bluuebunny/crossref_metadata_2025 huggingface dataset:
Sound Power: Musical Diplomacy Within the Franciscan Custody in Mandate Jerusalem
Authors: Rioli Maria Chiara , Castagnetti Riccardo
Published: November 2020

Although often underestimated or barely quoted by historical studies, music plays a crucial role in the cultural agenda of Church institutions and missionary congregations. Among the Catholic actors, the Franciscan Custody of the Holy Land was a central one connecting two of their main goals: evangelisation and education. These two tasks were strictly linked: music was a central element in the liturgies celebrated in the parishes and in the Holy Places and at the same time a pedagogical tool, taught in the schools ruled by the Friars. Music reveals also the complex process of encounter of Palestinian and Western patterns in modern Palestine. In this way the music sung and taught in the St Saviour also contributed to shape the soundscape of Jerusalem. The chapter discusses various sources related to Augustine Lama, at that time the director of theschola cantorumof St Saviour.
Middle Powers in International Development Cooperation: Assessing the Roles of South Korea and Turkey
Authors: Baydag R. Melis
Published: November 2020

This chapter analyses the foreign aid discourses of South Korea and Turkey in international development cooperation under the framework of middle-power theory. Korea and Turkey make use of their middle-power identity with the aim of increasing their presence around the globe, where foreign aid is used as an important foreign policy tool. They claim to be like-minded peers playing a bridging role between the developed and developing worlds. Despite opting for similar results in global politics, they show divergent strategic and ideational pathways in foreign aid. This creates significant implications for cooperation at the global level, especially because it questions the role of middle-power collaboration in facilitating possible rapprochement between traditional and emerging donors as well as within the Southern providers.
Partnerships with the Private Sector: Success Factors and Levels of Engagement in Development Cooperation
Authors: Pérez-Pineda Jorge A. , Wehrmann Dorothea
Published: November 2020

Partnerships with private-sector actors are widely considered crucial for achieving the 2030 Agenda for Sustainable Development, but the ways of how to engage best with actors from the private sector in development cooperation are contested. Often it is feared that influential companies will hijack unregulated partnership initiatives for their own benefits. This chapter investigates different levels of engagement for partnerships with private-sector actors and discusses how they can be more successful. We show that it matters whether it is envisioned to incentivise and regulate private-sector engagement at the global or at the country level. The chapter’s main findings support context-specific approaches and emphasise the need to strengthen national development agencies as focal points for private-sector engagement in development cooperation.
Structure, Dynamics and Function of the 26S Proteasome
Authors: Mao Youdong
Published: November 2020

The 26S proteasome is the most complex ATP-dependent protease machinery, of ~2.5 MDa mass, ubiquitously found in all eukaryotes. It selectively degrades ubiquitin-conjugated proteins and plays fundamentally indispensable roles in regulating almost all major aspects of cellular activities. To serve as the sole terminal “processor” for myriad ubiquitylation pathways, the proteasome evolved exceptional adaptability in dynamically organizing a large network of proteins, including ubiquitin receptors, shuttle factors, deubiquitinases, AAA-ATPase unfoldases, and ubiquitin ligases, to enable substrate selectivity and processing efficiency and to achieve regulation precision of a vast diversity of substrates. The inner working of the 26S proteasome is among the most sophisticated, enigmatic mechanisms of enzyme machinery in eukaryotic cells. Recent breakthroughs in three-dimensional atomic-level visualization of the 26S proteasome dynamics during polyubiquitylated substrate degradation elucidated an extensively detailed picture of its functional mechanisms, owing to progressive methodological advances associated with cryogenic electron microscopy (cryo-EM). Multiple sites of ubiquitin binding in the proteasome revealed a canonical mode of ubiquitin-dependent substrate engagement. The proteasome conformation in the act of substrate deubiquitylation provided insights into how the deubiquitylating activity of RPN11 is enhanced in the holoenzyme and is coupled to substrate translocation. Intriguingly, three principal modes of coordinated ATP hydrolysis in the heterohexameric AAA-ATPase motor  were discovered to regulate intermediate functional steps of the proteasome, including ubiquitin-substrate engagement, deubiquitylation, initiation of substrate translocation and processive substrate degradation. The atomic dissection of the innermost working of the 26S proteasome opens up a new era in our understanding of the ubiquitin-proteasome system and has far-reaching implications in health and disease.
Trade-Offs and Turnstiles as the Main Drivers of the Transformation Process Towards Sustainability
Authors: Hernandez Ariel Macaspac
Published: November 2020

This chapter is a major pillar of the theoretical framework and reiterates how this book understands the intricacies of decision-making in the context of transformation towards sustainability. It looks at how power, identities, path dependence, emotions, norms, institutions and paradigms can promote or inhibit effective decision-making. This understanding aims not only to achieve the ‘deconstruction’ of paradigmatically ‘given’ terms, which are widespread within and across disciplines, but, equally importantly, to also develop and/or refine decision tools to address complexity and uncertainty.
Berücksichtigung der globalen Entwicklung
Authors: Prettenthaler Franz , Gössling Stefan , Damm Andrea , Neger Christoph , Köberl Judith , Haas Willi
Published: November 2020

Der österreichische Tourismus ist in hohem Maß von Auslandsmärkten abhängig. Dies gilt umso mehr, als rund die Hälfte der Reisen der Österreicherinnen und Österreicher ins Ausland erfolgt (Statistik Austria 2018a). In dieser Hinsicht ist eine umfassende Abschätzung der zukünftigen Entwicklung des Sektors nur unter Berücksichtigung von Veränderungen auf globaler und europäischer Ebene möglich. Das vorliegende Kapitel bietet daher einen Überblick über Studien, die sich mit dieser Thematik befassen, sowohl mit den direkten Auswirkungen des Klimawandels auf den europäischen Tourismus (insbesondere aufgrund von Temperatur- und Niederschlagsänderungen) als auch mit übrigen Einflussfaktoren auf die internationalen Touristenströme (z. B. demografische und ökonomische Entwicklungen, geopolitische Risiken, allgemeine Trends). Generell ist die vorliegende Thematik noch mit großen Unsicherheiten verbunden, unter anderem in Hinblick darauf, wie hoch die globale Erwärmung in bestimmten Zeitabschnitten sein wird. Wichtig ist dabei auch, inwieweit es gelingen wird, die anthropogenen Treibhausgasemissionen zu senken und herauszuarbeiten, inwieweit der Tourismus hierzu beitragen könnte. Daher beschäftigt sich der zweite Abschnitt des Kapitels mit Studien, die versuchen, den Anteil des Tourismus an den Emissionen zu berechnen, zuerst auf globaler Ebene und dann auch hinsichtlich der österreichischen Reisenden und der heimischen Tourismuswirtschaft.
Städte, denkmalgeschützte Anlagen und kulturelles Erbe
Authors: Jiricka-Pürrer Alexandra , Brandenburg Christiane , Pröbstl-Haider Ulrike , Allex Brigitte
Published: November 2020

Neben dem Gesundheitstourismus ist auch die Nachfrage nach Städtereisen1 in den letzten zehn Jahren im österreichischen Sommertourismus konstant gestiegen (Fleischhacker 2019). Die verstärkte Nachfrage nach Städtereisen spiegelt den Gesamttrend zur kurzfristigen flexibleren Urlaubsplanung (Zellmann und Mayrhofer 2015, 2017) sowie zu mehrmaligen Kurzurlauben (Wirtschaftskammer Tirol 2018; WKO 2018) wider. In der ganzjährigen Betrachtung machen Kultur‑, Besichtigungs- und Städteurlaube knapp 10 % der Reisearten in Österreich aus (Statistik Austria 2016, 2017). Für Wien, als größte österreichische Stadtdestination, zeigen die Ankünfte einen positiven Trend in den letzten zehn Jahren (MA 23 Dezernat Statistik Wien 2018a). Bei den Herkunftsmärkten ist Deutschland das wichtigste Land. Bei den Gästen aus dem Inland, die den zweitwichtigsten Herkunftsmarkt für den Wientourismus darstellen, zeigen die aktuellsten Statistiken aus 2018 ein deutliches Plus von 6 % bei den Nächtigungen im Vergleich zu 2017. Mit größerem Abstand finden sich danach die USA als Herkunftsmarkt auf Platz drei für Wienreisen (MA 23 Dezernat Statistik Wien 2018b).
Anders denken und handeln – Bewusstsein für das Klima
Authors: Fritsch Sabine , Thiem Carolin , Sartori Oliver
Published: November 2020

Jede und jeder Einzelne kann einen Beitrag zu einer zukunftsfähigen und nachhaltigen Entwicklung unseres Planeten leisten und den eigenen CO2-Fußabdruck durch klimafreundliche Verhaltensweisen reduzieren. Warum nur fällt das so schwer? Mangelt es am Bewusstsein?
Herausforderungen einer klimafreundlichen Energieversorgung
Authors: Kleemann Janine , Neumann Kirsten , Zehm Antje
Published: November 2020

Sucht man nachhaltige Lösungen zur Begrenzung des globalen, anthropogenen Temperaturanstiegs, ist eine kritische Auseinandersetzung mit der Energieversorgung unablässig. In Deutschland wurde in einem ersten Schritt der Energiewende der Ausbau erneuerbarer Energien massiv forciert. Es zeigt sich, dass mit einer Vielzahl ausgereifter Technologien die Versorgungssicherheit gewährleistet werden kann.
Hack the School: A Creative Toolkit to Transform School Spaces
Authors: Sasot Sílvia , Belvis Esther
Published: November 2020

The ‘Hack the School’ project provides school communities a guided experience to support the transformation of their learning spaces. The aim is to foster change through a comprehensive and co-creative approach facilitating the transition from traditional uses of space to innovative ones with the concept of wellbeing as primary agency. A conceptual framework based on seven principles—welcome, belonging, communication, cooperation, diversity, movement and transduction—and an applied creative toolkit equip the process and provide a unique and novel perspective to the topic of innovative learning environments. Thus, the project channels the emerging needs regarding educational spaces challenging the current regulations that the public administration applies in Spain and initiates a dialogical collaboration between the field of education and architecture. The challenge open to all schools and funded by the Jaume Bofill Foundation received over 170 proposals in the Catalan context, where 30 schools were selected and are now becoming effective ‘hackers’.
School Change: Emerging Findings of How to Achieve the “Buzz”
Authors: French Raechel
Published: November 2020

This chapter explores emerging findings from the research question, “What characterizes a successful transition of a school from traditional classrooms to an innovative learning environment in the context of the design and construction process?” Many schools today are trading in their identical classroom model for activity-driven, technology-infused spaces and envision a future in which teaching, culture, and space align seamlessly resulting in the intangible “buzz” of engaged learning. However, research and experience show many of these schools fail to supplement the design and construction process with initiatives to align teaching practices, organizational structures, and leadership with the intended vision. This often results in a misalignment between the pedagogical goals of the building and its subsequent use. To provide a research-based course of action for transitioning schools and a basis for future Ph.D. study, exploratory case studies were completed of schools operating in new buildings and having achieved this “buzz”. Emerging best-practice processes and tools are shared.
The cardiovascular determinants of physical function in patients with end-stage kidney disease on haemodialysis
Authors: Adenwalla Sherna F. , Billany Roseanne E. , March Daniel S. , Gulsin Gaurav S. , Young Hannah M. L. , Highton Patrick , Churchward Darren C. , Young Robin , Careless Alysha , Tomlinson Clare L. , McCann Gerry P. , Burton James O. , Graham-Brown Matthew P. M.
Published: November 2020

Patients with end-stage kidney disease (ESKD) are often sedentary and decreased functional capacity associates with mortality. The relationship between cardiovascular disease (CVD) and physical function has not been fully explored. Understanding the relationships between prognostically relevant measures of CVD and physical function may offer insight into how exercise interventions might target specific elements of CVD. 130 patients on haemodialysis (mean age 57 ± 15 years, 73% male, dialysis vintage 1.3 years (0.5, 3.4), recruited to the CYCLE-HD trial (ISRCTN11299707), underwent cardiovascular phenotyping with cardiac MRI (left ventricular (LV) structure and function, pulse wave velocity (PWV) and native T1 mapping) and cardiac biomarker assessment. Participants completed the incremental shuttle walk test (ISWT) and sit-to-stand 60 (STS60) as field-tests of physical function. Linear regression models identified CV determinants of physical function measures, adjusted for age, gender, BMI, diabetes, ethnicity and systolic blood pressure. Troponin I, PWV and global native T1 were univariate determinants of ISWT and STS60 performance. NT pro-BNP was a univariate determinant of ISWT performance. In multivariate models, NT pro-BNP and global native T1 were independent determinants of ISWT and STS60 performance. LV ejection fraction was an independent determinant of ISWT distance. However, age and diabetes had the strongest relationships with physical function. In conclusion, NT pro-BNP, global native T1 and LV ejection fraction were independent CV determinants of physical function. However, age and diabetes had the greatest independent influence. Targeting diabetic care may ameliorate deconditioning in these patients and a multimorbidity approach should be considered when developing exercise interventions.
Measuring the presence of organized crime across Italian provinces: a sensitivity analysis
Authors: Bernardo Giovanni , Brunetti Irene , Pinar Mehmet , Stengos Thanasis
Published: November 2020

The existing literature identifies different indicators to construct organized crime indices and places equal importance to different concepts of organized crime. This paper examines the sensitivity of organized crime across Italian provinces when different set of indicators and weights are used to combine crime indicators. Our findings suggest that there is a remarkable variation in the distribution of organized crime across Italian provinces based on the choice of indicators and the importance given to different crime indicators. It is also found that the relationship of organized crime with socioeconomic and political factors varies depending on the normative choices made in the construction of an organized crime index.
The Role of Children’s Dietary Pattern and Physical Activity in the Association Between Breastfeeding and BMI at Age 5: The GECKO Drenthe Cohort
Authors: Vinke Petra Corianne , Tigelaar Carolien , Küpers Leanne Karen , Corpeleijn Eva
Published: November 2020

Objectives

Breastfeeding is protective against childhood obesity, but the role of childhood lifestyle in this association is unclear. We investigated whether physical activity and dietary pattern at age 5 differed between breastfed and non-breastfed children, and how they relate to Body Mass Index (BMI) Z-scores.

Methods

1477 children of the Dutch GECKO Drenthe birth cohort were included. At one month, children were categorized as breastfed (receiving breast milk exclusively or in combination with formula milk) or non-breastfed (receiving formula milk exclusively). At age 5, height and weight were objectively measured, physical activity was measured by ActiGraph GT3x and dietary patterns were assessed with a parent-reported food pattern questionnaire, assessing the consumption frequency of selected food items at seven occasions over the day.

Results

Non-breastfed children had higher BMI Z-scores (0.36 ± 0.90 vs. 0.20 ± 0.80 SD, p = 0.002), more frequently consumed sugar-sweetened beverages (25.0 ± 10.5 vs. 22.5 ± 9.71 times per week, p < 0.001), and consumed relatively less whole-wheat or brown bread (p = 0.007). Differences in sugar-sweetened beverage consumption were most pronounced during main meals. Total fruit consumption, sedentary time and moderate-to-vigorous physical activity levels did not differ between the groups. Multivariable adjusted linear regression analyses showed that the differences in BMI-z score between non-breastfed and breastfed children were not explained by the differences in sugar-sweetened beverages or type of bread consumed.

Conclusions

Infant breastfeeding itself is indicative of healthy dietary behaviors in early life, and is also more likely to be followed by a favorable dietary pattern at toddler age. However, the differences in dietary habits between breastfed and non-breastfed children did not explain the difference in BMI Z-score at the age of 5.
Thermodynamic Prediction and Experimental Verification of Multiphase Composition of Scale Formed on Reheated Alloy Steels
Authors: Osei Richard , Lekakh Simon , O’Malley Ronald
Published: November 2020

The structure, phase, and composition of scale formed on a continuously cast steel slab during reheating depend on intrinsic factors (steel chemistry, microstructure, and as-cast surface condition) and extrinsic parameters (temperature, time, composition, and velocity of combustion gas atmosphere). The scale that forms on a slab normally has several layers with differing compositions and phases and knowledge of this scale structure is important in subsequent descaling and hot rolling processing steps. Formation of multiphase scale structures on steel during high temperature oxidation in reheat furnace proceeds according to a local thermodynamic equilibrium, while thickness of layers depends on kinetic conditions (mostly by diffusion). In this study, the local thermodynamic equilibrium conditions through the scale layer were simulated using different oxygen/steel ratios, which mimicked the conditions for scale formation at the external, internal, and sublayer oxide region at metal/scale boundary. Experiments were performed in a simulated combustion atmosphere using typical industrial reheat time/temperature conditions. The phases that developed in layered scale structure were documented using SEM/EDX and Raman spectroscopy. The predicted scale compositions and phases were in good agreement with the experimental results for studies with Mn and Si-alloyed carbon steel, Cr-alloyed ferritic, and Cr, Ni-alloyed austenitic steels.
Targeting the alternative bile acid synthetic pathway for metabolic diseases
Authors: Jia Wei , Wei Meilin , Rajani Cynthia , Zheng Xiaojiao
Published: November 2020

The gut microbiota is profoundly involved in glucose and lipid metabolism, in part by regulating bile acid (BA) metabolism and affecting multiple BA-receptor signaling pathways. BAs are synthesized in the liver by multi-step reactions catalyzed via two distinct routes, the classical pathway (producing the 12α-hydroxylated primary BA, cholic acid), and the alternative pathway (producing the non-12α-hydroxylated primary BA, chenodeoxycholic acid). BA synthesis and excretion is a major pathway of cholesterol and lipid catabolism, and thus, is implicated in a variety of metabolic diseases including obesity, insulin resistance, and nonalcoholic fatty liver disease. Additionally, both oxysterols and BAs function as signaling molecules that activate multiple nuclear and membrane receptor-mediated signaling pathways in various tissues, regulating glucose, lipid homeostasis, inflammation, and energy expenditure. Modulating BA synthesis and composition to regulate BA signaling is an interesting and novel direction for developing therapies for metabolic disease. In this review, we summarize the most recent findings on the role of BA synthetic pathways, with a focus on the role of the alternative pathway, which has been under-investigated, in treating hyperglycemia and fatty liver disease. We also discuss future perspectives to develop promising pharmacological strategies targeting the alternative BA synthetic pathway for the treatment of metabolic diseases.
Fractional Paley–Wiener and Bernstein spaces
Authors: Monguzzi Alessandro , Peloso Marco M. , Salvatori Maura
Published: November 2020

We introduce and study a family of spaces of entire functions in one variable that generalise the classical Paley–Wiener and Bernstein spaces. Namely, we consider entire functions of exponential typeawhose restriction to the real line belongs to the homogeneous Sobolev space$$\dot{W}^{s,p}$$W˙s,pand we call these spaces fractional Paley–Wiener if$$p=2$$p=2and fractional Bernstein spaces if$$p\in (1,\infty )$$p∈(1,∞), that we denote by$$PW^s_a$$PWasand$${\mathcal {B}}^{s,p}_a$$Bas,p, respectively. For these spaces we provide a Paley–Wiener type characterization, we remark some facts about the sampling problem in the Hilbert setting and prove generalizations of the classical Bernstein and Plancherel–Pólya inequalities. We conclude by discussing a number of open questions.
Erratum to: Anthropomorphism Indexes of the Kinematic Chain for Artificial Hands
Authors: Llop-Harillo Immaculada , Pérez-González Antonio , Andrés-Esperanza Javier
Published: November 2020

The article “Anthropomorphism Indexes of the Kinematic Chain for Artificial Hands”, written by Immaculada Llop-Harillo, Antonio Pérez-González, Javier Andrés-Esperanza, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on May 23th 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed in October 2020 to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The original article has been corrected.
Solo Dance in Archaic and Classical Greek Literature
Authors: Olsen Sarah
Published: November 2020

“Ancient Greek dance” traditionally evokes images of stately choruses or lively Dionysiac revels – communal acts of performance. This is the first book to look beyond the chorus to the diverse and complex representation of solo dancers in Archaic and Classical Greek literature. It argues that dancing alone signifies transgression and vulnerability in the Greek cultural imagination, as isolation from the chorus marks the separation of the individual from a range of communal social structures. It also demonstrates that the solo dancer is a powerful figure for literary exploration and experimentation, highlighting the importance of the singular dancing body in the articulation of poetic, narrative, and generic interests across Greek literature. Taking a comparative approach and engaging with current work in dance and performance studies, this book reveals the profound literary and cultural importance of the unruly solo dancer in the ancient Greek world.
The Israeli Settler Movement
Authors: Hirsch-Hoefler Sivan , Mudde Cas
Published: November 2020

The Israeli settler movement plays a key role in Israeli politics and the Arab-Israeli conflict, yet very few empirical studies of the movement exist. This is the first in-depth examination of the contemporary Israeli settler movement from a structural (rather than purely historical or political) perspective, and one of the few studies to focus on a longstanding, radical right-wing social movement in a non-western political context. A trailblazing systematic assessment of the role of the settler movement in Israeli politics writ large, as well as in relation to Israel's policy towards the West Bank, this book analyzes the movement both as a whole and as a combination of its parts (i.e. branches) - institutions, networks, and individuals. Whether you are a student, researcher, or policymaker, this book offers a comprehensive and original theoretical framework alongside a rich empirical analysis which illuminates social movements in general, and the Israeli settler movement in particular.
Khongso
Authors: Wright Jonathan
Published: November 2020

Khongso /kʰɔŊ˦so˧/ is an SVO Tibeto-Burman language spoken by between two and three thousand speakers in Paletwa Township, Southern Chin State, Myanmar (Dryer 2008, Wright 2009). The speakers live in 17 villages primarily along the Michaung River (see Figure 1).1 Khongso is mutually intelligible with Anu, which has a population of 700 and is spoken west of the Khongso area (So-Hartmann 1988, Wright 2009, Lewis, Simons & Fennig 2016). The ISO code for Khongso and Anu is anl and the glottolog code is anuu1241.
Essentially non-oscillatory and weighted essentially non-oscillatory schemes
Authors: Shu Chi-Wang
Published: November 2020

Essentially non-oscillatory (ENO) and weighted ENO (WENO) schemes were designed for solving hyperbolic and convection–diffusion equations with possibly discontinuous solutions or solutions with sharp gradient regions. The main idea of ENO and WENO schemes is actually an approximation procedure, aimed at achieving arbitrarily high-order accuracy in smooth regions and resolving shocks or other discontinuities sharply and in an essentially non-oscillatory fashion. Both finite volume and finite difference schemes have been designed using the ENO or WENO procedure, and these schemes are very popular in applications, most noticeably in computational fluid dynamics but also in other areas of computational physics and engineering. Since the main idea of the ENO and WENO schemes is an approximation procedure not directly related to partial differential equations (PDEs), ENO and WENO schemes also have non-PDE applications. In this paper we will survey the basic ideas behind ENO and WENO schemes, discuss their properties, and present examples of their applications to different types of PDEs as well as to non-PDE problems.
Systematic Review of Sensory Stimulation Programs in the	Rehabilitation of Acquired Brain Injury
Authors: Pinto Joana O. , Dores Artemisa R. , Peixoto Bruno , Geraldo Andreia , Barbosa Fernando
Published: November 2020

Abstract. Acquired Brain Injury (ABI) can lead to sensory deficits and compromise functionality. However, most studies have been focused on motor stimulation in stroke and traumatic brain injury (TBI). Sensory stimulation in stroke and mild/moderate TBI has received reduced interest. The main objective of this review is to know the methodological characteristics and effects of sensory programs in ABI. Studies with the purpose of testing the efficacy of those programs were identified through a literature search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Collaboration Guidelines. Twenty-three studies were included in this review. The results show that in most studies sensory stimulation started within 12 months after injury and there is no consensus regarding frequency, duration and number of sessions, duration of intervention, and instruments used to assess outcomes. Most programs involved unisensory stimulation, and vision was the predominant target. The most used methods were compensation and somatosensory discrimination training. Most studies used a pre- and post-intervention assessment, with few studies comprising follow-up assessment. Regarding the studies revised, the interventions with positive outcomes in ABI are: compensation, cognitive training, vestibular intervention, somatosensory discrimination training, proprioceptive stimulation with muscle vibration, and sustained attention training with olfactory stimulation. Available findings suggest that sensory stimulation has positive results with immediate and long-term improvements in sensory functioning. This review provides useful information to improve rehabilitation and to design future investigation.
Local Earthquake Tomography at Los Humeros Geothermal Field (Mexico)
Authors: Toledo T. , Gaucher E. , Jousset P. , Jentsch A. , Haberland C. , Maurer H. , Krawczyk C. , Calò M. , Figueroa A.
Published: November 2020

A passive seismic experiment using 25 broadband and 20 short‐period stations was conducted between September 2017 and September 2018 at Los Humeros geothermal field, an important natural laboratory for superhot geothermal systems in Mexico. From the recorded local seismicity, we derive a minimum 1‐D velocity model and obtain 3‐D Vp and Vp/Vs structures of Los Humeros. We improved the classical local earthquake tomography by using a postprocessing statistical approach. Several inversions were computed and averaged to reduce artifacts introduced by the model parametrization and to increase the resolution of the investigated region. Finally, the resulting Vp and Vp/Vs structures and associated seismicity were integrated with newly acquired geophysical and petrophysical data for comprehensive interpretation. The recorded seismicity is mainly grouped in three clusters, two of which seem directly related to exploitation activities. By combining new laboratory measurements and existing well data with our Vp model, we estimate possible geological unit boundaries. One large intrusion‐like body in the Vp model, together with neighboring high Vp/Vs anomalies, hints at a region of active resurgence or uplift due to the intrusion of new magma at the northern portion of the geothermal field. We interpret high Vp/Vs features as fluid bearing regions potentially favorable for further geothermal exploitation. Deep reaching permeable faults cutting the reservoir unit could explain fluid flow from a deeper local heat source in the area.
Measuring the Impact of a New Snow Model Using Surface Energy Budget Process Relationships
Authors: Day Jonathan J. , Arduini Gabriele , Sandu Irina , Magnusson Linus , Beljaars Anton , Balsamo Gianpaolo , Rodwell Mark , Richardson David
Published: November 2020

Energy exchange at the snow‐atmosphere interface in winter is important for the evolution of temperature at the surface and within the snow, preconditioning the snowpack for melt during spring. This study illustrates a set of diagnostic tools that are useful for evaluating the energy exchange at the Earth's surface in an Earth System Model, from a process‐based perspective, using in situ observations. In particular, a new way to measure model improvement using the response of the surface temperature and other surface energy budget (SEB) terms to radiative forcing is presented. These process‐oriented diagnostics also provide a measure of the coupling strength between the incoming radiation and the various terms in the SEB, which can be used to ensure that improvements in predictions of user‐relevant properties, such as 2 m temperature, are happening for the right reasons. Correctly capturing such process relationships is a necessary step toward achieving more skilful weather forecasts and climate projections. These diagnostic techniques are applied to assess the impact of a new multi‐layer snow scheme in the European Centre for Medium‐Range Weather Forecasts'‐Integrated Forecast System at two high‐Arctic sites (Summit, Greenland and Sodankylä, Finland). A previous study showed that it will enhance 2 m temperature forecast skill across the Northern Hemisphere in boreal winter compared to forecasts with the single layer model, reducing a warm bias. In this study we use the diagnostics to show that the bias is improved for the right reasons.
BRDT promotes ovarian cancer cell growth
Authors: Chen Ling , Cai Shang , Wang Jing-mei , Huai Ying-ying , Lu Pei-Hua , Chu Qian
Published: November 2020

Bromodomain testis-specific factor (BRDT) is a member of the bromodomain and extra-terminal (BET) family proteins. Its expression and potential functions in ovarian cancer were examined. We show that BRDT is overexpressed in human ovarian cancer tissues and in established (CaOV3)/primary ovarian cancer cells. However, its expression is low in ovarian epithelial tissues and cells. Significantly, shRNA-induced silencing or CRISPR/Cas9-mediated knockout of BRDT inhibited ovarian cancer cell growth, viability, proliferation and migration, and induced significant apoptosis activation. Conversely, exogenous overexpression of BRDT, by a lentiviral construct, augmented CaOV3 cell proliferation and migration. In CaOV3 cells expression of two key BRDT target genes, polo-like kinase 1 (PLK1) and aurora kinase C (AURKC), was downregulated by BRDT shRNA or knockout, but upregulated with BRDT overexpression. In vivo, xenograft tumors-derived from BRDT-knockout CaOV3 cells grew significantly slower than control tumors in severe combined immunodeficient (SCID) mice. Furthermore, intratumoral injection of BRDT shRNA lentivirus potently inhibited the growth of primary ovarian cancer xenografts in SCID mice. Downregulation of PLK1 and AURKC was detected in BRDT-knockout and BRDT-silenced tumor tissues. Collectively, BRDT overexpression promotes ovarian cancer cell progression. Targeting BRDT could be a novel strategy to treat ovarian cancer.
(D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model
Authors: Chiu Ching-Chi , Weng Yi-Hsin , Huang Ying-Zu , Chen Rou-Shayn , Liu Yu-Chuan , Yeh Tu-Hsueh , Lu Chin-Song , Lin Yan-Wei , Chen Yu-Jie , Hsu Chia-Chen , Chiu Chi-Han , Wang Yu-Ting , Chen Wan-Shia , Liu Shu-Yu , Wang Hung-Li
Published: November 2020

Patients with familial type 17 of Parkinson’s disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson’s disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/β-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/β-catenin pathway. Protein levels of Wnt1 and nuclear β-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear β-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/β-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.
Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant
Authors: Fichtner Michael , Bozkurt Emir , Salvucci Manuela , McCann Christopher , McAllister Katherine A. , Halang Luise , Düssmann Heiko , Kinsella Sinéad , Crawford Nyree , Sessler Tamas , Longley Daniel B. , Prehn Jochen H. M.
Published: November 2020

Colorectal cancer is a molecularly heterogeneous disease. Responses to genotoxic chemotherapy in the adjuvant or palliative setting vary greatly between patients, and colorectal cancer cells often resist chemotherapy by evading apoptosis. Antagonists of an inhibitor of apoptosis proteins (IAPs) can restore defective apoptosis signaling by degrading cIAP1 and cIAP2 proteins and by inhibition of XIAP. Due to the multiple molecular mechanisms-of-action of these targets, responses to IAP antagonist may differ between molecularly distinct colon cancer cells. In this study, responses to the IAP antagonist Birinapant and oxaliplatin/5-fluorouracil (5-FU) were investigated in 14 colon cancer cell lines, representing the consensus molecular subtypes (CMS). Treatment with Birinapant alone did not result in a substantial increase in apoptotic cells in this cell line panel. Annexin-V/PI assays quantified by flow cytometry and high-content screening showed that Birinapant increased responses of CMS1 and partially CMS3 cell lines to oxaliplatin/5-FU, whereas CMS2 cells were not effectively sensitized. FRET-based imaging of caspase-8 and -3 activation validated these differences at the single-cell level, with CMS1 cells displaying sustained activation of caspase-8-like activity during Birinapant and oxaliplatin/5-FU co-treatment, ultimately activating the intrinsic mitochondrial apoptosis pathway. In CMS2 cell lines, Birinapant exhibited synergistic effects in combination with TNFα, suggesting that Birinapant can restore extrinsic apoptosis signaling in the context of inflammatory signals in this subtype. To explore this further, we co-cultured CMS2 and CMS1 colon cancer cells with peripheral blood mononuclear cells. We observed increased cell death during Birinapant single treatment in these co-cultures, which was abrogated by anti-TNFα-neutralizing antibodies. Collectively, our study demonstrates that IAP inhibition is a promising modulator of response to oxaliplatin/5-FU in colorectal cancers of the CMS1 subtype, and may show promise as in the CMS2 subtype, suggesting that molecular subtyping may aid as a patient stratification tool for IAP antagonists in this disease.
Scope and costs of autorefraction and photoscreening for childhood amblyopia—a systematic narrative review in relation to the EUSCREEN project data
Authors:   on behalf of The EUSCREEN Foundation, Horwood Anna M. , Griffiths Helen J. , Carlton Jill , Mazzone Paolo , Channa Arinder , Nordmann Mandy , Simonsz Huibert J.
Published: November 2020

Background

Amblyopia screening can target reduced visual acuity (VA), its refractive risk factors, or both. VA testing is imprecise under 4 years of age, so automated risk-factor photoscreening appears an attractive option. This review considers photoscreening used in community services, focusing on costs, cost-effectiveness and scope of use, compared with EUSCREEN project Country Reports describing how photo- and automated screening is used internationally.

Methods

A systematic narrative review was carried out of all English language photoscreening literature to September 10th 2018, using publicly available search terms. Where costs were considered, a CASP economic evaluation checklist was used to assess data quality.

Results

Of 370 abstracts reviewed, 55 reported large-scale community photoscreening projects. Five addressed cost-effectiveness specifically, without original data. Photoscreening was a stand-alone, single, test event in 71% of projects. In contrast, 25 of 45 EUSCREEN Country Reports showed that if adopted, photoscreening often supplements other tests in established programmes and is rarely used as a stand-alone test. Reported costs varied widely and evidence of cost-effectiveness was sparse in the literature, or in international practice. Only eight (13%) papers compared the diagnostic accuracy or cost-effectiveness of photoscreening and VA testing, and when they did, cost-effectiveness of photoscreening compared unfavourably.

Discussion

Evidence that photoscreening reduces amblyopia or strabismus prevalence or improves overall outcomes is weak, as is evidence of cost-effectiveness, compared to later VA screening. Currently, the most cost-effective option seems to be a later, expert VA screening with the opportunity for a re-test before referral.
Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the mouse developing brain
Authors: Madore C. , Leyrolle Q. , Morel L. , Rossitto M. , Greenhalgh A. D. , Delpech J. C. , Martinat M. , Bosch-Bouju C. , Bourel J. , Rani B. , Lacabanne C. , Thomazeau A. , Hopperton K. E. , Beccari S. , Sere A. , Aubert A. , De Smedt-Peyrusse V. , Lecours C. , Bisht K. , Fourgeaud L. , Gregoire S. , Bretillon L. , Acar N. , Grant N. J. , Badaut J. , Gressens P. , Sierra A. , Butovsky O. , Tremblay M. E. , Bazinet R. P. , Joffre C. , Nadjar A. , Layé S.
Published: November 2020

Omega-3 fatty acids (n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3 PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in Humans. However, the n-3 PUFAs deficiency-mediated mechanisms affecting the development of the central nervous system are poorly understood. Active microglial engulfment of synapses regulates brain development. Impaired synaptic pruning is associated with several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development in mice. Our results show that maternal dietary n-3 PUFA deficiency increases microglia-mediated phagocytosis of synaptic elements in the rodent developing hippocampus, partly through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, altering neuronal morphology and affecting cognitive performance of the offspring. These findings provide a mechanistic insight into neurodevelopmental defects caused by maternal n-3 PUFAs dietary deficiency.
Location-specific inhibition of Akt reveals regulation of mTORC1 activity in the nucleus
Authors: Zhou Xin , Zhong Yanghao , Molinar-Inglis Olivia , Kunkel Maya T. , Chen Mingyuan , Sun Tengqian , Zhang Jiao , Shyy John Y.-J. , Trejo JoAnn , Newton Alexandra C. , Zhang Jin
Published: November 2020

The mechanistic target of rapamycin complex 1 (mTORC1) integrates growth, nutrient and energy status cues to control cell growth and metabolism. While mTORC1 activation at the lysosome is well characterized, it is not clear how this complex is regulated at other subcellular locations. Here, we combine location-selective kinase inhibition, live-cell imaging and biochemical assays to probe the regulation of growth factor-induced mTORC1 activity in the nucleus. Using a nuclear targeted Akt Substrate-based Tandem Occupancy Peptide Sponge (Akt-STOPS) that we developed for specific inhibition of Akt, a critical upstream kinase, we show that growth factor-stimulated nuclear mTORC1 activity requires nuclear Akt activity. Further mechanistic dissection suggests that nuclear Akt activity mediates growth factor-induced nuclear translocation of Raptor, a regulatory scaffolding component in mTORC1, and localization of Raptor to the nucleus results in nuclear mTORC1 activity in the absence of growth factor stimulation. Taken together, these results reveal a mode of regulation of mTORC1 that is distinct from its lysosomal activation, which controls mTORC1 activity in the nuclear compartment.
Identification of regulators of poly-ADP-ribose polymerase inhibitor response through complementary CRISPR knockout and activation screens
Authors: Clements Kristen E. , Schleicher Emily M. , Thakar Tanay , Hale Anastasia , Dhoonmoon Ashna , Tolman Nathanial J. , Sharma Anchal , Liang Xinwen , Imamura Kawasawa Yuka , Nicolae Claudia M. , Wang Hong-Gang , De Subhajyoti , Moldovan George-Lucian
Published: November 2020

Inhibitors of poly-ADP-ribose polymerase 1 (PARPi) are highly effective in killing cells deficient in homologous recombination (HR); thus, PARPi have been clinically utilized to successfully treat BRCA2-mutant tumors. However, positive response to PARPi is not universal, even among patients with HR-deficiency. Here, we present the results of genome-wide CRISPR knockout and activation screens which reveal genetic determinants of PARPi response in wildtype or BRCA2-knockout cells. Strikingly, we report that depletion of the ubiquitin ligase HUWE1, or the histone acetyltransferase KAT5, top hits from our screens, robustly reverses the PARPi sensitivity caused by BRCA2-deficiency. We identify distinct mechanisms of resistance, in which HUWE1 loss increases RAD51 levels to partially restore HR, whereas KAT5 depletion rewires double strand break repair by promoting 53BP1 binding to double-strand breaks. Our work provides a comprehensive set of putative biomarkers that advance understanding of PARPi response, and identifies novel pathways of PARPi resistance in BRCA2-deficient cells.
Bismuth atom tailoring of indium oxide surface frustrated Lewis pairs boosts heterogeneous CO2 photocatalytic hydrogenation
Authors: Yan Tingjiang , Li Na , Wang Linlin , Ran Weiguang , Duchesne Paul N. , Wan Lili , Nguyen Nhat Truong , Wang Lu , Xia Meikun , Ozin Geoffrey A.
Published: November 2020

The surface frustrated Lewis pairs (SFLPs) on defect-laden metal oxides provide catalytic sites to activate H2 and CO2 molecules and enable efficient gas-phase CO2 photocatalysis. Lattice engineering of metal oxides provides a useful strategy to tailor the reactivity of SFLPs. Herein, a one-step solvothermal synthesis is developed that enables isomorphic replacement of Lewis acidic site In3+ ions in In2O3 by single-site Bi3+ ions, thereby enhancing the propensity to activate CO2 molecules. The so-formed BixIn2-xO3 materials prove to be three orders of magnitude more photoactive for the reverse water gas shift reaction than In2O3 itself, while also exhibiting notable photoactivity towards methanol production. The increased solar absorption efficiency and efficient charge-separation and transfer of BixIn2-xO3 also contribute to the improved photocatalytic performance. These traits exemplify the opportunities that exist for atom-scale engineering in heterogeneous CO2 photocatalysis, another step towards the vision of the solar CO2 refinery.
Pharmacological targeting of c-FLIPL and Bcl-2 family members promotes apoptosis in CD95L-resistant cells
Authors: König Corinna , Hillert-Richter Laura K. , Ivanisenko Nikita V. , Ivanisenko Vladimir A. , Lavrik Inna N.
Published: November 2020

The development of efficient combinatorial treatments is one of the key tasks in modern anti-cancer therapies. An apoptotic signal can either be induced by activation of death receptors (DR) (extrinsic pathway) or via the mitochondria (intrinsic pathway). Cancer cells are characterized by deregulation of both pathways. Procaspase-8 activation in extrinsic apoptosis is controlled by c-FLIP proteins. We have recently reported the small molecules FLIPinB/FLIPinBγ targeting c-FLIPL in the caspase-8/c-FLIPL heterodimer. These small molecules enhanced caspase-8 activity in the death-inducing signaling complex (DISC), CD95L/TRAIL-induced caspase-3/7 activation and subsequent apoptosis. In this study to increase the pro-apoptotic effects of FLIPinB/FLIPinBγ and enhance its therapeutic potential we investigated costimulatory effects of FLIPinB/FLIPinBγ in combination with the pharmacological inhibitors of the anti-apoptotic Bcl-2 family members such as ABT-263 and S63845. The combination of these inhibitors together with FLIPinB/FLIPinBγ increased CD95L-induced cell viability loss, caspase activation and apoptosis. Taken together, our study suggests new approaches for the development of combinatorial anti-cancer therapies specifically targeting both intrinsic and extrinsic apoptosis pathways.