bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the expressive power of user-defined effects: Effect handlers, monadic reflection, delimited control
Authors: FORSTER YANNICK , KAMMAR OHAD , LINDLEY SAM , PRETNAR MATIJA 
Published: October 2019

AbstractWe compare the expressive power of three programming abstractions for user-defined computational effects: Plotkin and Pretnar’s effect handlers, Filinski’s monadic reflection, and delimited control. This comparison allows a precise discussion about the relative expressiveness of each programming abstraction. It also demonstrates the sensitivity of the relative expressiveness of user-defined effects to seemingly orthogonal language features. We present three calculi, one per abstraction, extending Levy’s call-by-push-value. For each calculus, we present syntax, operational semantics, a natural type-and-effect system, and, for effect handlers and monadic reflection, a set-theoretic denotational semantics. We establish their basic metatheoretic properties: safety, termination, and, where applicable, soundness and adequacy. Using Felleisen’s notion of a macro translation, we show that these abstractions can macro express each other, and show which translations preserve typeability. We use the adequate finitary set-theoretic denotational semantics for the monadic calculus to show that effect handlers cannot be macro expressed while preserving typeability either by monadic reflection or by delimited control. Our argument fails with simple changes to the type system such as polymorphism and inductive types. We supplement our development with a mechanised Abella formalisation.
Germ plasm-related structures in marine medaka gametogenesis; novel sites of Vasa localization and the unique mechanism of germ plasm granule arising
Authors: Reunov Arkadiy A. , Au Doris W. T. , Alexandrova Yana N. , Chiang Michael W. L. , Wan Miles T. , Yakovlev Konstantin V. , Reunova Yulia A. , Komkova Alina V. , Cheung Napo K. M. , Peterson Drew R. , Adrianov Andrey V. 
Published: October 2019

SummaryGerm plasm, a cytoplasmic factor of germline cell differentiation, is suggested to be a perspective tool forin vitromeiotic differentiation. To discriminate between the: (1) germ plasm-related structures (GPRS) involved in meiosis triggering; and (2) GPRS involved in the germ plasm storage phase, we investigated gametogenesis in the marine medakaOryzias melastigma. The GPRS of the mitosis-to-meiosis period are similar in males and females. In both sexes, five events typically occur: (1) turning of the primary Vasa-positive germ plasm granules into the Vasa-positive intermitochondrial cement (IMC); (2) aggregation of some mitochondria by IMC followed by arising of mitochondrial clusters; (3) intramitochondrial localization of IMC-originated Vasa; followed by (4) mitochondrial cluster degradation; and (5) intranuclear localization of Vasa followed by this protein entering the nuclei (gonial cells) and synaptonemal complexes (zygotene–pachytene meiotic cells). In post-zygotene/pachytene gametogenesis, the GPRS are sex specific; the Vasa-positive chromatoid bodies are found during spermatogenesis, but oogenesis is characterized by secondary arising of Vasa-positive germ plasm granules followed by secondary formation and degradation of mitochondrial clusters. A complex type of germ plasm generation, ‘the follicle cell assigned germ plasm formation’, was found in late oogenesis. The mechanisms discovered are recommended to be taken into account for possible reconstruction of those underin vitroconditions.
Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele
Authors: Al-Mossawi Hussein , Yager Nicole , Taylor Chelsea A. , Lau Evelyn , Danielli Sara , de Wit Jelle , Gilchrist James , Nassiri Isar , Mahe Elise A. , Lee Wanseon , Rizvi Laila , Makino Seiko , Cheeseman Jane , Neville Matt , Knight Julian C. , Bowness Paul , Fairfax Benjamin P. 
Published: October 2019

AbstractIL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases.
Photoactivation of silicon rhodamines via a light-induced protonation
Authors: Frei Michelle S. , Hoess Philipp , Lampe Marko , Nijmeijer Bianca , Kueblbeck Moritz , Ellenberg Jan , Wadepohl Hubert , Ries Jonas , Pitsch Stefan , Reymond Luc , Johnsson Kai 
Published: October 2019

AbstractPhotoactivatable fluorophores are important for single-particle tracking and super-resolution microscopy. Here we present a photoactivatable fluorophore that forms a bright silicon rhodamine derivative through a light-dependent protonation. In contrast to other photoactivatable fluorophores, no caging groups are required, nor are there any undesired side-products released. Using this photoactivatable fluorophore, we create probes for HaloTag and actin for live-cell single-molecule localization microscopy and single-particle tracking experiments. The unusual mechanism of photoactivation and the fluorophore’s outstanding spectroscopic properties make it a powerful tool for live-cell super-resolution microscopy.
Sound-driven single-electron transfer in a circuit of coupled quantum rails
Authors: Takada Shintaro , Edlbauer Hermann , Lepage Hugo V. , Wang Junliang , Mortemousque Pierre-André , Georgiou Giorgos , Barnes Crispin H. W. , Ford Christopher J. B. , Yuan Mingyun , Santos Paulo V. , Waintal Xavier , Ludwig Arne , Wieck Andreas D. , Urdampilleta Matias , Meunier Tristan , Bäuerle Christopher 
Published: October 2019

AbstractSurface acoustic waves (SAWs) strongly modulate the shallow electric potential in piezoelectric materials. In semiconductor heterostructures such as GaAs/AlGaAs, SAWs can thus be employed to transfer individual electrons between distant quantum dots. This transfer mechanism makes SAW technologies a promising candidate to convey quantum information through a circuit of quantum logic gates. Here we present two essential building blocks of such a SAW-driven quantum circuit. First, we implement a directional coupler allowing to partition a flying electron arbitrarily into two paths of transportation. Second, we demonstrate a triggered single-electron source enabling synchronisation of the SAW-driven sending process. Exceeding a single-shot transfer efficiency of 99%, we show that a SAW-driven integrated circuit is feasible with single electrons on a large scale. Our results pave the way to perform quantum logic operations with flying electron qubits.
Direct imaging of light-element impurities in graphene reveals
triple-coordinated oxygen
Authors: Hofer Christoph , Skákalová Viera , Görlich Tobias , Tripathi Mukesh , Mittelberger Andreas , Mangler Clemens , Monazam Mohammad Reza Ahmadpour , Susi Toma , Kotakoski Jani , Meyer Jannik C. 
Published: October 2019

AbstractAlong with hydrogen, carbon, nitrogen and oxygen are the arguably most
important elements for organic chemistry. Due to their rich variety of possible
bonding configurations, they can form a staggering number of compounds. Here, we
present a detailed analysis of nitrogen and oxygen bonding configurations in a
defective carbon (graphene) lattice. Using aberration-corrected scanning
transmission electron microscopy and single-atom electron energy loss spectroscopy,
we directly imaged oxygen atoms in graphene oxide, as well as nitrogen atoms
implanted into graphene. The collected data allows us to compare nitrogen and oxygen
bonding configurations, showing clear differences between the two elements. As
expected, nitrogen forms either two or three bonds with neighboring carbon atoms,
with three bonds being the preferred configuration. Oxygen, by contrast, tends to
bind with only two carbon atoms. Remarkably, however, triple-coordinated oxygen with
three carbon neighbors is also observed, a configuration that is exceedingly rare in
organic compounds.
Insights into the ecological roles and evolution of methyl-coenzyme M reductase-containing hot spring Archaea
Authors: Hua Zheng-Shuang , Wang Yu-Lin , Evans Paul N. , Qu Yan-Ni , Goh Kian Mau , Rao Yang-Zhi , Qi Yan-Ling , Li Yu-Xian , Huang Min-Jun , Jiao Jian-Yu , Chen Ya-Ting , Mao Yan-Ping , Shu Wen-Sheng , Hozzein Wael , Hedlund Brian P. , Tyson Gene W. , Zhang Tong , Li Wen-Jun 
Published: October 2019

AbstractSeveral recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.
Structure of ribosome-bound azole-modified peptide phazolicin rationalizes its species-specific mode of bacterial translation inhibition
Authors: Travin Dmitrii Y. , Watson Zoe L. , Metelev Mikhail , Ward Fred R. , Osterman Ilya A. , Khven Irina M. , Khabibullina Nelli F. , Serebryakova Marina , Mergaert Peter , Polikanov Yury S. , Cate Jamie H. D. , Severinov Konstantin 
Published: October 2019

AbstractRibosome-synthesized post-translationally modified peptides (RiPPs) represent a rapidly expanding class of natural products with various biological activities. Linear azol(in)e-containing peptides (LAPs) comprise a subclass of RiPPs that display outstanding diversity of mechanisms of action while sharing common structural features. Here, we report the discovery of a new LAP biosynthetic gene cluster in the genome of Rhizobium Pop5, which encodes the precursor peptide and modification machinery of phazolicin (PHZ) – an extensively modified peptide exhibiting narrow-spectrum antibacterial activity against some symbiotic bacteria of leguminous plants. The cryo-EM structure of the Escherichia coli 70S-PHZ complex reveals that the drug interacts with the 23S rRNA and uL4/uL22 proteins and obstructs ribosomal exit tunnel in a way that is distinct from other compounds. We show that the uL4 loop sequence determines the species-specificity of antibiotic action. PHZ expands the known diversity of LAPs and may be used in the future as biocontrol agent for agricultural needs.
5-Fluorouracil treatment induces characteristic T>G mutations in human cancer
Authors: Christensen Sharon , Van der Roest Bastiaan , Besselink Nicolle , Janssen Roel , Boymans Sander , Martens John W. M. , Yaspo Marie-Laure , Priestley Peter , Kuijk Ewart , Cuppen Edwin , Van Hoeck Arne 
Published: October 2019

Abstract5-Fluorouracil (5-FU) is a chemotherapeutic drug commonly used for the treatment of solid cancers. It is proposed that 5-FU interferes with nucleotide synthesis and incorporates into DNA, which may have a mutational impact on both surviving tumor and healthy cells. Here, we treat intestinal organoids with 5-FU and find a highly characteristic mutational pattern that is dominated by T>G substitutions in a CTT context. Tumor whole genome sequencing data confirms that this signature is also identified in vivo in colorectal and breast cancer patients who have received 5-FU treatment. Taken together, our results demonstrate that 5-FU is mutagenic and may drive tumor evolution and increase the risk of secondary malignancies. Furthermore, the identified signature shows a strong resemblance to COSMIC signature 17, the hallmark signature of treatment-naive esophageal and gastric tumors, which indicates that distinct endogenous and exogenous triggers can converge onto highly similar mutational signatures.
Dissecting splicing decisions and cell-to-cell variability with designed sequence libraries
Authors: Mikl Martin , Hamburg Amit , Pilpel Yitzhak , Segal Eran 
Published: October 2019

AbstractMost human genes are alternatively spliced, allowing for a large expansion of the proteome. The multitude of regulatory inputs to splicing limits the potential to infer general principles from investigating native sequences. Here, we create a rationally designed library of >32,000 splicing events to dissect the complexity of splicing regulation through systematic sequence alterations. Measuring RNA and protein splice isoforms allows us to investigate both cause and effect of splicing decisions, quantify diverse regulatory inputs and accurately predict (R2 = 0.73–0.85) isoform ratios from sequence and secondary structure. By profiling individual cells, we measure the cell-to-cell variability of splicing decisions and show that it can be encoded in the DNA and influenced by regulatory inputs, opening the door for a novel, single-cell perspective on splicing regulation.
Realisation of high-fidelity nonadiabatic CZ gates with superconducting qubits
Authors: Li Shaowei , Clark Juno , Wang Shiyu , Wu Yulin , Gong Ming , Yan Zhiguang , Rong Hao , Deng Hui , Zha Chen , Guo Cheng , Sun Lihua , Peng Chengzhi , Zhu Xiaobo , Pan Jian-Wei 
Published: October 2019

Abstract
Entangling gates with error rates reaching the threshold for quantum error correction have been reported for CZ gates using adiabatic longitudinal control based on the interaction between the |11〉 and |20〉 states. Here, we design and implement nonadiabatic CZ gates, which outperform adiabatic gates in terms of speed and fidelity, with gate times reaching

$$1.25/(2\sqrt 2 g_{01,10})$$

1.25
∕

(

2

2

g

01
,
10

)

, and fidelities reaching 99.54 ± 0.08%. Nonadiabatic gates are found to have proportionally less incoherent error than adiabatic gates thanks to their fast gate times, which leave more room for further improvements in the design of the control pules to eliminate coherent errors. We also show that state leakage can be reduced to below 0.2% with optimisation. Furthermore, the gate optimisation process is highly feasible: experimental optimisation can be expected to take less than four hours. Finally, the gate design process can be extended to CCZ gates, and our preliminary results suggest that this process would be feasible as well, if we can measure the CCZ fidelity separate from the initialisation and readout errors in experimental optimisation.
ModelBricks—modules for reproducible modeling improving model annotation and provenance
Authors: Cowan Ann E. , Mendes Pedro , Blinov Michael L. 
Published: October 2019

AbstractMost computational models in biology are built and intended for “single-use”; the lack of appropriate annotation creates models where the assumptions are unknown, and model elements are not uniquely identified. Simply recreating a simulation result from a publication can be daunting; expanding models to new and more complex situations is a herculean task. As a result, new models are almost always created anew, repeating literature searches for kinetic parameters, initial conditions and modeling specifics. It is akin to building a brick house starting with a pile of clay. Here we discuss a concept for building annotated, reusable models, by starting with small well-annotated modules we call ModelBricks. Curated ModelBricks, accessible through an open database, could be used to construct new models that will inherit ModelBricks annotations and thus be easier to understand and reuse. Key features of ModelBricks include reliance on a commonly used standard language (SBML), rule-based specification describing species as a collection of uniquely identifiable molecules, association with model specific numerical parameters, and more common annotations. Physical bricks can vary substantively; likewise, to be useful the structure of ModelBricks must be highly flexible—it should encapsulate mechanisms from single reactions to multiple reactions in a complex process. Ultimately, a modeler would be able to construct large models by using multiple ModelBricks, preserving annotations and provenance of model elements, resulting in a highly annotated model. We envision the library of ModelBricks to rapidly grow from community contributions. Persistent citable references will incentivize model creators to contribute new ModelBricks.
Compendiums of cancer transcriptomes for machine learning applications
Authors: Lim Su Bin , Tan Swee Jin , Lim Wan-Teck , Lim Chwee Teck 
Published: October 2019

AbstractThere are massive transcriptome profiles in the form of microarray. The challenge is that they are processed using diverse platforms and preprocessing tools, requiring considerable time and informatics expertise for cross-dataset analyses. If there exists a single, integrated data source, data-reuse can be facilitated for discovery, analysis, and validation of biomarker-based clinical strategy. Here, we present merged microarray-acquired datasets (MMDs) across 11 major cancer types, curating 8,386 patient-derived tumor and tumor-free samples from 95 GEO datasets. Using machine learning algorithms, we show that diagnostic models trained from MMDs can be directly applied to RNA-seq-acquired TCGA data with high classification accuracy. Machine learning optimized MMD further aids to reveal immune landscape across various carcinomas critically needed in disease management and clinical interventions. This unified data source may serve as an excellent training or test set to apply, develop, and refine machine learning algorithms that can be tapped to better define genomic landscape of human cancers.
Risk of African swine fever virus introduction into the United States through smuggling of pork in air passenger luggage
Authors: Jurado Cristina , Mur Lina , Pérez Aguirreburualde María Sol , Cadenas-Fernández Estefanía , Martínez-López Beatriz , Sánchez-Vizcaíno José Manuel , Perez Andrés 
Published: October 2019

AbstractAfrican swine fever causes substantial economic losses in the swine industry in affected countries. Traditionally confined to Africa with only occasional incursions into other regions, ASF began spreading into Caucasian countries and Eastern Europe in 2007, followed by Western Europe and Asia in 2018. Such a dramatic change in the global epidemiology of ASF has resulted in concerns that the disease may continue to spread into disease-free regions such as the US. In this study, we estimated the risk of introduction of ASF virus into the US through smuggling of pork in air passenger luggage. Results suggest that the mean risk of ASFV introduction into the US via this route has increased by 183.33% from the risk estimated before the disease had spread into Western Europe or Asia. Most of the risk (67.68%) was associated with flights originating from China and Hong Kong, followed by the Russian Federation (26.92%). Five US airports accounted for >90% of the risk. Results here will help to inform decisions related to the design of ASF virus surveillance strategies in the US.
Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion
Authors: Rabieifar Parisa , Zhuang Ting , Costa Tânia D. F. , Zhao Miao , Strömblad Staffan 
Published: October 2019

Abstractp21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.
Nanoscale graphene Hall sensors for high-resolution ambient magnetic imaging
Authors: Collomb David , Li Penglei , Bending Simon J. 
Published: October 2019

AbstractA major challenge to routine non-invasive, nanoscale magnetic imaging is the development of Hall sensors that are stable under ambient conditions and retain low minimum detectable fields down to nanoscale dimensions. To address these issues we have fabricated and characterised chemical vapour deposition (CVD) graphene Hall sensors with wire widths between 50 nm and 1500 nm, in order to exploit the high carrier mobility and tuneability of this material. The measured Hall voltage noise is in good agreement with theoretical models and we demonstrate that minimum detectable fields at fixed drive current are lowest in the vicinity of the charge neutrality point. Our best performing deep sub-micron sensors, based on a wire width of 85 nm, display the excellent room temperature resolution of 59 µT/√Hz at a dc drive current of 12 µA and measurement frequency of 531 Hz. We observe a weak increase in minimum detectable field as the active sensor area is reduced while the Hall offset field is largely independent of size. These figures-of-merit significantly surpass prior results on larger probes in competing materials systems, with considerable scope for further optimisation. Our results clearly demonstrate the feasibility of using CVD graphene to realise very high spatial resolution nanosensors for quantitative room temperature magnetic imaging.