bluuebunny/crossref_metadata_2025 huggingface dataset:
The low beta anomaly: A corporate bond investor's perspective
Authors: Bektić Demir
Published: April 2018

The low beta anomaly is well documented for equity markets. However, the existence of such a factor in corporate bond markets is less explored. I find that European corporate bonds of firms with a low equity beta have higher risk‐adjusted returns, on average, than European corporate bonds of firms with a high equity beta. The results are economically and statistically significant as low beta credit portfolios improve the Sharpe ratio up to 30%. Moreover, even after accounting for transaction costs and by considering long‐only portfolios, the risk‐adjusted return remains substantial indicating practical implementability of the strategy for corporate bond investors.
Bootstrap inference when using multiple imputation
Authors: Schomaker Michael , Heumann Christian
Published: April 2018

Many modern estimators require bootstrapping to calculate confidence intervals because either no analytic standard error is available or the distribution of the parameter of interest is nonsymmetric. It remains however unclear how to obtain valid bootstrap inference when dealing with multiple imputation to address missing data. We present 4 methods that are intuitively appealing, easy to implement, and combine bootstrap estimation with multiple imputation. We show that 3 of the 4 approaches yield valid inference, but that the performance of the methods varies with respect to the number of imputed data sets and the extent of missingness. Simulation studies reveal the behavior of our approaches in finite samples. A topical analysis from HIV treatment research, which determines the optimal timing of antiretroviral treatment initiation in young children, demonstrates the practical implications of the 4 methods in a sophisticated and realistic setting. This analysis suffers from missing data and uses theg‐formula for inference, a method for which no standard errors are available.
A flexible and coherent test/estimation procedure based on restricted mean survival times for censored time‐to‐event data in randomized clinical trials
Authors: Horiguchi Miki , Cronin Angel M. , Takeuchi Masahiro , Uno Hajime
Published: April 2018

In randomized clinical trials where time‐to‐event is the primary outcome, almost routinely, the logrank test is prespecified as the primary test and the hazard ratio is used to quantify treatment effect. If the ratio of 2 hazard functions is not constant, the logrank test is not optimal and the interpretation of hazard ratio is not obvious. When such a nonproportional hazards case is expected at the design stage, the conventional practice is to prespecify another member of weighted logrank tests, eg, Peto‐Prentice‐Wilcoxon test. Alternatively, one may specify a robust test as the primary test, which can capture various patterns of difference between 2 event time distributions. However, most of those tests do not have companion procedures to quantify the treatment difference, and investigators have fallen back on reporting treatment effect estimates not associated with the primary test. Such incoherence in the “test/estimation” procedure may potentially mislead clinicians/patients who have to balance risk‐benefit for treatment decision. To address this, we propose a flexible and coherent test/estimation procedure based on restricted mean survival time, where the truncation time τ is selected data dependently. The proposed procedure is composed of a prespecified test and an estimation of corresponding robust and interpretable quantitative treatment effect. The utility of the new procedure is demonstrated by numerical studies based on 2 randomized cancer clinical trials; the test is dramatically more powerful than the logrank, Wilcoxon tests, and the restricted mean survival time–based test with a fixed τ, for the patterns of difference seen in these cancer clinical trials.
Comparative review of novel model‐assisted designs for phase I clinical trials
Authors: Zhou Heng , Murray Thomas A. , Pan Haitao , Yuan Ying
Published: April 2018

A number of novel phase I trial designs have been proposed that aim to combine the simplicity of algorithm‐based designs with the superior performance of model‐based designs, including the modified toxicity probability interval, Bayesian optimal interval, and Keyboard designs. In this article, we review these “model‐assisted” designs, contrast their statistical foundations and pros and cons, and compare their operating characteristics with the continual reassessment method. To provide unbiased and reliable results, our comparison is based on 10 000 dose‐toxicity scenarios randomly generated using the pseudo‐uniform algorithm recently proposed in the literature. The results showed that the continual reassessment method, Bayesian optimal interval, and Keyboard designs provide comparable, superior operating characteristics, and each outperforms the modified toxicity probability interval design. These designs are more likely to correctly select the maximum tolerated dose and less likely to overdose patients.
Multivariate generalized hidden Markov regression models with random covariates: Physical exercise in an elderly population
Authors: Punzo Antonio , Ingrassia Salvatore , Maruotti Antonello
Published: April 2018

A time‐varying latent variable model is proposed to jointly analyze multivariate mixed‐support longitudinal data. The proposal can be viewed as an extension of hidden Markov regression models with fixed covariates (HMRMFCs), which is the state of the art for modelling longitudinal data, with a special focus on the underlying clustering structure. HMRMFCs are inadequate for applications in which a clustering structure can be identified in the distribution of the covariates, as the clustering is independent from the covariates distribution. Here, hidden Markov regression models with random covariates are introduced by explicitly specifying state‐specific distributions for the covariates, with the aim of improving the recovering of the clusters in the data with respect to a fixed covariates paradigm. The hidden Markov regression models with random covariates class is defined focusing on the exponential family, in a generalized linear model framework. Model identifiability conditions are sketched, an expectation‐maximization algorithm is outlined for parameter estimation, and various implementation and operational issues are discussed. Properties of the estimators of the regression coefficients, as well as of the hidden path parameters, are evaluated through simulation experiments and compared with those of HMRMFCs. The method is applied to physical activity data.
Phthalocyanine‐containing polymer derived porous carbon as a solid‐phase extraction adsorbent for the enrichment of phenylurea herbicides from water and vegetable samples
Authors: Wang Yao , Xiao Ruobai , Yang Ershun , Wu Qiuhua , Wang Chun , Wang Zhi
Published: April 2018

In this study, a porous carbon was prepared by the carbonization of a phthalocyanines‐containing polymer. The carbon material was characterized by using scanning electron microscope, transmission electron microscope, X‐ray diffraction and N2 adsorption–desorption isotherms. The material was used as the solid phase extraction adsorbent for the enrichment of five phenylurea herbicides (monuron, monolinuron, isoproturon, chlortoluron, and buturon) from water and vegetable samples prior to high performance liquid chromatographic analysis. Under the optimized conditions, a good linearity for the analytes existed in the range of 0.1–80.0 ng/mL for water samples, 0.5–80.0 ng/g for white turnip samples, and 0.2–80.0 ng/g for cucumber samples, with determination coefficients of 0.9987–0.9998. The limits of detection for the five analytes at a signal to noise ratio of 3 were 0.01–0.02 ng/mL for water, 0.05–0.10 ng/g for white turnip and 0.03–0.05 ng/g for cucumber. The limits of quantification at the signal to noise ratio of 9 were 0.03–0.06 ng/mL for water, 0.15–0.3 ng/g for white turnip, and 0.1–0.15 ng/g for cucumber.
Modeling prize‐based open design challenges: General framework and FANG‐1 case study
Authors: Suh Eun Suk , de Weck Olivier Ladislas
Published: April 2018

Many organizations are resorting to open prize‐based challenges and competitions to identify the best possible designs for their future products or services. As an example, the Defense Advanced Research Projects Agency (DARPA) hosted an open challenge for designing the drivetrain and mobility subsystem of a Fast Adaptable Next‐Generation Ground Vehicle (FANG‐1) in early 2013. A $1 million prize was awarded to the team with the highest concept score and the design was subsequently physically implemented and tested. The competition was the first attempt by DARPA to utilize crowdsourcing for the design of complex military systems, which is in contrast with contracting directly with a small number of incumbent firms within the defense industry. The competition attracted over 200 participating teams and the winning team was announced in April 2013. In this paper, inspired by the FANG‐1 challenge, a generalizable simulation model for predicting the dynamics of open prize‐based design challenges and competitions is developed using a combination of several modeling methods. The model is then applied to simulate the dynamics of the FANG‐1 challenge ex post facto, including an approximation of the distribution of team scores as well as the interteam motivational interactions. Using the simulation model, various sensitivity analyses were then performed to identify factors that could enhance future design challenges and competitions in terms of resulting innovation and productivity.
A disclosure of social and environmental results/economy resulting from the implementation of reverse logistics and final disposal of the post‐consumption product: The case of computer peripherals industry
Authors: Slomski Valmor , Slomski Vilma Geni , Valim Gilson Giungi , Vasconcelos Ana Lúcia Fontes de Souza
Published: April 2018

This research was conducted with the objective of determining and evidencing the social and environmental/economic results from the implementation of a reverse logistics program providing for the recycling, reuse, and, when necessary, final, environmentally correct disposal of post‐consumption products and product wastes by a multinational manufacturer of computer peripherals with an operation based in the city of São Paulo, Brazil. The reverse logistics process (logisticareversa, or, in this paper, LR) was intended to meet the objectives and principles of the regulatory framework defined in the National Solid Waste Policy (PNRS) in Brazil. A single case study was carried out. The results showed that after the adoption of the solid waste management policy, the study company no longer disposed of 1,413,552 kilograms (kg) of materials classified as mixed iron, polystyrene, cardboard, toner powder, and plastic in landfills. The LR process made a profit in two companies: the company surveyed made, in Brazilian reais (R), R$ 9,188,185.51, and the company contracted to carry out the process made, R$ 411,325.97. This latter profit is called by us the “social profit.” The measurement of the environmental/economic, social, and financial results by internalizing the expenses of the LR program into the costs of production shows that reuse and recycling better meets the needs of society and the company than landfilling these post‐consumption materials. Furthermore, the use of cost accounting allows the verification of other goals not indicated in the current model, such as the generation of employment, income, mitigation of environmental problems, and the profit earned by the company contracted to implement the LR process. We also conclude that cost accounting makes it possible to obtain necessary information for decision makers, who are seeking to neutralize environmental impacts and promote sustainable development, thus harmonizing the economic, social, and environmental aspects, to understand the impacts of the LR process.
A comparative study on cost analysis, efficiency, and process mechanism of effluent treatment plants in Bangladesh
Authors: Sarker Nilay Kumar , Sarkar Suman
Published: April 2018

Investigations were conducted into the treatment of effluents produced during manufacturing processes at both a chemicals production facility and a paint manufacturing facility. A comparison of costs of wastewater treatment at both facilities was also performed. The untreated effluents from both facilities were high in biological oxygen demand (BOD), chemical oxygen demand (COD), and total dissolved solids (TDS). In addition, the effluents from the two facilities deviated significantly in dissolved oxygen (DO) content and pH levels. However, both facilities ultimately released treated wastewater with allowable amounts or levels of BOD, COD, TDS, DO, and pH as permitted by the Department of the Environment, Ministry of Environment and Forests, Bangladesh (DOE). The effluent treatment plants (ETP) at both facilities contained combinations of chemical and biological treatment processes. The treatment processes used at the chemicals production facility and at the paint manufacturing facility were continuous and semi‐batch processes, respectively. The biological treatment section of the ETP at the chemicals production facility has both anaerobic and aerobic units, while the paint manufacturing facility has only an aerobic unit. Annual installation and operation costs of the ETP at the chemicals production facility was Bangladeshi Taka (Tk) 1,300,000 ($16,667 US dollars) and Tk 800,000 ($10,257), respectively. The annual installation and operation costs of the ETP at the paint manufacturing facility were Tk 3,050,000 ($39,103) and Tk 6,200,000 ($79,488), respectively.
Sometimes determination and compromise thwart success: lessons learned from an effort to study copying and pasting in the electronic medical record
Authors: Gagliardi Jane P. , Rudd Mariah J.
Published: April 2018

None
JUSTIFIED GROUP BELIEF IS EVIDENTIALLY RESPONSIBLE GROUP BELIEF
Authors: Silva Paul
Published: April 2018

What conditions must be satisfied if a group is to count as having a justified belief? Jennifer Lackey (2016) has recently argued that any adequate account of group justification must be sensitive (in certain ways) to both the evidence actually possessed by enough of a group's operative members as well as the evidence those members should have possessed. I first draw attention to a range of objections to Lackey's specific view of group justification and a range of concrete case intuitions any plausible view of group justification must explain. I then offer an alternative view of group justification where the basic idea is that group justification is a matter of groups responsibly responding to their total evidence. This view both avoids the problems facing Lackey's account and also explains the relevant concrete case intuitions.
Maternal relations, feminism and surrogate motherhood in the Italian context
Authors: Cossutta Carlotta
Published: April 2018

This article examines the surrogacy debate that has developed within contemporary feminist and LGBT movements in Italy, following the approval of the law on civil unions at the beginning of 2016. This debate has been marked by a deep fracture between those who see in surrogate motherhood a chance to imagine new forms of social bonds and those who consider that women’s wombs and newborn children can never be the object of an economic ‘exchange’. I will first analyse the most controversial positions held by some feminists who have participated in the debate, which revolve around the centrality of the maternal figure. Then I will outline a brief history of the social construction of pregnancy, linking it to changes in the marketplace and the birth of biopolitics. Finally, with the help of Angela Putino’s philosophical thought I will advance a potentially different feminist approach to the issue of surrogate motherhood.
Mobilizing the Young: The Role of Social Networks
Authors: Anderson Cameron D. , Stephenson Laura B.
Published: April 2018

Disaffection of youth from politics is a well-documented phenomenon in many countries. In this article, we consider whether the social networks of young people have the same influence on political engagement as they have been found to have for older adults. We use a single dataset to test the effects of discussion and disagreement on the political engagement of young people (30 and under) and older adults. We find that social network discussion has a stronger effect on the engagement of young people but that disagreement has no clear differential effect.
Do Canadian Mining Firms Behave Worse Than Other Companies? Quantitative Evidence from Latin America
Authors: Haslam Paul Alexander , Ary Tanimoune Nasser , Razeq Zarlasht M.
Published: April 2018

The effects of Canadian mining companies on local communities abroad is an increasingly contentious topic as activists and academics, citing case studies, have drawn attention to alleged problems. Despite the policy relevance of this issue, there have been no generalizable analyses of whether mining companies headquartered in Canada behave differently from mining firms headquartered in other countries. This paper conducts the first rigorous statistical analysis of the effect of country of origin, or more specifically, “being Canadian,” on the occurrence of known social conflicts in Latin America. We use an original database of 634 mining properties in five Latin American countries, which allows us to differentiate between a country-of-origin effect and other probable determinants of social conflict in communities near mining properties. We find that Canadian mining firms perform slightly better than other foreign firms, but worse than locally owned firms.
Prosodic properties of formality in conversational Japanese
Authors: Sherr-Ziarko Ethan
Published: April 2018

This paper examines potential prosodic cues for level of formality in Japanese conversational speech using speech data gathered via one-on-one interviews. Based on previous work on the phonetic properties of formality in Japanese (Ofuka et al. 2000, Ito 2002), further studies of Korean (Winter & Grawunder 2012) and Catalan Spanish (Hübscher, Borràs-Comes & Prieto 2017), and on a lab-based pilot study, the study examined properties off0, intensity, pause frequency, and articulation rate via mixed effects regression models and a functional data analysis (Grabe, Kochanski & Coleman 2007, Ramsay 2006). Analysis of the speech data shows significant relationships between a number of prosodic variables and level of formality, and suggests that some of these relationships may apply cross-linguistically.
An improbable opportunistic predator: the functional morphology ofPinna nobilis(Bivalvia: Pterioida: Pinnidae)
Authors: Morton Brian , Puljas Sanja
Published: April 2018

The functional morphology ofPinna nobilisis described, with special reference to the uniquely pinnid pallial organ, the similarly unique buccal (formerly pallial) gland, the stomach and its contents. The pallial gland produces sulphuric acid which as well as functioning as a shell cleaning swab may be involved in prey capture. The buccal gland discharging into the oesophagus has proteolytic digestive functions while the stomach is adapted for the reception and digestion of captured, mucous-bound, mesozooplanktonic and epi- and endo-benthic, prey items.Pinna nobilisis thus not simply either an accidental or incidental predator of such species but is opportunistic. The buccal glands and stomachs of other Pinnidae are not so specialized as inP. nobilis,possibly indicating that in the particular, oligotrophic, environment of the Mediterranean and Adriatic Seas, and in which it is endemic,P. nobilishas, in addition to being a typical ctenidial suspension feeder, become an opportunistic predator. Although the deep sea representatives of the Septibranchia (Anomalodesmata) and Propeamussidae are obligate predators, this is the first record of any bivalve functioning as an opportunistic predator with unique morphological adaptations to facilitate this.
DE VITI DE MARCO, THE “EUROPEAN WAR,” AND PRESIDENT WILSON
Authors: Martelloni Francesco , Mosca Manuela
Published: April 2018

Italy entered the war in May 1915; the USA, in April 1917. One hundred years on, this paper examines the viewpoint of Antonio de Viti de Marco, the renowned Italian economist who was one of the founders of the pure theory of public finance. It first focuses on De Viti’s interpretation of the economic and political aspects of the Great War, and reconstructs his vision of the world conflict as a struggle between liberal democracies and authoritarian states. Second, the paper highlights the convergence of De Viti’s ideals with those of President Wilson, seen as the powerful international leader of the Italian democratic interventionists. It also clarifies that the “Wilsonianism” of this movement originated in the Italian Risorgimento, and suggests that this convergence was not coincidental. Finally, it shows how, after the war, the unconditional admiration De Viti felt for the American positions gave way to bitter disappointment.
Slamming the Door on Trade Policy Discretion? The WTO Appellate Body’s Ruling on Market Distortions and Production Costs in EU–Biodiesel (Argentina)
Authors: CROWLEY MEREDITH A. , HILLMAN JENNIFER A.
Published: April 2018

This paper presents a legal–economic analysis of the Appellate Body's decision in EU–Biodiesel (Argentina) that the WTO's Anti-Dumping Agreement (ADA) does not permit countries to take into account government-created price distortions of major inputs when calculating anti-dumping duties. In this case, the EU made adjustments to the price of biodiesel's principal input – soybeans – in determining the cost of production of biodiesel in Argentina. The adjustment was made based on the uncontested finding that the price of soybeans in Argentina was distorted by the existence of an export tax scheme that resulted in artificially low soybean prices. The Appellate Body found that the EU was not permitted to take tax policy-induced price distortions into account in calculating dumping margins. We analyze the economic rationale for Argentina's export tax system, distortions in biodiesel markets in Argentina and the EU, and the remaining trade policy options for addressing distorted international prices. We also assess whether existing subsidies disciplines would be more effective in addressing this problem and conclude that they would not.
United States – Anti-Dumping Measures on Certain Oil Country Tubular Goods from Korea (US–OCTG (Korea)), DS488
Authors: Kugler Kholofelo
Published: April 2018

The dispute relates to anti-dumping measures imposed by the United States (US) on oil country tubular goods (OCTG) imported from the Republic of Korea (Korea). Korea challenged the ‘laws, regulations, administrative procedures and other measures’ through which the US maintains a ‘viability test’ in anti-dumping investigations, administrative reviews, and other aspects of anti-dumping proceedings ‘as such’ and ‘as applied’ in the underlying investigation in this dispute. Korea also challenged certain aspects of the final anti-dumping measure that was applied by the US on imports of Korean OCTG subsequent to a final determination of dumping by the US Department of Commerce (USDOC) in the underlying investigation. Moreover, Korea challenged certain conduct of the USDOC during the course of the investigation at issue. Finally, Korea challenged the USDOC's remand determination of 22 February 2016 that was issued while the current dispute was pending before the panel. This determination was taken by the USDOC subsequent to a review conducted by the US Court of International Trade (USCIT) on the final determination challenged by Korea in this dispute. The USCIT found aspects of the final determination to be inconsistent with US law and remanded that final determination to the USDOC to cure the relevant inconsistencies.
Pregnancy risk factors related to autism: an Italian case–control study in mothers of children with autism spectrum disorders (ASD), their siblings and of typically developing children
Authors: Grossi E. , Migliore L. , Muratori F.
Published: April 2018

This study, carried out in two Italian Institutions, assesses the frequency of 27 potential autism risk factors related to pregnancy and peri- and postnatal periods by interviewing mothers who had children with autism, children with autism and one or two typically developing siblings, or only typically developing children. The clinical sample included three case groups: 73 children and adolescents with autism (Group A), 35 children and adolescents with autism (Group A1) having 45 siblings (Group B) and 96 typically developing children (Group C) matched for gender and age. Twenty-five out of 27 of risk factors presented a higher frequency in Group A in comparison with Group C and for nine of them a statistically significant difference was found. Twenty-one out of 27 of risk factors presented a higher frequency in Group A in comparison with Group B. A higher prevalence of environmental risk factors was observed in 11 risk factors in the Group A1 in comparison with Group B and for nine of them an odds ratio higher than 1.5 was found. For 13 factors there was a progressive increase in frequency going from Group C, B and A and a statistically higher prevalence of the mean number of stressful events per pregnancy was recorded in Group A when compared with Groups B and C. The results suggest that environmental, incidental phenomena and stressful life events can influence pregnancy outcome in predisposed subjects, pointing out a possible threshold effect in women who are predisposed to have suboptimal pregnancies.
Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects
Authors: Hui Tianqian , Zhou Yachuan , Wang Tingyu , Li Jun , Zhang Shanxing , Liao Lifan , Gu Jianhong , Ye Ling , Zhao Lan , Chen Di
Published: April 2018

β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis (OA) development in temporomandibular joint (TMJ), we have generatedβ-cateninconditional activation mice (β-cat(ex3)Agc1CreER) by breedingAgc1-CreERmice withβ-cateninflox(ex3)/+mice. Results of histologic analysis showed the progressive TMJ defects in 3- and 6-month-oldβ-cat(ex3)Agc1CreERmice (tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype ofβ-cat(ex3)Col2CreERmice,β-cat(ex3)Agc1CreERmice showed much severe morphological defects in the superficial layer of TMJ. This may reflect thatAgc1-CreERmice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4, and Adamts5 in TMJ ofβ-cat(ex3)Agc1CreERmice. Results of proliferating cell nuclear antigen (PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage ofβ-cat(ex3)Agc1CreERmice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.
Lysosomal damage after spinal cord injury causes accumulation of RIPK1 and RIPK3 proteins and potentiation of necroptosis
Authors: Liu Shuo , Li Yun , Choi Harry M. C. , Sarkar Chinmoy , Koh Eugene Y. , Wu Junfang , Lipinski Marta M.
Published: April 2018

Necroptosis, a regulated necrosis pathway mediated by the receptor-interacting protein kinases 1 and 3 (RIPK1 and RIPK3), is induced following spinal cord injury (SCI) and thought to contribute to neuronal and glial cell death. However, mechanisms leading to activation of necroptosis after SCI remain unclear. We have previously shown that autophagy, a catabolic pathway facilitating degradation of cytoplasmic proteins and organelles in a lysosome-dependent manner, is inhibited following SCI in rats. Our current data confirm that inhibition of autophagy also occurs after thoracic contusive SCI in the mouse model, as indicated by accumulation of both the autophagosome marker, LC3-II and autophagy cargo protein, p62/SQSTM1. This was most pronounced in the ventral horn neurons and was caused by rapid inhibition of lysosomal function after SCI. Interestingly, RIPK1, RIPK3, and the necroptosis effector protein MLKL also rapidly accumulated after SCI and localized to neurons with disrupted autophagy, suggesting that these events may be related. To determine if lysosomal dysfunction could contribute to induction of necroptosis, we treated PC12 cells and primary rat cortical neurons with lysosomal inhibitors. This led to rapid accumulation of RIPK1 and RIPK3, confirming that they are normally degraded by the lysosomal pathway. In PC12 cells lysosomal inhibition also sensitized cells to necroptosis induced by tumor necrosis factor α (TNFα) and caspase inhibitor. Imaging studies confirmed that RIPK1 partially localized to lysosomes in both untreated and lysosomal inhibitor treated cells. Similarly, we detected presence of RIPK1, RIPK3 and MLKL in both cytosol and at lysosomes after SCI in vivo. Furthermore, stimulation of autophagy and lysosomal function with rapamycin treatment led to decreased accumulation of RIPK1 and attenuated cell death after SCI. These data suggest that lysosomal dysfunction after SCI may contribute to both inhibition of autophagy and sensitize cells to necroptosis by promoting RIPK1 and RIPK3 accumulation.
Class I histone deacetylase (HDAC) inhibitor CI-994 promotes functional recovery following spinal cord injury
Authors: Zhang Suxiang , Fujita Yuki , Matsuzaki Rieko , Yamashita Toshihide
Published: April 2018

Spinal cord injury (SCI) induces severe and long-lasting neurological disability. Accumulating evidence has suggested that histone deacetylase (HDAC) inhibitors exert neuroprotective effects against various insults and deficits in the central nervous system. In the present study, we assessed the effect of the class I HDAC inhibitor CI-994 in a mouse model of SCI. Following SCI, mice were treated with either dimethyl sulfoxide (control vehicle) or 1, 10, or 30 mg/kg CI-994. Level of acetylated histone H3 expression was increased in the motor cortex and spinal cord of 10 mg/kg CCI-994-treated mice after SCI. CI-994 increased histone H3 acetylation in the myeloperoxidase-positive neutrophils and CD68-positive microglia/macrophages in the spinal cord. Although it did not appear to contribute to corticospinal tract axonal reorganization, intraperitoneal injection of CI-994 promoted behavioral recovery following SCI. Furthermore, administration of CI-994 suppressed neutrophil accumulation, inflammatory cytokine expressions, and neuronal loss as early as 3 days following injury. Thus, our findings indicate that HDAC inhibitors may improve functional recovery following SCI, especially during the early stages of the disease.
A dual role for glucocorticoid-induced leucine zipper in glucocorticoid function: tumor growth promotion or suppression?
Authors: Ayroldi Emira , Cannarile Lorenza , Delfino Domenico V. , Riccardi Carlo
Published: April 2018

Glucocorticoids (GCs), important therapeutic tools to treat inflammatory and immunosuppressive diseases, can also be used as part of cancer therapy. In oncology, GCs are used as anticancer drugs for lymphohematopoietic malignancies, while in solid neoplasms primarily to control the side effects of chemo/radiotherapy treatments. The molecular mechanisms underlying the effects of GCs are numerous and often overlapping, but not all have been elucidated. In normal, cancerous, and inflammatory tissues, the response to GCs differs based on the tissue type. The effects of GCs are dependent on several factors: the tumor type, the GC therapy being used, the expression level of the glucocorticoid receptor (GR), and the presence of any other stimuli such as signals from immune cells and the tumor microenvironment. Therefore, GCs may either promote or suppress tumor growth via different molecular mechanisms. Stress exposure results in dysregulation of the hypothalamic–pituitary–adrenal axis with increased levels of endogenous GCs that promote tumorigenesis, confirming the importance of GCs in tumor growth. Most of the effects of GCs are genomic and mediated by the modulation of GR gene transcription. Moreover, among the GR-induced genes, glucocorticoid-induced leucine zipper (GILZ), which was cloned and characterized primarily in our laboratory, mediates many GC anti-inflammatory effects. In this review, we analyzed the possible role for GILZ in the effects GCs have on tumors cells. We also suggest that GILZ, by affecting the immune system, tumor microenvironment, and directly cancer cell biology, has a tumor-promoting function. However, it may also induce apoptosis or decrease the proliferation of cancer cells, thus inhibiting tumor growth. The potential therapeutic implications of GILZ activity on tumor cells are discussed here.
Two-in-one: UV radiation simultaneously induces apoptosis and NETosis
Authors: Azzouz Dhia , Khan Meraj A. , Sweezey Neil , Palaniyar Nades
Published: April 2018

NETosis is a unique form of neutrophil death that differs from apoptosis and necrosis. However, whether NETosis and apoptosis can occur simultaneously in the same neutrophil is unknown. In this paper, we show that increasing doses of ultraviolet (UV) irradiation increases NETosis, which is confirmed by myeloperoxidase colocalisation to neutrophil extracellular DNA. Increasing UV irradiation increases caspase 3 activation, mitochondrial reactive oxygen species (ROS) generation and p38, but not ERK, phosphorylation. Inhibition of mitochondrial ROS production and p38 activation, but not NADPH oxidase (NOX) activity, suppresses UV-induced NETosis, indicating that UV induces NOX-independent NETosis. Like classical NOX-dependent and -independent NETosis, UV-induced NETosis requires transcriptional firing for chromatin decondensation. Cell death-specific inhibitor studies indicate that UV-mediated NETosis is not apoptosis, necrosis or necroptosis. Collectively, these studies indicate that increasing doses of UV irradiation induce both apoptosis and NETosis simultaneously, but the ultimate outcome is the induction of a novel form of NOX-independent NETosis, or “ApoNETosis”.
Long non-coding RNAs: crucial regulators of gastrointestinal cancer cell proliferation
Authors: Chen Jiaxin , Liu Shuiping , Hu Xiaotong
Published: April 2018

Studies of long non-coding RNAs (lncRNAs) have been prevalent in the field of non-coding RNA regulation in recent years. LncRNAs exert crucial effects on malignant cell processes in the gastrointestinal system, including proliferation. Aberrant lncRNA expression, through both oncogenes and tumor suppressor genes, is instrumental to tumor cell proliferation. Here, we summarize the different molecular mechanisms and relevant signaling pathways through which multifarious lncRNAs regulate cell proliferation and we show that lncRNAs are potential biomarkers for gastrointestinal cancers.
Neuro-computational account of how mood fluctuations arise and affect decision making
Authors: Vinckier Fabien , Rigoux Lionel , Oudiette Delphine , Pessiglione Mathias
Published: April 2018

The influence of mood on choices is a well-established but poorly understood phenomenon. Here, we suggest a three-fold neuro-computational account: (1) the integration of positive and negative events over time induce mood fluctuations, (2) which are underpinned by variations in the baseline activities of critical brain valuation regions, (3) which in turn modulate the relative weights assigned to key dimensions of choice options. We validate this model in healthy participants, using feedback in a quiz task to induce mood fluctuations, and a choice task (accepting vs. declining a motor challenge) to reveal their effects. Using fMRI, we demonstrate the pivotal role of the ventromedial prefrontal cortex and anterior insula, in which baseline activities respectively increase and decrease with theoretical mood level and respectively enhance the weighting of potential gains and losses during decision making. The same mechanisms might explain how decisions are biased in mood disorders at longer timescales.
CVD-grown monolayer MoS2 in bioabsorbable electronics and biosensors
Authors: Chen Xiang , Park Yong Ju , Kang Minpyo , Kang Seung-Kyun , Koo Jahyun , Shinde Sachin M. , Shin Jiho , Jeon Seunghyun , Park Gayoung , Yan Ying , MacEwan Matthew R. , Ray Wilson Z. , Lee Kyung-Mi , Rogers John A , Ahn Jong-Hyun
Published: April 2018

Transient electronics represents an emerging technology whose defining feature is an ability to dissolve, disintegrate or otherwise physically disappear in a controlled manner. Envisioned applications include resorbable/degradable biomedical implants, hardware-secure memory devices, and zero-impact environmental sensors. 2D materials may have essential roles in these systems due to their unique mechanical, thermal, electrical, and optical properties. Here, we study the bioabsorption of CVD-grown monolayer MoS2, including long-term cytotoxicity and immunological biocompatibility evaluations in biofluids and tissues of live animal models. The results show that MoS2 undergoes hydrolysis slowly in aqueous solutions without adverse biological effects. We also present a class of MoS2-based bioabsorbable and multi-functional sensor for intracranial monitoring of pressure, temperature, strain, and motion in animal models. Such technology offers specific, clinically relevant roles in diagnostic/therapeutic functions during recovery from traumatic brain injury. Our findings support the broader use of 2D materials in transient electronics and qualitatively expand the design options in other areas.
Population size changes and selection drive patterns of parallel evolution in a host–virus system
Authors: Frickel Jens , Feulner Philine G. D. , Karakoc Emre , Becks Lutz
Published: April 2018

Predicting the repeatability of evolution remains elusive. Theory and empirical studies suggest that strong selection and large population sizes increase the probability for parallel evolution at the phenotypic and genotypic levels. However, selection and population sizes are not constant, but rather change continuously and directly affect each other even on short time scales. Here, we examine the degree of parallel evolution shaped through eco-evolutionary dynamics in an algal host population coevolving with a virus. We find high degrees of parallelism at the level of population size changes (ecology) and at the phenotypic level between replicated populations. At the genomic level, we find evidence for parallelism, as the same large genomic region was duplicated in all replicated populations, but also substantial novel sequence divergence between replicates. These patterns of genome evolution can be explained by considering population size changes as an important driver of rapid evolution.
The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation
Authors: Capper Michael J. , Wright Gareth S. A. , Barbieri Letizia , Luchinat Enrico , Mercatelli Eleonora , McAlary Luke , Yerbury Justin J. , O’Neill Paul M. , Antonyuk Svetlana V. , Banci Lucia , Hasnain S. Samar
Published: April 2018

Superoxide dismutase-1 (SOD1) mutants, including those with unaltered enzymatic activity, are known to cause amyotrophic lateral sclerosis (ALS). Several destabilizing factors contribute to pathogenicity including a reduced ability to complete the normal maturation process which comprises folding, metal cofactor acquisition, intra-subunit disulphide bond formation and dimerization. Immature SOD1 forms toxic oligomers and characteristic large insoluble aggregates within motor system cells. Here we report that the cysteine-reactive molecule ebselen efficiently confers the SOD1 intra-subunit disulphide and directs correct SOD1 folding, depopulating the globally unfolded precursor associated with aggregation and toxicity. Assisted formation of the unusual SOD1 cytosolic disulphide bond could have potential therapeutic applications. In less reducing environments, ebselen forms a selenylsulphide with Cys111 and restores the monomer–dimer equilibrium of A4V SOD1 to wild-type. Ebselen is therefore a potent bifunctional pharmacological chaperone for SOD1 that combines properties of the SOD1 chaperone hCCS and the recently licenced antioxidant drug, edaravone.
Recent strengthening of the stratospheric Arctic vortex response to warming in the central North Pacific
Authors: Hu Dingzhu , Guan Zhaoyong , Tian Wenshou , Ren Rongcai
Published: April 2018

The stratospheric Arctic vortex (SAV) plays a critical role in forecasting cold winters in northern mid-latitudes. Its influence on the tropospheric mid- and high-latitudes has attracted growing attention in recent years. However, the trend in the SAV during the recent two decades is still unknown. Here, using three reanalysis datasets, we found that the SAV intensity during 1998–2016 has a strengthening trend, in contrast to the weakening trend before that period. Approximately 25% of this strengthening is contributed by the warming of sea-surface temperature (SST) over the central North Pacific (CNP). Observational analysis and model experiments show that the warmed CNP SST tends to weaken the Aleutian low, subsequently weakening the upward propagation of wavenumber-1 planetary wave flux, further strengthening the SAV. This strengthened SAV suggests important implications in understanding the Arctic warming amplification and in predicting the surface temperature changes over the northern continents.
Comparative transcriptomic analysis identifies genes responsible for fruit count and oil yield in the oil tea plant Camellia chekiangoleosa
Authors: Xie Yun , Wang Xuewen
Published: April 2018

Fruit yield is an important trait for horticultural crops. However, the limited fruit yield of Camellia chekiangoleosa, a novel promising oil tree, restricts the production of oil. The breeding improvement is little due to its long generation time and lack of available genomic sequence. We identified distinct fruit count phenotypes, high-yield (HY) and low-yield (LY). To understand the underlying genetic basis, we focused on global gene discovery and expression levels in floral buds, which affect fruit count. A total of 140,299 de novo assembled unigenes were obtained using RNA-seq technology, and more genes were expressed in HY than in LY. 2395 differentially expressed genes (DEGs) were identified and enriched in membrane, energy metabolism, secondary metabolism, fatty acid biosynthesis and metabolism, and 18 other metabolic pathways. Of the DEGs, twelve identified transcription factors, including AP2, mostly involve in inflorescence and flower development and in hormone networks. Key DEGs in fatty acid biosynthesis (Fab) FabB, FabF, FabZ, and AccD were highly expressed in floral buds and associated with high oil yield in fruits. We hypothesized that a potential link exists between fruit count and its oil yield. These findings help to elucidate the molecular cues affecting fruit count and oil yield.
Author Correction: N-terminal gelsolin fragment potentiates TRAIL mediated death in resistant hepatoma cells
Authors: Meyer Keith , Kwon Young-Chan , Ray Ratna B. , Ray Ranjit
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection
Authors: Vecchione María Belén , Eiras Javier , Suarez Guadalupe Verónica , Angerami Matías Tomás , Marquez Cecilia , Sued Omar , Ben Graciela , Pérez Héctor Miguel , Gonzalez Diego , Maidana Patricia , Mesch Viviana , Quiroga María Florencia , Bruttomesso Andrea Claudia
Published: April 2018

An estimated one third of the world’s population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.
Author Correction: Virtual screening for inhibitors of the human TSLP:TSLPR interaction
Authors: Van Rompaey Dries , Verstraete Kenneth , Peelman Frank , Savvides Savvas N. , Augustyns Koen , Van Der Veken Pieter , De Winter Hans
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Declaration of local chemical eradication of the Argentine ant: Bayesian estimation with a multinomial-mixture model
Authors: Sakamoto Yoshiko , Kumagai Naoki H. , Goka Koichi
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Health state dependent multiphoton induced autofluorescence in human 3D in vitro lung cancer model
Authors: Kilin Vasyl , Mas Christophe , Constant Samuel , Wolf Jean-Pierre , Bonacina Luigi
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Spin polarized semimagnetic exciton-polariton condensate in magnetic field
Authors: Król Mateusz , Mirek Rafał , Lekenta Katarzyna , Rousset Jean-Guy , Stephan Daniel , Nawrocki Michał , Matuszewski Michał , Szczytko Jacek , Pacuski Wojciech , Piętka Barbara
Published: April 2018

Owing to their integer spin, exciton-polaritons in microcavities can be used for observation of non-equilibrium Bose-Einstein condensation in solid state. However, spin-related phenomena of such condensates are difficult to explore due to the relatively small Zeeman effect of standard semiconductor microcavity systems and the strong tendency to sustain an equal population of two spin components, which precludes the observation of condensates with a well defined spin projection along the axis of the system. The enhancement of the Zeeman splitting can be achieved by introducing magnetic ions to the quantum wells, and consequently forming semimagnetic polaritons. In this system, increasing magnetic field can induce polariton condensation at constant excitation power. Here we evidence the spin polarization of a semimagnetic polaritons condensate exhibiting a circularly polarized emission over 95% even in a moderate magnetic field of about 3 T. Furthermore, we show that unlike nonmagnetic polaritons, an increase on excitation power results in an increase of the semimagnetic polaritons condensate spin polarization. These properties open new possibilities for testing theoretically predicted phenomena of spin polarized condensate.