bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing dissimilarity of employment history information from survey and administrative data using sequence analysis techniques
Authors: Bühler Babette , Möhring Katja , Weiland Andreas P.
Published: February 2022

Life course data is frequently gathered either using retrospective surveys or linking records with administrative data. Yet, each strategy has specific advantages and disadvantages. We study the consistency between both types of data sources and reasons for mismatch using the linked data set SHARE-RV, which combines retrospective life history data from the Survey of Health, Ageing and Retirement in Europe (SHARE) with respondents’ administrative data from German pension insurance records (N = 1679). Utilizing sequence analysis techniques with Hamming distance, Optimal Matching and OMspell as matching algorithms, we examine mismatches between survey and administrative data covering detailed, 30-year employment histories, and analyze how inconsistencies are associated with life-course characteristics, demographic and socio-economic factors. Our results show that life-course complexity and spells of atypical employment are associated with more mismatches. Furthermore, gender differences are pronounced and appear to be sensitive to the applied matching algorithm.
Berberine-loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
Authors: Paudel Keshav R. , Mehta Meenu , Yin Geena Hew Suet , Yen Lee Li , Malyla Vamshikrishna , Patel Vyoma K. , Panneerselvam Jithendra , Madheswaran Thiagarajan , MacLoughlin Ronan , Jha Niraj Kumar , Gupta Piyush Kumar , Singh Sachin Kumar , Gupta Gaurav , Kumar Pradeep , Oliver Brian G. , Hansbro Philip M. , Chellappan Dinesh Kumar , Dua Kamal
Published: February 2022

Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3 nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.
Disagreement, Points of View, and Truth-Relativism
Authors: Hautamäki Antti
Published: February 2022

Truth-relativism is the claim that the truth of statements is dependent on the context in which they are made. In this article, truth-relativism is considered as a way to explain disagreements. Viewpoint relativism, a recent version of truth-relativism, is introduced as a useful framework to analyse how truth-relativism approaches disagreements. Viewpoint relativism is based on contextual semantics and the logic of viewpoint, which is a two-dimensional modal logic. In viewpoint relativism, the central concept is a point of view in relation to which truth claims are evaluated. Viewpoint relativism is compared to the truth-relativism of Peter Lasersohn and John MacFarlane. Finally, truth-relativism is defended against the critique of Paul Boghossian that it represents untenable ‘replacement relativism’.
Nighttime lights, urban features, household poverty, depression, and obesity
Authors: Liao Yi-An , Garcia-Mondragon Liliana , Konac Deniz , Liu Xiaoxuan , Ing Alex , Goldblatt Ran , Yu Le , Barker Edward D.
Published: February 2022

Nighttime Light Emission (NLE) is associated with diminished mental and physical health. The present study examines how NLE and associated urban features (e.g., air pollution, low green space) impact mental and physical wellbeing. We included 200,393 UK Biobank Cohort participants with complete data. The study was carried out in two steps. In Step1, we assessed the relationship between NLE, deprivation, pollution, green space, household poverty and mental and physical symptoms. In Step2, we examined the role of NLE on environment-symptom networks. We stratified participants into high and low NLE and used gaussian graphical model to identify nodes which bridged urban features and mental and physical health problems. We then compared the global strength of these networks in high vs low NLE. We found that higher NLE associated with higher air pollution, less green space, higher economic and neighborhood deprivation, higher household poverty and higher depressed mood, higher tiredness/lethargy and obesity (Rtraining_mean = 0.2624, Ptraining_mean < .001; Rtest_mean = 0.2619, Ptest_mean < .001). We also found that the interaction between environmental risk factors and mental, physical problems (overall network connectivity) was higher in the high NLE network than in the low NLE network (t = 0.7896, P < .001). In areas with high NLE, economic deprivation, household poverty and waist circumference acted as bridge factors between the key urban features and mental health symptoms. In conclusion, NLE, urban features, household poverty and mental and physical symptoms are all interrelated. In areas with high NLE, urban features associate with mental and physical health problems at a greater magnitude than in areas with low NLE.
Memory Modification and Authenticity: A Narrative Approach
Authors: Leuenberger Muriel
Published: February 2022

The potential of memory modification techniques (MMTs) has raised concerns and sparked a debate in neuroethics, particularly in the context of identity and authenticity. This paper addresses the question whether and how MMTs influence authenticity. I proceed by drawing two distinctions within the received views on authenticity. From this, I conclude that an analysis of MMTs based on a dual-basis, process view of authenticity is warranted, which implies that the influence of MMTs on authenticity crucially depends on the specifics of how memory modification would eventually work. Therefore, I continue with a systematic analysis of possible properties of MMTs in which I distinguish between the dimensions of memories and the kinds of experiences that can be modified as well as the properties of the process of memory modification. The impact of MMTs on authenticity is analyzed regarding the possible properties of MMTs and based on a narrative approach to authenticity which fulfills the requirements of a dual-basis, process view of authenticity. Lastly, I explore the potential of MMTs to shift the balance between self-discovery and self-creation within authenticity and thereby alter the concept itself as well as the value of authenticity.
Boson stars with negative Gauss–Bonnet coupling
Authors: Tojiev Sardor
Published: February 2022

In this paper, we discuss asymptotically flat and anti-de Sitter (AdS) boson star in $$(4+1)$$

(
4
+
1
)

-dimensional Gauss–Bonnet gravity. We describe the dependence of the mass, the charge and the radius of the boson star on the model parameters, such as Gauss–Bonnet coupling $$\alpha $$
α
, cosmological constant $$\Lambda $$
Λ
and gravitational constant $$\kappa $$
κ
. The basic properties of the solutions of boson stars have been studied for the different negative values of Gauss–Bonnet coupling. We found that when $$\kappa $$
κ
is large and $$\alpha $$
α
is negative enough, the spiral shrinks and pulls back to the larger internal frequency $$\omega $$
ω
, and there is only one branch exists. We have also observed that when $$\kappa $$
κ
is small enough and if $$\alpha $$
α
is close to zero, the spiral will unfold.
A necessary step back?
Authors: Alwardt Christian , Schörnig Niklas
Published: February 2022

A few years back, the rapid progress of international efforts to ban lethal autonomous weapon systems (LAWS) left arms controllers amazed: only five years after the founding of the International Committee for Robot Arms Control (ICRAC), the dangers of autonomous weapons were being debated in a UN context, the Convention on Certain Conventional Weapons (CCW), with non-state actors and state actors alike finding common ground in rejecting weapon systems beyond human control. Since then, however, the debate has made little progress, despite increasing pressure by activists and a strong international campaign. In this article, we will argue that the strategies used by campaigners, based on ethical and legal concerns, must be complemented by classic security-related arguments. Unfortunately, key lessons of the Cold War, including the mutual security benefits of arms control, seem to have been forgotten. Many concepts that are central to arms control—such as stability and verification—are by no means intuitively understood and must apparently be (re-)“learned”. Some of the world’s most important actors have not been exposed to these concepts, e.g. China, but also other players. Deconstructing military expectations regarding autonomous weapons and focusing on a preventive arms control approach could help the currently stalled process to regain the momentum it needs.
Financial Entrepreneurial Ecosystems: An Analysis of Urban and Rural Regions of Norway
Authors: Frimanslund Tore
Published: February 2022

Based on the entrepreneurial ecosystem (EE) perspective, this paper examines the role of finance and interrelated value-adding activities in ecosystems. The study employs a multiple-case design and interviews with 11 rural and urban innovative start-ups and stakeholders in the Norwegian market for entrepreneurial financing. The analysis disentangles the term recycling of entrepreneurial resources in ecosystems, explained here as a self-enhancing cycle of finance under certain conditions that allows enhancement of the ecosystem and members. The aim is to explain these mechanisms in business-level ecosystems, why they are important, and how they are new to entrepreneurship theories. The study argues that the robustness of ecosystems is characterised by the extent of such activities and how they affect entrepreneurial and regional growth. Bottom-up ecosystems can be spatially scattered and enable start-ups in disadvantageous localities to harvest critical resources from more advantageous places. This study provides a theoretical extension of EEs.
Statistical analysis on egalitarian land redistribution in Ethiopia: policy evaluation using repeated cross-sectional data
Authors: Takada Jun , Workneh Wubamlak Ayichew , Matsushita Shusuke
Published: February 2022

Rural livelihood in Ethiopia is dependent on subsistence agriculture that has been challenged by farmland shrinkage as a result of rapid population growth. The Amhara regional state government has implemented egalitarian farmland redistribution in 1997 in the region for small-scale and landless farmers. This study aimed to seek new insights from the perspective of equity, rather than efficiency such as agricultural investment and productivity which other previous studies have focused on, and quantitatively evaluated the effect of the land redistribution on the size of farmland holdings of subsistence farmers. Large-scale repeated cross-sectional national statistics, the Ethiopian Agricultural Sample Survey (AgSS) from 1995 to 1999 were used as the data of this analysis. The difference-in-differences (DiD) estimation was applied to evaluate how the land redistribution affected farmers' farmland holdings. The results showed that farmland holding size per farmer in the Amhara Region has significantly decreased after the land redistribution, therefore, this policy achieved certain results from the egalitarian perspective since national land endowments were redistributed from large-scale farmers to small-scale and landless farmers. However, this study focused on only the short-term effect of the land redistribution and more studies are needed to clarify the long-term effect.
Predicting High School Students’ Global Civic Engagement: A Multiple Regression Analysis
Authors: Tarman Bulent , Kilinc Emin
Published: February 2022

The world is getting increasingly interconnected. For this reason, schools should apply strategies to develop students’ civic skills and global civic engagement. The purpose of this paper is to examine the influence of multicultural exposure, multicultural interaction, social media usage, and study abroad experience on global civic engagement. The correlational survey model was applied for the study. The participants were selected through cluster random sampling during the 2018-2019 academic year. This study was implemented with 425 high school students who attend private schools. The authors used Global Citizenship Scale (Morais & Ogden, 2011) and Multicultural Experience Assessment (Aytug, Kern, & Dilchert, 2018). The findings showed that multicultural exposure, multicultural interaction, and social media usage were positively correlated to global civic engagement. In addition, multicultural exposure, multicultural interaction, social media usage, and study abroad experience significantly predicted global civic engagement.
Towards a decolonial feminist fashion design reading list
Authors: Ahmed Tanveer
Published: February 2022

Although reading lists are an important part of curricula and play an essential role in decolonizing education, the work to diversify them can often neglect intersectional approaches that consider both racialized and gendered dimensions of knowledge construction. The consequence can be an additive approach in which black authors and authors of colour are included to diversify reading lists, reproducing racist and sexist biases. This paper examines how reading lists are constructed in curricula and presents an alternative decolonial feminist approach to creating a reading list in fashion design. The value of decolonial feminism lies in addressing the gaps in thinking by using a racializedandgendered framework. The Decolonizing the Curriculum Toolkit project at Westminster University, UK is introduced to which the author contributed a Decolonising Fashion Design Reading List, as an example of counter-hegemonic curricula which aimed to reveal the unequal power dynamics that support colonial logics in fashion design education. Exposing hegemonic distinctions in fashion that represent Western fashion as modern and non-Western fashion as traditional can then allow marginalized and excluded fashion narratives to become centred. Such an approach can then provide a key tool towards building a more pluralised and de-hierarchised set of fashion design resources.
Doing art history in the digital age
Authors: Sonal
Published: February 2022

This paper explores the dimensions of visual history in the digital age. Do digital repositories offer newer paradigms in art historical research? At the most elementary level, it can be easily said that digital tools do allow for closer scrutiny and analysis of art objects with respect to its material composition. A deeper question that needs to be explored is whether the digital age allows for newer theoretical approaches to doing art history. As inventories, museums, art galleries and libraries have been digitizing their collections, there has been a definite shift in the ways of seeing art objects due to the comfort and ease of digital devices. Given the fact that artifacts have a historical process of conceptualization, production, circulation and reception, historical art objects can be seen as a unique entry point into the larger global history of circulation of art works right from the time of their initial production to their later reproduction in print and finally to the times of digitization.
Does housing liquidity matter? Housing property rights and labour market participation of older migrants in China
Authors: Xiao Chengrui , Chen Lijuan
Published: February 2022

This paper adds to the literature by identifying the effect of home ownership on rural-to-urban older migrants’ labour market participation in China. Using the 2016 wave of the China Migrants Dynamic Survey, we find that older migrants who do not own houses are more likely to participate in the labour market than home owners. To alleviate endogeneity caused by the potential sample selection problem, the propensity score matching method is employed. Our results imply that home ownership can be used as a type of precautionary/retirement savings for older migrants, especially for the ones lacking in financial security. We also show that older migrants owning houses with a higher level of liquidity are less likely to participate in the labour market. It indicates that liquidity may significantly affect the effectiveness for older migrants to use home ownership as precautionary/retirement savings.
A dynamic model for engineering change propagations in multiple product development stages
Authors: Li Yulaing , Zhao Wei , Zhang Wenqi , Chen Meng
Published: February 2022

To accurately predict propagation dynamics for single or multiple change propagations across different product development stages in a sequential or concurrent way is critical for decision-making of implementing change requests. In this paper, a change propagation dynamic model is built based on the compartmentalization of engineering entities into susceptible engineering entities and affected engineering entities (SA), the ordinary differential equations for describing the rate of affected entities with respect to the total ones and the duration for resolving all the changes for every moment are presented by combining the calculations of change impacts with different split and joint junctions. Considering the difficulty of finding analytical solutions to the differential equations, algorithms for sequential and concurrent simulations of change propagations across different development stages, and random and GA (Genetic Algorithm)-based optimal selections of feasible propagation paths are developed to obtain numerical solutions for single and multiple change requests. Simulation results show that change ripples and blossoms can be observed in both sequential and concurrent change propagations, and these propagation patterns are not sensitive to the initial change effect and the threshold value for propagations, while critical change propagation paths and the number of initiated changes have important effects on both concurrent and sequential change propagation process. It is also demonstrated that concurrent propagation strategy is advantageous for processing single or few of initiated changes since it can shorten product redevelopment time, sequential propagation strategy has an advantage of robustness for handling multiple initiated change requests.
Sex differences in patients with Tourette syndrome
Authors: Baizabal-Carvallo José Fidel , Jankovic Joseph
Published: February 2022

Background

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. It is at least three times more common in males compared with females; however, the clinical phenomenology between sexes has not been fully examined. We aimed to contrast the clinical features between males and females with TS and chronic tic disorder.

Methods

We studied 201 consecutive patients fulfilling the diagnostic criteria for TS, persistent (or chronic) motor and vocal tic disorder and provisional tic disorder that were considered within the TS spectrum disorder. We performed blinded evaluations of video-recordings and retrospectively reviewed the clinical charts of all patients.

Results

Age ranges between 4 and 65 years. Males represented 77.6% of patients in the cohort. Overall, no differences were observed in the frequency, distribution and complexity of tics between sexes, except for a higher frequency of attention-deficit/hyperactivity disorder (ADHD) (P = .003) among males. Patients younger than 18-years old, in addition to a higher frequency of ADHD (P = .026), males had a statistically higher frequency of complex motor tics (P = .049) and earlier age at onset (P = .072) than females in the multivariate regression analysis. However, these differences were lost in patients older than 18 years, due to increased complexity of tics in females with aging.

Conclusions

A sexual dimorphism was observed between patients with TS mainly before age of 18 years, suggesting an earlier onset of some types of tics and ADHD in males compared to females.
COL0RME: Super-resolution microscopy based on sparse blinking/fluctuating fluorophore localization and intensity estimation
Authors: Stergiopoulou Vasiliki , Calatroni Luca , de Morais Goulart Henrique , Schaub Sébastien , Blanc-Féraud Laure
Published: February 2022

To overcome the physical barriers caused by light diffraction, super-resolution techniques are often applied in fluorescence microscopy. State-of-the-art approaches require specific and often demanding acquisition conditions to achieve adequate levels of both spatial and temporal resolution. Analyzing the stochastic fluctuations of the fluorescent molecules provides a solution to the aforementioned limitations, as sufficiently high spatio-temporal resolution for live-cell imaging can be achieved using common microscopes and conventional fluorescent dyes. Based on this idea, we present COL0RME, a method for covariance-based

$ {\mathrm{\ell}}_0 $

super-resolution microscopy with intensity estimation, which achieves good spatio-temporal resolution by solving a sparse optimization problem in the covariance domain and discuss automatic parameter selection strategies. The method is composed of two steps: the former where both the emitters’ independence and the sparse distribution of the fluorescent molecules are exploited to provide an accurate localization; the latter where real intensity values are estimated given the computed support. The paper is furnished with several numerical results both on synthetic and real fluorescence microscopy images and several comparisons with state-of-the art approaches are provided. Our results show that COL0RME outperforms competing methods exploiting analogously temporal fluctuations; in particular, it achieves better localization, reduces background artifacts, and avoids fine parameter tuning.
A Unifying Model for Pyroclastic Surge Genesis and Pyroclastic Flow Fluidization
Authors: Kelfoun Karim , Gueugneau Valentin
Published: February 2022

Pyroclastic density currents (PDCs) are hot and fast ground‐hugging mixtures of volcanic fragments and gases, which represent a major threat to people living near explosive volcanoes. Mechanisms causing the separation into the concentrated (the pyroclastic flow) and dilute (the pyroclastic surge) layers, as well as the mechanism causing their remarkably high mobility are still unclear. Here, we present a conceptual model based on field observations of lava dome collapses, laboratory experiments, and numerical modeling that unifies these mechanisms. Our model shows that they are caused by the fall of fine volcanic particles onto steep, irregular topography. The ambient air entrapped during the fall both creates the pyroclastic surge through elutriation and induces high fluidity in the pyroclastic flow by increasing its pore pressure. Our conclusion reveals the importance of topography in the destructive capacity of PDCs.
Ultralow Melting of Iron Nitrides and the Fe–N–C System at High Pressure
Authors: Lv Chaojia , Liu Jin
Published: February 2022

Iron nitrides and carbonitrides are the two primary hosts of deep nitrogen in the Earth’s interior; hence, the storage and circulation of deep nitrogen can be largely controlled by the melting behavior of iron nitrides and the Fe–N–C system. In this study, the melting temperatures of these minerals were determined individually and jointly using the new diagnostics of electrical resistance jump up to 80 GPa in laser‐heated diamond‐anvil cells. The solidus curves of these samples are extremely low at mantle pressures, and are marginally affected by the iron spin transition, nitrogen concentration, and carbon incorporation, suggesting that nitrogen‐rich metallic liquids likely exist at depths of <1,500 km in the present‐day mantle. Meanwhile, our Raman spectra are indicative of N2 degassing out of iron nitride liquids at <12 GPa. These results suggest that low‐pressure N2 degassing in the proto‐Earth coupled with nitrogen‐rich liquids hidden in present‐day lower mantle play important roles in the redistribution of deep nitrogen through geologic time and space.
Nitrogen Oxide Production in Laser‐Induced Breakdown Simulating Impacts on the Hadean Atmosphere
Authors: Heays Alan N. , Kaiserová Tereza , Rimmer Paul B. , Knížek Antonín , Petera Lukáš , Civiš Svatopluk , Juha Libor , Dudžák Roman , Krůs Miroslav , Scherf Manuel , Lammer Helmut , Pascal Robert , Ferus Martin
Published: February 2022

The high‐energy‐density synthesis of NxOy species is simulated in gas mixtures representing an O2‐free early‐Earth atmosphere by terawatt‐kilojoule‐class laser‐induced dielectric breakdown (LIDB). These experiments differ from previous LIDB experiments due to the 100 times greater energy delivered per pulse and sensitive analysis of products by high‐resolution infrared spectroscopy. The measured yields of NO, N2O, and NO2 are 0.08–8 × 1015, 5 × 1012, and 0.03–7 × 1014 molec J −1. The high N2O yield is above the upper‐limit constraint of previous tabletop LIDB experiments and the expected yield of a thermochemical freeze‐out at any temperature between 2000 and 5000 K, while the NO and NO2 yields are in broad agreement with freeze‐out models. Using a one dimensional chemical model of the Hadean atmosphere and a simple model of late bombardment, we compute the source flux of N2O assuming the same high production yield as measured experimentally and find the steady‐state partial pressure of N2O is insufficient to warm the climate.
Gradient Studies Reveal the True Drivers of Extreme Life in the Atacama Desert
Authors: Boy D. , Moeller R. , Sauheitl L. , Schaarschmidt F. , Rapp S. , van den Brink L. , Gschwendtner S. , Borquez R. Godoy , Matus Francisco J. , Horn M. A. , Guggenberger G. , Boy J.
Published: February 2022

Studies of hyper‐arid sites contribute to our understanding on how life adapted to extreme conditions. They are often used to further deduce implications for extraterrestrial biology by the so‐called analogue site‐approach. The Atacama Desert, Chile, is one of the most prominent analogue sites despite its neighboring productive ecosystems due to its hyper‐aridity and geochemical features resembling Martian environments. We hypothesize that many drivers of extremophile life in analogue sites are only mistakenly attributed to aridity alone, thus obscuring a clear view of the far more complex process interactions originating in nearby earthly ecosystems. To test this, we investigated 54 soil profiles up to 60 cm of soil depth along of four transects in the Atacama Desert, either running parallel (S‐N) or perpendicular (W‐E) to the Andes. Our objective was to reveal the processes controlling the formation of soil organic carbon (SOC) as the most reliable proxy for microbial life in order to understand the boundary conditions of life in extreme habitats. Further, we aimed at identifying analogue sites as uncompromised as possible by external influences of for example, vegetated or marine ecosystems. We found a mixture of influences driving habitable conditions on gradients perpendicular to the Andes, for example, fog and precipitation scavenging caused by altitudinal variations and differing proximity to the Pacific Ocean, while transects parallel to the Andes were much less biased by external factors. Our results show that studies on life under extreme conditions should clarify the explanatory strength of the investigated factors by a gradient study approach.
Process Interactions Can Change Process Ranking in a Coupled Complex System Under Process Model and Parametric Uncertainty
Authors: Yang Jing , Ye Ming , Chen Xingyuan , Dai Heng , Walker Anthony P.
Published: February 2022

For a complex hydrologic system with multiple processes and process interactions, global sensitivity analysis is often used to identify important or influential parameters for model development and improvement. The identification is complicated by process model uncertainty, when a system process can be represented by multiple process models. This study develops a new total‐effect process sensitivity index to identify influential processes under model uncertainty. This is done by extending Sobol's total‐effect parameter sensitivity index for one system model to total‐effect process sensitivity index for multiple system models to account for uncertainty in process models and model parameters. The total‐effect process sensitivity index includes not only the first‐order process sensitivity index for measuring the importance of individual processes but also higher‐order indices that account for process interactions. The total‐effect process sensitivity index can identify an influential process that itself and its interactions with other processes influence a model output. The total‐effect process sensitivity index is applied to two numerical examples: (a) Sobol's G*‐functions with analytical solutions of first‐order and total‐effect process sensitivity indices, and (b) groundwater flow models with interactions between recharge, geology, and snowmelt processes. The second evaluation shows that, due to second‐order and higher‐order process interactions, the first‐order and total‐effect process sensitivity indices give different process ranking. It is thus necessary to estimate both first‐order and total‐effect process sensitivity indices to appreciate the difference between the first‐order impact of a process alone and the overall total‐effect impact of the process itself and its interactions with other processes on a model output.
Structure of Energy Precipitation Induced by Superbolt‐Lightning Generated Whistler Waves
Authors: Kang Ning , Bortnik Jacob
Published: February 2022

Lightning superbolts are unusually intense lightning strokes. It has been well known that lightning can induce electron precipitation through the whistler waves it generates, but the characteristic of such precipitation in the extreme case of a superbolt has not yet been investigated. In this work, we use the numerical method developed by Bortnik et al. (2006a, https://doi.org/10.1029/2005ja011182, 2006b, https://doi.org/10.1029/2005ja011398) to model the precipitation induced by a superbolt event reported by Ripoll et al. (2021, https://doi.org/10.1038/s41467021237406). The modeled frequency spectrum agrees well with in situ measurements, adding confidence to the model performance. The precipitation flux is decomposed into contributions from different frequency components and different resonance types, thus revealing the underlying structure of the precipitation. The temporal signature of global precipitation on the ground surface is produced for potential comparison with observations by upcoming satellite missions.
Targeting the NOTCH1-MYC-CD44 axis in leukemia-initiating cells in T-ALL
Authors: Piya Sujan , Yang Yaling , Bhattacharya Seemana , Sharma Priyanka , Ma Huaxian , Mu Hong , He Hua , Ruvolo Vivian , Baran Natalia , Davis R. Eric , Jain Abhinav K. , Konopleava Marina , Kantarjian Hagop , Andreeff Michael , You M. James , Borthakur Gautam
Published: February 2022

The NOTCH1-MYC-CD44 axis integrates cell-intrinsic and extrinsic signaling to ensure the persistence of leukemia-initiating cells (LICs) in T-cell acute lymphoblastic leukemia (T-ALL) but a common pathway to target this circuit is poorly defined. Bromodomain-containing protein 4 (BRD4) is implicated to have a role in the transcriptional regulation of oncogenes MYC and targets downstream of NOTCH1, and here we demonstrate its role in transcriptional regulation of CD44. Hence, targeting BRD4 will dismantle the NOTCH1-MYC-CD44 axis. As a proof of concept, degrading BRD4 with proteolysis targeting chimera (PROTAC) ARV-825, prolonged the survival of mice in Notch1 mutated patient-derived xenograft (PDX) and genetic models (ΔPTEN) of T-ALL. Single-cell proteomics analysis from the PDX model, demonstrated quantitative reduction of LICs (CD34+ CD7+ CD19−) and downregulation of the NOTCH1-MYC-CD44 axis, along with cell cycle, apoptosis and PI3K/Akt pathways. Moreover, secondary transplantation from PDX and ΔPTEN models of T-ALL, confirmed delayed leukemia development and extended survival of mice engrafted with T-ALL from ARV-825 treated mice, providing functional confirmation of depletion of LICs. Hence, BRD4 degradation is a promising LIC-targeting therapy for T-ALL.
Synergy between TMZ and individualized multimodal immunotherapy to improve overall survival of IDH1 wild-type MGMT promoter-unmethylated GBM patients
Authors: Van Gool Stefaan W. , Makalowski Jennifer , Bitar Michael , Van de Vliet Peter , Schirrmacher Volker , Stuecker Wilfried
Published: February 2022

The prognosis of IDH1 wild-type MGMT promoter-unmethylated GBM patients remains poor. Addition of Temozolomide (TMZ) to first-line local treatment shifted the median overall survival (OS) from 11.8 to 12.6 months. We retrospectively analyzed the value of individualized multimodal immunotherapy (IMI) to improve OS in these patients. All adults meeting the criteria and treated 06/2015–06/2021 were selected. Thirty-two patients (12f, 20m) had a median age of 47 y (range 18–69) and a KPI of 70 (50–100). Extent of resection was complete (11), <complete (12) or not documented (9). Seven patients were treated with surgery/radio(chemo)therapy and subsequent IMI (Group-1); 25 patients were treated with radiochemotherapy followed by maintenance TMZ plus IMI during and after TMZ (Group-2). Age, KPI and extent of resection were not different amongst both groups. The median OS of group-1 patients was 11 m (2 y OS: 0%). Surprisingly the median OS of group-2 patients was 22 m with 2 y OS of 36% (CI95%: 16–57), which was significantly (Log-rank: p = 0.0001) different from group-1. The data suggest that addition of IMI after local therapy on its own has no relevant effect on OS in these GBM patients, similar to maintenance TMZ. However, the combination of both TMZ + IMI significantly improved OS.
The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system
Authors: Ji Chang Hoon , Kim Hee Yeon , Lee Min Ju , Heo Ah Jung , Park Daniel Youngjae , Lim Sungsu , Shin Seulgi , Ganipisetti Srinivasrao , Yang Woo Seung , Jung Chang An , Kim Kun Young , Jeong Eun Hye , Park Sun Ho , Bin Kim Su , Lee Su Jin , Na Jeong Eun , Kang Ji In , Chi Hyung Min , Kim Hyun Tae , Kim Yun Kyung , Kim Bo Yeon , Kwon Yong Tae
Published: February 2022

Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC50 values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.
RETRACTED ARTICLE: Pharmacological perturbation of CXCL1 signaling alleviates neuropathogenesis in a model of HEVA71 infection
Authors: Gunaseelan Saravanan , Ariffin Mohammed Zacky , Khanna Sanjay , Ooi Mong How , Perera David , Chu Justin Jang Hann , Chua John Jia En
Published: February 2022

Hand, foot and mouth disease (HFMD) caused by Human Enterovirus A71 (HEVA71) infection is typically a benign infection. However, in minority of cases, children can develop severe neuropathology that culminate in fatality. Approximately 36.9% of HEVA71-related hospitalizations develop neurological complications, of which 10.5% are fatal. Yet, the mechanism by which HEVA71 induces these neurological deficits remain unclear. Here, we show that HEVA71-infected astrocytes release CXCL1 which supports viral replication in neurons by activating the CXCR2 receptor-associated ERK1/2 signaling pathway. Elevated CXCL1 levels correlates with disease severity in a HEVA71-infected mice model. In humans infected with HEVA71, high CXCL1 levels are only present in patients presenting neurological complications. CXCL1 release is specifically triggered by VP4 synthesis in HEVA71-infected astrocytes, which then acts via its receptor CXCR2 to enhance viral replication in neurons. Perturbing CXCL1 signaling or VP4 myristylation strongly attenuates viral replication. Treatment with AZD5069, a CXCL1-specific competitor, improves survival and lessens disease severity in infected animals. Collectively, these results highlight the CXCL1-CXCR2 signaling pathway as a potential target against HFMD neuropathogenesis.
Large-gap insulating dimer ground state in monolayer IrTe2
Authors: Hwang Jinwoong , Kim Kyoo , Zhang Canxun , Zhu Tiancong , Herbig Charlotte , Kim Sooran , Kim Bongjae , Zhong Yong , Salah Mohamed , El-Desoky Mohamed M. , Hwang Choongyu , Shen Zhi-Xun , Crommie Michael F. , Mo Sung-Kwan
Published: February 2022

Monolayers of two-dimensional van der Waals materials exhibit novel electronic phases distinct from their bulk due to the symmetry breaking and reduced screening in the absence of the interlayer coupling. In this work, we combine angle-resolved photoemission spectroscopy and scanning tunneling microscopy/spectroscopy to demonstrate the emergence of a unique insulating 2 × 1 dimer ground state in monolayer 1T-IrTe2 that has a large band gap in contrast to the metallic bilayer-to-bulk forms of this material. First-principles calculations reveal that phonon and charge instabilities as well as local bond formation collectively enhance and stabilize a charge-ordered ground state. Our findings provide important insights into the subtle balance of interactions having similar energy scales that occurs in the absence of strong interlayer coupling, which offers new opportunities to engineer the properties of 2D monolayers.
Electrochemical corrosion of multiphase stainless steel-based alloy nuclear waste forms
Authors: Gattu Vineeth Kumar , Ebert William L. , Indacochea J. E. , Cruse Terry A. , Fortner Jeffrey A.
Published: February 2022

The electrochemical corrosion behaviors of two multiphase alloys representing waste forms made with 316 L stainless steel and different amounts of surrogate metallic fuel wastes were measured and related to the microstructures. Potentiodynamic (PD) scans were performed in an acid brine solution and the corroded surfaces were characterized with scanning electron microscopy (SEM) to compare the electrochemical responses to the corrosion of specific phases. PD scans for the two multiphase alloys, 316 L stainless steel, and pure palladium were compared to understand the complex corrosion behavior of these multiphase alloys also recently classified as multi principle element alloys (MPEAs) and to determine the effects of alloying elements and noble metals present in constituent phases on the corrosion behavior.
Finite key effects in satellite quantum key distribution
Authors: Sidhu Jasminder S. , Brougham Thomas , McArthur Duncan , Pousa Roberto G. , Oi Daniel K. L.
Published: February 2022

Global quantum communications will enable long-distance secure data transfer, networked distributed quantum information processing, and other entanglement-enabled technologies. Satellite quantum communication overcomes optical fibre range limitations, with the first realisations of satellite quantum key distribution (SatQKD) being rapidly developed. However, limited transmission times between satellite and ground station severely constrains the amount of secret key due to finite-block size effects. Here, we analyse these effects and the implications for system design and operation, utilising published results from the Micius satellite to construct an empirically-derived channel and system model for a trusted-node downlink employing efficient Bennett-Brassard 1984 (BB84) weak coherent pulse decoy states with optimised parameters. We quantify practical SatQKD performance limits and examine the effects of link efficiency, background light, source quality, and overpass geometries to estimate long-term key generation capacity. Our results may guide design and analysis of future missions, and establish performance benchmarks for both sources and detectors.
Semiquantitative microscopic pore characterizations of the metamorphic rock reservoir in the central paleo-uplift belt, Songliao Basin
Authors: Zeng Zhouqiang , Shan Xuanlong , Hao Guoli , He Wentong , Zheng Changqing , Yi Jian , Guo Jiannan
Published: February 2022

Currently, metamorphic rock is a common target for natural gas exploration, and reservoirs are the key factors restricting natural gas exploration and development in metamorphic rocks. The deep metamorphic rock gas reservoir in the central paleo-uplift of the northern Songliao Basin has good exploration and development potential. In this study, we use a combination of qualitative descriptions and quantitative analysis to comprehensively analyze the pore characteristics of the reservoir and explore the factors controlling the pore characteristics of the metamorphic rock reservoir in the central paleo-uplift belt of the Songliao Basin. The metamorphic rock reservoir in the central paleo-uplift belt contains three types of lithologies: chlorite schist, mica schist and mylonite, each with different protoliths and metamorphic histories. The results of high-pressure mercury intrusion and nitrogen adsorption indicate that the pore size distributions of the schist and mylonite differ. Compared with the mylonite, the schist has larger reservoir space, more heterogeneity, smaller pore size, larger specific surface area and larger adsorbed gas storage capacity. This paper also studies the formation process of the reservoir and divides it into four stages. Finally, this article discusses in detail the factors controlling the microscopic pore characteristics of metamorphic rock reservoirs in the central paleo-uplift belt; the metamorphic rock protolith is the most important controlling factor.
RETRACTED ARTICLE: Evaluating the role of propolis and bee venom on the oxidative stress induced by gamma rays in rats
Authors: El Adham Eithar K. , Hassan Amal I. , A. Dawoud M. M.
Published: February 2022

Honeybee products consist of many substances, which have long been known for their medicinal and health-promoting properties. This study set out to appraise the protective potential of Egyptian propolis (EP) and bee venom (BV) separately or combined against total body irradiation (TBI) induced oxidative injury in rats. Besides, we assessed the bioactive components in EP and BV using HPLC and UPLC/ ESI–MS analysis in the positive ion mode. The animals were subjected to a source of gamma ionizing radiation at a dose of 6 Gy. Propolis and BV were administered independently and in combination before 14 days of γ-irradiation. Liver and kidney functions were estimated besides, DNA damage index (8- OHdG) by ELISA. Antioxidants, including glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were detected. Gene expression technique investigated for BAX, BCL2, and in plasma also miR125b expression in serum of rats. Besides, the histopathological for the brain, liver, kidney, and heart were investigated. In addition, lipid peroxidation was investigated in plasma and in the previous organs. The present results provide opportunities to advance the use of bee products as promising medicinal sources.
A multimodal deep learning system to distinguish late stages of AMD and to compare expert vs. AI ocular biomarkers
Authors: Thakoor Kaveri A. , Yao Jiaang , Bordbar Darius , Moussa Omar , Lin Weijie , Sajda Paul , Chen Royce W. S.
Published: February 2022

Within the next 1.5 decades, 1 in 7 U.S. adults is anticipated to suffer from age-related macular degeneration (AMD), a degenerative retinal disease which leads to blindness if untreated. Optical coherence tomography angiography (OCTA) has become a prime technique for AMD diagnosis, specifically for late-stage neovascular (NV) AMD. Such technologies generate massive amounts of data, challenging to parse by experts alone, transforming artificial intelligence into a valuable partner. We describe a deep learning (DL) approach which achieves multi-class detection of non-AMD vs. non-neovascular (NNV) AMD vs. NV AMD from a combination of OCTA, OCT structure, 2D b-scan flow images, and high definition (HD) 5-line b-scan cubes; DL also detects ocular biomarkers indicative of AMD risk. Multimodal data were used as input to 2D-3D Convolutional Neural Networks (CNNs). Both for CNNs and experts, choroidal neovascularization and geographic atrophy were found to be important biomarkers for AMD. CNNs predict biomarkers with accuracy up to 90.2% (positive-predictive-value up to 75.8%). Just as experts rely on multimodal data to diagnose AMD, CNNs also performed best when trained on multiple inputs combined. Detection of AMD and its biomarkers from OCTA data via CNNs has tremendous potential to expedite screening of early and late-stage AMD patients.