bluuebunny/crossref_metadata_2025 huggingface dataset:
A PRIMER ON BOOTSTRAP TESTING OF HYPOTHESES IN TIME SERIES MODELS: WITH AN APPLICATION TO DOUBLE AUTOREGRESSIVE MODELS
Authors: Cavaliere Giuseppe , Rahbek Anders
Published: March 2020

In this article, we discuss the bootstrap as a tool for statistical inference in econometric time series models. Importantly, in the context of testing, properties of the bootstrap under the null (size) as well as under the alternative (power) are discussed. Although properties under the alternative are crucial to ensure the consistency of bootstrap-based tests, it is often the case in the literature that only validity under the null is discussed. We provide new results on bootstrap inference for the class of double-autoregressive (DAR) models. In addition, we review key examples from the bootstrap time series literature in order to emphasize the importance of properly defining and analyzing the bootstrap generating process and associated bootstrap statistics, while also providing an up-to-date review of existing approaches. DAR models are particularly interesting for bootstrap inference: first, standard asymptotic inference is usually difficult to implement due to the presence of nuisance parameters; second, inference involves testing whether one or more parameters are on the boundary of the parameter space; third, even second-order moments may not exist. In most of these cases, the bootstrap is not considered an appropriate tool for inference. Conversely, and taking testing nonstationarity to illustrate, we show that although a standard bootstrap based on unrestricted parameter estimation is invalid, a correct implementation of the bootstrap based on restricted parameter estimation (restricted bootstrap) is first-order valid. That is, it is able to replicate, under the null hypothesis, the correct limiting distribution. Importantly, we also show that the behavior of this bootstrap under the alternative hypothesis may be more involved because of possible lack of finite second-order moments of the bootstrap innovations. This feature makes for some parameter configurations, the restricted bootstrap unable to replicate the null asymptotic distribution when the null is false. We show that this possible drawback can be fixed by using a novel bootstrap in this framework. For this “hybrid bootstrap,” the parameter estimates used to construct the bootstrap data are obtained with the null imposed, while the bootstrap innovations are sampled with replacement from unrestricted residuals. We show that the hybrid bootstrap mimics the correct asymptotic null distribution, irrespective of the null being true or false. Monte Carlo simulations illustrate the behavior of both the restricted and the hybrid bootstrap, and we find that both perform very well even for small sample sizes.
Legal smart contracts for derivative trading in mining
Authors: Wise Julian Adam , Chan Meng Chak , Tadic Dihon , Miles Stephanie , Cornish Jack , Sellers Ewan , Brenecki David , Dzakpata Isaac , Murugesan Barti
Published: March 2020

This research demonstrates financial derivative trade of unprocessed materials, for the mining industry through legal smart contracts. Within the mining supply chain, a stock of mined resources can reside in a mineral stockpile for over twenty years without gaining financial interest and without undergoing the mineral extraction process to derive value from the asset. This research elaborates on a blockchain solution implemented to increase miners’ short-term cash flow for business operations through the issuance of derivative assets on mineral stockpiles which can be traded through legally binding smart contracts. The system is the first to enable mining companies’ access to the underlying asset’s value earlier in the production lifecycle through smart contract technology whilst providing hedge funds with access to new financial products for investment portfolios.
PREDICTING L2 FLUENCY FROM L1 FLUENCY BEHAVIOR
Authors: Duran-Karaoz Zeynep , Tavakoli Parvaneh
Published: March 2020

The article reports on the findings of a study investigating the relationship between first language (L1) and second language (L2) fluency behavior. Drawing on data collected from Turkish learners of English, the study also addresses the question of whether proficiency level mediates the relationship, if any. The data were coded for a range of breakdown, repair, speed, and composite measures. Language proficiency was measured by means of two tests: Oxford Placement Test (OPT) and an Elicited Imitation Task (EIT). The results show that some breakdown and repair measures were positively correlated in L1 and L2, but no correlations were observed for articulation rate and speech rate. The relationships were not mediated by proficiency level. Regression analyses show that a number of models predicted L2 fluency. L1 fluency contributed significantly to models predicting pausing behavior; EIT scores predicted L2 speech rate; and L1 fluency and OPT scores predicted L2 repair and mid-clause pauses. The important implications of the findings for fluency research and second language pedagogy are discussed.
A citizen science survey discloses the current distribution of the endangered Yellow CardinalGubernatrix cristatain Argentina
Authors: DOMÍNGUEZ MARISOL , LAPIDO ROCÍO , GORRINDO ADRIÁN , ARCHUBY DIEGO , CORREA EMILIO , LLANOS FABIÁN , REALES FABRICIO , PIANTANIDA FABRIZIO , MARATEO GERMÁN , MERIGGI JORGE , ANDREANI LUCAS , ENCABO MANUEL , VINASSA MARÍA LAURA GÓMEZ , BERTINI MAXIMILIANO , PERELLÓ MILTON , BANCHS RICARDO , CIRIGNOLI SEBASTIÁN , VERÓN SILVINA , MAHLER BETTINA
Published: March 2020

The Yellow CardinalGubernatrix cristatais a globally endangered passerine from the southern cone of South America. Because of its conspicuous plumage and very attractive song, it suffers considerably from illegal pet trade. The largest remaining populations are found in Argentina, but no coordinated efforts have been made thus far to understand better its current distribution and conservation status. During three annual surveys supported by a citizen science programme, more than 140 volunteers surveyed 644 geographical points during spring and detected 221 Yellow Cardinals. Based on the survey results, we evaluated the presence of cardinals within protected areas in Argentina and found that the species was only detected in four of them, two of which were private reserves with a low level of protection. We also found that the species was not restricted to the ‘Espinal’ ecoregion, but also inhabited ‘Monte’ and ‘Chaco’ ecoregions, which are generally drier. This citizen science programme allowed us to obtain up-to-date information on the remaining populations of the Yellow Cardinal and helped to increase public awareness about the conservation problems faced by the species. We propose some future strategies for monitoring Yellow Cardinals and taking informed conservation decisions.
Investigation of transfer results of human embryos that were vitrified and thawed at the cleavage, morula and blastocyst stages
Authors: Korkmaz Cem , Gül Yıldız Ümmü , Fidan Ulaş , Baykal Barış , Temel Ceyhan Seyit , Ağaçayak Elif
Published: March 2020

The objective of this study was to compare the rates of clinical pregnancy after the transfer of vitrified and thawed human embryos on days 3, 4 and 5 of embryonic development. In this retrospective study, the results of 148 embryo transfer cycles, using embryos frozen and thawed over the 3-year period between January 2016 and December 2018 at the Gülhane Training and Research Hospital Department of Gynecology and Obsterics Reproductive Medical Center of the University of Health Sciences, Ankara, Turkey were examined. Following embryo transfer – including 29 dissolved embryos frozen on day 3, 80 frozen on day 4, and 39 frozen on day 5 – results were examined in terms of clinical pregnancy rates. In this study, across all three groups, no significant differences were observed in terms of patient age, the number of oocytes collected, infertility reasons, the number of embryos dissolved, transfer day, or the number of embryos transferred. According to the transfer day, the rates of clinical pregnancy and ongoing pregnancy were significantly higher for embryos frozen on day 4 and transferred on day 5. Significantly higher rates of pregnancy and live birth were determined during in vitro fertilization (IVF) treatment with the freezing of human embryos on day 4 and the transfer of those embryos on day 5.
Value of transferring embryos derived from monopronucleated (1PN) zygotes at the time of fertilization assessment
Authors: Li Ming , Dang Yujiao , Wang Ying , Li Junsheng , Liu Ping
Published: March 2020

This paper is a retrospective analysis of the sole transfer of monopronucleated zygotes (1PN) embryos both in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to determine the value of transferring embryos formed from 1PN. In fresh cycles, 1PN cleavage-stage embryos (1PN cleavage fresh) were transferred. In frozen–thawed cycles, 1PN blastocyst-stage embryos (1PN blast frozen) were transferred. We used comparison groups: for fresh cycles, 2PN cleavage-stage embryos (2PN cleavage fresh) were transferred; and for frozen–thawed cycles, 2PN blastocyst-stage embryos (2PN blast frozen) were transferred. Comparison groups were matched for cycle and patient characteristics to the 1PN group. Finally, for fresh cycles, live birth rates (LBR) in the 1PN cleavage group were significantly lower than those in 2PN cleavage group, both for IVF [LBR = 7.64% vs. pregnancy rate (PR) = 22.12%, P = 0.003, respectively] and ICSI (LBR = 0% vs. LBR = 20.00%, P < 0.001, respectively). For frozen–thawed IVF cycles, the PR in the 1PN blastocyst group were comparable with those of the 2PN blastocyst group (1PN: LBR = 33.14% vs. 2PN: LBR = 37.24%, P = 0.289, respectively), while in ICSI, the PR in the 1PN blastocyst group were lower than those in the 2PN blastocyst group (LBR = 15.25% vs. LBR = 40.68%, P = 0.002, respectively). So, for IVF, blastocyst culture was capable of selecting normal 1PN embryos for transfer and achieves satisfying outcomes. However, for ICSI, blastocyst culture was not effective enough to eliminate abnormal embryos and 1PN embryo transfer needed to be treated with caution.
A brief history of the criminalization of mental illness
Authors: Dvoskin Joel A. , Knoll James L. , Silva Mollie
Published: March 2020

This article traces the history of the way in which mental disorders were viewed and treated, from before the birth of Christ to the present day. Special attention is paid to the process of deinstitutionalization in the United States and the failure to create an adequately robust community mental health system to care for the people who, in a previous era, might have experienced lifelong hospitalization. As a result, far too many people with serious mental illnesses are living in jails and prisons that are ill-suited and unprepared to meet their needs.
Mental health consequences for survivors of the 2011 Fukushima nuclear disaster: a systematic review. Part 1: psychological consequences
Authors: Shigemura Jun , Terayama Takero , Kurosawa Mie , Kobayashi Yuki , Toda Hiroyuki , Nagamine Masanori , Yoshino Aihide
Published: March 2020

To integrate scholastic literature regarding the prevalence and characteristics of the psychological consequences faced by survivors of the 2011 Fukushima earthquake/tsunami/nuclear disaster, we conducted a systematic review of survivor studies concerning the Fukushima disaster. In August 2019, four literature databases (PubMed, PsycINFO, Psychology and Behavioral Sciences Collection, and ICHUSHI) were used in the literature search. Peer-reviewed manuscripts reporting psychological consequences, either in English or Japanese, were selected. A total of 79 studies were selected for the review. Twenty-four studies (30.4%) were conducted as part of the Fukushima Health Management Survey—large-scale cohort study recruiting the residents of the entire Fukushima prefecture. Study outcomes were primarily nonspecific psychological distress, depressive symptoms, post-traumatic stress symptoms, and anxiety symptoms. The rates of high-risk individuals determined by the studies varied significantly owing to methodological differences. Nevertheless, these rates were mostly high (nonspecific psychological distress, 8.3%-65.1%; depressive symptoms, 12%-52.0%; and post-traumatic stress symptoms, 10.5%-62.6%). Many studies focused on vulnerable populations such as children, mothers of young children, evacuees, and nuclear power plant workers. However, few studies reported on the intervention methods used or their effect on the survivors. As a conclusion, high rates of individuals with psychological conditions, as well as a wide range of mental conditions, were reported among the Fukushima nuclear disaster survivors in the first 8 years after the disaster. These findings demonstrate the substantial impact of this compound disaster, especially in the context of a nuclear catastrophe.
Open‐Source Software Analysis Tool to Investigate Space Plasma Turbulence and Nonlinear DYNamics (ODYN)
Authors: Teodorescu E. , Echim M.M.
Published: March 2020

We have designed and built a versatile modularized software library—ODYN—that wraps a comprehensive set of advanced data analysis methods meant to facilitate the study of turbulence, nonlinear dynamics, and complexity in space plasmas. The Python programming language is used for the algorithmic implementation of models and methods devised to understand fundamental phenomena of space plasma physics like elements of spectral analysis, probability distribution functions and their moments, multifractal analysis, or information theory. ODYN is an open‐source software analysis tool and freely available to any user interested in turbulence and nonlinear dynamics analysis and provides a tool to perform automatic analysis on large collections of space measurements, in situ or simulations, a feature that distinguishes ODYN from other similar software. A user‐friendly configurator is provided, which allows customization of key parameters of the analysis methods, most useful for nonprogrammers.
Future Changes in the Occurrence of Hybrid Cyclones: The Added Value of Cyclone Classification for the East Australian Low‐Pressure Systems
Authors: Cavicchia L. , Pepler A. , Dowdy A. , Evans J. , Di Luca A. , Walsh K.
Published: March 2020

Several regions of the world, including the east coast of Australia, are characterized by the occurrence of low‐pressure systems with a range of different dynamical structures, including tropical, extratropical, and hybrid cyclones. Future changes in the occurrence of cyclones are better understood if storms are classified according to their dynamical structure. Therefore, we apply a classification of cyclones according to their cold‐core or warm‐core structure to an ensemble of regional climate model simulations. First, we show that historical simulations reproduce well the reanalysis results in terms of cyclone classification. We then show that once cyclone classification is applied, projections of future cyclone activity become more robust, including a decrease in the occurrence of both cold‐core and warm‐core cyclones. Finally, we show that in a warmer climate warm‐core hybrid cyclone activity could increase close to the coast, while the associated rainfall and wind are projected to increase.
Disturbance Extraction for Burst Detection in Water Distribution Networks Using Pressure Measurements
Authors: Xu Weirong , Zhou Xiao , Xin Kunlun , Boxall Joby , Yan Hexiang , Tao Tao
Published: March 2020

Pipe bursts in water distribution networks cause considerable water losses and lead to potential environmental hazards. Effective burst detection methods enable water companies to repair broken pipes in a timely manner and minimize damage and disruption. A data‐driven detection method is developed and proven for real‐time leak and burst detection in water distribution networks. The method uses a unique integration of disturbance extraction and isolation forest techniques to enable detection of subtle burst signals from normally noisy pressure data. Verification and validation progress from synthetic data to the application to real‐life data from large‐scale open networks. The method is shown to generate comparable levels of detection, with low false positive rates, to other published techniques but without the need to introduce closed valves and expensive flow meters of district meter area structures and the loss of resilience these cause. The method offers the potential to effectively detect bursts from pressure data alone, helping to better manage the distribution of increasingly stressed water resources through aging pipe networks.
Comprehensive review of targeted therapy for colorectal cancer
Authors: Xie Yuan-Hong , Chen Ying-Xuan , Fang Jing-Yuan
Published: March 2020

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world and was responsible for nearly 881,000 cancer-related deaths in 2018. Surgery and chemotherapy have long been the first choices for cancer patients. However, the prognosis of CRC has never been satisfying, especially for patients with metastatic lesions. Targeted therapy is a new optional approach that has successfully prolonged overall survival for CRC patients. Following successes with the anti-EGFR (epidermal growth factor receptor) agent cetuximab and the anti-angiogenesis agent bevacizumab, new agents blocking different critical pathways as well as immune checkpoints are emerging at an unprecedented rate. Guidelines worldwide are currently updating the recommended targeted drugs on the basis of the increasing number of high-quality clinical trials. This review provides an overview of existing CRC-targeted agents and their underlying mechanisms, as well as a discussion of their limitations and future trends.
Treosulfan–fludarabine–thiotepa-based conditioning treatment before allogeneic hematopoietic stem cell transplantation for pediatric patients with hematological malignancies
Authors: Kalwak Krzysztof , Mielcarek Monika , Patrick Katharine , Styczynski Jan , Bader Peter , Corbacioglu Selim , Burkhardt Birgit , Sykora Karl Walter , Drabko Katarzyna , Gozdzik Jolanta , Fagioli Franca , Greil Johann , Gruhn Bernd , Beier Rita , Locatelli Franco , Müller Ingo , Schlegel Paul Gerhardt , Sedlacek Petr , Stachel Klaus Daniel , Hemmelmann Claudia , Möller Ann-Kristin , Baumgart Joachim , Vora Ajay
Published: March 2020

Treosulfan-based conditioning prior to allogeneic transplantation has been shown to have myeloablative, immunosuppressive, and antineoplastic effects associated with reduced non-relapse mortality (NRM) in adults. Therefore, we prospectively evaluated the safety and efficacy of treosulfan-based conditioning in children with hematological malignancies in this phase II trial. Overall, 65 children with acute lymphoblastic leukemia (35.4%), acute myeloid leukemia (44.6%), myelodysplastic syndrome (15.4%), or juvenile myelomonocytic leukemia (4.6%) received treosulfan intravenously at a dose of 10 mg/m2/day (7.7%), 12 g/m2/day (35.4%), or 14 g/m2/day (56.9%) according to their individual body surface area in combination with fludarabine and thiotepa. The incidence of complete donor chimerism at day +28 was 98.4% with no primary and only one secondary graft failure. At 36 months, NRM was only 3.1%, while relapse incidence was 21.7%, and overall survival was 83.0%. The cumulative incidence of acute graft-vs.-host disease was 45.3% for grades I–IV and 26.6% for grades II–IV. At 36 months, 25.8% overall and 19.4% moderate/severe chronic graft-vs.-host disease were reported. These data confirm the safe and effective use of treosulfan-based conditioning in pediatric patients with hematological malignancies. Therefore, treosulfan/fludarabine/thiotepa can be recommended for myeloablative conditioning in children with hematological malignancies.
An injectable photopolymerized hydrogel with antimicrobial and biocompatible properties for infected skin regeneration
Authors: Sun Ao , He Xinye , Li Lang , Li Tao , Liu Qinya , Zhou Xinli , Ji Xiao , Li Wei , Qian Zhiyong
Published: March 2020

Currently, wound infection is an important health problem for the public. Wound infection can not only hinder healing but it can also lead to serious complications. Injectable wound dressings with biocompatible and antibacterial properties can promote wound healing during skin infections and reduce antibiotic use. Here, we used glycidyl methacrylate (GMA) to modify ε-polylysine (ε-PL) and γ-poly(glutamic acid) (γ-PGA) to produce ε-polylysine-glycidyl methacrylate (ε-PL-GMA) and γ-poly(glutamic acid)-glycidyl methacrylate (γ-PGA-GMA). Subsequently, ε-PL-GMA- and γ-PGA-GMA-based hydrogels were developed through photopolymerization using visible light. The hydrogels were injectable, could rapidly gelatinize, were biocompatible, and showed a wide spectrum of antibacterial activity. The hydrogels also promoted wound healing. The results show that these hydrogels inhibit bacterial infection and shorten the wound healing time of skin defects in Staphylococcus aureus models. This demonstrates that the hydrogels hold potential for clinical antimicrobial and wound healing therapy.
Post-translational coordination of chlorophyll biosynthesis and breakdown by BCMs maintains chlorophyll homeostasis during leaf development
Authors: Wang Peng , Richter Andreas S. , Kleeberg Julius R. W. , Geimer Stefan , Grimm Bernhard
Published: March 2020

Chlorophyll is indispensable for life on Earth. Dynamic control of chlorophyll level, determined by the relative rates of chlorophyll anabolism and catabolism, ensures optimal photosynthesis and plant fitness. How plants post-translationally coordinate these two antagonistic pathways during their lifespan remains enigmatic. Here, we show that two Arabidopsis paralogs of BALANCE of CHLOROPHYLL METABOLISM (BCM) act as functionally conserved scaffold proteins to regulate the trade-off between chlorophyll synthesis and breakdown. During early leaf development, BCM1 interacts with GENOMES UNCOUPLED 4 to stimulate Mg-chelatase activity, thus optimizing chlorophyll synthesis. Meanwhile, BCM1’s interaction with Mg-dechelatase promotes degradation of the latter, thereby preventing chlorophyll degradation. At the onset of leaf senescence, BCM2 is up-regulated relative to BCM1, and plays a conserved role in attenuating chlorophyll degradation. These results support a model in which post-translational regulators promote chlorophyll homeostasis by adjusting the balance between chlorophyll biosynthesis and breakdown during leaf development.
Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
Authors: von Roemeling Christina A. , Wang Yifan , Qie Yaqing , Yuan Hengfeng , Zhao Hai , Liu Xiujie , Yang Zhaogang , Yang Mingming , Deng Weiye , Bruno Katelyn A. , Chan Charles K. , Lee Andrew S. , Rosenfeld Stephen S. , Yun Kyuson , Johnson Aaron J. , Mitchell Duane A. , Jiang Wen , Kim Betty Y. S.
Published: March 2020

Tumour cell phagocytosis by antigen presenting cells (APCs) is critical to the generation of antitumour immunity. However, cancer cells can evade phagocytosis by upregulating anti-phagocytosis molecule CD47. Here, we show that CD47 blockade alone is inefficient in stimulating glioma cell phagocytosis. However, combining CD47 blockade with temozolomide results in a significant pro-phagocytosis effect due to the latter’s ability to induce endoplasmic reticulum stress response. Increased tumour cell phagocytosis subsequently enhances antigen cross-presentation and activation of cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) in APCs, resulting in more efficient T cell priming. This bridging of innate and adaptive responses inhibits glioma growth, but also activates immune checkpoint. Sequential administration of an anti-PD1 antibody overcomes this potential adaptive resistance. Together, these findings reveal a dynamic relationship between innate and adaptive immune regulation in tumours and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.
Toward a generalized Bienenstock-Cooper-Munro rule for spatiotemporal learning via triplet-STDP in memristive devices
Authors: Wang Zhongqiang , Zeng Tao , Ren Yanyun , Lin Ya , Xu Haiyang , Zhao Xiaoning , Liu Yichun , Ielmini Daniele
Published: March 2020

The close replication of synaptic functions is an important objective for achieving a highly realistic memristor-based cognitive computation. The emulation of neurobiological learning rules may allow the development of neuromorphic systems that continuously learn without supervision. In this work, the Bienenstock-Cooper-Munro learning rule, as a typical case of spike-rate-dependent plasticity, is mimicked using a generalized triplet-spike-timing-dependent plasticity scheme in a WO3−x memristive synapse. It demonstrates both presynaptic and postsynaptic activities and remedies the absence of the enhanced depression effect in the depression region, allowing a better description of the biological counterpart. The threshold sliding effect of Bienenstock-Cooper-Munro rule is realized using a history-dependent property of the second-order memristor. Rate-based orientation selectivity is demonstrated in a simulated feedforward memristive network with this generalized Bienenstock-Cooper-Munro framework. These findings provide a feasible approach for mimicking Bienenstock-Cooper-Munro learning rules in memristors, and support the applications of spatiotemporal coding and learning using memristive networks.
Single-molecule imaging reveals molecular coupling between transcription and DNA repair machinery in live cells
Authors: Ho Han Ngoc , van Oijen Antoine M. , Ghodke Harshad
Published: March 2020

The Escherichia coli transcription-repair coupling factor Mfd displaces stalled RNA polymerase and delivers the stall site to the nucleotide excision repair factors UvrAB for damage detection. Whether this handoff from RNA polymerase to UvrA occurs via the Mfd-UvrA2-UvrB complex or alternate reaction intermediates in cells remains unclear. Here, we visualise Mfd in actively growing cells and determine the catalytic requirements for faithful recruitment of nucleotide excision repair proteins. We find that ATP hydrolysis by UvrA governs formation and disassembly of the Mfd-UvrA2 complex. Further, Mfd-UvrA2-UvrB complexes formed by UvrB mutants deficient in DNA loading and damage recognition are impaired in successful handoff. Our single-molecule dissection of interactions of Mfd with its partner proteins inside live cells shows that the dissociation of Mfd is tightly coupled to successful loading of UvrB, providing a mechanism via which loading of UvrB occurs in a strand-specific manner.
500 microkelvin nanoelectronics
Authors: Sarsby Matthew , Yurttagül Nikolai , Geresdi Attila
Published: March 2020

Fragile quantum effects such as single electron charging in quantum dots or macroscopic coherent tunneling in superconducting junctions are the basis of modern quantum technologies. These phenomena can only be observed in devices where the characteristic spacing between energy levels exceeds the thermal energy, kBT, demanding effective refrigeration techniques for nanoscale electronic devices. Commercially available dilution refrigerators have enabled typical electron temperatures in the 10 to 100 mK regime, however indirect cooling of nanodevices becomes inefficient due to stray radiofrequency heating and weak thermal coupling of electrons to the device substrate. Here, we report on passing the millikelvin barrier for a nanoelectronic device. Using a combination of on-chip and off-chip nuclear refrigeration, we reach an ultimate electron temperature of Te = 421 ± 35 μK and a hold time exceeding 85 h below 700 μK measured by a self-calibrated Coulomb-blockade thermometer.
Polycyclic aromatic chains on metals and insulating layers by repetitive [3+2] cycloadditions
Authors: Riss Alexander , Richter Marcus , Paz Alejandro Pérez , Wang Xiao-Ye , Raju Rajesh , He Yuanqin , Ducke Jacob , Corral Eduardo , Wuttke Michael , Seufert Knud , Garnica Manuela , Rubio Angel , V. Barth Johannes , Narita Akimitsu , Müllen Klaus , Berger Reinhard , Feng Xinliang , Palma Carlos-Andres , Auwärter Willi
Published: March 2020

The vast potential of organic materials for electronic, optoelectronic and spintronic devices entails substantial interest in the fabrication of π-conjugated systems with tailored functionality directly at insulating interfaces. On-surface fabrication of such materials on non-metal surfaces remains to be demonstrated with high yield and selectivity. Here we present the synthesis of polyaromatic chains on metallic substrates, insulating layers, and in the solid state. Scanning probe microscopy shows the formation of azaullazine repeating units on Au(111), Ag(111), and h-BN/Cu(111), stemming from intermolecular homo-coupling via cycloaddition reactions of CN-substituted polycyclic aromatic azomethine ylide (PAMY) intermediates followed by subsequent dehydrogenation. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry demonstrates that the reaction also takes place in the solid state in the absence of any catalyst. Such intermolecular cycloaddition reactions are promising methods for direct synthesis of regioregular polyaromatic polymers on arbitrary insulating surfaces.
Molecular vibrations reduce the maximum achievable photovoltage in organic solar cells
Authors: Panhans Michel , Hutsch Sebastian , Benduhn Johannes , Schellhammer Karl Sebastian , Nikolis Vasileios C. , Vangerven Tim , Vandewal Koen , Ortmann Frank
Published: March 2020

The low-energy edge of optical absorption spectra is critical for the performance of solar cells, but is not well understood in the case of organic solar cells (OSCs). We study the microscopic origin of exciton bands in molecular blends and investigate their role in OSCs. We simulate the temperature dependence of the excitonic density of states and low-energy absorption features, including low-frequency molecular vibrations and multi-exciton hybridisation. For model donor-acceptor blends featuring charge-transfer excitons, our simulations agree very well with temperature-dependent experimental absorption spectra. We unveil that the quantum effect of zero-point vibrations, mediated by electron-phonon interaction, causes a substantial exciton bandwidth and reduces the open-circuit voltage, which is predicted from electronic and vibronic molecular parameters. This effect is surprisingly strong at room temperature and can substantially limit the OSC’s efficiency. Strategies to reduce these vibration-induced voltage losses are discussed for a larger set of systems and different heterojunction geometries.
Chromosome organization by a conserved condensin-ParB system in the actinobacterium Corynebacterium glutamicum
Authors: Böhm Kati , Giacomelli Giacomo , Schmidt Andreas , Imhof Axel , Koszul Romain , Marbouty Martial , Bramkamp Marc
Published: March 2020

Higher-order chromosome folding and segregation are tightly regulated in all domains of life. In bacteria, details on nucleoid organization regulatory mechanisms and function remain poorly characterized, especially in non-model species. Here, we investigate the role of DNA-partitioning protein ParB and SMC condensin complexes in the actinobacterium Corynebacterium glutamicum. Chromosome conformation capture reveals SMC-mediated long-range interactions around ten centromere-like parS sites clustered at the replication origin (oriC). At least one oriC-proximal parS site is necessary for reliable chromosome segregation. We use chromatin immunoprecipitation and photoactivated single-molecule localization microscopy to show the formation of distinct, parS-dependent ParB-nucleoprotein subclusters. We further show that SMC/ScpAB complexes, loaded via ParB at parS sites, mediate chromosomal inter-arm contacts (as previously shown in Bacillus subtilis). However, the MukBEF-like SMC complex MksBEFG does not contribute to chromosomal DNA-folding; instead, this complex is involved in plasmid maintenance and interacts with the polar oriC-tethering factor DivIVA. Our results complement current models of ParB-SMC/ScpAB crosstalk and show that some condensin complexes evolved functions that are apparently uncoupled from chromosome folding.
Playing games with multiple access channels
Authors: Leditzky Felix , Alhejji Mohammad A. , Levin Joshua , Smith Graeme
Published: March 2020

Communication networks have multiple users, each sending and receiving messages. A multiple access channel (MAC) models multiple senders transmitting to a single receiver, such as the uplink from many mobile phones to a single base station. The optimal performance of a MAC is quantified by a capacity region of simultaneously achievable communication rates. We study the two-sender classical MAC, the simplest and best-understood network, and find a surprising richness in both a classical and quantum context. First, we find that quantum entanglement shared between senders can substantially boost the capacity of a classical MAC. Second, we find that optimal performance of a MAC with bounded-size inputs may require unbounded amounts of entanglement. Third, determining whether a perfect communication rate is achievable using finite-dimensional entanglement is undecidable. Finally, we show that evaluating the capacity region of a two-sender classical MAC is in fact NP-hard.
Distinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes
Authors: Kraus Amelie J. , Vanselow Jens T. , Lamer Stephanie , Brink Benedikt G. , Schlosser Andreas , Siegel T. Nicolai
Published: March 2020

Despite histone H2A variants and acetylation of histones occurring in almost every eukaryotic organism, it has been difficult to establish direct functional links between canonical histones or H2A variant acetylation, deposition of H2A variants and transcription. To disentangle these complex interdependent processes, we devised a highly sensitive strategy for quantifying histone acetylation levels at specific genomic loci. Taking advantage of the unusual genome organization inTrypanosoma brucei, we identified 58 histone modifications enriched at transcription start sites (TSSs). Furthermore, we found TSS-associated H4 and H2A.Z acetylation to be mediated by two different histone acetyltransferases, HAT2 and HAT1, respectively. Whereas depletion of HAT2 decreases H2A.Z deposition and shifts the site of transcription initiation, depletion of HAT1 does not affect H2A.Z deposition but reduces total mRNA levels by 50%. Thus, specifically reducing H4 or H2A.Z acetylation levels enabled us to reveal distinct roles for these modifications in H2A.Z deposition and RNA transcription.
Machine learning for cluster analysis of localization microscopy data
Authors: Williamson David J. , Burn Garth L. , Simoncelli Sabrina , Griffié Juliette , Peters Ruby , Davis Daniel M. , Owen Dylan M.
Published: March 2020

Quantifying the extent to which points are clustered in single-molecule localization microscopy data is vital to understanding the spatial relationships between molecules in the underlying sample. Many existing computational approaches are limited in their ability to process large-scale data sets, to deal effectively with sample heterogeneity, or require subjective user-defined analysis parameters. Here, we develop a supervised machine-learning approach to cluster analysis which is fast and accurate. Trained on a variety of simulated clustered data, the neural network can classify millions of points from a typical single-molecule localization microscopy data set, with the potential to include additional classifiers to describe different subtypes of clusters. The output can be further refined for the measurement of cluster area, shape, and point-density. We demonstrate this approach on simulated data and experimental data of the kinase Csk and the adaptor PAG in primary human T cell immunological synapses.
Reproductive tract extracellular vesicles are sufficient to transmit intergenerational stress and program neurodevelopment
Authors: Chan Jennifer C. , Morgan Christopher P. , Adrian Leu N. , Shetty Amol , Cisse Yasmine M. , Nugent Bridget M. , Morrison Kathleen E. , Jašarević Eldin , Huang Weiliang , Kanyuch Nickole , Rodgers Ali B. , Bhanu Natarajan V. , Berger Dara S. , Garcia Benjamin A. , Ament Seth , Kane Maureen , Neill Epperson C. , Bale Tracy L.
Published: March 2020

Extracellular vesicles (EVs) are a unique mode of intercellular communication capable of incredible specificity in transmitting signals involved in cellular function, including germ cell maturation. Spermatogenesis occurs in the testes, behind a protective barrier to ensure safeguarding of germline DNA from environmental insults. Following DNA compaction, further sperm maturation occurs in the epididymis. Here, we report reproductive tract EVs transmit information regarding stress in the paternal environment to sperm, potentially altering fetal development. Using intracytoplasmic sperm injection, we found that sperm incubated with EVs collected from stress-treated epididymal epithelial cells produced offspring with altered neurodevelopment and adult stress reactivity. Proteomic and transcriptomic assessment of these EVs showed dramatic changes in protein and miRNA content long after stress treatment had ended, supporting a lasting programmatic change in response to chronic stress. Thus, EVs as a normal process in sperm maturation, can also perform roles in intergenerational transmission of paternal environmental experience.
The ribosome-associated complex RAC serves in a relay that directs nascent chains to Ssb
Authors: Zhang Ying , Valentín Gesé Genís , Conz Charlotte , Lapouge Karine , Kopp Jürgen , Wölfle Tina , Rospert Sabine , Sinning Irmgard
Published: March 2020

The conserved ribosome-associated complex (RAC) consisting of Zuo1 (Hsp40) and Ssz1 (non-canonical Hsp70) acts together with the ribosome-bound Hsp70 chaperone Ssb in de novo protein folding at the ribosomal tunnel exit. Current models suggest that the function of Ssz1 is confined to the support of Zuo1, however, it is not known whether RAC by itself serves as a chaperone for nascent chains. Here we show that, via its rudimentary substrate binding domain (SBD), Ssz1 directly binds to emerging nascent chains prior to Ssb. Structural and biochemical analyses identify a conserved LP-motif at the Zuo1 N-terminus forming a polyproline-II helix, which binds to the Ssz1-SBD as a pseudo-substrate. The LP-motif competes with nascent chain binding to the Ssz1-SBD and modulates nascent chain transfer. The combined data indicate that Ssz1 is an active chaperone optimized for transient, low-affinity substrate binding, which ensures the flux of nascent chains through RAC/Ssb.
Highly selective phonon diffusive scattering in superionic layered AgCrSe2
Authors: Wang Chen , Chen Yue
Published: March 2020

Superionic materials that exhibit coexistence of rigid crystalline lattices and liquid-like fluctuating substructures have emerged as promising thermoelectric materials. The inadequate understanding of the phonon behavior in the superionic state, however, still prevents further revealing of the underlying correlation between the thermally induced liquid-like atomic dynamics and anomalous thermal transport properties. Herein, by adopting a hybrid scheme to directly characterize anharmonic phonon quasiparticles from ab-initio molecular dynamics, we manifest that low-energy transverse phonons dominated by Ag atoms totally collapse, whereas longitudinal optical phonons remain largely intact during the superionic transition. The ultralow thermal conductivity originates from the atomic level structural heterogeneity can be ultimately attributed to diffusive phonon dynamics. Our study also reveals that the extremely large selective phonon diffusive scattering can be counteracted by hydrostatic pressure induced deactivation of the liquid-like flow of Ag atoms. These results demonstrate the decisive role of ion superionicity in phonon scattering across superionic transition and may pave the way for new phonon engineering strategies in related superionic materials.
CD4+ Th immunogenicity of the Ascaris spp. secreted products
Authors: Ebner Friederike , Morrison Eliot , Bertazzon Miriam , Midha Ankur , Hartmann Susanne , Freund Christian , Álvaro-Benito Miguel
Published: March 2020

Ascaris spp. is a major health problem of humans and animals alike, and understanding the immunogenicity of its antigens is required for developing urgently needed vaccines. The parasite-secreted products represent the most relevant, yet complex (>250 proteins) antigens ofAscaris spp. as defining the pathogen-host interplay. We applied an in vitro antigen processing system coupled to quantitative proteomics to identify potential CD4+Thcell epitopes inAscaris-secreted products. This approach considerably restricts the theoretical list of epitopes using conventional CD4+Thcell epitope prediction tools. We demonstrate the specificity and utility of our approach on two sets of candidate lists, allowing us identifying hits excluded by either one or both computational methods. More importantly, one of the candidates identified experimentally, clearly demonstrates the presence of pathogen-reactive T cells in healthy human individuals against these antigens. Thus, our work pipeline identifies the first human T cell epitope againstAscaris spp. and represents an easily adaptable platform for characterization of complex antigens, in particular for those pathogens that are not easily amenable for in vivo experimental validation.
The distinctive structure and composition of arterial and venous thrombi and pulmonary emboli
Authors: Chernysh Irina N. , Nagaswami Chandrasekaran , Kosolapova Sofia , Peshkova Alina D. , Cuker Adam , Cines Douglas B. , Cambor Carolyn L. , Litvinov Rustem I. , Weisel John W.
Published: March 2020

Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo. Polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. The structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro. There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders.
The X-Ray Emission Effectiveness of Plasma Mirrors: Reexamining Power-Law Scaling for Relativistic High-Order Harmonic Generation
Authors: Edwards Matthew R. , Mikhailova Julia M.
Published: March 2020

Ultrashort pulsed lasers provide uniquely detailed access to the ultrafast dynamics of physical, chemical, and biological systems, but only a handful of wavelengths are directly produced by solid-state lasers, necessitating efficient high-power frequency conversion. Relativistic plasma mirrors generate broadband power-law spectra, that may span the gap between petawatt-class infrared laser facilities and x-ray free-electron lasers; despite substantial theoretical work the ultimate efficiency of this relativistic high-order-harmonic generation remains unclear. We show that the coherent radiation emitted by plasma mirrors follows a power-law distribution of energy over frequency with an exponent that, even in the ultrarelativistic limit, strongly depends on the ratio of laser intensity to plasma density and exceeds the frequently quoted value of  −8/3 over a wide range of parameters. The coherent synchrotron emission model, when adequately corrected for the finite width of emitting electron bunches, is not just valid for p-polarized light and thin foil targets, but generally describes relativistic harmonic generation, including at normal incidence and with finite-gradient plasmas. Our numerical results support the ω−4/3 scaling of the synchrotron emission model as a limiting efficiency of the process under most conditions. The highest frequencies that can be generated with this scaling are usually restricted by the width of the emitting electron bunch rather than the Lorentz factor of the fastest electrons. The theoretical scaling relations developed here suggest, for example, that with a 20-PW 800-nm driving laser, 1 TW/harmonic can be produced for 1-keV photons.
Association of induced abortion with hypertensive disorders of pregnancy risk among nulliparous women in China: a prospective cohort study
Authors: Su Yinhua , Xie Xiaoping , Zhou Yanfang , Lin Hong , Li Yamei , Feng Na , Luo Jiayou
Published: March 2020

The relationship between induced abortion(IA) and hypertensive disorders of pregnancy(HDP) is inconclusive. Few studies have been conducted in China. In order to clarify the association between previous IA and risk of HDP, including gestational hypertension(GH) and pre-eclampsia(PE), we performed a community-based prospective cohort study enrolling 5191 eligible nulliparous women in selected 2 districts and 11 towns of Liuyang from 2013 to 2015. Multivariable logistic regression was conducted to examine whether IA was associated with HDP, GH and PE. Of the gravidea, 1378(26.5%) had a previous IA and 258(5.0%) diagnosed with HDP, including 141(2.7%) GH and 117(2.3%) PE. The difference in the incidence of GH and PE between gravidae having one versus those with two or more IAs was minimal. After adjustment for maternal age, body mass index at first antenatal visit, education, virus infection and history of medical disorders, previous IA was significantly associated with HDP (OR = 0.67, 95%CI = 0.49 to 0.91) and PE (OR = 0.61, 95%CI = 0.38 to 0.97), but not with GH (OR = 0.73, 95%CI = 0.49 to 1.10). Additional adjustment for occupation, living area, anemia, gestational diabetes mellitus, psychological stress, conception climate and infant sex, multivariable analysis provided similar results. In conclusion, previous IA was associated with a lower risk of PE among nulliparous women.