bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of body mass index on breast cancer incidence among women at increased risk: an observational study from the International Breast Intervention Studies
Authors: Smith Samuel G. , Sestak Ivana , Morris Michelle. A. , Harvie Michelle , Howell Anthony , Forbes John , Cuzick Jack
Published: March 2021

Background

We investigated the association between body mass index (BMI) and breast cancer risk in women at increased risk of breast cancer receiving tamoxifen or anastrozole compared with placebo using data from the International Breast Cancer Intervention Studies [IBIS-I (tamoxifen) and IBIS-II (anastrozole)].

Methods

Baseline BMI was calculated from nurse assessed height and weight measurements for premenopausal (n = 3138) and postmenopausal (n = 3731) women in IBIS-I and postmenopausal women in IBIS-II (n = 3787). The primary endpoint was any breast cancer event (invasive and ductal carcinoma in situ). We used Cox proportional hazards regression to calculate hazard ratios (HRs) for risk after adjustment for covariates.

Results

There were 582 (IBIS-I) and 248 (IBIS-II) breast cancer events [median follow-up = 16.2 years (IQR 14.4–17.7) and 10.9 years (IQR 8.8–13.0), respectively]. In adjusted analysis, women with a higher BMI had an increased breast cancer risk in both IBIS-I [HR = 1.06 per 5 kg/m2 (0.99–1.15), p = 0.114] and in IBIS-II [HR per 5 kg/m2 = 1.21 (1.09–1.35), p < 0.001]. In IBIS-I, the association between BMI and breast cancer risk was positive in postmenopausal women [adjusted HR per 5 kg/m2 = 1.14 (1.03–1.26), p = 0.01] but not premenopausal women [adjusted HR per 5 kg/m2 = 0.97 (0.86–1.09), p = 0.628]. There was no interaction between BMI and treatment group for breast cancer risk in either IBIS-I (p = 0.62) or IBIS-II (p = 0.55).

Conclusions

Higher BMI is associated with greater breast cancer risk in postmenopausal women at increased risk of the disease, but no effect was observed in premenopausal women. The lack of interaction between BMI and treatment group on breast cancer risk suggests women are likely to experience benefit from preventive therapy regardless of their BMI.

Trial registration Both trials were registered [IBIS-I: ISRCTN91879928 on 24/02/2006, retrospectively registered (http://www.isrctn.com/ISRCTN91879928); IBIS-II: ISRCTN31488319 on 07/01/2005, retrospectively registered (http://www.isrctn.com/ISRCTN31488319)]
The Effects of Serum Removal on Gene Expression and Morphological Plasticity Markers in Differentiated SH-SY5Y Cells
Authors: Thomson Alix C. , Schuhmann Teresa , de Graaf Tom A. , Sack Alexander T. , Rutten Bart P. F. , Kenis Gunter
Published: March 2021

Despite the widespread use of the SH-SY5Y human neuroblastoma cell line in modeling human neurons in vitro, protocols for growth, differentiation and experimentation differ considerably across the literature. Many studies fully differentiate SH-SY5Y cells before experimentation, to investigate plasticity measures in a mature, human neuronal-like cell model. Prior to experimentation, serum is often removed from cell culture media, to arrest the cell growth cycle and synchronize cells. However, the exact effect of this serum removal before experimentation on mature, differentiated SH-SY5Y cells has not yet been described. In studies using differentiated SH-SY5Y cells, any effect of serum removal on plasticity markers may influence results. The aim of the current study was to systematically characterize, in differentiated, neuronal-like SH-SY5Y cells, the potentially confounding effects of complete serum removal in terms of morphological and gene expression markers of plasticity. We measured changes in commonly used morphological markers and in genes related to neuroplasticity and synaptogenesis, particularly in the BDNF-TrkB signaling pathway. We found that complete serum removal from already differentiated SH-SY5Y cells increases neurite length, neurite branching, and the proportion of cells with a primary neurite, as well as proportion of βIII-Tubulin and MAP2 expressing cells. Gene expression results also indicate increased expression of PSD95 and NTRK2 expression 24 h after serum removal. We conclude that serum deprivation in differentiated SH-SY5Y cells affects morphology and gene expression and can potentially confound plasticity-related outcome measures, having significant implications for experimental design in studies using differentiated SH-SY5Y cells as a model of human neurons.
Self-Adjointness in Klein-Gordon Theory on Globally Hyperbolic Spacetimes
Authors: Much Albert , Oeckl Robert
Published: March 2021

We prove essential self-adjointness of the spatial part of the linear Klein-Gordon operator with external potential for a large class of globally hyperbolic manifolds. The proof is conducted by a fusion of new results concerning globally hyperbolic manifolds, the theory of weighted Hilbert spaces and related functional analytic advances.
Radical interpretation and decision theory
Authors: Hattiangadi Anandi , Stefánsson H. Orri
Published: March 2021

This paper takes issue with an influential interpretationist argument for physicalism about intentionality based on the possibility of radical interpretation. The interpretationist defends the physicalist thesis that the intentional truths supervene on the physical truths by arguing that it is possible for a radical interpreter, who knows all of the physical truths, to work out the intentional truths about what an arbitrary agent believes, desires, and means without recourse to any further empirical information. One of the most compelling arguments for the possibility of radical interpretation, associated most closely with David Lewis and Donald Davidson, gives a central role to decision theoretic representation theorems, which demonstrate that if an agent’s preferences satisfy certain constraints, it is possible to deduce probability and utility functions that represent her beliefs and desires. We argue that an interpretationist who wants to rely on existing representation theorems in defence of the possibility of radical interpretation faces a trilemma, each horn of which is incompatible with the possibility of radical interpretation.
Synthesis of Silicon Sulfide by Using CS2 Gas
Authors: Suzuki Ryosuke O. , Yashima Yuta , Kaneko Takumi , Ahmadi Eltefat , Kikuchi Tatsuya , Watanabe Takafumi , Nogami Genki
Published: March 2021

Silicon sulfide (SiS2) was synthesized from Si, SiC, Si3N4, and a eutectic Al-Si liquid. An Ar-CS2 gas mixture, after bubbling through liquid CS2, was passed over pulverized Si, SiC, Si3N4, or a eutectic Al-Si alloy liquid. White, needle-shaped SiS2 was precipitated as a single phase on the colder downstream surface when Si powder in a SiO2 liner was heated over 1273 K. This deposition mechanism involves a reaction between Si and CS2 to form SiS2, with the vaporization of SiS(g) and deposition as SiS2(s) from SiS(g) and S2(g). Quartz was unaffected by the reaction gases. Notably, Si, SiC, Si3N4, and the eutectic Al-Si liquid were found to be suitable sources for SiS2 synthesis, although this was suppressed owing to Al2S3 formation on the latter.
Online program engagement and audience size during television ads
Authors: Fossen Beth L. , Bleier Alexander
Published: March 2021

This research explores how television viewers’ online program engagement (OPE)—engagement in social media conversations about television programs—relates to audience size during ads in those programs. We leverage a multisource dataset of 8417 ad instances, volume and deviation measures of OPE activity (program-related Twitter mentions), and audience size during ads. We show that increases in OPE volume and positive deviations from the episode’s average level of OPE before an ad relate to higher ad audience size. To explain, we argue that OPE reflects viewers’ program involvement which attenuates their channel-changing behavior during ads. Positive OPE deviations moreover relate to higher ad audience sizes most strongly for earlier ads in a break. Our results help television networks and advertisers strategically determine ad placements for increased ad audience size by highlighting social episodes (characterized by high OPE volume) and social moments (characterized by positive OPE deviations) as attractive advertising environments.
Africa’s evolving vegetable seed sector: status, policy options and lessons from Asia
Authors: Schreinemachers Pepijn , Howard Julie , Turner Michael , Groot Simon N. , Dubey Bhupen , Mwadzingeni Learnmore , Chagomoka Takemore , Ngugi Michael , Afari-Sefa Victor , Hanson Peter , Wopereis Marco C. S.
Published: March 2021

Fostering better access to more nutritious foods across sub-Saharan Africa will be critical to ending hunger and malnutrition. In Asia, vegetable production and consumption have grown rapidly since the 1990s and the development of a dynamic vegetable seed industry, led by the private sector, played a pivotal role in this process. The availability of locally-bred and adapted varieties facilitated the rapid expansion of production and increased the supply of affordable vegetables to consumers. In contrast, the vegetable seed sector in sub-Saharan Africa has been slow to develop and has received little attention in the development agenda. Drawing from Asia’s experience, this paper outlines a four-point strategy to accelerate the vegetable seed sector in sub-Saharan Africa. First, there is a need to strengthen the technical capacity of African seed companies to allow them to develop varieties that are well-adapted to local conditions and consumer preferences. Second, seed regulations, originally designed with food grains in mind, should be reviewed and revised to facilitate domestic vegetable breeding research and seed production. Third, more farmer extension is needed to exploit improved varieties together with good management practices. Fourth, vegetable marketing systems should be strengthened to reduce risks to farmers and traders. Investment in these four areas will help energize private sector investment in the vegetable seed sector. Asian experience suggests that investment in locally adapted vegetable varieties is a critical step in improving productivity, availability and ultimately consumption of nutritious vegetables.
2D Nanomaterials for Effective Energy Scavenging
Authors: Hasan Md Al Mahadi , Wang Yuanhao , Bowen Chris R. , Yang Ya
Published: March 2021

The development of a nation is deeply related to its energy consumption. 2D nanomaterials have become a spotlight for energy harvesting applications from the small-scale of low-power electronics to a large-scale for industry-level applications, such as self-powered sensor devices, environmental monitoring, and large-scale power generation. Scientists from around the world are working to utilize their engrossing properties to overcome the challenges in material selection and fabrication technologies for compact energy scavenging devices to replace batteries and traditional power sources. In this review, the variety of techniques for scavenging energies from sustainable sources such as solar, air, waste heat, and surrounding mechanical forces are discussed that exploit the fascinating properties of 2D nanomaterials. In addition, practical applications of these fabricated power generating devices and their performance as an alternative to conventional power supplies are discussed with the future pertinence to solve the energy problems in various fields and applications.
Correction to: Cyborg Persons: Humanity Played in a Different Key
Authors: Fuller Steve
Published: March 2021

The article was published with an error in the reference entry of Haraway, D. (1985/1991) and Wiener, N. (1948/1961). Thus, this erratum is presented to fix this error.
Negotiating Peace
Authors: Jeffery Renée
Published: March 2021

In the past two decades, peace negotiators around the world have increasingly accepted that granting amnesties for human rights violations is no longer an acceptable bargaining tool or incentive, even when the signing of a peace agreement is at stake. While many states that previously saw sweeping amnesties as integral to their peace processes now avoid amnesties for human rights violations, this anti-amnesty turn has been conspicuously absent in Asia. In Negotiating Peace: Amnesties, Justice and Human Rights Renée Jeffery examines why peace negotiators in Asia have resisted global anti-impunity measures more fervently and successfully than their counterparts around the world. Drawing on a new global dataset of 146 peace agreements (1980–2015) and with in-depth analysis of four key cases - Timor-Leste, Aceh Indonesia, Nepal and the Philippines - Jeffery uncovers the legal, political, economic and cultural reasons for the persistent popularity of amnesties in Asian peace processes.
Large- and small-amplitude shock-wave oscillations over axisymmetric bodies in high-speed flow
Authors: Sasidharan Vaisakh , Duvvuri Subrahmanyam
Published: March 2021

The phenomena of self-sustained shock-wave oscillations over conical bodies with a blunt axisymmetric base subject to uniform high-speed flow are investigated in a hypersonic wind tunnel at Mach number

$M = 6$

. The flow and shock-wave dynamics is dictated by two non-dimensional geometric parameters presented by the three length scales of the body, two of which are associated with the conical forebody and one with the base. Time-resolved schlieren imagery from these experiments reveals the presence of two disparate states of shock-wave oscillations in the flow, and allows for the mapping of unsteadiness boundaries in the two-parameter space. Physical mechanisms are proposed to explain the oscillations and the transitions of the shock-wave system from steady to oscillatory states. In comparison with the canonical single-parameter problem of shock-wave oscillations over spiked-blunt bodies reported in literature, the two-parameter nature of the present problem introduces distinct elements to the flow dynamics.
An updated generic classification of Cenozoic pleurotomariid gastropods, with new records from the Oligocene and early Miocene of India
Authors: Bose Kanishka , Das Shiladri S. , Mondal Subhronil
Published: March 2021

Although taxonomically distinct, the Cenozoic pleurotomariids are the bottlenecked remnants of the Mesozoic members of the family in terms of morphology, with only conical forms surviving the end-Cretaceous mass extinction. Here, we propose an updated classification scheme for the Cenozoic representatives of this group, based on data from the entire Cenozoic pleurotomariid fossil record. We consider all conventional as well as several new characters so that this scheme can readily help to distinguish Cenozoic pleurotomariid genera. Following the new classification scheme, a revision of the generic status of Cenozoic species previously assigned to ‘Pleurotomaria’ Defrance, 1826 is presented.

Only a few Cenozoic pleurotomariid gastropods have been reported from the Indian subcontinent. Here we report four species from the Oligocene of the Kutch Basin and the early Miocene (Burdigalian) of the Dwarka Basin of Gujarat, western India, of which two are described as new: Perotrochus bermotiensis n. sp., Entemnotrochus kathiawarensis n. sp., Entemnotrochus cf. E. bianconii, and Entemnotrochus? sp. 1.

UUID: http://zoobank.org/89b6ff67-2834-477f-862b-67691104aca4
Becoming Global Lawyers: A Comparative Study of Civic Professionalism
Authors: Bliss John
Published: March 2021

Through their professional education and training, new lawyers are generally encouraged to adopt a civic vision of professional identity. This article explores convergences and divergences in how new lawyers entering an increasingly globalized legal profession conceive of their civic roles in different national contexts. In particular, I draw on interviews and a cross-cultural identity-mapping method to examine the lived experiences of civic professionalism among corporate-lawyers-in-training in the United States and China. I found that professional identity formation in the US sample is largely marked by role distancing and a sense of constrained public-interest expression. In contrast, Chinese respondents generally identified strongly with their civic roles, while framing their public contributions in pragmatic, state-aligned terms. I conclude with a comparative analysis of young lawyers’ bottom-up efforts to expand their civic impact.
Association between complement component 4A expression, cognitive performance and brain imaging measures in UK Biobank
Authors: O'Connell Kevin S. , Sønderby Ida E. , Frei Oleksandr , van der Meer Dennis , Athanasiu Lavinia , Smeland Olav B. , Alnæs Dag , Kaufmann Tobias , Westlye Lars T. , Steen Vidar M. , Andreassen Ole A. , Hughes Timothy , Djurovic Srdjan
Published: March 2021

Abstract

Background

Altered expression of the complement component C4A gene is a known risk factor for schizophrenia. Further, predicted brain C4A expression has also been associated with memory function highlighting that altered C4A expression in the brain may be relevant for cognitive and behavioral traits.

Methods

We obtained genetic information and performance measures on seven cognitive tasks for up to 329 773 individuals from the UK Biobank, as well as brain imaging data for a subset of 33 003 participants. Direct genotypes for variants (n = 3213) within the major histocompatibility complex region were used to impute C4 structural variation, from which predicted expression of the C4A and C4B genes in human brain tissue were predicted. We investigated if predicted brain C4A or C4B expression were associated with cognitive performance and brain imaging measures using linear regression analyses.

Results

We identified significant negative associations between predicted C4A expression and performance on select cognitive tests, and significant associations with MRI-based cortical thickness and surface area in select regions. Finally, we observed significant inconsistent partial mediation of the effects of predicted C4A expression on cognitive performance, by specific brain structure measures.

Conclusions

These results demonstrate that the C4 risk locus is associated with the central endophenotypes of cognitive performance and brain morphology, even when considered independently of other genetic risk factors and in individuals without mental or neurological disorders.
The role of modality and awareness in language learning
Authors: Zhao Chuqi , Kormos Judit , Rebuschat Patrick , Suzuki Shungo
Published: March 2021

There is conflicting empirical evidence regarding the role of awareness in second language learning. Possible explanations for the contradictory results include the modality in the exposure and assessment phases of previous experiments. Our study investigated the acquisition of a novel determiner system under incidental exposure conditions and examined the effect of modality in both exposure and assessment phases. Animacy served as a hidden regularity in the determiners, which were embedded in sentences and presented to Chinese speakers of English either in auditory or in visual mode. Learning was assessed by a two-alternative forced-choice test either auditorily or in writing. Implicit and explicit knowledge were measured using retrospective verbal reports and source judgements. Bayesian analysis provided moderate evidence for above chance level learning. Significant learning effects were observed regardless of whether participants based their accuracy judgements on explicit or implicit knowledge. Bayesian analysis showed moderate evidence for above chance learning effects for aware participants. Generalized linear mixed-effects modeling revealed a small-size significant benefit of the auditory exposure modality over the written modality but indicated no significant effect of the modality of assessment or awareness. Our research underscores the importance of considering the role of modality of exposure in incidental second language learning contexts.
SCALING PROPERTIES OF QUEUES WITH TIME-VARYING LOAD PROCESSES: EXTENSIONS AND APPLICATIONS
Authors: Vesilo Rein , Harchol-Balter Mor , Scheller-Wolf Alan
Published: March 2021

New computing and communications paradigms will result in traffic loads in information server systems that fluctuate over much broader ranges of time scales than current systems. In addition, these fluctuation time scales may only be indirectly known or even be unknown. However, we should still be able to accurately design and manage such systems. This paper addresses this issue: we consider anM/M/1 queueing system operating in a random environment (denotedM/M/1(R)) that alternates between HIGH and LOW phases, where the load in the HIGH phase is higher than in the LOW phase. Previous work on the performance characteristics ofM/M/1(R) systems established fundamental properties of the shape of performance curves. In this paper, we extend monotonicity results to include convexity and concavity properties, provide a partial answer to an open problem on stochastic ordering, develop new computational techniques, and include boundary cases and various degenerateM/M/1(R) systems. The basis of our results are novel representations for the mean number in system and the probability of the system being empty. We then apply these results to analyze practical aspects of system operation and design; in particular, we derive the optimal service rate to minimize mean system cost and provide a bias analysis of the use of customer-level sampling to estimate time-stationary quantities.
AL-ʿAQL DANS LA TRADITION LATINE DU LIBER DE CAUSIS
Authors: Calma Dragos
Published: March 2021

L'article propose une première approche systématique de la tradition manuscrite du Liber de causis, en étudiant à la fois les variantes manuscrites et les difficultés doctrinales suscitées par la translittération de l'arabe al-ʿaql conservée dans la traduction latine. Certains médiévaux (tel Albert le Grand) l'entendent comme un concept sans équivalent en latin, forgé par des philosophes arabes dont on ignore tout. D'autres médiévaux (tels Thomas d'Aquin et Gilles de Rome), qui ont probablement connu une branche différente de la tradition manuscrite du Liber de causis, n'en font aucune mention. En examinant cent dix manuscrits latins du Liber de causis (sur deux cent soixantecinq actuellement connus), on constate de nombreuses variations tant pour la présence de cette translittération dans les propositions du texte que pour les formes et les graphies (alatyr, alachili, adlahic, etc.). Cette analyse permet de comprendre tant la position d'Albert que la grande diversité, jusqu’à présent insoupçonnée, de la transmission du Liber de causis dans le monde latin.
Implementing WordNet Measures of Lexical Semantic Similarity in a Fuzzy Logic Programming System
Authors: JULIÁN-IRANZO PASCUAL , SÁENZ-PÉREZ FERNANDO
Published: March 2021

This paper introduces techniques to integrate WordNet into a Fuzzy Logic Programming system. Since WordNet relates words but does not give graded information on the relation between them, we have implemented standard similarity measures and new directives allowing the proximity equations linking two words to be generated with an approximation degree. Proximity equations are the key syntactic structures which, in addition to a weak unification algorithm, make a flexible query-answering process possible in this kind of programming language. This addition widens the scope of Fuzzy Logic Programming, allowing certain forms of lexical reasoning, and reinforcing Natural Language Processing (NLP) applications.
Porites Calcifying Fluid pH on Seasonal to Diurnal Scales
Authors: Knebel Oliver , Carvajal Carlos , Standish Christopher D. , Vega Elwyn de la , Chalk Thomas B. , Ryan Emma J. , Guo Weifu , Ford Murray , Foster Gavin L. , Kench Paul
Published: March 2021

Coral resilience to ocean acidification is largely determined by the degree of physiological control corals can exert on their calcifying fluid carbonate chemistry. In this study, the boron isotopic composition (δ11B) of a Porites colony growing on a reef flat on Kiritimati Island in the equatorial central Pacific is examined to quantify the sensitivity of calcifying fluid pH (pHcf) to ambient environmental conditions. Skeletal δ11B along the growth axis of one annual growth band was determined with bulk analysis and by laser ablation (LA) MC‐ICP‐MS. Furthermore, the oxygen and carbon isotopic composition, trace element ratios, and skeletal density were quantified. Sclerochronological data were interpreted in the context of simultaneous recordings of reef flat seawater pH (pHsw), temperature, salinity, and water depth, and by measurements of these parameters on the fore‐reef. A recent model of pHcf upregulation, after optimization with seasonally resolved data, was used to simulate pHcf variability on a diurnal scale. Results showed that on a seasonal scale, Porites pHcf is upregulated compared to ambient seawater: both bulk and LA‐MC‐ICP‐MS derived δ11B resulted in a mean pHcf of 8.35 pH units. Calcifying fluid pH upregulation primarily followed variations in seawater temperatures, that is likely related to the control of temperature on calcification rate. On the reef flat, the diurnal range in pHsw was substantially higher (0.29 pH units) than on the fore‐reef (0.07 pH units). However, model results suggest that the high diurnal variability in reef flat pHsw resulted only in a limited variability in Porites pHcf.
Ethnic and trans-ethnic genome-wide association studies identify new loci influencing Japanese Alzheimer’s disease risk
Authors: Shigemizu Daichi , Mitsumori Risa , Akiyama Shintaro , Miyashita Akinori , Morizono Takashi , Higaki Sayuri , Asanomi Yuya , Hara Norikazu , Tamiya Gen , Kinoshita Kengo , Ikeuchi Takeshi , Niida Shumpei , Ozaki Kouichi
Published: March 2021

Alzheimer’s disease (AD) has no cure, but early detection and risk prediction could allow earlier intervention. Genetic risk factors may differ between ethnic populations. To discover novel susceptibility loci of AD in the Japanese population, we conducted a genome-wide association study (GWAS) with 3962 AD cases and 4074 controls. Out of 4,852,957 genetic markers that passed stringent quality control filters, 134 in nine loci, includingAPOEandSORL1, were convincingly associated with AD. Lead SNPs located in seven novel loci were genotyped in an independent Japanese AD case–control cohort. The novel locusFAM47Ereached genome-wide significance in a meta-analysis of association results. This is the first report associating theFAM47Elocus with AD in the Japanese population. A trans-ethnic meta-analysis combining the results of the Japanese data sets with summary statistics from stage 1 data of the International Genomics of Alzheimer’s Project identified an additional novel susceptibility locus inOR2B2. Our data highlight the importance of performing GWAS in non-European populations.
Correction: Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury
Authors: Wu Jingchuan , Li Hui , He Junchi , Tian Xiaocui , Luo Shuilian , Li Jiankang , Li Wei , Zhong Jianjun , Zhang Hongrong , Huang Zhijian , Sun Xiaochuan , Jiang Tao
Published: March 2021

A correction to this paper has been published: https://doi.org/10.1038/s41419-021-03429-w
WW domain-binding protein 2 overexpression prevents diet-induced liver steatosis and insulin resistance through AMPKβ1
Authors: Zheng Zhe , Li Yue , Fan Siyuan , An Jie , Luo Xi , Liang Minglu , Zhu Feng , Huang Kai
Published: March 2021

Nonalcoholic fatty liver disease (NAFLD) is prevalent clinically and can lead to more serious chronic liver disease. However, the pathological mechanism is still unclear, and thus, there are no approved drugs on the market. Transcriptional coactivator WW domain-binding protein 2 (WBP2) is a newly discovered oncogene that has an important relationship with the occurrence and development of breast cancer and mediates the interaction between Wnt and various other signaling pathways. The expression level of WBP2 was decreased in NAFLD. Overexpression of WBP2 with AAV in vivo alleviated liver fat deposition and insulin resistance induced by a high-fat diet (HFD). Knockdown of WBP2 with AAV aggravated HFD-induced fatty liver and insulin resistance. In vitro experiments showed that in the human normal hepatocyte cell line LO2 and primary hepatocytes isolated from mice, overexpression of WBP2 reduced fat deposition, and knocking out or knocking down WBP2 aggravated PA-induced fat deposition. Through mass spectrometry, we found that WBP2 can bind to AMPKβ1, and by mutating AMPKβ1, we found that WBP2 can induce phosphorylation of AMPKβ1 at S108 and then activate the AMPK pathway to affect lipid metabolism. The effect of WBP2 on NAFLD provides a possible new direction for future research on NAFLD.
Integrative pan cancer analysis reveals epigenomic variation in cancer type and cell specific chromatin domains
Authors: Gopi Lijin K. , Kidder Benjamin L.
Published: March 2021

Epigenetic mechanisms contribute to the initiation and development of cancer, and epigenetic variation promotes dynamic gene expression patterns that facilitate tumor evolution and adaptation. While the NCI-60 panel represents a diverse set of human cancer cell lines that has been used to screen chemical compounds, a comprehensive epigenomic atlas of these cells has been lacking. Here, we report an integrative analysis of 60 human cancer epigenomes, representing a catalog of activating and repressive histone modifications. We identify genome-wide maps of canonical sharp and broad H3K4me3 domains at promoter regions of tumor suppressors, H3K27ac-marked conventional enhancers and super enhancers, and widespread inter-cancer and intra-cancer specific variability in H3K9me3 and H4K20me3-marked heterochromatin domains. Furthermore, we identify features of chromatin states, including chromatin state switching along chromosomes, correlation of histone modification density with genetic mutations, DNA methylation, enrichment of DNA binding motifs in regulatory regions, and gene activity and inactivity. These findings underscore the importance of integrating epigenomic maps with gene expression and genetic variation data to understand the molecular basis of human cancer. Our findings provide a resource for mining epigenomic maps of human cancer cells and for identifying epigenetic therapeutic targets.
Self-powered multifunctional sensing based on super-elastic fibers by soluble-core thermal drawing
Authors: Chen Mengxiao , Wang Zhe , Zhang Qichong , Wang Zhixun , Liu Wei , Chen Ming , Wei Lei
Published: March 2021

The well-developed preform-to-fiber thermal drawing technique owns the benefit to maintain the cross-section architecture and obtain an individual micro-scale strand of fiber with the extended length up to thousand meters. In this work, we propose and demonstrate a two-step soluble-core fabrication method by combining such an inherently scalable manufacturing method with simple post-draw processing to explore the low viscosity polymer fibers and the potential of soft fiber electronics. As a result, an ultra-stretchable conductive fiber is achieved, which maintains excellent conductivity even under 1900% strain or 1.5 kg load/impact freefalling from 0.8-m height. Moreover, by combining with triboelectric nanogenerator technique, this fiber acts as a self-powered self-adapting multi-dimensional sensor attached on sports gears to monitor sports performance while bearing sudden impacts. Next, owing to its remarkable waterproof and easy packaging properties, this fiber detector can sense different ion movements in various solutions, revealing the promising applications for large-area undersea detection.
Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes
Authors: Chen Yung-Che , Tsai Ying-Huang , Wang Chin-Chou , Liu Shih-Feng , Chen Ting-Wen , Fang Wen-Feng , Lee Chiu-Ping , Hsu Po-Yuan , Chao Tung-Ying , Wu Chao-Chien , Wei Yu-Feng , Chang Huang-Chih , Tsen Chia-Cheng , Chang Yu-Ping , Lin Meng-Chih ,   Taiwan Clinical Trial Consortium of Respiratory Disease (TCORE) group, Yu Chong-Jen , Wang Hao-Chien , Chiang Chi-Huei , Perng Diahn-Warng , Cheng Shih-Lung , Hsu Jeng-Yuan , Hsu Wu-Huei , Hsiue Tzuen-Ren , Lin Hen-I. , Wang Cheng-Yi , Chang Yeun-Chung , Chen Chung-Ming , Lin Cing-Syong , Chen Likwang , Chong Inn-Wen
Published: March 2021

We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (− 296), and hypomethylated SEPT8 (− 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (− 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (− 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (− 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2′-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.
From diffusion in compartmentalized media to non-Gaussian random walks
Authors: Ślęzak Jakub , Burov Stanislav
Published: March 2021

In this work we establish a link between two different phenomena that were studied in a large and growing number of biological, composite and soft media: the diffusion in compartmentalized environment and the non-Gaussian diffusion that exhibits linear or power-law growth of the mean square displacement joined by the exponential shape of the positional probability density. We explore a microscopic model that gives rise to transient confinement, similar to the one observed for hop-diffusion on top of a cellular membrane. The compartmentalization of the media is achieved by introducing randomly placed, identical barriers. Using this model of a heterogeneous medium we derive a general class of random walks with simple jump rules that are dictated by the geometry of the compartments. Exponential decay of positional probability density is observed and we also quantify the significant decrease of the long time diffusion constant. Our results suggest that the observed exponential decay is a general feature of the transient regime in compartmentalized media.
Beneficial effects of elafibranor on NASH in E3L.CETP mice and differences between mice and men
Authors: van den Hoek Anita M. , Verschuren Lars , Caspers Martien P. M. , Worms Nicole , Menke Aswin L. , Princen Hans M. G.
Published: March 2021

Non-alcoholic steatohepatitis (NASH) is the most rapidly growing liver disease that is nevertheless without approved pharmacological treatment. Despite great effort in developing novel NASH therapeutics, many have failed in clinical trials. This has raised questions on the adequacy of preclinical models. Elafibranor is one of the drugs currently in late stage development which had mixed results for phase 2/interim phase 3 trials. In the current study we investigated the response of elafibranor in APOE*3Leiden.CETP mice, a translational animal model that displays histopathological characteristics of NASH in the context of obesity, insulin resistance and hyperlipidemia. To induce NASH, mice were fed a high fat and cholesterol (HFC) diet for 15 weeks (HFC reference group) or 25 weeks (HFC control group) or the HFC diet supplemented with elafibranor (15 mg/kg/d) from week 15–25 (elafibranor group). The effects on plasma parameters and NASH histopathology were assessed and hepatic transcriptome analysis was used to investigate the underlying pathways affected by elafibranor. Elafibranor treatment significantly reduced steatosis and hepatic inflammation and precluded the progression of fibrosis. The underlying disease pathways of the model were compared with those of NASH patients and illustrated substantial similarity with molecular pathways involved, with 87% recapitulation of human pathways in mice. We compared the response of elafibranor in the mice to the response in human patients and discuss potential pitfalls when translating preclinical results of novel NASH therapeutics to human patients. When taking into account that due to species differences the response to some targets, like PPAR-α, may be overrepresented in animal models, we conclude that elafibranor may be particularly useful to reduce hepatic inflammation and could be a pharmacologically useful agent for human NASH, but probably in combination with other agents.
Multi-criteria of PV solar site selection problem using GIS-intuitionistic fuzzy based approach in Erzurum province/Turkey
Authors: Türk Seda , Koç Ahmet , Şahin Gökhan
Published: March 2021

Renewable energy sources have been placed as the key to facilitating to provide source of electricity generation. Solar power is one of the most preferable one among renewable energy sources due to the easy to generate in suitable environment. However, there are concerns with the location of solar power plants installation which causes low efficiency and ineffective use. Hence, determining the location for the usage of solar power sources is critical to mitigating those concerns. In addition, Turkey has been focused on investments on sustainable renewable energy sources and there are few studies which work on cities to reveal potential sources. In this study, GIS and intuitionistic fuzzy set based multi-criteria decision-making method is proposed for determining the most suitable areas for solar energy power plant potential site selection in Erzurum province, Turkey. Firstly, a solar energy power plant potential site selection map is made using a GIS program along with considering ecological risks and ecological criteria. Secondly, 20 districts of Erzurum are investigated in terms of 10 criteria (slope, aspect, solar irradiation, land use, wind speed, air temperature, air pressure, air humidity, land surface temperature and transmission line) using intuitionistic fuzzy sets. In these parameters the first time we looked the land use surface. The land use surface is affected the efficiency of the solar power plant. Finally, the comparisons of two methods are done to check consistency of results obtained. The results indicate that both approaches achieve same areas as the most suitable locations for solar power plants installations for Erzurum province in Turkey. The aim of this work is first to investigate possible locations for solar power plant installation using a mapping method, GIS, and then, Intuitionistic Fuzzy is applied to the problem to obtain optimum areas for solar energy. Also, more accurate results are provided comparing results of two methods, GIS and Intuitionistic Fuzzy. The results expose that 25,065.3 km2 for solar power plant suitable for solar power plan installation.
Functional analysis of the cotton CLE polypeptide signaling gene family in plant growth and development
Authors: Wan Ke , Lu Kening , Gao Mengtao , Zhao Ting , He Yuxin , Yang Dong-Lei , Tao Xiaoyuan , Xiong Guosheng , Guan Xueying
Published: March 2021

The CLAVATA3 (CLV3)/EMBRYO SURROUNDING REGION (ESR)–RELATED (CLE) gene family encodes a large number of polypeptide signaling molecules involved in the regulation of shoot apical meristem division and root and vascular bundle development in a variety of plants. CLE family genes encode important short peptide hormones; however, the functions of these signaling polypeptides in cotton remain largely unknown. In the current work, we studied the effects of the CLE family genes on growth and development in cotton. Based on the presence of a conserved CLE motif of 13 amino acids, 93 genes were characterized as GhCLE gene family members, and these were subcategorized into 7 groups. A preliminary analysis of the cotton CLE gene family indicated that the activity of its members tends to be conserved in terms of both the 13-residue conserved domain at the C-terminus and their subcellular localization pattern. Among the 14 tested genes, the ectopic overexpression of GhCLE5::GFP partially mimicked the phenotype of the clv3 mutant in Arabidopsis. GhCLE5 could affect the endogenous CLV3 in binding to the receptor complex, comprised of CLV1, CLV2, and CRN, in the yeast two-hybrid assay and split-luciferase assay. Silencing GhCLE5 in cotton caused a short seedling phenotype. Therefore, we concluded that the cotton GhCLE gene family is functionally conserved in apical shoot development regulation. These results indicate that CLE also plays roles in cotton development as a short peptide hormone.
Microbial carbon source utilization in rice rhizosphere soil with different tillage practice in a double cropping rice field
Authors: Tang Haiming , Xiao Xiaoping , Li Chao , Shi Lihong , Cheng Kaikai , Li Weiyan , Wen Li , Xu Yilan , Wang Ke
Published: March 2021

Carbon (C) plays an important role in maintaining soil fertility and increasing soil microbial community, but there is still limited information about how source utilization characteristics respond to soil fertility changes under double-cropping rice (Oryza sativa L.) system in southern China paddy field. Therefore, the effects of different short-term (5-years) tillage management on characteristics of C utilization in rice rhizosphere and non-rhizosphere soils under double-cropping rice field in southern China were investigated by using 18O incorporation into DNA. Therefore, a field experiment were included four tillage treatments: conventional tillage with crop residue incorporation (CT), rotary tillage with crop residue incorporation (RT), no-tillage with crop residue retention (NT), rotary tillage with crop residue removed as control (RTO). The results showed that soil microbial biomass C content with CT, RT, NT treatments were increased by 29.71–47.27% and 3.77–21.30% in rhizosphere and non-rhizosphere soils, compared with RTO treatment, respectively. Compared with RTO treatment, soil microbial basal respiration and microbial growth rate with CT treatment were increased 30.56%, 30.94% and 11.91%, 12.34% in rhizosphere and non-rhizosphere soils, respectively. The soil microbial C utilization efficiency were promoted with NT treatment. Compared with RTO treatment, the metabolic capacity of soil microorganism to exogenous C source with CT, RT and NT treatments were increased. The largest type of exogenous C source was saccharides, followed by amino acid and polymers, and complex compounds was the smallest. The redundancy analysis results indicated that tillage treatments significantly changed the utilization characteristics of soil microorganism to exogenous C source. Compared with RTO treatment, the grain yield of early rice and late rice with CT treatment were increased by 409.5 kg ha−1 and 387.0 kg ha−1, respectively. Therefore, the CT and RT treatments could significantly increase soil microbial biomass C content, but the NT treatment promote microbial C utilization efficiency in the double-cropping paddy field of southern China.
Brain injury after 50 h of lung-protective mechanical ventilation in a preclinical model
Authors: Bassi Thiago G. , Rohrs Elizabeth C. , Fernandez Karl C. , Ornowska Marlena , Nicholas Michelle , Gani Matt , Evans Doug , Reynolds Steven C.
Published: March 2021

Mechanical ventilation is the cornerstone of the Intensive Care Unit. However, it has been associated with many negative consequences. Recently, ventilator-induced brain injury has been reported in rodents under injurious ventilation settings. Our group wanted to explore the extent of brain injury after 50 h of mechanical ventilation, sedation and physical immobility, quantifying hippocampal apoptosis and inflammation, in a normal-lung porcine study. After 50 h of lung-protective mechanical ventilation, sedation and immobility, greater levels of hippocampal apoptosis and neuroinflammation were clearly observed in the mechanically ventilated group, in comparison to a never-ventilated group. Markers in the serum for astrocyte damage and neuronal damage were also higher in the mechanically ventilated group. Therefore, our study demonstrated that considerable hippocampal insult can be observed after 50 h of lung-protective mechanical ventilation, sedation and physical immobility.
Synthesis of titanium nitride via hybrid nanocomposites based on mesoporous TiO2/acrylonitrile
Authors: Locovei Claudiu , Chiriac Anita-Laura , Miron Andreea , Iftimie Sorina , Antohe Vlad-Andrei , Sârbu Andrei , Dumitru Anca
Published: March 2021

In the present study, the synthesis of titanium nitride (TiN) by carbothermal reduction nitridation (CRN) reaction using nanocomposites made of mesoporous TiO2/acrylonitrile with different content of inorganic phase were explored. The choice of hybrid nanocomposite as precursor for the synthesis of TiN was made due to the possibility of having an intimate interface between the organic and inorganic phases in the mixture that can favours CRN reaction. Subsequently, the hybrid composites have been subjected to four-step thermal treatments at 290 °C, 550 °C, 1000 °C and 1400 °C under nitrogen atmosphere. The XRD results after thermal treatment at 1000 °C under nitrogen flow show the coexistence of two crystalline phases of TiO2, i.e. anatase and rutile, as well as TiN phase, together with the detection of amorphous carbon that proved the initiation of CRN reaction. Furthermore, the observations based on XRD patterns of samples thermally treated at 1400 °C in nitrogen atmosphere were in agreement with SEM analysis, that shows the formation of TiN by CRN reaction via hybrid nanocomposites mesoporous TiO2/acrylonitrile.
Non-monotonic kilohertz frequency neural block thresholds arise from amplitude- and frequency-dependent charge imbalance
Authors: Peña Edgar , Pelot Nicole A. , Grill Warren M.
Published: March 2021

Reversible block of nerve conduction using kilohertz frequency electrical signals has substantial potential for treatment of disease. However, the ability to block nerve fibers selectively is limited by poor understanding of the relationship between waveform parameters and the nerve fibers that are blocked. Previous in vivo studies reported non-monotonic relationships between block signal frequency and block threshold, suggesting the potential for fiber-selective block. However, the mechanisms of non-monotonic block thresholds were unclear, and these findings were not replicated in a subsequent in vivo study. We used high-fidelity computational models and in vivo experiments in anesthetized rats to show that non-monotonic threshold-frequency relationships do occur, that they result from amplitude- and frequency-dependent charge imbalances that cause a shift between kilohertz frequency and direct current block regimes, and that these relationships can differ across fiber diameters such that smaller fibers can be blocked at lower thresholds than larger fibers. These results reconcile previous contradictory studies, clarify the mechanisms of interaction between kilohertz frequency and direct current block, and demonstrate the potential for selective block of small fiber diameters.