bluuebunny/crossref_metadata_2025 huggingface dataset:
How far do indirect signal production mechanisms influence regularity in the three-dimensional Keller–Segel–Navier–Stokes system?
Authors: Dai Feng , Liu Bin
Published: October 2023

This paper reconsiders the Keller–Segel–Navier–Stokes model with indirect signal production and weak logistic-type degradation in a three-dimensional (3D) bounded and smooth domain. One recent literature has asserted that for all reasonably regular initial data, the associated initial-boundary value problem with certain sub-quadratic degradation possesses at least one global generalized solution which is uniformly bounded and converges to the constant equilibrium in [Formula: see text] with any [Formula: see text]. Nevertheless, the knowledge on regularity properties of solution has not yet exceeded some information on fairly basic integrability features. The present study firstly elevates the regularities of some solution components under the same assumption on degradation exponent, especially establishes the global boundedness in [Formula: see text] with [Formula: see text], and secondly asserts that each of these generalized solutions becomes eventually classical and bounded in [Formula: see text] under some suitably strong sub-quadratic degradation assumption and an explicit smallness condition on the intrinsic growth rate of cells relative to some powers of the degradation coefficient. As a by-product of the latter, these solutions are shown to stabilize toward the corresponding spatially homogeneous state in [Formula: see text]. Our results indeed provide a more in-depth understanding on the global dynamics of solutions, and significantly improve previously known ones. In comparison to the related contributions in the case of direct signal production, our findings inter alia rigorously reveal that the indirect signal production mechanism results in some genuine regularizing effects in the sense that the possibly destabilizing action of chemotactic cross-diffusion in the 3D Keller–Segel–Navier–Stokes system can be greatly weakened or even completely excluded by this indirectness.
SURFACE CHARACTERISTICS INFLUENCED BY LASER TEXTURING PARAMETERS ON BIOMEDICAL-GRADE AISI 316LVM STAINLESS STEEL
Authors: KASMAN ŞEFIKA , UÇAR I. CAN , OZAN SERTAN
Published: October 2023

Surface roughness and wettability, which characterize the texture formed on the implant surface, are critical features for the functionality of the implant. Laser texturing is a promising processing method because of the advantages it provides in creating a particular surface topography on the surface of a metallic implant material with a nanosecond pulsed laser beam. Different experimental combinations were created using a fiber pulsed marking device on the surface of AISI 316LVM implant material using the hatch strategy; textures depending on the scan speed, frequency, and hatch distance were created on the surface. The surface roughness and wettability evaluated the effects of parameters on the texture form. Based on the experimental and statistical results, while the scan speed was the most significant parameter affecting the wettability behavior and surface roughness, the hatch strategy and frequency also affected the surface roughness to some extent. Many textured surfaces showed super-hydrophilic behavior with a contact angle of [Formula: see text]. It has been determined that surface textures with the same or close roughness values did not exhibit the same wettability behavior. The lowest surface roughness of 2 [Formula: see text]m with a [Formula: see text] contact angle was obtained at a hatch strategy of [Formula: see text]/[Formula: see text], a scan speed of 900 mm/s, a frequency of 100 kHz, and a hatch distance of 0.03 mm. Three-dimensional surface images show that while many craters formed the surface textures, overlapping consecutive beams and hatch strategies significantly affected the surface topography.
INVESTIGATION OF CORRELATION BETWEEN PROCESS PARAMETERS AND VIBRATION WITH USE OF WASTE CBN INSERTS IN DEEP ROLLING
Authors: ADIYAMAN OKTAY
Published: October 2023

Vibration is a mechanical phenomenon in which oscillations occur around an equilibrium point. In addition, the used and waste-cutting inserts create a great problem for the industry; therefore, these inserts constitute a problem to be solved in terms of both recycling and waste costs. The aim of this study is to analyze the correlation between vibration process parameters, formed during deep rolling, and surface roughness, micro-hardness with the using of the waste CBN inserts. For this, in total, 27 experiments in total were conducted with the help of a specially designed tool holder after parameters had been selected. The surface roughness, micro-hardness and vibration values of the specimens that were applied deep rolling were measured and the correlation between these values was investigated. When deep rolling was applied to the workpieces with used and waste CBN inserts, it was seen that the waste CBN inserts could be used in deep rolling and that the surface roughness improved and the surface hardness increased. In addition, it was seen that with the increase of the number of passes and rolling forces, the micro-hardness increased, and that feed rate, the number of passes and rolling forces had the biggest effect on vibration, respectively.
Valued rank-metric codes
Authors: El Maazouz Yassine , Hahn Marvin Anas , Neri Alessandro , Stanojkovski Mima
Published: October 2023

In this paper, we study linear spaces of matrices defined over discretely valued fields and discuss their dimension and minimal rank drops over the associated residue fields. To this end, we take first steps into the theory of rank-metric codes over discrete valuation rings by means of skew algebras derived from Galois extensions of rings. Additionally, we model projectivizations of rank-metric codes via Mustafin varieties, which we then employ to give sufficient conditions for a decrease in the dimension.
How to Develop a Corporate Incubator? Lessons Learned from a Multinational
Authors: Souza Wesley Canedo , Bagno Raoni Barros , de Souza Matheus Luiz Pontelo , Ribeiro Rodrigo , de Melo Filho Leonel Del Rey
Published: October 2023

Multinationals are showing a growing interest in developing corporate incubation programs. However, only a few papers analyzed this emerging topic. We conducted a study at a Brazilian multinational steel company subsidiary, aiming to elucidate the process of designing a corporate incubator through a three-phase Action Research program that spanned 12 months. As a result of this study, we offer (i) a sequential and evolutionary framework for implementing corporate incubators; (ii) an information management tool that captures and utilizes data for decision-making during venture development; and (iii) an uncertainty-based evaluation tool for venture evolution.
Differential Harnack inequality for the Newell–Whitehead–Segel equation under Finsler-geometric flow
Authors: Azami Shahroud
Published: October 2023

Let [Formula: see text] be a compact Finsler manifold. This paper will obtain a global estimate and a differential Harnack inequality for positive solutions to the Newell–Whitehead–Segal equation [Formula: see text] on compact Finsler manifolds, where [Formula: see text] are real constants.
(k,ℓ)-Kernels in the generalized Mycielskian of digraphs
Authors: Lakshmi R. , Sindhu D. G.
Published: October 2023

Let [Formula: see text] and [Formula: see text] be positive integers. A set [Formula: see text] is said to be a [Formula: see text]-kernel of a digraph [Formula: see text] if for all [Formula: see text] [Formula: see text] and for every [Formula: see text] there exists [Formula: see text] such that [Formula: see text] A (2,1)-kernel is called a kernel. The generalized Mycielskian [Formula: see text] of a loopless digraph [Formula: see text] is defined in [S. F. Raj, Connectivity of the generalized Mycielskian of digraphs, Graphs Combin. 29 (2013) 893–900] as the digraph whose vertex set is [Formula: see text] where [Formula: see text] [Formula: see text] and arc set [Formula: see text] It is proved in [S. Vidhyapriya, Contributions to the theory of Kernels in digraphs, Doctoral Dissertation, Annamalai University, India (2016)] that [Formula: see text] the Mycielskian of [Formula: see text] has a kernel. In this paper, we generalize this result to [Formula: see text] Further, we completely study the structure of [Formula: see text]-kernels (if exist) in [Formula: see text] Besides these, for [Formula: see text] [Formula: see text] and [Formula: see text] we give some results concerning the existence and non-existence of [Formula: see text]-kernels in [Formula: see text] where, for some pairs [Formula: see text] we provide a Characterization, too.
HOW MUCH IMPACT DO BANKS AND INSURANCE COMPANIES HAVE ON THE ENVIRONMENT? EVIDENCE FROM ITALY
Authors: D’APOLITO ELISABETTA , BIASE PASQUALE DI , LABINI STEFANIA SYLOS
Published: October 2023

All companies pollute, financial firms included. How much does the financial sector pollute? How much does it impact climate change?

This paper contributes to the debate on the relationships between the European financial sector and environmental sustainability. By examining the ESG score — in particular, the environmental indicators — of a sample of Italian banks and insurance companies over the period 2015–2020, the research intends to verify (i) whether financial intermediaries adopt policies and make efforts to reduce the environmental impact of their operations; (ii) the observable trend in the environmental performance of the examined companies and (iii) the existence of a relationship between the environmental performance and the characteristics of the examined companies.

The results show an increasing trend in the environmental performance of the examined intermediaries and a wide dissemination of policies aimed at reducing their impact on the environment. According to our analysis, environmental performance is significantly related to company size. The study can be useful for managers and decision-makers in providing an in-depth analysis of the measures adopted to reduce environmental impact. In addition, it can have important repercussions on the financial markets and also for investors in increasing awareness about environmental scores.
A Graph Deep Learning-Based Framework for Drug-Disease Association Identification with Chemical Structure Similarities
Authors: Zhao Bo-Wei , Su Xiao-Rui , Li Dong-Xu , Li Guo-Dong , Hu Peng-Wei , Zhao Yong-Gang , Hu Lun
Published: October 2023

Traditional drug development requires a lot of time and effort, while computational drug repositioning enables to discover the underlying mechanisms of drugs, thereby reducing the cost of drug discovery and development. However, existing computational models utilize only low-order biological information at the level of individual drugs, diseases and their associations, making it difficult to dig deeper and fuse higher-order structural information. In this paper, we develop a novel prediction model, namely DRGDL, based on graph deep learning to infer potential drug-disease associations (DDAs) by coming chemical structural similarity information, which can more comprehensively make use of the biological features of drugs and diseases. First, the lower-order and higher-order representations of drugs and diseases are captured by two different graph deep learning strategies. Then, suitable negative samples are select by use of k-means algorithm. At last, the Random Forest classifier is applied to complete the prediction task of DDAs by integrating two representations of drugs and diseases. Experiment results indicate that DRGDL achieves excellent performance under ten-fold cross-validation on two benchmark datasets.
The Infrapolitics of Algorithmic Resistance
Authors: Mendonça Ricardo Fabrino , Filgueiras Fernando , Almeida Virgilio
Published: October 2023

Exploring the complex interactions between humans and machines governed by algorithms.
Machine Learning Sensors
Authors: Warden Pete , Stewart Matthew , Plancher Brian , Katti Sachin , Reddi Vijay Janapa
Published: October 2023

A design paradigm for the future of intelligent sensors.
On Being a Computer Science Communicator
Authors: Jacobson Sheldon H.
Published: October 2023

Facilitating more effective public engagement with a computer science perspective.
Informatics Higher Education in Europe: A Data Portal and Case Study
Authors: Di Nitto Elisabetta , García-Varea Ismael , Jazayeri Mehdi , Tamburri Damian A. , Tikhonenko Svetlana
Published: October 2023

A discussion on the need for coordinated, governed, data-driven computing education initiatives of the future.
Boosting Fuzzer Efficiency: An Information Theoretic Perspective
Authors: Böhme Marcel , Manès Valentin J. M. , Cha Sang Kil
Published: October 2023

In this paper, we take the fundamental perspective of fuzzing as a learning process. Suppose before fuzzing, we know nothing about the behaviors of a program
P
: What does it do? Executing the first test input, we learn how
P
behaves for this input. Executing the next input, we either observe the same or discover a new behavior. As such, each execution reveals "some amount" of information about
P
's behaviors. A classic measure of information is Shannon's entropy. Measuring entropy allows us to quantify how much is learned from each generated test input about the behaviors of the program. Within a probabilistic model of fuzzing, we show how entropy also measures fuzzer efficiency. Specifically, it measures the general
rate
at which the fuzzer discovers new behaviors. Intuitively,
efficient fuzzers maximize information.
From this information theoretic perspective, we develop ENTROPIC, an entropy-based power schedule for greybox fuzzing that assigns more energy to seeds that maximize information. We implemented ENTROPIC into the popular greybox fuzzer LIBFUZZER. Our experiments with more than 250 open-source programs (60
million
LoC) demonstrate a substantially improved efficiency and
confirm
our hypothesis that an efficient fuzzer maximizes information. ENTROPIC has been independently evaluated and integrated into the main-line LIBFUZZER as the default power schedule. ENTROPIC now runs on more than 25,000 machines fuzzing hundreds of security-critical software systems simultaneously and continuously.
Accessibility and Inclusion through Technology
Authors: Kirkpatrick Keith
Published: October 2023

Helping the sensory-impaired overcome their impediments.
What's Old Is New Again
Authors: Kugler Logan
Published: October 2023

Analog computing offers one possible solution to the downsides of digital computing.
SIGAI Annual Report: July 1 2022 --- August 30 2023
Authors: Das Sanmay , Mattei Nicholas , Dickerson John P. , Koenig Sven , Dennis Louise , Medsker Larry , Yao Ziyu , Karpatne Anuj , Tsang Alan , Luckcuck Matt
Published: October 2023

We are delighted to share our annual report with membership. This highlights some of the many activities we do as a SIG, and could provide some inspiration for members who wish to get more involved about the types of activities they could participate in or where they feel new initiatives might be most welcome. If you are interested in being more involved with SIGAI or have ideas for future initiatives, please reach out to any or all of the leadership team.
Model-based Gradient Search for Permutation Problems
Authors: Ceberio Josu , Santucci Valentino
Published: October 2023

Global random search algorithms are characterized by using probability distributions to optimize problems. Among them, generative methods iteratively update the distributions by using the observations sampled. For instance, this is the case of the well-known Estimation of Distribution Algorithms. Although successful, this family of algorithms iteratively adopts numerical methods for estimating the parameters of a model or drawing observations from it. This is often a very time-consuming task, especially in permutation-based combinatorial optimization problems. In this work, we propose using a generative method, under the model-based gradient search framework, to optimize permutation-coded problems and address the mentioned computational overheads. To that end, the Plackett–Luce model is used to define the probability distribution on the search space of permutations. Not limited to that, a parameter-free variant of the algorithm is investigated. Conducted experiments, directed to validate the work, reveal that the gradient search scheme produces better results than other analogous competitors, reducing the computational cost and showing better scalability.
Mapi-Pro: An Energy Efficient Memory Mapping Technique for Intermittent Computing
Authors: Badri Satya Jaswanth , Saini Mukesh , Goel Neeraj
Published: October 2023

Battery-less technology evolved to replace battery usage in space, deep mines, and other environments to reduce cost and pollution. Non-volatile memory (NVM) based processors were explored for saving the system state during a power failure. Such devices have a small SRAM and large non-volatile memory. To make the system energy efficient, we need to use SRAM efficiently. So we must select some portions of the application and map them to either SRAM or FRAM. This paper proposes an ILP-based memory mapping technique for intermittently powered IoT devices. Our proposed technique gives an optimal mapping choice that reduces the system’s Energy-Delay Product (EDP). We validated our system using TI-based MSP430FR6989 and MSP430F5529 development boards. Our proposed memory configuration consumes 38.10% less EDP than the baseline configuration and 9.30% less EDP than the existing work under stable power. Our proposed configuration achieves 20.15% less EDP than the baseline configuration and 26.87% less EDP than the existing work under unstable power. This work supports intermittent computing and works efficiently during frequent power failures.
Robotics Software: Past, Present, and Future
Authors: Haviland Jesse , Corke Peter
Published: October 2023

Robotics is powered by software. Software tools control the rate of innovation in robotics research, drive the growth of the robotics industry, and power the education of future innovators and developers. Nearly 900,000 open-source repositories on GitHub are tagged with the keyword robotics—a potentially vast resource, but only a fraction of those are truly accessible in terms of quality, licensability, understandability, and total cost of ownership. The challenge is to match this resource to the needs of students, researchers, and companies to power cutting-edge research and real-world industrial solutions. This article reviews software tools for robotics, including both those created by the community at large and those created by the authors, as well as their impact on education, research, and industry.
US Legal and Regulatory Framework for Nuclear Waste from Present and Future Reactors and Their Fuel Cycles
Authors: Park Sulgiye , Ewing Rodney C.
Published: October 2023

The nuclear waste management and disposal program in the United States for highly radioactive waste (spent nuclear fuel and high-level waste) has thus far been unsuccessful despite an effort that spans 40 years and the expenditure of tens of billions of dollars. Yet, today, there is considerable interest in and promotion of advanced reactor technologies, such as small modular reactors that will expand spent fuel inventories that may very well remain at the site where they are generated, awaiting permanent, geologic disposal. We examine critical elements of the US legal and regulatory framework that have impeded the success of the US program. We make recommendations on steps that are required for a successful nuclear waste program, particularly considering the development of advanced nuclear reactors and their fuel cycles.
Analogy in Inflection
Authors: Lindsay-Smith Emily , Baerman Matthew , Beniamine Sacha , Sims-Williams Helen , Round Erich R.
Published: October 2023

Analogy has returned to prominence in the field of inflectional morphology as a basis for new explanations of inflectional productivity. Here we review the rising profile of analogy, identifying key theoretical and methodological developments, areas of success, and priorities for future work. In morphological theory, work within so-called abstractive approaches places analogy at the center of productive processes, though significant conceptual and technical details remain to be settled. The computational modeling of inflectional analogy has a rich and diverse history, and attention is now increasingly directed to understanding inflectional systems through their internal complexity and cross-linguistic diversity. A tension exists between the prima facie promise of analogy to lead to new explanations and its relative lack of theoretical articulation. We bring this to light as we examine questions regarding inflectional defectiveness and whether analogy is reducible to grammar optimization resulting from simplicity biases in learning and language use.
Mechanosensing by Vascular Endothelium
Authors: Lim Xin Rui , Harraz Osama F.
Published: October 2023

Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology.
Quenched Electrochemical Biosensor Based on Adsorption Between GO and Aptamer for the Detection of ERα
Authors: Li Weiming , Gao Tianyu , Guo Liang , Wang Mengli , Liu Jingwen , Yang Huaixia , Liu Yanju
Published: October 2023

Breast cancer is one of the three most common cancers in the world, and is the most prevalent malignancy in women. Estrogen receptor alpha (ERα), an important marker for early diagnosis of breast cancer, shows positivity in more than 75% of breast cancers. Herein, a quenched electrochemical biosensor based on the adsorption interaction between graphene oxide (GO) and aptamer (Apt) and the ATRP signal amplification strategy for sensitive detection of ERα was constructed. The Apt was immobilized on the electrode surface by gold-sulfur bonding and adsorbed GO-BIBB by π–π stacking. In the ATRP reaction solution, ferrocene polymerized on the electrode surface in the presence of a catalyst and initiator and generated electrochemical signal. After the addition of ERα, a large number of electrical signal molecules were shed from the electrode surface with GO, causing quenching of the signal. By optimizing the reaction conditions, the detection limit (LOD) of the biosensor can reach 0.17 pg·ml−1, and the logarithm of the current intensity and concentration shows a good linearity in the range of 1 pg·ml−1 to 100 ng·ml−1. The biosensor also has excellent selectivity, stability, interference resistance and reproducibility. More importantly, the biosensor enabled the detection of ERα in real samples.
The Influence of Thermal Aging on the Surface Trap Characteristics and Surface Flashover of Epoxy Resin
Authors: Li Guochang , Hu Kai , Sun Weixin , Xu Fengyuan , Zhu Yuanwei , Wei Yanhui
Published: October 2023

Surface charge accumulation of epoxy resin is easy to cause surface flashover under DC voltage, and thermal aging is an important factor affecting surface charge and trapping characteristics. In this paper, the electron and hole trap characteristics of epoxy resin were studied by changing the polarity and amplitude of charging voltage. Then, the influence of thermal aging on the trap energy level distribution of epoxy resin is researched by conducting the thermal aging experiment, based on which the influence of the energy level distribution of electron trap on the negative DC flashover characteristics is furtherly studied. Experimental results show that the energy level of electron trap and hole trap on the surface of epoxy resin ranges from 0.70 eV to 0.96 eV, the peak energy level of hole trap is slightly higher than that of electron trap. The maximum of the density of trapped charge in the electron trap and hole trap is 1.98 × 1020eV−1·m−3 and 1.82 × 1020eV−1·m−3 respectively. The energy level of traps on the surface of epoxy resin generally shows a deepening trend after thermal aging. The peak energy level of electron trap increases from 0.84 eV to 0.98 eV after 29 d of thermal aging, which is due to the product containing strongly polar group produced by thermal aging. The results of flashover testing shows that the flashover voltage first increases and then decreases with the extension of thermal aging time. With the extension of aging time from 7 d to 29 d, the flashover voltage decreases by about 11.2%, the change of flashover voltage is related to the change of trap energy level distribution on the surface of dielectric. This paper can provide theoretical and experimental basis for the insulation design of epoxy resin applied in electric equipment.
Adjusting for muscle strength and body size attenuates sex differences in the exercise pressor reflex in young adults
Authors: Tharpe McKenna A. , Linder Braxton A. , Babcock Matthew C. , Watso Joseph C. , Pollin Kamila U. , Hutchison Zach J. , Barnett Alex M. , Culver Meral N. , Kavazis Andreas N. , Brian Michael S. , Robinson Austin T.
Published: October 2023

When compared with young males, females typically exhibit lower blood pressure (BP) during exercise. Adjusting for maximal strength attenuates sex differences in BP during isometric handgrip (HG) exercise and postexercise ischemia (PEI), but the contribution of body size is unknown. Novel findings include adjustments for muscle strength and body size attenuate sex differences in BP reactivity during exercise and PEI, and sex differences in body size contribute to HG strength differences.
Study on Carbohydrate Metabolism in Adult Zebrafish (Danio rerio)
Authors: Xi Longwei , Lu Qisheng , Liu Yulong , Gong Yulong , Liu Haokun , Jin Junyan , Zhang Zhimin , Yang Yunxia , Zhu Xiaoming , Han Dong , Xie Shouqi
Published: October 2023

Excessive carbohydrate intake leads to metabolic disorders in fish. However, few literatures have reported the appropriate carbohydrate level for zebrafish, and the metabolic response to dietary carbohydrate remains largely unknown in zebrafish. This study assessed the responses of zebrafish and zebrafish liver cell line (ZFL) to different carbohydrate levels. In vivo results showed that ≥30% dietary dextrin levels significantly increased the plasma glucose content, activated the expression of hepatic glycolysis-related genes, and inhibited the expression of hepatic gluconeogenesis-related genes in zebrafish. Oil red O staining, triglyceride content, and Hematoxylin-Eosin staining results showed that dietary dextrin levels of ≥30% significantly increased lipid accumulation and liver damage, as well as processes related to glycolipid metabolism and inflammation in zebrafish. In ZFL, the transcription factor sterol regulatory element binding protein-1c signal intensity, 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene (BODIPY 493/503) signal intensity, and triglyceride content were also significantly increased when incubated in high glucose, along with abnormal glycolipid metabolism and increased inflammation-related genes. In conclusion, we demonstrated that the maximum dietary carbohydrate level in adult zebrafish should be less than 30%. Excess dietary carbohydrates (30%–50%) caused hepatic steatosis and damage to zebrafish, similar to that seen in aquaculture species. Thus, this study assessed responses to different carbohydrate levels in zebrafish and illustrated that zebrafish is an optimal model for investigating glucose metabolism in some aquatic animals.
Study on O3 Variations in Nanjing and the Surrounding Source Analysis
Authors: Shi Jiaqi , Wang Jinhu , Zhang Yuqing , Liang Dinyuan , Xiao Anhong
Published: October 2023

To understand the transport patterns and major sources of ozone (O3) in Nanjing, this study carried out the 48-hour backward trajectories of air masses in Nanjing from March 2021 to March 2022, based on the HYSPLIT backward trajectory model driven by GDAS global reanalysis data. The primary transmission routes and putative source locations of O3 pollution in Nanjing were determined through the integration of trajectory clustering analysis, potential source contribution function (PSCF), and concentration-weighted trajectory (CWT) analysis with meteorological data and O3 concentration data. The results showed that the high O3 concentrations and exceedance rates in Nanjing were in late spring and early summer, with the highest in June. The diurnal variation of O3 concentrations in all seasons exhibited a single peak with a maximum from 13:00 to 16:00. The southeasterly flow passing through Zhenjiang, Changzhou, Wuxi, Suzhou, and Shanghai dominated the O3 pollution in Nanjing. The PSCF and CWT presented a high consistency of O3 potential sources in Nanjing. Zhenjiang, Ma’anshan, Changzhou, Wuxi, Suzhou, and Huzhou were identified as the main potential source regions of O3 pollution in Nanjing. This study provides accurate theoretical references for regional joint prevention and control of O3 pollution in Nanjing.
Effect of Dual- versus Single-Antiplatelet Therapy on Early Neurological Deterioration in Minor Stroke of Undetermined Cause
Authors: Xu Bingdong , Xin Xiufeng , Ding Yan , Xu Anding , Zhang Yusheng
Published: October 2023

Background. There is insufficient evidence about the suitability of dual-antiplatelet therapy (DAPT) for different stroke subtypes. We aimed to determine the relationship between DAPT and early neurological deterioration (END) in patients with minor stroke of undetermined cause. Methods. We retrospectively collected data on patients with minor stroke treated with aspirin alone or in combination with clopidogrel and aspirin. Efficacy was the incidence of END defined as the National Institutes of Health Stroke Scale score increase of ≥2 within 7 days after admission. Safety was defined as the rate of any bleeding event. These were investigated in subtypes including the stroke of undetermined cause (SUC), large artery atherosclerosis (LAA), cardioembolism (CE), and small artery occlusion (SAO). Results. 442 patients were assigned to the SUC (

n
=
91

), LAA (

n
=
157

), CE (

n
=
30

), and SAO (

n
=
164

) groups. The incidences of END were not significantly different between patients treated with dual- versus single-antiplatelet therapy in any stroke subtypes: LAA, 17.6% vs. 12.1% (

P
=
0.348

); CE, 0% vs. 20.0% (

P
=
0.224

); SAO, 8.8% vs. 2.4% (

P
=
0.093

); and SUC, 13.6% vs. 2.1% (

P
=
0.053

). Multivariable analysis showed that after adjusting for confounding factors, DAPT was the independent factor associated with END (odds ratio 13.39, 95% confidence interval (1.16-154.81),

P
=
0.038

) in the SUC group, rather than the LAA, CE, and SAO groups. Conclusion. Combined clopidogrel and aspirin is a risk factor for the rate of END only in minor stroke patients with the SUC subtype. This suggests that cryptogenic stroke may not be suitable for DAPT in the acute phase.
Drivers of the Australian Health System towards Health Care for All: A Scoping Review and Qualitative Synthesis
Authors: Khatri Resham B. , Assefa Yibeltal
Published: October 2023

Background. Australia has made significant progress towards universal access to primary health care (PHC) services. However, disparities in the utilisation of health services and health status remain challenges in achieving the global target of universal health coverage (UHC). This scoping review aimed at synthesizing the drivers of PHC services towards UHC in Australia. Methods. We conducted a scoping review of the literature published from 1 January 2010 to 30 July 2021 in three databases: PubMed, Scopus, and Embase. Search terms were identified under four themes: health services, Australia, UHC, and successes or challenges. Data were analysed using an inductive thematic analysis approach. Drivers (facilitators and barriers) of PHC services were explained by employing a multilevel framework that included the proximal level (at the level of users and providers), intermediate level (organisational and community level), and distal level (macrosystem or distal/structural level). Results. A total of 114 studies were included in the review. Australia has recorded several successes in increased utilisation of PHC services, resulting in an overall improvement in health status. However, challenges remain in poor access and high unmet needs of health services among disadvantaged/priority populations (e.g., immigrants and Indigenous groups), those with chronic illnesses (multiple chronic conditions), and those living in rural and remote areas. Several drivers have contributed in access to and utilisation of health services (especially among priority populations)operating at multilevel health systems, such as proximal level drivers (health literacy, users’ language, access to health facilities, providers’ behaviours, quantity and competency of health workforce, and service provision at health facilities), intermediate drivers (community engagement, health programs, planning and monitoring, and funding), and distal (structural) drivers (socioeconomic disparities and discriminations). Conclusion. Australia has had several successes towards UHC. However, access to health services poses significant challenges among specific priority populations and rural residents. To achieve universality and equity of health services, health system efforts (supply‐ and demand‐side policies, programs and service interventions) are required to be implemented in multilevel health systems. Implementation of targeted health policy and program approaches are needed to provide comprehensive PHC and address the effects of structural disparities.
AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer
Authors: Nolan-Stevaux Olivier , Li Cong , Liang Lingming , Zhan Jinghui , Estrada Juan , Osgood Tao , Li Fei , Zhang Hanzhi , Case Ryan , Murawsky Christopher M. , Estes Bram , Moore Gregory L. , Bernett Matthew J. , Muchhal Umesh , Desjarlais John R. , Staley Binnaz K. , Stevens Jennitte , Cooke Keegan S. , Aeffner Famke , Thomas Oliver , Stieglmaier Julia , Lee Jae-Lyun , Coxon Angela , Bailis Julie M.
Published: October 2023

The tumor-associated antigen STEAP1 is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate cancer cells that express STEAP1. AMG 509 mediates potent T cell–dependent cytotoxicity of prostate cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse models of prostate cancer in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a patient with mCRPC who achieved an objective response on AMG 509 treatment.

Significance:

Immunotherapy in prostate cancer has met with limited success due to the immunosuppressive microenvironment and lack of tumor-specific targets. AMG 509 provides a targeted immunotherapy approach to engage a patient's T cells to kill STEAP1-expressing tumor cells and represents a new treatment option for mCRPC and potentially more broadly for prostate cancer.

See related commentary by Hage Chehade et al., p. 20.

See related article by Kelly et al., p. 76.

This article is featured in Selected Articles from This Issue, p. 5
FIGURE 5 from Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma
Authors: Secrier Maria , McGrath Lara , Ng Felicia , Gulati Sakshi , Raymond Amelia , Nuttall Barrett R. B. , Berthe Julie , Jones Emma V. , Sidders Ben S. , Galon Jérôme , Barrett J. Carl , Angell Helen K.
Published: October 2023

Links between risk factors of HNSCC, exhaustion, and TCR repertoire. A, PD-L1–positive patients display higher productive clonality, observed richness and TLS signature scores. B, HPV-positive tumors have higher PC and DC content as well as lower M2 macrophage infiltration. C, Never smokers display higher observed richness of the TCR repertoires and stronger TLS TFC signals. ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05; ns, nonsignificant (P > 0.05).
FIGURE 3 from Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma
Authors: Secrier Maria , McGrath Lara , Ng Felicia , Gulati Sakshi , Raymond Amelia , Nuttall Barrett R. B. , Berthe Julie , Jones Emma V. , Sidders Ben S. , Galon Jérôme , Barrett J. Carl , Angell Helen K.
Published: October 2023

Modeling TME outcomes based on signaling in tyrosine kinase pathways. A, Multinomial logistic regression model that was applied to integrate expression signals across relevant pathways to predict the immunogenic/high immunity (cytotoxic, PC/DC rich) versus low immunity (immune-excluded/macrophage rich) phenotypes (as indicated by the color legend). B, Example genes in the PI3KA/AKT pathway that are significantly differently expressed among immunity subgroups. C, The genes with most significant trends included in the final model and their predictive power to distinguish between immunity subgroups. The top panel shows the predicted immunity state (low/high) depending on expression of individual genes in the model; the bottom panel shows the true distribution of expression values for the respective genes among the high and low immunity groups. The curves in the prediction model were fitted with a loess function. Extreme values of the expression distribution seem to most clearly define immune state.
PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies
Authors: Carter Jack , Hulse Michael , Sivakumar Monisha , Burtell Jessica , Thodima Venkat , Wang Min , Agarwal Anjana , Vykuntam Komali , Spruance Jacob , Bhagwat Neha , Rager Joseph , Ruggeri Bruce , Scherle Peggy , Ito Koichi
Published: October 2023

Expression of protein arginine methyltransferase 5 (PRMT5) is highly positively correlated to DNA damage repair (DDR) and DNA replication pathway genes in many types of cancer cells, including ovarian and breast cancer. In the current study, we investigated whether pharmacologic inhibition of PRMT5 downregulates DDR/DNA replication pathway genes and sensitizes cancer cells to chemotherapy and PARP inhibition. Potent and selective PRMT5 inhibitors significantly downregulate expression of multiple DDR and DNA replication genes in cancer cells. Mechanistically, PRMT5 inhibition reduces the presence of PRMT5 and H4R3me2s on promoter regions of DDR genes such as BRCA1/2, RAD51, and ATM. PRMT5 inhibition also promotes global alternative splicing changes. Our data suggest that PRMT5 inhibition regulates expression of FANCA, PNKP, and ATM by promoting exon skipping and intron retention. Combining C220 or PRT543 with olaparib or chemotherapeutic agents such as cisplatin demonstrates a potent synergistic interaction in breast and ovarian cancer cells in vitro. Moreover, combination of PRT543 with olaparib effectively inhibits the growth of patient-derived breast and ovarian cancer xenografts. Furthermore, PRT543 treatment significantly inhibits growth of olaparib-resistant tumors in vivo. These studies reveal a novel mechanism of PRMT5 inhibition and suggest beneficial combinatorial effects with other therapies, particularly in patients with tumors that are resistant to therapies dependent on DNA damage as their mechanism of action.

Significance:

Patients with advanced cancers frequently develop resistance to chemotherapy or PARP inhibitors mainly due to circumvention and/or restoration of the inactivated DDR pathway genes. We demonstrate that inhibition of PRMT5 significantly downregulates a broad range of the DDR and DNA replication pathway genes. PRMT5 inhibitors combined with chemotherapy or PARP inhibitors demonstrate synergistic suppression of cancer cell proliferation and growth in breast and ovarian tumor models, including PARP inhibitor–resistant tumors.
Fostamatinib or Thrombopoietin for the Treatment of Chronic Immune Thrombocytopenia in Adult Patients: A Real-World Assessment of Safety, Effectiveness and Cost
Authors: Dranitsaris George , Peevyhouse Aaron , Wood Tiffany , Kreychman Yuliya , Neuhalfen Heather , Moezi Mehdi
Published: October 2023

Introduction: Chronic immune thrombocytopenia purpura (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment starts with corticosteroids. In patients who become resistant or intolerant to corticosteroids, the thrombopoietic agents (TPOs), consisting of romiplostim (ROM), eltrombopag (ELT), and avatrombopag (AVA), or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety, effectiveness, and cost of care between fostamatinib and the TPOs were evaluated in a real-world setting. Methods: A retrospective analysis of 17 community hematology practices across the USA was conducted to identify adult ITP patients who received one of the four agents. Data collection consisted of patient demographics, disease characteristics, as well as number and type of prior treatments. From the first day until the end of treatment, data were also collected on platelet (PLT) counts, adverse events, the use of rescue IVIG, platelet transfusions, and corticosteroids. Multivariable logistic regression analysis was used to compare PLT-related endpoints between agents. Results: A sample of 179 ITP patients who had received at least one of the four agents was identified. This resulted in a final sample of 51, 87, 127, and 44 patients who received FOS, ELT, ROM, or AVA, respectively. At month six, there were no significant differences between FOS and the TPOs in terms of the proportion of patients with the PLT count being ≥30 × 103/μL, ≥50 × 103/μL as well as the proportion of patients whose PLT levels doubled relative to baseline. The frequency of thromboembolic events (TEs) was 3.9% in FOS patients compared to 9.2%, 4.7%, and 11.4% in the ELT, ROM, and AVA groups. The mean cost per patient with FOS was $99,209 (95% CI: $59,595–$115,074), compared to $92,426 (95% CI: $68,331–$115,519), $108,482 (95% CI: $84,782–$132,182), and $131,050 (95% CI: $83,327–$179,897) for ELT, ROM, or AVA, respectively. Conclusions: In this real-world analysis, FOS was comparable to the TPOs in maintaining PLTs at clinically beneficial levels. Given these findings, the choice of therapy should be based on overall patient safety, preexisting risk factors for TEs, and cost effectiveness.
From Organ Trafficking to the Kosovo Specialist Chambers
Authors: Muharremi Robert
Published: October 2023

The paper discusses how strategic narratives determine our understanding of politics and justice, and how such narratives can be deliberately constructed to achieve political ends through judicial means and by instrumentalizing international criminal law and courts. The article discusses the concept of strategic narratives from an inter-disciplinary perspective and explores the impact of strategic narratives on international criminal justice. For this purpose, it analyzes as a case study the Council of Europe Parliamentary Assembly Report on “Inhuman treatment of people and illicit trafficking in human organs in Kosovo” of 2011, which led to the establishment of the Kosovo Specialist Chambers and the Kosovo Specialist Prosecutor’s Office.
Advisory Opinion on Obligations of States in Respect of Climate Change: Potential Contribution of Human Rights Bodies
Authors: McMenamin Rebecca
Published: October 2023

On 29 March 2023, the UN General Assembly adopted a resolution requesting an advisory opinion from the International Court of Justice on the obligations of states in respect of climate change. The icj’s opinion, if given, will be the first of an international court determining the elements of human rights obligations in the context of climate change. These issues have already been grappled with by UN human rights treaty bodies. I argue that the icj is entitled to take account of these jurisprudential developments, and should do so.
A Novel Framework for Spatiotemporal Analysis of Temperature Profiles Applied to Europe
Authors: Jamaer S. , Allaerts D. , Meyers J. , van Lipzig N. P. M.
Published: October 2023

Vertical temperature profiles influence the wind power generation of large offshore wind farms through stability-dependent effects such as blockage and gravity waves. However, numerical tools that are used to model these effects are often computationally too expensive to cover the large variety of atmospheric states occurring over time. Generally, an informed decision about which representative nonidealized situations to simulate is missing because of the lack of easily available information on representative vertical profiles, taking into account their spatiotemporal variability. Therefore, we present a novel framework that allows a smart selection of vertical temperature profiles. The framework consists of an improved analytical temperature model for the atmospheric boundary layer and lower troposphere, a subsequent clustering of these profiles to identify representatives, and last, a determination of areas with similar spatiotemporal characteristics of vertical profiles. When applying this framework on European ERA5 data, physically realistic representatives were identified for Europe, excluding the Mediterranean. Two or three profiles were found to be dominant for the open ocean, whereas more profiles prevail for land. Over the open ocean, weak temperature gradients in the boundary layer and a clear capping inversions are widespread, and stable profiles are absent except in the region of the East Icelandic Current. Interestingly, according to the ERA5 data, at its resolution, coastal areas and seas surrounded by land behave more similar to the land areas than to the open ocean, implying that a larger set of model integrations are needed for these areas to obtain representative results for offshore wind power assessments in comparison with the open ocean.

Significance Statement

Numerical tools used to simulate the effect of large, offshore wind farms on neighboring farms and the atmosphere are very expensive. Therefore, they can only be computed for a limited number of cases. As temperature is one of the most important parameters in these kinds of simulations, this work provides a new vertical temperature model and an analysis framework that allows for a smart selection of these cases such that they ideally represent the full variation of the atmosphere’s temperature profiles.