bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Link Prediction Framework Based on Gravitational Field
Authors: Yang Yanlin , Ye Zhonglin , Zhao Haixing , Meng Lei
Published: January 2023

Currently, most researchers only utilize the network information or node characteristics to calculate the connection probability between unconnected node pairs. Therefore, we attempt to project the problem of connection probability between unconnected pairs into the physical space calculating it. Firstly, the definition of gravitation is introduced in this paper, and the concept of gravitation is used to measure the strength of the relationship between nodes in complex networks. It is generally known that the gravitational value is related to the mass of objects and the distance between objects. In complex networks, the interrelationship between nodes is related to the characteristics, degree, betweenness, and importance of the nodes themselves, as well as the distance between nodes, which is very similar to the gravitational relationship between objects. Therefore, the importance of nodes is used to measure the mass property in the universal gravitational equation and the similarity between nodes is used to measure the distance property in the universal gravitational equation, and then a complex network model is constructed from physical space. Secondly, the direct and indirect gravitational values between nodes are considered, and a novel link prediction framework based on the gravitational field, abbreviated as LPFGF, is proposed, as well as the node similarity framework equation. Then, the framework is extended to various link prediction algorithms such as Common Neighbors (CN), Adamic-Adar (AA), Preferential Attachment (PA), and Local Random Walk (LRW), resulting in the proposed link prediction algorithms LPFGF-CN, LPFGF-AA, LPFGF-PA, LPFGF-LRW, and so on. Finally, four real datasets are used to compare prediction performance, and the results demonstrate that the proposed algorithmic framework can successfully improve the prediction performance of other link prediction algorithms, with a maximum improvement of 15%.
Environmental Activism and the Fairness of Costs Argument for Uncivil Disobedience
Authors: LAI TEN-HERNG , LIM CHONG-MING
Published: January 2023

Social movements often impose nontrivial costs on others against their wills. Civil disobedience is no exception. How can social movements in general, and civil disobedience in particular, be justifiable despite this apparent wrong-making feature? We examine an intuitively plausible account—it is fair that everyone should bear the burdens of tackling injustice. We extend this fairness-based argument for civil disobedience to defend some acts of uncivil disobedience. Focusing on uncivil environmental activism—such as ecotage (sabotage with the aim of protecting the environment)—we argue that some acts of uncivil disobedience can be morally superior to their civil counterparts, when and because such acts target people who are responsible for environmental threats. Indeed, insofar as some acts of uncivil disobedience can more accurately target responsible people, they can better satisfy the demands of fairness compared to their civil counterparts. In some circumstances, our argument may require activists to engage in uncivil disobedienceeven whencivil disobedience is available.
Predicting the last zero before an exponential time of a spectrally negative Lévy process
Authors: Baurdoux Erik J. , Pedraza José M.
Published: January 2023

Given a spectrally negative Lévy process, we predict, in an
$L_1$
sense, the last passage time of the process below zero before an independent exponential time. This optimal prediction problem generalises [2], where the infinite-horizon problem is solved. Using a similar argument as that in [24], we show that this optimal prediction problem is equivalent to solving an optimal prediction problem in a finite-horizon setting. Surprisingly (unlike the infinite-horizon problem), an optimal stopping time is based on a curve that is killed at the moment the mean of the exponential time is reached. That is, an optimal stopping time is the first time the process crosses above a non-negative, continuous, and non-increasing curve depending on time. This curve and the value function are characterised as a solution of a system of nonlinear integral equations which can be understood as a generalisation of the free boundary equations (see e.g. [21, Chapter IV.14.1]) in the presence of jumps. As an example, we numerically calculate this curve in the Brownian motion case and for a compound Poisson process with exponential-sized jumps perturbed by a Brownian motion.
Portfolio performance under benchmarking relative loss and portfolio insurance: From omega ratio to loss aversion
Authors: Ng Tak Wa , Nguyen Thai
Published: January 2023

We study an optimal investment problem under a joint limited expected relative loss and portfolio insurance constraint with a general random benchmark. By making use of a static Lagrangian method in a complete market setting, the optimal wealth and investment strategy can be fully determined along with the existence and uniqueness of the Lagrangian multipliers. Our numerical demonstration for various commonly used random benchmarks shows a trade-off between the portfolio outperformance and underperformance relative to the benchmark, which may not be captured by the widely used Omega ratio and its utility-transformed version, reflecting the impact of the benchmarking loss constraint. Furthermore, we develop a new portfolio performance measurement indicator that incorporates the agent’s utility loss aversion relative to the benchmark via solving an equivalent optimal asset allocation problem with a benchmark-reference-based preference. We show that the expected utility performance is well depicted by looking at this new portfolio performance ratio, suggesting a more suitable portfolio performance measurement under a limited loss constraint relative to a possibly random benchmark.
Something Valid This Way Comes: A Study of Neologicism and Proof-Theoretic Validity
Authors: Stafford Will
Published: January 2023

The interplay of philosophical ambitions and technical reality have given birth to rich and interesting approaches to explain the oft-claimed special character of mathematical and logical knowledge. Two projects stand out both for their audacity and their innovativeness. These are logicism and proof-theoretic semantics. This dissertation contains three chapters exploring the limits of these two projects. In both cases I find the formal results offer a mixed blessing to the philosophical projects.

Chapter 1. Is a logicist bound to the claim that as a matter of analytic truth there is an actual infinity of objects? If Hume’s Principle is analytic then in the standard setting the answer appears to be yes. Hodes’s work pointed to a way out by offering a modal picture in which only a potential infinity was posited. However, this project was abandoned due to apparent failures of cross-world predication. I re-explore this idea and discover that in the setting of the potential infinite one can interpret first-order Peano arithmetic, but not second-order Peano arithmetic. I conclude that in order for the logicist to weaken the metaphysically loaded claim of necessary actual infinities, they must also weaken the mathematics they recover.

Chapter 2. There have been several recent results bringing into focus the super-intuitionistic nature of most notions of proof-theoretic validity. But there has been very little work evaluating the consequences of these results. In this chapter, I explore the question of whether these results undermine the claim that proof-theoretic validity shows us which inferences follow from the meaning of the connectives when defined by their introduction rules. It is argued that the super-intuitionistic inferences are valid due to the correspondence between the treatment of the atomic formulas and more complex formulas. And so the goals of proof-theoretic validity are not undermined.

Chapter 3. Prawitz (1971) conjectured that proof-theoretic validity offers a semantics for intuitionistic logic. This conjecture has recently been proven false by Piecha and Schroeder-Heister (2019). This chapter resolves one of the questions left open by this recent result by showing the extensional alignment of proof-theoretic validity and general inquisitive logic. General inquisitive logic is a generalisation of inquisitive semantics, a uniform semantics for questions and assertions. The chapter further defines a notion of quasi-proof-theoretic validity by restricting proof-theoretic validity to allow double negation elimination for atomic formulas and proves the extensional alignment of quasi-proof-theoretic validity and inquisitive logic.

Abstract prepared by Will Stafford extracted partially from the dissertation.

E-mail: stafford@flu.cas.cz

URL: https://escholarship.org/uc/item/33c6h00c
Punitive Justice: When Race and Mental Illness Collide in the Early Stages of the Criminal Justice System
Authors: Rampersaud Marsha
Published: January 2023

Youths in care are among the most vulnerable youths in our society. All youths in care have experienced trauma and sometimes exhibit trauma-induced behaviours which are perceived by others as disruptive or dangerous. The police are frequently called, which begins a cycle of criminalization for many youths, with racialized youths overrepresented in this group. Using an intersectional theoretical framework, this article shows how discriminatory perceptions of race and mental health influence justice system actors’ decision-making, from arrest to bail. Drawing on data from qualitative interviews with twenty-five young adults (ages 18 to 24) who have had contact with the child welfare and criminal justice systems and ten practicing lawyers in Ontario, the analysis reveals race-based differences in justice system actors’ responses to mental illness. Discriminatory views function as a lens through which racialized and mentally ill youths leaving care are perceived as threats and met with more punitive responses.
Making Swadeshi Managers: The Antecedents of Professional Management Education in India, 1860s–1950s
Authors: Patel Dinyar Phiroze
Published: January 2023

The history of Indian management education is overwhelmingly focused on the period from the 1950s and 1960s onward. This article traces the hitherto underexplored history of how, from the 1860s until the 1950s, Indians thought about and implemented education and training for managers. In particular, it demonstrates how Indian nationalist politicians articulated the nation-building utility of managers and managerial training, and how business education became yoked to nationalists’ broader visions of India’s economic regeneration. Beginning in the early twentieth century, Indian nationalists championed commercial education, advocating its evolution out of its vocational roots into something more scientific and specialized for producing skilled indigenous managers. The precise evolution of Indian commercial education exercised long-term influences on postcolonial management programs. First, Indians established a tradition of surveying the latest pedagogical methods and institutional models from around the world and adapting them to Indian conditions. Second, Indian advocates of commercial education carved out an important role for the state, working on commercial education endeavors with British officials in the colonial era and, later on, placing management education within the ambit of centralized state planning. Management had a fundamentally political valence in India. For this reason, commercial and management education programs in India, unlike in the West, largely avoided questions about their legitimacy.
Equivariant Brill–Noether theory for elliptic operators and superrigidity of J-holomorphic maps
Authors: Doan Aleksander , Walpuski Thomas
Published: January 2023

The space of Fredholm operators of fixed index is stratified by submanifolds according to the dimension of the kernel. Geometric considerations often lead to questions about the intersections of concrete families of elliptic operators with these submanifolds: Are the intersections nonempty? Are they smooth? What are their codimensions? The purpose of this article is to develop tools to address these questions in equivariant situations. An important motivation for this work are transversality questions for multiple covers of J-holomorphic maps. As an application, we use our framework to give a concise exposition of Wendl’s proof of the superrigidity conjecture.
Outlet glacier flow response to surface melt: based on analysis of a high-resolution satellite data set
Authors: Larsen Signe H. , Ahlstrøm Andreas P. , Karlsson Nanna B. , Kusk Anders , Langen Peter L. , Hvidberg Christine S.
Published: January 2023

The dynamics of the Greenland Ice Sheet are affected by surface meltwater reaching the base of the ice, altering ice contact with the bedrock. Lack of understanding of this evolution hampers the ability to predict the effects of increasing temperatures on the Greenland Ice Sheet mass balance. Here we present a unique high-resolution study of ice velocity response to surface melting based on data from a COSMO-SkyMed satellite campaign over Upernavik Isstrøm (Northwest Greenland) for two months around the end of the 2014 melt season. We show that the velocity variations, due to both short-term (days) and seasonal variations in surface melt rates, are increasing in relative strength farther from the glacier terminus. Furthermore, we observe how ice dynamic response to frontal retreat, reaching several kilometres inland, can obscure the meltwater-induced velocity change close to the terminus. Future studies should consider the flow velocity dependence on the distance to the terminus, and local geometry, to distinguish subglacial hydrologic system changes from frontal processes and local basal conditions.
Transition density of an infinite-dimensional diffusion with the jack parameter
Authors: Zhou Youzhou
Published: January 2023

From the Poisson–Dirichlet diffusions to theZ-measure diffusions, they all have explicit transition densities. We show that the transition densities of theZ-measure diffusions can also be expressed as a mixture of a sequence of probability measures on the Thoma simplex. The coefficients are the same as the coefficients in the Poisson–Dirichlet diffusions. This fact will be uncovered by a dual process method in a special case where theZ-measure diffusions are established through an up–down chain in the Young graph.
Not in the Eye of the Beholder: Racialization, Whiteness, and Beauty Standards in Mexico
Authors: Krozer Alice , Gómez Andrea
Published: January 2023

This article explores the role “whiteness” takes on in Mexico, where colonial, religious, and social heritages elevate it as an aesthetic ideal, simultaneously denying its underlying racism. It argues that skin tone is one of many physical and nonphysical features that together shape the concept of whiteness in a context of fluid, relational, and intertwined categories of class and racial classifications. Women in particular are pressured to “whiten” their bodies in adherence to beauty standards that reflect the collective aspiration of the country’s ethnically mixed society. Using empirical evidence, the article outlines Mexicans’ aesthetic perceptions and explores their attempts to approach these through bodily presentations and adjustments. It then discusses how the local beauty industry acts as a practical tool and a discursive mediator toward racialized appearances. Possessing its own historical, political, and racial background deeply entangled with whiteness, this sector reinforces the subjective basis of discriminatory practices in Mexico.
No decrease in perseverance and performance on cognitive tasks in Danish cohort of hormonal contraceptive users
Authors: Byg Maria Nissen , Dioni Andrea , Winterdahl Michael
Published: January 2023

Cognitive consequences of hormonal contraceptives (HCs) are largely underexplored, despite the popularity of use. This study investigates the association between perseverance during cognitively challenging tasks and the use of HCs among Danish women. We hypothesised that women using HCs show decreased perseverance across tasks compared to their naturally cycling counterparts. We further hypothesised that HC using women would show decreased performance as a measure of accuracy (i.e. more incorrect answers) compared to naturally cycling women. The study used a cross-sectional repeated measures design, consisting of a Danish version of the Anagram Persistence Task and the Hagen Matrices Test, followed by an extensive survey documenting menstrual and HC history for each participant. The study was conducted online. Data processing was conducted on data from 129 participants. The former hypothesis was analysed through multilevel regression with a nested random effects structure on log-transformed data. The latter hypothesis was analysed through a multilevel generalised linear model with a nested random effects structure using the binomial family. No support was found for either of the hypotheses.
Factors influencing the sex ratio at birth in the United States from a historical perspective
Authors: Sánchez-Barricarte Jesús J.
Published: January 2023

Many of the studies on the sex ratio at birth (SRB) are based on a small number of cases over a short period of time. Taking a multivariate approach to a dataset consisting of nearly 199 million birth records in the United States from 1968 to 2019, we present a detailed analysis of several possible factors that might affect the sex ratio at birth (SRB) and its patterns of variation. We found that race/ethnicity is the variable with the strongest influence on this index. Parental age, birth order and solar radiation also have a bearing on the SRB, albeit only to a moderate degree. The historical evolution of the SRB among Black and American Indian and Alaska Native populations remains unexplained.
Trader Competition in Fragmented Markets: Liquidity Supply Versus Picking-Off Risk
Authors: Bernales Alejandro , Garrido Nicolás , Sagade Satchit , Valenzuela Marcela , Westheide Christian
Published: January 2023

By employing a dynamic model with two limit order books, we show that fragmentation is associated with reduced competition among liquidity suppliers and lower picking-off risk of limit orders. Due to these countervailing channels, the impact of fragmentation on liquidity and welfare differs with asset volatility: When volatility is high (low), liquidity and aggregate welfare in a fragmented market are higher (lower) than in a single market. However, fragmentation always shifts welfare away from agents with exogenous trading motives and toward intermediaries. We empirically corroborate our model’s predictions about liquidity. Our model reconciles the mixed results in the empirical literature.
Intonation correlates of canonical and non-canonical wh-in-situ questions in Spanish
Authors: GONZÁLEZ CAROLINA , REGLERO LARA
Published: January 2023

This project investigates the intonation of canonical (information-seeking) and non-canonical wh-in-situ echo questions conveying repetition and surprise in Northern Peninsular Spanish. Data from 14 female participants were collected via a contextualised elicitation task. The following correlates were examined: (i) the melodic curve of the wh-in-situ question, (ii) the nuclear peak (in Hz), (iii) the wh-tonal range (i.e. the difference between the lowest nuclear Low and the highest boundary High), and (iv) the nuclear contour. Results show that all wh-in-situ questions investigated display similar melodic curves and nuclear contours, but canonical questions have significantly lower nuclear peaks and wh-tonal ranges than non-canonical questions. Echo-repetition and echo-surprise questions also differ in nuclear peak and wh-tonal range. We propose a tentative analysis, whereby canonical in-situ questions have a final H% boundary tone, in contrast to non-canonical questions, which have an extra-High (upstepped) final boundary tone (¡H%).
PLOT: a 3D point cloud object detection network for autonomous driving
Authors: Zhang Yihuan , Wang Liang , Dai Yifan
Published: January 2023

3D object detection using point cloud is an essential task for autonomous driving. With the development of infrastructures, roadside perception can extend the view range of the autonomous vehicles through communication technology. Computation time and power consumption are two main concerns when deploying object detection tasks, and a light-weighted detection model applied in an embedded system is a convenient solution for both roadside and vehicleside. In this study, a 3D Point cLoud Object deTection (PLOT) network is proposed to reduce heavy computing and ensure real-time object detection performance in an embedded system. First, a bird’s eye view representation of the point cloud is calculated using pillar-based encoding method. Then a cross-stage partial network-based backbone and a feature pyramid network-based neck are implemented to generate the high-dimensional feature map. Finally, a multioutput head using a shared convolutional layer is attached to predict classes, bounding boxes, and the orientations of the objects at the same time. Extensive experiments using the Waymo Open Dataset and our own dataset are conducted to demonstrate the accuracy and efficiency of the proposed method.
Belgium and probability in the nineteenth century: The case of Paul Mansion
Authors: Mazliak Laurent
Published: January 2023

Argument

This paper explores how the Belgian mathematician Paul Mansion became interested in probability theory. In comparison to many other countries at the time, probability theory had a much stronger presence in Belgium. In addition, Mansion, who was an avowed Catholic militant, had found probability theory to be a useful means of reflecting on certain problems pertaining to determinism and randomness that were arising in scientific debates at the time. Mansion’s work took place during a time of consolidation of mathematical education in Belgium, as well as a new interest in probabilistic results and the foundation of the Institute for Philosophy in Louvain by his friend Désiré Mercier. The present paper addresses how these aspects intersected at the turn of the twentieth century.
Moral Significance and Overpermissiveness
Authors: Akova Fırat
Published: January 2023

As opposed to overdemanding principles which ask individuals to sacrifice too much, there are overpermissive principles which ask individuals to sacrifice too little. Determining the extent to which one should sacrifice often comes with the need of understanding what is of moral significance. By analysing different readings of moral significance, and singling out one specific interpretation of moral significance which links moral significance to gaining or losing a considerable amount of welfare, I demonstrate that one of the well-known principles of Peter Singer, the Weaker Principle of Sacrifice, is overpermissive as it exempts deliberately cultivated morally significant lavish pursuits from the domain of sacrifice. Overpermissiveness not only renders moral principles unreasonably broad but also causes burdens to be distributed unjustifiably in a comparative sense, where some parties are assigned a moral obligation whereas others are not.
Battleship, tomography and quantum annealing
Authors: Casper W. Riley , Grimes Taylor
Published: January 2023

The classic game of Battleship involves two players taking turns attempting to guess the positions of a fleet of vertically or horizontally positioned enemy ships hidden on a
$10\times 10$
grid. One variant of this game, also referred to as Battleship Solitaire, Bimaru or Yubotu, considers the game with the inclusion of X-ray data, represented by knowledge of how many spots are occupied in each row and column in the enemy board. This paper considers the Battleship puzzle problem: the problem of reconstructing an enemy fleet from its X-ray data. We generate non-unique solutions to Battleship puzzles via certain reflection transformations akin to Ryser interchanges. Furthermore, we demonstrate that solutions of Battleship puzzles may be reliably obtained by searching for solutions of the associated classical binary discrete tomography problem which minimise the discrete Laplacian. We reformulate this optimisation problem as a quadratic unconstrained binary optimisation problem and approximate solutions via a simulated annealer, emphasising the future practical applicability of quantum annealers to solving discrete tomography problems with predefined structure.
Science in Washington, DC An Introduction to Memorials (A Pictorial Essay)
Authors: Hargittai Istvan , Hargittai Magdolna
Published: January 2023

There are profound expressions of remembrance of science and scientists, innovators and educators in Washington, DC. In this article, we survey the outdoor memorials and also include a few indoor memorials, if they are accessible to the public. There appears to be some predominance of physics and physicists, especially related to electricity among the memorials, but other areas of science are also represented. British and European scientists predominate, reflecting the time gap between memorials and contemporary science. Our coverage extends to a few concepts, such as education, with an emphasis on African American participation, energy, and the protection and conservation of the environment.
Mathematikspiele in der Familie
Authors: Niklas Frank , Ogrissek Lena , Lehrl Simone , Grolig Lorenz , Berner Valérie-D.
Published: January 2023

Zusammenfassung: Mathematische Aktivitäten im Familienkontext hängen mit frühen mathematischen Kompetenzen zusammen. Die Erfassung der Home Numeracy Environment (HNE) mittels Fragebögen birgt aber die Gefahr der sozial erwünschten Beantwortung. Diese Studie stellt den mathematischen Titelrekognitionstest für das Kindergartenalter (TRT-Mathe-K) vor, durch den sozial erwünschtes Antwortverhalten begrenzt wird. In einer Pilotstudie mit N = 76 Eltern wurde eine Liste von 87 mathematischen und nicht-mathematischen Kinderspielen hinsichtlich ihrer Bekanntheit abgefragt. Die Berücksichtigung der Kinderspieltitel mit einer Trennschärfe > .2 führte zur Entwicklung zweier Parallelversionen des TRT-Mathe-K. In einer Studie mit N = 193 Familien wurden Kindergartenkinder hinsichtlich nonverbaler Intelligenz, Sprachfähigkeit und früher mathematischer Kompetenzen untersucht und zum familiären Hintergrund befragt. Der TRT-Mathe-K erwies sich als ein ökonomisches, reliables und valides Messinstrument für die Nutzung von mathematischen Kinderspielen in der HNE, das signifikant mit frühen mathematischen Kompetenzen korrelierte und diese auch unter Berücksichtigung von Kontrollvariablen vorhersagen konnte.
Rainfall Wet Spells Variability Across Temperature Mean‐Change Years in the Northwestern Himalayan Region
Authors: Suri Ankur , Jena Pravat , Azad Sarita
Published: January 2023

Temperatures have risen at a faster rate across various mountainous regions around the world. A study of the changing rainfall patterns and their spatiotemporal variability is critical for agricultural, water resource, and hydrological planning and management. The goal of this research is twofold: first, using functional data analysis climate change hotspots are determined, which in turn identified most temperature increases in high elevations. Second, these hotspots are utilized to investigate the impact of temperature changes on the frequency of extreme rainfall events in this Northwestern Himalaya region. Our study observed that the frequency of rainfall extremes, such as, at the 90th, 95th, and 99.99th percentile values, is found to be increasing mostly in lower Himalayan regions. A warmer atmosphere leads to heavy precipitation events as the capacity of air to hold moisture increases with the increase in temperature. The continuous temperature rise possibly indicates an increase in extreme rainfall events in the region. Further, this study reports an interesting finding that can help us better understand the impact of climate change in the region: the frequency of shorter wet spells has increased around the recent mean‐change year, whereas the frequency of long spells has reduced. The frequency of longest wet spells shows a decrease across all seasons, leading to drought in the higher altitude region, whereas the short‐wet spell frequency has increased in the lower altitude regions. Insight into the changing patterns of rainfall is crucial for hydrological and agricultural management.
Investigation on the Anomalous Weakening of Diurnal Tides in the Mesosphere‐Lower Thermosphere
Authors: Prijith S. S. , Kumar K. Kishore
Published: January 2023

Variations in tidal characteristics assume importance as far as the atmosphere‐ionosphere coupling is concerned. The present study examines short‐term variabilities in diurnal tidal characteristics, using one decade (2006–2015) of wind measurements in the mesosphere‐lower thermosphere (MLT) region over a near equatorial location, Thumba (8.5°N, 77°E). The study presents two distinct events of anomalous tidal weakening, with decrease in monthly mean tidal amplitude by −38 ms−1 (−26 ms−1) in February 2010 and −17 ms−1 (−8 ms−1) in January 2012 at 98 km (91 km). These events are observed to be coinciding with the occurrence of strong quasi‐two‐day wave (QTDW). Compared to pre‐event conditions, decrease (increase) in tidal (QTDW) amplitudes at 91 km is −13.03 ms−1 (34.97 ms−1) and −15.65 ms−1 (52.81 ms−1) during the first and second event, respectively. However, causative mechanisms are found to be different for both the events. While the former event is primarily due to parametric excitation of phase locked 2‐day waves by diurnal tide, the latter one is mainly due to non‐linear interaction between tide and QTDW and subsequent generation of secondary waves. While QTDW phase is relatively stable during the former event, it shows steep temporal variations during the latter one. Changes in background wind conditions are also found to be more conducive for weakening of diurnal tide during the former event. These anomalous changes in tidal characteristics would have significant impacts on ionospheric processes. The significance of this study lies in providing observational evidence for the existence of different pathways through which QTDW affects tidal amplitudes over the low‐latitude MLT region.
Three‐Dimensional Thermoporoelastic Modeling of Hydrofracturing and Fluid Circulation in Hot Dry Rock
Authors: Li Sanbai , Zhang Dongxiao
Published: January 2023

Geothermal energy, featured as a renewable low‐carbon energy resource, exhibits great potential in mitigating global warming. However, efficient mining of geothermal energy from hot dry rock remains challenging due to the lack of a thermoporoelastic modeling approach that allows for integrated simulation of hydrofracturing and fluid circulation, and poor understanding of the mechanisms of hydraulic stimulations. To conquer these challenges, we propose an advanced modeling approach, which enables us to deal with the interplay between fluid transport, heat transfer, rock deformation, and three‐dimensional fractures' growth and interaction. Based on the thermoporoelastic model, a refined investigation is performed to determine the hydrofracturing and fluid circulation processes, using data collected from the EGS Collab Experiment 1. This meso‐scale testbed involves creating major hydraulic fractures, accompanied by numerous secondary hydroshearing fractures, hydraulically connecting two horizontal wellbores to build a fluid circulation system. All wellbores in the testbed were heavily instrumented with monitoring devices, offering high‐quality data to properly constrain the geomechanical model. Our study provides insights into: (a) how the EGS Collab testbed responds to propagating fractures with strong stress shadowing and long‐term injection of chilled water; (b) why the parallel pattern of two hydraulic fractures with a distance much smaller than the fracture dimension forms during multi‐staged hydraulic stimulations; and (c) what the mechanisms are that determine hydrofracturing performance. Overall, this work not only contributes to a novel modeling approach for integrated simulation of hydrofracturing and fluid circulation, but advances our understanding of creating enhanced geothermal systems with interconnected fracture networks.
Estimation of Geometric Factors for the Particle Detecting Instruments of the Geostationary Satellite GK2A at 128.2°E Longitude Based on Observations of the Outer Radiation Belt During Geomagnetically Quiet Periods
Authors: Seol W.‐H. , Lee C.‐H. , Seon J. , Shin Y.‐C. , Kim K.‐H. , Larson D. E. , Parks G. K. , Sample J.
Published: January 2023

We present a method to determine energy‐dependent geometric factors for charged particle instruments in electron energy range of 125–2,200 keV aboard the geostationary satellite GEO‐KOMPSAT‐2A (GK2A), stationed at 128.2°E longitude. As deduced from the GEANT4 Monte Carlo simulation, the response function of the instrument in a matrix form was employed to undertake forward‐fitting of the differential energy spectra against various functions such as the double Maxwellian (DM), relativistic kappa (KP), and power‐law (PL). Thereby, we determined the energy‐dependent geometric factors for each energy channel and instrument. The forward‐fitting method was performed for a selected period of geomagnetically quiet days from May to November 2019, by applying stringent conditions to geomagnetic indices and the residual from the fit. It was found that the KP and DM functions provided better fits overall, whereas the PL function yielded considerably worse fits to the measurements. For the KP and DM functions, the validity of the geometric factors was examined against the distributions of the measured count rates and inferred model fluxes. The estimated model parameters, such as the spectral index from the KP function or the temperature from the DM functions, were also analyzed. The present study shows that the instruments provided quantitative observations of the outer radiation belt at a vantage point of 128.2°E longitude and allowed for a simple and reliable means to obtain electron fluxes based on combinations of results from numerical simulation, ground calibration, and space measurements.
Thermoelastic damping in MEMS gyroscopes at high frequencies
Authors: Schiwietz Daniel , Weig Eva M. , Degenfeld-Schonburg Peter
Published: January 2023

Microelectromechanical systems (MEMS) gyroscopes are widely used, e.g., in modern automotive and consumer applications, and require signal stability and accuracy in rather harsh environmental conditions. In many use cases, device reliability must be guaranteed under large external loads at high frequencies. The sensitivity of the sensor to such external loads depends strongly on the damping, or rather quality factor, of the high-frequency mechanical modes of the structure. In this paper, we investigate the influence of thermoelastic damping on several high-frequency modes by comparing finite element simulations with measurements of the quality factor in an application-relevant temperature range. We measure the quality factors over different temperatures in vacuum, to extract the relevant thermoelastic material parameters of the polycrystalline MEMS device. Our simulation results show a good agreement with the measured quantities, therefore proving the applicability of our method for predictive purposes in the MEMS design process. Overall, we are able to uniquely identify the thermoelastic effects and show their significance for the damping of the high-frequency modes of an industrial MEMS gyroscope. Our approach is generic and therefore easily applicable to any mechanical structure with many possible applications in nano- and micromechanical systems.
Chemotherapy-induced tumor immunogenicity is mediated in part by megakaryocyte-erythroid progenitors
Authors: Vorontsova Avital , Cooper Tim J. , Haj-Shomaly Jozafina , Benguigui Madeleine , Levin Sapir , Manobla Bar , Menachem Rotem , Timaner Michael , Raviv Ziv , Shaked Yuval
Published: January 2023

Chemotherapy remains one of the main treatment modalities for cancer. While chemotherapy is mainly known for its ability to kill tumor cells directly, accumulating evidence indicates that it also acts indirectly by enhancing T cell-mediated anti-tumor immunity sometimes through immunogenic cell death. However, the role of immature immune cells in chemotherapy-induced immunomodulation has not been studied. Here, we utilized a mouse pancreatic cancer model to characterize the effects of gemcitabine chemotherapy on immature bone marrow cells in the context of tumor immunogenicity. Single cell RNA sequencing of hematopoietic stem and progenitor cells revealed a 3-fold increase in megakaryocyte-erythroid progenitors (MEPs) in the bone marrow of gemcitabine-treated mice in comparison to untreated control mice. Notably, adoptive transfer of MEPs to pancreatic tumor-bearing mice significantly reduced tumor growth and increased the levels of anti-tumor immune cells in tumors and peripheral blood. Furthermore, MEPs increased the tumor cell killing activity of CD8 + T cells and NK cells, an effect that was dependent on MEP-secreted CCL5 and CXCL16. Collectively, our findings demonstrate that chemotherapy-induced enrichment of MEPs in the bone marrow compartment contributes to anti-tumor immunity.
Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies
Authors: Mei Husheng , Wu Hong , Yang Jing , Zhou Bin , Wang Aoli , Hu Chen , Qi Shuang , Jiang Zongru , Zou Fengming , Wang Beilei , Liu Feiyang , Chen Yongfei , Wang Wenchao , Liu Jing , Liu Qingsong
Published: January 2023

Enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of PRC2 complex, plays an important role in tumor development and progression through its catalytic and noncatalytic activities. Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL). As a result, it has gained interest as a potential therapeutic target. The currently available EZH2 inhibitors, such as EPZ6438 and GSK126, are of benefit for clinical using or reached clinical trials. However, certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins. Thus, it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition. Here, through a rational design and chemical screening, we discovered a new irreversible EZH2 inhibitor, IHMT-337, which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway. Moreover, we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4, a novel PRC2 complex- and enzymatic activity-independent function of EZH2. More significantly, our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo. Taken together, our findings demonstrate that in addition to enzymatic inhibition, destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.
CRISPR/Cas9 therapeutics: progress and prospects
Authors: Li Tianxiang , Yang Yanyan , Qi Hongzhao , Cui Weigang , Zhang Lin , Fu Xiuxiu , He Xiangqin , Liu Meixin , Li Pei-feng , Yu Tao
Published: January 2023

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.
Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma
Authors: Geng Qishun , Li Lifeng , Shen Zhibo , Zheng Yuanyuan , Wang Longhao , Xue Ruyue , Xue Wenhua , Peng Mengle , Zhao Jie
Published: January 2023

Background

Mental stress-induced neurotransmitters can affect the immune system in various ways. Therefore, a better understanding of the role of neurotransmitters in the tumour immune microenvironment is expected to promote the development of novel anti-tumour therapies.

Methods

In this study, we analysed the plasma levels of neurotransmitters in anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb)-resistance patients and sensitive patients, to identify significantly different neurotransmitters. Subsequently, animal experiments and experiments in vitro were used to reveal the specific mechanism of norepinephrine’s (NE) effect on immunotherapy.

Results

The plasma NE levels were higher in anti-PD-1 mAb-resistance patients, which may be the main cause of anti-PD-1 mAb resistance. Then, from the perspective of the immunosuppressive microenvironment to explore the specific mechanism of NE-induced anti-PD-1 mAb resistance, we found that NE can affect the secretion of C-X-C Motif Chemokine Ligand 9 (CXCL9) and adenosine (ADO) in tumour cells, thereby inhibiting chemotaxis and function of CD8+ T cells. Notably, the WNT7A/β-catenin signalling pathway plays a crucial role in this progression.

Conclusion

NE can affect the secretion of CXCL9 and ADO in tumour cells, thereby inhibiting chemotaxis and the function of CD8+ T cells and inducing anti-PD-1 mAb resistance in lung adenocarcinoma (LUAD).
Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives
Authors: Guan Tianshu , Zhou Xv , Zhou Wenwen , Lin Hui
Published: January 2023

Acute lung injury (ALI) describes the injury to endothelial cells in the lungs and associated vessels due to various factors. Furthermore, ALI accompanied by inflammation and thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that inflammation and the cytokine storm are main causes of ALI. Two classical anti-inflammatory cell types, regulatory T cells (Tregs) and M2 macrophages, are theoretically capable of resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs and macrophages involving their mutual activation. In this review, we discuss the current findings related to ALI pathogenesis and the role of Tregs and macrophages. In particular, we review the molecular mechanisms underlying the crosstalk between Tregs and macrophages in ALI pathogenesis. Understanding the role of Tregs and macrophages will provide the potential targets for treating ALI.
Inter-decadal climate variability induces differential ice response along Pacific-facing West Antarctica
Authors: Christie Frazer D. W. , Steig Eric J. , Gourmelen Noel , Tett Simon F. B. , Bingham Robert G.
Published: January 2023

West Antarctica has experienced dramatic ice losses contributing to global sea-level rise in recent decades, particularly from Pine Island and Thwaites glaciers. Although these ice losses manifest an ongoing Marine Ice Sheet Instability, projections of their future rate are confounded by limited observations along West Antarctica’s coastal perimeter with respect to how the pace of retreat can be modulated by variations in climate forcing. Here, we derive a comprehensive, 12-year record of glacier retreat around West Antarctica’s Pacific-facing margin and compare this dataset to contemporaneous estimates of ice flow, mass loss, the state of the Southern Ocean and the atmosphere. Between 2003 and 2015, rates of glacier retreat and acceleration were extensive along the Bellingshausen Sea coastline, but slowed along the Amundsen Sea. We attribute this to an interdecadal suppression of westerly winds in the Amundsen Sea, which reduced warm water inflow to the Amundsen Sea Embayment. Our results provide direct observations that the pace, magnitude and extent of ice destabilization around West Antarctica vary by location, with the Amundsen Sea response most sensitive to interdecadal atmosphere-ocean variability. Thus, model projections accounting for regionally resolved ice-ocean-atmosphere interactions will be important for predicting accurately the short-term evolution of the Antarctic Ice Sheet.
mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function
Authors: Scheefhals Nicky , Westra Manon , MacGillavry Harold D.
Published: January 2023

The unique perisynaptic distribution of postsynaptic metabotropic glutamate receptors (mGluRs) at excitatory synapses is predicted to directly shape synaptic function, but mechanistic insight into how this distribution is regulated and impacts synaptic signaling is lacking. We used live-cell and super-resolution imaging approaches, and developed molecular tools to resolve and acutely manipulate the dynamic nanoscale distribution of mGluR5. Here we show that mGluR5 is dynamically organized in perisynaptic nanodomains that localize close to, but not in the synapse. The C-terminal domain of mGluR5 critically controlled perisynaptic confinement and prevented synaptic entry. We developed an inducible interaction system to overcome synaptic exclusion of mGluR5 and investigate the impact on synaptic function. We found that mGluR5 recruitment to the synapse acutely increased synaptic calcium responses. Altogether, we propose that transient confinement of mGluR5 in perisynaptic nanodomains allows flexible modulation of synaptic function.
High-performance Kerr microresonator optical parametric oscillator on a silicon chip
Authors: Perez Edgar F. , Moille Grégory , Lu Xiyuan , Stone Jordan , Zhou Feng , Srinivasan Kartik
Published: January 2023

Optical parametric oscillation (OPO) is distinguished by its wavelength access, that is, the ability to flexibly generate coherent light at wavelengths that are dramatically different from the pump laser, and in principle bounded solely by energy conservation between the input pump field and the output signal/idler fields. As society adopts advanced tools in quantum information science, metrology, and sensing, microchip OPO may provide an important path for accessing relevant wavelengths. However, a practical source of coherent light should additionally have high conversion efficiency and high output power. Here, we demonstrate a silicon photonics OPO device with unprecedented performance. Our OPO device, based on the third-order (χ(3)) nonlinearity in a silicon nitride microresonator, produces output signal and idler fields widely separated from each other in frequency ( > 150 THz), and exhibits a pump-to-idler conversion efficiency up to 29 % with a corresponding output idler power of > 18 mW on-chip. This performance is achieved by suppressing competitive processes and by strongly overcoupling the output light. This methodology can be readily applied to existing silicon photonics platforms with heterogeneously-integrated pump lasers, enabling flexible coherent light generation across a broad range of wavelengths with high output power and efficiency.