bluuebunny/crossref_metadata_2025 huggingface dataset:
Body-force and mean-line models for the generation of axial compressor sub-idle characteristics
Authors: Righi M. , Ferrer-Vidal L.E. , Pachidis V.
Published: July 2020

This paper describes the application of low-order models to the prediction of the steady performance of axial compressors at sub-idle conditions. An Euler body-force method employing sub-idle performance correlations is developed and presented alongside a mean-line approach employing the same set of correlations. The low-order tools are used to generate the characteristic lines of the compressor in the locked-rotor and zero-torque windmilling conditions. The results are compared against steady-state operating points from three-dimensional (3D) Reynolds-averaged Navier–Stokes (RANS) computational fluid dynamics (CFD) simulations. The accuracy of the low-order tools in reproducing the results from high-fidelity CFD is analysed, and the trade-off with the computational cost of each method is discussed. The low-order tools presented are shown to offer a fast alternative to traditional CFD which can be used to predict the performance in sub-idle conditions of a new compressor design during early development stages.
Implications for Conducting Special Education Research Drawn From the Reflexive Accounts of a Deaf With Disabilities Professor and Three Student Researchers
Authors: Singer Steven , Cacciato Kimberly , Kamenakis Julianna , Shapiro Allison
Published: July 2020

A Deaf with disabilities (DWD) male professor, 2 hearing female teacher candidates, 11 parents (4 of whom were immigrants), and 6 DWD children sought to better understand the experiences of parents of DWD children by conducting an ethnographic study (Singer, Kamenakis, Shapiro, & Cacciato, in press). The research team recorded reflexive journals as a way to analyse their methodology. In this essay, we reflect on 3 themes developed from the reflexive journals: (a) researcher positionality, (b) negotiating power in research, and (c) language variation in practice. We discuss our experiences and contextualise these accounts within relevant scholarship, attempting to locate some amount of resolution to the very human experiences upon which we reflect. We provide key takeaways for doing research with and among people with disabilities in special educational settings, particularly focusing on people who communicate in nonnormative ways. We conclude with a culminating discussion of the significance of creating emancipatory special education research.
Quantification of damages for non-pecuniary losses deriving from breach of contract
Authors: Zlatev Zlatin
Published: July 2020

The existing principles of quantification of damages for non-pecuniary losses deriving from breach of contract which are adopted by the courts or advanced in the legal scholarship appear to be arbitrary and founded on certain misconceptions. This paper proposes three different models for assessment based on the consequences of breach. When the performance is possible after the breach, the damages are equal to the value of an alternative subject matter if such is available from elsewhere. If there are no other sources from where the bargained-for subject matter can be obtained, then the amount of the damages is based on the value of a substitutive benefit which leads to attainment of the initial contractual aim. If the promisee has no interest in delayed performance, the damages are quantified with respect to a different non-pecuniary benefit which is commensurable to the one that was pursued with the contract initially.
The Two Faces of Party Ambiguity: A Comprehensive Model of Ambiguous Party Position Perceptions
Authors: Nyhuis Dominic , Stoetzer Lukas F.
Published: July 2020

Recent research on electoral behavior has suggested that policy-informed vote choices are frequently obstructed by uncertainty about party positions. Given the significance of clear and distinct party platforms for meaningful representation, several studies have investigated the conditions under which parties are perceived as ambiguous. Yet previous studies have often relied on measures of perceived positional ambiguity that are fairly remote from the concept, casting doubt on their substantive conclusions. This article introduces a statistical model to estimate a comprehensive measure of perceived ambiguity that incorporates the two principal factors: non-positions and positional inconsistency. The two-faces model employs issue perceptions in an item response framework to explicitly parametrize the perceived ambiguity of party positions. The model is applied to data from the Chapel Hill Expert Survey and subsequently associated with party characteristics that drive perceptions of party ambiguity. The results suggest that (a) there are notable differences between the proposed and competing measures, highlighting the need to be mindful of the intricacies of political information processing in research on perceptions of ambiguity and (b) involuntary ambiguity might be an underexplored explanation for unclear party perceptions.
Divided by the Vote: Affective Polarization in the Wake of the Brexit Referendum
Authors: Hobolt Sara B. , Leeper Thomas J. , Tilley James
Published: July 2020

A well-functioning democracy requires a degree of mutual respect and a willingness to talk across political divides. Yet numerous studies have shown that many electorates are polarized along partisan lines, with animosity towards the partisan out-group. This article further develops the idea of affective polarization, not by partisanship, but instead by identification with opinion-based groups. Examining social identities formed during Britain's 2016 referendum on European Union membership, the study uses surveys and experiments to measure the intensity of partisan and Brexit-related affective polarization. The results show that Brexit identities are prevalent, felt to be personally important and cut across traditional party lines. These identities generate affective polarization as intense as that of partisanship in terms of stereotyping, prejudice and various evaluative biases, convincingly demonstrating that affective polarization can emerge from identities beyond partisanship.
An Examination of the Relevance of the Codification and Application of the American Business Judgment Rule to Nigerian Corporate Law
Authors: Ubochioma Wiseman
Published: July 2020

The business judgment rule is an ancient doctrine that was developed in the US. It seeks to prevent courts from reviewing directors’ decisions, on the basis that directors have the capacity and expertise to make business decisions. This article examines the desirability of applying the US business judgment rule in Nigeria. Through a comparative analysis, it argues that the peculiarities of Nigeria's corporate law and environment do not justify the application of the rule. More specifically, it contends that differences in the legal regime for derivative suits, standards of duty of care and skill, corporate law culture, and the distinct epoch in which the business judgment rule and the duty of care and skill were recognized in the US, make its application unnecessary in Nigeria. It concludes that the current statutory duty of care and skill should be retained to hold directors accountable for reckless business decisions.
Gender, sexual experiences and sexual behavioural differences in Turkish university students
Authors: Nazik Feyza , Omaç Sönmez Mehtap , Akben Mine
Published: July 2020

This study was conducted to determine sexual experiences and gender differences in sexual behaviour in university students. In this cross-sectional and descriptive study conducted between 1st February and 12th November 2017. A total of 491 volunteer students were selected at a state university in the Mediterranean region of Turkey using a systematic sampling method. Questionnaires were distributed to the students in sealed envelopes and collected on completion. The data were collected using a socio-demographic form and a sexual experiences and sexual health behaviours form. A total of 414 students (78 males; 336 females) were included in this study. The prevalence of sexual intercourse among these was 4.3%, and total oral and anal sex experiences were 35% and 16.7%, respectively. A significantly higher number of female students of those who reported having sexual intercourse (n = 9; 50.0%), oral sex (n = 81; 55.9%) and anal sex (n = 60; 87.0%), also reported not telling anyone about his/her partner (77.2%), not talking about sex (82.4%) and not buying contraceptive products, even when necessary (78.3%). Hidden sexuality was seen to affect female students more often and this may lead to risky sexual behaviours, sexually transmitted diseases, an unhealthy sexual life with multiple partners and even unplanned, unwanted pregnancies.
Whole Person, Whole Journey: Developing a Person-Centred Regional Dementia Strategy
Authors: Stolee Paul , Ashbourne Jessica , Elliott Jacobi , Main Sarah , Holland Nicole , Edick Cole , Ropp Courtney , Tong Catherine , Bodemer Sheila
Published: July 2020

We present the development of a regional dementia strategy in Southwestern Ontario, Canada. We worked with stakeholders in a regional health authority to develop a dementia strategy. We conducted interviews with persons with dementia and their care partners (n = 26) and health care administrators and policy makers (n = 33); and administered a priority-setting survey (n = 64). Both participant groups identified provider compassion, professionalism, and care in the early stages of dementia as system strengths. Both groups also highlighted a need for more integration and coordination, a need for more person-centred care, support for care partners, and more flexibility in the provision and receipt of services. The highest-ranked priorities were improving care partner support, improving access to care, and improving system-wide quality. We integrate these strengths, needs, and priorities in a strategic framework, “Whole Person, Whole Journey”. Organizations developing a dementia strategy may use this framework as a springboard for their own work.
T. J. Woofter Jr. and Government Social Science Research During the New Deal, World War II, and the Cold War
Authors: ELLIS MARK
Published: July 2020

The work of southern sociologist Thomas Jackson Woofter Jr. (1893–1972) is frequently cited by American historians, but his contribution to government policy on agriculture in the New Deal, Social Security in the 1940s, and demography in the Cold War remains underappreciated. He left the University of North Carolina to direct government research on rural relief in the 1930s, Social Security enhancement during and after World War II, and foreign population and manpower projections during the Cold War. Contributing to the delivery of essential programs in key agencies, he participated in internal and external debates over policy and social attitudes between 1930 and 1960. Woofter worked for the Federal Emergency Relief Administration, the Works Progress Administration, the Farm Security Agency, the Federal Security Agency, and the Central Intelligence Agency, improving data-gathering and assisting transitions in federal policymaking. This article assesses his role in those agencies, using official records, other primary materials, and secondary sources.
Privatizing Employment Law: The Expansion of Mandatory Arbitration in the Workplace
Authors: Staszak Sarah
Published: July 2020

This article examines the institutional, political, and legal development of employment arbitration as it shifted from a Progressive Era form of justice enhancement to one co-opted by business-friendly conservatives arguably more concerned with protecting employers from litigation. While arbitration has a long history in the United States, the expanding use of mandatory, employer-promulgated arbitration clauses has more than doubled since the 2000s. In examining the nature of the shift, this article argues that it occurred through a gradual process of conversion in three institutional realms (1) legislative conversion, (2) private-sector conversion of public regulation, and (3) judicial conversion. Facilitated by a growing divide among Democrats on the value of arbitration, conservatives began to promote it in the 1970s and 1980s as backlash to the expansion of statutory employment rights. I argue that they did so by converting the institutional infrastructures of labor and commercial arbitration, a process continued by the private sector and Supreme Court. As such, this article argues that conversion is the product of multiple actors targeting multiple institutions, over decades, and with consequences for both the literature on institutional change and conceptions of equality under the law.
Cognitive behavioural therapy for co-morbid anxiety and depression in heart failure: a case report
Authors: Slaughter Charlotte , Allen Chris
Published: July 2020

Heart failure increases the likelihood of an individual experiencing co-morbid anxiety and depression, which can affect their physical as well as mental health. There is a need to develop non-pharmacological interventions for the psychological consequences of heart failure. Evidence shows that cognitive behavioural therapy (CBT) can be helpful, but there is less clarity about CBT’s effectiveness for people with heart failure who have complex multi-morbid difficulties.

This paper presents a case report of a man with heart failure. He was part of a research trial for cardiac resynchronisation therapy with defibrillation (CRT-D), after other physical procedures had been unsuccessful, and was experiencing severe anxiety and moderately severe depression. The intervention used was based on transdiagnostic CBT, provided at home over six sessions. Self-report measures were completed at each session and at 3-month follow-up. A measure of his use of clinical services was also carried out at pre-, post- and 3-month follow up. Post-intervention, the client showed non-clinical levels of depression and anxiety and these improvements were maintained at 3 months. Use of clinical services also reduced, with fewer admissions to hospital and fewer visits by specialist nurses and GPs.

This case suggests that CBT, and particularly transdiagnostic CBT, can be helpful in reducing anxiety and depression in people with heart failure. Further work evaluating the impact on quality of life and the utility of this approach with a wider group of people with heart failure and psychological distress would be advantageous.

Key learning aims

(1)

Depression and anxiety are prevalent in people with heart failure.

(2)

Cognitive behavioural therapy can be an effective intervention for reducing depression and anxiety in people living with heart failure.

(3)

There are benefits to integrating care with this population because they present with interlinked physical and psychological needs.
Towards a model of uncertainty distress in the context of Coronavirus (COVID-19)
Authors: Freeston Mark , Tiplady Ashley , Mawn Lauren , Bottesi Gioia , Thwaites Sarah
Published: July 2020

The paper forms part of a series of papers outlining the theoretical framework for a new model of uncertainty distress (this paper), treatment implications arising from the model, and empirical tests of the model. We define uncertainty distress asthe subjective negative emotions experienced in response to the as yet unknown aspects of a given situation. In the first paper we draw on a robust body of research on distinct areas including: threat models of anxiety, perceived illness uncertainty and intolerance of uncertainty. We explore how threat and uncertainty are separable in anxiety and how we can understand behaviours in response to uncertainty. Finally, we propose a clinically, theoretically and empirically informed model for uncertainty distress, and outline how this model can be tested. Caveats, clinical applications and practitioner key points are briefly included, although these are more fully outlined in the treatment implications article. While we outline this model in the context of novel coronavirus (COVID-19), the model has broader applications to both mental and physical health care settings.

Key learning aims

(1)

To define the concept of uncertainty distress.

(2)

To understand the role of threat, over-estimation of threat, perceived uncertainty, actual uncertainty, and intolerance of uncertainty in distress maintenance.

(3)

To understand how people may behave in response to uncertainty distress.

(4)

To describe a model of uncertainty distress.
Magnetresonanztomographie der Leber
Authors: Stocker Daniel , Reiner Cäcilia
Published: July 2020

Zusammenfassung. Die Magnetresonanztomographie (MRI) der Leber spielt eine wichtige Rolle bei der Detektion und Charakterisierung fokaler und diffuser Lebererkrankungen und hat viele Vorteile gegenüber anderen bildgebenden Verfahren. Mit Hilfe einer MR-Untersuchung der Leber können die meisten benignen und malignen Läsionen detektiert und diagnostiziert werden. Neben der Evaluierung fokaler Leberläsionen haben sich in den letzten Jahren neue MR-Techniken zur nicht-invasiven Quantifizierung von Fett und Eisen in der Leber etabliert. Durch diese technischen Fortschritte wird eine akkurate Diagnose von fokalen als auch diffusen Lebererkrankungen ohne die Notwenigkeit einer Leberbiopsie möglich. Es ist jedoch wichtig, die richtigen Indikationen als auch die Kontraindikationen und Limitationen des MRI zu kennen. Der folgende Artikel gibt einen Überblick über die wichtigsten diagnostischen Möglichkeiten und Limitationen des Leber MRI als auch einen Ausblick auf neuartige Einsatzgebiete.
Increased Climate Response and Earth System Sensitivity From CCSM4 to CESM2 in Mid‐Pliocene Simulations
Authors: Feng Ran , Otto‐Bliesner Bette L. , Brady Esther C. , Rosenbloom Nan
Published: July 2020

Three new equilibrium mid‐Pliocene (MP) simulations are implemented with the Community Climate System Model version 4 (CCSM4) and Community Earth System Model versions 1.2 (CESM1.2) and 2 (CESM2). All simulations are carried out with the same boundary and forcing conditions following the protocol of Pliocene Model Intercomparison Project Phase 2 (PlioMIP2). These simulations reveal amplified MP climate change relative to the preindustrial going from CCSM4 to CESM2, seen in global and polar averages of surface warming, sea ice reduction in both the Arctic and the Antarctic, and weakened Hadley circulation. The enhanced global mean warming arises from enhanced Earth system sensitivity (ESS) to not only CO2change but also changes in boundary conditions primarily from vegetation and ice sheets. ESS is amplified by up to 70% in CCSM4 and up to 100% in CESM1.2 and CESM2 relative to the equilibrium climate sensitivity of respective models. Simulations disagree on several climate metrics. Different from CCSM4, both CESM1.2 and CESM2 show reduction of cloud cover, and weakened Walker circulation accompanied by an El Niño‐like mean state of the tropical Pacific in MP simulations relative to the preindustrial. This El Niño‐like mean state is consistent with paleo‐observational sea surface temperatures, suggesting an improvement upon CCSM4. The performances of MP simulations are assessed with a new compilation of observational MP sea surface temperature. The model‐data comparison suggests that CCSM4 is not sensitivity enough to the MP forcings, but CESM2 is likely too sensitive, especially in the tropics.
Five Things Spy Satellites Have Taught Us About Earth
Authors: Duncombe Jenessa
Published: July 2020

Long before we had satellites beaming terabytes of data back to Earth, we had covert spacecraft the size of school buses snapping photos on rolls of film 50 kilometers long.
Particle Simulation of the Generation of Plasmaspheric Hiss
Authors: Hikishima Mitsuru , Omura Yoshiharu , Summers Danny
Published: July 2020

We have conducted a one‐dimensional electromagnetic particle simulation with a parabolic magnetic field to reproduce whistler‐mode hiss emissions in the plasmasphere. We assume a bi‐Maxwellian distribution with temperature anisotropy for energetic electrons injected into the plasmasphere and find that hiss emissions are generated with spectrum characteristics typical of those observed by spacecraft near the magnetic equator. The hiss emissions contain fine structures involving rising tone and falling tone elements with variation in frequencies. The amplitude profile of the spectra agrees with the optimum wave amplitude derived from the nonlinear wave growth theory. The simulation demonstrates that hiss emissions are generated locally near the magnetic equator through linear and nonlinear interactions with energetic electrons with temperature anisotropy. The coherent hiss emissions efficiently scatter resonant electrons of 2.5–80 keV into the loss cone.
Technical Report—Methods: A Diagnostic Approach to Analyze the Direction of Change in Model Outputs Based on Global Variations in the Model Inputs
Authors: Wang Anqi , Pianosi Francesca , Wagener Thorsten
Published: July 2020

Hydrologic models are used to simulate natural phenomena while making different assumptions about the levels of complexity with which natural processes should be represented. Global Sensitivity Analysis is regularly applied to understand how the inputs (including forcing, parameters, and initial states) of these models control their outputs. A less widely explored strategy to support such diagnostic analysis is the assessment of direction of change (DOC), which addresses the question whether the increase (or decrease) of a model input leads to a positive (or negative) change in the model output. We propose a metric, called Direction Index, to quantitatively assess the DOC and develop an approach to calculate it. The basic idea of our approach is twofolded: (1) Estimate the zeroth and first‐order term of the High Dimensional Model Representation (HDMR) decomposition. (2) Calculate the derivatives of the first‐order term of the HDMR decomposition with respect to a given input. We demonstrate our approach on a widely used conceptual lumped hydrological model (Hymod) with a time‐varying analysis applied to the Leaf River Catchment in the USA. The results show that our approach provides new insights into the behavior of the model, which can be used to guide model structure improvement or to improve calibration efficiency.
Intranasal oxytocin modulates brain responses to voice-identity recognition in typically developing individuals, but not in ASD
Authors: Borowiak Kamila , von Kriegstein Katharina
Published: July 2020

Faces and voices are prominent cues for person-identity recognition. Face recognition behavior and associated brain responses can be enhanced by intranasal administration of oxytocin. It is unknown whether oxytocin can also augment voice-identity recognition mechanisms. To find it out is particularly relevant for individuals who have difficulties recognizing voice identity such as individuals diagnosed with autism spectrum disorder (ASD). We conducted a combined behavioral and functional magnetic resonance imaging (fMRI) study to investigate voice-identity recognition following intranasal administration of oxytocin or placebo in a group of adults diagnosed with ASD (full-scale intelligence quotient > 85) and pairwise-matched typically developing (TD) controls. A single dose of 24 IU oxytocin was administered in a randomized, double-blind, placebo-controlled and cross-over design. In the control group, but not in the ASD group, administration of oxytocin compared to placebo increased responses to recognition of voice identity in contrast to speech in the right posterior superior temporal sulcus/gyrus (pSTS/G) — a region implicated in the perceptual analysis of voice-identity information. In the ASD group, the right pSTS/G responses were positively correlated with voice-identity recognition accuracy in the oxytocin condition, but not in the placebo condition. Oxytocin did not improve voice-identity recognition performance at the group level. The ASD compared to the control group had lower right pSTS/G responses to voice-identity recognition. Since ASD is known to have atypical pSTS/G, the results indicate that the potential of intranasal oxytocin to enhance mechanisms for voice-identity recognition might be variable and dependent on the functional integrity of this brain region.
The role of omega-3 fatty acids in preventing glucocorticoid-induced reduction in human hippocampal neurogenesis and increase in apoptosis
Authors: Borsini Alessandra , Stangl Doris , Jeffries Aaron R. , Pariante Carmine M. , Thuret Sandrine
Published: July 2020

Glucocorticoids have been suggested to be involved in several neuropsychiatric disorders, including depression. One of the possible mechanisms through which glucocorticoids contribute to the development of the depressive symptomatology is via regulation of distinct neurogenic mechanisms in the brain. A preventive or protective approach for these patients might be the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are known for they neuroprotective properties. We used the human hippocampal progenitor cell line HPC0A07/03C and pre-treated cells with either EPA or DHA, followed by treatment with the glucocorticoid cortisol either alone, or in co-treatment with the same n-3 PUFA during subsequent 3 days of proliferation and 7 days of differentiation. During proliferation, both EPA and DHA were able to prevent cortisol-induced reduction in proliferation and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment. During differentiation, EPA was able to prevent cortisol-induced reduction in neurogenesis and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment only during the proliferation stage; however, DHA required continuous treatment also during the differentiation stage to prevent cortisol-induced reduction in neurogenesis. Using transcriptomic analyses, we showed that both EPA and DHA regulated pathways involved in oxidative stress and immune response [e.g., nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Signal transducer and activator of transcription 3 (STAT3), Interferon (IFN) and Interleukin (IL)-1 signaling], whereas DHA also regulated pathways involved in cell development and neuronal formation [e.g., cAMP-response element binding protein (CREB) signaling]. We provide the first evidence for treatment with both EPA and DHA to prevent cortisol-induced reduction in human hippocampal neurogenesis, and identify novel molecular mechanisms underlying these effects.
Infection with novel coronavirus (SARS-CoV-2) causes pneumonia in Rhesus macaques
Authors: Shan Chao , Yao Yan-Feng , Yang Xing-Lou , Zhou Yi-Wu , Gao Ge , Peng Yun , Yang Lian , Hu Xue , Xiong Jin , Jiang Ren-Di , Zhang Hua-Jun , Gao Xiao-Xiao , Peng Cheng , Min Juan , Chen Ying , Si Hao-Rui , Wu Jia , Zhou Peng , Wang Yan-Yi , Wei Hong-Ping , Pang Wei , Hu Zheng-Fei , Lv Long-Bao , Zheng Yong-Tang , Shi Zheng-Li , Yuan Zhi-Ming
Published: July 2020

The 2019 novel coronavirus (SARS-CoV-2) outbreak is a major challenge for public health. SARS-CoV-2 infection in human has a broad clinical spectrum ranging from mild to severe cases, with a mortality rate of ~6.4% worldwide (based on World Health Organization daily situation report). However, the dynamics of viral infection, replication and shedding are poorly understood. Here, we show that Rhesus macaques are susceptible to the infection by SARS-CoV-2. After intratracheal inoculation, the first peak of viral RNA was observed in oropharyngeal swabs one day post infection (1 d.p.i.), mainly from the input of the inoculation, while the second peak occurred at 5 d.p.i., which reflected on-site replication in the respiratory tract. Histopathological observation shows that SARS-CoV-2 infection can cause interstitial pneumonia in animals, characterized by hyperemia and edema, and infiltration of monocytes and lymphocytes in alveoli. We also identified SARS-CoV-2 RNA in respiratory tract tissues, including trachea, bronchus and lung; and viruses were also re-isolated from oropharyngeal swabs, bronchus and lung, respectively. Furthermore, we demonstrated that neutralizing antibodies generated from the primary infection could protect the Rhesus macaques from a second-round challenge by SARS-CoV-2. The non-human primate model that we established here provides a valuable platform to study SARS-CoV-2 pathogenesis and to evaluate candidate vaccines and therapeutics.
Roads as a contributor to landscape-scale variation in bird communities
Authors: Cooke Sophia C. , Balmford Andrew , Donald Paul F. , Newson Stuart E. , Johnston Alison
Published: July 2020

Roads and their traffic can affect wildlife over large areas and, in regions with dense road networks, may influence a high proportion of the ecological landscape. We assess the abundance of 75 bird species in relation to roads across Great Britain. Of these, 77% vary significantly in abundance with increasing road exposure, just over half negatively so. The effect distances of these negative associations average 700 m from a road, covering over 70% of Great Britain and over 40% of the total area of terrestrial protected sites. Species with smaller national populations generally have lower relative abundance with increasing road exposure, whereas the opposite is true for more common species. Smaller-bodied and migratory species are also more negatively associated with road exposure. By creating environmental conditions that benefit generally common species at the expense of others, road networks may echo other anthropogenic disturbances in bringing about large-scale simplification of avian communities.
Nampt-mediated spindle sizing secures a post-anaphase increase in spindle speed required for extreme asymmetry
Authors: Wei Zhe , Greaney Jessica , Loh Wei-Guo Nicholas , Homer Hayden Anthony
Published: July 2020

Meiotic divisions in oocytes are extremely asymmetric and require pre- and post-anaphase-onset phases of spindle migration. The latter induces membrane protrusion that is moulded around the spindle thereby reducing cytoplasmic loss. Here, we find that depleting the NAD biosynthetic enzyme, nicotinamide phosphoribosyl-transferase (Nampt), in mouse oocytes results in markedly longer spindles and compromises asymmetry. By analysing spindle speed in live oocytes, we identify a striking and transient acceleration after anaphase-onset that is severely blunted following Nampt-depletion. Slow-moving midzones of elongated spindles induce cortical furrowing deep within the oocyte before protrusions can form, altogether resulting in larger oocyte fragments being cleaved off. Additionally, we find that Nampt-depletion lowers NAD and ATP levels and that reducing NAD using small molecule Nampt inhibitors also compromises asymmetry. These data show that rapid midzone displacement is critical for extreme asymmetry by delaying furrowing to enable protrusions to form and link metabolic status to asymmetric division.
A nanotrap improves survival in severe sepsis by attenuating hyperinflammation
Authors: Shi Changying , Wang Xiaojing , Wang Lili , Meng Qinghe , Guo Dandan , Chen Li , Dai Matthew , Wang Guirong , Cooney Robert , Luo Juntao
Published: July 2020

Targeting single mediators has failed to reduce the mortality of sepsis. We developed a telodendrimer (TD) nanotrap (NT) to capture various biomolecules via multivalent, hybrid and synergistic interactions. Here, we report that the immobilization of TD-NTs in size-exclusive hydrogel resins simultaneously adsorbs septic molecules, e.g. lipopolysaccharides (LPS), cytokines and damage- or pathogen-associated molecular patterns (DAMPs/PAMPs) from blood with high efficiency (92–99%). Distinct surface charges displayed on the majority of pro-inflammatory cytokines (negative) and anti-inflammatory cytokines (positive) allow for the selective capture via TD NTs with different charge moieties. The efficacy of NT therapies in murine sepsis is both time-dependent and charge-dependent. The combination of the optimized NT therapy with a moderate antibiotic treatment results in a 100% survival in severe septic mice by controlling both infection and hyperinflammation, whereas survival are only 50–60% with the individual therapies. Cytokine analysis, inflammatory gene activation and tissue histopathology strongly support the survival benefits of treatments.
Interferon-independent STING signaling promotes resistance to HSV-1 in vivo
Authors: Yamashiro Lívia H. , Wilson Stephen C. , Morrison Huntly M. , Karalis Vasiliki , Chung Jing-Yi J. , Chen Katherine J. , Bateup Helen S. , Szpara Moriah L. , Lee Angus Y. , Cox Jeffery S. , Vance Russell E.
Published: July 2020

The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA. To initiate signaling, serine 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I interferons (IFNs). Additionally, evolutionary conserved responses such as autophagy also occur downstream of STING, but their relative importance during in vivo infections remains unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) mutation in STING are unexpectedly resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT, suggesting that the STING CTT initiates protective responses against HSV-1, independently of type I IFNs. Interestingly, we find that STING-induced autophagy is a CTT- and TBK1-dependent but IRF3-independent process that is conserved in the STING S365A mice. Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in vivo.
Discovery and population genomics of structural variation in a songbird genus
Authors: Weissensteiner Matthias H. , Bunikis Ignas , Catalán Ana , Francoijs Kees-Jan , Knief Ulrich , Heim Wieland , Peona Valentina , Pophaly Saurabh D. , Sedlazeck Fritz J. , Suh Alexander , Warmuth Vera M. , Wolf Jochen B. W.
Published: July 2020

Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus. Combining short-read (N = 127) and long-read re-sequencing (N = 31), as well as optical mapping (N = 16), we apply both assembly- and read mapping approaches to detect SV and characterize a total of 220,452 insertions, deletions and inversions. We exploit sampling across wide phylogenetic timescales to validate SV genotypes and assess the contribution of SV to evolutionary processes in an avian model of incipient speciation. We reveal an evolutionary young (~530,000 years) cis-acting 2.25-kb LTR retrotransposon insertion reducing expression of the NDP gene with consequences for premating isolation. Our results attest to the wealth and evolutionary significance of SV segregating in natural populations and highlight the need for reliable SV genotyping.
Extracting local nucleation fields in permanent magnets using machine learning
Authors: Gusenbauer Markus , Oezelt Harald , Fischbacher Johann , Kovacs Alexander , Zhao Panpan , Woodcock Thomas George , Schrefl Thomas
Published: July 2020

Microstructural features play an important role in the quality of permanent magnets. The coercivity is greatly influenced by crystallographic defects, like twin boundaries, as is well known for MnAl-C. It would be very useful to be able to predict the macroscopic coercivity from microstructure imaging. Although this is not possible now, in the present work we examine a related question, namely the prediction of simulated nucleation fields of a quasi-three-dimensional (rescaled and extruded) system constructed from a two-dimensional image. We extract features of the image and analyze them via machine learning. A large number of extruded systems are constructed from 10 × 10 pixel sub-images of an Electron Backscatter Diffraction (EBSD) image using an automated meshing procedure. A local nucleation field is calculated by micromagnetic simulation of each quasi-three-dimensional system. Decision trees, trained with the simulation results, can predict nucleation fields of these quasi-three-dimensional systems from new images within seconds. As for now we cannot quantitatively predict the macroscopic coercivity, nevertheless we can identify weak spots in the magnet and see trends in the nucleation field distribution.
Ultra-flat twisted superlattices in 2D heterostructures
Authors: Szendrő Márton , Süle Péter , Dobrik Gergely , Tapasztó Levente
Published: July 2020

Moiré-superlattices are ubiquitous in 2D heterostructures, strongly influencing their electronic properties. They give rise to new Dirac cones and are also at the origin of the superconductivity observed in magic-angle bilayer graphene. The modulation amplitude (corrugation) is an important yet largely unexplored parameter in defining the properties of 2D superlattices. The generally accepted view is that the corrugation monotonically decreases with increasing twist angle, while its effects on the electronic structure diminish as the layers become progressively decoupled. Here we found by lattice relaxation of around 8000 different Moiré-superstructures using high scale Classical Molecular Simulations combined with analytical calculations, that even a small amount of external strain can substantially change this picture, giving rise to more complex behavior of superlattice corrugation as a function of twist angle. One of the most surprising findings is the emergence of an ultra-flat phase that can be present for arbitrary small twist angle having a much lower corrugation level than the decoupled phase at large angles. Furthermore, Moiré-phase maps evidence that the state with no external strain is located in the close vicinity of a triple Moiré-phase boundary, implying that very small external strain variations can cause drastic changes in the realized superlattice morphology and corrugation. This renders the practical realization of 2D heterostructures with large-area homogeneous superlattice morphology highly challenging.
Liver transcriptome resources of four commercially exploited teleost species
Authors: Machado André M. , Muñoz-Merida Antonio , Fonseca Elza , Veríssimo Ana , Pinto Rui , Felício Mónica , da Fonseca Rute R. , Froufe Elsa , Castro L. Filipe C.
Published: July 2020

The generation of omic resources is central to develop adequate management strategies for species with economic value. Here, we provide high-coverage RNA-seq datasets of liver tissue (containing between 80,2 and 88,4 million of paired-end reads) from four wildtype teleost species with high commercial value: Trachurus trachurus (TTR; Atlantic horse mackerel), Scomber scombrus (SSC; Atlantic mackerel), Trisopterus luscus (TLU; pout), and Micromesistius poutassou (MPO; blue whiting). A comprehensive assembly pipeline, using de novo single and multi-kmer assembly approaches, produced 64 single high-quality liver transcriptomes – 16 per species. The final assemblies, with N50 values ranging from 2,543–3,700 bp and BUSCO (Benchmarking Universal Single-Copy Orthologs) completeness values between 81.8–86.5% of the Actinopterygii gene set, were subjected to open reading frame (ORF) prediction and functional annotation. Our study provides the first transcriptomic resources for these species and offers valuable tools to evaluate both neutral and selected genetic variation among populations, and to identify candidate genes for environmental adaptation assisting in the investigation of the effects of global changes in fisheries.
The actin nucleator Cobl organises the terminal web of enterocytes
Authors: Beer Anne J. , González Delgado Jule , Steiniger Frank , Qualmann Britta , Kessels Michael M.
Published: July 2020

Brush borders of intestinal epithelial cells are mandatory for nutrient uptake. Yet, which actin nucleators are crucial for forming the F-actin bundles supporting microvilli and the actin filaments of the terminal web, in which microvilli are rooted, is unknown. We show that mice lacking the actin nucleator Cobl surprisingly did not display reduced microvilli densities or changes in microvillar F-actin bundles or microvilli diameter but particularly in the duodenum displayed increased microvillar length. Interestingly, Cobl-deficient mice furthermore showed a significant widening of the terminal web. Quantitative analyses of high-resolution cryo-scanning electron microscopy (EM) of deep-etched duodenum samples revealed that Cobl is specifically important for the formation of fine filaments in the central terminal web that connect the apical structure of the terminal web underlying the plasma membrane, the microvilli rootlets and the basal structure of the terminal web with each other. Thus, the actin nucleator Cobl is critically involved in generating one of the cellular structures of the brush border-decorated apical cortex of enterocytes representing the absorptive intestinal surface.
Living with parents who smoke predicts levels of toxicant exposure in children
Authors: Park Myung-Bae
Published: July 2020

The detrimental effect of secondhand smoke (SHS) on health is well known; due to various factors, efforts to prevent SHS cannot completely eliminate the effect of smoking substances, and SHS has not been sufficiently investigated among children. This study aimed to assess children’s smoke exposure with respect to parents smoking patterns using biomarkers. This study used data from the 2016/2017 Korea National Health and Nutrition Examination Survey. Data pertaining to 486 subjects was extracted. Exposure to smoking among non-smoking children was assessed based on urine levels of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The urine NNAL concentration was highest among children with smoking parents and SHS exposure at home (3.829 pg/mg, 95% confidence interval [CI: 1.499–8.330), followed by children with smoking parents and no SHS exposure at home (1.297, 95% CI: 1.080–1.536), and children with nonsmoking parents and no SHS exposure at home (0.996 pg/mg, 95% CI: 1.026–1.427). Living with a smoking parent was associated with exposure to carcinogens, and a critical predictor of tobacco-specific nitrosamine. Prohibition of smoking at home is effective at preventing SHS in children. However, it cannot completely prevent passive smoking, which might be attributable to thirdhand smoking and undetected secondhand smoke.
Demystifying the factors associated with rural–urban gaps in severe acute malnutrition among under-five children in low- and middle-income countries: a decomposition analysis
Authors: Fagbamigbe A. F. , Kandala N. B. , Uthman A. O.
Published: July 2020

What explains the underlying causes of rural–urban differentials in severe acute malnutrition (SAM) among under-five children is poorly exploited, operationalized, studied and understood in low- and middle-income countries (LMIC). We decomposed the rural–urban inequalities in the associated factors of SAM while controlling for individual, household, and neighbourhood factors using datasets from successive demographic and health survey conducted between 2010 and 2018 in 51 LMIC. The data consisted of 532,680 under-five children nested within 55,823 neighbourhoods across the 51 countries. We applied the Blinder–Oaxaca decomposition technique to quantify the contribution of various associated factors to the observed rural–urban disparities in SAM. In all, 69% of the children lived in rural areas, ranging from 16% in Gabon to 81% in Chad. The overall prevalence of SAM among rural children was 4.8% compared with 4.2% among urban children. SAM prevalence in rural areas was highest in Timor-Leste (11.1%) while the highest urban prevalence was in Honduras (8.5%). Nine countries had statistically significant pro-rural (significantly higher odds of SAM in rural areas) inequality while only Tajikistan and Malawi showed statistically significant pro-urban inequality (p < 0.05). Overall, neighbourhood socioeconomic status, wealth index, toilet types and sources of drinking water were the most significant contributors to pro-rural inequalities. Other contributors to the pro-rural inequalities are birth weight, maternal age and maternal education. Pro-urban inequalities were mostly affected by neighbourhood socioeconomic status and wealth index. Having SAM among under-five children was explained by the individual-, household- and neighbourhood-level factors. However, we found variations in the contributions of these factors. The rural–urban dichotomy in the prevalence of SAM was generally significant with higher odds found in the rural areas. Our findings suggest the need for urgent intervention on child nutrition in the rural areas of most LMIC.
Transversely isotropic elastic-plastic properties in thermal arc sprayed Al–Zn coating: a microporomechanics approach
Authors: Huen Wai Yeong , Lee Hyuk , Vimonsatit Vanissorn , Mendis Priyan , Lee Han-Seung
Published: July 2020

The transversely isotropic behaviour of thermal sprayed aluminium and zinc coating has been investigated based on a combination of nanoindentation experimental data and microporomechanics theory. A recently developed strength homogenisation approach comprises of the solid and porous medium is adopted to investigate the morphology properties of thermal sprayed aluminum and zinc coating. The finding of this paper demonstrates that the individual aluminum and zinc phases in the coating have a characteristic packing density close to the theoretical highest spherical packing ratio for face-centred cubic and hexagonal close packed. Also, the plasticity properties of solid particles in both aluminum and zinc are found to have a significant transversely isotropic condition, while the elasticity properties are close to isotropic. These findings led to the conclusion that the anisotropic condition of the coating is dominantly affected by the plasticity properties, in terms of cohesion and friction coefficient.
Beta 1 integrin signaling mediates pancreatic ductal adenocarcinoma resistance to MEK inhibition
Authors: Brannon Arthur , Drouillard Donovan , Steele Nina , Schoettle Shadae , Abel Ethan V. , Crawford Howard C. , Pasca di Magliano Marina
Published: July 2020

Pancreatic cancer, one of the deadliest human malignancies, has a dismal 5-year survival rate of 9%. KRAS is the most commonly mutated gene in pancreatic cancer, but clinical agents that directly target mutant KRAS are not available. Several effector pathways are activated downstream of oncogenic Kras, including MAPK signaling. MAPK signaling can be inhibited by targeting MEK1/2; unfortunately, this approach has been largely ineffective in pancreatic cancer. Here, we set out to identify mechanisms of MEK inhibitor resistance in pancreatic cancer. We optimized the culture of pancreatic tumor 3D clusters that utilized Matrigel as a basement membrane mimetic. Pancreatic tumor 3D clusters recapitulated mutant KRAS dependency and recalcitrance to MEK inhibition. Treatment of the clusters with trametinib, a MEK inhibitor, had only a modest effect on these cultures. We observed that cells adjacent to the basement membrane mimetic Matrigel survived MEK inhibition, while the cells in the interior layers underwent apoptosis. Our findings suggested that basement membrane attachment provided survival signals. We thus targeted integrin β1, a mediator of extracellular matrix contact, and found that combined MEK and integrin β1 inhibition bypassed trametinib resistance. Our data support exploring integrin signaling inhibition as a component of combination therapy in pancreatic cancer.