bluuebunny/crossref_metadata_2025 huggingface dataset:
High Temperature Corrosion of HVOF Coatings in Laboratory-Simulated Biomass Combustion Superheater Environments
Authors: Pidcock Andy , Mori Stefano , Sumner Joy , Simms Nigel , Nicholls John , Oakey John
Published: December 2022

This study examines the fireside corrosion of FeCrAl, NiCr, NiCrAlY and A625 coatings applied by ‘high velocity oxy fuel’(HVOF) and exposed to simulated biomass firing conditions (gas composition CO2, N2, SO2 and HCl). The coatings and a typical base steel alloy (T92) were exposed to simulated conditions at 600 °C for 1000 h in a laboratory scale furnace. Samples were coated with a potassium chloride deposit. Samples were then cold mounted in a low-shrinkage epoxy resin and then cross-sectioned. Corrosion was assessed by dimensional metrology comparing the coating thickness change of the samples. The cross-sections of the ‘worst’ and ‘best’ coatings were examined. Results show that all but one coating (HVOF NiCr) outperformed the T92 alloy. No coating composition or method was conclusively better. Evidence of Cr depletion as well as the formation of a sulphidation layer have been found in the exposed samples with coatings. The formation of a K2SO4 layer has also been observed on all coated specimens.
Development of a Novel, Impurity-Scavenging, Corrosion-Resistant Coating for Ni-Based Superalloy CMSX-4
Authors: Pek M. E. , Ackerman A. K. , Appleton M. , Ryan M. P. , Pedrazzini S.
Published: December 2022

Sulfur, a common impurity arising from atmospheric and environmental contamination, is highly corrosive and detrimental to the lifespan of nickel superalloys in jet engines. However, sulfur-scavenging coatings have yet to be explored. Our study presents the successful development of a stable, uniform, impurity-scavenging Ni-Mn coating on Ni-based superalloy CMSX-4, through electroplating. The coating was characterised via combined scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy. An optimal coating thickness of > 600 nm was deposited. The coated alloy was exposed to corrosive salt mixture 98% Na2SO4–2% NaCl at 550 °C for 100 h, mimicking engine exposure conditions, thereby proving that the coating successfully trapped sulfur and prevented its diffusion into an underlying alloy. This work presents a promising development for the prevention of sulfur-induced corrosion in industrial setting such as gas turbine engine, where the effects of sulfur diffusion into the bulk alloy could lead to premature failure.

Graphical Abstract
Chronic physical conditions, physical multimorbidity, and quality of life among adults aged ≥ 50 years from six low- and middle-income countries
Authors: Olanrewaju Olawale , Trott Mike , Smith Lee , López Sánchez Guillermo F. , Carmichael Christina , Oh Hans , Schuch Felipe , Jacob Louis , Veronese Nicola , Soysal Pinar , Shin Jae Il , Butler Laurie , Barnett Yvonne , Koyanagi Ai
Published: December 2022

Purpose

Multimorbidity (i.e., ≥ 2 chronic conditions) poses a challenge for health systems and governments, globally. Several studies have found inverse associations between multimorbidity and quality of life (QoL). However, there is a paucity of studies from low- and middle-income countries (LMICs), especially among the older population, as well as studies examining mediating factors in this association. Thus, the present study aimed to explore the associations, and mediating factors, between multimorbidity and QoL among older adults in LMICs.

Methods

Cross-sectional nationally representative data from the Study on Global Ageing and Adult Health were analyzed. A total of 11 chronic conditions were assessed. QoL was assessed with the 8-item WHO QoL instrument (range 0–100) with higher scores representing better QoL. Multivariable linear regression and mediation analyses were conducted to assess associations.

Results

The final sample consisted of 34,129 adults aged ≥ 50 years [mean (SD) age 62.4 (16.0) years; age range 50–114 years; 52.0% females]. Compared to no chronic conditions, 2 (b-coefficient − 5.89; 95% CI − 6.83, − 4.95), 3 (− 8.35; − 9.63, − 7.06), 4 (− 10.87; − 12.37, − 9.36), and ≥ 5 (− 13.48; − 15.91, − 11.06) chronic conditions were significantly associated with lower QoL, dose-dependently. The mediation analysis showed that mobility (47.9%) explained the largest proportion of the association between multimorbidity and QoL, followed by pain/discomfort (43.5%), sleep/energy (35.0%), negative affect (31.9%), cognition (20.2%), self-care (17.0%), and interpersonal activities (12.0%).

Conclusion

A greater number of chronic conditions was associated with lower QoL dose-dependently among older adults in LMICs. Public health and medical practitioners should aim to address the identified mediators to improve QoL in patients with multimorbidity.
Variable selection using conditional AIC for linear mixed models with data-driven transformations
Authors: Lee Yeonjoo , Rojas-Perilla Natalia , Runge Marina , Schmid Timo
Published: December 2022

When data analysts use linear mixed models, they usually encounter two practical problems: (a) the true model is unknown and (b) the Gaussian assumptions of the errors do not hold. While these problems commonly appear together, researchers tend to treat them individually by (a) finding an optimal model based on the conditional Akaike information criterion (cAIC) and (b) applying transformations on the dependent variable. However, the optimal model depends on the transformation and vice versa. In this paper, we aim to solve both problems simultaneously. In particular, we propose an adjusted cAIC by using the Jacobian of the particular transformation such that various model candidates with differently transformed data can be compared. From a computational perspective, we propose a step-wise selection approach based on the introduced adjusted cAIC. Model-based simulations are used to compare the proposed selection approach to alternative approaches. Finally, the introduced approach is applied to Mexican data to estimate poverty and inequality indicators for 81 municipalities.
Hormonal homeostasis associated with effective induction of triticale microspore embryogenesis
Authors: Juzoń-Sikora Katarzyna , Nowicka Anna , Plačková Lenka , Doležal Karel , Żur Iwona
Published: December 2022

The endogenous level of cytokinins (CKs) and auxins (Auxs) was analyzed in isolated microspores and ovaries of two doubled haploid (DH) lines of triticale (× Triticosecale Wittm.) to better understand the mechanism of microspore embryogenesis (ME)—the most efficient and widely applied method of producing DHs. The responsiveness of the studied lines to ME significantly varied. ME was induced by pre-treating tillers with low temperature (4 °C for 3 weeks) alone or in combination with synthetic auxin (2,4-D), auxin inhibitor (PCIB) or melatonin (MEL) applied for 4 days before microspore isolation. Hormonal profile analyses, accompanied by ME effectiveness evaluation confirmed the multi-level crosstalk of Auxs/CKs and the specific hormonal homeostasis required for effective microspore reprogramming. It was found that triticale microspores contained mainly cis zeatin derivatives: cis-zeatin-O-glucoside (cZOG), cis-zeatin riboside (cZR) and cis-zeatin (cZ), as well as indole-3-acetic acid (IAA) and IAA-aspartate (IAAsp). Increased ME efficiency was associated with higher contents of most of the identified CKs and Auxs, as well as the higher active Aux/active CK ratio. Trans CK isoforms were detected only in ovaries, confirming their importance as a source of bioactive molecules stimulating embryogenic development. Two of the pre-treatments tested: 12.5 μM PCIB and 50 μM MEL decreased the active Aux/active CK ratio, which was accompanied by an increase in the regeneration efficiency.
Preparation of Porous and Durable Metakaolin-Based Alkali-Activated Materials with Active Metal as Composites for Catalytic Wet Air Oxidation
Authors: Christophliemk M. P. , Heponiemi A. , Hu T. , Lassi U.
Published: December 2022

Novel porous and durable metakaolin-based alkali-activated materials (MK-AAMs) with active metal as composites were produced to degrade bisphenol A (BPA) in catalytic wet air oxidation (CWAO). Two composite producing processes were employed. The first process consisted of mixing metakaolin (MK), a foaming agent and active metal oxide (CuO, MnO2) in a strongly alkaline solution of K2SiO3 and KOH. Paste was cured under microwave radiation to produce porous CuO and MnO2 composites. A porous blank MK-AAM was produced as described above but without active metal and was used as a reference as well. Cu(OH)2 composite was produced by refluxing a blank MK-AAM in 0.5 M CuSO4 solution for 24 h. The specific surface area (SSA) of the reference, CuO, MnO2, and Cu(OH)2 composites were 36, 53, 61, 89 m2/g, respectively. Mechanical durability was determined in terms of compressive strength and 2.8, 3.4, 3.2, 3.6 MPa were received, respectively. The activity of the reference and the composites were tested in CWAO at 1 MPa and 150 °C for 5 h by using an aqueous model solution of BPA. Under the optimal conditions for CWAO (pressure: 1 MPa; temperature: 150 °C; initial pH 5–6; c[catalyst]: 4.0 g/L) with Cu(OH)2 composite, the BPA and total organic carbon (TOC) conversions of 100% and 53% were reached. During 5 h oxidation, the composites degraded due to the combined effect of erosion (1.5 wt%) and active metal (Cu, Mn) leaching (1.1 wt%, 3.6 wt%). It was proposed that BPA can be degraded energy-efficiently via CWAO into less harmful compounds under mild reaction conditions without losing the desired properties of the composites.
Spatially explicit model of the Cryptosporidium and Giardia disease burden from surface and ground waters in urban and rural areas of the Three Gorges Reservoir watershed in Chongqing, China
Authors: Huang Qian , Huang Shan , Li Bo , Xiong Yanhong , Kuang Weijie , Xiao Shunxin , Yi Jianghui , Zhao Feng , Xiao Guosheng
Published: December 2022

Cryptosporidium and Giardia (major causes of diarrhea) are widely distributed in Chinese source waters and threaten human health. A new spatially explicit GloWPa-TGR-Crypt-Giar C1 model is presented to simultaneously estimate mean monthly (oo)cyst concentrations in surface and ground waters in the Three Gorges Reservoir (TGR) watershed. A quantitative risk assessment of protozoal infections considered different source waters, transmission pathways, regions, susceptible subpopulations, and drinking water treatments. Monthly mean Cryptosporidium oocyst and Giardia cyst concentrations ranged between 0.5–19.3 oocysts/10 L and 0.2–5.0 cysts/10 L in surface water, respectively, and 0.007–0.3 oocysts/10 L and 0.002–0. 2 cysts/10 L in groundwater. The cumulative disease burdens attributable to cryptosporidiosis and giardiasis were, respectively, 5.77×10−5 DALYs (disability-adjusted life years/person/year) and 4.63×10−6 DALYs in urban areas, and 6.35×10−4 DALYs and 8.84×10−5 DALYs in rural areas, which were much higher than the reference risk level recommended by the World Health Organization ($${10}^{-6}$$

10

-
6

DALYs). The annual burden associated with consuming surface water was calculated to be 3.84×10−4 DALYs for Cryptosporidium and $$5.10\times {10}^{-5}$$

5.10
×

10

-
5

DALYs for Giardia, whereas consuming groundwater entailed the lower burdens (1.26×10−5 and 3.50×10−6 DALYs, respectively). Most DALYs were a consequence of consumption of directly supplied surface water. Fifty percent of the health burden was carried by immunodeficiency with HIV. Children (0–4 years) were more likely to have an individual disease burden than adults (15–64 years). Males were more susceptible than females. Improving sanitation through adequate ozone and microfiltration treatment should be considered when attempting to reduce disease burden. Sensitivity analysis highlighted the importance of reducing (oo)cyst loads to protect the watershed. The methodology and results described will help in evaluating and reducing the burden of protozoal infection associated with surface and ground waters in the TGR and similar watersheds.

Graphical Abstract
Bifurcations from degenerate orbits of solutions of nonlinear elliptic systems
Authors: Gołȩbiewska Anna , Kluczenko Joanna , Stefaniak Piotr
Published: December 2022

The aim of this paper is to study global bifurcations of non-constant solutions of some nonlinear elliptic systems, namely the system on a sphere and the Neumann problem on a ball. We study the bifurcation phenomenon from families of constant solutions given by critical points of the potentials. Considering this problem in the presence of additional symmetries of a compact Lie group, we study orbits of solutions and, in particular, we do not require the critical points to be isolated. Moreover, we allow the considered orbits of critical points to be degenerate. To prove the bifurcation, we compute the index of an isolated degenerate critical orbit in an abstract situation. This index is given in terms of the degree for equivariant gradient maps.
Impact of Hurricane Maria on mold levels in the homes of Piñones, Puerto Rico
Authors: Bolaños-Rosero B. , Hernández-González X. , Cavallín-Calanche H. E. , Godoy-Vitorino F. , Vesper S.
Published: December 2022

Hurricane Maria struck Puerto Rico on September 20, 2017, severely impacting the island. In order to quantify the impact of the hurricane on the indoor air quality, we evaluated the fungal levels in households (n = 20) of the Piñones community for the period of 2018 and 2019. For each dust sample collected, the 36 Environmental Relative Moldiness Index (ERMI) molds were quantified using qPCR assays, and then Shannon Diversity Index (SDI) values for the fungal populations were calculated. Homes were in five separate regions, regarding their proximity in the studied area. We found that for regions with reported least water damage, the SDI values were similar for both sampled years, but for regions that reported mid-to-high level of damage region, the SDI values were significantly higher. Households that reported remediation actions between the two sampled years showed similar values for the second year as those that did not report any major impact. Our preliminary data provides insights into the significant impacts of hurricanes into indoor fungal environment.
What do we know about treating breast-cancer-related lymphedema? Review of the current knowledge about therapeutic options
Authors: Anuszkiewicz Karolina , Jankau Jerzy , Kur Martyna
Published: December 2022

Breast-cancer-related lymphedema (BCRL) is a common consequence of oncological treatment. Its management is a complicated, chronic, and arduous process. Therapeutic options can be divided on non-surgical and surgical methods, although there is still no clear consensus about their effectiveness in preventing or stopping the disease. That brings problems in everyday practice, as there are no guidelines about proper time for starting therapy and no agreement about which management will be beneficial for each patient. The aim of this review is to summarize current knowledge about possible treatment choices, non-surgical so as surgical, indicate knowledge gaps, and try to direct pathways for future studies.
Identifying nutrition-sensitive development options in Madagascar through a positive deviance approach
Authors: Rafanomezantsoa Arielle Sandrine , Coral Claudia , Randrianarison Narilala , Kubitza Christoph , Randriamampionona Denis , Andriamaniraka Harilala , Sieber Stefan , Tojo-Mandaharisoa Sarah , Steinke Jonathan
Published: December 2022

Context-adapted interventions are needed to alleviate the burden of food and nutrition insecurity on resource-poor rural households in southeastern Madagascar. The Positive Deviance approach implies identifying locally viable development solutions by focusing on particularly successful, innovative individuals. To identify promising practices that could be promoted as part of food and nutrition security (FNS) interventions in the Atsimo Atsinanana region of southeastern Madagascar, positive deviance was searched among smallholder farmers. Positive deviants are defined as households with overall optimal performance across four aspects of FNS: household-level food security, women’s diet quality, child’s diet quality, and low diarrhea incidence. To identify positive deviants, a two-step procedure was followed. Based on quantitative survey data from 413 rural smallholder households (mother-child pairs) with a child aged between 6 and 23 months, each household’s four performance scores were adjusted by removing the average effects of household resources. Then, households with Pareto-optimal performance were identified regarding the four aspects. Subsequently, 16 positive deviants were revisited and positive deviant practices were identified through in-depth interviews. A set of practices were validated through focus group discussions with local nutrition and agriculture experts. Positive deviant practices include the adoption of agricultural innovation, such as new cash crops, as well as nutrition-sensitive market behaviors and reliance on off-farm activities. In addition, some ethno-cultural factors help to explain positive deviance. These diverse positive deviant practices may serve as examples and inspiration for locally grounded development interventions targeting FNS in southeastern Madagascar.
Waves in planetary dynamos
Authors: Hori K. , Nilsson A. , Tobias S. M.
Published: December 2022

This Special Topic focuses on magnetohydrodynamic (MHD) processes in the deep interiors of planets, in which their fluid dynamos are in operation. The dynamo-generated, global, magnetic fields provide a background for our solar-terrestrial environment. Probing the processes within the dynamos is a significant theoretical and computational challenge and any window into interior dynamics greatly increases our understanding. Such a window is provided by exploring rapid dynamics, particularly MHD waves about the dynamo-defined basic state. This field is the subject of current attention as geophysical observations and numerical modellings advance. We here pay particular attention to torsional Alfvén waves/oscillations and magnetic Rossby waves, which may be regarded as typical axisymmetric and nonaxisymmetric modes, respectively, amongst a wide variety of wave classes of rapidly rotating MHD fluids. The excitation of those waves has been evidenced for the Earth — whilst their presence has also been suggested for Jupiter. We shall overview their dynamics, summarise our current understanding, and give open questions for future perspectives.
How can entrepreneurial interventions in a university context impact the entrepreneurial intention of their students?
Authors: Bozward David , Rogers-Draycott Matthew , Angba Cynthia , Zhang Carol , Ma Hongyu , An Fulin , Topolansky Federico , Sabia Luca , Bell Robin , Beaumont Emily
Published: December 2022

This paper explores the link between the entrepreneurial intention of students in higher education and the entrepreneurial interventions an institution can provide to support them. The study uses data collected from 679 undergraduate students from Chinese and UK Universities. The instrument for data collection was a paper-based questionnaire. This study uses the integrated model of entrepreneurial intentions as the theoretical underpinning for this approach. The initial findings highlight the perceived need for a range of entrepreneurship interventions, with business training programmes being the highest priority, followed by mentoring, specialist business advice, low-cost finance, business networking events and enterprise clubs. It also shows that those with different Intention Horizons do request a different portfolio of interventions. The paper provides an evidence-based approach to entrepreneurship education design and the development of interventions to support a range of students with and without entrepreneurial intention. This work suggests a previously under-articulated relationship between the nascent entrepreneur’s Intention Horizon, university interventions, and entrepreneurial action. There are numerous calls for further contextualisation of entrepreneurship education which this paper fulfils (Baron and Shane in Psychol Entrepreneurship 19-39, 2007; Byrne et al. in Edward Elgar Publishing, 2014). It further develops the narrative around both contextualisation, the previous experience of the students and the range and importance of these interventions to support the creation of a new venture.
Think Twice: First for Tech, Then for Ed
Authors: Photopoulos Panos , Triantis Dimos
Published: December 2022

The embodiment of technology in education can make learning easier, more enjoyable, and more accessible. From Learning Machines to artificial intelligence (AI), educational technology has repeatedly tested its strength as an aider or a substitute to in-person teaching. During the COVID-19 pandemic international organisations promoted the idea of the transformation of education using technology. Comparison of their texts published in 2020 with texts published in 2021 indicates that much of the early enthusiasm concerning the transition from in-person to remote learning gave its position to more thoughtful accounts after considering the learning losses and students’ disappointment from the disruption of in-person relationships. This publication highlights aspects of education technology usually overlooked in futuristic accounts of education. Adopting a non-deterministic view of technology attempts to contribute to the more human-centred incorporation of technologies in education.
Evaluating the performance of AIC and BIC for selecting spatial econometric models
Authors: Agiakloglou Christos , Tsimpanos Apostolos
Published: December 2022

This study investigates using a Monte Carlo analysis the performance of the two most important information criteria, such as the Akaike’s Information Criterion and the Bayesian Information Criterion, not only in terms of selecting the true spatial econometric model but also in term of detecting spatial dependence in comparison with the LM tests for the simple two spatial models SLM and SEM. The analysis is also extended by incorporating several other spatial econometric models, such as the SLX, SDM, SARAR and SDEM, along with heteroscedastic and non-normal errors. Simulation results show that under ideal conditions these criteria can assist the analyst to select the true spatial econometric model and detect properly spatial dependence.
Computational Methods for Single-Cell Multi-Omics Integration and Alignment
Authors: Stanojevic Stefan , Li Yijun , Ristivojevic Aleksandar , Garmire Lana X.
Published: December 2022

Recently developed technologies to generate single-cell genomic data have made a revolutionary impact in the field of biology. Multi-omics assays offer even greater opportunities to understand cellular states and biological processes. The problem of integrating different omics data with very different dimensionality and statistical properties remains, however, quite challenging. A growing body of computational tools is being developed for this task, leveraging ideas ranging from machine translation to the theory of networks, and represents another frontier on the interface of biology and data science. Our goal in this review is to provide a comprehensive, up-to-date survey of computational techniques for the integration of single-cell multi-omics data, while making the concepts behind each algorithm approachable to a non-expert audience.
‘Willing’ ethnic-nationalists, diffusion, and resentment in India: A micro-foundational account
Authors: Sinha Aseema , Priyam Manisha
Published: December 2022

Using evidence regarding the consolidation of Hindu nationalism in India we put forward new ethnographic data about the variety of popular support for a Hindutva project and a new framework that proposes an interactive theory of social identity. This framework helps us understand how Hindu nationalism becomes embedded in society. We assert that Hindu nationalism in India could be fruitfully analysed by focusing on the processes through which ideas of exclusive nationalism spread among ordinary middle-class people and are expressed in micro-level psychological changes at the individual level. The consolidation of Hindu nationalism in India is being authored not only by parties or the state, but also by societal actors, specifically, ordinary middle-class Indians. Hindu nationalism has been spreading in micro-public spheres in a time of apparent peace and between elections, and with the participation of willing supporters. Building on our fieldwork and research in psychology and history, our conversations have also helped us to identify profiles of different types of nationalists, which we categorize as willing ethnic-nationalists, hardliners, bystanders, and moderates. Further, we suggest the need to focus on inter-linked micro-level mechanisms such as diffusion and emulation of Hindu-centric beliefs and ideas, mobilization by hardliners and organizations, and impunity resulting from protection by state agencies, which helps to create willing ethnic-nationalists and sustains Hindu nationalism. Evidence regarding social interactions from a variety of survey organizations concurs with our findings and our ethnographic material allows us to delve deeper into varieties of Hindu nationalist support across diverse ordinary people.
Modal FRP for all: Functional reactive programming without space leaks in Haskell
Authors: BAHR PATRICK
Published: December 2022

Functional reactive programming (FRP) provides a high-level interface for implementing reactive systems in a declarative manner. However, this high-level interface has to be carefully reigned in to ensure that programs can in fact be executed in practice. Specifically, one must ensure that FRP programs are causal and can be implemented without introducing space leaks. In recent years, modal types have been demonstrated to be an effective tool to ensure these operational properties. In this paper, we present

$\mathsf{Rattus}$

, a modal FRP language that extends and simplifies previous modal FRP calculi while still maintaining the operational guarantees for productivity, causality, and space leaks. The simplified type system makes

$\mathsf{Rattus}$

a practical programming language that can be integrated with existing functional programming languages. To demonstrate this, we have implemented a shallow embedding of

$\mathsf{Rattus}$

in Haskell that allows the programmer to write

$\mathsf{Rattus}$

code in familiar Haskell syntax and seamlessly integrate it with regular Haskell code. Thus,

$\mathsf{Rattus}$

combines the benefits enjoyed by FRP libraries such as Yampa, namely access to a rich library ecosystem (e.g., for graphics programming), with the strong operational guarantees offered by a bespoke type system. To establish the productivity, causality, and memory properties of the language, we prove type soundness using a logical relations argument fully mechanised in the Coq proof assistant.
Southern Ocean Control of 2°C Global Warming in Climate Models
Authors: Shin So‐Jung , Yeh Sang‐Wook , An Soon‐Il , Keenlyside Noel , Xie Shang‐Ping , Park Jae‐Heung
Published: December 2022

Global warming will soon reach the Paris Agreement targets of 1.5°C/2°C temperature increase above pre‐industrial levels. Under a business‐as‐usual scenario, the time to reach these targets varies widely among climate models. Using Coupled Model Intercomparison Project Phase 5 and 6, we show that a 2°C global warming is determined by Southern Ocean (SO) state closely tied with a low‐level cloud (LLC) amount feedback strength during reference (1861–1900) period; climate models with cold SO tend to accompany more low‐level cloudiness and Antarctic sea ice concentration due to a strong LLC amount feedback. Consequently, initially cold SO models tend to simulate a fast global warming by absorbing more downward shortwave radiation compared to initially warm SO models because more LLC disappears due to a strong LLC amount feedback during the 2°C rise. Our results demonstrate that climate models that correctly simulate initial SO state can improve 2°C warming projections with reduced uncertainties.
Long‐Lived and Continual Volcanic Eruptions, Tectonic Activity, Pit Chains Formation, and Boulder Avalanches in Northern Tharsis Region: Implications for Late Amazonian Geodynamics and Seismo‐Tectonic Processes on Mars
Authors: Krishnan Vivek , Kumar P. Senthil
Published: December 2022

Tharsis is the largest volcanic province on Mars. It consists of a few large shield volcanoes, one of which is Alba Mons (AM), located in northern Tharsis, with the Ceraunius Fossae (CF) graben system to the south of it. Previous workers argued in favor of episodic building of Tharsis volcanoes. In contrast, we show that volcanism in the AM and CF regions occurred continually, at least in the last few hundred million years, based on ages of >1,000 stratigraphically young lava flows. Central volcanism in AM terminated around 200 Ma, while subsequent young volcanism, fed by both small shields and fissures, migrated to the south in CF. Several generations of grabens hosting thousands of simple to complex pit chains were formed by magmatic intrusion through feeder dikes, and these activities also migrated to the south during the Late Amazonian epoch. Thousands of boulder avalanches mark the slopes of grabens, pit chains, and impact craters, with ages ranging from a few tens to thousands of years. The local geological settings of the boulder falls suggest that both tectonic and volcanic marsquakes triggered the boulder avalanches. The broad zone of boulder falls in northern Tharsis defines the potential epicentral zone of (MW 4.1) 18 September 2021 marsquake. We infer that long‐lived and active magma chambers and subcrustal magma underplating driven by a mantle plume are present beneath the AM volcano and that these probably migrated south toward CF in the Late Amazonian epoch.
Orogens of Big Sky Country: Reconstructing the Deep‐Time Tectonothermal History of the Beartooth Mountains, Montana and Wyoming, USA
Authors: Ronemus Chance B. , Orme Devon A. , Guenthner William R. , Cox Stephen E. , Kussmaul Christopher A. L.
Published: December 2022

Archean rocks exposed in the Beartooth Mountains, Montana and Wyoming, have experienced a complex >2.5 Gyr thermal history related to the long‐term geodynamic evolution of Laurentia. We constrain this history using “deep‐time” thermochronology, reporting zircon U‐Pb, biotite40Ar/39Ar, and zircon and apatite [U‐Th(‐Sm)]/He results from three transects across the basement‐core of the range. Our central transect yielded a zircon U‐Pb concordia age of 2,805.6 ± 6.4 Ma. Biotite40Ar/39Ar plateau ages from western samples are ≤1,775 ± 27 Ma, while those from samples further east are ≥2,263 ± 76 Ma. Zircon (U‐Th)/He dates span 686.4 ± 11.9 to 13.5 ± 0.3 Ma and show a negative relationship with effective uranium—a proxy for radiation damage. Apatite (U‐Th)/He dates are 109.2 ± 23.9 to 43.6 ± 1.9 Ma and correlate with sample elevation. Multi‐chronometer Bayesian time‐temperature inversions suggest: (a) Cooling between ∼1.90 and ∼1.80 Ga, likely related to Big Sky orogeny thermal effects; (b) Reheating between ∼1.80 Ga and ∼1.35 Ga consistent with Mesoproterozoic burial; (c) Cooling to ≤100°C between Mesoproterozoic and early Paleozoic time, likely reflecting continental erosion; (d) Variable Paleozoic–Jurassic cooling, possibly related to Paleozoic tectonism and/or low eustatic sea level; (e) Rapid Cretaceous–Paleocene cooling, preceding accepted proxies for flat‐slab subduction; (f) Eocene–Miocene reheating consistent with reburial by Cenozoic volcanics and/or sediments; (g) Post‐20 Ma cooling consistent with Neogene development of topographic relief. Our results emphasize the utility of multi‐chronometer thermochronology in recovering complex, non‐monotonic multi‐billion‐year thermal histories.
Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children
Authors: Stratmann Svea , Vesterlund Mattias , Umer Husen M. , Eshtad Saeed , Skaftason Aron , Herlin Morten Krogh , Sundström Christer , Eriksson Anna , Höglund Martin , Palle Josefine , Abrahamsson Jonas , Jahnukainen Kirsi , Munthe-Kaas Monica Cheng , Zeller Bernward , Tamm Katja Pokrovskaja , Lindskog Cecilia , Cavelier Lucia , Lehtiö Janne , Holmfeldt Linda
Published: December 2022

Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.
Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia
Authors: Rastogi Namrata , Gonzalez Juan Bautista Menendez , Srivastava Vikas Kumar , Alanazi Bader , Alanazi Rehab N. , Hughes Owen M. , O’Neill Niamh S. , Gilkes Amanda F. , Ashley Neil , Deshpande Sumukh , Andrews Robert , Mead Adam , Rodrigues Neil P. , Knapper Steve , Darley Richard L. , Tonks Alex
Published: December 2022

Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML.
Hydroxychloroquine lowers Alzheimer’s disease and related dementias risk and rescues molecular phenotypes related to Alzheimer’s disease
Authors: Varma Vijay R. , Desai Rishi J. , Navakkode Sheeja , Wong Lik-Wei , Anerillas Carlos , Loeffler Tina , Schilcher Irene , Mahesri Mufaddal , Chin Kristyn , Horton Daniel B. , Kim Seoyoung C. , Gerhard Tobias , Segal Jodi B. , Schneeweiss Sebastian , Gorospe Myriam , Sajikumar Sreedharan , Thambisetty Madhav
Published: December 2022

We recently nominated cytokine signaling through the Janus-kinase–signal transducer and activator of transcription (JAK/STAT) pathway as a potential AD drug target. As hydroxychloroquine (HCQ) has recently been shown to inactivate STAT3, we hypothesized that it may impact AD pathogenesis and risk. Among 109,124 rheumatoid arthritis patients from routine clinical care, HCQ initiation was associated with a lower risk of incident AD compared to methotrexate initiation across 4 alternative analyses schemes addressing specific types of biases including informative censoring, reverse causality, and outcome misclassification (hazard ratio [95% confidence interval] of 0.92 [0.83–1.00], 0.87 [0.81–0.93], 0.84 [0.76–0.93], and 0.87 [0.75–1.01]). We additionally show that HCQ exerts dose-dependent effects on late long-term potentiation (LTP) and rescues impaired hippocampal synaptic plasticity prior to significant accumulation of amyloid plaques and neurodegeneration in APP/PS1 mice. Additionally, HCQ treatment enhances microglial clearance of Aβ1-42,lowers neuroinflammation, and reduces tau phosphorylation in cell culture-based phenotypic assays. Finally, we show that HCQ inactivates STAT3 in microglia, neurons, and astrocytes suggesting a plausible mechanism associated with its observed effects on AD pathogenesis. HCQ, a relatively safe and inexpensive drug in current use may be a promising disease-modifying AD treatment. This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression.
UBE2J1 inhibits colorectal cancer progression by promoting ubiquitination and degradation of RPS3
Authors: Wang Tuo , Jin Chi , Yang Peng , Chen Zhihao , Ji Jiangzhou , Sun Qingyang , Yang Sheng , Feng Yifei , Tang Junwei , Sun Yueming
Published: December 2022

Ubiquitin-conjugating enzyme E2 J1 (UBE2J1) has been proven to participate in the ubiquitination of multiple substrate proteins. However, the underlying mechanisms of UBE2J1 as a ubiquitin-conjugating enzyme participating in cancer development and progression remain largely unknown. Here, we identified that UBE2J1 is downregulated in colorectal cancer (CRC) tissues and cell lines which are mediated by DNA hypermethylation of its promoter, and decreased UBE2J1 is associated with poor prognosis. Functionally, UBE2J1 serving as a suppressor gene inhibits the proliferation and metastasis of CRC cells. Mechanistically, UBE2J1-TRIM25, forming an E2-E3 complex, physically interacts with and targets RPS3 for ubiquitination and degradation at the K214 residue. The downregulated RPS3 caused by UBE2J1 overexpression restrains NF-κB translocation into the nucleus and therefore inactivates the NF-κB signaling pathway. Our study revealed a novel role of UBE2J1-mediated RPS3 poly-ubiquitination and degradation in disrupting the NF-κB signaling pathway, which may serve as a novel and promising biomarker and therapeutic target for CRC.
The immunological role of ADAMs in the field of gastroenterological chronic inflammatory diseases and cancers: a review
Authors: Arai Jun , Otoyama Yumi , Nozawa Hisako , Kato Naoya , Yoshida Hitoshi
Published: December 2022

Metalloproteinases cleave transmembrane proteins that play critical roles in inflammation and cancers. Metalloproteinases include a disintegrin and metalloprotease (ADAM), which we previously examined using a fluorescence assay system, and described their association with resistance to systemic therapy in cancer patients. There are also many reports on the relation between ADAM expression and the prognosis of patients with gastroenterological chronic inflammatory diseases and cancers. Inhibiting their immunomodulating activity in chronic inflammation restores innate immunity and potentially prevents the development of various cancers. Among the numerous critical immune system-related molecules, we focus on major histocompatibility complex class I polypeptide-related sequence A (MICA), MICB, intracellular adhesion molecule (ICAM)-1, TNF-α, IL-6 receptor (IL-6R), and Notch. This review summarizes our current understanding of the role of ADAMs in gastroenterological diseases with regard to the immune system. Several Food and Drug Administration (FDA)-approved inhibitors of ADAMs have been identified, and potential therapies for targeting ADAMs in the treatment of chronic inflammatory diseases and cancers are discussed. Some ongoing clinical trials for cancers targeting ADAMs are also introduced.
The neurobiology of apathy in depression and neurocognitive impairment in older adults: a review of epidemiological, clinical, neuropsychological and biological research
Authors: Steffens David C. , Fahed Mario , Manning Kevin J. , Wang Lihong
Published: December 2022

Apathy is a common condition that involves diminished initiative, diminished interest and diminished emotional expression or responsiveness. It is highly prevalent in the context of a variety of neuropsychiatric disorders and is related to poor health outcomes. Presence of apathy is associated with cognitive and functional decline in dementia. Despite its negative impact on health, there is no definitive treatment for apathy, a clinical reality that may be due in part to lack of knowledge about assessment, neuropsychological features and neurobiological underpinnings. Here, we review and synthesize evidence from clinical, epidemiological, neuropsychological, peripheral biomarker and neuroimaging research. Apathy is a common feature of depression and cognitive disorders and is associated with impairment in executive function. Neuropsychological and neuroimaging studies point to dysfunction of brain circuitry involving the prefrontal cortex, especially the dorsolateral prefrontal cortex circuit, the dorsomedial prefrontal cortex circuit, and the ventromedial prefrontal cortex circuit. However, inconsistent findings, particularly in neuroimaging may be due to heterogeneity of apathy symptoms (with a need to better elucidate subtypes), neuropsychiatric comorbidities, the severity of cognitive impairment and other factors. These factors need to be accounted for in future studies so that biomarker research can make progress. On the whole, the literature on apathy has identified likely neurocognitive, peripheral biomarker and neuroimaging targets for understanding apathy, but also points to the need to address methodological issues that will better inform future studies. In turn, as we learn more about the underpinning of apathy and its subtypes, subsequent research can focus on new neurally based interventions that will strengthen the clinical management of apathy in the context of its comorbidities.
3D collagen migration patterns reveal a SMAD3-dependent and TGF-β1-independent mechanism of recruitment for tumour-associated fibroblasts in lung adenocarcinoma
Authors: Juste-Lanas Yago , Díaz-Valdivia Natalia , Llorente Alejandro , Ikemori Rafael , Bernardo Alejandro , Arshakyan Marselina , Borau Carlos , Ramírez Josep , Ruffinelli José Carlos , Nadal Ernest , Reguart Noemí , García-Aznar José M. , Alcaraz Jordi
Published: December 2022

Background

The TGF-β1 transcription factor SMAD3 is epigenetically repressed in tumour-associated fibroblasts (TAFs) from lung squamous cell carcinoma (SCC) but not adenocarcinoma (ADC) patients, which elicits a compensatory increase in SMAD2 that renders SCC-TAFs less fibrotic. Here we examined the effects of altered SMAD2/3 in fibroblast migration and its impact on the desmoplastic stroma formation in lung cancer.

Methods

We used a microfluidic device to examine descriptors of early protrusions and subsequent migration in 3D collagen gels upon knocking down SMAD2 or SMAD3 by shRNA in control fibroblasts and TAFs.

Results

High SMAD3 conditions as in shSMAD2 fibroblasts and ADC-TAFs exhibited a migratory advantage in terms of protrusions (fewer and longer) and migration (faster and more directional) selectively without TGF-β1 along with Erk1/2 hyperactivation. This enhanced migration was abrogated by TGF-β1 as well as low glucose medium and the MEK inhibitor Trametinib. In contrast, high SMAD2 fibroblasts were poorly responsive to TGF-β1, high glucose and Trametinib, exhibiting impaired migration in all conditions.

Conclusions

The basal migration advantage of high SMAD3 fibroblasts provides a straightforward mechanism underlying the larger accumulation of TAFs previously reported in ADC compared to SCC. Moreover, our results encourage using MEK inhibitors in ADC-TAFs but not SCC-TAFs.
Nanowire-assisted freestanding liquid metal thin-film patterns for highly stretchable electrodes on 3D surfaces
Authors: Kim Minwoo , Cho Chulmin , Shin Wooseop , Park Jung Jae , Kim Jaewon , Won Phillip , Majidi Carmel , Ko Seung Hwan
Published: December 2022

Stretchable electronics is playing an integral role in fields such as wearable electronics and soft robots. Among soft conductive materials, liquid metal is drawing intense attention as an electrode material due to its liquid nature at room temperature. However, the merits of liquid metal conductor are limited by the presence of substrates or enclosed microchannels from physical disturbances by the underlying substrate when applying it to 3D surface and modifying complex circuit. To overcome this limitation, we develop freestanding patterned liquid metal thin-film conductor (FS-GaIn). FS-GaIn was achieved by introducing metal nanowires to liquid metal and subsequent sequential selective laser processing and etching of directly patterned traces. FS-GaIn can be applied directly to nonflat surface without substrates. When incorporated into electrical circuits, FS-GaIn shows high electrical conductivity, stretchability, and stability. The concept of freestanding liquid metal can open a functionality to the conventional liquid metal electronics.
Experiencing a slow passage of time was an indicator of social and temporal disorientation during the Covid-19 pandemic
Authors: Fernandez Velasco Pablo , Perroy Bastien , Gurchani Umer , Casati Roberto
Published: December 2022

Time dilation was experienced in most countries and across the several years of the Covid-19 crisis: the passage of time was deemed slower than before the pandemic, and the distance to the beginning of the pandemic seemed longer than it really was. An outstanding question is how these two aspects of time judgements relate to other temporal, social and affective disturbances. We developed and validated a 59-item questionnaire to explore these questions. 3306 participants completed the questionnaire in France in May and June 2021. Here, we analyse group differences and find that both slow passage of time and long distance judgements were associated with larger disturbances across all domains under study. These included temporal disruptions—the aptness to project oneself into the future, the sense of a rift between pre-pandemic and pandemic time, the ability to locate oneself in time, the capacity to recall the order of past events—, as well as an overall sense of social disorientation, and trauma-specific disturbances. In contrast, both fast passage of time and short distance judgements were associated with beneficial effects across all of the mentioned domains. Our results indicate that perceived passage of time and temporal distance judgements are key indicators of social and temporal disorientation.