bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis
Authors: Gallagher C. S. , Mäkinen N. , Harris H. R. , Rahmioglu N. , Uimari O. , Cook J. P. , Shigesi N. , Ferreira T. , Velez-Edwards D. R. , Edwards T. L. , Mortlock S. , Ruhioglu Z. , Day F. , Becker C. M. , Karhunen V. , Martikainen H. , Järvelin M.-R. , Cantor R. M. , Ridker P. M. , Terry K. L. , Buring J. E. , Gordon S. D. , Medland S. E. , Montgomery G. W. , Nyholt D. R. , Hinds D. A. , Tung J. Y. ,   the 23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Vacic Vladimir , Wilson Catherine H. , Perry J. R. B. , Lind P. A. , Painter J. N. , Martin N. G. , Morris A. P. , Chasman D. I. , Missmer S. A. , Zondervan K. T. , Morton C. C. 
Published: October 2019

AbstractUterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10−8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.
Ultrafast growth of nanocrystalline graphene films by quenching and grain-size-dependent strength and bandgap opening
Authors: Zhao Tong , Xu Chuan , Ma Wei , Liu Zhibo , Zhou Tianya , Liu Zhen , Feng Shun , Zhu Mengjian , Kang Ning , Sun Dong-Ming , Cheng Hui-Ming , Ren Wencai 
Published: October 2019

AbstractNanocrystallization is a well-known strategy to dramatically tune the properties of materials; however, the grain-size effect of graphene at the nanometer scale remains unknown experimentally because of the lack of nanocrystalline samples. Here we report an ultrafast growth of graphene films within a few seconds by quenching a hot metal foil in liquid carbon source. Using Pt foil and ethanol as examples, four kinds of nanocrystalline graphene films with average grain size of ~3.6, 5.8, 8.0, and 10.3 nm are synthesized. It is found that the effect of grain boundary becomes more pronounced at the nanometer scale. In comparison with pristine graphene, the 3.6 nm-grained film retains high strength (101 GPa) and Young’s modulus (576 GPa), whereas the electrical conductivity is declined by over 100 times, showing semiconducting behavior with a bandgap of ~50 meV. This liquid-phase precursor quenching method opens possibilities for ultrafast synthesis of typical graphene materials and other two-dimensional nanocrystalline materials.
Longitudinal ridges imparted by high-speed granular flow mechanisms in martian landslides
Authors: Magnarini Giulia , Mitchell Thomas M. , Grindrod Peter M. , Goren Liran , Schmitt Harrison H. 
Published: October 2019

AbstractThe presence of longitudinal ridges documented in long runout landslides across our solar system is commonly associated with the existence of a basal layer of ice. However, their development, the link between their occurrence and the emplacement mechanisms of long runout landslides, and the necessity of a basal ice layer remain poorly understood. Here, we analyse the morphometry of longitudinal ridges of a martian landslide and show that the wavelength of the ridges is 2–3 times the average thickness of the landslide deposit, a unique scaling relationship previously reported in ice-free rapid granular flow experiments. We recognize en-echelon features that we interpret as kinematic indicators, congruent with experimentally-measured transverse velocity gradient. We suggest that longitudinal ridges should not be considered as unequivocal evidence for presence of ice, rather as inevitable features of rapid granular sliding material, that originate from a mechanical instability once a kinematic threshold is surpassed.
Phase separation-deficient TDP43 remains functional in splicing
Authors: Schmidt Hermann Broder , Barreau Ariana , Rohatgi Rajat 
Published: October 2019

AbstractIntrinsically disordered regions (IDRs) are often fast-evolving protein domains of low sequence complexity that can drive phase transitions and are commonly found in many proteins associated with neurodegenerative diseases, including the RNA processing factor TDP43. Yet, how phase separation contributes to the physiological functions of TDP43 in cells remains enigmatic. Here, we combine systematic mutagenesis guided by evolutionary sequence analysis with a live-cell reporter assay of TDP43 phase dynamics to identify regularly-spaced hydrophobic motifs separated by flexible, hydrophilic segments in the IDR as a key determinant of TDP43 phase properties. This heuristic framework allows customization of the material properties of TDP43 condensates to determine effects on splicing function. Remarkably, even a mutant that fails to phase-separate at physiological concentrations can still efficiently mediate the splicing of a quantitative, single-cell splicing reporter and endogenous targets. This suggests that the ability of TDP43 to phase-separate is not essential for its splicing function.
Critical dependence of morphodynamic models of fluvial and tidal systems on empirical downslope sediment transport
Authors: Baar A. W. , Boechat Albernaz M. , van Dijk W. M. , Kleinhans M. G. 
Published: October 2019

AbstractThe morphological development of fluvial and tidal systems is forecast more and more frequently by models in scientific and engineering studies for decision making regarding climate change mitigation, flood control, navigation and engineering works. However, many existing morphodynamic models predict unrealistically high channel incision, which is often dampened by increased gravity-driven sediment transport on side-slopes by up to two orders of magnitude too high. Here we show that such arbitrary calibrations dramatically bias sediment dynamics, channel patterns, and rate of morphological change. For five different models bracketing a range of scales and environments, we found that it is impossible to calibrate a model on both sediment transport magnitude and morphology. Consequently, present calibration practice may cause an order magnitude error in either morphology or morphological change. We show how model design can be optimized for different applications. We discuss the major implications for model interpretation and a critical knowledge gap.
Unraveling the thermodynamic criteria for size-dependent spontaneous phase separation in soft porous crystals
Authors: Rogge Sven M. J. , Waroquier Michel , Van Speybroeck Veronique 
Published: October 2019

AbstractSoft porous crystals (SPCs) harbor a great potential as functional nanoporous materials owing to their stimuli-induced and tuneable morphing between different crystalline phases. These large-amplitude phase transitions are often assumed to occur cooperatively throughout the whole material, which thereby retains its perfect crystalline order. Here, we disprove this paradigm through mesoscale first-principles based molecular dynamics simulations, demonstrating that morphological transitions do induce spatial disorder under the form of interfacial defects and give rise to yet unidentified phase coexistence within a given sample. We hypothesize that this phase coexistence can be stabilized by carefully tuning the experimental control variables through, e.g., temperature or pressure quenching. The observed spatial disorder helps to rationalize yet elusive phenomena in SPCs, such as the impact of crystal downsizing on their flexible nature, thereby identifying the crystal size as a crucial design parameter for stimuli-responsive devices based on SPC nanoparticles and thin films.
Random auxetics from buckling fibre networks
Authors: Domaschke S. , Morel A. , Fortunato G. , Ehret A. E. 
Published: October 2019

AbstractAuxetic materials have gained increasing interest in the last decades, fostered by auspicious applications in various fields. While the design of new auxetics has largely focused on meta-materials with deterministic, periodically arranged structures, we show here by theoretical and numerical analysis that pronounced auxetic behaviour with negative Poisson’s ratios of very large magnitude can occur in random fibre networks with slender, reasonably straight fibre segments that buckle and deflect. We further demonstrate in experiments that such auxetic fibre networks, which increase their thickness by an order of magnitude and more than quintuple their volume when moderately extended, can be produced by electrospinning. Our results thus augment the class of auxetics by a large group of straightforwardly fabricable meta-materials with stochastic microstructure.
A domino reaction for generating β-aryl aldehydes from alkynes by substrate recognition catalysis
Authors: Fang Weiwei , Bauer Felix , Dong Yaxi , Breit Bernhard 
Published: October 2019

AbstractThe development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance. Here we develop a domino process comprising three consecutive reaction steps based on the strategy of supramolecular substrate recognition. This approach provides valuable β-aryl aldehydes from readily accessible α-alkynoic acids and arenes under mild reaction conditions, employing a supramolecular Rh catalyst containing an acylguanidine-bearing phosphine ligand. Furthermore, the synthesis of a key intermediate of Avitriptan using this protocol is accomplished. The first step of the reaction sequence is proved to be the regioselective hydroformylation of α-alkynoic acids. Remarkably, molecular recognition of the ligand and the substrate via hydrogen bonding plays a key role in this step. Control experiments indicate that the reaction further proceeds via 1,4-addition of an arene nucleophile to the unsaturated aldehyde intermediate and subsequent decarboxylation.
Mild photothermal therapy potentiates anti-PD-L1 treatment for immunologically cold tumors via an all-in-one and all-in-control strategy
Authors: Huang Liping , Li Yanan , Du Yunai , Zhang Yiyi , Wang Xiuxia , Ding Yuan , Yang Xiangliang , Meng Fanling , Tu Jiasheng , Luo Liang , Sun Chunmeng 
Published: October 2019

AbstractOne of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors.
Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
Authors: Sonner Jana K. , Keil Melanie , Falk-Paulsen Maren , Mishra Neha , Rehman Ateequr , Kramer Magdalena , Deumelandt Katrin , Röwe Julian , Sanghvi Khwab , Wolf Lara , von Landenberg Anna , Wolff Hendrik , Bharti Richa , Oezen Iris , Lanz Tobias V. , Wanke Florian , Tang Yilang , Brandao Ines , Mohapatra Soumya R. , Epping Lisa , Grill Alexandra , Röth Ralph , Niesler Beate , Meuth Sven G. , Opitz Christiane A. , Okun Jürgen G. , Reinhardt Christoph , Kurschus Florian C. , Wick Wolfgang , Bode Helge B. , Rosenstiel Philip , Platten Michael 
Published: October 2019

AbstractThe interaction between the mammalian host and its resident gut microbiota is known to license adaptive immune responses. Nutritional constituents strongly influence composition and functional properties of the intestinal microbial communities. Here, we report that omission of a single essential amino acid - tryptophan – from the diet abrogates CNS autoimmunity in a mouse model of multiple sclerosis. Dietary tryptophan restriction results in impaired encephalitogenic T cell responses and is accompanied by a mild intestinal inflammatory response and a profound phenotypic shift of gut microbiota. Protective effects of dietary tryptophan restriction are abrogated in germ-free mice, but are independent of canonical host sensors of intracellular tryptophan metabolites. We conclude that dietary tryptophan restriction alters metabolic properties of gut microbiota, which in turn have an impact on encephalitogenic T cell responses. This link between gut microbiota, dietary tryptophan and adaptive immunity may help to develop therapeutic strategies for protection from autoimmune neuroinflammation.
Structural transitions during the scaffolding-driven assembly of a viral capsid
Authors: Ignatiou Athanasios , Brasilès Sandrine , El Sadek Fadel Mehdi , Bürger Jörg , Mielke Thorsten , Topf Maya , Tavares Paulo , Orlova Elena V. 
Published: October 2019

AbstractAssembly of tailed bacteriophages and herpesviruses starts with formation of procapsids (virion precursors without DNA). Scaffolding proteins (SP) drive assembly by chaperoning the major capsid protein (MCP) to build an icosahedral lattice. Here we report near-atomic resolution cryo-EM structures of the bacteriophage SPP1 procapsid, the intermediate expanded procapsid with partially released SPs, and the mature capsid with DNA. In the intermediate state, SPs are bound only to MCP pentons and to adjacent subunits from hexons. SP departure results in the expanded state associated with unfolding of the MCP N-terminus and straightening of E-loops. The newly formed extensive inter-capsomere bonding appears to compensate for release of SPs that clasp MCP capsomeres together. Subsequent DNA packaging instigates bending of MCP A domain loops outwards, closing the hexons central opening and creating the capsid auxiliary protein binding interface. These findings provide a molecular basis for the sequential structural rearrangements during viral capsid maturation.
Orbitofrontal signals for two-component choice options comply with indifference curves of Revealed Preference Theory
Authors: Pastor-Bernier Alexandre , Stasiak Arkadiusz , Schultz Wolfram 
Published: October 2019

AbstractEconomic choice options contain multiple components and constitute vectorial bundles. The question arises how they are represented by single-dimensional, scalar neuronal signals that are suitable for economic decision-making. Revealed Preference Theory provides formalisms for establishing preference relations between such bundles, including convenient graphic indifference curves. During stochastic choice between bundles with the same two juice components, we identified neuronal signals for vectorial, multi-component bundles in the orbitofrontal cortex of monkeys. A scalar signal integrated the values from all bundle components in the structured manner of the Theory; it followed the behavioral indifference curves within their confidence limits, was indistinguishable between differently composed but equally revealed preferred bundles, predicted bundle choice and complied with an optimality axiom. Further, distinct signals in other neurons coded the option components separately but followed indifference curves as a population. These data demonstrate how scalar signals represent vectorial, multi-component choice options.
Reverberant 3D optical coherence elastography maps the elasticity of individual corneal layers
Authors: Zvietcovich Fernando , Pongchalee Pornthep , Meemon Panomsak , Rolland Jannick P. , Parker Kevin J. 
Published: October 2019

AbstractThe elasticity mapping of individual layers in the cornea using non-destructive elastography techniques advances diagnosis and monitoring of ocular diseases and treatments in ophthalmology. However, transient Lamb waves, currently used in most dynamic optical coherence and ultrasound elastography techniques, diminish the translation of wave speed into shear/Young’s modulus. Here, we present reverberant 3D optical coherence elastography (Rev3D-OCE), a novel approach leveraging the physical properties of diffuse fields in detecting elasticity gradients not only in the lateral direction, but also along the depth axis of the cornea. A Monte Carlo analysis, finite element simulations, and experiments in layered phantoms are conducted to validate the technique and to characterize the axial elastography resolution. Experiments in ex vivo porcine cornea at different intraocular pressures reveal that Rev3D-OCE enables the elastic characterization of single layers that matches the anatomical description of corneal layers with unprecedented contrast in the dynamic OCE field.
NSD2 overexpression drives clustered chromatin and transcriptional changes in a subset of insulated domains
Authors: Lhoumaud Priscillia , Badri Sana , Rodriguez-Hernaez Javier , Sakellaropoulos Theodore , Sethia Gunjan , Kloetgen Andreas , Cornwell MacIntosh , Bhattacharyya Sourya , Ay Ferhat , Bonneau Richard , Tsirigos Aristotelis , Skok Jane A. 
Published: October 2019

AbstractCTCF and cohesin play a key role in organizing chromatin into topologically associating domain (TAD) structures. Disruption of a single CTCF binding site is sufficient to change chromosomal interactions leading to alterations in chromatin modifications and gene regulation. However, the extent to which alterations in chromatin modifications can disrupt 3D chromosome organization leading to transcriptional changes is unknown. In multiple myeloma, a 4;14 translocation induces overexpression of the histone methyltransferase, NSD2, resulting in expansion of H3K36me2 and shrinkage of antagonistic H3K27me3 domains. Using isogenic cell lines producing high and low levels of NSD2, here we find oncogene activation is linked to alterations in H3K27ac and CTCF within H3K36me2 enriched chromatin. A logistic regression model reveals that differentially expressed genes are significantly enriched within the same insulated domain as altered H3K27ac and CTCF peaks. These results identify a bidirectional relationship between 2D chromatin and 3D genome organization in gene regulation.
Ultrabroadband 3D invisibility with fast-light cloaks
Authors: Tsakmakidis K. L. , Reshef O. , Almpanis E. , Zouros G. P. , Mohammadi E. , Saadat D. , Sohrabi F. , Fahimi-Kashani N. , Etezadi D. , Boyd R. W. , Altug H. 
Published: October 2019

AbstractAn invisibility cloak should completely hide an object from an observer, ideally across the visible spectrum and for all angles of incidence and polarizations of light, in three dimensions. However, until now, all such devices have been limited to either small bandwidths or have disregarded the phase of the impinging wave or worked only along specific directions. Here, we show that these seemingly fundamental restrictions can be lifted by using cloaks made of fast-light media, termed tachyonic cloaks, where the wave group velocity is larger than the speed of light in vacuum. On the basis of exact analytic calculations and full-wave causal simulations, we demonstrate three-dimensional cloaking that cannot be detected even interferometrically across the entire visible regime. Our results open the road for ultrabroadband invisibility of large objects, with direct implications for stealth and information technology, non-disturbing sensors, near-field scanning optical microscopy imaging, and superluminal propagation.
A vertical silicon-graphene-germanium transistor
Authors: Liu Chi , Ma Wei , Chen Maolin , Ren Wencai , Sun Dongming 
Published: October 2019

AbstractGraphene-base transistors have been proposed for high-frequency applications because of the negligible base transit time induced by the atomic thickness of graphene. However, generally used tunnel emitters suffer from high emitter potential-barrier-height which limits the transistor performance towards terahertz operation. To overcome this issue, a graphene-base heterojunction transistor has been proposed theoretically where the graphene base is sandwiched by silicon layers. Here we demonstrate a vertical silicon-graphene-germanium transistor where a Schottky emitter constructed by single-crystal silicon and single-layer graphene is achieved. Such Schottky emitter shows a current of 692 A cm−2and a capacitance of 41 nF cm−2, and thus the alpha cut-off frequency of the transistor is expected to increase from about 1 MHz by using the previous tunnel emitters to above 1 GHz by using the current Schottky emitter. With further engineering, the semiconductor-graphene-semiconductor transistor is expected to be one of the most promising devices for ultra-high frequency operation.
Regulation of the ER stress response by a mitochondrial microprotein
Authors: Chu Qian , Martinez Thomas F. , Novak Sammy Weiser , Donaldson Cynthia J. , Tan Dan , Vaughan Joan M. , Chang Tina , Diedrich Jolene K. , Andrade Leo , Kim Andrew , Zhang Tong , Manor Uri , Saghatelian Alan 
Published: October 2019

AbstractCellular homeostasis relies on having dedicated and coordinated responses to a variety of stresses. The accumulation of unfolded proteins in the endoplasmic reticulum (ER) is a common stress that triggers a conserved pathway called the unfolded protein response (UPR) that mitigates damage, and dysregulation of UPR underlies several debilitating diseases. Here, we discover that a previously uncharacterized 54-amino acid microprotein PIGBOS regulates UPR. PIGBOS localizes to the mitochondrial outer membrane where it interacts with the ER protein CLCC1 at ER–mitochondria contact sites. Functional studies reveal that the loss of PIGBOS leads to heightened UPR and increased cell death. The characterization of PIGBOS reveals an undiscovered role for a mitochondrial protein, in this case a microprotein, in the regulation of UPR originating in the ER. This study demonstrates microproteins to be an unappreciated class of genes that are critical for inter-organelle communication, homeostasis, and cell survival.