bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatigue analysis of selective laser melting Inconel 718 and the mechanism of ductile–brittle continuous alternating steps during fatigue process
Authors: Xue Suqi , Yang Shanglei , Li Yanlei , Fang Yu
Published: August 2024

In this paper, Inconel 718 powber fabricated by selective laser melting were studied to explore the mechanical characteristics and microstructures. The results of microstructure show that the material exhibits the columnar, honeycomb, and mixed crystal structures. The microhardness is very uniform, with a average value of 317 HV. Tensile test shows the ultimate tensile strength of 785Mpa, elongation of 4.93%, which is high stress brittle fracture. The fatigue strength of 180 MPa was obtained from the fatigue test. The fatigue life was sensitive to the effect of stress. In the scanning electron microscope observation, small crack propagation was found in the fracture, and a large number of step-like fracture characteristics of repeated transformation of toughness and brittleness were found. The mechanism analysis of the step-like ductile–brittle fracture is carried out, which is divided into four stages. Mathematically analyzing the tough-brittle fracture of the step type, where the crack is subjected to both the stress field around the pore and the stress field at the crack tip on the way to extension, a stress field model for crack propagation around the pore and a fracture toughness formula for transverse and longitudinal propagation of tough-brittle steps applicable to this paper are proposed.
Existence of uncountably many periodic solutions for second-order superlinear difference equations with continuous time
Authors: Lin Genghong , Zhou Zhan , Shen Zupei , Yu Jianshe
Published: August 2024

Due to the essential difficulty of establishing an appropriate variational framework on a suitable working space, how to apply the critical point theory for showing the existence and multiplicity of periodic solutions of continuous-time difference equations remains a completely open problem. New ideas including gluing arguments are introduced in this work to overcome such a difficulty. This enables us to employ the critical point theory to construct uncountably many periodic solutions for a class of superlinear continuous-time difference equations without assuming symmetry properties on the nonlinear terms. The obtained solutions are piecewise differentiable in some cases, distinguishing continuous-time difference equations from ordinary differential equations qualitatively. To the best of our knowledge, this is the first time in the literature that the critical point theory has been used for such types of problems. Our work may open an avenue for studying discrete nonlinear systems with continuous time via the critical point theory.
Rumor Forwarding Prediction Model on Weibo Based on Uncertain Time Series
Authors: Wang Ruihong , Liu Fengming
Published: August 2024

The rapid spread of rumors on social media is mainly caused by individual retweets. This paper applies uncertain time series analysis to analyze a rumor retweeting behavior on Weibo. First, the rumor forwarding is modeled using uncertain time series, including order selection, parameter estimation, residual analysis, uncertain hypothesis test and forecast and the validity of using uncertain time series analysis is further supported by analyzing the characteristics of the residual plot. The experimental results show that the uncertain time series analysis can better predict the next stage of rumor forwarding. The results of the study have important practical significance for rumor management and the management of social media information dissemination.
Deep Learning-Meshless Method for Inverse Potential Problems
Authors: Yan Jin , Cheng Yumin
Published: August 2024

This paper combines the deep learning method with the meshless method to propose a new numerical method, which is the deep learning-improved element-free Galerkin (DL-IEFG) method, for solving inverse potential problems. In this method, the unknown term in the governing equation of the inverse potential problem is represented by the feedforward neural network (FNN). By employing the improved element-free Galerkin (IEFG) method to solve the inverse potential problem, the solution equations are established to obtain numerical solutions. The training set is constructed on the valid values obtained from discretized observation spatial points. The predicted values at the training sample points are calculated by combining the numerical solutions with the approximation function built by the improved moving least-squares (MLS) approximation. Then, the FNN representing the unknown term is iterated using the loss function. The effectiveness of the DL-IEFG method for solving potential inverse problems is validated through numerical examples. In addition, the factors impacting the calculation accuracy and efficiency of the DL-IEFG method are investigated.
Compositing of rGO to TiO2 by Low-Temperature Treatment and Their Photocatalytic Properties
Authors: Zhao Shikai , Liang Baoyan , Zheng Xinyang , Luo Yitong , Jiao Mingli
Published: August 2024

Reduced graphene oxide (rGO)/TiO2 nanocomposites were prepared by low-temperature and low-pressure heat treatment. The structure and photocatalysis performance of the composites were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and UV-visible diffuse reflectance spectrum (UV-Vis DRS). The photocatalytic degradation performance of methyl orange (MO) by composites with different raw material ratios was studied under simulated solar-irradiation conditions. Results indicated that graphene oxide (GO) was reduced to graphene during heat treatment and bonded well with TiO2. Compared with TiO2, GO addition greatly improved its photocatalytic efficiency. Under simulated sunlight irradiation, the samples exhibited good photocatalysis performance. Within 50[Formula: see text]min, MO can be rapidly degraded by TiO2/40% rGO composite.
Experimental and Numerical Investigation of Propeller Propulsion System Behavior Considering the Ground Effect
Authors: Hadipour Mohammad , Kamali Reza
Published: August 2024

The aerodynamic characteristics of a propeller near the rigid ground and static water surface have been investigated numerically and experimentally. The aerodynamic performance of the propeller in various elevations from the ground and the static water surface and tilt angle settings at constant propeller rotational speed have been evaluated. The results indicated that ground and water surface can strongly affect the aerodynamic performance of rotating propellers in close distances up to 1.24 times its diameter. A decrease in the distance between the propeller rotation plane and the surface leads to a remarkable increase of the propeller efficiency up to 15%. Similarly, it has been found that the tilt angle has also noticeable effect on the near-surface aerodynamic characteristics of the propeller. At a tilt angle above 25∘ almost at any distance from the surface, near-surface effects tend to vanish and propeller thrust reaches its value of free flight condition. Drawing a comparison between near-ground thrust values of the propeller and the thrust values over the surface of water at any predetermined distance from surfaces and tilt angle indicated that the rigid ground has notably higher thrust efficiency than the flexible water surface. At a height of 0.3D (D is propeller diameter) from the ground surface, thrust increased by about 15% while the growth of thrust efficiency near the water surface was about 8%. CFD and Experimental results confirm each other.
Vibroacoustic Analysis of Laminated Composite L-shaped Acoustic Cavity Using Multi-Domain Coupled BE-FE Method
Authors: Pramanik Subhankar , Das Sreyashi , Niyogi Arup Guha
Published: August 2024

In this paper, vibroacoustic analysis of an L-shaped acoustic cavity comprising of rigid and laminated composite thin and flexible walls with opening has been performed by coupling multi-domain boundary element (BE) method with finite element (FE) method, where the cavity is divided into several domains with intermediate interface layers and the continuity conditions have been established at the interface. Finite element structural analysis of the interacting enclosure has been conducted to extract the mobility relationship between pressure and velocity at the interacting walls and apply that to the pressure-velocity multi-domain BE formulation of the interior acoustic cavity. Absorbent layers have been applied at multiple walls to investigate their effects on sound pressure levels at the boundary and inside the domain. Radiation impedance and admittance relationship have been implemented to model the opening and the absorbent layers at the boundary respectively. An in-house software incorporating the aforementioned features has been developed to solve practical vibroacoustic engineering problems of irregular-shaped cavities. The present program has been verified with analytical and experimental data available in the literature to ensure accuracy. It has been demonstrated that the shape of the acoustic domain along with the presence of opening alters the modal characteristics of the structure causing considerable modifications in the sound pressure level (SPL) pattern. Examples reveal that one can restrict the acoustic output at the resonant frequencies by suitably adding absorbents.
Signals of Transition in Support Systems: A Study of the use of Social Media Analytics in Crisis Management
Authors: Herrera Lucia Castro , Gjøsæter Terje , Majchrzak Tim A. , Thapa Devinder
Published: August 2024

In crisis informatics, little attention is placed on how transitions occur between periods of crisis and non-crisis. The analysis of transition behaviors in public organizations could help in understanding the duality between the need for continuity of services provided to the community, and the cyclical nature of risk and crisis management. This study uniquely highlights the transitions occurring when organizations need to stop day-to-day activities to focus on responding to a crisis while continuing to provide services to their communities. We focus on the use of social media analytics as a support system to study transitions and, with the objective to gain an insight into how sociotechnical systems navigate through periods of crisis and non-crisis, we leverage individual experiences of use of social media as a source of information in public service organizations and developers of social media analytics support tools. In doing so, we employed a process study approach, conducted semi-structured interviews, and used thematic analysis to trace patterns of transitions between crisis and non-crisis states. Furthermore, we formulate five signals that public organizations exhibit to illustrate and guide organizational transition behaviors. The main contribution of this study is the explanation and conceptualization of how transitions happen by framing social media as a support information system. In addition, we highlight the return to a new steady state, an overlooked area of organizational transitions and continuity. Our study will help streamline processes of continuity in organizations and inspires the design and improvement of current and future support systems. Future research could apply and extend our propositions to other support systems such as geospatial technologies, robots, and even artificial intelligence.
CURRICULUM MATTERS
Authors: Goldweber Mikey
Published: August 2024

How to Read the CS2023 Report
Complexity of High-Dimensional Identity Testing with Coordinate Conditional Sampling
Authors: Blanca Antonio , Chen Zongchen , ŠTefankovič Daniel , Vigoda Eric
Published: August 2024

We study the identity testing problem for high-dimensional distributions. Given as input an explicit distribution

\(\mu\)

, an

\(\varepsilon \gt 0\)

, and access to sampling oracle(s) for a hidden distribution

\(\pi\)

, the goal in identity testing is to distinguish whether the two distributions

\(\mu\)

and

\(\pi\)

are identical or are at least

\(\varepsilon\)

-far apart. When there is only access to full samples from the hidden distribution

\(\pi\)

, it is known that exponentially many samples (in the dimension) may be needed for identity testing, and hence previous works have studied identity testing with additional access to various “conditional” sampling oracles. We consider a significantly weaker conditional sampling oracle, which we call the

\(\mathsf{Coordinate\ Oracle}\)

, and provide a computational and statistical characterization of the identity testing problem in this new model.

We prove that if an analytic property known as approximate tensorization of entropy holds for an

\(n\)

-dimensional visible distribution

\(\mu\)

, then there is an efficient identity testing algorithm for any hidden distribution

\(\pi\)

using

\(\widetilde{O}(n/\varepsilon)\)

queries to the

\(\mathsf{Coordinate\ Oracle}\)

. Approximate tensorization of entropy is a pertinent condition as recent works have established it for a large class of high-dimensional distributions. We also prove a computational phase transition: For a well-studied class of

\(n\)

-dimensional distributions, specifically sparse anti-ferromagnetic Ising models over

\(\{+1,-1\}^{n}\)

, we show that in the regime where approximate tensorization of entropy fails, there is no efficient identity testing algorithm unless

\(\mathsf{RP}=\mathsf{NP}\)

. We complement our results with a matching

\(\Omega(n/\varepsilon)\)

statistical lower bound for the sample complexity of identity testing in the

\(\mathsf{Coordinate\ Oracle}\)

model.
A
2
: Towards Accelerator Level Parallelism for Autonomous Micromobility Systems
Authors: Sun Lingyu , Hou Xiaofeng , Li Chao , Liu Jiacheng , Wang Xinkai , Chen Quan , Guo Minyi
Published: August 2024

Autonomous micromobility systems (AMS) such as low-speed minicabs and robots are thriving. In AMS, multiple Deep Neural Networks execute in parallel on heterogeneous AI accelerators. An emerging paradigm called Accelerator Level Parallelism (ALP) suggests managing accelerators holistically. However, there lacks a specialized and practical solution populating ALP for an AMS, where the varying real-time requirements under different working scenarios bring an opportunity to dynamically tradeoff between latency and efficiency. Furthermore, accelerator heterogeneity introduces enormous configuration space, and the shared-memory architecture results in dynamic bandwidth interference.

In this article, we propose

A
2

, a novel AMS resource manager optimizing energy and memory space efficiency under variable latency constraints. We gain insight from prior
Learn&Control
scheme to design an
Analyze&Adapt
scheme specialized for heterogeneous AI accelerators under shared-memory architecture. It features analyzing the system thoroughly offline to support two-step adaptation online. We build a prototype of

A
2

and evaluate it on a commercial edge platform. We show that

A
2

achieves 32.8% improvements in power and 13.8% in memory compared with control-based methods. As for timeliness enhancement,

A
2

reduces the deadline violation rate by 9.2 percentage points (12.8% → 3.6%) on average compared to directly porting
Learn&Control
methods.
A Model-Driven Framework for Composition-Based Quantum Circuit Design
Authors: Gemeinhardt Felix , Garmendia Antonio , Wimmer Manuel , Wille Robert
Published: August 2024

Quantum programming languages support the design of quantum applications. However, to create such programs, one needs to understand the fundamental characteristics of quantum computing and quantum information theory. Furthermore, quantum algorithms frequently make use of abstract operations with a hidden low-level realization (e.g., Quantum Fourier Transform). Thus, turning from elementary quantum operations to a higher-level view of quantum circuit design not only reduces the development effort but also lowers the entry barriers for non-quantum computing experts.

To this end, this article proposes a modeling language and design framework for quantum circuits. This allows the definition of composite operators to advocate a higher-level quantum algorithm design, together with automated code generation for the circuit execution. To demonstrate the benefits of the proposed approach, coined
Composition-based Quantum Circuit Designer
, we applied it for realizing the Quantum Counting algorithm and the Quantum Approximate Optimization Algorithm. Our evaluation results show that, compared to an existing state-of-the-art editor, the proposed approach allows for the realization of both quantum algorithms on a high level with a substantially reduced development effort. In particular, the proposed approach shows constant scaling when increasing the size of the investigated quantum circuits and a lower change criticality when evolving existing quantum circuits.
GenAI in the Context of African Universities: A Crisis of Tertiary Education or Its New Dawn?
Authors: Zlotnikova Irina , Hlomani Hlomani
Published: August 2024

The rapid progression of generative artificial intelligence (GenAI) tools has raised significant interest and concern in academia. Instances of students submitting AI-generated assignments prompt investigations into implications for teaching, learning, and academic integrity. Recent publications highlight concerns such as a lack of conceptual understanding, threats to academic integrity, and disruptions to traditional assessment methods. While recognizing benefits like automated scoring and personalized learning, authors stress the responsible use of GenAI, emphasizing the educator's role in guiding students. This commentary identifies opportunities and threats of GenAI in African university contexts. Opportunities include increased operational efficiency, content generation, automated assessment, recognition of accessibility needs, overcoming language barriers, and accelerated research. However, these tools require human correction and cautious consideration of job displacement concerns. Threats encompass job displacement, privacy and security issues, threats to academic integrity, hallucinations/confabulations of GenAI, access and infrastructure challenges, technological overemphasis, lack of customization for local needs and cultural contexts, dependency on external providers, and unaffordable costs. The need for robust guidelines that balance technological advances with traditional teaching methods in African universities is emphasized. Given digital transformation initiatives like the African Union's Agenda 2063 and Botswana's SmartBots strategy, integrating GenAI could shape the future of African tertiary education. Proactive policies should address ethical concerns, ensure access, and make GenAI tools available, requiring a collaborative effort to navigate its impact responsibly.
Clicktivism on Government E-petition: A legitimate emotional outlet?
Authors: Han M. Tony
Published: August 2024

Clicktivism, an emerging form of activism in the digital era, is a concept that can be applied to government-hosted e-petitions. However, an integrative approach combining these two has been scarce. Addressing this gap, this study aims to investigate the dynamics that occur in the process of clicktivism on government-hosted e-petitions, focusing on their themes and intentions. To address our research question, we collected data from South Korea's “National Petition of the Blue House” and applied multinomial logistic and simple linear regression models to e-petitions that met the criteria for eliciting an official government response. The findings indicate that among the e-petitions meeting the official criteria, those related to political or minority issues received a higher number of supports compared to others. Furthermore, citizens were more inclined to endorse e-petitions seeking punitive actions against specific individuals or organizations, rather than those proposing specific policy or legislative changes. These results suggest that participation through clicktivism is often driven by emotional appeals in petitions. This provides a preliminary framework for understanding citizen engagement behaviors with government-hosted e-petitions and the dynamics that occur in the policy process.
Formal Methods in Industry
Authors: ter Beek Maurice H. , Chapman Rod , Cleaveland Rance , Garavel Hubert , Gu Rong , ter Horst Ivo , Keiren Jeroen J. A. , Lecomte Thierry , Leuschel Michael , Rozier Kristin Yvonne , Sampaio Augusto , Seceleanu Cristina , Thomas Martyn , Willemse Tim A. C. , Zhang Lijun
Published: August 2024

Formal methods encompass a wide choice of techniques and tools for the specification, development, analysis, and verification of software and hardware systems. Formal methods are widely applied in industry, in activities ranging from the elicitation of requirements and the early design phases all the way to the deployment, configuration, and runtime monitoring of actual systems. Formal methods allow one to precisely specify the environment in which a system operates, the requirements and properties that the system should satisfy, the models of the system used during the various design steps, and the code embedded in the final implementation, as well as to express conformance relations between these specifications. We present a broad scope of successful applications of formal methods in industry, not limited to the well-known success stories from the safety-critical domain, like railways and other transportation systems, but also covering other areas such as lithography manufacturing and cloud security in e-commerce, to name but a few. We also report testimonies from a number of representatives from industry who, either directly or indirectly, use or have used formal methods in their industrial project endeavours. These persons are spread geographically, including Europe, Asia, North and South America, and the involved projects witness the large coverage of applications of formal methods, not limited to the safety-critical domain. We thus make a case for the importance of formal methods, and in particular of the capacity to abstract and mathematical reasoning that are taught as part of any formal methods course. These are fundamental Computer Science skills that graduates should profit from when working as computer scientists in industry, as confirmed by industry representatives.
Blockchain Takeovers in Web 3.0: An Empirical Study on the TRON-Steem Incident
Authors: Li Chao , Xu Runhua , Palanisamy Balaji , Duan Li , Shen Meng , Liu Jiqiang , Wang Wei
Published: August 2024

A fundamental goal of Web 3.0 is to establish a decentralized network and application ecosystem, thereby enabling users to retain control over their data while promoting value exchange. However, the recent Tron-Steem takeover incident poses a significant threat to this vision. In this paper, we present a thorough empirical analysis of the Tron-Steem takeover incident. By conducting a fine-grained reconstruction of the stake and election snapshots within the Steem blockchain, one of the most prominent social-oriented blockchains, we quantify the marked shifts in decentralization pre and post the takeover incident, highlighting the severe threat that blockchain network takeovers pose to the decentralization principle of Web 3.0. Moreover, by employing heuristic methods to identify anomalous voters and conducting clustering analyses on voter behaviors, we unveil the underlying mechanics of takeover strategies employed in the Tron-Steem incident and suggest potential mitigation strategies, which contribute to the enhanced resistance of Web 3.0 networks against similar threats in the future. We believe the insights gleaned from this research help illuminate the challenges imposed by blockchain network takeovers in the Web 3.0 era, suggest ways to foster the development of decentralized technologies and governance, as well as to enhance the protection of Web 3.0 user rights.
Pregnancy Establishment and Diagnosis in Livestock
Authors: Ott Troy L. , Tibary Ahmed , Waqas Muhammad , Geisert Rodney , Giordano Julio
Published: August 2024

This comprehensive review explores the complex processes of reproduction, pregnancy establishment, and pregnancy diagnostic methods in cattle, sheep, goats, swine, horses, and camelids. It provides an overview of the history of pregnancy detection and an in-depth exploration of the physiology of pregnancy in livestock. The detection of conceptus tissue and fluids, conceptus-produced hormones, and maternal responses to conceptus signals, crucial for pregnancy diagnosis, are also discussed in detail, as are emerging methods for pregnancy diagnosis in livestock species. Overall, this review emphasizes the direct impact of pregnancy diagnosis and efficient pregnancy management for profitability of livestock enterprises.
Why Should Developmental Scientists Engage in Research on Adolescent Suicide? The Case for Developmentally Informed Suicidology
Authors: Morris-Perez Pamela A. , Benzekri Adam , Boccieri Gianna Rose
Published: August 2024

Adolescent suicide is a critical and prevalent issue yet is rarely studied by developmental psychologists. We assert that developmentalists’ lack of engagement has stymied progress on adolescent suicide research and practice, and we demonstrate how developmental perspectives can contribute to the next decade of research and practice in suicidology. Specifically, we (a) review theories in suicidology (that are largely a-developmental); (b) discuss how developmental phenomena may explain findings regarding the epidemiology of adolescent suicide; (c) review the evidence on the etiology of adolescent suicide, where efforts to identify risk factors have not led to strong predictions, highlighting underutilized approaches from the developmental risk and resilience literature; and (d) review strategies and developmental gaps across the suicide prevention continuum from primary prevention to postvention, recommending an adolescent developmental perspective on the development and study of school- and community-based suicide prevention and postvention. In doing so, we propose a new subfield of Developmentally Informed Suicidology.
Effect of Mechanical Pressure on Rate Capability, Lifetime, and Expansion in Multilayer Pouch Cells with Silicon-Dominant Anodes
Authors: Friedrich S. , Helmer S. , Reuter L. , Dickmanns J. L. S. , Durdel A. , Jossen A.
Published: August 2024

Microscale silicon particles have a higher specific capacity but larger volume expansion than graphite particles, leading to particle decoupling and lifetime limitations. This study investigates a wide range of external mechanical pressures from zero (ZP - 0.00 MPa) to high (HP - 0.50 MPa) pressure to determine the optimal pressure for high rate capability, cyclic lifetime, energy density, low temperature rise, and low cell thickness gain. The cells are characterized by rate tests and impedance spectroscopy, and are aged until 70% state of health (SoH). The post-mortem analysis after 70% SoH and thickness measurements over 360 cycles in a compression test bench offer insights into the thickness gain. Electrochemical results reveal an immediate reduction in discharge capacity upon transitioning from normal pressure (NP - 0.20 MPa) to ZP, with NP and HP exhibiting superior performance over aging. The impedance was reduced initially and over aging for higher mechanical pressures, especially the cathode contact resistance, resulting in lower temperature rises during the rate tests. Overall, applying higher pressures reduced the anode and cell thickness gain. Moreover, the porosity decreased with increasing pressure, as determined by mercury intrusion porosimetry and pycnometer measurements. The increase of the anode mass correlates to the total charge throughput, which is pressure-dependent and the highest for NP.
Deciphering the Role of p-Type ZnCo2O4 Semiconductor Nanoflakes for Selective Enhancement of Voltammetric Responses Toward Redox Species System: Interfacial Electron-Transfer Kinetics and Adsorption Capacity
Authors: Ngo Xuan Dinh , Nguyen Ngoc Huyen , Phung Thi Lan Huong , Nguyen Tuan Anh , Vinh Nguyen Thanh , Nguyen Van Quy , Tran Vinh Hoang , Tuyet Nhung Pham , Le Anh-Tuan
Published: August 2024

In this study, we describe experimental efforts to decipher the role of ZnCo2O4 nanoflakes (ZCO-NFs) for selective enhancement of voltammetric responses of screen-printed electrode (SPE) toward redox species system. The ZCO-NFs sample was characterized by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and UV–vis spectroscopy. The electrochemical characterization of bare SPE and modified SPE electrodes was investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Mott−Schottky analysis. A series of redox systems including paracetamol (PA), dopamine (DA), chloramphenicol (CAP), furazolidone (FZD), p-nitrophenol (p-NP), carbaryl (CBR), ofloxacin (OXF), and erythromycin (ERY) were selected to investigate for (i) reversible redox process, (ii) irreversible electrochemical oxidation process, and (iii) irreversible electrochemical reduction process on both bare-SPE and ZCO-NFs/SPE electrodes. The obtained results showed that ZCO-NFs possess the selective enhancement of electrochemical response for redox systems with an increase of 24%–90% for PAR, DA, FZD, CAP, and CBR and a decrease of 13%–49% for p-NP, ERY, and OFX. The different electrochemical response of redox species at nanostructured semiconductor electrodes is attributed to the contribution of both the adsorption capacity of redox species and the interfacial electron transfer process between electrode and redox species. An insight into the interfacial electron transfer kinetics and its contribution to the enhancement of electrochemical response on p-type semiconductor electrode is helpful in designing high-performance sensing platforms based on spinel oxide nanostructures.
Whole Blood Theophylline Measurements Using an Electrochemical DNA Aptamer-based Biosensor
Authors: Nguyen Minh-Dat , Prevot Guy Terence , Fontaine Nicolas , Dauphin-Ducharme Philippe
Published: August 2024

Theophylline, a bronchodilator used in the treatment of respiratory diseases, displays a narrow therapeutic range requiring therapeutic drug monitoring to maximize its effectiveness and safety. Current measurements of theophylline concentrations are, however, achieved using chromatography or immunoassays, which, in spite of their high accuracy and sensitivity, rely on expensive laboratory-based instruments operated by trained personnel or provide only semi-quantitative results, respectively. In response, we developed an electrochemical DNA aptamer-based (E-AB) sensor for theophylline on screen-printed electrodes. Our sensors enable rapid (<30 s) and selective measurements against theophylline structural analogs in clinically relevant range (55–110 μM) in finger-pricked-sized volumes of undiluted blood samples (<100 μL). Given these attributes, we envision that our results contribute to the development of a low-cost and convenient sensing device for molecular monitoring at the point-of-care.
The Influence of 3D Printing Methods and Materials on the Response of Printed Symmetric Carbon Supercapacitors
Authors: Ferguson Matthew , Egorov Vladimir , Zhang Yan , Gulzar Umair , O’Dwyer Colm
Published: August 2024

We compare the electrochemical response and intrinsic limitations of symmetric carbon-based supercapacitors using two 3D-printing techniques, vat polymerization (Vat-P) and fused deposition modelling (FDM). Two cell types were made in this study, one with metallized Vat-P-printed current collectors, the other with PLA (polylactic acid) FDM-printed current collectors in a similarly designed printed coin cell. Carbon-based electrode slurry (various combinations of SWCNT, GNP, Super-P, PVDF) and aqueous 6 M KOH electrolyte were used in these cells. We demonstrate the influence of internal resistance of each 3D-printing method by direct comparison of cyclic voltammetry and galvanostatic charge-discharge tests. The metallized conductive Vat-P cells display better conductivity and more ideal rectangular cyclic voltammetry response but suffer from poor cycle life in initial experiments (∼5,000 charge-discharge cycles before losing all specific capacitance). The FDM current collector cells using graphite-containing PLA materials have poorer conductivity, less ideal cyclic voltammetry curves, and are structurally less robust and partially porous, but offer very stable cycle life for supercapacitor cells retaining most of their specific capacitance after 100,000 charge-discharge cycles. The cycle life of the metallized Vat-P cells are improved by reducing the voltage window to 0.2–0.7 V to limit metal delamination and using Super-P and PVDF additives.
Shisha Consumption and Presence of Cotinine in Saliva Samples among Students in Public Universities in Coastal Kenya
Authors: Halima Allahdad Abdulrehman , Ngari Moses , Mwiti Kibiti Cromwell , Udu Yusuf Rahma , Mutua Sylvia , Budambula Valentine
Published: August 2024

Background. Despite the well‐known adverse health effects of tobacco, shisha use among students in tertiary institutions remains a public health concern. In Kenya, the literature on status of shisha after the 2017 ban is scanty. This study sought to ascertain actual shisha use among university students along the coastal strip. Methods. We investigated confirmed and self‐reported shisha use. Using proportionate‐to‐size and snowball sampling methods, 380 respondents were enrolled from three universities. Sociodemographic characteristics and self‐reported history of shisha use were documented using a participant‐assisted questionnaire. Actual shisha use was determined qualitatively using 6 panel plus alcohol saliva test kit that detected cotinine use among other selected drugs. Results. Of the 380 participants, 278 (73%) were males and their median (IQR) age was 22 (20–23) years. This study reports 29% current use based on testing positive for cotinine. Among those who reported current ever use of shisha, 19% tested positive for cotinine, respectively. In the multivariable analysis, being separated (adjusted risk ratio (aRR): 2.06 (95% CI: 1.45–2.94)) compared to being single and studying for a degree compared to a diploma (aRR: 1.32 (95% CI: 1.10–1.58)) were associated with cotinine positive. The 4th year of study (aRR: 1.68 (95% CI: 1.22–2.33)) compared to the 1st year and reported knowledge of shisha (aRR: 1.84 (95% CI: 1.18–2.87)) were associated with cotinine positive. Conclusion. Nearly one‐third of university students along the Kenyan coast are active shisha users. Saliva testing for cotinine is a more reliable method of reporting tobacco use. We recommend upscaling of health education, re‐enforcement of the current ban on shisha consumption by concerned authorities, and saliva testing for cotinine while assessing current tobacco use.
A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies
Authors: Desai Pinkal , Lonial Sagar , Cashen Amanda , Kamdar Manali , Flinn Ian , O’Brien Susan , Garcia Jacqueline S. , Korde Neha , Moslehi Javid , Wey Margaret , Cheung Patricia , Sharma Shringi , Olabode Damilola , Chen Hong , Ali Syed Firasath , Liu Mary , Saeh Jamal , Andrade-Campos Marcio , Kadia Tapan M. , Blachly James S.
Published: August 2024

Purpose:

AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

Patients and Methods:

In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; secondary objectives included plasma pharmacokinetics and antitumor activity.

Results:

The most common (≥30%) adverse events were diarrhea (59.0%), nausea (55.1%), and vomiting (47.4%). Four deaths occurred because of adverse events: cardiac arrest, sepsis, tumor lysis syndrome, and acute respiratory failure; only tumor lysis syndrome was related to AZD5991. Dose-limiting toxicities occurred in five patients. Three patients with myelodysplastic syndrome achieved an objective response: one marrow complete remission without hematologic improvement, one partial remission with AZD5991 monotherapy, and one marrow complete remission with AZD5991 + venetoclax. Asymptomatic elevations of troponin I or T were observed in eight (10.3%) patients. Post hoc retrospective analysis revealed elevated troponin T in 14/31 patients before any AZD5991 dose and in 54/65 patients after any AZD5991 dose at or after Cycle 1. No associations were found between elevated troponin and cardiovascular risk factors.

Conclusions:

Treatment with AZD5991 was associated with high incidence of laboratory troponin elevation and a low overall response rate.
Supplementary Table S4 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Table S4 depicts MBM patient characteristics.
Supplementary Table S3 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Table S3 lists all genes included in the M1 phenotypic marker gene set, including respective references.
Supplementary Table S2 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Table S2 lists antibodies and dyes used.
Supplementary Table S1 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Table S1 lists primers used.
Supplementary Figure S4 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Figure S4 shows type I IFN response signature gene expression in human melanoma brain metastasis macrophages.
Supplementary Figure S3 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Figure S3 shows characterization of intracranial tumor microenvironment and macrophages after IFN-beta exposure.
Supplementary Figure S2 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Supplementary Figure S2 depicts flow cytometry gating strategies for all assays.
Figure 5 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Irradiation induces the proinflammatory type I IFN-response signature in TAM associated with increased overall survival in patients with melanoma brain metastases. A, Heatmap of normalized gene counts of the myeloid type I IFN-response signature in previously irradiated MBM not expressing the myeloid type I IFN-response signature (neg., negative) compared to MBM expressing the myeloid type I IFN-response signature (pos., positive; n = 12 and n = 9). B, GSEA of a curated M1 phenotypic marker gene set in MBM from non-irradiated patients compared to MBM from previously irradiated patients. Enrichment Score = 0.55, NES = 2.06, adjusted P value = 1.9e–8 (n = 48 and n = 21). C and D, Deconvolution of TAM abundances in previously irradiated MBM not expressing the myeloid type I IFN-response signature (neg.) compared to MBM expressing the myeloid type I IFN-response signature (pos.) using CIBERSORTx (n = 12 and n = 9). Displayed as absolute proportion of each cell type in each sample in C or mean percentage per group and M1/M2 ratio in D. E, Kaplan–Meier survival estimates for the association of type I IFN-signature expression with the overall survival of irradiated MBM patients (n = 12 and n = 9). For the M1 phenotypic marker gene set see Supplementary Table S3. Data are expressed as individual values for A, median + IQR and individual values for C and mean for D. Statistical significance was determined by paired t test for C and log-rank test for E.
Figure 2 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

YUMM5.2 Ifnb1eGFP-derived IFNβ modulates macrophage polarization and function. A–D, Quantitative flow cytometry analysis of myeloid populations in the YUMM5.2 Ifnb1eGFP TME after control diet (light pink) or Dox diet (dark red). Displayed as percentage of parental population (n = 6 for each group). E, Ratio of TAM polarization states in the YUMM5.2 Ifnb1eGFP TME after control diet or Dox diet. Displayed as mean percentage per group (n = 6 for each group). F, Quantitative flow cytometry analysis of TAM polarization states in YUMM5.2 eGFP tumors after Dox diet compared to control diet. Displayed as log2 fold change (Log2FC; n = 6 for each group). G and H, Quantitative flow cytometry analysis of CD206 (G) and CD86 (H) in bone marrow-derived and M2-like polarized macrophages after 72 hours of indicated treatments. Displayed as mean fluorescence intensity (MFI) in G or percentage of macrophages in H. sn, supernatant, collected after Dox pretreatment (n = 3). I–L, M2-like polarized BMDM generated from C57BL6/J mice were pretreated as indicated and subsequently co-cultured 1:1 (J and K) or 1:10 (L) with CTFR-stained T cells isolated from BALB/c mice. T cells were analyzed on day 5 by flow cytometry. Displayed as percentage of CD8+ T cells (J and K) or of CD4+ T cells (L). For gating strategies see Supplementary Figs. S2 and S3G. M1-like macrophages were defined as MHCII+CD206−, intermediate macrophages as MHCII+CD206+ and M2-like macrophages as MHCII−CD206+ in D–F. Data are expressed as median + IQR and individual values for A–D, G, and J–L, mean for E and individual values and mean for F and H. Statistical significance was determined by paired t test for A–D, by Mann–Whitney U test for G and by one-way analysis of variance (ANOVA) with Tukey post hoc testing for H and J–L. ES, effect size. (I, Created with BioRender.com.)
Data from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: August 2024

Abstract
Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate and adaptive immune cells. Macrophages are one of the most abundant innate immune cells in the immune microenvironment of melanoma brain metastases (MBM) and can exert potent immune-suppressive functions. Here, we investigate the potential of tumoral type I IFNs to repolarize tumor-associated macrophages (TAM) in two murine MBM models and assess the effects of radiotherapy-induced type I IFN on TAMs in a transcriptomic MBM patient dataset. In mice, we describe a proinflammatory M1-like TAM phenotype induced by tumoral IFNβ and identify a myeloid type I IFN-response signature associated with a high M1/M2-like TAM ratio. Following irradiation, patients with MBM displaying a myeloid type I IFN-response signature showed increased overall survival, providing evidence that tumoral IFNβ supports an effective antitumor immune response by re-educating immune-regulatory TAM. These findings uncover type I IFN–inducing therapies as a potential macrophage-targeting therapeutic approach and provide a rationale for combining radiotherapy with concomitant immunotherapy to improve treatment response in patients with MBM.
Significance:
Our study shows that re-education of tumor-associated macrophages by tumoral IFNβ translates into improved clinical outcome in patients with melanoma brain metastases, providing pathomechanistic insights into synergistic type I interferon–inducing therapies with immunotherapies and warranting investigation of IFNβ as a predictive biomarker for combined radioimmunotherapy.