeloid leukemia (AML), these genetic screen approaches have been used to identify effector genes with previously unknown roles in AML. These AML-related genes centralize alongside the cellular pathways mediating epigenetics, signaling transduction, transcriptional regulation, and energy metabolism. The shRNA/CRISPR genetic screens also realized an array of candidate genes amenable to pharmaceutical targeting. This review aims to summarize genes, mechanisms, and potential therapeutic strategies found via high-throughput genetic screens in AML. We also discuss the potential of these findings to instruct novel AML therapies for combating drug resistance in this genetically heterogeneous disease.
On the Applicability of Stereological Methods for the Modelling of a Local Plastic Deformation in Grained Structure: Mathematical Principles
Authors: Minárik Stanislav , Martinkovič Maroš
Published: August 2020

Analysis of systems and structures from their cross-sectional images finds applications in many branches. Therefore, the question of content, quantity, and accuracy of information obtained from various techniques based on cross-sectional views of structures is particularly important. Application of conventional techniques for two-dimensional imaging on the analysis of structure from a cross-sectional image is limited. The reason for this limitation is the fact that these techniques use a fixed cross-sectional plane and therefore cannot check the 3D structural changes caused by deformation. Geometric orientation of a grained structure must be considered when data, scanned from a cross section, is processed in order to obtain information about local deformation in this structure. The so-called degree of structure orientation in 3D can be estimated experimentally from the cross-sectional image of the structure by the statistical (Saltykov) method of oriented testing lines. Subsequently if the correlation between orientation and deformation were to be known a detailed map of local deformation in the structure could be revealed. Unfortunately, exact theoretical works dealing with the assessment of local deformation by means of change of structure orientation in 3D are still missing. Our work seeks to partially remove this shortcoming. In our work we are interested in how the transformation of the image of a grained structure in a cross-sectional plane reflects structure deformation. An initial shape of grains is assumed which is transformed into a deformed shape by analytic calculation. We present brief mathematical derivations aimed at the problem of single grain-surface area deformation. The main goal of this work led to the design of a computationally low consuming procedure for quantification of local deformation in a grained structure based on the distortion of the image of this structure in a cross-sectional view.
Low-Grade Gliomas in Patients with Noonan Syndrome: Case-Based Review of the Literature
Authors: Lodi Mariachiara , Boccuto Luigi , Carai Andrea , Cacchione Antonella , Miele Evelina , Colafati Giovanna Stefania , Diomedi Camassei Francesca , De Palma Luca , De Benedictis Alessandro , Ferretti Elisabetta , Catanzaro Giuseppina , Pò Agnese , De Luca Alessandro , Rinelli Martina , Lepri Francesca Romana , Agolini Emanuele , Tartaglia Marco , Locatelli Franco , Mastronuzzi Angela
Published: August 2020

Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling.
Optimization of a New Design of Molten Salt-to-CO2 Heat Exchanger Using Exergy Destruction Minimization
Authors: Montes María José , Linares José Ignacio , Barbero Rubén , Moratilla Beatriz Yolanda
Published: August 2020

One of the ways to make cost-competitive electricity, from concentrated solar thermal energy, is increasing the thermoelectric conversion efficiency. To achieve this objective, the most promising scheme is a molten salt central receiver, coupled to a supercritical carbon dioxide cycle. A key element to be developed in this scheme is the molten salt-to-CO2 heat exchanger. This paper presents a heat exchanger design that avoids the molten salt plugging and the mechanical stress due to the high pressure of the CO2, while improving the heat transfer of the supercritical phase, due to its compactness with a high heat transfer area. This design is based on a honeycomb-like configuration, in which a thermal unit consists of a circular channel for the molten salt surrounded by six smaller trapezoidal ducts for the CO2. Further, an optimization based on the exergy destruction minimization has been accomplished, obtained the best working conditions of this heat exchanger: a temperature approach of 50 °C between both streams and a CO2 pressure drop of 2.7 bar.
Maximum Likelihood Estimation for the Fractional Vasicek Model
Authors: Tanaka Katsuto , Xiao Weilin , Yu Jun
Published: August 2020

This paper estimates the drift parameters in the fractional Vasicek model from a continuous record of observations via maximum likelihood (ML). The asymptotic theory for the ML estimates (MLE) is established in the stationary case, the explosive case, and the boundary case for the entire range of the Hurst parameter, providing a complete treatment of asymptotic analysis. It is shown that changing the sign of the persistence parameter changes the asymptotic theory for the MLE, including the rate of convergence and the limiting distribution. It is also found that the asymptotic theory depends on the value of the Hurst parameter.
Multi-Label Learning for Appliance Recognition in NILM Using Fryze-Current Decomposition and Convolutional Neural Network
Authors: Faustine Anthony , Pereira Lucas
Published: August 2020

The advance in energy-sensing and smart-meter technologies have motivated the use of a Non-Intrusive Load Monitoring (NILM), a data-driven technique that recognizes active end-use appliances by analyzing the data streams coming from these devices. NILM offers an electricity consumption pattern of individual loads at consumer premises, which is crucial in the design of energy efficiency and energy demand management strategies in buildings. Appliance classification, also known as load identification is an essential sub-task for identifying the type and status of an unknown load from appliance features extracted from the aggregate power signal. Most of the existing work for appliance recognition in NILM uses a single-label learning strategy which, assumes only one appliance is active at a time. This assumption ignores the fact that multiple devices can be active simultaneously and requires a perfect event detector to recognize the appliance. In this paper proposes the Convolutional Neural Network (CNN)-based multi-label learning approach, which links multiple loads to an observed aggregate current signal. Our approach applies the Fryze power theory to decompose the current features into active and non-active components and use the Euclidean distance similarity function to transform the decomposed current into an image-like representation which, is used as input to the CNN. Experimental results suggest that the proposed approach is sufficient for recognizing multiple appliances from aggregated measurements.
Impact of Alternative Paraffinic Fuels on the Durability of a Modern Common Rail Injection System
Authors: Mata Carmen , Piaszyk Jakub , Soriano José Antonio , Herreros José Martín , Tsolakis Athanasios , Dearn Karl
Published: August 2020

Common rail (CR) diesel fuel injection systems are very sensitive to variations in fuel properties, thus the impact of alternative fuels on the durability of the injection system should be investigated when considering the use of alternative fuels. This work studies a high-pressure CR (HPCR) diesel fuel injection system operating for 400 h in an injection test bench, using a fuel blend composed of an alternative paraffinic fuel and conventional diesel (50PF50D). The alternative fuel does not have aromatic components and has lower density than conventional diesel fuel. The injection system durability study was carried out under typical injection pressure and fuel temperature for the fuel pump, the common rail and the injector. The results show that the HPCR fuel injection system and its components (e.g., piston, spring, cylinder, driveshaft and cam) have no indication of damage, wear or change in surface roughness. The absence of internal wear to the components of the injection system is supported by the approximately constant total flow rate that reaches the injector during the whole the 400 h of the experiment. However, the size of the injector nozzle holes was decreased (approximately 12%), being consistent with the increase in the return fuel flow of the injector and rail (approximately 13%) after the completion of the study. Overall, the injection system maintained its operability during the whole duration of the durability study, which encourages the use of paraffinic fuels as an alternative to conventional diesel fuel.