bluuebunny/crossref_metadata_2025 huggingface dataset:
Grundrentenplan der großen Koalition
Authors: Klammer Ute , Wagner Gert G.
Published: January 2020

Zusamenfasung

Unabhängig davon, ob der Grundrenten-Beschluss der Koalitionsparteien tatsächlich umgesetzt wird, ist er von Interesse, da die Diskussion über die noch offene Finanzierung der geplanten Grundrente auf die grundsätzliche Frage verweist, welche Risiken die Gesetzliche Rentenversicherung eigentlich versichert. Es gibt Argumente dafür, dass die konventionelle Sichtweise auf die versicherten Risiken abgelöst werden könnte bzw. erweitert werden sollte. Das Risiko, trotz langjähriger Erwerbstätigkeit und Beitragszahlung im Alter auf bedarfsgeprüfte Grundsicherung angewiesen zu sein, lässt sich als durch die Rentenversicherung versicherbares Risiko ansehen. Dann ist eine Beitragsfinanzierung nicht nur systematisch möglich, sondern zur Gewährleistung eines verlässlichen Generationsvertrags geradezu geboten.
Geburtsstunde des modernen Steuerstaats in Deutschland 1919/1920
Authors: Bach Stefan , Buggeln Marc
Published: January 2020

Vor 100 Jahren haben die “Erzbergerschen Steuerund Finanzreformen” die öffentlichen Finanzen in Deutschland grundlegend umgestaltet. Sie zentralisierten die Finanzverfassung und modernisierten das Steuersystem umfassend. Einkommensteuer, Körperschaftsteuer und Erbschaftsteuer wurden deutschlandweit vereinheitlicht und deutlich erhöht, ferner wurden eine Vermögensabgabe eingeführt und die indirekten Steuern ausgebaut. Die gesamtwirtschaftliche Steuer- und Abgabenbelastung verdoppelte sich bis 1925. Diese Reformen prägen die Grundlagen der öffentlichen Finanzen und des Steuersystems bis heute.
Ökonomische Effekte ausländischer Unternehmen in Deutschland
Authors: Jungbluth Cora , Sunesen Eva Rytter , Hansen Morten May , Brown Joshua
Published: January 2020

Die Globalisierung ist mit komplexen Wertschöpfungsketten und den Wirtschaftstätigkeiten von Unternehmen verbunden, die von ausländischen Investoren kontrolliert werden. Welche ökonomischen Effekte haben ausländische Unternehmen auf das Bruttoinlandsprodukt und die Beschäftigung in Deutschland? Sie leisten einen Beitrag zur lokalen Wirtschaft, indem sie Arbeitskräfte beschäftigen, Waren und Dienstleistungen von lokalen Lieferanten kaufen und durch Spillover-Effekte die Produktivität lokaler Unternehmen steigern.
Simulation of mineral dissolution at the pore scale with evolving fluid-solid interfaces: review of approaches and benchmark problem set
Authors: Molins Sergi , Soulaine Cyprien , Prasianakis Nikolaos I. , Abbasi Aida , Poncet Philippe , Ladd Anthony J. C. , Starchenko Vitalii , Roman Sophie , Trebotich David , Tchelepi Hamdi A. , Steefel Carl I.
Published: January 2020

This manuscript presents a benchmark problem for the simulation of single-phase flow, reactive transport, and solid geometry evolution at the pore scale. The problem is organized in three parts that focus on specific aspects: flow and reactive transport (part I), dissolution-driven geometry evolution in two dimensions (part II), and an experimental validation of three-dimensional dissolution-driven geometry evolution (part III). Five codes are used to obtain the solution to this benchmark problem, including Chombo-Crunch, OpenFOAM-DBS, a lattice Boltzman code, Vortex, and dissolFoam. These codes cover a good portion of the wide range of approaches typically employed for solving pore-scale problems in the literature, including discretization methods, characterization of the fluid-solid interfaces, and methods to move these interfaces as a result of fluid-solid reactions. A short review of these approaches is given in relation to selected published studies. Results from the simulations performed by the five codes show remarkable agreement both quantitatively—based on upscaled parameters such as surface area, solid volume, and effective reaction rate—and qualitatively—based on comparisons of shape evolution. This outcome is especially notable given the disparity of approaches used by the codes. Therefore, these results establish a strong benchmark for the validation and testing of pore-scale codes developed for the simulation of flow and reactive transport with evolving geometries. They also underscore the significant advances seen in the last decade in tools and approaches for simulating this type of problem.
Perioperative fatigue in patients with diffuse glioma
Authors: Schei Stine , Solheim Ole , Jakola Asgeir Store , Sagberg Lisa Millgård
Published: January 2020

Purpose

Few studies have assessed fatigue in relation to glioma surgery. The purpose of this study was to explore the prevalence of pre- and postoperative high fatigue, perioperative changes, and factors associated with pre- and postoperative high fatigue in patients undergoing primary surgery for diffuse glioma.

Methods

A total of 112 adult patients were prospectively included. Patient-reported fatigue was assessed before and one month after surgery using the cancer-specific European Organization for Research and Treatment of Cancer questionnaire fatigue subscale. The scores were dichotomized as high fatigue (≥ 39) or low fatigue (< 39). A change in score of ≥ 10 was considered as a clinically significant change. Factors associated with pre- and postoperative high fatigue were explored in multivariable regression analyses.

Results

High fatigue was reported by 45% of the patients preoperatively and by 42% of the patients postoperatively. Female gender and low Karnofsky Performance Status (KPS) were associated with preoperative high fatigue, while postoperative complications, low KPS and low-grade histopathology were associated with postoperative high fatigue. In total 35/92 (38%) patients reported a clinically significant improvement of fatigue scores after surgery, 36/92 (39%) patients reported a clinically significant worsening of fatigue scores after surgery, and 21/92 (23%) patients reported no clinically significant change in fatigue scores after surgery. Patients with low-grade gliomas more often reported low fatigue before surgery and high fatigue after surgery, while patients with high-grade gliomas more often reported high fatigue before surgery and low fatigue after surgery.

Conclusions

Our findings indicate that fatigue is a common symptom in patients with diffuse glioma, both pre- and postoperatively. Perioperative changes were frequently seen. This is important knowledge when informing patients before and after surgery.
Developing an Evidence-Based Technical Assistance Model: a Process Evaluation of the National Training and Technical Assistance Center for Child, Youth, and Family Mental Health
Authors: Olson Jonathan R. , Coldiron Jennifer Schurer , Parigoris Ryan M. , Zabel Michelle D. , Matarese Marlene , Bruns Eric J.
Published: January 2020

The National Training and Technical Assistance Center for Child, Youth, and Family Mental Health (NTTAC) supports the development and implementation of systems of care (SOC) for youth with serious emotional disorders (SED) and their families. This article presents results from a process evaluation of NTTAC, conducted to support the Center’s quality improvement and contribute to the knowledge base around provision of technical assistance (TA). The evaluation used a mixed methods approach with data collection focused on a defined subset of NTTAC TA recipients—recipients of federal Comprehensive Community Mental Health Services for Children SOC grants. Data sources included coded administrative records from SOC grant sites, administrative data from NTTAC, standardized measures of SOC development, and stakeholder survey data. Results indicate that TA dosage matched needs and goals of TA recipients (SOC sites), overall levels of satisfaction with TA were high, and TA content was generally aligned with need. TA recipients reported significant progress on indicators of SOC development over time. Together, these findings suggest that it is possible to develop TA methods that reflect the level and type of TA recipients’ goals and needs, and, in turn, positively impact SOC development and behavioral health service delivery.
Chronic Burping and Belching
Authors: Zad M. , Bredenoord A. J.
Published: January 2020

Belching is a physiological event that allows venting of swallowed gastric air. Excessive belching is a common presentation to gastroenterology clinics and could be isolated complains or associated with other gastrointestinal problems.

Purpose of this Review

It is to describe the presentation, diagnosis, and treatment of belching disorders

Recent Findings

These demonstrate that learned abnormal behaviors in response to unpleasant feeling in the abdomen are the driving causes for excessive belching and addressing these behaviors by speech pathology and cognitive behavior therapy considered as the keystone in its management

The gold standard in the diagnosis of belching is impedance monitoring by which belching is classified into supragastric belching and gastric belching.
The Romance Publishing Industry and Its Reputation
Authors: Cameron Lauren
Published: January 2020

Romance has always had a negative reputation, but is this reputation justified? This study examines the negative stigma surrounding the billion dollar romance publishing industry in the USA and UK. The potential causes are discussed, and testimonials from contemporary romance readers and writers provide a basis for the case that this judgemental stance should be removed.
Effect of Combined Prenatal and Adult Benzophenone-3 Dermal Exposure on Factors Regulating Neurodegenerative Processes, Blood Hormone Levels, and Hematological Parameters in Female Rats
Authors: Skórkowska Alicja , Maciejska Alicja , Pomierny Bartosz , Krzyżanowska Weronika , Starek-Świechowicz Beata , Bystrowska Beata , Broniowska Żaneta , Kazek Grzegorz , Budziszewska Bogusława
Published: January 2020

Benzophenone-3 (BP-3), the most widely used UV chemical filter, is absorbed well through the skin and gastrointestinal tract and can affect some body functions, including the survival of nerve cells. Previously, we showed that BP-3 evoked a neurotoxic effect in male rats, but since the effects of this compound are known to depend on gender, the aim of the present study was to show the concentration and potential neurotoxic action of this compound in the female rat brain. BP-3 was administered dermally to female rats during pregnancy, and then in the 7th and 8th weeks of age to their female offspring. The effect of BP-3 exposure on short-term and spatial memory, its concentrations in blood, the liver, the frontal cortex, and the hippocampus, and the effect on selected markers of brain damage were determined. Also, the impact of BP-3 on sex and thyroid hormone levels in blood and hematological parameters was examined. It has been found that this compound was present in blood and brain structures in females at a lower concentration than in males. BP-3 in both examined brain structures increased extracellular glutamate concentration and enhanced lipid peroxidation, but did not induce the apoptotic process. The tested compound also evoked hyperthyroidism and decreased the blood progesterone level and the number of erythrocytes. The presented data indicated that, after the same exposure to BP-3, this compound was at a lower concentration in the female brain than in that of the males. Although BP-3 did not induce apoptosis in the hippocampus and frontal cortex, the increased extracellular glutamate concentration and lipid peroxidation, as well as impaired spatial memory, suggested that this compound also had adverse effects in the female brain yet was weaker than in males. In contrast to the weaker effects of the BP-3 on females than the brain of males, this compound affected the endocrine system and evoked a disturbance in hematological parameters more strongly than in male rats.
Role of phosphoglucomutase in regulating trehalose metabolism in Nilaparvata lugens
Authors: Pan Bi-Ying , Liu Yong-Kang , Wu Hong-Kai , Pang Xiao-Qing , Wang Shi-Gui , Tang Bin , Xu Cai-Di
Published: January 2020

Phosphoglucomutase (PGM) is a key enzyme in glycolysis and gluconeogenesis, regulating both glycogen and trehalose metabolism in insects. In this study, we explored the potential function of phosphoglucomutase (PGM) using RNA interference technology in Nilaparvata lugens, the brown planthopper. PGM1 and PGM2 were found highly expressed in the midgut of brown planthoppers, with different expression levels in different instar nymphs. The glycogen, glucose, and trehalose levels were also significantly increased after brown planthoppers were injected with dsRNA targeting PGM1 (dsPGM1) or PGM2 (dsPGM2). In addition, injection of dsPGM1 or dsPGM2 resulted in increased membrane-bound trehalase activity but not soluble trehalase activity. Furthermore, the expression of genes related to trehalose and glycogen metabolism decreased significantly after injection with dsPGM1 and dsPGM2. The expression levels of genes involved in chitin metabolism in the brown planthopper were also significantly decreased and the insects showed wing deformities and difficulty molting following RNAi. We suggest that silencing of PGM1 and PGM2 expression directly inhibits trehalose metabolism, leading to impaired chitin synthesis.
Advanced microstructural characterisation of cast ATI 718Plus®—effect of homogenisation heat treatments on secondary phases and repair welding behaviour
Authors: Hanning Fabian , Khan Abdul Khaliq , Andersson Joel , Ojo Olanrewaju
Published: January 2020

The influence of base metal conditions on the weld cracking behaviour of cast ATI 718Plus® is investigated by comparing 4 h and 24 h dwell time pseudo-hip homogenisation heat treatments at 1120, 1160 and 1190 °C with the as-cast microstructure. Scanning electron microscopy (SEM), X-ray diffraction (XRD) on electrolytically extracted powder and transmission electron microscopy (TEM) were used to identify Nb-rich secondary phases in interdendritic areas as the C14 Laves phase and Nb(Ti) MC-type carbides. All homogenisation heat treatments but the 1120 °C 4-h condition dissolve the Laves phase. A repair welding operation was simulated by linear groove multi-pass manual gas tungsten arc welding (GTAW). The Laves phase containing microstructures resulted in lower total crack length for heat affected zone cracking. Constitutional liquation of Nb(Ti) MC-type carbides is observed as a liquation mechanism in Laves-free microstructure, while thick liquid film formation due to the Laves eutectic melting could reduce the formation of weld cracks in microstructures containing the Laves phase.
Beyond Normative Control: Against the Will Theory of Rights
Authors: Bowen Joseph
Published: January 2020

The Will Theory of Rights says that having control over another’s duties grounds rights. The Will Theory has commonly been objected to on the grounds that it undergenerates right-ascriptions along three fronts. This paper systematically examines a range of positions open to the Will Theory in response to these counterexamples, while being faithful to the Will Theory’s focus on normative control. It argues that of the seemingly plausible ways the defender of the Will Theory can proceed, one cannot both be faithful to the theory’s focus on normative control as the grounds of rights and achieve extensional adequacy.
A Critical Take on the Policy Recommendations of the EU High-Level Expert Group on Artificial Intelligence
Authors: VEALE Michael
Published: January 2020

The European Commission recently published the policy recommendations of its “High-Level Expert Group on Artificial Intelligence”: a heavily anticipated document, particularly in the context of the stated ambition of the new Commission President to regulate in that area. This article argues that these recommendations have significant deficits in a range of areas. It analyses a selection of the Group’s proposals in context of the governance of artificial intelligence more broadly, focusing on issues of framing, representation and expertise, and on the lack of acknowledgement of key issues of power and infrastructure underpinning modern information economies and practices of optimisation.
Career Opportunities in Law: Some Evidence on Career Choices of Nigerian Law Students
Authors: Onoyeyan Glory O. , Bamgbose Oludayo J.
Published: January 2020

The significance of career choice in human life cannot be overstated. Many law students upon graduation do not proceed to mainstream legal practice. They pursue careers in public administration, Alternative Dispute Resolution (ADR), as corporate secretaries, and so on. The aim of this study is to confirm the readiness of law students to proceed to legal practice upon graduation and to assess their level of career awareness in relation to law-related careers. The study also determined the areas of interest of law students in law-related careers. The study employed the survey research design in which questionnaires were used to collect data from the twelve universities that run the approved undergraduate law program up to 500 level in south-west Nigeria. Krejcie and Morgan's formula was used to select the sample size of 597. Data were analyzed using descriptive statistics. The results showed that a majority of law students do not wish to proceed into mainstream legal practice. Law students’ career intentions are in a variety of legal careers.
Disinformation Operations Aimed at (Democratic) Elections in the Context of Public International Law: The Conduct of the Internet Research Agency During the 2016 US Presidential Election
Authors: Rodriguez Manuel
Published: January 2020

Due to new technologies, the speed and volume of disinformation is unprecedented today. As seen in the 2016 US presidential election, especially with the conduct of the Internet Research Agency, this poses challenges and threats for the (democratic) political processes of internal State affairs, and in particular, (democratic) elections are under increasing risk. Disinformation has the potential to sway the outcome of an election and therefore discredits the idea of free and fair elections. Given the growing prevalence of disinformation operations aimed at (democratic) elections, the question arises as to how international law applies to such operations and how States under international law might counter such hostile operations launched by their adversaries.

From a legal standpoint, it appears that such disinformation operations do not fully escape existing international law. However, due to open questions and the geopolitical context, many States refrain from clearly labelling them as internationally wrongful acts under international law. Stretching current international legal norms to cover the issue does not seem to be the optimal solution and a binding international treaty would also need to overcome various hurdles. The author suggests that disinformation operations aimed at (democratic) elections in the context of public international law will most likely be regulated (if) by a combination of custom and bottom-up law-making influencing and reinforcing each other.
Space resources activities from the perspective of sustainability: legal aspects
Authors: Hofmann Mahulena , Bergamasco Federico
Published: January 2020

Non-technical abstract

The new forms of the use of outer space, such as space resources activities, not only will provide a vital contribution to research and industry, but could also entail a negative impact to the space environment. The present article aims at discussing from a legal perspective crucial problems such as how we shall ensure that the entities active in the area of space resources take environmental concerns into account, how we shall ensure that they utilize the best possible and least invasive technology and whether they should restore the ‘mining’ area when finishing their tasks.
In silico, in-vitro and in vivo screening of biological activities of citral
Authors: Habib Shagufta , Gupta Pawan , Bhat Sana Shafi , Gupta Jeena
Published: January 2020

Abstract. Citral, one of the main components of lemongrass oil (65–85%), is known to possess various medicinal properties like enhancing skin health and vision-improvement. It also acts as flavoring agent, used in perfumes and skin care products. The objective of this work was to elucidate the biological properties of citral at molecular level using an integrated in silico, in vitro and in vivo approaches. To elucidate this in silico molecular docking studies were performed with in vitro validation by DPPH scavenging activity, MTT assays, enzymatic assays and Chorio Allantoic Membrane (CAM) assay. The in silico analysis demonstrated the potential binding of citral with PPARγ ligand binding domain and vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2). Citral is already a proven anti-oxidant which is further confirmed by increased DPPH inhibition with increased citral concentration (IC50: 6.9 ± 1.68 μg/ml, p < 0.05). The results demonstrated that citral protect yeast cells from cytotoxic effects of hydrogen peroxide and also increase the activities of antioxidant enzymes like GST, SOD and LPO. It was also demonstrated to be cytotoxic to cancerous HeLa cells (IC50: 3.9 ± 0.38 μM, p < 0.01) and was found anti-angiogenic by CAM assay. This study highlights many important pharmaceutical properties of citral which can be explored further to increase its industrial applications.
Vitamin D signaling in a mouse allergic sensitization model
Authors: Lucas Renata , Mihály Johanna , Gericke Janine , Törőcsik Dániel , Rühl Ralph
Published: January 2020

Abstract. Vitamin D mediated signalling in the skin is discussed controversially for its beneficial or detrimental influence. In this study we examined various factors involved in Vitamin D-mediated signalling in a mouse model for allergic dermatitis with systemic (OVA IP) and systemic plus topical allergic sensitization (OVA IP + EC). We found that the major enzyme responsible for 1,25-Vitamin D3 synthesis, the 1-hydoxylase CYP27B1 (3,6-fold for OVA IP and 2,7-fold for OVA IP + EC), the vitamin D receptor (not altered) and the sensitive Vitamin D-mediated signalling target gene CYP24A1 (65-fold in OVA IP and 726-fold in OVA IP + EC) are upregulated after systemic and systemic plus topical allergic sensitization (OVA IP + EC). In consequence, active Vitamin D-mediated signalling is involved in systemic as well as systemic/topical allergic sensitization in mouse skin.
Role of Westerly Jet in Torrential Rainfall During Monsoon Over Northern Pakistan
Authors: Bibi Amna , Ullah Kalim , Yushu Zhou , Wang Ziqian , Gao Shouting
Published: January 2020

Pakistan experiences several torrential rainfall events for many years due to interactive role of midlatitude atmospheric and warm moist monsoon circulations. Deadly events such as flash flooding, runoff, and mudslides may trigger by torrential rainfall events which pose significant threat to human assets. This study was undertaken based on three severe weather events (1988, 2010, and 2013) by using percentage departure to identify wet and dry years during the period 1985–2016, which occurred over northern Pakistan. Rainfall data were obtained from 14 synoptic stations of Pakistan Meteorological Department, which were analyzed at daily, monthly, and annual bases. The data sets of Climate Research Unit, Global Precipitation Climatology Centre, and Pakistan Meteorological Department are used to justify the Weather Research and Forecasting model simulation and for analyzing the various atmospheric and diagnostic variables. Results showed teleconnection between large‐scale circulation pattern and South Asian summer monsoon during the selected events. Detailed analysis revealed that during all three events, a westerly trough was moving in the north of Pakistan and well‐marked monsoon circulations were present at the lower levels. It was observed that the interaction of two weather systems triggered heavy rainfall over area of interest. In addition, high vorticity at all levels and extension of westerly trough to the surface resulted in heavy rainfall and the penetration of upper‐level circulations anomalies consists of blocking signature over Eurasia along with Tibetan anticyclone. Hence, the monsoon low‐pressure system provides moisture convergence and upper‐level westerly trough results in upper‐level divergence to enhance the extreme rainfall events.
Using the Index Over the Last 14 Solar Cycles to Characterize Extreme Geomagnetic Activity
Authors: Chapman S. C. , Horne R. B. , Watkins N. W.
Published: January 2020

Geomagnetic indices are routinely used to characterize space weather event intensity. The
index is well resolved but is only available over five solar cycles. The
index extends over 14 cycles but is highly discretized with poorly resolved extremes. We parameterize extreme
activity by the annual‐averaged top few percent of observed values, show that these are exponentially distributed, and they track annual
index minima. This gives a 14‐cycle average of
4% chance of at least one great (
 nT) storm and
28% chance of at least one severe (
 nT) storm per year. At least one

 nT event in a given year would be a 1:151 year event. Carrington event estimate
 nT is within the same distribution as other extreme activity seen in
since 1868 so that its likelihood can be deduced from that of more moderate events. Events with
 nT are in a distinct class, requiring special conditions.
On the Broadband Instrument Response of Fiber‐Optic DAS Arrays
Authors: Lindsey Nathaniel J. , Rademacher Horst , Ajo‐Franklin Jonathan B.
Published: January 2020

Distributed Acoustic Sensing (DAS) is a novel tool in array seismology that measures the phase of backscattered laser pulses traveling in a fiber‐optic cable, and relates this measurement to the axial strain induced on the cable by a propagating seismic wavefield. Combining DAS with telecommunications optical fiber networks has begun to address a range of earth science questions where cost and field logistics have historically hindered observations. Unlike classic inertial seismometers, DAS instrument response is presently unquantified. This topic includes a variable sensing element—the fiber, including packaging and installation—which changes between experiments. Ignoring this element, one DAS record should approximate a fixed‐length strain gauge, which exactly measures Earth's motion down to quasi‐static frequencies relevant to geodesy. In this paper, we test this hypothesis using seismological observations of teleseismic earthquakes and microseism noise spanning the 1 to 120 s period range. We use a commercial DAS interrogator unit connected to an optical fiber previously used for telecommunication and a colocated broadband seismometer to estimate the DAS transfer function. We find a 1:1 correspondence with actual ground motion from 10–120 s. At shorter periods (1–10 s), DAS amplitude response is enhanced by 3–11 dB. Phase response is flat over this range of periods. We interpret the recovered DAS response function in terms of hypothesized fiber coupling and photonic effects. We propose this calibration methodology for future DAS experiments where seismic amplitude information is desired.
Seismic Structure Beneath the Tibetan Plateau From Iterative Finite‐Frequency Tomography Based on ChinArray: New Insights Into the Indo‐Asian Collision
Authors: Xiao Zhuo , Fuji Nobuaki , Iidaka Takashi , Gao Yuan , Sun Xinlei , Liu Qi
Published: January 2020

Indo‐Asian continental collision has contributed to the growth of the Tibetan Plateau, which is one of the most prominent uplifts worldwide since Cenozoic. The crustal and upper‐mantle structures are key factors in understanding the evolutionary process as well as lateral growth of the plateau. We present a new 3‐D seismic model beneath the Tibetan Plateau and its surrounding areas, which uses a large‐scale dense array from iterative finite‐frequency tomography. The new tomographic images show obvious east‐west geometrical change of the northward Indian lithosphere by high‐velocity anomalies beneath Tibet. The high‐velocity anomaly extends to Pamir in the western side, but it only reaches north Lhasa in central and eastern Tibet. A convective removal of the thickened Tibetan lithosphere is observed as a high‐velocity anomaly, followed by a subvertical subduction of the Indian mantle lithosphere beneath the Bangong‐Nujiang Suture in central Tibet. We speculate its link to the widespread magmatism and rapid uplift of central Tibet in late Miocene. A high‐velocity gap between 100 and 250 km underneath the Longmenshan fault indicates that lithospheric delamination may play an important role in surface evolution between eastern Tibet and surrounding rigid blocks. Our detailed seismological model will give an insight into how the continents collide.
Correction: A20 protects cells from TNF-induced apoptosis through linear ubiquitin-dependent and -independent mechanisms
Authors: Priem Dario , Devos Michael , Druw Sarah , Martens Arne , Slowicka Karolina , Ting Adrian T. , Pasparakis Manolis , Declercq Wim , Vandenabeele Peter , van Loo Geert , Bertrand Mathieu J. M.
Published: January 2020

The original version of this article contained an error in the name of one of the co-authors (Wim Declercq). This has been corrected in the PDF and HTML versions.
Wild primates copy higher-ranked individuals in a social transmission experiment
Authors: Canteloup Charlotte , Hoppitt William , van de Waal Erica
Published: January 2020

Little is known about how multiple social learning strategies interact and how organisms integrate both individual and social information. Here we combine, in a wild primate, an open diffusion experiment with a modeling approach: Network-Based Diffusion Analysis using a dynamic observation network. The vervet monkeys we study were not provided with a trained model; instead they had access to eight foraging boxes that could be opened in either of two ways. We report that individuals socially learn the techniques they observe in others. After having learnt one option, individuals are 31x more likely to subsequently asocially learn the other option than individuals naïve to both options. We discover evidence of a rank transmission bias favoring learning from higher-ranked individuals, with no evidence for age, sex or kin bias. This fine-grained analysis highlights a rank transmission bias in a field experiment mimicking the diffusion of a behavioral innovation.
The C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus
Authors: Orrell Kathleen E. , Mansfield Michael J. , Doxey Andrew C. , Melnyk Roman A.
Published: January 2020

Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane translocation apparatus. Despite much effort, LCT translocation remains poorly understood. Here we report the identification of 1104 LCT-T homologs, with 769 proteins from bacteria outside of clostridia. Sequences are widely distributed in pathogenic and host-associated species, in a variety of contexts and architectures. Consistent with these homologs being functional toxins, we show that a distant LCT-T homolog from Serratia marcescens acts as a pH-dependent translocase to deliver its effector into host cells. Based on evolutionary footprinting of LCT-T homologs, we further define an evolutionarily conserved translocase region that we show is an autonomous translocase capable of delivering heterologous cargo into host cells. Our work uncovers a broad class of translocating toxins and provides insights into LCT translocation.
Enhanced energy-constrained quantum communication over bosonic Gaussian channels
Authors: Noh Kyungjoo , Pirandola Stefano , Jiang Liang
Published: January 2020

Quantum communication is an important branch of quantum information science, promising unconditional security to classical communication and providing the building block of a future large-scale quantum network. Noise in realistic quantum communication channels imposes fundamental limits on the communication rates of various quantum communication tasks. It is therefore crucial to identify or bound the quantum capacities of a quantum channel. Here, we consider Gaussian channels that model energy loss and thermal noise errors in realistic optical and microwave communication channels and study their various quantum capacities in the energy-constrained scenario. We provide improved lower bounds to various energy-constrained quantum capacities of these fundamental channels and show that higher communication rates can be attained than previously believed. Specifically, we show that one can boost the transmission rates of quantum information and private classical information by using a correlated multi-mode thermal state instead of the single-mode thermal state of the same energy.
Impaired lipid biosynthesis hinders anti-tumor efficacy of intratumoral iNKT cells
Authors: Fu Sicheng , He Kaixin , Tian Chenxi , Sun Hua , Zhu Chenwen , Bai Shiyu , Liu Jiwei , Wu Qielan , Xie Di , Yue Ting , Shen Zhuxia , Dai Qingqing , Yu Xiaojun , Zhu Shu , Liu Gang , Zhou Rongbin , Duan Shengzhong , Tian Zhigang , Xu Tao , Wang Hua , Bai Li
Published: January 2020

Dysfunction of invariant natural killer T (iNKT) cells in tumor microenvironment hinders their anti-tumor efficacy, and the underlying mechanisms remain unclear. Here we report that iNKT cells increase lipid biosynthesis after activation, and that is promoted by PPARγ and PLZF synergically through enhancing transcription ofSrebf1. Among those lipids, cholesterol is required for the optimal IFN-γ production from iNKT cells. Lactic acid in tumor microenvironment reduces expression of PPARγ in intratumoral iNKT cells and consequently diminishes their cholesterol synthesis and IFN-γ production. Importantly, PPARγ agonist pioglitazone, a thiazolidinedione drug for type 2 diabetes, successfully restores IFN-γ production in tumor-infiltrating iNKT cells from both human patients and mouse models. Combination of pioglitazone and alpha-galactosylceramide treatments significantly enhances iNKT cell-mediated anti-tumor immune responses and prolongs survival of tumor-bearing mice. Our studies provide a strategy to augment the anti-tumor efficacy of iNKT cell-based immunotherapies via promoting their lipid biosynthesis.
WASP family proteins regulate the mobility of the B cell receptor during signaling activation
Authors: Rey-Suarez Ivan , Wheatley Brittany A. , Koo Peter , Bhanja Anshuman , Shu Zhou , Mochrie Simon , Song Wenxia , Shroff Hari , Upadhyaya Arpita
Published: January 2020

Regulation of membrane receptor mobility tunes cellular response to external signals, such as in binding of B cell receptors (BCR) to antigen, which initiates signaling. However, whether BCR signaling is regulated by BCR mobility, and what factors mediate this regulation, are not well understood. Here we use single molecule imaging to examine BCR movement during signaling activation and a novel machine learning method to classify BCR trajectories into distinct diffusive states. Inhibition of actin dynamics downstream of the actin nucleating factors, Arp2/3 and formin, decreases BCR mobility. Constitutive loss or acute inhibition of the Arp2/3 regulator, N-WASP, which is associated with enhanced signaling, increases the proportion of BCR trajectories with lower diffusivity. Furthermore, loss of N-WASP reduces the diffusivity of CD19, a stimulatory co-receptor, but not that of FcγRIIB, an inhibitory co-receptor. Our results implicate a dynamic actin network in fine-tuning receptor mobility and receptor-ligand interactions for modulating B cell signaling.
Learning algorithms allow for improved reliability and accuracy of global mean surface temperature projections
Authors: Strobach Ehud , Bel Golan
Published: January 2020

Climate predictions are only meaningful if the associated uncertainty is reliably estimated. A standard practice is to use an ensemble of climate model projections. The main drawbacks of this approach are the fact that there is no guarantee that the ensemble projections adequately sample the possible future climate conditions. Here, we suggest using simulations and measurements of past conditions in order to study both the performance of the ensemble members and the relation between the ensemble spread and the uncertainties associated with their predictions. Using an ensemble of CMIP5 long-term climate projections that was weighted according to a sequential learning algorithm and whose spread was linked to the range of past measurements, we find considerably reduced uncertainty ranges for the projected global mean surface temperature. The results suggest that by employing advanced ensemble methods and using past information, it is possible to provide more reliable and accurate climate projections.
Flagellin adjuvanted F1/V subunit plague vaccine induces T cell and functional antibody responses with unique gene signatures
Authors: Hamzabegovic Fahreta , Goll Johannes B. , Hooper William F. , Frey Sharon , Gelber Casey E. , Abate Getahun
Published: January 2020

Yersinia pestis, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers. Here, we report for the first time in humans that inverse caspase-3 levels, which are measures of protective antibody, significantly increased by 29% and 75% on days 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T-cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4+ T-cell responses. Several genes associated with these responses were identified that could serve as potential correlates of protection.
Domestic waste emissions to European waters in the 2010s
Authors: Vigiak Olga , Grizzetti Bruna , Zanni Michela , Aloe Alberto , Dorati Chiara , Bouraoui Fayçal , Pistocchi Alberto
Published: January 2020

Estimation of domestic waste emissions to waters is needed for pollution assessment and modelling. We assessed quantity and location of domestic waste emissions to European waters for the 2010s. Specifically, we considered discharges of domestic waste Population Equivalent (PE, the amount of waste that equals to 60 g per day of Biochemical Oxygen Demand), and mean annual loads (t/y) of total nitrogen, total phosphorus, and 5-days Biochemical Oxygen Demand. The spatial resolution and extent of the analysis corresponded to the CCM2 River and Catchment Database for Europe, for catchments of mean area of 6.4 km2. The assessment is based on available European databases that allowed pinpointing waste emissions to a high spatial and conceptual resolution. Content gaps, particularly concerning domestic waste from isolated dwellings, were filled through alternative sources of information, exploiting population density and national statistics data. The dataset is of interest for assessing waste emissions to and fate through European fresh and marine waters also beyond the three pollutants evaluated in this study.
Evaluation of screening platforms for virus-like particle production with the baculovirus expression vector system in insect cells
Authors: Strobl Florian , Ghorbanpour Sahar Masoumeh , Palmberger Dieter , Striedner Gerald
Published: January 2020

Recombinant protein and virus-like particle (VLP) production based on the baculovirus expression vector system is fast, flexible, and offers high yields. Independent from the product, a multitude of parameters are screened during process development/optimisation. Early development acceleration is a key requirement for economic efficiency, and µ-scale bioreactor systems represent an attractive solution for high-throughput (HTP) experimentation. However, limited practical knowledge is available on the relevance and transferability of screening data to pilot scales and manufacturing. The main goal of the present study was to evaluate a HTP µ-bioreactor platform with respect to its aptitude as a screening platform mainly based on transferability of results to benchtop bioreactors representing the conventional production regime. Second question was to investigate to what extent the online sensors of the µ-bioreactor contribute to process understanding and development. We demonstrated that transferability of infection screening results from the HTP µ-bioreactor scale to the benchtop bioreactor was equal or better than that from shaker cultivation. However, both experimental setups turned out to be sub-optimal solutions that only allowed for a first and rough ranking with low relevance in the case of absolute numbers. Bioreactor yields were up to one order of magnitude higher than the results of screening experiments.
Irisin levels in genetic and essential obesity: clues for a potential dual role
Authors: Mai Stefania , Grugni Graziano , Mele Chiara , Vietti Roberta , Vigna Luisella , Sartorio Alessandro , Aimaretti Gianluca , Scacchi Massimo , Marzullo Paolo
Published: January 2020

Irisin is conventionally regarded as a myokine involved in the browning of white adipose tissue, energy expenditure and glucose tolerance. Its potential link to fat accumulation and metabolic dysfunction is debated. We sought to explore the relationship between circulating irisin and components of body composition in two different phenotypes of severe obesity. For this purpose, 30 obese adults with Prader-Will syndrome (PWS) (age 35.7 ± 1.5 y, BMI 45.5 ± 1.5 kg/m2) and 30 adult controls with common obesity (age 34.9 ± 1.7 y, BMI 46.8 ± 1.4 kg/m2) underwent analysis of irisin levels, metabolic profile, body composition and resting energy expenditure (REE). Normal irisin levels were obtained from a group of 20 lean donors (age 32.4 ± 1.5 y, BMI 23.8 ± 0.8 kg/m2). Expected differences in body composition and metabolic profile existed between study groups. PWS exhibited lower muscle mass (p < 0.001), FFM (p < 0.001), REE (p < 0.001), as well as insulin (p < 0.05), HOMA-IR (p < 0.05) and triglycerides levels (p < 0.05) than controls with common obesity. In PWS, irisin levels were significantly lower and overall less dispersed than in controls with common obesity (p < 0.05), while being similar to values recorded in lean subjects. To explore the relation between irisin and body composition in obesity, univariate correlation analysis in the obese populations as a whole showed positive associations between irisin and muscle mass (p = 0.03) as well as REE (p = 0.01), which disappeared when controlled for the PWS status. Noticeably, a positive association became evident between irisin and %FM after controlling for the PWS status (p = 0.02). Also positive were associations between irisin and insulin (p = 0.02), HOMA-IR (p = 0.02) and triglycerides (p = 0.04). In stepwise multivariable regression analysis, irisin levels were independently predicted by the PWS status (p = 0.001), %FM (p = 0.004) and triglycerides (p = 0.008). Current results suggest that obese adults with PWS harbor lower irisin levels than individuals with common obesity. The divergent models of obesity herein studied suggest a potential link between circulating irisin and muscle mass and metabolic dysfunction relating to adiposity.
Formation of S. pombe Erh1 homodimer mediates gametogenic gene silencing and meiosis progression
Authors: Hazra Ditipriya , Andrić Vedrana , Palancade Benoit , Rougemaille Mathieu , Graille Marc
Published: January 2020

Timely and accurate expression of the genetic information relies on the integration of environmental cues and the activation of regulatory networks involving transcriptional and post-transcriptional mechanisms. In fission yeast, meiosis-specific transcripts are selectively targeted for degradation during mitosis by the EMC complex, composed of Erh1, the ortholog of human ERH, and the YTH family RNA-binding protein Mmi1. Here, we present the crystal structure of Erh1 and show that it assembles as a homodimer. Mutations of amino acid residues to disrupt Erh1 homodimer formation result in loss-of-function phenotypes, similar to erh1∆ cells: expression of meiotic genes is derepressed in mitotic cells and meiosis progression is severely compromised. Interestingly, formation of Erh1 homodimer is dispensable for interaction with Mmi1, suggesting that only fully assembled EMC complexes consisting of two Mmi1 molecules bridged by an Erh1 dimer are functionally competent. We also show that Erh1 does not contribute to Mmi1-dependent down-regulation of the meiosis regulator Mei2, supporting the notion that Mmi1 performs additional functions beyond EMC. Overall, our results provide a structural basis for the assembly of the EMC complex and highlight its biological relevance in gametogenic gene silencing and meiosis progression.
Association between non-alcoholic fatty liver disease and coronary calcification depending on sex and obesity
Authors: Kim Seok-hyung , Park Hae Yeul , Lee Hye Sun , Jung Kwon Soo , Lee Moon Hyoung , Jhee Jong Hyun , Kim Tae Hoon , Lee Jung Eun , Kim Hyung Jong , Kim Beom Seok , Park Hyeong Cheon , Lee Byoung Kwon , Choi Hoon Young
Published: January 2020

Non-alcoholic fatty liver disease (NAFLD) is considered a hepatic manifestation of metabolic syndrome and is associated with cardiovascular outcomes. We investigated whether NAFLD was associated with coronary artery calcification (CAC) in participants without a previous history of cardiovascular disease and whether this association differed according to sex and obesity status after adjustment for other atherosclerosis risk factors, alcohol intake, and liver enzyme levels. Among 67,441 participants, data from 8,705 participants who underwent a fatty liver status and CAC assessment during routine health screening were analysed. CAC scores were calculated using computed tomography. NAFLD was diagnosed in patients with evidence of liver steatosis on ultrasonography. Obesity was defined as a body mass index of ≥25 kg/m2. Multivariate analysis showed a significant association between NAFLD and CAC in non-obese participants (odds ratio, 1.24 [95% confidence interval, 1.01–1.53]), whereas NAFLD and CAC were not associated in obese participants. Interaction analysis showed that the association between NAFLD and CAC was influenced by sex and obesity. Subgroup analysis revealed a significant association between NAFLD and CAC in non-obese male participants (odds ratio, 1.36 [1.07–1.75]), but not in female participants. Our study indicates that non-obese men with NAFLD are prone to CAC.