bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized laws of thermodynamics in the presence of correlations
Authors: Bera Manabendra N. , Riera Arnau , Lewenstein Maciej , Winter Andreas
Published: December 2017

The laws of thermodynamics, despite their wide range of applicability, are known to break down when systems are correlated with their environments. Here we generalize thermodynamics to physical scenarios which allow presence of correlations, including those where strong correlations are present. We exploit the connection between information and physics, and introduce a consistent redefinition of heat dissipation by systematically accounting for the information flow from system to bath in terms of the conditional entropy. As a consequence, the formula for the Helmholtz free energy is accordingly modified. Such a remedy not only fixes the apparent violations of Landauer’s erasure principle and the second law due to anomalous heat flows, but also leads to a generally valid reformulation of the laws of thermodynamics. In this information-theoretic approach, correlations between system and environment store work potential. Thus, in this view, the apparent anomalous heat flows are the refrigeration processes driven by such potentials.
Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington’s Disease Model through the Application of Quantitative Systems Pharmacology
Authors: Pei Fen , Li Hongchun , Henderson Mark J. , Titus Steven A. , Jadhav Ajit , Simeonov Anton , Cobanoglu Murat Can , Mousavi Seyed H. , Shun Tongying , McDermott Lee , Iyer Prema , Fioravanti Michael , Carlisle Diane , Friedlander Robert M. , Bahar Ivet , Taylor D. Lansing , Lezon Timothy R. , Stern Andrew M. , Schurdak Mark E.
Published: December 2017

Quantitative Systems Pharmacology (QSP) is a drug discovery approach that integrates computational and experimental methods in an iterative way to gain a comprehensive, unbiased understanding of disease processes to inform effective therapeutic strategies. We report the implementation of QSP to Huntington’s Disease, with the application of a chemogenomics platform to identify strategies to protect neuronal cells from mutant huntingtin induced death. Using the STHdh
Q111
cell model, we investigated the protective effects of small molecule probes having diverse canonical modes-of-action to infer pathways of neuronal cell protection connected to drug mechanism. Several mechanistically diverse protective probes were identified, most of which showed less than 50% efficacy. Specific combinations of these probes were synergistic in enhancing efficacy. Computational analysis of these probes revealed a convergence of pathways indicating activation of PKA. Analysis of phospho-PKA levels showed lower cytoplasmic levels in STHdh
Q111
cells compared to wild type STHdh
Q7
cells, and these levels were increased by several of the protective compounds. Pharmacological inhibition of PKA activity reduced protection supporting the hypothesis that protection may be working, in part, through activation of the PKA network. The systems-level studies described here can be broadly applied to any discovery strategy involving small molecule modulation of disease phenotype.
Estimation of land-surface evaporation at four forest sites across Japan with the new nonlinear complementary method
Authors: Ai Zhipin , Wang Qinxue , Yang Yonghui , Manevski Kiril , Zhao Xin , Eer Deni
Published: December 2017

Evaporation from land surfaces is a critical component of the Earth water cycle and of water management strategies. The complementary method originally proposed by Bouchet, which describes a linear relation between actual evaporation (E), potential evaporation (Epo) and apparent potential evaporation (Epa) based on routinely measured weather data, is one of the various methods for evaporation calculation. This study evaluated the reformulated version of the original method, as proposed by Brutsaert, for forest land cover in Japan. The new complementary method is nonlinear and based on boundary conditions with strictly physical considerations. The only unknown parameter (αe) was for the first time determined for various forest covers located from north to south across Japan. The values of αe ranged from 0.94 to 1.10, with a mean value of 1.01. Furthermore, the calculated evaporation with the new method showed a good fit with the eddy-covariance measured values, with a determination coefficient of 0.78 and a mean bias of 4%. Evaluation results revealed that the new nonlinear complementary relation performs better than the original linear relation in describing the relationship between E/Epa and Epo/Epa, and also in depicting the asymmetry variation between Epa/Epo and E/Epo.
JAK/STAT and TGF-ß activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans
Authors: Kim Hunbeen , Jeong Jaeseong , Chatterjee Nivedita , Roca Carlos P. , Yoon Dahye , Kim Suhkmann , Kim Younghun , Choi Jinhee
Published: December 2017

Titanium dioxide nanoparticles (TiO2NPs) are widely used nanoparticles, whose catalytic activity is mainly due to photoactivation. In this study, the toxicity of TiO2NPs was investigated on the nematode Caenorhabditis elegans, with and without UV activation. Comparative analyses across the four treatments revealed that UV-activated TiO2NPs led to significant reproductive toxicity through oxidative stress. To understand the underlying molecular mechanism, transcriptomics and metabolomics analyses were conducted, followed by whole-genome network-based pathway analyses. Differential expression analysis from microarray data revealed only 4 DEGs by exposure to TiO2NPs alone, compared to 3,625 and 3,286 DEGs by UV alone and UV-activated TiO2NPs, respectively. Pathway analyses suggested the possible involvement of the JAK/STAT and TGF-ß pathways in the phototoxicity of TiO2NPs, which correlated with the observation of increased gene expression of those pathways. Comparative analysis of C. elegans response across UV activation and TiO2NPs exposure was performed using loss-of-function mutants of genes in these pathways. Results indicated that the JAK/STAT pathway was specific to TiO2NPs, whereas the TGF-ß pathway was specific to UV. Interestingly, crosstalk between these pathways was confirmed by further mutant analysis. We consider that these findings will contribute to understand the molecular mechanisms of toxicity of TiO2NPs in the natural environment.
Milder degenerative effects of Carfilzomib vs. Bortezomib in the Drosophila model: a link to clinical adverse events
Authors: Tsakiri Eleni N. , Terpos Evangelos , Papanagnou Eleni-Dimitra , Kastritis Efstathios , Brieudes Vincent , Halabalaki Maria , Bagratuni Tina , Florea Bogdan I. , Overkleeft Herman S. , Scorrano Luca , Skaltsounis Alexios-Leandros , Dimopoulos Meletios A. , Trougakos Ioannis P.
Published: December 2017

Proteasome inhibitors, e.g. Bortezomib (BTZ) and Carfilzomib (CFZ), have demonstrated clinical efficacy against haematological cancers. Interestingly, several adverse effects are less common, compared to BTZ, in patients treated with CFZ. As the molecular details of these observations remain not well understood we assayed the pathophysiological effects of CFZ vs. BTZ in the Drosophila experimental model. Mass Spectrometry analyses showed that neither CFZ nor BTZ are hydrolysed in flies’ tissues, while at doses inducing similar inhibition of the rate limiting for protein breakdown chymotrypsin-like (CT-L) proteasomal activity, CFZ treatment resulted in less intense increase of oxidative stress or activation of antioxidant and proteostatic modules. Also, despite comparable cardiotoxicity likely due to disrupted mitochondrial function, CFZ did not affect developmental processes, showed minimal neuromuscular defects and reduced to a lesser extent flies’ healthspan. Studies in flies, human cancer cell lines and blood cells isolated from Multiple Myeloma patients treated with CFZ or BTZ revealed, that the increased BTZ toxicity likely relates to partial co-inhibition of the caspase-like (C-L) proteasomal activity Supportively, co-treating flies with CFZ and a C-L selective proteasome inhibitor exacerbated CFZ-mediated toxicity. Our findings provide a reasonable explanation for the differential adverse effects of CFZ and BTZ in the clinic.
Subthalamic nucleus detects unnatural android movement
Authors: Ikeda Takashi , Hirata Masayuki , Kasaki Masashi , Alimardani Maryam , Matsushita Kojiro , Yamamoto Tomoyuki , Nishio Shuichi , Ishiguro Hiroshi
Published: December 2017

An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android’s slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.
Conditions and Regulation of Mixed Culture to Promote Shiraia bambusicola and Phoma sp. BZJ6 for Laccase Production
Authors: Du Wen , Sun Chunlong , Wang Jun , Xie Wenjun , Wang Baoqin , Liu Xuehong , Zhang Yumiao , Fan Yanhui
Published: December 2017

Mixing cultures induces the biosynthesis of laccase in mixed cells, produces signal molecules, and regulates the production of mixed-cell metabolites. The fungal strain, which promotes laccase production, has been isolated and screened from the host bamboos of endophytic fungi and identified as Phoma sp. BZJ6. When the culture medium is mainly composed of soluble starch, yeast extract, and Phoma sp., the laccase output can reach 4,680 U/L. Nitric oxide (NO) and reactive oxygen species (ROS) were found to promote the regulation of laccase synthesis. Plasma membrane NAD(P)H oxidase inhibitors and NO-specific quenchers can inhibit not only the accumulation of ROS induced and NO synthesis but also the biosynthesis of laccase. The results indicate that the accumulation of superoxide anion radical (O2−) and hydrogen peroxide (H2O2) induced by the mixed culture was partially dependent on NO. The mixed culture can also reduce the biomass, increase the synthesis of total phenolics and flavonoids, and enhance the activity of phenylalanine ammonia-lyase and chalcone isomerase. This phenomenon is probably the result of the activated phenylpropanoids–flavonoid pathway. Results confirmed that the mixture culture is advantageous for laccase production and revealed that NO, O2−, and H2O2 are necessary signal molecules to induce laccase synthesis.
Metabolomics reveals novel blood plasma biomarkers associated to the BRCA1-mutated phenotype of human breast cancer
Authors: Roig Bàrbara , Rodríguez-Balada Marta , Samino Sara , Lam Eric W.-F. , Guaita-Esteruelas Sandra , Gomes Ana R. , Correig Xavier , Borràs Joan , Yanes Oscar , Gumà Josep
Published: December 2017

Hereditary breast and ovarian cancer syndrome (HBOC) is partly due to the presence of mutations in the BRCA genes. Triple-negative (TN) breast cancer (BC) shares histological characteristics with germline BRCA1 mutation-associated tumours. We have investigated the metabolic profiles of human breast cancer (BC) cell lines carrying BRCA1 pathogenic mutations by non-targeted liquid chromatography coupled to mass spectrometry technology. Based on our in vitro results, we performed a targeted metabolomic analysis of plasma samples from TN HBOC patients taking into account their BRCA1 genotype. BRCA1 promoter hypermethylation and the BRCAness phenotype of BC cell lines were also studied. The purpose of this study was to determine the metabolic signature of HBOC syndrome and TNBC patients and to evaluate the potential contribution of the metabolites identified to the genetic diagnosis of breast cancer. The present results show the existence of a differential metabolic signature for BC cells based on the BRCA1 functionality. None of the studied BC cell lines presented hypermethylation of the BRCA1 promoter region. We provide evidence of the existence of free methylated nucleotides capable of distinguishing plasma samples from HBOC patients as BRCA1-mutated and BRCA1 non-mutated, suggesting that they might be considered as BRCA1-like biomarkers for TNBC and HBOC syndrome.
Active, passive, and electronic cigarette smoking is associated with asthma in adolescents
Authors: Kim So Young , Sim Songyong , Choi Hyo Geun
Published: December 2017

The present study investigated the associations of active, passive, and electronic cigarette (E-cigarette) smoking with asthma in Korean adolescents. We used the cross-sectional study of Korea Youth Risk Behavior Web-based Survey conducted in 2011, 2012 and 2013. Active smoking was classified into 4 groups (0 days, 1–5 days, 6–19 days, and ≥20 days a month). Passive smoking was also categorized into 4 groups (0 days, 1–2 days, 3–4 days, and ≥5 days a week). E-cigarette was defined as yes or no in the last 30 days. Age, sex, obesity, region of residence, economic level, and parental educational level were adjusted for as confounders. Smoking variables were adjusted for one another. Adjusted odd ratios (AORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression analysis with complex sampling. In total, 2.3% (4,890/216,056) of participants reported asthma in the past 12 months. Active smoking was significantly associated with asthma (AOR [95% CI] of smoking ≥20 days/month = 1.57 [1.38–1.77], P < 0.001). Passive smoking was also related with asthma (AOR [95% CI] of smoking ≥5 days/week = 1.40 [1.28–1.53], P < 0.001). E-cigarette showed positive relation with asthma, although the effects of past smoking history could not be excluded (AOR [95% CI] = 1.12 [1.01–1.26], P = 0.027).
Transcriptomic analysis of mitochondrial TFAM depletion changing cell morphology and proliferation
Authors: Lee Woo Rin , Na Heeju , Lee Seon Woo , Lim Won-Jun , Kim Namshin , Lee J. Eugene , Kang Changwon
Published: December 2017

Human mitochondrial transcription factor A (TFAM) has been implicated in promoting tumor growth and invasion. TFAM activates mitochondrial DNA (mtDNA) transcription, and affects nuclear gene expression through mitochondrial retrograde signaling. In this study, we investigated the effects of TFAM depletion on the morphology and transcriptome of MKN45 gastric cancer cells. Morphology alteration became visible at 12 h after TFAM knockdown: the proportion of growth-arrested polygonal cells versus oval-shaped cells increased, reaching a half-maximum at 24 h and a near-maximum at 36 h. TFAM knockdown upregulated four genes and downregulated six genes by more than threefold at 24 h and similarly at 48 h. Among them, the knockdown of CFAP65 (cilia and flagella associated protein 65) or PCK1 (cytoplasmic phosphoenolpyruvate carboxykinase) rescued the effects of TFAM depletion on cell morphology and proliferation. PCK1 was found to act downstream of CFAP65 in calcium-mediated retrograde signaling. Furthermore, mtDNA depletion by 2′,3′-dideoxycytidine was sufficient for induction of CFAP65 and PCK1 expression and inhibition of cell proliferation, but oxidative phosphorylation blockade or mitochondrial membrane potential depolarization was not. Thus, the TFAM–mtDNA–calcium–CFAP65–PCK1 axis participates in mitochondrial retrograde signaling, affecting tumor cell differentiation and proliferation.
Cardiac Depression in Pigs after Multiple Trauma – Characterization of Posttraumatic Structural and Functional Alterations
Authors: Kalbitz M. , Schwarz S. , Weber B. , Bosch B. , Pressmar J. , Hoenes F. M. , Braun C. K. , Horst K , Simon T. P. , Pfeifer R. , Störmann P. , Hummler H , Gebhard F. , Pape H. C. , Huber-Lang M. , Hildebrand F. ,   TREAT Research Group, Auner B. , Relja B. , Marzi I. , Marx G. , Haug A. , Egerer L. , Griensven M. v. , Tolba R. , Reiss K. , Uhlig S. , Teuben M. , Almahmoud K. , Kalbas Y. , Lüken H. , Almahmoud K.
Published: December 2017

The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1β generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.
Electrophysiology of the rhythmic defecation program in nematode Heterorhabditis megidis
Authors: Kuznetsov Victor P. , Slivko-Koltchik Georgy A. , Voronov Dmitry A. , Panchin Yuri V.
Published: December 2017

The nervous system controls most rhythmic behaviors, with a remarkable exception. In Caenorhabditis elegans periodic defecation rhythm does not appear to involve the nervous system. Such oscillations are studied in detail with genetic and molecular biology tools. The small size of C. elegans cells impairs the use of standard electrophysiological methods. We studied a similar rhythmic pacemaker in the noticeably larger gut cells of Heterorhabditis megidis nematode. H. megidis defecation cycle is driven by a central pattern generator (CPG) associated with unusual all-or-none hyper-polarization “action potential”. The CPG cycle period depends on the membrane potential and CPG cycling also persisted in experiments where the membrane potential of gut cells was continuously clamped at steady voltage levels. The usual excitable tissue description does not include the endoderm or imply the generation of hyper-polarization spikes. The nematode gut cells activity calls for a reevaluation of the excitable cells definition.
The after-hours circadian mutant has reduced phenotypic plasticity in behaviors at multiple timescales and in sleep homeostasis
Authors: Maggi Silvia , Balzani Edoardo , Lassi Glenda , Garcia-Garcia Celina , Plano Andrea , Espinoza Stefano , Mus Liudmila , Tinarelli Federico , Nolan Patrick M. , Gainetdinov Raul R. , Balci Fuat , Nieus Thierry , Tucci Valter
Published: December 2017

Circadian clock is known to adapt to environmental changes and can significantly influence cognitive and physiological functions. In this work, we report specific behavioral, cognitive, and sleep homeostatic defects in the after hours (Afh) circadian mouse mutant, which is characterized by lengthened circadian period. We found that the circadian timing irregularities in Afh mice resulted in higher interval timing uncertainty and suboptimal decisions due to incapability of processing probabilities. Our phenotypic observations further suggested that Afh mutants failed to exhibit the necessary phenotypic plasticity for adapting to temporal changes at multiple time scales (seconds-to-minutes to circadian). These behavioral effects of Afh mutation were complemented by the specific disruption of the Per/Cry circadian regulatory complex in brain regions that govern food anticipatory behaviors, sleep, and timing. We derive statistical predictions, which indicate that circadian clock and sleep are complementary processes in controlling behavioral/cognitive performance during 24 hrs. The results of this study have pivotal implications for understanding how the circadian clock modulates sleep and behavior.
Effects of resistance exercise on endothelial progenitor cell mobilization in women
Authors: Ribeiro Fernando , Ribeiro Ilda P. , Gonçalves Ana C. , Alves Alberto J. , Melo Elsa , Fernandes Raquel , Costa Rui , Sarmento-Ribeiro Ana B. , Duarte José A. , Carreira Isabel M. , Witkowski Sarah , Oliveira José
Published: December 2017

This study aimed to determine the effect of a single bout of resistance exercise at different intensities on the mobilization of circulating EPCs over 24 hours in women. In addition, the angiogenic factors stromal cell-derived factor 1 (SDF-1α), vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1-alpha (HIF-1α) and erythropoietin (EPO) were measured as potential mechanisms for exercise-induced EPCs mobilization. Thirty-eight women performed a resistance exercise session at an intensity of 60% (n = 13), 70% (n = 12) or 80% (n = 13) of one repetition maximum. Each session was comprised of three sets of 12 repetitions of four exercises: bench press, dumbbell curl, dumbbell squat, and standing dumbbell upright row. Blood was sampled at baseline and immediately, 6 hours, and 24 hours post-exercise. Circulating EPC and levels of VEGF, HIF-1α and EPO were significantly higher after exercise (P < 0.05). The change in EPCs from baseline was greatest in the 80% group (P < 0.05), reaching the highest at 6 hours post-exercise. The change in EPCs from baseline to 6 hours post-exercise was correlated with the change in VEGF (r = 0.492, P = 0.002) and HIF-1α (r = 0.388, P = 0.016). In general, a dose-response relationship was observed, with the highest exercise intensities promoting the highest increases in EPCs and angiogenic factors.
Comparing Stroop-like and Simon Effects on Perceptual Features
Authors: Scerrati Elisa , Lugli Luisa , Nicoletti Roberto , Umiltà Carlo
Published: December 2017

Stroop-like and Simon tasks produce two sources of interference in human information processing. Despite being logically similar, it is still debated whether the conflicts ensuing from the two tasks are resolved by the same or different mechanisms. In the present study, we compare two accounts of the Stroop-like effect. According to the Perceptual Account, the Stroop-like effect is due to Stimulus-Stimulus congruence. According to the Decisional Account, the Stroop-like effect results from the same mechanisms that produce the Simon effect, that is, Stimulus-Response compatibility. In two experiments we produced Stroop-like and Simon effects by presenting left/right-located stimuli consisting of a colored square surrounded by a frame of the same color as the square or of a different color. Results showed that discriminating either the color of the square (Experiment 1) or that of the frame (Experiment 2) yielded additive Stroop-like and Simon effects. In addition, the patterns of temporal distributions of the two effects were different. These results support the Perceptual Account of the Stroop-like effect and the notion that the Stroop-like effect and the Simon effect occur at different processing stages and are attributable to different mechanisms.
Impact of the G84E variant on HOXB13 gene and protein expression in formalin-fixed, paraffin-embedded prostate tumours
Authors: FitzGerald Liesel M. , Raspin Kelsie , Marthick James R. , Field Matt A. , Malley Roslyn C. , Thomson Russell J. , Blackburn Nicholas B. , Banks Annette , Charlesworth Jac C. , Donovan Shaun , Dickinson Joanne L.
Published: December 2017

The HOXB13 G84E variant is associated with risk of prostate cancer (PCa), however the role this variant plays in PCa development is unknown. This study examined 751 cases, 450 relatives and 355 controls to determine the contribution of this variant to PCa risk in Tasmania and investigated HOXB13 gene and protein expression in tumours from nine G84E heterozygote variant and 13 wild-type carriers. Quantitative PCR and immunohistochemistry showed that HOXB13 gene and protein expression did not differ between tumour samples from variant and wild-type carriers. Allele-specific transcription revealed that two of seven G84E carriers transcribed both the variant and wild-type allele, while five carriers transcribed the wild-type allele. Methylation of surrounding CpG sites was lower in the variant compared to the wild-type allele, however overall methylation across the region was very low. Notably, tumour characteristics were less aggressive in the two variant carriers that transcribed the variant allele compared to the five that did not. This study has shown that HOXB13 expression does not differ between tumour tissue of G84E variant carriers and non-carriers. Intriguingly, the G84E variant allele was rarely transcribed in carriers, suggesting that HOXB13 expression may be driven by the wild-type allele in the majority of carriers.
Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr
−/− mice
Authors: Xu Jiesi , Xu Yang , Xu Yanyong , Yin Liya , Zhang Yanqiao
Published: December 2017

Atherosclerotic cardiovascular disease is a leading cause of death in the western world. Increased plasma triglyceride and cholesterol levels are major risk factors for this disease. Carboxylesterase 1 (Ces1/Ces1g) has been shown to play a role in metabolic control. So far, the role of mouse Ces1/Ces1g deficiency in atherosclerosis is not elucidated. We generated Ces1/Ces1g−/− mice. Compared to wild-type mice, Ces1/Ces1g−/− mice had reduced plasma cholesterol levels. We then generated Ces1g−/−Ldlr−/− double knockout (DKO) mice, which were fed a Western diet for 16 weeks. Compared to Ldlr−/− mice, DKO mice displayed decreased plasma cholesterol and TG levels and reduced atherosclerotic lesions. Interestingly, knockdown of hepatic Ces1/Ces1g in Apoe−/− mice resulted in hyperlipidemia and exacerbated Western diet-induced atherogenesis. Mechanistically, global inactivation of Ces1/Ces1g inhibited intestinal cholesterol and fat absorption and Niemann-Pick C1 like 1 expression, and increased macrophage cholesterol efflux by inducing ATP-binding cassette subfamily A member 1 (ABCA1) and ABCG1. Ces1/Ces1g ablation also promoted M2 macrophage polarization and induced hepatic cholesterol 7α-hydroxylase and sterol 12α-hydroxylase expression. In conclusion, global loss of Ces1/Ces1g protects against the development of atherosclerosis by inhibiting intestinal cholesterol and triglyceride absorption and promoting macrophage cholesterol efflux.
CRISPR/Cas9-based knockouts reveal that CpRLP1 is a negative regulator of the sex pheromone PR-IP in the Closterium peracerosum-strigosum-littorale complex
Authors: Kanda Naho , Ichikawa Machiko , Ono Ayaka , Toyoda Atsushi , Fujiyama Asao , Abe Jun , Tsuchikane Yuki , Nishiyama Tomoaki , Sekimoto Hiroyuki
Published: December 2017

Heterothallic strains of the Closterium peracerosum-strigosum-littorale (C. psl.) complex have two sexes, mating-type plus (mt+) and mating-type minus (mt−). Conjugation between these two sexes is regulated by two sex pheromones, protoplast-release-inducing protein (PR-IP) and PR-IP Inducer, which are produced by mt+ and mt− cells, respectively. PR-IP mediates the release of protoplasts from mt− cells during mating. In this study, we examined the mechanism of action of CpRLP1 (receptor-like protein 1), which was previously identified in a cDNA microarray analysis as one of the PR-IP-inducible genes. Using CRISPR/Cas9 technology, we generated CpRLP1 knockout mutants in mt− cells of the C. psl. complex. When the knockout mt− cells were mixed with wild-type mt+ cells, conjugation was severely reduced. Many cells released protoplasts without pairing, suggesting a loss of synchronization between the two mating partners. Furthermore, the knockout mutants were hypersensitive to PR-IP. We conclude that CpRLP1 is a negative regulator of PR-IP that regulates the timing of protoplast release in conjugating C. psl. cells. As the first report of successful gene knockout in the class Charophyceae, this study provides a basis for research aimed at understanding the ancestral roles of genes that are indispensable for the development of land plants.
Noble-metal-free ternary CN–ZCS–NiS nanocomposites for enhanced solar photocatalytic H2-production activity
Authors: Yu Yanchun , Wang Enbo
Published: December 2017

The nanocomposite of ZCS/CN heterojunctions loaded with NiS possesses photocatalytic hydrogen production activity 405 times higher than the pure CN.
Capsaicin and nonivamide similarly modulate outcome measures of mitochondrial energy metabolism in HepG2 and 3T3-L1 cells
Authors: Hochkogler Christina M. , Lieder Barbara , Schachner Daniel , Heiss Elke , Schröter Annett , Hans Joachim , Ley Jakob P. , Krammer Gerhard E. , Somoza Veronika
Published: December 2017

Nonivamide, a less pungent capsaicin analog, has similar effects on the outcome measures of energy metabolism to capsaicin.
Mono-fullerenols modulating cell stiffness by perturbing actin bundling
Authors: Gu Weihong , Bai Xue , Ren Keli , Zhao Xiaoyi , Xia Shibo , Zhang Jiaxin , Qin Yanxia , Lei Runhong , Chen Kui , Chang Ya-nan , Zeng Li , Li Juan , Xing Gengmei
Published: December 2017

The first evidence of how mono-fullerenols modulate the cell stiffness: direct adhesion to f-actin and consequent perturbation of actin bundling.
Comparison between mandibular and femur derived bone marrow stromal cells: osteogenic and angiogenic potentials in vitro and bone repairing ability in vivo
Authors: Zhou Wenhui , Zhang Jinkai , Lin Kaili , Chen Fengshan
Published: December 2017

M-BMSCs contains stronger osteogenic and angiogenic potentials, and better bone repairing ability.
Liquid crystal elastomer foams with elastic properties specifically engineered as biodegradable brain tissue scaffolds
Authors: Prévôt M. E. , Andro H. , Alexander S. L. M. , Ustunel S. , Zhu C. , Nikolov Z. , Rafferty S. T. , Brannum M. T. , Kinsel B. , Korley L. T. J. , Freeman E. J. , McDonough J. A. , Clements R. J. , Hegmann E.
Published: December 2017

3D liquid crystal elastomer foams (LCEs) scaffold materials as dynamic substrates for cell culture, going beyond designing only a physical static 3D scaffold.
Functional adlayers on Au electrodes: some recent applications in hydrogen evolution and oxygen reduction
Authors: Chattopadhyay Samir , Sarkar Ankita , Chatterjee Sudipta , Dey Abhishek
Published: December 2017

The Mo–S based inorganic salt ATM (ammonium tetrathiomolybdate) and cysteine containing peptides can form self-assembled adlayers on Au surfaces and these modified electrode materials exhibit miscellaneous catalytic activities.
Adaptive fault estimation and fault‐tolerant tracking control for a class of non‐linear systems with output constraints
Authors: Wu Li‐Bing , Wang Heng , He Xi‐Qin , Zhang Da‐Qing , Huang Sheng‐Juan
Published: December 2017

This study investigates the problem of adaptive fault estimation and fault‐tolerant control for a class of non‐linear systems with output constraints. In order to estimate system faults and unmeasurable system states, a novel non‐linear fault estimator with adaptive update law is constructed, which can receive better estimation accuracy, and the fault estimation error can be confined into a prescribed region. Moreover, a fault‐tolerant tracking controller is designed to compensate the effect of faults based on backstepping techniques. It is proved that all the closed‐loop system signals are uniformly ultimately bounded and the system output tracking error converges to a desired neighbourhood of origin. Finally, simulation results are provided to illustrate the efficiency of the proposed approach.
Fixed‐time leader–follower consensus tracking of second‐order multi‐agent systems with bounded input uncertainties using non‐singular terminal sliding mode technique
Authors: Khanzadeh Alireza , Pourgholi Mahdi
Published: December 2017

This study investigates the fixed‐time consensus tracking problem for second‐order multi‐agent systems. A new fixed‐time stability condition and a new non‐singular‐terminal sliding surface are introduced. Using Gudermannian function, the fixed‐time stability of sliding mode dynamics is proved and its guaranteed convergence time is obtained. Based on this condition and utilising the proposed surface, a non‐singular sliding mode distributed protocol is proposed in which the guaranteed convergence times of reaching and sliding modes exist as design parameters. By employing the proposed protocol, fixed‐time leader–follower consensus tracking for uncertain second‐order multi‐agent systems before a prescribed time by only using relative information can be accomplished. Simulation results are reported to show the effectiveness of the proposed method.
Gallium arsenide 0.5–18 GHz antenna front‐end with integrated limiter and differential to single ended low‐noise amplifier
Authors: Pantoli Leonardo , Stornelli Vincenzo , Leuzzi Giorgio , Bartocci Marco , Trotta Fabrizio , Gaetano Domenico , Manna Antonio , Ciacia Egidio , Di Paolo Franco
Published: December 2017

In this study, the authors present a 36:1 relative bandwidth active front‐end low‐noise amplifier (LNA) with power limiter that has been developed for airborne ultra‐wideband receiver systems. The proposed system is driven by an external antenna with a balanced mode with an input impedance of 150 Ω. The whole microwave monolithic integrated circuit (MMIC) embeds a protection from the presence of high‐level signals, an ultra‐wideband amplifier circuit, an active balun and an impedance transformer. It has a bandwidth ranging from 0.5 to 18.0 GHz with 14 dB gain, 4.5 dB noise figure (NF), 20 dB common‐mode rejection and 30 dBm input overload protection. The circuit has a single bias from the output port greatly simplifying its use within a receiving system and can be directly integrated into the antenna mechanical support. Test measurements are also provided.
Update battery model for photovoltaic application based on comparative analysis and parameter identification of lead–acid battery models behaviour
Authors: Degla Aicha , Chikh Madjid , Chouder Aissa , Bouchafaa Farid , Taallah Ayoub
Published: December 2017

Energy storage using electrochemical battery systems has been widely addressed as a key element to enable widespread integration of renewable energy. Here, an updated battery model is investigated in order to allow accurate standalone photovoltaic (PV) systems simulation, for performance assessment and long‐term energy prediction. Battery models have been largely described in the literature. However, this study reviews the most commonly used models in PV application such as Shepherd, Manegon, and Coppetti models in order to validate the suitable mathematical model. The updated battery model based on experimental results and parameter extraction procedure is carried out using sealed gelled lead/acid battery during charge and discharge processes. A comparative analysis based on statistical tests and optimisation method confirms the effectiveness of the most accurate model among the three models using new proposed parameters. The simulation results of the model with new coefficients are compared with measured data, recorded from battery charge and discharge test bench to validate the accuracy of the updated model.
Influence of cogging force on solar thermo acoustic generation systems
Authors: Ding Wang , Yu Shi , Tao Meng , Ye Yuan , Chen Liu
Published: December 2017

Here, the model of a solar thermoacoustic generation (STAG) system is presented, and the influences of cogging force on the resonance of STAG system are investigated by simulation. The samples of cogging force are taken from three typical linear alternator designs, and their consequent influences on STAG system are described.
Cooperative game‐based method to determine the weights of load forecasting solution incorporated with various algorithms
Authors: Ngo VietCuong , Wu Wenchuan , Yang Yi , Zhang Boming
Published: December 2017

Ultra‐short‐term load forecasting is one of the core techniques for distribution networks operation. Since individual load in distribution networks is small and with strong randomness, single prediction model cannot guarantee the forecasting accuracy and combined forecasting solution is usually used. In such forecasting scheme, how to weight the different forecasting model is a challenge. By introducing the concept of cooperative game, the weight of every algorithm can be determined according to the error distribution. The proposed method has been tested for a real distribution networks and the results show this scheme has good prediction precision, and can control the error distribution at the inflection points.
Evaluating the capacity of power and energy balance for cascaded H‐bridge multilevel inverter using different PWM techniques
Authors: Gadalla Abuzaid Saeed , Yan Xiangwu , Altahir Sara Yahia , Hasabelrasul Hashim
Published: December 2017

Among the different multilevel topologies for inverters, cascaded H‐bridge multilevel topology has been a good solution for high‐power medium‐voltage applications because of its modularity structure, voltage balancing, separated DC sources, harmonics reduction, reliability and lower stresses on switching devices. The most widely used pulse width modulation (PWM) techniques for cascaded H‐bridge multilevel inverter are known as phase shifted and level shifted. This study presents a comparison of power and energy distribution (inter‐phase and inter‐bridge power and energy) of three‐phase cascaded H‐bridge multilevel inverter for the phase‐shifted and the level‐shifted carrier PWM (phase disposition). A detailed comparison of different PWM techniques with reference to total harmonic distortion in the output voltages, both cases using a filter and without filter are presented also in this study. Simulation for 11‐level cascaded H‐bridge inverter is carried out in MATLAB/SIMULINK and simulation results are presented.
Compound frequency modulation strategy of DFIG‐based wind turbines dealing with stator winding inter‐turn short‐circuit fault
Authors: Sun Li‐ling , Hu Lan‐qing , Xu Bo‐qiang
Published: December 2017

Stator winding inter‐turn short‐circuit fault (SWITSC) is a kind of common and high risk fault of doubly fed induction generator (DFIG), which would cause mutation of motor power. DFIG‐based wind turbine is common in weak grid and its power fluctuation triggers the drop of system frequency. However, due to the decoupling control between speed and frequency, it is difficult to provide dynamic response to the system when the frequency fluctuation. To solve the above problems, two kinds of frequency control are proposed: integrated inertial and improved pitch angle control frequency modulation (FM). The effects of the FM of the two methods dealing with the frequency drop caused by SWITSC fault are analysed and compared, and results show: integrated inertial FM reduces the rate of change of frequency and provides the dynamic support of frequency; improved pitch angle control raises the lowest frequency and reduces the amplitude of frequency fluctuation. Finally, a new composite frequency control strategy considering the integrated inertial control and improved pitch angle control is proposed, which can elevate the transient and steady‐state performance of system frequency and ameliorate the problem of frequency drop in weak grid under SWITSC fault effectively. These methods are applied to models developed in Matlab/Simulink and indicative results are presented.
A dynamic multi-level optimal design method with embedded finite-element modeling for power transformers
Authors: Zhang Yunpeng , Ho Siu-lau , Fu Weinong
Published: December 2017

This paper proposes a dynamic multi-level optimal design method for power transformer design optimization (TDO) problems. A response surface generated by second-order polynomial regression analysis is updated dynamically by adding more design points, which are selected by Shifted Hammersley Method (SHM) and calculated by finite-element method (FEM). The updating stops when the accuracy requirement is satisfied, and optimized solutions of the preliminary design are derived simultaneously. The optimal design level is modulated through changing the level of error tolerance. Based on the response surface of the preliminary design, a refined optimal design is added using multi-objective genetic algorithm (MOGA). The effectiveness of the proposed optimal design method is validated through a classic three-phase power TDO problem.
Turning the threat into a solution: using roadways to survey cryptic species and to identify locations for conservation
Authors: Baxter-Gilbert James H. , Riley Julia L. , Boyle Sean P. , Lesbarrères David , Litzgus Jacqueline D.
Published: December 2017

Freshwater turtles are one of the most imperilled groups of vertebrates globally, and roads have been associated with their decline. Although roads are typically viewed as an imminent threat to population persistence, because of direct mortality and increased landscape fragmentation, we argue that they are an important sampling tool for collecting a wide variety of data that can inform conservation efforts. Road surveys can yield important presence data when conducting species inventories, particularly for cryptic species, and can also indicate where to implement road mitigation measures. Our research examined three road survey methods from two previous studies (walking versus bicycling and walking versus driving) to test their relative effectiveness at locating turtles. We found that walking surveys yielded the highest number of turtles per kilometre; however, bicycling and driving surveys also presented advantages (specifically, the ability to survey longer lengths of road more quickly). We recommend using walking surveys in areas of specific interest (e.g. to investigate suitable habitat for imperilled species or to investigate the presence of cryptic species), and bicycling or driving surveys between sections of specific interest. Road survey methods could be used in addition to more traditional sampling approaches (e.g. trapping and visual surveys), and do not need to be restricted to areas where roadwork projects are in progress or being planned. Road surveys could also be used during general environmental assessments and ecological research, to effectively incorporate turtle presence data into conservation efforts.
Transition phase clothing strategies and their effect on body temperature and 100‐m swimming performance
Authors: Galbraith Andy , Willmott Aimee
Published: December 2017

Objective: Effective warm‐ups are attributed to several temperature‐related mechanisms. Strategies during the transition phase, preceding swimming competition, have been shown to prolong temperature‐related warm‐up effects. The purpose of this study was to evaluate the effects of two different clothing strategies during the transition phase, on subsequent 100‐m maximal swimming performance. Methods: Nine competitive swimmers (3 female, 21 ± 3 yrs; 6 male 20 ± 2 yrs, mean performance standard 702 FINA Points, mean 100‐m seasons best time 61.54 s) completed their own 30‐min individual pool warm‐up, followed by 7‐min changing time and a 30‐min transition phase, straight into a 100‐m maximal effort time‐trial. During the transition phase, swimmers remained seated, either wearing warm or limited clothing. Swimmers returned 1 week later, where clothing conditions were alternated. Results: Post‐transition phase skin and core temperature remained higher in the warm clothing condition compared to the limited clothing condition (Mean Core: 36.90 ± 0.17°C, 36.61 ± 0.15°C, P < .01; Mean Skin: 33.49 ± 0.59°C, 31.94 ± 0.59°C, P < .01). One hundred‐metre finish times were 0.6% faster in the warm clothing condition compared to the limited clothing condition (62.63 ± 7.69 s, 63.00 ± 7.75 s, P < .01). Conclusion: Wearing warm clothing during a 30‐min transition phase improved swimming performance by 0.6%, compared to limited clothing.
Global social policy: an application of welfare state theory
Authors: Holden Chris
Published: December 2017

Global social policy (GSP) takes different forms from those of national welfare states, since it depends on the activities of an array of international organisations and transnational actors. Three broad theoretical approaches have dominated the literature on national welfare state development: those focused on processes of economic development, industrialisation and urbanisation; those focused on class struggle and political mobilisation; and those focused on the effects of political institutions. This article applies each of these broad theoretical approaches to the development of GSP in order to illuminate the nature of GSP, its likely future development, and the constraints upon such development. It is concluded that the dominant forms taken by GSP will continue to be piecemeal, minimalist and essentially neoliberal for as long as an effective global political movement in favour of a more extensive GSP is absent.
gene2drug: a computational tool for pathway-based rational drug repositioning
Authors: Napolitano Francesco , Carrella Diego , Mandriani Barbara , Pisonero-Vaquero Sandra , Sirci Francesco , Medina Diego L , Brunetti-Pierri Nicola , di Bernardo Diego
Published: December 2017

Motivation

Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects.

Results

We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritization of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target. We performed in silico validation and comparison with a state-of-art technique based on similar principles. We next performed experimental validation in two different real-case drug repositioning scenarios: (i) upregulation of the glutamate-pyruvate transaminase (GPT), which has been shown to induce reduction of oxalate levels in a mouse model of primary hyperoxaluria, and (ii) activation of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, whose modulation may be beneficial in neurodegenerative disorders.

Availability and implementation

A web tool for Gene2drug is freely available at http://gene2drug.tigem.it. An R package is under development and can be obtained from https://github.com/franapoli/gep2pep.

Supplementary information

Supplementary data are available at Bioinformatics online.