bluuebunny/crossref_metadata_2025 huggingface dataset:
Active Ageing Index in Russia - Identifying Determinants for Inequality
Authors: Varlamova Maria , Sinyavskaya Oxana
Published: May 2020

This paper is aimed at the development of a tool analysing the AAI results for the Russian older citizens from different population groups, as well as at identifying factors underlying the inequalities in active ageing outcomes by calculation the AAI on the national and individual levels. The adaptation of the methodology of the AAI to the individual-level data and the limitations of the approach are explicitly explained. The older generations of Russia show relatively high levels of education, financial security and engagement in family care, especially in the care to children. The most significant potential for development have employment, volunteering, political engagement, physical activity, lifelong learning and use of the Internet. The calculation of the AAI at the individual level has revealed significant inequalities in the degree of realisation of potential in different areas of active ageing. The results of the project provide scientific evidence for the implementation of policy measures in the target groups. The high correlation of the index values with human capital indicators (health and education) underlines the importance of the early interventions aimed at promoting and supporting human capital at the earlier stages of the life course till the old age. The substantial positive connection of employment with other forms of activity stresses the necessity of developing a package of activation policy measures aimed at the retention of older adults in the labour market. At the same time, the statistical analysis showed the absence of a “dilemma of choice” between certain types of activity of the older generation, for example, between caring for grandchildren and employment, or employment and volunteering - the potential in different areas may be increased simultaneously.
The value of coordinated hydropower bidding in the Nordic day-ahead and balancing market
Authors: Aasgård Ellen Krohn
Published: May 2020

Modern power markets often consist of a series of sequential markets where power is traded. Market agents must coordinate their trading strategy across all markets. In this paper, we formulate the mult-market bidding problem for power producers as a stochastic program. This formulation is implemented within the framework of optimization models used by the Nordic hydropower industry. We also present how input to the stochastic program may be generated by using a forecast-based scenario generation method combined with time-series models that predicts future prices and turnovers in the markets. The model is applied in a case study to investigate the value of participating in the Nordic day-ahead and balancing market. A producer may participate in the balancing market either by considering the markets sequentially or coordinated. Using cases with limited and perfect information about the balancing market to calculate lower and upper bounds, we find that the value of participating in the balancing market using the sequential approach is between 0.8 and 2.6%. Using the coordinated approach, the producer may gain between 1.4 and 2.9%. The value of coordination, i.e. the value of using the coordinated over the sequential approach, is found to be higher in the limited information case (1.7%) than in the perfect information case (1.1%). This indicates that, the more uncertainty, the higher is the value of coordination.
Deficient Values of Solutions of Linear Differential Equations
Authors: Gundersen Gary G. , Heittokangas Janne , Wen Zhi-Tao
Published: May 2020

Differential equations of the form $$f'' + A(z)f' + B(z)f = 0$$

f

′
′

+
A

(
z
)

f
′

+
B

(
z
)

f
=
0

(*) are considered, where A(z) and $$B(z) \not \equiv 0$$

B
(
z
)
≢
0

are entire functions. The Lindelöf function is used to show that for any $$\rho \in (1/2, \infty )$$

ρ
∈
(
1
/
2
,
∞
)

, there exists an equation of the form (*) which possesses a solution f with a Nevanlinna deficient value at 0 satisfying $$\rho =\rho (f)\ge \rho (A)\ge \rho (B)$$

ρ
=
ρ
(
f
)
≥
ρ
(
A
)
≥
ρ
(
B
)

, where $$\rho (h)$$

ρ
(
h
)

denotes the order of an entire function h. It is known that such an example cannot exist when $$\rho \le 1/2$$

ρ
≤
1
/
2

. For smaller growth functions, a geometrical modification of an example of Anderson and Clunie is used to show that for any $$\rho \in (2, \infty )$$

ρ
∈
(
2
,
∞
)

, there exists an equation of the form (*) which possesses a solution f with a Valiron deficient value at 0 satisfying $$\rho =\rho _{\log }(f)\ge \rho _{\log }(A)\ge \rho _{\log }(B)$$

ρ
=

ρ
log

(
f
)

≥

ρ
log

(
A
)

≥

ρ
log

(
B
)

, where $$\rho _{\log }(h)$$

ρ
log

(
h
)

denotes the logarithmic order of an entire function h. This result is essentially sharp. In both proofs, the separation of the zeros of the indicated solution plays a key role. Observations on the deficient values of solutions of linear differential equations are also given, which include a discussion of Wittich’s theorem on Nevanlinna deficient values, a modified Wittich theorem for Valiron deficient values, consequences of Gol’dberg’s theorem, and examples to illustrate possibilities that can occur.
A new approach for prediction of the wear loss of PTA surface coatings using artificial neural network and basic, kernel-based, and weighted extreme learning machine
Authors: Ulas Mustafa , Altay Osman , Gurgenc Turan , Özel Cihan
Published: May 2020

Wear tests are essential in the design of parts intended to work in environments that subject a part to high wear. Wear tests involve high cost and lengthy experiments, and require special test equipment. The use of machine learning algorithms for wear loss quantity predictions is a potentially effective means to eliminate the disadvantages of experimental methods such as cost, labor, and time. In this study, wear loss data of AISI 1020 steel coated by using a plasma transfer arc welding (PTAW) method with FeCrC, FeW, and FeB powders mixed in different ratios were obtained experimentally by some of the researchers in our group. The mechanical properties of the coating layers were detected by microhardness measurements and dry sliding wear tests. The wear tests were performed at three different loads (19.62, 39.24, and 58.86 N) over a sliding distance of 900 m. In this study, models have been developed by using four different machine learning algorithms (an artificial neural network (ANN), extreme learning machine (ELM), kernel-based extreme learning machine (KELM), and weighted extreme learning machine (WELM)) on the data set obtained from the wear test experiments. The R2 value was calculated as 0.9729 in the model designed with WELM, which obtained the best performance [with 11among the models evaluated.
Project Stakeholder Management as the Integration of Stakeholder Salience, Public Participation, and Nonmarket Strategies
Authors: Joos Hannah Charlotte , zu Knyphausen-Aufseß Dodo , Pidun Ulrich
Published: May 2020

Despite the increasingly active role of civic actors, there is often no possibility for them to participate in project planning and decision-making. This discrepancy leads to costly conflicts and even failures. Unfortunately, the literature on project stakeholder management does not have sufficient theoretical substantiation to address this issue. To fill this knowledge gap, we integrate the concepts of stakeholder salience, public participation, and nonmarket strategy, and apply them to two urban infrastructure projects in Germany. This study contributes to the literature in two dimensions. First, it offers a dynamic and conceptual model for project stakeholder management, providing explanations for different conflict intensities. Second, it advances each individual area of research. Examples include the identification and clustering of so-called nonmarket assets, an examination of the influence of nonmarket strategies on managers’ perceptions of stakeholder salience, and the study of public participation in a corporate–political context, rather than a purely political one.
Surface tension stabilization of the Rayleigh-Taylor instability for a fluid layer in a porous medium
Authors: Granero-Belinchón Rafael , Gancedo Francisco , Scrobogna Stefano
Published: May 2020

This paper studies the dynamics of an incompressible fluid driven by gravity and capillarity forces in a porous medium. The main interest is the stabilization of the fluid in Rayleigh-Taylor unstable situations where the fluid lays on top of a dry region. An important feature considered here is that the layer of fluid is under an impervious wall. This physical situation has been widely study by mean of thin film approximations in the case of small characteristic high of the fluid considering its strong interaction with the fixed boundary. Here, instead of considering any simplification leading to asymptotic models, we deal with the complete free boundary problem. We prove that, if the fluid interface is smaller than an explicit constant, the solution is global in time and it becomes instantly analytic. In particular, the fluid does not form drops in finite time. Our results are stated in terms of Wiener spaces for the interface together with some non-standard Wiener-Sobolev anisotropic spaces required to describe the regularity of the fluid pressure and velocity. These Wiener-Sobolev spaces are of independent interest as they can be useful in other problems. Finally, let us remark that our techniques do not rely on the irrotational character of the fluid in the bulk and they can be applied to other free boundary problems.
Just the Facts: Management of cyclopeptide mushroom ingestion
Authors: Connors Nicholas J. , Hoffman Robert S. , Gosselin Sophie
Published: May 2020

A 54-year-old woman prepares dinner around 8:00 pm that includes mushrooms that she picked from her yard. The next morning, around 8:00 am, the woman (patient), her daughter, and son-in-law all develop abdominal cramps, violent vomiting, and diarrhea. They present to the emergency department and are admitted for dehydration and intractable vomiting with a presumed diagnosis of food poisoning. Twenty-four hours later, they appear well with stable vital signs and improved symptoms. Four hours later, 36 hours post-ingestion, the patient becomes lethargic. A venous blood gas reveals pH, 7.1; PCO2, 16 mmHg; and her AST was 3140 units/L with an ALT of 4260 units/L and an INR of 3.7.
Whiteness, Imperial Anxiety, and the “Global 1930s”: The White British League Debate in Hong Kong
Authors: Kong Vivian
Published: May 2020

What is a British colony for, and who is it for? These were the questions at the crux of a public debate in 1933 in Hong Kong sparked by a British resident claiming to have formed an organization for the “protection and advancement” of the “British white race.” This article explores how anxieties about fascism, white privilege, and “others” in the empire allowed the very idea of such a political movement to be elevated to the subject of heated debate. The discussion on British unemployment, poor whites, and European “intruders” in the colony tells us less about the actual socioeconomic conditions that Hong Kong Britons faced than about their subjective experience of being “British” in an imperial context. The articulation of imperial anxiety also shows us how the fluid, ambiguous borders of whiteness and Britishness were negotiated at the intersections of nationalism, ethnicity, class, and race. Highlighting the global perspectives demonstrated in the debate and the various transnational networks across Hong Kong, this article argues that the debate was as much about global sociopolitical circumstances as about what was happening in Hong Kong. It therefore offers a timely opportunity to rethink how the local, “national,” regional, and global were interwoven in the “global 1930s,” even among the English reading public in the British colony of Hong Kong.
Do People Like Mandatory Rules? The Impact of Framing and Phrasing
Authors: Zamir Eyal , Katz Ori
Published: May 2020

Market regulation has traditionally focused on disclosure duties, yet mounting evidence questions their effectiveness. The efficacy of nudges is similarly doubted, especially when suppliers counter their effects. Consequently, there is growing interest in mandatory regulation of the content of contracts. Previous studies have examined public opinion about nudges but not about mandatory rules.

We explore how the formulation of mandatory rules might affect their judged desirability, focusing on the choices: (1) between negative and positive formulation; and (2) between merely establishing substantive mandatory rules and supervising the wording of the contract as well. We also examine laypersons’ general attitude toward mandatory rules.

We report the results of four studies, conducted with a representative sample of 968 US adults and 795 MTurk master workers. Contrary to our conjecture, we found that subjects generally judged wording rules as more desirable than merely substantive ones, and positive rules as more desirable than negative ones. There also appears to be strong support for pro-customer mandatory rules, even among conservative people. These results arguably legitimize more, and more effective, mandatory rules. They also suggest that the relative paucity of mandatory rules in US law is not due to public opposition to them but to other reasons.
RADIOCARBON AND DENDROCHRONOLOGY APPLIED IN A LEGAL DISPUTE: A CASE FROM COLOMBIA
Authors: del Valle Jorge I , Giraldo Jorge A
Published: May 2020

In 2015 a dispute arose between an electricity company (EC) and smallholder of a teak plantation when the EC felled 80 trees (without consent of the owner) in a linear transect under a rural power-line-corridor (PLC), fragmenting the teak stand in two portions. The EC stated that there were no planted trees in the area when the PLC was established in 2008. The owner asserted he planted the stand in 2006 so in 2008 the company should have seen the planted trees. We used the bomb radiocarbon (14C) signal of three felled trees and dendrochronological dating of five trees, three felled by the EC and two felled by us in 2016, to do this study to determine the age. We found that the first growth rings were dated to 2005 both in the trees felled by the EC in 2015 and felled by us in 2016, one year before that reported by the owner (2006). This year corresponds to the wood present in the cuttings during the stand’s planting year. These facts are in agreement with the owner’s testimony. The plantation was 10 years old in 2015.
TOWARDS A HISTORY OF GLOBAL HUMANITARIANISM
Authors: O'LEARY MCNEICE AOIFE
Published: May 2020

We are currently witnessing the emergence of global humanitarianism as a fully fledged historical field. Eighteenth-century transatlantic abolitionists, nineteenth-century imperial missionaries, twentieth-century aid workers, and twenty-first-century activists inhabit the pages of more and more published books and articles. Global humanitarianism denotes a sphere of action as well as an object of study. Questions as to where or what the global is persist. The books under review all operate within the sphere of Western influence: North America, the British empire, or former colonies. They also have similar protagonists. They are largely populated with practitioners of humanitarianism, rather than the objects of their beneficence. This raises some questions. Where does global humanitarianism take place and who does it encompass? Is global humanitarianism inherently enmeshed with Western expansionism and unequal power dynamics?
The Quantification and Interpretation of Ceramic Building Material (CBM) Assemblages in Britain
Authors: Warry Peter
Published: May 2020

Quantification of assemblages of ceramic building material (CBM) is now normal excavation practice, but there is insufficient standardisation of methodology and little study of the validity or uses of these analyses. Consequently, it is difficult to interpret confidently the resulting analyses or make comparisons between sites. This paper suggests a simple approach and tests its validity empirically in urban environments where the high level of constructional churn should generate assemblage homogeneity. It then shows how the results can help with site and building interpretation.
TESTING A PARAMETRIC TRANSFORMATION MODEL VERSUS A NONPARAMETRIC ALTERNATIVE
Authors: Szydłowski Arkadiusz
Published: May 2020

Despite an abundance of semiparametric estimators of the transformation model, no procedure has been proposed yet to test the hypothesis that the transformation function belongs to a finite-dimensional parametric family against a nonparametric alternative. In this article, we introduce a bootstrap test based on integrated squared distance between a nonparametric estimator and a parametric null. As a special case, our procedure can be used to test the parametric specification of the integrated baseline hazard in a semiparametric mixed proportional hazard model. We investigate the finite sample performance of our test in a Monte Carlo study. Finally, we apply the proposed test to Kennan’s strike durations data.
Long-term safety and durability of effect with a combination of olanzapine and samidorphan in patients with schizophrenia: results from a 1-year open-label extension study
Authors: Yagoda Sergey , Graham Christine , Simmons Adam , Arevalo Christina , Jiang Ying , McDonnell David
Published: May 2020

Background

Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.

Methods

Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.

Results

In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively).

Conclusion

OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.
Temperature Inversion and Clouds Over the Arctic Ocean Observed by the 5th Chinese National Arctic Research Expedition
Authors: Wang Ding , Guo Jianping , Chen Aijun , Bian Lingen , Ding Minghu , Liu Lin , Lv Yanmin , Li Jian , Guo Xiaoran , Han Yi
Published: May 2020

The Arctic is of great significance to global weather and climate systems. However, its atmospheric conditions have yet to be fully understood, partly because of the lack of intensive observations. Here we reported on the characteristics of lower troposphere over the Arctic Ocean using high‐resolution radiosonde data collected during the 5th Chinese National Arctic Research Expedition from July to September 2014. Statistical analyses showed that temperature inversion (TI) occurred most frequently below 700 m, without apparent temporal variability between morning and noon. In contrast, the occurrence frequency of morning surface‐based inversion (SBI) was always higher than at noon in the whole boundary layer, whereas the elevated inversion (EI) frequency seemed much lower in the morning compared with at noon. More frequent deeper clouds tended to occur in the morning than at noon, which led to more frequent EI than SBI. SBI was found to dominate the clear‐sky condition, whereas EI was generally observed under cloudy conditions. Regarding the seasonal variation, deep TI and clouds dominated during the first intensive observational period (IOP‐1; July 21–31) because of warm advection in combination with heating effects induced by long‐range transported black carbon (BC). During IOP‐2 (August 1–18), synoptic scale subsidence prevailed, with frequent EI and SBI partly caused by BC accumulation over the Arctic Ocean. In comparison, more clouds and less TI occurred during IOP‐3 (August 27–September 11) largely due to the outbreaking polar vortex. These observations contribute to a better understanding of vertical temperature and cloud structures under global warming.
Space Weather Forecasting Takes Inspiration from Meteorology
Authors: Stanley Sarah
Published: May 2020

Solar features analogous to major atmospheric waves on Earth could offer more advanced warning of harmful solar storms.
Creating Data Tool Kits That Everyone Can Use
Authors: Liu Zhong , Mantas Vasco , Wei Jennifer , Jin Menglin , Meyer David
Published: May 2020

Earth scientists outline challenges to making the growing wealth of available data more accessible and to using data services for interdisciplinary research and applications.
A Comparative Study on the Discontinuous Luminosities of Two Upward Lightning Leaders With Opposite Polarities
Authors: Wang Xiankang , Wang Daohong , He Junjia , Takagi Nobuyuki
Published: May 2020

We have performed a comparative study on the luminosity of 12 steps in an upward positive leader and eight steps in an upward negative leader recorded under similar conditions. Through analyzing their so‐called differential luminosity profiles along leader channels, we found that the steps of positive leaders can be classified into two types. The type I step luminosity is similar to the luminosity produced by a negative leader step and is generally featured with a rapid increase near the leader tip and accompanied by a backward propagation along the leader channel. The type II step is featured with continuous luminosity variation along the leader channel. No apparent backward propagation has been identified in the type II step luminosity of the positive leader. Based on these observations, we have discussed how the two types of steps of positive leaders are produced.
Epigenome-wide association study and multi-tissue replication of individuals with alcohol use disorder: evidence for abnormal glucocorticoid signaling pathway gene regulation
Authors: Lohoff Falk W. , Roy Arunima , Jung Jeesun , Longley Martha , Rosoff Daniel B. , Luo Audrey , O’Connell Emma , Sorcher Jill L. , Sun Hui , Schwandt Melanie , Hodgkinson Colin A. , Goldman David , Momenan Reza , McIntosh Andrew M. , Adams Mark J. , Walker Rosie M. , Evans Kathryn L. , Porteous David , Smith Alicia K. , Lee Jisoo , Muench Christine , Charlet Katrin , Clarke Toni-Kim , Kaminsky Zachary A.
Published: May 2020

Alcohol use disorder (AUD) is a chronic debilitating disorder with limited treatment options and poorly defined pathophysiology. There are substantial genetic and epigenetic components; however, the underlying mechanisms contributing to AUD remain largely unknown. We conducted the largest DNA methylation epigenome-wide association study (EWAS) analyses currently available for AUD (total N = 625) and employed a top hit replication (N = 4798) using a cross-tissue/cross-phenotypic approach with the goal of identifying novel epigenetic targets relevant to AUD. Results show that a network of differentially methylated regions in glucocorticoid signaling and inflammation-related genes were associated with alcohol use behaviors. A top probe consistently associated across all cohorts was located in the long non-coding RNA growth arrest specific five gene (GAS5) (p < 10−24). GAS5 has been implicated in regulating transcriptional activity of the glucocorticoid receptor and has multiple functions related to apoptosis, immune function and various cancers. Endophenotypic analyses using peripheral cortisol levels and neuroimaging paradigms showed that methylomic variation in GAS5 network-related probes were associated with stress phenotypes. Postmortem brain analyses documented increased GAS5 expression in the amygdala of individuals with AUD. Our data suggest that alcohol use is associated with differential methylation in the glucocorticoid system that might influence stress and inflammatory reactivity and subsequently risk for AUD.
Drug repositioning for psychiatric and neurological disorders through a network medicine approach
Authors: Lüscher Dias Thomaz , Schuch Viviane , Beltrão-Braga Patrícia Cristina Baleeiro , Martins-de-Souza Daniel , Brentani Helena Paula , Franco Glória Regina , Nakaya Helder Imoto
Published: May 2020

Psychiatric and neurological disorders (PNDs) affect millions worldwide and only a few drugs achieve complete therapeutic success in the treatment of these disorders. Due to the high cost of developing novel drugs, drug repositioning represents a promising alternative method of treatment. In this manuscript, we used a network medicine approach to investigate the molecular characteristics of PNDs and identify novel drug candidates for repositioning. Using IBM Watson for Drug Discovery, a powerful machine learning text-mining application, we built knowledge networks containing connections between PNDs and genes or drugs mentioned in the scientific literature published in the past 50 years. This approach revealed several drugs that target key PND-related genes, which have never been used to treat these disorders to date. We validate our framework by detecting drugs that have been undergoing clinical trial for treating some of the PNDs, but have no published results in their support. Our data provides comprehensive insights into the molecular pathology of PNDs and offers promising drug repositioning candidates for follow-up trials.
CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions
Authors: He Yangke , Huang Hui , Jin Li , Zhang Fang , Zeng Ming , Wei Liang , Tang Shijia , Chen Dongqin , Wang Wansheng
Published: May 2020

Emerging evidence has revealed that aberrantly expressed circular RNAs (circRNAs) play vital roles in tumorigenesis and progression of diverse human malignancies. Although an existing literature has elucidated the regulatory role of circZNF609 in breast cancer, the crucial function that circZNF609 exerted on hepatocellular carcinoma (HCC) remains unclear. Herein, we determined to explore the molecular mechanism of circZNF609 in HCC. In this study, circZNF609 was conspicuously overexpressed and featured with loop structure in HCC. Functional tests revealed that decreased expression of circZNF609 suppressed cell proliferation, metastasis and stemness, whereas induced cell apoptosis in HCC. Subsequent molecular mechanism assays indicated that circZNF609 contributed to HCC progression through activation of Hedgehog pathway. Moreover, circZNF609 was found to be negatively correlated with miR-15a-5p/15b-5p but positively correlated with GLI2. Moreover, there was a negative correlation between miR-15a-5p/15b-5p and GLI2. Rescue experiments testified that GLI2 overexpression could recover circZNF609 depletion-mediated function on HCC development while miR-15a-5p/15b-5p inhibition could partially rescue circZNF609 silencing-mediated effect on HCC progression. Final experiments in vivo further elucidated the suppressive function of circZNF609 knockdown on the tumorigenesis of HCC. Briefly, circZNF609 enhances HCC cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions.
Machine-learning-guided discovery of the gigantic magnetocaloric effect in HoB2 near the hydrogen liquefaction temperature
Authors: Castro Pedro Baptista de , Terashima Kensei , Yamamoto Takafumi D , Hou Zhufeng , Iwasaki Suguru , Matsumoto Ryo , Adachi Shintaro , Saito Yoshito , Song Peng , Takeya Hiroyuki , Takano Yoshihiko
Published: May 2020

Magnetic refrigeration exploits the magnetocaloric effect, which is the entropy change upon the application and removal of magnetic fields in materials, providing an alternate path for refrigeration other than conventional gas cycles. While intensive research has uncovered a vast number of magnetic materials that exhibit a large magnetocaloric effect, these properties remain unknown for a substantial number of compounds. To explore new functional materials in this unknown space, machine learning is used as a guide for selecting materials that could exhibit a large magnetocaloric effect. By this approach, HoB2 is singled out and synthesized, and its magnetocaloric properties are evaluated, leading to the experimental discovery of a gigantic magnetic entropy change of 40.1 J kg−1 K−1 (0.35 J cm−3 K−1) for a field change of 5 T in the vicinity of a ferromagnetic second-order phase transition with a Curie temperature of 15 K. This is the highest value reported so far, to the best of our knowledge, near the hydrogen liquefaction temperature; thus, HoB2 is a highly suitable material for hydrogen liquefaction and low-temperature magnetic cooling applications.
Child volunteers in a women's paramilitary organization in World War II have accelerated reproductive schedules
Authors: Lynch Robert , Lummaa Virpi , Briga Michael , Chapman Simon N. , Loehr John
Published: May 2020

Understanding how conditions experienced during development affect reproductive timing is of considerable cross-disciplinary interest. Life-history theory predicts that organisms will accelerate reproduction when future survival is unsure. In humans, this can be triggered by early exposure to mortality. Previous studies, however, have been inconclusive due to several confounds that are also likely to affect reproduction. Here we take advantage of a natural experiment in which a population is temporarily divided by war to analyze how exposure to mortality affects reproduction. Using records of Finnish women in World War II, we find that young girls serving in a paramilitary organization wait less time to reproduce, have shorter inter-birth intervals, and have more children than their non-serving peers or sisters. These results support the hypothesis that exposure to elevated mortality rates during development can result in accelerated reproductive schedules and adds to our understanding of how participation in warfare affects women.
Integration of multiple biological contexts reveals principles of synthetic lethality that affect reproducibility
Authors: Ku Angel A. , Hu Hsien-Ming , Zhao Xin , Shah Khyati N. , Kongara Sameera , Wu Di , McCormick Frank , Balmain Allan , Bandyopadhyay Sourav
Published: May 2020

Synthetic lethal screens have the potential to identify new vulnerabilities incurred by specific cancer mutations but have been hindered by lack of agreement between studies. In the case of KRAS, we identify that published synthetic lethal screen hits significantly overlap at the pathway rather than gene level. Analysis of pathways encoded as protein networks could identify synthetic lethal candidates that are more reproducible than those previously reported. Lack of overlap likely stems from biological rather than technical limitations as most synthetic lethal phenotypes are strongly modulated by changes in cellular conditions or genetic context, the latter determined using a pairwise genetic interaction map that identifies numerous interactions that suppress synthetic lethal effects. Accounting for pathway, cellular and genetic context nominates a DNA repair dependency in KRAS-mutant cells, mediated by a network containing BRCA1. We provide evidence for why most reported synthetic lethals are not reproducible which is addressable using a multi-faceted testing framework.
Transient-axial-chirality controlled asymmetric rhodium-carbene C(sp2)-H functionalization for the synthesis of chiral fluorenes
Authors: Dong Kuiyong , Fan Xing , Pei Chao , Zheng Yang , Chang Sailan , Cai Ju , Qiu Lihua , Yu Zhi-Xiang , Xu Xinfang
Published: May 2020

In catalytic asymmetric reactions, the formation of chiral molecules generally relies on a direct chirality transfer (point or axial chirality) from a chiral catalyst to products in the stereo-determining step. Herein, we disclose a transient-axial-chirality transfer strategy to achieve asymmetric reaction. This method relies on transferring point chirality from the catalyst to a dirhodium carbene intermediate with axial chirality, namely a transient-axial-chirality since this species is an intermediate of the reaction. The transient chirality is then transferred to the final product by C(sp2)-H functionalization reaction with exceptionally high enantioselectivity. We also generalize this strategy for the asymmetric cascade reaction involving dual carbene/alkyne metathesis (CAM), a transition-metal-catalyzed method to access chiral 9-aryl fluorene frameworks in high yields with up to 99% ee. Detailed DFT calculations shed light on the mode of the transient-axial-chirality transfer and the detailed mechanism of the CAM reaction.
Peroxisomal targeting of a protein phosphatase type 2C via mitochondrial transit
Authors: Stehlik Thorsten , Kremp Marco , Kahnt Jörg , Bölker Michael , Freitag Johannes
Published: May 2020

Correct intracellular distribution of proteins is critical for the function of eukaryotic cells. Certain proteins are targeted to more than one cellular compartment, e.g. to mitochondria and peroxisomes. The protein phosphatase Ptc5 from Saccharomyces cerevisiae contains an N-terminal mitochondrial presequence followed by a transmembrane domain, and has been detected in the mitochondrial intermembrane space. Here we show mitochondrial transit of Ptc5 to peroxisomes. Translocation of Ptc5 to peroxisomes depended both on the C-terminal peroxisomal targeting signal (PTS1) and N-terminal cleavage by the mitochondrial inner membrane peptidase complex. Indirect targeting of Ptc5 to peroxisomes prevented deleterious effects of its phosphatase activity in the cytosol. Sorting of Ptc5 involves simultaneous interaction with import machineries of both organelles. We identify additional mitochondrial proteins with PTS1, which localize in both organelles and can increase their physical association. Thus, a tug-of-war-like mechanism can influence the interaction and communication of two cellular compartments.
The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs
Authors: Zorzan Irene , Pellegrini Marco , Arboit Mattia , Incarnato Danny , Maldotti Mara , Forcato Mattia , Tagliazucchi Guidantonio Malagoli , Carbognin Elena , Montagner Marco , Oliviero Salvatore , Martello Graziano
Published: May 2020

Human pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of the transcriptional programme controlled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to identify factors mediating TGF-beta activity. We identify a quartet of transcriptional regulators promoting hPSC self-renewal including ZNF398, a human-specific mediator of pluripotency and epithelial character in hPSCs. Mechanistically, ZNF398 binds active promoters and enhancers together with SMAD3 and the histone acetyltransferase EP300, enabling transcription of TGF-beta targets. In the context of somatic cell reprogramming, inhibition of ZNF398 abolishes activation of pluripotency and epithelial genes and colony formation. Our findings have clear implications for the generation of bona fide hPSCs for regenerative medicine.
Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination
Authors: Puvar Kedar , Iyer Shalini , Fu Jiaqi , Kenny Sebastian , Negrón Terón Kristos I. , Luo Zhao-Qing , Brzovic Peter S. , Klevit Rachel E. , Das Chittaranjan
Published: May 2020

The bacterial effector MavC modulates the host immune response by blocking Ube2N activity employing an E1-independent ubiquitin ligation, catalyzing formation of a γ-glutamyl-ε-Lys (Gln40Ub-Lys92Ube2N) isopeptide crosslink using a transglutaminase mechanism. Here we provide biochemical evidence in support of MavC targeting the activated, thioester-linked Ube2N~ubiquitin conjugate, catalyzing an intramolecular transglutamination reaction, covalently crosslinking the Ube2N and Ub subunits effectively inactivating the E2~Ub conjugate. Ubiquitin exhibits weak binding to MavC alone, but shows an increase in affinity when tethered to Ube2N in a disulfide-linked substrate that mimics the charged E2~Ub conjugate. Crystal structures of MavC in complex with the substrate mimic and crosslinked product provide insights into the reaction mechanism and underlying protein dynamics that favor transamidation over deamidation, while revealing a crucial role for the structurally unique insertion domain in substrate recognition. This work provides a structural basis of ubiquitination by transglutamination and identifies this enzyme’s true physiological substrate.
Publisher Correction: Comparative genomics of Salmonella enterica serovar Enteritidis ST-11 isolated in Uruguay reveals lineages associated with particular epidemiological traits
Authors: D’Alessandro Bruno , Pérez Escanda Victoria , Balestrazzi Lucía , Grattarola Florencia , Iriarte Andrés , Pickard Derek , Yim Lucía , Chabalgoity José Alejandro , Betancor Laura
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Locomotor rib kinematics in two species of lizards and a new hypothesis for the evolution of aspiration breathing in amniotes
Authors: Cieri Robert L. , Hatch Samuel T. , Capano John G. , Brainerd Elizabeth L.
Published: May 2020

Most lizards walk and run with a sprawling gait in which the limbs are partly advanced by lateral undulation of the axial skeleton. Ribs and vertebrae are integral to this locomotor mode, but 3D motion of the axial skeleton has not been reported for lizard locomotion. Here, we use XROMM to quantify the relative motions of the vertebrae and ribs during slow treadmill locomotion in three savannah monitor lizards (Varanus exanthematicus) and three Argentine black and white tegus (Salvator merianae). To isolate locomotion, we selected strides with no concurrent lung ventilation. Rib rotations can be decomposed into bucket-handle rotation around a dorsoventral axis, pump-handle rotation around a mediolateral axis, and caliper rotations around a craniocaudal axis. During locomotion, every rib measured in both species rotated substantially around its costovertebral joint (8–17 degrees, summed across bucket, pump and caliper rotations). In all individuals from both species, the middle ribs rotated cranially through bucket and pump-handle motion during the propulsive phase of the ipsilateral forelimb. Axial kinematics during swing phase of the ipsilateral forelimb were mirror images of the propulsive phase. Although further work is needed to establish what causes these rib motions, active contraction of the hypaxial musculature may be at least partly responsible. Unilateral locomotor rib movements are remarkably similar to the bilateral pattern used for lung ventilation, suggesting a new hypothesis that rib motion during locomotion may have been an exaptation for the evolution of costal aspiration breathing in stem amniotes.
Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression
Authors: Huerta-Yepez Sara , Tirado-Rodriguez Ana , Montecillo-Aguado Mayra R. , Yang Jun , Hammock Bruce D. , Hankinson Oliver
Published: May 2020

The Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can metabolize PUFA to epoxides. Mice fed ω3-rich or ω6-rich diets were treated with TCDD and injected subcutaneously with AHR-competent Hepa1-GFP hepatoma cells or AHR-deficient LLC lung cancer cells. TCDD reduced the growth rates of the resulting tumors in ω3-fed mice and inhibited their metastasis to the liver and/or lung, but had the opposite effects in mice fed ω6 PUFA. These responses were likely attributable to the corresponding PUFA epoxides generated in tumor cells and/or host, since many depended upon co-administration of a soluble epoxide hydrolase (EPHX2) inhibitor in males, and/or were associated with increases in epoxide levels in tumors and sites of metastasis. Equivalent effects occurred in females in the absence of EPHX2 inhibition, probably because this sex expressed reduced levels of EPHX2. The responses elicited by TCDD were associated with effects on tumor vascularity, tumor cell proliferation and/or apoptosis. Thus environmental AHR agonists, and potentially also endogenous, nutritional, and microbiome-derived agonists, may reduce or enhance cancer progression depending on the composition of dietary PUFA, particularly in females.
Eye-tracking reveals agency in assisted autistic communication
Authors: Jaswal Vikram K. , Wayne Allison , Golino Hudson
Published: May 2020

About one-third of autistic people have limited ability to use speech. Some have learned to communicate by pointing to letters of the alphabet. But this method is controversial because it requires the assistance of another person—someone who holds a letterboard in front of users and so could theoretically cue them to point to particular letters. Indeed, some scientists have dismissed the possibility that any nonspeaking autistic person who communicates with assistance could be conveying their own thoughts. In the study reported here, we used head-mounted eye-tracking to investigate communicative agency in a sample of nine nonspeaking autistic letterboard users. We measured the speed and accuracy with which they looked at and pointed to letters as they responded to novel questions. Participants pointed to about one letter per second, rarely made spelling errors, and visually fixated most letters about half a second before pointing to them. Additionally, their response times reflected planning and production processes characteristic of fluent spelling in non-autistic typists. These findings render a cueing account of participants’ performance unlikely: The speed, accuracy, timing, and visual fixation patterns suggest that participants pointed to letters they selected themselves, not letters they were directed to by the assistant. The blanket dismissal of assisted autistic communication is therefore unwarranted.
Detection of low-frequency resistance-mediating SNPs in next-generation sequencing data of Mycobacterium tuberculosis complex strains with binoSNP
Authors: Dreyer Viola , Utpatel Christian , Kohl Thomas A. , Barilar Ivan , Gröschel Matthias I. , Feuerriegel Silke , Niemann Stefan
Published: May 2020

Accurate drug resistance detection is key for guiding effective tuberculosis treatment. While genotypic resistance can be rapidly detected by molecular methods, their application is challenged by mixed mycobacterial populations comprising both susceptible and resistant cells (heteroresistance). For this, next-generation sequencing (NGS) based approaches promise the determination of variants even at low frequencies. However, accurate methods for a valid detection of low-frequency variants in NGS data are currently lacking. To tackle this problem, we developed the variant detection tool binoSNP which allows the determination of low-frequency single nucleotide polymorphisms (SNPs) in NGS datasets from Mycobacterium tuberculosis complex (MTBC) strains. By taking a reference-mapped file as input, binoSNP evaluates each genomic position of interest using a binomial test procedure. binoSNP was validated using in-silico, in-vitro, and serial patient isolates datasets comprising varying genomic coverage depths (100-500×) and SNP allele frequencies (1-30%). Overall, the detection limit for low-frequency SNPs depends on the combination of coverage depth and allele frequency of the resistance-associated mutation. binoSNP allows for valid detection of resistance associated SNPs at a 1% frequency with a coverage ≥400×. In conclusion, binoSNP provides a valid approach to detect low-frequency resistance-mediating SNPs in NGS data from clinical MTBC strains. It can be implemented in automated, end-user friendly analysis tools for NGS data and is a step forward towards individualized TB therapy.
Genetic Polymorphisms, Mediterranean Diet and Microbiota-Associated Urolithin Metabotypes can Predict Obesity in Childhood-Adolescence
Authors: Cortés-Martín Adrián , Colmenarejo Gonzalo , Selma María Victoria , Espín Juan Carlos
Published: May 2020

Environmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolescents (n = 415, 5−17 years-old) by estimating the odds ratios for different predictor variables, and their relative importance in the prediction. The predictor variables were ethnicity, age, sex, adherence to the Mediterranean diet (KIDMED), physical activity, urolithin metabotypes (UM-A, UM-B and UM-0) as biomarkers of the gut microbiota, and 53 single-nucleotide polymorphisms (SNPs) from 43 genes mainly related to obesity and cardiometabolic diseases. A proportional-odds logistic ordinal regression, validated through bootstrap, was used to model the data. While every variable was not independently associated with overweight-obesity, however, the ordinal logistic model revealed that overweight-obesity prevalence was related to being a young boy with either UM-B or UM-0, low KIDMED score and high contribution of a consortium of 24 SNPs, being rs1801253-ADRB1, rs4343-ACE, rs8061518-FTO, rs1130864-CRP, rs659366-UCP2, rs6131-SELP, rs12535708-LEP, rs1501299-ADIPOQ, rs708272-CETP and rs2241766-ADIPOQ the top-ten contributing SNPs. Additional research should confirm and complete this model by including dietary interventions and the individuals’ gut microbiota composition.