bluuebunny/crossref_metadata_2025 huggingface dataset:
Irishwomen United, the Contraception Action Programme and the feminist campaign for free, safe and legal contraception in Ireland, c.1975–81
Authors: Kelly Laura
Published: December 2019

This article explores the contraception campaigns of Irishwomen United (I.W.U.) and their offshoot, the Contraception Action Programme (CAP), in the Republic of Ireland from 1975 to 1981. It draws on ten oral history interviews with former members of I.W.U. and CAP conducted by the author, in addition to feminist magazines, newspaper sources and the Roisin Conroy/Attic Press archive. For Irish feminists, the issue of class was paramount to their contraception campaigns while, in common with their counterparts in the United States, they were also concerned about the increasing medicalisation of women's bodies and the potential health risks of the contraceptive pill, commonly prescribed as a ‘cycle regulator’ in Ireland. Fundamentally, I.W.U. and CAP members believed in a women's movement that allowed for the equal distribution of sexual knowledge and access to contraception. In this way, they foregrounded the connection between health and economic rights. Through their demonstrations, meetings and service provision, in unconventional spaces such as shops, markets, community centres and caravans, they challenged not only the law, but also the authority of both religious patriarchy and medical expertise in Ireland. Through an exploration of the activities of I.W.U./CAP, this article will contribute to understandings of campaigns around contraception and, with my commitment to profiling the experiences of ‘rank and file’ women, it will highlight class inequalities and concerns surrounding the medicalisation of women's bodies to a larger extent than has been done before. It also seeks to show the importance of informal women's networks in providing access to contraception and information about contraception pre-legalisation. Moreover, the article seeks to further elucidate the contribution of Irish grassroots organisations which have received limited historical attention.
Effects of establishment method and water management on yield and water productivity of tropical lowland rice
Authors: Ullah Hayat , Giri Suman , Attia Ahmed , Datta Avishek
Published: December 2019

Modification of the existing cropping practice is needed to maintain rice (Oryza sativa L.) productivity and reduce irrigation water input. A 2-year field experiment was conducted during the dry rice growing season of 2016 and 2017 at the Asian Institute of Technology, Pathum Thani, Thailand, to investigate the effects of establishment method and irrigation level on growth, yield, and water productivity of irrigated lowland rice. The treatments consisted of two Thai rice cultivars (Pathumthani 1 and RD57), two establishment methods (dry direct seeding [DDS] and transplanting [TP]), and three irrigation levels (continuous flooding [CF], 15 cm threshold water level below the soil surface for irrigation [AWD15], and 30 cm threshold water level below the soil surface for irrigation [AWD30]). Overall, the performance of RD57 was better than Pathumthani 1 under DDS with 50% higher grain yield and 90% higher water productivity at AWD15. RD57 also had higher shoot dry matter, number of tiller m–2, and number of panicle m–2 across establishment methods and irrigation levels. Grain yield and water productivity of RD57 were similar under two establishment methods across irrigation levels, whereas the performance of TP was better than DDS for Pathumthani 1 irrespective of irrigation levels. The highest grain yield and water productivity of Pathumthani 1 was observed at AWD15 under TP and that of RD57 under both establishment methods at the same irrigation level. AWD15 saved 26 and 32% irrigation water under TP and DDS, respectively, compared with TP-CF treatment combination. AWD15 irrigation level could be recommended for greater water productivity without compromising yield when Pathumthani 1 is cultivated through TP and RD57 is cultivated through either DDS or TP. Although water-saving potential was higher compared with CF, AWD30 is not recommended for irrigated lowland rice cultivation due to significant yield reduction.
A permutation method for detecting trend correlations in rare variant association studies
Authors: Liu Lifeng , Wang Pengfei , Meng Jingbo , Chen Lili , Zhu Wensheng , Ma Weijun
Published: December 2019

In recent years, there has been an increasing interest in detecting disease-related rare variants in sequencing studies. Numerous studies have shown that common variants can only explain a small proportion of the phenotypic variance for complex diseases. More and more evidence suggests that some of this missing heritability can be explained by rare variants. Considering the importance of rare variants, researchers have proposed a considerable number of methods for identifying the rare variants associated with complex diseases. Extensive research has been carried out on testing the association between rare variants and dichotomous, continuous or ordinal traits. So far, however, there has been little discussion about the case in which both genotypes and phenotypes are ordinal variables. This paper introduces a method based on theγ-statistic, called OV-RV, for examining disease-related rare variants when both genotypes and phenotypes are ordinal. At present, little is known about the asymptotic distribution of theγ-statistic when conducting association analyses for rare variants. One advantage of OV-RV is that it provides a robust estimation of the distribution of theγ-statistic by employing the permutation approach proposed by Fisher. We also perform extensive simulations to investigate the numerical performance of OV-RV under various model settings. The simulation results reveal that OV-RV is valid and efficient; namely, it controls the type I error approximately at the pre-specified significance level and achieves greater power at the same significance level. We also apply OV-RV for rare variant association studies of diastolic blood pressure.
Divining Value: Cowries, the Ancestral Realm and the Global in Southern Africa
Authors: Moffett Abigail Joy , Hall Simon
Published: December 2019

The global distribution of cowrie shells (Monetaria annulusandMonetaria moneta) attests to their exchange over long distances and their value in diverse cultural contexts. In addition to their commodification, cowries functioned as adornment, ritual, art and in the elaboration of both living and ancestral beings in many settings through time. Examining the circulation and usage of cowries in these different contexts facilitates an exploration of the ways in which a global commodity may carry, lose and acquire value. An ethnographic review of cowrie use in the hitherto overlooked context of southern Africa suggests that particular qualities of the shell imbued it with culturally specific value. It is suggested that cowries, as part of divination sets, were active in divination because of their white colour and their origin in the (maritime) ancestral realm that anchored divination in notions of ancestry, fertility and healing. Furthermore, in certain contexts, cowries were conceived of as animate objects, metonymically active in ‘cooling’ and healing. These observations, set within a broader discussion relating to archaeological approaches to the accumulation of value, indicate the importance of exploring alternative ontologies in the biographies of global commodities, and reveal the potential of a biographical ontology of the ‘ancestral’.
Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD
Authors: Jain Rakesh , Manning Sloan , Cutler Andrew J.
Published: December 2019

Depression is among the most prevalent mental disorders worldwide, and a substantial proportion of patients do not respond adequately to standard antidepressants. Our understanding of the pathophysiology of depression is no longer limited to the chemical imbalance of neurotransmitters, but also involves the interplay of proinflammatory modulators in the central nervous system, as well as folate metabolism. Additional factors such as stress and metabolic disorders also may contribute. Multiple inflammatory, metabolic, and genetic markers have been identified and may provide critical information to help clinicians individualize treatments for patients to achieve optimal outcomes. Recent advancements in research have clarified underlying causes of depression and have led to possible new avenues for adjunctive treatment. Among these is L-methylfolate, a medical food that is thought to enhance synthesis of monoamines (serotonin, norepinephrine, and dopamine), suppress inflammation, and promote neural health. Clinical studies that assessed supplemental use of L-methylfolate in patients with usual care-resistant depression found that it resulted in improved outcomes. Patients with selective serotonin reuptake inhibitor-resistant depression, and particularly subgroups with biomarkers of inflammation or metabolic disorders or folate metabolism-related genetic polymorphisms (or ≥2 of these factors), had the best responses. Considering this, the goals of this review are to 1) highlight recent advances in the pathophysiology of major depressive disorder as it pertains to folate and associated biomarkers and 2) establish the profiles of patients with depression who could benefit most from supplemental use of L-methylfolate.
Magnetic Force Microscopy Study of Multiscale Ion-Implanted Platinum in Silica Glass, Recorded by an Ultrafast Two-Wave Mixing Configuration
Authors: Torres-Torres David , Bornacelli Jhovani , Vega-Becerra Oscar , Garay-Tapia Andres M. , Aguirre-Tostado Francisco S. , Torres-Torres Carlos , Oliver Alicia
Published: December 2019

This study explores magnetization exhibited by nanoscale platinum-based structures embedded in pure silica plates. A superposition of laser pulses in the samples produced periodic linear arrangements of micro-sized structures. The samples were integrated by PtO2 microstructures (PtOΣs) with dispersed Pt oxide nanoparticles in their surroundings. The characterization of the materials was performed by high transmission electron microscopy studies. Furthermore, topographical and magnetic effects on the sample surfaces were analyzed by atomic force microscopy and magnetic force microscopy, respectively. The magnetic measurements indicated an enhancement in the gradient phase shift and in the gradient force related to the magnetic PtOΣs. The possibility of tuning the magnetic characteristics of the samples through contact with a Nd2Fe14B magnet was demonstrated. This process corresponds to an innovative method for obtaining magnetic PtOΣs induced by laser pulses. Moreover, an increase in the compactness of the silica with platinum-based structures was confirmed by an evaluation of the effective elastic modulus with reference to pure silica. The multimodal magnetic structures studied in this work seem to be candidates for developing high-density magnetic storage media.
Validation of Surface Temperature Derived From MERRA‐2 Reanalysis Against IMD Gridded Data Set Over India
Authors: Gupta Priyanshu , Verma Sunita , Bhatla R. , Chandel Amit Singh , Singh Janhavi , Payra Swagata
Published: December 2019

The first detailed validation of maximum temperature of Modern‐Era Retrospective analysis for Research and Application Version 2 (TMERRA‐2) against Indian Meteorological Department (TIMD) has been carried out for 35 years (1981–2015) over India. For this purpose, India has been divided into seven different zones, i.e Western Himalaya (WH), Northwest, North Central, Northeast (NE), West Peninsula India, East Peninsula India, and South Peninsula India. The descriptive statistics and correlation between TMERRA‐2 and TIMD have been determined for monthly, seasonal, and annual basis. A significant correlation (>0.9) has been found for monthly TMERRA‐2 and TIMD with a root‐mean‐square error value closer to 1 except for WH where a high root‐mean‐square error value of 18.2 is obtained. Seasonal analysis also indicates a significant correlation for all the zones except for WH and NE with a correlation value of <0.3 during monsoon season; this may be due to sparse network, cold climate, and heterogeneity due to topography. Percent bias indicates that TMERRA‐2 generally overestimates the TIMD monthly observations for all the zones, that is, Northwest, North Central, NE, West Peninsula India, East Peninsula India, and South Peninsula India by 4.1%, 2.4%, 1.6%, 0.5%, 0.2%, and 0.8%, respectively, except WH where an underestimation (−82.5%) is determined. Thus, after calibration, MERRA‐2 Reanalysis maximum temperature may be used for further study of extreme weather events.
CCN Spectral Shape and Cumulus Cloud and Drizzle Microphysics
Authors: Hudson James G. , Noble Stephen
Published: December 2019

The shapes of high‐resolution cloud condensation nucleus (CCN) spectra are compared with cloud and precipitation characteristics observed in the Ice in Clouds Experiment–Tropical. These high‐resolution spectra often revealed bimodality that is usually caused by in‐cloud processing. Bimodal CCN spectra were associated with clouds that had a third of the droplet concentrations, twice as broad droplet spectra and 2 to 3 orders of magnitude more drizzle than clouds associated with unimodal CCN spectra. These findings are opposite of a similar earlier study of stratus clouds that suggested enhancement of the indirect aerosol effect. The observations were consistent over the full range of cloud droplet liquid water content (LWCc) thresholds and bands. But the largest differences between clouds associated with bimodal and unimodal CCN were at intermediate LWCc bins where drizzle and droplet spectral width was greatest in the clouds associated with bimodal CCN.
Correction: Meta-analysis of cortical thickness abnormalities in medication-free patients with major depressive disorder
Authors: Li Qian , Zhao Youjin , Chen Ziqi , Long Jingyi , Dai Jing , Huang Xiaoqi , Lui Su , Radua Joaquim , Vieta Eduard , Kemp Graham J. , Sweeney John A. , Li Fei , Gong Qiyong
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Integrative analysis of DNA methylation and gene expression identified cervical cancer-specific diagnostic biomarkers
Authors: Xu Wanxue , Xu Mengyao , Wang Longlong , Zhou Wei , Xiang Rong , Shi Yi , Zhang Yunshan , Piao Yongjun
Published: December 2019

Cervical cancer is the leading cause of death among women with cancer worldwide. Here, we performed an integrative analysis of Illumina HumanMethylation450K and RNA-seq data from TCGA to identify cervical cancer-specific DNA methylation markers. We first identified differentially methylated and expressed genes and examined the correlation between DNA methylation and gene expression. The DNA methylation profiles of 12 types of cancers, including cervical cancer, were used to generate a candidate set, and machine-learning techniques were adopted to define the final cervical cancer-specific markers in the candidate set. Then, we assessed the protein levels of marker genes by immunohistochemistry by using tissue arrays containing 93 human cervical squamous cell carcinoma samples and cancer-adjacent normal tissues. Promoter methylation was negatively correlated with the local regulation of gene expression. In the distant regulation of gene expression, the methylation of hypermethylated genes was more likely to be negatively correlated with gene expression, while the methylation of hypomethylated genes was more likely to be positively correlated with gene expression. Moreover, we identified four cervical cancer-specific methylation markers, cg07211381 (RAB3C), cg12205729 (GABRA2), cg20708961 (ZNF257), and cg26490054 (SLC5A8), with 96.2% sensitivity and 95.2% specificity by using the tenfold cross-validation of TCGA data. The four markers could distinguish tumors from normal tissues with a 94.2, 100, 100, and 100% AUC in four independent validation sets from the GEO database. Overall, our study demonstrates the potential use of methylation markers in cervical cancer diagnosis and may boost the development of new epigenetic therapies.
Detection and prevalence of monoclonal gammopathy of undetermined significance: a study utilizing mass spectrometry-based monoclonal immunoglobulin rapid accurate mass measurement
Authors: Murray David , Kumar Shaji K. , Kyle Robert A. , Dispenzieri Angela , Dasari Surendra , Larson Dirk R. , Vachon Celine , Cerhan James R. , Rajkumar S. Vincent
Published: December 2019

High-sensitivity mass spectrometry assays are available to detect monoclonal immunoglobulins. To better assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS), we identified 300 patients diagnosed with MGUS or related gammopathy who had a prior negative work-up for monoclonal proteins as part of the Olmsted County MGUS screening study. Two mass spectrometry-based detection methods (matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and monoclonal immunoglobulin rapid accurate mass measurements (miRAMM) along with traditional immunofixation were performed on the Olmsted baseline and MGUS diagnostics serum samples. Among the 226 patients considered negative for MGUS based on protein electrophoresis and serum-free light-chain assay, a monoclonal protein could be detected at baseline in 24 patients (10.6%) by immunofixation, 113 patients (50%) by MADLI-TOF mass spectrometry, and 149 patients (65.9%) by miRAMM mass spectrometry. In addition, using miRAMM, some patients demonstrated an oligoclonal to monoclonal transition giving insight into the origin of MGUS. Using the sensitive miRAMM, MGUS is present in 887 of 17,367 persons from the Olmsted County cohort, translating into a prevalence of 5.1% among persons 50 years of age and older. This represents the most accurate prevalence estimate of MGUS thus far.
Principles and mechanisms of non-genetic resistance in cancer
Authors: Bell Charles C. , Gilan Omer
Published: December 2019

As well as undergoing genetic evolution, cancer cells can alter their epigenetic state to adapt and resist treatment. This non-genetic evolution is emerging as a major component of cancer resistance. Only now are we beginning to acquire the necessary data and tools to establish some of the underlying principles and mechanisms that define when, why and how non-genetic resistance occurs. Preliminary studies suggest that it can exist in a number of forms, including drug persistence, unstable non-genetic resistance and, most intriguingly, stable non-genetic resistance. Exactly how they each arise remains unclear; however, epigenetic heterogeneity and plasticity appear to be important variables. In this review, we provide an overview of these different forms of non-genetic resistance, before exploring how epigenetic heterogeneity and plasticity influence their emergence. We highlight the distinction between non-genetic Darwinian selection and Lamarckian induction and discuss how each is capable of generating resistance. Finally, we discuss the potential interaction between genetic and non-genetic adaptation and propose the idea of ‘the path of most resistance’, which outlines the variables that dictate whether cancers adapt through genetic and/or epigenetic means. Through these discussions, we hope to provide a conceptual framework that focuses future studies, whose insights might help prevent or overcome non-genetic resistance.
Reconfigurable and programmable origami dielectric elastomer actuators with 3D shape morphing and emissive architectures
Authors: Wang Jiangxin , Li Shaohui , Gao Dace , Xiong Jiaqing , Lee Pooi See
Published: December 2019

Soft actuators with the capability to generate programmable and reconfigurable motions without the use of complicated and rigid infrastructures are of great interest for the development of smart, interactive, and adaptive soft electronic systems. Here, we report a new strategy to achieve a transparent and reconfigurable actuator by using a dielectric elastomer actuator (DEA), which provides mechanical strains under electrical bias, integrated with origami ethyl cellulose (EC) paper that “instructs” the shape changes of the actuator. The actuator can be reconfigured and multiple mechanical motions can be programmed in the device by creating crease patterns that induce variations in the local stiffness to direct the actuations. With the versatile design and fabrication approach, a light emission device with dynamic shape changes was demonstrated.
Organic molecular crystal-based photosynaptic devices for an artificial visual-perception system
Authors: Deng Wei , Zhang Xiujuan , Jia Ruofei , Huang Liming , Zhang Xiaohong , Jie Jiansheng
Published: December 2019

Recreating the visual-perception properties using organic electronic devices is highly desired for visual prosthetics and artificial intelligence. Although the integration of organic light-sensing components with synaptic devices can realize the recognition and memory functions for perceived images, complicated problems in device integration for practical applications are generally encountered. Here we demonstrate a new type of organic photosynaptic device based on organic molecular crystals, which can provide optical-sensing and synaptic functions together in one device by means of a unique photon-induced charge transfer effect. This device successfully emulates the working principles of human visual perception in terms of short-term plasticity, long-term potentiation, and spike-timing-dependent plasticity. Moreover, a proof-of-concept artificial image-perception system is demonstrated by integrating the photosynapses on a flexible substrate. The new devices using organic semiconductors may open up innovative application areas, such as artificially intelligent electronic and perception systems, and facilitate the integration of such devices into next-generation flexible and stretchable electronics.
Diagnostic yield of panel-based genetic testing in syndromic inherited retinal disease
Authors:   UK Inherited Retinal Disease Consortium, Jiman Omamah A. , Taylor Rachel L. , Lenassi Eva , Smith Jill Clayton , Douzgou Sofia , Ellingford Jamie M. , Barton Stephanie , Hardcastle Claire , Fletcher Tracy , Campbell Christopher , Ashworth Jane , Biswas Susmito , Ramsden Simon C. , Manson Forbes D. , Black Graeme C.
Published: December 2019

Thirty percent of all inherited retinal disease (IRD) is accounted for by conditions with extra-ocular features. This study aimed to establish the genetic diagnostic pick-up rate for IRD patients with one or more extra-ocular features undergoing panel-based screening in a clinical setting. One hundred and six participants, tested on a gene panel which contained both isolated and syndromic IRD genes, were retrospectively ascertained from the Manchester Genomic Diagnostics Laboratory database spanning 6 years (2012–2017). Phenotypic features were extracted from the clinical notes and classified according to Human Phenotype Ontology; all identified genetic variants were interpreted in accordance to the American College of Medical Genetics and Genomics guidelines. Overall, 49% (n = 52) of patients received a probable genetic diagnosis. A further 6% (n = 6) had a single disease-associated variant in an autosomal recessive disease-relevant gene. Fifty-two percent (n = 55) of patients had a clinical diagnosis at the time of testing. Of these, 71% (n = 39) received a probable genetic diagnosis. By contrast, for those without a provisional clinical diagnosis (n = 51), only 25% (n = 13) received a probable genetic diagnosis. The clinical diagnosis of Usher (n = 33) and Bardet–Biedl syndrome (n = 10) was confirmed in 67% (n = 22) and 80% (n = 8), respectively. The testing diagnostic rate in patients with clinically diagnosed multisystemic IRD conditions was significantly higher than those without one (71% versus 25%;pvalue < 0.001). The lower pick-up rate in patients without a clinical diagnosis suggests that panel-based approaches are unlikely to be the most effective means of achieving a molecular diagnosis for this group. Here, we suggest that genome-wide approaches (whole exome or genome) are more appropriate.
Molecular determinants of nephron vascular specialization in the kidney
Authors: Barry David M. , McMillan Elizabeth A. , Kunar Balvir , Lis Raphael , Zhang Tuo , Lu Tyler , Daniel Edward , Yokoyama Masataka , Gomez-Salinero Jesus M. , Sureshbabu Angara , Cleaver Ondine , Di Lorenzo Annarita , Choi Mary E. , Xiang Jenny , Redmond David , Rabbany Sina Y. , Muthukumar Thangamani , Rafii Shahin
Published: December 2019

Although kidney parenchymal tissue can be generated in vitro, reconstructing the complex vasculature of the kidney remains a daunting task. The molecular pathways that specify and sustain functional, phenotypic and structural heterogeneity of the kidney vasculature are unknown. Here, we employ high-throughput bulk and single-cell RNA sequencing of the non-lymphatic endothelial cells (ECs) of the kidney to identify the molecular pathways that dictate vascular zonation from embryos to adulthood. We show that the kidney manifests vascular-specific signatures expressing defined transcription factors, ion channels, solute transporters, and angiocrine factors choreographing kidney functions. Notably, the ontology of the glomerulus coincides with induction of unique transcription factors, including Tbx3, Gata5, Prdm1, and Pbx1. Deletion of Tbx3 in ECs results in glomerular hypoplasia, microaneurysms and regressed fenestrations leading to fibrosis in subsets of glomeruli. Deciphering the molecular determinants of kidney vascular signatures lays the foundation for rebuilding nephrons and uncovering the pathogenesis of kidney disorders.
Structural basis of denuded glycan recognition by SPOR domains in bacterial cell division
Authors: Alcorlo Martín , Dik David A. , De Benedetti Stefania , Mahasenan Kiran V. , Lee Mijoon , Domínguez-Gil Teresa , Hesek Dusan , Lastochkin Elena , López Daniel , Boggess Bill , Mobashery Shahriar , Hermoso Juan A.
Published: December 2019

SPOR domains are widely present in bacterial proteins that recognize cell-wall peptidoglycan strands stripped of the peptide stems. This type of peptidoglycan is enriched in the septal ring as a product of catalysis by cell-wall amidases that participate in the separation of daughter cells during cell division. Here, we document binding of synthetic denuded glycan ligands to the SPOR domain of the lytic transglycosylase RlpA from Pseudomonas aeruginosa (SPOR-RlpA) by mass spectrometry and structural analyses, and demonstrate that indeed the presence of peptide stems in the peptidoglycan abrogates binding. The crystal structures of the SPOR domain, in the apo state and in complex with different synthetic glycan ligands, provide insights into the molecular basis for recognition and delineate a conserved pattern in other SPOR domains. The biological and structural observations presented here are followed up by molecular-dynamics simulations and by exploration of the effect on binding of distinct peptidoglycan modifications.
Intense attosecond pulses carrying orbital angular momentum using laser plasma interactions
Authors: Wang J. W. , Zepf M. , Rykovanov S. G.
Published: December 2019

Light beams with helical phase-fronts are known to carry orbital angular momentum (OAM) and provide an additional degree of freedom to beams of coherent light. While OAM beams can be readily derived from Gaussian laser beams with phase plates or gratings, this is far more challenging in the extreme ultra-violet (XUV), especially for the case of high XUV intensity. Here, we theoretically and numerically demonstrate that intense surface harmonics carrying OAM are naturally produced by the intrinsic dynamics of a relativistically intense circularly-polarized Gaussian beam (i.e. non-vortex) interacting with a target at normal incidence. Relativistic surface oscillations convert the laser pulses to intense XUV harmonic radiation via the well-known relativistic oscillating mirror mechanism. We show that the azimuthal and radial dependence of the harmonic generation process converts the spin angular momentum of the laser beam to orbital angular momentum resulting in an intense attosecond pulse (or pulse train) with OAM.
Functional significance of U2AF1 S34F mutations in lung adenocarcinomas
Authors: Esfahani Mohammad S. , Lee Luke J. , Jeon Young-Jun , Flynn Ryan A. , Stehr Henning , Hui Angela B. , Ishisoko Noriko , Kildebeck Eric , Newman Aaron M. , Bratman Scott V. , Porteus Matthew H. , Chang Howard Y. , Alizadeh Ash A. , Diehn Maximilian
Published: December 2019

The functional role of U2AF1 mutations in lung adenocarcinomas (LUADs) remains incompletely understood. Here, we report a significant co-occurrence of U2AF1 S34F mutations with ROS1 translocations in LUADs. To characterize this interaction, we profiled effects of S34F on the transcriptome-wide distribution of RNA binding and alternative splicing in cells harboring the ROS1 translocation. Compared to its wild-type counterpart, U2AF1 S34F preferentially binds and modulates splicing of introns containing CAG trinucleotides at their 3′ splice junctions. The presence of S34F caused a shift in cross-linking at 3′ splice sites, which was significantly associated with alternative splicing of skipped exons. U2AF1 S34F induced expression of genes involved in the epithelial-mesenchymal transition (EMT) and increased tumor cell invasion. Finally, S34F increased splicing of the long over the short SLC34A2-ROS1 isoform, which was also associated with enhanced invasiveness. Taken together, our results suggest a mechanistic interaction between mutant U2AF1 and ROS1 in LUAD.
Sub-cycle time resolution of multi-photon momentum transfer in strong-field ionization
Authors: Willenberg Benjamin , Maurer Jochen , Mayer Benedikt W. , Keller Ursula
Published: December 2019

During multi-photon ionization of an atom it is well understood how the involved photons transfer their energy to the ion and the photoelectron. However, the transfer of the photon linear momentum is still not fully understood. Here, we present a time-resolved measurement of linear momentum transfer along the laser pulse propagation direction. We can show that the linear momentum transfer to the photoelectron depends on the ionization time within the laser cycle using the attoclock technique. We can mostly explain the measured linear momentum transfer within a classical model for a free electron in a laser field. However, corrections are required due to the parent-ion interaction and due to the initial momentum when the electron enters the continuum. The parent-ion interaction induces a negative attosecond time delay between the appearance in the continuum of the electron with minimal linear momentum transfer and the point in time with maximum ionization rate.
Heterogeneity and dynamics of active Kras-induced dysplastic lineages from mouse corpus stomach
Authors: Min Jimin , Vega Paige N. , Engevik Amy C. , Williams Janice A. , Yang Qing , Patterson Loraine M. , Simmons Alan J. , Bliton R. Jarrett , Betts Joshua W. , Lau Ken S. , Magness Scott T. , Goldenring James R. , Choi Eunyoung
Published: December 2019

Dysplasia is considered a key transition state between pre-cancer and cancer in gastric carcinogenesis. However, the cellular or phenotypic heterogeneity and mechanisms of dysplasia progression have not been elucidated. We have established metaplastic and dysplastic organoid lines, derived from Mist1-Kras(G12D) mouse stomach corpus and studied distinct cellular behaviors and characteristics of metaplastic and dysplastic organoids. We also examined functional roles for Kras activation in dysplasia progression using Selumetinib, a MEK inhibitor, which is a downstream mediator of Kras signaling. Here, we report that dysplastic organoids die or show altered cellular behaviors and diminished aggressive behavior in response to MEK inhibition. However, the organoids surviving after MEK inhibition maintain cellular heterogeneity. Two dysplastic stem cell (DSC) populations are also identified in dysplastic cells, which exhibited different clonogenic potentials. Therefore, Kras activation controls cellular dynamics and progression to dysplasia, and DSCs might contribute to cellular heterogeneity in dysplastic cell lineages.
An effector protein of the wheat stripe rust fungus targets chloroplasts and suppresses chloroplast function
Authors: Xu Qiang , Tang Chunlei , Wang Xiaodong , Sun Shutian , Zhao Jinren , Kang Zhensheng , Wang Xiaojie
Published: December 2019

Chloroplasts are important for photosynthesis and for plant immunity against microbial pathogens. Here we identify a haustorium-specific protein (Pst_12806) from the wheat stripe rust fungus, Puccinia striiformis f. sp. tritici (Pst), that is translocated into chloroplasts and affects chloroplast function. Transient expression of Pst_12806 inhibits BAX-induced cell death in tobacco plants and reduces Pseudomonas-induced hypersensitive response in wheat. It suppresses plant basal immunity by reducing callose deposition and the expression of defense-related genes. Pst_12806 is upregulated during infection, and its knockdown (by host-induced gene silencing) reduces Pst growth and development, likely due to increased ROS accumulation. Pst_12806 interacts with the C-terminal Rieske domain of the wheat TaISP protein (a putative component of the cytochrome b6-f complex). Expression of Pst_12806 in plants reduces electron transport rate, photosynthesis, and production of chloroplast-derived ROS. Silencing TaISP by virus-induced gene silencing in a susceptible wheat cultivar reduces fungal growth and uredinium development, suggesting an increase in resistance against Pst infection.
Compact and ultra-efficient broadband plasmonic terahertz field detector
Authors: Salamin Yannick , Benea-Chelmus Ileana-Cristina , Fedoryshyn Yuriy , Heni Wolfgang , Elder Delwin L. , Dalton Larry R. , Faist Jérôme , Leuthold Juerg
Published: December 2019

Terahertz sources and detectors have enabled numerous new applications from medical to communications. Yet, most efficient terahertz detection schemes rely on complex free-space optics and typically require high-power lasers as local oscillators. Here, we demonstrate a fiber-coupled, monolithic plasmonic terahertz field detector on a silicon-photonics platform featuring a detection bandwidth of 2.5 THz with a 65 dB dynamical range. The terahertz wave is measured through its nonlinear mixing with an optical probe pulse with an average power of only 63 nW. The high efficiency of the scheme relies on the extreme confinement of the terahertz field to a small volume of 10−8(λTHz/2)3. Additionally, on-chip guided plasmonic probe beams sample the terahertz signal efficiently in this volume. The approach results in an extremely short interaction length of only 5 μm, which eliminates the need for phase matching and shows the highest conversion efficiency per unit length up to date.
Resonant optical Stark effect in monolayer WS2
Authors: Cunningham Paul D. , Hanbicki Aubrey T. , Reinecke Thomas L. , McCreary Kathleen M. , Jonker Berend T.
Published: December 2019

Breaking the valley degeneracy in monolayer transition metal dichalcogenides through the valley-selective optical Stark effect (OSE) can be exploited for classical and quantum valleytronic operations such as coherent manipulation of valley superposition states. The strong light-matter interactions responsible for the OSE have historically been described by a two-level dressed-atom model, which assumes noninteracting particles. Here we experimentally show that this model, which works well in semiconductors far from resonance, does not apply for excitation near the exciton resonance in monolayer WS2. Instead, we show that an excitonic model of the OSE, which includes many-body Coulomb interactions, is required. We confirm the prediction from this theory that many-body effects between virtual excitons produce a dominant blue-shift for photoexcitation detuned from resonance by less than the exciton binding energy. As such, we suggest that our findings are general to low-dimensional semiconductors that support bound excitons and other many-body Coulomb interactions.
Superhydrophobic hemostatic nanofiber composites for fast clotting and minimal adhesion
Authors: Li Zhe , Milionis Athanasios , Zheng Yu , Yee Marcus , Codispoti Lukas , Tan Freddie , Poulikakos Dimos , Yap Choon Hwai
Published: December 2019

Hemostatic materials are of great importance in medicine. However, their successful implementation is still challenging as it depends on two, often counteracting, attributes; achieving blood coagulation rapidly, before significant blood loss, and enabling subsequent facile wound-dressing removal, without clot tears and secondary bleeding. Here we illustrate an approach for achieving hemostasis, rationally targeting both attributes, via a superhydrophobic surface with immobilized carbon nanofibers (CNFs). We find that CNFs promote quick fibrin growth and cause rapid clotting, and due to their superhydrophobic nature they severely limit blood wetting to prevent blood loss and drastically reduce bacteria attachment. Furthermore, minimal contact between the clot and the superhydrophobic CNF surface yields an unforced clot detachment after clot shrinkage. All these important attributes are verified in vitro and in vivo with rat experiments. Our work thereby demonstrates that this strategy for designing hemostatic patch materials has great potential.
Controlling energy levels and Fermi level en route to fully tailored energetics in organic semiconductors
Authors: Warren Ross , Privitera Alberto , Kaienburg Pascal , Lauritzen Andreas E. , Thimm Oliver , Nelson Jenny , Riede Moritz K.
Published: December 2019

Simultaneous control over both the energy levels and Fermi level, a key breakthrough for inorganic electronics, has yet to be shown for organic semiconductors. Here, energy level tuning and molecular doping are combined to demonstrate controlled shifts in ionisation potential and Fermi level of an organic thin film. This is achieved by p-doping a blend of two host molecules, zinc phthalocyanine and its eight-times fluorinated derivative, with tunable energy levels based on mixing ratio. The doping efficiency is found to depend on host mixing ratio, which is explained using a statistical model that includes both shifts of the host’s ionisation potentials and, importantly, the electron affinity of the dopant. Therefore, the energy level tuning effect has a crucial impact on the molecular doping process. The practice of comparing host and dopant energy levels must consider the long-range electrostatic shifts to consistently explain the doping mechanism in organic semiconductors.
All-fiber tribo-ferroelectric synergistic electronics with high thermal-moisture stability and comfortability
Authors: Yang Weifeng , Gong Wei , Hou Chengyi , Su Yun , Guo Yinben , Zhang Wei , Li Yaogang , Zhang Qinghong , Wang Hongzhi
Published: December 2019

Developing fabric-based electronics with good wearability is undoubtedly an urgent demand for wearable technologies. Although the state-of-the-art fabric-based wearable devices have shown unique advantages in the field of e-textiles, further efforts should be made before achieving “electronic clothing” due to the hard challenge of optimally unifying both promising electrical performance and comfortability in single device. Here, we report an all-fiber tribo-ferroelectric synergistic e-textile with outstanding thermal-moisture comfortability. Owing to a tribo-ferroelectric synergistic effect introduced by ferroelectric polymer nanofibers, the maximum peak power density of the e-textile reaches 5.2 W m−2 under low frequency motion, which is 7 times that of the state-of-the-art breathable triboelectric textiles. Electronic nanofiber materials form hierarchical networks in the e-textile hence lead to moisture wicking, which contributes to outstanding thermal-moisture comfortability of the e-textile. The all-fiber electronics is reliable in complicated real-life situation. Therefore, it is an idea prototypical example for electronic clothing.
The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization
Authors: Barrière D. A. , Magalhães R. , Novais A. , Marques P. , Selingue E. , Geffroy F. , Marques F. , Cerqueira J. , Sousa J. C. , Boumezbeur F. , Bottlaender M. , Jay T. M. , Cachia A. , Sousa N. , Mériaux S.
Published: December 2019

Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo $${\mathrm{T}}_2^ \ast$$

T

2

*

-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.
Transcription-mediated organization of the replication initiation program across large genes sets common fragile sites genome-wide
Authors: Brison Olivier , El-Hilali Sami , Azar Dana , Koundrioukoff Stéphane , Schmidt Mélanie , Nähse Viola , Jaszczyszyn Yan , Lachages Anne-Marie , Dutrillaux Bernard , Thermes Claude , Debatisse Michelle , Chen Chun-Long
Published: December 2019

Common fragile sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription could elicit their instability; however, the underlying mechanisms remain elusive. Genome-wide replication timing analyses here show that stress-induced delayed/under-replication is the hallmark of CFSs. Extensive genome-wide analyses of nascent transcripts, replication origin positioning and fork directionality reveal that 80% of CFSs nest in large transcribed domains poor in initiation events, replicated by long-travelling forks. Forks that travel long in late S phase explains CFS replication features, whereas formation of sequence-dependent fork barriers or head-on transcription–replication conflicts do not. We further show that transcription inhibition during S phase, which suppresses transcription–replication encounters and prevents origin resetting, could not rescue CFS stability. Altogether, our results show that transcription-dependent suppression of initiation events delays replication of large gene bodies, committing them to instability.
Engineering protein assemblies with allosteric control via monomer fold-switching
Authors: Campos Luis A. , Sharma Rajendra , Alvira Sara , Ruiz Federico M. , Ibarra-Molero Beatriz , Sadqi Mourad , Alfonso Carlos , Rivas Germán , Sanchez-Ruiz Jose M. , Romero Garrido Antonio , Valpuesta José M. , Muñoz Victor
Published: December 2019

The macromolecular machines of life use allosteric control to self-assemble, dissociate and change shape in response to signals. Despite enormous interest, the design of nanoscale allosteric assemblies has proven tremendously challenging. Here we present a proof of concept of allosteric assembly in which an engineered fold switch on the protein monomer triggers or blocks assembly. Our design is based on the hyper-stable, naturally monomeric protein CI2, a paradigm of simple two-state folding, and the toroidal arrangement with 6-fold symmetry that it only adopts in crystalline form. We engineer CI2 to enable a switch between the native and an alternate, latent fold that self-assembles onto hexagonal toroidal particles by exposing a favorable inter-monomer interface. The assembly is controlled on demand via the competing effects of temperature and a designed short peptide. These findings unveil a remarkable potential for structural metamorphosis in proteins and demonstrate key principles for engineering protein-based nanomachinery.
Structural insights into ubiquitin recognition and Ufd1 interaction of Npl4
Authors: Sato Yusuke , Tsuchiya Hikaru , Yamagata Atsushi , Okatsu Kei , Tanaka Keiji , Saeki Yasushi , Fukai Shuya
Published: December 2019

Npl4 is likely to be the most upstream factor recognizing Lys48-linked polyubiquitylated substrates in the proteasomal degradation pathway in yeast. Along with Ufd1, Npl4 forms a heterodimer (UN), and functions as a cofactor for the Cdc48 ATPase. Here, we report the crystal structures of yeast Npl4 in complex with Lys48-linked diubiquitin and with the Npl4-binding motif of Ufd1. The distal and proximal ubiquitin moieties of Lys48-linked diubiquitin primarily interact with the C-terminal helix and N-terminal loop of the Npl4 C-terminal domain (CTD), respectively. Mutational analysis suggests that the CTD contributes to linkage selectivity and initial binding of ubiquitin chains. Ufd1 occupies a hydrophobic groove of the Mpr1/Pad1 N-terminal (MPN) domain of Npl4, which corresponds to the catalytic groove of the MPN domain of JAB1/MPN/Mov34 metalloenzyme (JAMM)-family deubiquitylating enzyme. This study provides important structural insights into the polyubiquitin chain recognition by the Cdc48–UN complex and its assembly.
Palladium-catalyzed Suzuki-Miyaura coupling of thioureas or thioamides
Authors: Mai Shaoyu , Li Wendong , Li Xue , Zhao Yingwei , Song Qiuling
Published: December 2019

Cross-coupling reactions involving metal carbene intermediates play an increasingly important role in C–C bond formation. Expanding the carbene precursors to a broader range of starting materials and more diverse products is an ongoing challenge in synthetic organic chemistry. Herein, we report a Suzuki-Miyaura coupling reaction of in situ-generated Pd–carbene complexes via desulfurization of thioureas or thioamides. This strategy enables the preparation of a broad array of substituted amidinium salts and unsymmetrical diaryl ketones. The reaction is readily scalable, compatible with bromo groups on aromatic rings, tolerant to moisture and air and has a broad substrate scope. Furthermore, a single crystal structure of Pd-diaminocarbene complex is obtained and proven to be the key intermediate in both catalytic and stoichiometric reactions. Preliminary mechanistic studies demonstrate the dual role of the silver salt as a desulfurating reagent assisting the elimination of sulfur and as oxidant facilitating the PdII/Pd0/PdII catalytic cycle.