bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmable money: next-generation blockchain-based conditional payments
Authors: Weber Ingo , Staples Mark
Published: September 2022

Conditional payments allow the transfer of money only when pre-defined rules hold. Example uses could include welfare payments, employee expenses, insurance payouts, or tied donations. Normally, conditions are checked manually in reimbursement or pre-approval/audit processes, either at accounts before funds are distributed, or using account records after distribution. Blockchain’s capabilities for smart contract and digital assets can be used to implement next-generation conditional payments, on a decentralized ledger. We conducted a project with an industry partner where we conceptualized, implemented, and evaluated a novel programmable money concept using blockchain. In the system, programmed policies are not attached to accounts, but instead to money itself. Policies here specify the conditions when money may be spent, and can be automatically checked by the money as it is spent. Policies can also define auxiliary actions to be taken as part of payment transactions, including side-payments. Policies can be dynamically added to and removed from money as it flows through an economy. These policies could be budget rules for tied funds, but could also enable new forms of “values-based money” that respect ethical or other rules which relate to societal values or social norms. We report on some of our experiences and insights regarding blockchain architecture, software engineering with blockchain, and blockchain-based programmable money. We also identify opportunities and open research questions in these areas.
Analysis of the change in the structure of the Japanese power supply using the GTAP-E-power model
Authors: Higashi Akiko , Itakura Ken , Inoue Yushi , Otake Hiroaki
Published: September 2022

This study analyzes the effect of the change in the structure of the Japanese power supply, which disaggregates the power sector based on the GTAP-E model framework. We analyze the impact of the change in the power structure on Japan’s macroeconomy, power sector, and industry by comparing the results of four scenarios. In our simulations, which are divided into two periods, shocks are introduced to the growth rate in real GDP, labor force, population, and Japanese zero-emission power supply; nuclear power, hydropower, wind power, solar power, and other types of power. First, simulations from 2011 to 2018 were performed to update the GTAP-E-Power database. Next, simulations from 2019 to 2030 were performed for policy scenarios with different growth rates of zero-emission power supply in Japan. The simulation results show that if Japan maintains the same growth rate of zero-emission power supply as that of the Sustainable Development Scenario of the World Energy Outlook 2019, the share of zero-emission power supply in 2030 will achieve the government’s target. The simulation results also show that an increase in zero-emission power supply has a positive effect on the Japanese trade balance.
Matrix compression along isogenic blocks
Authors: Belton Alexander , Guillot Dominique , Khare Apoorva , Putinar Mihai
Published: September 2022

A matrix-compression algorithm is derived from a novel isogenic
block decomposition for square matrices. The resulting compression and
inflation operations possess strong functorial and spectral-permanence
properties. The basic observation that Hadamard entrywise functional
calculus preserves isogenic blocks has already proved to be of paramount
importance for thresholding large correlation matrices. The proposed
isogenic stratification of the set of complex matrices bears similarities to
the Schubert cell stratification of a homogeneous algebraic manifold. An
array of potential applications to current investigations in computational
matrix analysis is briefly mentioned, touching concepts such as symmetric
statistical models, hierarchical matrices and coherent matrix organization
induced by partition trees.
Understanding Forensic DNA
Authors: Bell Suzanne , Butler John M.
Published: September 2022

Forensic DNA analysis plays a central role in the judicial system. A DNA sample can change the course of an investigation with immense consequences. Because DNA typing is recognized as the epitome of forensic science, increasing public awareness in this area is vital. Through several cases, examples and illustrations, this book explains the basic principles of forensic DNA typing, and how it integrates with law enforcement investigations and legal decisions. Written for a general readership, Understanding Forensic DNA explains both the power and the limitations of DNA analysis. This book dispels common misunderstandings regarding DNA analysis and shows how astounding match probabilities such as one-in-a-trillion are calculated, what they really mean, and why DNA alone never solves a case.
Unsteady motions in the turbulent separation bubble of a two-dimensional wing
Authors: Wang Sen , Ghaemi Sina
Published: September 2022

The unsteadiness of a turbulent separation bubble (TSB) formed close to the trailing edge of a two-dimensional wing was investigated using time-resolved particle image velocimetry. The angle of attack was set to 9.7° and the chord-based Reynolds number was 720 000. The TSB consisted of two shear layers and formed a triangular shape in the streamwise–wall-normal plane. The vertices of this triangle consisted of an intermittent detachment point, a fixed corner close to the airfoil trailing edge and an intermittent endpoint in the wake region. The velocity field had three energetic regions each with different Strouhal numbers (Stl): (a) an upstream turbulent boundary layer (TBL) with Stl = 0.1 to 4, (b) a TSB with Stl = 0.03 to 0.08 and (c) two shear layers with Stl = 0.4 to 0.8. The low-frequency motions in the TSB consisted of large zones of positive and negative streamwise velocity fluctuation that were several times wider than the large-scale structures of the upstream TBL. These zones forced an undulation of the separation line and were attributed to Görtler structures. They were also correlated with the velocity fluctuations between the two shear layers. The breathing motion of the TSB occurred at Stl = 0.05. This breathing correlated with the location of the TSB endpoint and the flapping of the upper shear layer. The detachment point of the TSB featured broad fluctuations and did not demonstrate a strong correlation with the breathing motion.
Large-scale influence of numerical noises as artificial stochastic disturbances on a sustained turbulence
Authors: Qin Shijie , Liao Shijun
Published: September 2022

We investigate the large-scale influence of numerical noises as tiny artificial stochastic disturbances on a sustained turbulence. Using two-dimensional (2-D) turbulent Rayleigh–Bénard convection (RBC) as an example, we solve numerically the Navier–Stokes equations, separately, by means of a traditional algorithm with double precision (denoted RKwD) and the so-called clean numerical simulation (CNS). The numerical simulation given by RKwD is a mixture of the ‘true’ physical solution and the ‘false’ numerical noises that are random and can be regarded as a kind of artificial stochastic disturbances; unfortunately, the ‘true’ physical solution is mostly at the same level as the ‘false’ numerical noises. By contrast, the CNS can greatly reduce the background numerical noise to any a required level so that the ‘false’ numerical noises are negligible compared with the ‘true’ physical solution, thus the CNS solution can be used as a ‘clean’ benchmark solution for comparison. It is found that the numerical noises as tiny artificial stochastic disturbances could indeed lead to large-scale deviations of simulations not only in spatio-temporal trajectories but also even in statistics. In particular, these numerical noises (as artificial stochastic disturbances) even lead to different types of flows. The shearing convection occurs for the RKwD simulations, and its corresponding flow field turns to a kind of zonal flow thereafter; however, the CNS benchmark solution always sustains the non-shearing vortical/roll-like convection during the whole process of simulation. Thus we provide rigorous evidence that numerical noises as a kind of small-scale artificial stochastic disturbances have quantitatively and qualitatively large-scale influences on a sustained turbulence, i.e. the 2-D turbulent RBC considered in this paper.
Potato consumption is not associated with cardiometabolic health outcomes in Framingham Offspring Study adults
Authors: Yiannakou Ioanna , Pickering R. Taylor , Yuan Mengjie , Singer Martha R. , Moore Lynn L.
Published: September 2022

Some consider potatoes to be unhealthy vegetables that may contribute to adverse cardiometabolic health outcomes. We evaluated the association between potato consumption (including fried and non-fried types) and three key cardiometabolic outcomes among middle-aged and older adults in the Framingham Offspring Study. We included 2523 subjects ≥30 years of age with available dietary data from 3-d food records. Cox-proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for hypertension, type 2 diabetes or impaired fasting glucose (T2DM/IFG), and elevated triglycerides, adjusting for anthropometric, demographic and lifestyle factors. In the present study, 36 % of potatoes consumed were baked, 28 % fried, 14 % mashed, 9 % boiled and the rest cooked in other ways. Overall, higher total potato intake (≥4 v. <1 cup-equivalents/week) was not associated with risks of T2DM/IFG (HR 0⋅97, 95 % CI 0⋅81, 1⋅15), hypertension (HR 0⋅95; 95 % CI 0⋅80, 1⋅12) or elevated triglycerides (HR 0⋅99, 95 % CI 0⋅86, 1⋅13). Stratified analyses were used to evaluate effect modification by physical activity levels and red meat consumption, and in those analyses, there were no adverse effects of potato intake. However, when combined with higher levels of physical activity, greater consumption of fried potatoes was associated with a 24 % lower risk (95 % CI 0⋅60, 0⋅96) of T2DM/IFG, and in combination with lower red meat consumption, higher fried potato intake was associated with a 26 % lower risk (95 % CI 0⋅56, 0⋅99) of elevated triglycerides. In this prospective cohort, there was no adverse association between fried or non-fried potato consumption and risks of T2DM/IFG, hypertension or elevated triglycerides.
A critical assessment of claims that human footprints in the Lake Otero basin, New Mexico date to the Last Glacial Maximum
Authors: Oviatt Charles G. , Madsen David B. , Rhode David , Davis Loren G.
Published: September 2022

The ancient human footprints in valley-bottom sediments in Tularosa Valley, New Mexico, are fascinating and potentially important because they suggest interactions between Pleistocene megafauna as well as great antiquity. The dating of those footprints is crucial in interpretations of when humans first came to North America from Asia, but the ages have larger uncertainties than has been reported. Some of that uncertainty is related to the possibility of a radiocarbon reservoir in the water in which the dated propagules ofRuppia cirrhosagrew. As a test of that possibility,Ruppiaspecimens collected in 1947 from nearby Malpais Spring returned a radiocarbon age of ca. 7400 cal yr BP. We think it would be appropriate to devise and implement independent means for dating the footprints, thus lowering the uncertainty in the proposed age of the footprints and leading to a better understanding of when humans first arrived in the Americas.
Community-based fish sanctuaries: untapped potential for freshwater fish conservation
Authors: Jumani Suman , Hull Vanessa , Dandekar Parineeta , Mahesh Neethi
Published: September 2022

Riverine systems and associated fish populations worldwide are threatened by human impacts, especially in tropical countries with emerging economies. In India, community-based fish sanctuaries are a key mechanism for the conservation of freshwater fish populations, but there are few peer-reviewed studies on this subject. Here we integrate over 35 combined years of field experience with a literature synthesis to define and classify community-based fish sanctuaries. We present a novel, critical analysis of fish sanctuaries as social–ecological systems with a functional characterization based on natural capital, ecosystem services, human well-being, and policy and governance. We find that such sanctuaries are shaped by complex social–ecological processes, including coevolution of religious practices and ecological change, feedback processes created by retaliatory conflicts between river users, and diverse and dynamic governance strategies. These sanctuaries hold great potential for the conservation of rare fish species in India, but are subject to myriad threats at local, regional and global scales. Given the complexity of these social–ecological systems, we outline their conservation potential and highlight directions for future research.
Regional Lydian pottery at Daskyleion: testing stylistic classification by chemical analysis
Authors: Gürtekin-Demir R. Gül , Mommsen Hans , Kerschner Michael
Published: September 2022

This paper presents the results of an interdisciplinary study of Lydian pottery excavated at Daskyleion between 1988 and 2002. Before becoming the satrapal centre of Hellespontine Phrygia in the Achaemenid period, to judge by the historical and archaeological evidence, Daskyleion had close interrelations with the Lydian kingdom. Previous stylistic and macroscopic fabric studies of Lydian pottery from Daskyleion have shown that as well as items produced in the Lydian capital of Sardis, ceramics may also have been imported from other production centres in the region of Greater Lydia (Gürtekin-Demir 2002). New chemical analysis by neutron activation (NAA) of 31 samples from Daskyleion presented here confirms this suggestion. We determined four chemical provenance groups of Lydian pottery, each of them defined by an element pattern which is distinct from the pottery made in Sardis. Although these four provenance groups cannot be located at present due to the lack of reference data from potential Lydian-style ceramic production centres in Anatolia, they prove that other production centres existed outside Sardis. Daskyleion may have been one of those.
The deprived or the devil? A content analysis of the media representation of older adults under COVID-19 in Hong Kong
Authors: Yang Frances Lu , Au Adelaide Tsz Nok , Wong Jason Yue Hei , Lou Vivian Wei Qun
Published: September 2022

Older adults have been statistically proved to be at a higher risk of getting severely infected by the coronavirus COVID-19, evoking sweeping narratives of compassionate ageism surrounding them in different discourses. By analysing the media content, scholars from different areas have alerted us about the amplified ageism aroused by the pandemic crisis. However, we are still short of empirical evidence to learn how ageism is constructed in diverse sociocultural contexts in the wake of this global pandemic crisis. This study provides the case of Hong Kong to reflect on how ageism, as a set of social inequalities, is constructed. By examining 814 articles collected from the three most popular newspapers with different political orientations in Hong Kong, this study uses quantitative and qualitative content analysis to examine how older people have been generally represented. Then it further compares how these representations have been influenced by the media's liberal or conservative preferences. Third, it examines the relationship between the political orientation of newspapers and how different forms of ageism are constructed. The findings indicate that despite the liberal or conservative inclination of the three newspapers, they portray the older population as frail, dependent and deprived not only at the biomedical level but in all aspects of life. This study also reveals that the newspapers with a populist inclination in both camps have shown more hostile attitudes in representing compassionate ageism. In contrast, liberal and conservative-leaning media affirmed the government's dominant role in taking full responsibility for caring for the older population. The findings indicate that the polarised ageism frame cannot fully explain the underpinnings of ageism and implied policy processing in different contexts.
A new comprehensive performance optimization approach for Earth-contact mechanism based on terrain-adaptability task
Authors: Tang Hongyan , Zhang James M. , Zhang Dan
Published: September 2022

Earth-contact mechanism (ECM), a type of mechanism to keep the system in contact with the earth and to move with the terrain changes. This paper uses the virtual equivalent parallel mechanism (VEPM) to convert the terrain data into the kinematical variables of the moving platform in the VEPM, and further analyzes the performance of the VEPM at each terrain point. Then, the comprehensive performance of the VEPM is chosen as the optimization goal, and a task-oriented dimensional optimization approach combined with the particle swarm algorithm and the neural network algorithm is proposed. This paper conducted a comparative experiment to verify the superiority of the new approach in optimizing the ECM’s comprehensive performance, whose performance analysis also can be applied into the layout design of the ECM. This paper proposed an analysis method to construct the ECM’s performance map based on the digital terrain map, which helps the control system and operator to make the optimal control decision.
Representing vulnerable populations in genetic studies: The case of the Roma
Authors: Lipphardt Veronika , Rappold Gudrun A. , Surdu Mihai
Published: September 2022

Argument

Moreau (2019) has raised concerns about the use of DNA data obtained from vulnerable populations, such as the Uighurs in China. We discuss another case, situated in Europe and with a research history dating back 100 years: genetic investigations of Roma. In our article, we focus on problems surrounding representativity in these studies. We claim that many of the circa 440 publications in our sample neglect the methodological and conceptual challenges of representativity. Moreover, authors do not account for problematic misrepresentations of Roma resulting from the conceptual frameworks and sampling schemes they use. We question the representation of Roma as a “genetic isolate” and the underlying rationales, with a strong focus on sampling strategies. We discuss our results against the optimistic prognosis that the “new genetics” could help to overcome essentialist understandings of groups.
Individuals and collectives in the philosophy of Boris Hessen: An introduction
Authors: Winkler Sean
Published: September 2022

Argument

This paper provides an introduction to three translations of articles by Soviet philosopher Boris Hessen: “Mechanical Materialism and Modern Physics,” “On Comrade Timiryazev’s Attitude towards Contemporary Science” and “Marian Smoluchowski (On the Tenth Anniversary of His Death)”. It begins by presenting a central tension in Hessen’s work; namely, how even though he is better known for the externalism of his 1931 Newton paper, much of his work has been considered exemplary of an internalist approach. I then show that for Hessen, the history of modern science was defined by the discovery of the dialectical unity in opposition between dynamic and statistical regularity. This not only sheds important light on Hessen’s understanding of causation, but also reconciles the aforementioned tension by showing his approach to the relationship between individuals and collectives in the study of physical phenomena, along with the relationship between individual scientists and socioeconomic conditions.
Large Predator Hunting and Its Interpretation: Leopards, Bears and Lions in the Archaeological Record of the Southern Levant
Authors: Shimelmitz Ron , Reshef Hagar , Nativ Assaf , Marom Nimrod
Published: September 2022

In this paper, we discuss the occurrence of lions, bears and leopards in south Levantine archaeological assemblages between the last glacial maximum (c.25,000 years ago) and the Iron Age (c.2500 years ago). We argue that the occurrence of these large carnivores constitutes a significant long-term cultural feature that begins with the first settled hunter-gatherer communities of the Natufian culture. Importantly, we show that carnivoran species representation in the archaeological record shifts through time, with leopards common during the Neolithic and lions and bears during the Bronze and Iron ages. These shifts, we suggest, are best understood as reflecting the interplay between costly signalling and symbolism as they interacted through processes of increasing socio-political complexity.
Successful percutaneous closure of a recurrent aorto-left ventricular tunnel with an Amplatzer Vascular Plug II
Authors: Sathe Yogesh Chintaman , Tomar Munesh , Krasemann Thomas
Published: September 2022

Aorto-left ventricular tunnel is an extremely rare CHD clinically impressing as aortic regurgitation. This is usually corrected surgically, sometimes by percutaneous catheter intervention. Recurrent aorto-left ventricular tunnel has been reported occasionally. Reports of percutaneous closure of such recurrent aorto-left ventricular tunnels are rare. We hereby describe successful closure of a recurrent aorto-left ventricular tunnel with an Amplatzer Vascular Plug II.
Energy-Dispersive X-Ray Spectrum Simulation with NIST DTSA-II: Comparing Simulated and Measured Electron-Excited Spectra
Authors: Newbury Dale E , Ritchie Nicholas W M
Published: September 2022

Electron-excited X-ray microanalysis with energy-dispersive spectrometry (EDS) proceeds through the application of the software that extracts characteristic X-ray intensities and performs corrections for the physics of electron and X-ray interactions with matter to achieve quantitative elemental analysis. NIST DTSA-II is an open-access, fully documented, and freely available comprehensive software platform for EDS quantification, measurement optimization, and spectrum simulation. Spectrum simulation with DTSA-II enables the prediction of the EDS spectrum from any target composition for a specified electron dose and for the solid angle and window parameters of the EDS spectrometer. Comparing the absolute intensities for measured and simulated spectra reveals correspondence within ±25% relative to K-shell and L-shell characteristic X-ray peaks in the range of 1–11 keV. The predicted M-shell intensity exceeds the measured value by a factor of 1.4–2.2 in the range 1–3 keV. The X-ray continuum (bremsstrahlung) generally agrees within ±10% over the range of 1–10 keV. Simulated EDS spectra are useful for developing an analytical strategy for challenging problems such as estimating trace detection levels.
Early diagnosis of symptomatic ovarian cancer in primary care in the UK: opportunities and challenges
Authors: Rampes Sanketh , Choy Shern-Ping
Published: September 2022

Background:

Ovarian cancer is the sixth most common cause of cancer-related death in the UK amongst women. Ovarian cancer presents particular challenges for general practitioners (GPs) to diagnose due to its rarity and presentation with non-specific symptoms.

Methods:

A narrative overview of the literature was conducted by searching PubMed and Researchgate for relevant articles, using keywords such as “ovarian cancer,” “primary care” and “diagnosis.”

Results and Discussion:

Studies have shown that in the UK, GPs have a lower readiness to refer and investigate potential cancer symptoms compared with their international counterparts; and this has been correlated with reduced survival. Early diagnosis can be facilitated through a people-focussed and system-based approach which involves both educating GPs and using risk algorithms, rapid diagnostic centres/multi-disciplinary centres and being data-driven through the identification of best practice from national audits. Further research is required into the best evidence-based early investigations for ovarian cancer and more effective biomarkers.
Results From a Decade of Optical Fiber Strainmeters at Piñon Flat Observatory
Authors: Hatfield William , Elliott Don , Wyatt Frank K. , Xie Surui , Zumberge Mark A.
Published: September 2022

Optical fibers, stretched between anchors attached to the Earth and buried in boreholes and shallow trenches, offer an inexpensive and robust means to observe Earth strain. We have deployed several optical fiber strainmeters (OFSs) in boreholes, where thermal stability helps mitigate the noise from temperature changes. We have also constructed horizontal OFSs in 1‐m‐deep trenches of lengths 221 and 174 m. In these, a second optical fiber having a contrasting temperature coefficient provides a means to separate true strain from thermal noise. Signals in the seismic band from the horizontal strainmeters agree well with records from collocated seismometers, and the predominant ambient noise recorded by both techniques are consistent. Solid Earth strain tides with amplitude of 30 nε (nanostrain) are observed in these horizontal OFSs that agree well with those observed by collocated vacuum laser strainmeters. Noise at periods of a few days amounts to 50 nε. The two horizontal strainmeters show drift rates of up to 1 µε per month, and occasional false signals (evident from comparisons with the vacuum laser strainmeters) can accumulate occasionally to the order of 50 nε over times from hours to weeks. Results to date indicate that this technology on land could detect slow‐slip events of amplitude 100 nε and higher.
A Search for Large‐Scale Variations in the Fine‐Scale Structure of Earth's Inner Core
Authors: Wu Sin‐Mei , Pang Guanning , Koper Keith D. , Euler Garrett
Published: September 2022

A hemispherical pattern in inner core attenuation (Q) has been observed from the apparent Q of inner core transmitted waves (PKPDF). How the elastic scattering (QSC) originating from kilometer‐scale inner core heterogeneities relates to large‐scale apparent Q variations remains elusive. Such inner core scattered (ICS) energy is characterized by emergent, long‐lasting, high‐frequency (1–4 Hz) coda immediately following pre‐critical reflections (PKiKP) from the inner core boundary (ICB). In this study, we develop a framework to systematically investigate ICS and examine its hemispherical pattern using data from two arrays that sample opposing sides of the Pacific quasi‐hemispherical boundary. We use all the viable data from earthquakes (Mw ≥ 5.8) within the past 2–3 decades recorded at distances of 50°–75° by YKA and ILAR—small‐aperture (∼10–20 km) seismic arrays situated in northwestern North America. Two independent waveform stripping methods are applied to extract ICS from the background energy, and various stacks are performed to identify ICS and its spatial pattern. We found that individual beams lacking clear evidence of PKiKP coda waves reveal ICS characteristics when stacked together, implying that ICS is ubiquitous. We used a modified phonon‐based simulation to reinforce the idea that ICS is primarily created by volumetric heterogeneity within the inner core as opposed to ICB topography. With simplified two‐layer ICS models, our results suggest that ICS within the eastern quasi‐hemisphere is slightly stronger than in the western quasi‐hemisphere, although intra‐hemispherical variations are as significant, and our sampling is limited to patches of the northern hemisphere.
BMS794833 inhibits macrophage efferocytosis by directly binding to MERTK and inhibiting its activity
Authors: Bae Seung-Hyun , Kim Jung-Hoon , Park Tae Hyun , Lee Kyeong , Lee Byung Il , Jang Hyonchol
Published: September 2022

Myeloid epithelial reproductive proto-oncogene tyrosine kinase (MERTK) plays an essential role in modulating cancer immune tolerance by regulating macrophage efferocytosis. Studies are underway to develop small-molecule chemicals that inhibit MERTK as cancer immunotherapeutic agents, but these efforts are in their early stages. This study identified BMS794833, whose primary targets are MET and VEGFR2, as a potent MERTK inhibitor and developed a real-time efferocytosis monitoring system. The X-ray cocrystal structure revealed that BMS794833 was in contact with the ATP-binding pocket and the allosteric back pocket, rendering MERTK inactive. Homogeneous time-resolved fluorescence kinetic and Western blotting analyses showed that BMS794833 competitively inhibited MERTK activity in vitro and inhibited the autophosphorylation of MERTK in macrophages. We developed a system to monitor MERTK-dependent efferocytosis in real time, and using this system, we confirmed that BMS794833 significantly inhibited the efferocytosis of differentiated macrophages. Finally, BMS794833 significantly inhibited efferocytosis in vivo in a mouse model. These data show that BMS794833 is a type II MERTK inhibitor that regulates macrophage efferocytosis. In addition, the real-time efferocytosis monitoring technology developed in this study has great potential for future applications.
The schizophrenia-associated missense variant rs13107325 regulates dendritic spine density
Authors: Li Shiwu , Ma Changguo , Li Yifan , Chen Rui , Liu Yixing , Wan Li Pear , Xiong Qiuxia , Wang Chuang , Huo Yongxia , Dang Xinglun , Yang Yongfeng , Lv Luxian , Chen Xi , Sheng Nengyin , Li Wenqiang , Luo Xiong-Jian
Published: September 2022

The missense variant rs13107325 (C/T, p.Ala391Thr) in SLC39A8 consistently showed robust association with schizophrenia in recent genome-wide association studies (GWASs), suggesting the potential pathogenicity of this non-synonymous risk variant. Nevertheless, how this missense variant confers schizophrenia risk remains unknown. Here we constructed a knock-in mouse model (by introducing a threonine at the 393th amino acid of mouse SLC39A8 (SLC39A8-p.393T), which corresponds to rs13107325 (p.Ala391Thr) of human SLC39A8) to explore the potential roles and biological effects of this missense variant in schizophrenia pathogenesis. We assessed multiple phenotypes and traits (associated with rs13107325) of the knock-in mice, including body and brain weight, concentrations of metal ions (including cadmium, zinc, manganese, and iron) transported by SLC39A8, blood lipids, proliferation and migration of neural stem cells (NSCs), cortical development, behaviors and cognition, transcriptome, dendritic spine density, and synaptic transmission. Many of the tested phenotypes did not show differences in SLC39A8-p.393T knock-in and wild-type mice. However, we found that zinc concentration in brain and blood of SLC39A8-p.393T knock-in mice was dysregulated compared with wild-types, validating the functionality of rs13107325. Further analysis indicated that cortical dendritic spine density of the SLC39A8-p.393T knock-in mice was significantly decreased compared with wild-types, indicating the important role of SLC39A8-p.393T in dendritic spine morphogenesis. These results indicated that SLC39A8-p.393T knock-in resulted in decreased dendritic spine density, thus mimicking the dendritic spine pathology observed in schizophrenia. Our study indicates that rs13107325 might confer schizophrenia risk by regulating zinc concentration and dendritic spine density, a featured characteristic that was frequently reported to be decreased in schizophrenia.
CDC42 governs normal oviduct multiciliogenesis through activating AKT to ensure timely embryo transport
Authors: Jiang Ruiwei , Tang Xiaofang , Pan Jiale , Li Gaizhen , Yang Ningjie , Tang Yedong , Bi Shilei , Cai Han , Chen Qionghua , Chen Dunjin , Wang Haibin , Kong Shuangbo
Published: September 2022

Ciliated and secretory cells are two major cell types that comprise the oviduct epithelia. Accumulating evidences support a role of oviductal multiciliated epithelia for embryo transport, however the mechanisms underlying this specialized cell type differentiation remain elusive. Here, we report that CDC42 depletion in oviduct epithelia hampers the morphogenesis of multiciliated cell, and results in embryo retention, leading to early pregnancy failure. Utilizing the oviduct organoid model, we further observed that CDC42 guides secretory cells transition into multiciliated cells independent of its GTPase activity and the well-known Notch pathway. Further exploration uncovered the AKT as a novel indispensable regulator for multiciliated cells differentiation, whose activity was maintained by CDC42 through interacting with the p110β. Consistently, re-activating AKT partially incites multiciliated cells differentiation in Cdc42 knockout oviductal organoids. Finally, low levels of CDC42 and phospho-AKT with reduced multiciliated cells in the oviduct are observed in women with ectopic pregnancy. Collectively, we provide previously unappreciated evidence that CDC42-AKT signaling is a critical determinant for morphogenesis of oviduct multiciliated cell, which possesses the clinical application in understanding the pathology of ectopic pregnancy and facilitating the development of prevention strategies.
A dual role of lola in Drosophila ovary development: regulating stem cell niche establishment and repressing apoptosis
Authors: Zhao Ting , Xiao Yanhong , Huang Bo , Ran Mao-Jiu , Duan Xin , Wang Yu-Feng , Lu Yuzhen , Yu Xiao-Qiang
Published: September 2022

In Drosophila ovary, niche is composed of somatic cells, including terminal filament cells (TFCs), cap cells (CCs) and escort cells (ECs), which provide extrinsic signals to maintain stem cell renewal or initiate cell differentiation. Niche establishment begins in larval stages when terminal filaments (TFs) are formed, but the underlying mechanism for the development of TFs remains largely unknown. Here we report that transcription factor longitudinals lacking (Lola) is essential for ovary morphogenesis. We showed that Lola protein was expressed abundantly in TFCs and CCs, although also in other cells, and lola was required for the establishment of niche during larval stage. Importantly, we found that knockdown expression of lola induced apoptosis in adult ovary, and that lola affected adult ovary morphogenesis by suppressing expression of Regulator of cullins 1b (Roc1b), an apoptosis-related gene that regulates caspase activation during spermatogenesis. These findings significantly expand our understanding of the mechanisms controlling niche establishment and adult oogenesis in Drosophila.
KCTD9 inhibits the Wnt/β-catenin pathway by decreasing the level of β-catenin in colorectal cancer
Authors: Yao Hanhui , Ren Delong , Wang Yichun , Wu Liang , Wu Yang , Wang Wei , Li Qidong , Liu Lianxin
Published: September 2022

Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. However, the molecular mechanisms underlying CRC progression remain to be further defined to improve patient outcomes. In this study, we found that KCTD9, a member of the potassium channel tetramerization domain-containing (KCTD) gene family, was commonly downregulated in CRC tissues and that KCTD9 expression was negatively correlated with the clinical CRC stage. Survival analysis showed that patients whose tumors expressed low KCTD9 levels had poorer outcomes. Functional analyses revealed that KCTD9 overexpression inhibited CRC cell proliferation and metastasis, whereas KCTD9 knockdown promoted CRC cell proliferation and metastasis in both in vitro and in vivo models. Manipulating KCTD9 levels in CRC cells via overexpression or knockdown showed KCTD9 expression positively influenced the degradation of β-catenin levels leading to inhibition of Wnt signaling and reductions in Wnt pathway target gene expression. Mechanistically, we found KCTD9 associated with ZNT9 (Zinc Transporter 9), a coactivator of β-catenin-mediated gene transcription. The overexpression of KCTD9 or knockdown of ZNT9 in CRC cells increased the polyubiquitination and proteasomal degradation of β-catenin. In turn, the KCTD9-ZNT9 interaction disrupted interactions between β-catenin and ZNT9, thereby leading to decreased β-catenin target gene expression and the inhibition of Wnt signaling. In conclusion, our findings propose that KCTD9 functions as a tumor suppressor that inhibits CRC cell proliferation and metastasis by inactivating the Wnt/β-catenin pathway. Moreover, its frequent downregulation in CRC suggests KCTD9 as a potential prognostic and therapeutic target in CRC.
Astrocytic SARM1 promotes neuroinflammation and axonal demyelination in experimental autoimmune encephalomyelitis through inhibiting GDNF signaling
Authors: Jin Lingting , Zhang Jingjing , Hua Xin , Xu Xingxing , Li Jia , Wang Jiaojiao , Wang Mianxian , Liu Huitao , Qiu Haoyu , Chen Man , Zhang Xu , Wang Ying , Huang Zhihui
Published: September 2022

Astrocytes are important components of the innate immune response in the central nervous system (CNS), involving in the inflammatory and neurotoxic responses that occur in CNS diseases, such as multiple sclerosis (MS). Recent studies have shown that SARM1 plays a critical role in axonal degeneration and inflammation. However, the detailed role of astrocytic SARM1 in MS remains unclear. Here, we established the MS model of mice - experimental autoimmune encephalomyelitis (EAE) and found that SARM1 was upregulated in astrocytes of the spinal cords of EAE mice. Moreover, conditional knockout of astrocytic SARM1 (SARM1GFAP-CKO mice, SARM1Aldh1L1-CKO mice) delayed EAE with later onset, alleviated the inflammatory infiltration, and inhibited the demyelination and neuronal death. Mechanically, RNA-seq revealed that the expression of glial-derived neurotrophic factor (GDNF) was upregulated in SARM1−/− astrocytes. Western blot and immunostaining further confirmed the upregulation of GDNF in spinal cord astrocytes of SARM1GFAP-CKO EAE mice. Interestingly, the downregulation of GDNF by streptozotocin (STZ, a drug used to downregulate GDNF) treatment worsened the deficits of SARM1GFAP-CKO EAE mice. These findings identify that astrocytic SARM1 promotes neuroinflammation and axonal demyelination in EAE by inhibiting the expression of GDNF, reveal the novel role of SARM1/GDNF signaling in EAE, and provide new therapeutic ideas for the treatment of MS.
Downregulation of Elovl5 promotes breast cancer metastasis through a lipid-droplet accumulation-mediated induction of TGF-β receptors
Authors: Kieu Trinh-Le-Vi , Pierre Léa , Derangère Valentin , Perrey Sabrina , Truntzer Caroline , Jalil Antoine , Causse Sébastien , Groetz Emma , Dumont Adélie , Guyard Laura , Arnould Laurent , de Barros Jean-Paul Pais , Apetoh Lionel , Rébé Cédric , Limagne Emeric , Jourdan Tony , Demizieux Laurent , Masson David , Thomas Charles , Ghiringhelli François , Rialland Mickaël
Published: September 2022

Metastatic breast cancer cannot be cured, and alteration of fatty acid metabolism contributes to tumor progression and metastasis. Here, we were interested in the elongation of very long-chain fatty acids protein 5 (Elovl5) in breast cancer. We observed that breast cancer tumors had a lower expression of Elovl5 than normal breast tissues. Furthermore, low expression of Elovl5 is associated with a worse prognosis in ER+ breast cancer patients. In accordance with this finding, decrease of Elovl5 expression was more pronounced in ER+ breast tumors from patients with metastases in lymph nodes. Although downregulation of Elovl5 expression limited breast cancer cell proliferation and cancer progression, suppression of Elovl5 promoted EMT, cell invasion and lung metastases in murine breast cancer models. The loss of Elovl5 expression induced upregulation of TGF-β receptors mediated by a lipid-droplet accumulation-dependent Smad2 acetylation. As expected, inhibition of TGF-β receptors restored proliferation and dampened invasion in low Elovl5 expressing cancer cells. Interestingly, the abolition of lipid-droplet formation by inhibition of diacylglycerol acyltransferase activity reversed induction of TGF-β receptors, cell invasion, and lung metastasis triggered by Elovl5 knockdown. Altogether, we showed that Elovl5 is involved in metastasis through lipid droplets-regulated TGF-β receptor expression and is a predictive biomarker of metastatic ER+ breast cancer.
Redox regulation of the immune response
Authors: Morris Gerwyn , Gevezova Maria , Sarafian Victoria , Maes Michael
Published: September 2022

The immune-inflammatory response is associated with increased nitro-oxidative stress. The aim of this mechanistic review is to examine: (a) the role of redox-sensitive transcription factors and enzymes, ROS/RNS production, and the activity of cellular antioxidants in the activation and performance of macrophages, dendritic cells, neutrophils, T-cells, B-cells, and natural killer cells; (b) the involvement of high-density lipoprotein (HDL), apolipoprotein A1 (ApoA1), paraoxonase-1 (PON1), and oxidized phospholipids in regulating the immune response; and (c) the detrimental effects of hypernitrosylation and chronic nitro-oxidative stress on the immune response. The redox changes during immune-inflammatory responses are orchestrated by the actions of nuclear factor-κB, HIF1α, the mechanistic target of rapamycin, the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, mitogen-activated protein kinases, 5' AMP-activated protein kinase, and peroxisome proliferator-activated receptor. The performance and survival of individual immune cells is under redox control and depends on intracellular and extracellular levels of ROS/RNS. They are heavily influenced by cellular antioxidants including the glutathione and thioredoxin systems, nuclear factor erythroid 2-related factor 2, and the HDL/ApoA1/PON1 complex. Chronic nitro-oxidative stress and hypernitrosylation inhibit the activity of those antioxidant systems, the tricarboxylic acid cycle, mitochondrial functions, and the metabolism of immune cells. In conclusion, redox-associated mechanisms modulate metabolic reprogramming of immune cells, macrophage and T helper cell polarization, phagocytosis, production of pro- versus anti-inflammatory cytokines, immune training and tolerance, chemotaxis, pathogen sensing, antiviral and antibacterial effects, Toll-like receptor activity, and endotoxin tolerance.
Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importin α7 is counteracted by TBK1-p62 axis-mediated autophagy
Authors: Wang Xuyuan , Jiang Li , Wang Guangwen , Shi Wenjun , Hu Yuzhen , Wang Bo , Zeng Xianying , Tian Guobin , Deng Guohua , Shi Jianzhong , Liu Liling , Li Chengjun , Chen Hualan
Published: September 2022

As a major component of the viral ribonucleoprotein (vRNP) complex in influenza A virus (IAV), nucleoprotein (NP) interacts with isoforms of importin α family members, leading to the import of itself  and vRNP complex into the nucleus, a process pivotal in the replication cycle of IAV. In this study, we found that BinCARD1, an isoform of Bcl10-interacting protein with CARD (BinCARD), was leveraged by IAV for efficient viral replication. BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity. Moreover, we found that BinCARD1 interacted with NP to promote NP binding to importin α7, an adaptor in the host nuclear import pathway. However, we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3, and that TBK1 appeared to degrade BinCARD1. We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage, which was recognized by the TBK1-p62 axis for autophagic degradation. Overall, our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication, and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.
Genetic, maternal, and environmental influences on sociality in a pedigreed primate population
Authors: Godoy Irene , Korsten Peter , Perry Susan E.
Published: September 2022

Various aspects of sociality in mammals (e.g., dyadic connectedness) are linked with measures of biological fitness (e.g., longevity). How within- and between-individual variation in relevant social traits arises in uncontrolled wild populations is challenging to determine but is crucial for understanding constraints on the evolution of sociality. We use an advanced statistical method, known as the ‘animal model’, which incorporates pedigree information, to look at social, genetic, and environmental influences on sociality in a long-lived wild primate. We leverage a longitudinal database spanning 20 years of observation on individually recognized white-faced capuchin monkeys (Cebus capucinus imitator), with a multi-generational pedigree. We analyze two measures of spatial association, using repeat sampling of 376 individuals (mean: 53.5 months per subject, range: 6–185 months per subject). Conditioned on the effects of age, sex, group size, seasonality, and El Niño–Southern Oscillation phases, we show low to moderate long-term repeatability (across years) of the proportion of time spent social (posterior mode [95% Highest Posterior Density interval]: 0.207 [0.169, 0.265]) and of average number of partners (0.144 [0.113, 0.181]) (latent scale). Most of this long-term repeatability could be explained by modest heritability (h2social: 0.152 [0.094, 0.207];h2partners: 0.113 [0.076, 0.149]) with small long-term maternal effects (m2social: 0.000 [0.000, 0.045];m2partners: 0.000 [0.000, 0.041]). Our models capture the majority of variance in our behavioral traits, with much of the variance explained by temporally changing factors, such as group of residence, highlighting potential limits to the evolvability of our trait due to social and environmental constraints.
Active learning of reactive Bayesian force fields applied to heterogeneous catalysis dynamics of H/Pt
Authors: Vandermause Jonathan , Xie Yu , Lim Jin Soo , Owen Cameron J. , Kozinsky Boris
Published: September 2022

Atomistic modeling of chemically reactive systems has so far relied on either expensive ab initio methods or bond-order force fields requiring arduous parametrization. Here, we describe a Bayesian active learning framework for autonomous “on-the-fly” training of fast and accurate reactive many-body force fields during molecular dynamics simulations. At each time-step, predictive uncertainties of a sparse Gaussian process are evaluated to automatically determine whether additional ab initio training data are needed. We introduce a general method for mapping trained kernel models onto equivalent polynomial models whose prediction cost is much lower and independent of the training set size. As a demonstration, we perform direct two-phase simulations of heterogeneous H2turnover on the Pt(111) catalyst surface at chemical accuracy. The model trains itself in three days and performs at twice the speed of a ReaxFF model, while maintaining much higher fidelity to DFT and excellent agreement with experiment.
An image interaction approach to quantum-phase engineering of two-dimensional materials
Authors: Di Giulio Valerio , Gonçalves P. A. D. , García de Abajo F. Javier
Published: September 2022

Tuning electrical, optical, and thermal material properties is central for engineering and understanding solid-state systems. In this scenario, atomically thin materials are appealing because of their sensitivity to electric and magnetic gating, as well as to interlayer hybridization. Here, we introduce a radically different approach to material engineering relying on the image interaction experienced by electrons in a two-dimensional material when placed in proximity of an electrically neutral structure. We theoretically show that electrons in a semiconductor atomic layer acquire a quantum phase resulting from the image potential induced by the presence of a neighboring periodic array of conducting ribbons, which in turn modifies the optical, electrical, and thermal properties of the monolayer, giving rise to additional interband optical absorption, plasmon hybridization, and metal-insulator transitions. Beyond its fundamental interest, material engineering based on the image interaction represents a disruptive approach to tailor the properties of atomic layers for application in nanodevices.