bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing micro-EDM with carbon-coated electrodes: A multi-criteria approach
Authors: Huu Phan Nguyen , Shirguppikar Shailesh , Duc Toan Nguyen
Published: January 2024

The pursuit of precision machining in engineering materials has ignited an imperative to advance electrical discharge machining (EDM) techniques. This study is a deep dive into the domain of micro-electrical discharge machining ([Formula: see text]EDM) with a specific focus on the utilization of carbon-coated tool electrodes. The primary objective is to elucidate the influence of carbon-coated electrodes on vital machining parameters, including machining depth (Z coordinate), tool wear rate (TWR) and overcut (OC) in [Formula: see text]EDM operations. Moreover, the investigation extends to scrutinizing surface characteristics generated by [Formula: see text]EDM with carbon-coated tool electrodes. To enhance performance, carbon-coated tungsten carbide tool electrodes are employed for machining titanium alloy (Ti–6Al–4V) workpieces. The optimization process seeks to identify the optimal combination of process parameters using a Taguchi-DEAR-based multi-response approach. Experimental findings reveal that integrating carbon-coated electrodes significantly improves the [Formula: see text]EDM process, leading to enhanced surface performance metrics. Notably, this study identifies specific parameter settings that effectively optimize machining quality indicators. By achieving a voltage of 160[Formula: see text]V, a capacitance of 10,000[Formula: see text]pF and a tool rotation of 600[Formula: see text]RPM, the research contributes valuable insights into the intricate realm of [Formula: see text]EDM, highlighting the potential for enhanced surface performance through strategic parameter manipulation.
Toward Pointer-Analysis-Based Vulnerability Discovery in Human–Machine Pair Programming
Authors: Wang Pingyan , Liu Shaoying
Published: January 2024

Pointer analysis is the underlying technique of many static analysis tools for vulnerability discovery. It has proved to be effective in identifying a variety of vulnerabilities, such as buffer overflow vulnerabilities and injection vulnerabilities. However, most existing pointer analysis approaches require whole-program availability, i.e. the program to be analyzed should be complete, which may hinder a timely analysis during the coding phase. In this paper, we present two approaches, exhaustive and demand-driven pointer analyses, both of which are applied to a paradigm known as Human–Machine Pair Programming. The ideas enable us to discover security flaws as early as in the coding phase. In this paper, we describe in detail how our approaches maintain flow sensitivity and propagate points-to and taint information in an incremental fashion. We conduct an evaluation of our approaches on SecuriBench Micro and show that the approaches can capture all the potential vulnerabilities in the test cases, though several false alarms are reported.
Analysis of Key Influencing Factors of Track Dynamic Irregularity Induced by Earthquakes in the High-Speed Railway Track–Bridge System
Authors: Zhou Wangbao , Xiao Jun , Liu Shaohui , Jiang Lizhong , Yu Jian , Zu Lingzhi , Wu Lingxu , Ren Zhenbin
Published: January 2024

Stiffness degradation of track–bridge systems under earthquake excitations can lead to track dynamic irregularity, impacting the safety of train operations post-earthquake. In this paper, the nonlinear time-history analysis of CRTS II track–bridge system model established by ANSYS finite element analysis software is carried out under the action of transverse random earthquake. The train–track–bridge system model considering the stiffness degradation caused by earthquake is established by MATLAB, and the earthquake-induced track dynamic irregularity sample library is constructed. The probability distribution mode of the power spectral density sample of the earthquake-induced track dynamic irregularity is explored and the calculation method based on the probability guarantee rate is proposed. The influence of structural damping ratio, train running speed and train type on the power spectral density curve of the earthquake-induced track dynamic irregularity is analyzed. The results show that the power spectrum samples of track dynamic irregularity conform to the hypothesis test of a normal distribution. The power spectral density of earthquake-induced dynamic irregularity primarily consists of medium and low-frequency components. When the structural damping ratio increases from 0.03 to 0.04, 0.04 to 0.05, 0.05 to 0.06, and 0.06 to 0.07, the variation gradients are 0.1701, 0.1240, 0.1034 and 0.0999, respectively, which indicates that the structural damping ratio has a significant effect on the power spectral density of earthquake-induced irregularity, and the impacts of train speed and train type on the power spectral density of near-fault earthquake-induced irregularity are minimal.
On the Dynamic Performance of Higher-Order Smart Metal Foam Arches Coated with Piezoelectric Nanocomposite Actuators
Authors: Yang Wenbo , Wu Changjie , Alashker Yasser
Published: January 2024

This study delves into the dynamic characteristics of intelligent arches composed of metal foams, augmented with piezoelectric nanocomposite actuators. These arches are represented within the polar coordinate system, utilizing a higher-order shear and normal deformation theory that eliminates the need for shear correction factors. The structural properties exhibit thickness-dependent variations following predetermined functions. The model operates within a thermal environment and is supported by a Winkler–Pasternak elastic substrate. Hamilton’s principle is employed to derive the equations governing the structure’s motion. In solving these equations for a scenario with simply supported ends, Fourier series functions are employed as an analytical method. The outcomes are cross-verified against previously published studies with simpler configurations. The investigation explores the impacts of various critical parameters on the dynamic response of the structure. Findings reveal that an increase in pores within the metal foam core decreases the frequency, whereas an increase in the volume fraction of carbon nanotubes has the opposite effect. The primary objective of this study is to design and fabricate more efficient smart structures, through a comprehensive understanding and optimization of the behavior of metal foam arches when integrated with piezoelectric components.
Cohomology and deformation theory of crossed homomorphisms of Leibniz algebras
Authors: Li Yizheng , Wang Dingguo
Published: January 2024

In this paper, we construct a differential graded Lie algebra whose Maurer–Cartan elements are given by crossed homomorphisms on Leibniz algebras. This allows us to define cohomology for a crossed homomorphism. Finally, we study linear deformations, formal deformations and extendibility of finite order deformations of a crossed homomorphism in terms of the cohomology theory.
Defeaturing of CAD Models Using Machine Learning
Authors: Shinde Sudhir L. , Kukreja Aman , Pande S. S.
Published: January 2024

Part features, such as dents, holes, and bumps, are integral to the thin-walled sheet metal components used in the automobile and aerospace industries. These features are often required to be suppressed for more agile and reasonably accurate results during the CAE analysis. However, identifying these features is a critical task usually performed by experts. It requires a detailed analysis of the CAD model, which largely depends on the importance of each feature, feature size, and domain boundary conditions. Thus, identifying such features is a challenging task. This work proposes a novel data-driven approach to create an intuitive model that identifies suppressible features on CAD models of sheet metal parts. The dataset to train the supervised learning model is generated by extensive finite element analysis of the part models. The case studies show that the trained Machine learning model gave good test accuracy.
EnAMP: A novel deep learning ensemble antibacterial peptide recognition algorithm based on multi-features
Authors: Zhuang Jujuan , Gao Wanquan , Su Rui
Published: January 2024

Antimicrobial peptides (AMPs), as the preferred alternatives to antibiotics, have wide application with good prospects. Identifying AMPs through wet lab experiments remains expensive, time-consuming and challenging. Many machine learning methods have been proposed to predict AMPs and achieved good results. In this work, we combine two kinds of word embedding features with the statistical features of peptide sequences to develop an ensemble classifier, named EnAMP, in which, two deep neural networks are trained based on Word2vec and Glove word embedding features of peptide sequences, respectively, meanwhile, we utilize statistical features of peptide sequences to train random forest and support vector machine classifiers. The average of four classifiers is the final prediction result. Compared with other state-of-the-art algorithms on six datasets, EnAMP outperforms most existing models with similar computational costs, even when compared with high computational cost algorithms based on Bidirectional Encoder Representation from Transformers (BERT), the performance of our model is comparable. EnAMP source code and the data are available at https://github.com/ruisue/EnAMP .
Technology-Induced Stress and Employee Resistance in the Context of Digital Transformation and Identification of Countermeasures
Authors: Bausch David , Kraemer Tobias , Mauroner Oliver
Published: January 2024

In the face of increasing digitization, companies must make significant changes to their offerings and operations to remain competitive. This digital transformation of organizations includes a digital transformation of the workplace, which is often met with resistance from employees. While it is recognized that reducing employee resistance is crucial for organizations, there is a limited understanding of the antecedents of employee resistance in the context of digital transformation, different resistance behaviors, and potential countermeasures. Drawing on technostress and employee resistance theories, we address these research gaps. Results from two empirical studies support our central prediction that digital transformation of the workplace causes technostress, which in turn promotes passive and active resistance behaviors among employees. Additionally, we highlight that organizations can use digital literacy facilitation to reduce employee technostress and resistance.
Assessment of vaccination and underreporting on COVID-19 infections in Turkey based on effective reproduction number
Authors: Akman Tuğba , Köse Emek , Tuncer Necibe
Published: January 2024

In this paper, we introduce a SEIR-type COVID-19 model where the infected class is further divided into subclasses with individuals in intensive care (ICUs) and ventilation units. The model is calibrated with the symptomatic COVID-19 cases, deaths, and the number of patients in ICUs and ventilation units as reported by Republic of Turkey, Ministry of Health for the period 11 March 2020 through 30 May 2020 when the nationwide lockdown is in order. COVID-19 interventions in Turkey are incorporated into the model to detect the future trend of the outbreak accurately. We tested the effect of underreporting and we found that the peaks of the disease differ significantly depending on the rate of underreporting, however, the timing of the peaks remains constant. The lockdown is lifted on 1 June, and the model is modified to include a time-dependent transmission rate which is linked to the effective reproduction number [Formula: see text] through basic reproduction number [Formula: see text]. The modified model captures the changing dynamics and peaks of the outbreak successfully. With the onset of vaccination on 13 January 2021, we augment the model with the vaccination class to investigate the impact of vaccination rate and efficacy. We observe that vaccination rate is a more critical parameter than the vaccine efficacy to eliminate the disease successfully.
Biomarker evidence for the depositional environment of basinal UK Mississippian mudstones
Authors: Sims Michael James Edward , Sephton Mark A. , Watson Jonathan S. , Fraser Alastair J. , Vane Christopher H.
Published: January 2024

The regional character of organic matter types and depositional conditions of Pendleian, Brigantian and Arnsbergian mudstones between the Craven Basin and the Widmerpool Gulf was compared through interpretation of biomarker and pyrolysis data from 201 samples recovered from nine boreholes. The Carboniferous seaways have been determined to commonly host dysoxic conditions, enabling the preservation of a mixture of marine and terrestrial organic matter types. Photic zone anoxia, established by the presence of aryl isoprenoids, was determined to be persistent during ‘marine’ conditions represented by marine band, high-sea-level and carbonate facies. The observation and correlation of diasteranes and trisnorneohopane/trisnorhopane ratios within the samples and to other maturity parameters highlighted a significant clay mineral catalytic and/or hydrocarbon retention effect in the samples. This influenced both biomarkers and programmed pyrolysis thermal maturity indices such as
T
max
, reducing the reliability of such results for interpreting the burial depth, and ultimately reserve potential.
Assessing the Impact of Compiler Optimizations on GPUs Reliability
Authors: Santos Fernando Fernandes Dos , Carro Luigi , Vella Flavio , Rech Paolo
Published: January 2024

Graphics Processing Units (GPUs) compilers have evolved in order to support general-purpose programming languages for multiple architectures. NVIDIA CUDA Compiler (NVCC) has many compilation levels before generating the machine code and applies complex optimizations to improve performance. These optimizations modify how the software is mapped in the underlying hardware; thus, as we show in this article, they can also affect GPU reliability. We evaluate the effects on the GPU error rate of the optimization flags applied at the NVCC Parallel Thread Execution (PTX) compiling phase by analyzing two NVIDIA GPU architectures (Kepler and Volta) and two compiler versions (NVCC 10.2 and 11.3). We compare and combine fault propagation analysis based on software fault injection, hardware utilization distribution obtained with application-level profiling, and machine instructions radiation-induced error rate measured with beam experiments. We consider eight different workloads and 144 combinations of compilation flags, and we show that optimizations can impact the GPUs’ error rate of up to an order of magnitude. Additionally, through accelerated neutron beam experiments on a NVIDIA Kepler GPU, we show that the error rate of the unoptimized GEMM (-O0 flag) is lower than the optimized GEMM’s (-O3 flag) error rate. When the performance is evaluated together with the error rate, we show that the most optimized versions (-O1 and -O3) always produce a higher amount of correct data than the unoptimized code (-O0).
Multi-Task Learning with Sequential Dependence Toward Industrial Applications: A Systematic Formulation
Authors: Guo Xiaobo , Ha Mingming , Tao Xuewen , Li Shaoshuai , Li Youru , Zhu Zhenfeng , Shen Zhiyong , Ma Li
Published: January 2024

Multi-task learning (MTL) is widely used in the online recommendation and financial services for multi-step conversion estimation, but current works often overlook the sequential dependence among tasks. In particular, sequential dependence multi-task learning (SDMTL) faces challenges in dealing with complex task correlations and extracting valuable information in real-world scenarios, leading to negative transfer and a deterioration in the performance. Herein, a systematic learning paradigm of the SDMTL problem is established for the first time, which applies to more general multi-step conversion scenarios with longer conversion paths or various task dependence relationships. Meanwhile, an SDMTL architecture, named
Task-Aware Feature Extraction
(TAFE), is designed to enable the dynamic task representation learning from a sample-wise view. TAFE selectively reconstructs the implicit shared information corresponding to each sample case and performs the explicit task-specific extraction under dependence constraints, which can avoid the negative transfer, resulting in more effective information sharing and joint representation learning. Extensive experiment results demonstrate the effectiveness and applicability of the proposed theoretical and implementation frameworks. Furthermore, the online evaluations at MYbank showed that TAFE had an average increase of 9.22% and 3.76% in various scenarios on the post-view click-through & conversion rate (CTCVR) estimation task. Currently, TAFE is deployed in an online platform to provide various traffic services.
Small-Molecule Approaches to Target Transcription Factors
Authors: Cui Huarui , Stilgenbauer Morgan , Koehler Angela N.
Published: January 2024

Dysregulated transcription factor activity is a defining feature of various cancer types. As such, targeting oncogenic transcriptional dependency has long been pursued as a potential therapeutic approach. However, transcription factors have historically been deemed as undruggable targets due to their highly disordered structures and lack of well-defined binding pockets. Nevertheless, interest in their pharmacologic inhibition and destruction has not dwindled in recent years. Here, we discuss new small-molecule-based approaches to target various transcription factors. Ligands with different mechanisms of action, such as inhibitors, molecular glue degraders, and proteolysis targeting chimeras, have recently seen success preclinically and clinically. We review how these strategies overcome the challenges presented by targeting transcription factors.
Therapeutic Discovery for Chromatin Complexes: Where Do We Stand?
Authors: Owens Dominic D.G. , Maitland Matthew E.R. , Arrowsmith Cheryl H. , Barsyte-Lovejoy Dalia
Published: January 2024

In this review, we explore the current landscape of preclinical and clinical therapeutics targeting epigenetic complexes in cancer, focusing on targets with enzymatic inhibitors, degraders, or ligands capable of disrupting protein–protein interactions. Current strategies face challenges such as limited single-agent clinical efficacy due to insufficient disruption of chromatin complexes and incomplete dissociation from chromatin. Further complications arise from the adaptability of cancer cell chromatin and, in some cases, dose-limiting toxicity. The advent of targeted protein degradation (TPD) through degrader compounds such as proteolysis-targeting chimeras provides a promising approach. These innovative molecules exploit the endogenous ubiquitin–proteasome system to catalytically degrade target proteins and disrupt complexes, potentially amplifying the efficacy of existing epigenetic binders. We highlight the status of TPD-harnessing moieties in clinical and preclinical development, as these compounds may prove crucial for unlocking the potential of epigenetic complex modulation in cancer therapeutics.
Halogen Cycling in the Solid Earth
Authors: Kendrick Mark A.
Published: January 2024

Each of the halogens constrains a different aspect of volatile cycling in the solid Earth. F is moderately incompatible in the mantle and has a low mobility at Earth's surface, meaning that it is preferentially retained in the mantle and continental crust. In contrast, Cl, Br, and I are strongly incompatible and highly soluble. Chloride is the dominant anion in seawater and many geofluids and a major component of evaporite minerals. Br and I are essential for life and significantly incorporated into organic matter that accumulates in marine sediments. Surficial fluids circulated into continental and oceanic crust incorporate surface-derived halogens into alteration minerals. As a result, subducting slabs and arc lavas are weakly enriched in F and strongly enriched in Cl, Br, and I. Subduction has maintained mantle Cl and Br concentrations at relatively constant levels since Earth's early differentiation, but mantle I/Cl has decreased over time.
▪Halogen abundances on the early Earth were affected by I partitioning into Earth's core and possible loss of hydrophilic Cl, Br, and I in an early formed ocean.▪Halogens are powerful tracers of subduction zone processes on the modern Earth, with Cl, Br, and I having a dominantly subducted origin in Earth's mantle.▪The deep subduction cycles of Cl, Br, and I are more similar to that of H2O than they are to F, but the geochemical cycle of each halogen differs in detail.▪Halogen abundance ratios and stable isotope ratios vary systematically in Earth's surface reservoirs, meaning that halogens are powerful tracers of geological fluids and melts.
Stability of Ice Shelves and Ice Cliffs in a Changing Climate
Authors: Bassis Jeremy N. , Crawford Anna , Kachuck Samuel B. , Benn Douglas I. , Walker Catherine , Millstein Joanna , Duddu Ravindra , Åström Jan , Fricker Helen A. , Luckman Adrian
Published: January 2024

The largest uncertainty in future sea-level rise is loss of ice from the Greenland and Antarctic Ice Sheets. Ice shelves, freely floating platforms of ice that fringe the ice sheets, play a crucial role in restraining discharge of grounded ice into the ocean through buttressing. However, since the 1990s, several ice shelves have thinned, retreated, and collapsed. If this pattern continues, it could expose thick cliffs that become structurally unstable and collapse in a process called marine ice cliff instability (MICI). However, the feedbacks between calving, retreat, and other forcings are not well understood. Here we review observed modes of calving from ice shelves and marine-terminating glaciers, and their relation to environmental forces. We show that the primary driver of calving is long-term internal glaciological stress, but as ice shelves thin they may become more vulnerable to environmental forcing. This vulnerability—and the potential for MICI—comes from a combination of the distribution of preexisting flaws within the ice and regions where the stress is large enough to initiate fracture. Although significant progress has been made modeling these processes, theories must now be tested against a wide range of environmental and glaciological conditions in both modern and paleo conditions.
▪Ice shelves, floating platforms of ice fed by ice sheets, shed mass in a near-instantaneous fashion through iceberg calving.▪Most ice shelves exhibit a stable cycle of calving front advance and retreat that is insensitive to small changes in environmental conditions.▪Some ice shelves have retreated or collapsed completely, and in the future this could expose thick cliffs that could become structurally unstable called ice cliff instability.▪The potential for ice shelf and ice cliff instability is controlled by the presence and evolution of flaws or fractures within the ice.
Wild Birds as Drivers of Salmonella Braenderup and Multidrug Resistant Bacteria in Wetlands of Northern Italy
Authors: Smoglica Camilla , Graziosi Giulia , De Angelis Damiano , Lupini Caterina , Festino Annarita , Catelli Elena , Vergara Alberto , Di Francesco Cristina Esmeralda
Published: January 2024

In this study, the antimicrobial resistance profiles of bacterial strains obtained from wild avian species recovered in wetlands of Northern Italy were described. Cloacal swabs collected from 67 aquatic birds, hunted or found dead in two private hunting grounds, were submitted to microbiological investigations and antimicrobial susceptibility testing using the Vitek 2 system, while specific PCR protocols were applied to screen for genes associated with the resistance. One hundred fifty‐seven bacterial strains were characterized. The most frequent isolates were Enterococcus faecalis (36/157; 22.9%) and Escherichia coli (23/157; 14.6%). Seventy‐seven isolates (77/157; 49%) were resulted resistant to at least one antibiotic, and eight isolates (8/157; 5%) were classified as multidrug resistant bacteria. Resistance for critically important antibiotics (linezolid, vancomycin, carbapenems, third‐generation cephalosporins, and fluoroquinolones) was also described. Salmonella spp. was obtained from a Eurasian teal (Anas crecca), and it was subsequently analyzed by whole genome sequencing, revealing the serovar Salmonella Braenderup ST22. The phylogenetic analysis, performed with all ST22 described in 2021 and 2022, placed the strain under study in a large clade associated with human salmonellosis cases. These results suggest that migratory aquatic birds may be considered as relevant carriers of critically important antibiotic resistant bacteria and zoonotic food‐borne pathogens potentially able to impact public health.
Retinoid Therapy in a Case of Harlequin Ichthyosis with a Short Literature Review
Authors: Bahashwan Emad , Alfaifi Jaber , Mohamed Moursi Sahar Elmaghawri , Soliman Youssef Elbayoumi
Published: January 2024

Harlequin ichthyosis (HI) is a genetically inherited epidermal disorder due to the mutation of the ABCA12 gene, which is responsible for lipid transportation, and presents with large keratinised scales characterised by deep erythematous fissures, with ectropion and eclabium. A moderate number of cases and a high mortality rate have been recorded. In this case report, a pregnant lady gave birth to a 33-week-old premature foetus with characteristic symptoms of HI. After admitting him to the NICU, a multidisciplinary treatment approach was conducted with paediatric dermatologists, ophthalmologists, urologists, and dieticians. The prognosis is positive, with desquamation of the hyperkeratotic plate revealing an erythematous and shiny skin. A short literature review on HI characteristics, diagnostic aids, and management has also been added.
CD169 Expression in Lymph Nodes is Associated with Increased Infiltration of CD8+ T Cells in Tumors: A Systematic Review and Meta‐Analysis
Authors: Wang Yong , Wu Xiao-Ting , Chen Jing
Published: January 2024

The density of CD169+ macrophages has been reported to positively correlate with the number of CD8+ T cells, although this remains controversial. To better understand this topic, we conducted a meta‐analysis. We searched the PubMed, Medline, and Web of Science databases for studies that were published before May 2022 and performed a meta‐analysis of the incidence of low and high CD169 expression in groups based on CD8 expression using the random‐effects model. A total of 10 studies were included in the meta‐analysis. The incidence of high CD169 expression in lymph nodes was significantly lower than that of low CD169 expression in the low CD8 expression group (odds ratio (OR): 0.76, 95% confidence interval (CI): 0.6, 0.96); however, the incidence of high CD169 expression in lymph nodes was higher than that of low CD169 expression in the high CD8 expression group (OR: 1.50, 95% CI: 1.08, 2.07). We also found that the expression of CD169 in tumors was lower than that in nontumor tissues (standardized mean difference: −5.29, 95% CI: −7.47, −3.11). The overall survival and hazard ratio of patients with high and low CD169 expression was 0.45 (95% CI: 0.37, 0.55). This analysis showed that high CD169 expression was associated with a high CD8 expression, and low CD169 expression was associated with low CD8 expression. The risk of death was 55% lower for patients with high CD169 expression, and high CD169 expression may be associated with favorable survival outcomes in cancer patients. However, the number and heterogeneity of the studies should be taken into consideration when evaluating the analysis. High‐quality randomized controlled trials on the association between CD169 and CD8 expression are needed to verify these effects.
Table S9 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Supplemental Table 9 – Sequencing Coverages
Table S4 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Supplemental Table 4 – LFS Methylation Signature
Figure S9 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Figure S9 showing fragment length metrics in cfMeDIP libraries
Figure S4 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Figure S4 showing effects of germline copy number alterations on tumor fraction prediction
Figure S3 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Figure S3 showing copy number informed predicted tumor fractions
Figure S2 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Figure S2 showing panel-based TP53 copy number alterations
Figure S13 from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Figure S13 showing comparison of tumor and plasma copy number alterations
Table S1 from Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: January 2024

Key Resources Table
Figure S8 from Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: January 2024

Figure S8. SUV39H1 disruption enhances CAR T cell persistence.
Figure S6 from Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: January 2024

Figure S6.Increased proliferation and reduced effector function in 1928z CAR T cells upon SUV39H1 disruption.
Figure S1 from Disruption of SUV39H1-Mediated H3K9 Methylation Sustains CAR T-cell Function
Authors: Jain Nayan , Zhao Zeguo , Koche Richard P. , Antelope Chenling , Gozlan Yosi , Montalbano Antonino , Brocks David , Lopez Michael , Dobrin Anton , Shi Yuzhe , Gunset Gertrude , Giavridis Theodoros , Sadelain Michel
Published: January 2024

Figure S1. Phenotype of T cells (at isolation) and CAR T cells (pre-infusion).
Supplementary Table S1 from GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress
Authors: Zhou Weihua , Zhao Zitong , Lin Angelica , Yang John Z. , Xu Jie , Wilder-Romans Kari , Yang Annabel , Li Jing , Solanki Sumeet , Speth Jennifer M. , Walker Natalie , Scott Andrew J. , Wang Lu , Wen Bo , Andren Anthony , Zhang Li , Kothari Ayesha U. , Yao Yangyang , Peterson Erik R. , Korimerla Navyateja , Werner Christian K. , Ullrich Alexander , Liang Jessica , Jacobson Janna , Palavalasa Sravya , O’Brien Alexandra M. , Elaimy Ameer L. , Ferris Sean P. , Zhao Shuang G. , Sarkaria Jann N. , Győrffy Balázs , Zhang Shuqun , Al-Holou Wajd N. , Umemura Yoshie , Morgan Meredith A. , Lawrence Theodore S. , Lyssiotis Costas A. , Peters-Golden Marc , Shah Yatrik M. , Wahl Daniel R.
Published: January 2024

Supplementary Table S1 shows Supplementary Table S1 and relative references.
Supplementary Fig 7 from Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells
Authors: He Chunbo , Wang Dezhen , Shukla Surendra K. , Hu Tuo , Thakur Ravi , Fu Xiao , King Ryan J. , Kollala Sai Sundeep , Attri Kuldeep S. , Murthy Divya , Chaika Nina V. , Fujii Yuki , Gonzalez Daisy , Pacheco Camila G. , Qiu Yudong , Singh Pankaj K. , Locasale Jason W. , Mehla Kamiya
Published: January 2024

Supplementary Figure S7 shows that VB6 supplementation in combination with IDO and One carbon metabolism inhibition attenuates tumor burden in PDAC mice.
Supplementary Table S1 from Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study
Authors: Kelly William K. , Danila Daniel C. , Lin Chia-Chi , Lee Jae-Lyun , Matsubara Nobuaki , Ward Patrick J. , Armstrong Andrew J. , Pook David , Kim Miso , Dorff Tanya B. , Fischer Stefanie , Lin Yung-Chang , Horvath Lisa G. , Sumey Christopher , Yang Zhao , Jurida Gabor , Smith Kristen M. , Connarn Jamie N. , Penny Hweixian L. , Stieglmaier Julia , Appleman Leonard J.
Published: January 2024

Supplementary Table S1: Supplementary Table S1 showing representativeness of study patients, including age, race/ethnicity, geography, other considerations, and overall representativeness of this study.
Supplementary Fig 1 from Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells
Authors: He Chunbo , Wang Dezhen , Shukla Surendra K. , Hu Tuo , Thakur Ravi , Fu Xiao , King Ryan J. , Kollala Sai Sundeep , Attri Kuldeep S. , Murthy Divya , Chaika Nina V. , Fujii Yuki , Gonzalez Daisy , Pacheco Camila G. , Qiu Yudong , Singh Pankaj K. , Locasale Jason W. , Mehla Kamiya
Published: January 2024

Supplementary Figure S1 shows that PDAC cellsregulate NK cell function by altering vitamin B6 and Tryptophan metabolism.
Supplementary Figure S2 from Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study
Authors: Kelly William K. , Danila Daniel C. , Lin Chia-Chi , Lee Jae-Lyun , Matsubara Nobuaki , Ward Patrick J. , Armstrong Andrew J. , Pook David , Kim Miso , Dorff Tanya B. , Fischer Stefanie , Lin Yung-Chang , Horvath Lisa G. , Sumey Christopher , Yang Zhao , Jurida Gabor , Smith Kristen M. , Connarn Jamie N. , Penny Hweixian L. , Stieglmaier Julia , Appleman Leonard J.
Published: January 2024

Supplementary Figure S2: Supplementary Figure S2 swimlane plot showing time on treatment for xaluritamig patients in low-dose cohorts.
Supplementary Table S6 from 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: January 2024

Antibodies used in this study.
Supplementary Table S3 from 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: January 2024

STEAP1 plasmid constructs used for alanine-scanning mutagenesis.
Supplementary Note 1 and Note 2 from Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer
Authors: Suehnholz Sarah P. , Nissan Moriah H. , Zhang Hongxin , Kundra Ritika , Nandakumar Subhiksha , Lu Calvin , Carrero Stephanie , Dhaneshwar Amanda , Fernandez Nicole , Xu Benjamin W. , Arcila Maria E. , Zehir Ahmet , Syed Aijazuddin , Brannon A. Rose , Rudolph Julia E. , Paraiso Eder , Sabbatini Paul J. , Levine Ross L. , Dogan Ahmet , Gao Jianjiong , Ladanyi Marc , Drilon Alexander , Berger Michael F. , Solit David B. , Schultz Nikolaus , Chakravarty Debyani
Published: January 2024

Supplementary Note 1: The Methods on FDA-drug curation taken directly from Olivier T, Haslam A, Prasad V. Anticancer drugs approved by the US food and drug administration from 2009 to 2020 according to their mechanism of action. JAMA Netw Open. 2021;4:e2138793.
Supplementary Note 2: The Methods and References on FDA-drug curation taken directly from Sun J, Wei Q, Zhou Y, Wang J, Liu Q, Xu H. A systematic analysis of FDA-approved anticancer drugs. BMC Syst Biol. 2017;11:87.
Supplementary Table S2 from 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: January 2024

Cryo-EM data collection, refinement, and validation statistics.
Figure S3 from Quantifying the Expanding Landscape of Clinical Actionability for Patients with Cancer
Authors: Suehnholz Sarah P. , Nissan Moriah H. , Zhang Hongxin , Kundra Ritika , Nandakumar Subhiksha , Lu Calvin , Carrero Stephanie , Dhaneshwar Amanda , Fernandez Nicole , Xu Benjamin W. , Arcila Maria E. , Zehir Ahmet , Syed Aijazuddin , Brannon A. Rose , Rudolph Julia E. , Paraiso Eder , Sabbatini Paul J. , Levine Ross L. , Dogan Ahmet , Gao Jianjiong , Ladanyi Marc , Drilon Alexander , Berger Michael F. , Solit David B. , Schultz Nikolaus , Chakravarty Debyani
Published: January 2024

Among genes found to have limited to no clinical actionability (OncoKB Levels 3B or 4 as the highest level of clinical actionability, or no alteration with an OncoKB level) and altered in >1% of samples in the MSK-IMPACT subset of the AACR Project GENIE dataset, left: the breakdown of genes into different gene-function categories and right: the breakdown of genes as oncogenes, tumor suppressors, both or neither per www.oncokb.org.
Supplementary Table S1 from 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: January 2024

Binding properties of AMG 509 and monovalent anti-STEAP1 XmAb molecules.
Supplementary Methods from 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: January 2024

This file contains Methods for Supplementary Data.
Supplementary Figure S5 from 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: January 2024

AMG 509 cross-reactivity to other species.
Supplementary Figure S4 from 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: January 2024

STEAP1 expression in mCRPC cell lines and tumor samples
Data from Early Cancer Detection in Li–Fraumeni Syndrome with Cell-Free DNA
Authors: Wong Derek , Luo Ping , Oldfield Leslie E. , Gong Haifan , Brunga Ledia , Rabinowicz Ron , Subasri Vallijah , Chan Clarissa , Downs Tiana , Farncombe Kirsten M. , Luu Beatrice , Norman Maia , Sobotka Julia A. , Uju Precious , Eagles Jenna , Pedersen Stephanie , Wellum Johanna , Danesh Arnavaz , Prokopec Stephenie D. , Stutheit-Zhao Eric Y. , Znassi Nadia , Heisler Lawrence E. , Jovelin Richard , Lam Bernard , Lujan Toro Beatriz E. , Marsh Kayla , Sundaravadanam Yogi , Torti Dax , Man Carina , Goldenberg Anna , Xu Wei , Veit-Haibach Patrick , Doria Andrea S. , Malkin David , Kim Raymond H. , Pugh Trevor J.
Published: January 2024

Abstract
People with Li–Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS.
Significance:
By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients.

See related commentary by Latham et al., p. 23.

This article is featured in Selected Articles from This Issue, p. 5