bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Data Transfer Mechanism for DLMS/COSEM Enabled Smart Energy Metering Platform
Authors: Biswas Sudeshna , . Himanshu , Ghosh Sushmita , Das Payali , Saha Kaushik , De Swades
Published: April 2023

We report our implementation of DLMS/COSEM (Device Language Message Specification/Companion Specification for Energy Metering) enabled advanced smart metering data collection using our in-house developed data-driven multivariate data pruning technique. Aiming at near real-time smart metering data collection, a working model of a smart energy meter with a data pruning subsystem is developed and incorporated with the data pruning and communication module. The implementation of DLMS/COSEM service layer enables standard pull-based data collection from multiple meters that are connected with a commercial head-end system. Our implementation enables to fetch smart meter readings from multiple meters with significantly reduced data footprint. Our empirical results demonstrate that, dynamic data pruning capability reduces the number of samples by nearly 85%. The bandwidth saving increases with the increasing batch size, by accounting for all protocol overheads the endto- end communication bandwidth saving is up to 85%. The DLMS overhead is negligible for larger batch size.
Performance Analysis of Modified SRPT in Multiple-Processor Multitask Scheduling
Authors: Li Wenxin
Published: April 2023

In this paper we study the multiple-processor multitask scheduling problem in both deterministic and stochastic models, where each job have several tasks and is complete only when all its tasks are finished. We consider and analyze Modified Shortest Remaining Processing Time (M-SRPT) scheduling algorithm, a simple modification of SRPT, which always schedules jobs according to SRPT whenever possible, while satisfying the non-preemptive constraint. The M-SRPT algorithm is proved to achieve a competitive ratio of θ(log α + β) for minimizing response time, where α denotes the ratio between maximum job workload and minimum job workload, β represents the ratio between maximum non-preemptive task workload and minimum job workload. In addition, the competitive ratio achieved is shown to be optimal (up to a constant factor), when there are constant number of machines. We further consider the problem under Poisson arrival and general workload distribution (i. e., M/GI/N system), and show that M-SRPT achieves asymptotic optimal mean response time when the traffic intensity ρ approaches 1, if job size distribution has finite support. Beyond finite job workload, the asymptotic optimality of M-SRPT also holds for infinite job size distributions with certain probabilistic assumptions, for example, M/M/N system with finite task workload.
Addressing the Challenge of Biomedical Data Inequality: An Artificial Intelligence Perspective
Authors: Gao Yan , Sharma Teena , Cui Yan
Published: April 2023

Artificial intelligence (AI) and other data-driven technologies hold great promise to transform healthcare and confer the predictive power essential to precision medicine. However, the existing biomedical data, which are a vital resource and foundation for developing medical AI models, do not reflect the diversity of the human population. The low representation in biomedical data has become a significant health risk for non-European populations, and the growing application of AI opens a new pathway for this health risk to manifest and amplify. Here we review the current status of biomedical data inequality and present a conceptual framework for understanding its impacts on machine learning. We also discuss the recent advances in algorithmic interventions for mitigating health disparities arising from biomedical data inequality. Finally, we briefly discuss the newly identified disparity in data quality among ethnic groups and its potential impacts on machine learning.
The Brucella Cell Envelope
Authors: Alakavuklar Melene A. , Fiebig Aretha , Crosson Sean
Published: April 2023

The cell envelope is a multilayered structure that insulates the interior of bacterial cells from an often chaotic outside world. Common features define the envelope across the bacterial kingdom, but the molecular mechanisms by which cells build and regulate this critical barrier are diverse and reflect the evolutionary histories of bacterial lineages. Intracellular pathogens of the genus Brucella exhibit marked differences in cell envelope structure, regulation, and biogenesis when compared to more commonly studied gram-negative bacteria and therefore provide an excellent comparative model for study of the gram-negative envelope. We review distinct features of the Brucella envelope, highlighting a conserved regulatory system that links cell cycle progression to envelope biogenesis and cell division. We further discuss recently discovered structural features of the Brucella envelope that ensure envelope integrity and that facilitate cell survival in the face of host immune stressors.
Poly-Lactic Acid/Graphene Anode for Lithium-Ion Batteries Manufactured with a Facile Hot-Pressed Solvent-Free Process
Authors: Argyropoulos D.-P. , Selinis P. , Vrithias N. R. , Viskadourakis Z. , Salmas C. E. , Karakassides M. A. , Kenakakis G. , Elmasides C. , Farmakis F.
Published: April 2023

For environmental and cost purposes, solvent-free electrode manufacturing techniques are needed for lithium-ion cell technology. In this work, we present a stand-alone lithium-ion anode, containing graphene and Poly-lactic acid (PLA) as active and binding material, respectively, manufactured in a free-solvent process. To this purpose, PLA and graphene were thoroughly mixed and a hot-press was used to form the resulting electrode. At a half-cell configuration, the electrodes exhibited a stable reversible specific capacity of more than 300 mAh g−1 at C/15 for over 450 cycles and a promising C-rate performance of around 90 mAh g−1 at 6 C of constant current mode. After cyclic voltammetry analysis of the electrochemical behavior and the kinetics of the prepared electrodes, the Li atom diffusion coefficient was calculated around 1.2 × 10−8 cm2/s during lithiation and 0.6 × 10−8 cm2/s during delithiation. Finally, we show that this electrode manufacturing technique can be upscaled for higher mass loading and corresponding areal capacity at least up to 1 mAh/cm2 and thus it can be considered for practical applications.
Tailoring Electrochemical Activity of Acemetacin with Electrocatalytic Properties of Graphene Derivatives
Authors: Ivanovski Vladimir , Festinger Natalia , Karpowicz Rafał , Tokarz Paweł , Spilarewicz Kaja , Guziejewski Dariusz , Smarzewska Sylwia
Published: April 2023

In this study, differential pulse (DPV) and cyclic voltammetry (CV) were used to investigate the electrocatalytic effects of two oxygen-containing graphene derivatives, as surface modifiers, on the oxidation mechanism of acemetacin, a non-steroidal anti-inflammatory drug. Scanning electron microscopy was employed to examine the modified glassy carbon electrodes surface, and it was discovered, that the morphology and composition of the coatings strongly influenced the electroanalysis of ACM. Cyclic voltammetry was used to confirm the ACM adsorption dependence on the type and structure of modifier. Density functional theory (DFT) calculations were performed to analyse the electron density and spatial distribution of the HOMO orbital of ACM in order to determine the most probable oxidation site in the molecule. It was found that the composition and structure of the modifiers influenced the surface properties of the working electrodes and thus strongly affected ACM adsorption. Finally, it was observed that different oxidation mechanisms were preferred at each of the modifier layer. To determine the relationship between ACM oxidation mechanism and analytical usability of developed sensors, under optimized conditions, for both working electrodes calibration curves were developed, and the methods were applied to determine ACM in real samples. The performed studies confirm the need for rational design of used graphene-derivative materials as electrode surface modifiers.
Renal mitochondrial dysfunction in ovine experimental sepsis-associated acute kidney injury
Authors: Luther Tomas , Bülow-Anderberg Sara , Persson Patrik , Franzén Stephanie , Skorup Paul , Wernerson Annika , Hultenby Kjell , Palm Fredrik , Schiffer Tomas A. , Frithiof Robert
Published: April 2023

We studied the function of renal cortical mitochondria in relation to oxygen consumption in an ovine model of sepsis with acute kidney injury. We demonstrated changes in the electron transport chain induced by sepsis consisting of a reduced respiratory control ratio mainly by a reduced complex I-mediated respiration. Neither an increase in mitochondrial uncoupling nor a reduction in mitochondrial efficiency was demonstrated and cannot explain why oxygen consumption was unaffected despite reduced tubular transport.
Leveraging physiology and artificial intelligence to deliver advancements in health care
Authors: Zhang Angela , Wu Zhenqin , Wu Eric , Wu Matthew , Snyder Michael P. , Zou James , Wu Joseph C.
Published: April 2023

Artificial intelligence in health care has experienced remarkable innovation and progress in the last decade. Significant advancements can be attributed to the utilization of artificial intelligence to transform physiology data to advance health care. In this review, we explore how past work has shaped the field and defined future challenges and directions. In particular, we focus on three areas of development. First, we give an overview of artificial intelligence, with special attention to the most relevant artificial intelligence models. We then detail how physiology data have been harnessed by artificial intelligence to advance the main areas of health care: automating existing health care tasks, increasing access to care, and augmenting health care capabilities. Finally, we discuss emerging concerns surrounding the use of individual physiology data and detail an increasingly important consideration for the field, namely the challenges of deploying artificial intelligence models to achieve meaningful clinical impact.
Wireless Network-Aided Delay Information System Correlation with Airport Grid Distribution Based on Multideterminants Big Data
Authors: Yuan Yujie , Jiang Xiushan
Published: April 2023

The intelligent sensing and communication technology in the airports’ grid information system provides a multidimensional big data set for analyzing flight delays. These data from air traffic control, weather, and multiple determinants will cause initial flight delays. Due to the influence of adjacent flight time correlation, the initial delay causes the delay of subsequent flights, discovered by mining information sensing data, forming the phenomenon of flight delay diffusion. Different determinants will lead to the delay diffusion form of different regions, and more seriously, it will lead to “disaster area” delay in the whole regional grid information structure. To analyze the spatial impact of each factor on flight delay and explore the regional distribution of delay determinants, this paper combined the spatial regression model and determined the key explanatory variables by statistical and processing of the aviation system data. The case study showed the spatial airport delay characteristics in terms of aircraft movements in China. After processing intelligent sensing and communication data, the results show that there is a spatial effect between airports in terms of delay and determinants. The high-delay clusters of delay constraints principally occurred in the Beijing-Tianjin-Hebe and Yangtze River Delta urban agglomerations. Direct flights, weather, new flight routes, take-off, and landing capacity have a more critical impact on spatial airport delays. The use of Internet of Things technology to perceive, analyze, and integrate multiple information of airport delay and combine spatial analysis models can accurately mine delay characteristics and effectively achieve digital and intelligent flight delay management.
Enhanced Antimony Sulfide Sb2S3 Nanobars Solar Cell Performance with Doped PCDTBT Polymer
Authors: Mkawi Elmoiz Merghni , Al-Hadeethi Yas
Published: April 2023

In this paper, antimony sulfide (Sb2S3) nanobars were prepared via a facile poly[N-9

′

-heptadecanyl-2,7-carbazole-alt-5,5-(4

′

,7

′

-di-2-thienyl-2

′

,1

′

,3

′

-benzothiadiazole) (PCDTBT) organic polymer-assisted hydrothermal method. The impact of PCDTBT polymer concentration on the crystal structure, shape, optical, and electrical characteristics of Sb2S3 nanobars and thin films was studied. Analysis by X-ray diffraction indicated that raising the PCDTBT concentration caused the low-crystalline structure of the Sb2S3 nanobars to transform into a polycrystalline structure. In addition, the sample had a unique Sb2S3 (orthorhombic) crystalline phase, and the crystal size increased from 32 nm to 42.6 nm. Analysis of the data revealed that the Sb2S3 nanobars had a relatively high absorption coefficient (∼105 cm−1) in the visible spectrum, with band gap values ranging from 1.71 to 1.89 eV. At a high polymer concentration, the surface morphology and grain development were enhanced, and the chemical composition analysis peaks indicate a 2 : 3 atomic ratio for Sb : S. Transmission electron microscopy (TEM) micrograph examinations demonstrate the appearance of the produced Sb2S3, which is bar-like and made of nanobars with a typical width of 200–300 nm and confirm the crystallinity of the nanobars. The optimized Sb2S3 device has a power conversion efficiency (PCE) of 5.11%, a short-circuit current density of 16.5 mA/cm2, an open-circuit voltage of 456 mV, and a fill factor of 66.62% under AM1.5G illumination. It was observed that PCDTBT has a significant role in the creation of Sb2S3 nanobars and thin films.
A Novel Damage Assessment Method for RC Beam Using Force-Hammer Excitation and Piezoelectric Sensing Technology
Authors: Yang Xia , Zhang Minghui , Chen Hongbing , Hao Hong , Kong Qingzhao
Published: April 2023

Concrete is the most commonly used construction material in infrastructural projects, but it may suffer from damages because of the heavy loads, fatigue, and harsh service environments. Therefore, it is crucial to detect damage for evaluating the structural conditions and providing guidance for daily maintenance and timely alarm. This paper presents a novel method for damage assessment that offers an easy-carried detection process with a large monitoring range. The proposed method involves exciting stress waves using a force-hammer and receiving them with piezoceramics pasted on the structure. The structural conditions are then evaluated using the Pearson correlation coefficient (PCC) of stress waves received from different stages. To verify the feasibility of the proposed method, a numerical model is innovatively established to study the stress wave propagation in a reinforced concrete (RC) beam with actual damage induced by the external load based on the concrete damaged plasticity (CDP) model. The experimental study is then conducted to demonstrate the effectiveness of the method and the accuracy of the numerical simulation. The numerical and experimental results show a good correlation, illustrating that the proposed method can not only effectively distinguish whether damage occurs but also determine the structural condition from the elastic phase to failure. The proposed monitoring method in this study has great potential for fast damage assessment of RC structures for both lab research and practical applications.
Evaluation of Ibuprofen Prolonged Release of Biomedical PLA-PEG-PLA Hydrogel via Degradation Mechanism
Authors: Nguyen Hien Thi-Thanh , Nguyen Lam Thi-Truc , Ha Anh Cam , Huynh Phu Dai
Published: April 2023

A micellar hydrogel has long been considered an intelligent hydrophobic drug delivery material. In this study, synthesized PLA1750-PEG1750-PLA1750 micellar hydrogel aims to encapsulate ibuprofen (IBU) in the core PLA hydrophobic of the micelle and prolong the drug release time by an injectable route. The structure and morphology of the PLA1750-PEG1750-PLA1750 copolymer hydrogel were demonstrated by 1H NMR and TEM data. The hydrogel also achieved a gel state at a high concentration of 25 wt.% under the physiological conditions of the body (37°C, pH 7.4). Besides, the biocompatibility test displayed that the hydrogel slightly affected mice after injection one week and fully recovered after four weeks. Furthermore, the in vitro degradation of the hydrogel showed apparent gel erosion after the first three weeks, which is related to the IBU release rate: slow for the first three weeks and then fast. As a result, the total drug release after three and four weeks was 18 wt.% and 41 wt.%, respectively. However, in the first 24 hours, the amount of the drug released was 10 wt.%, suggesting that the IBU drug diffused from the surface hydrogel to the buffer solution. These show that PLA1750-PEG1750-PLA1750 hydrogel can be a potential IBU drug delivery candidate.
Climate Services for Agriculture: Tools for Informing Decisions Relating to Climate Change and Climate Variability in the Wine Industry
Authors: Webb Leanne , Tozer Carly , Bettio Lynette , Darbyshire Rebecca , Robinson Bella , Fleming Aysha , Tijs Sigrid , Bodman Roger , Prakash Mahesh
Published: April 2023

Background and Aims. Australia’s changing climate is already impacting the agriculture sector and will continue to do so in the future. To help respond to these impacts, the Climate Services for Agriculture (CSA) platform presents readily accessible climate data, including future climate projections, relevant to specific agricultural commodities. This wine industry example aims to demonstrate the functionality and utility of the CSA for national use across a broad range of commodities. Methods and Results. The platform includes commodity-relevant climate indices designed in consultation with experts to ensure that they are as salient to producers as possible; the wine-grape specific indices include measures of growing season temperature, rainfall, extreme heat, and frost. Here, we describe the research behind the wine-grape specific indices and present sample outputs from the CSA platform for a site within a selected winegrowing region. We note the CSA platform has been developed through an extensive and continuing user engagement initiative, ensuring it meets the needs of the agriculture community as they grapple with how to make decisions based on longer term climate projections. Conclusions. Provision of past, seasonal outlook, and future climate information for Australia and for a range of important agricultural commodities can help improve on-farm planning and decision-making to respond to climate risks. The wine industry provides a leading example of how to use these data for decision-making, noting ongoing adjustments will be needed. Significance of the Study. The CSA platform brings together historical climate data, seasonal climate outlooks, and future climate projections to assist agricultural producers to better manage climate variability and climate change. It aims to nationalise this information for all major agricultural commodities in Australia. We use wine production as a demonstration case here.
Study on the Dynamic Response of Composite Box Girder Bridges with Corrugated Steel Webs
Authors: Mao Ya-Na , Ma Chi , Liu Shi-Zhong , Li Li-Yuan
Published: April 2023

To more accurately consider the dynamic response of composite box girder bridges with corrugated steel webs under the effect of live loads, based on the theory of vehicle-bridge coupled vibration, a refined finite element model of vehicle-bridge coupled vibration analysis for composite box girders was established. The advanced dynamic response analysis of composite box girders with corrugated steel webs and traditional concrete box girders with 30 m single boxes and single cells, as well as with 50 m single boxes and multiple cells, was carried out. The research revealed that the natural vibration frequency of the composite box girder with corrugated steel webs is lower than that of the corresponding concrete box girder. When the bridge deck condition is poor, the dynamic impact coefficient of the composite box girder is much larger than that of the concrete box girder. When the bridge deck is in poor condition, the dynamic impact response is significantly enhanced, and the difference is significantly compared with that when the bridge deck is in good condition, which is greater than three times and even six times at the maximum. Both the difference in the vehicle model and the change in the vehicle speed influence the dynamic impact coefficient of the composite box girder.
A Highly Transparent Flexible Antenna Based on Liquid Metal Mesh Film
Authors: Qin Peng , Wang Qianyu , Zhang Pan , Huang Guanlong , Li Qian , Liu Bingxin , Li Lei , Gui Lin , Liu Jing , Deng Zhongshan
Published: April 2023

In this paper, a convenient process for the fabrication of flexible liquid metal mesh films (LMMF) is proposed first. Then, the light transmittance and square resistance characteristics of LMMF are studied theoretically and experimentally. The light transmittance of the LMMF can reach 85% when the line width and spacing are 50 μm and 1000 μm, respectively. Furthermore, as an example of LMMF, a coplanar waveguide loop antenna is designed and fabricated that contains an LMMF with a line width of 50 μm and a line spacing of 500 μm. The measured square resistance and transmittance for the LMMF are 0.0456 Ω/sq and 72%, respectively. The measured peak gain of the antenna is 3.38 dBi while the average efficiency is 61%. The antenna’s working frequency covers most of the S-band, C-band, and X-band, as well as multiple channels of fifth generation (5G) communication. Therefore, the antenna can be used in fields such as radar and mobile communication. Uniquely, the fabricated antenna performs well in terms of light transmission, conductivity, and flexibility. In particular, it remains stable in stretching and bending deformation. As a highly light-transmissive stretchable flexible antenna, the antenna is equipped with various functions such as concealability, conformability, and reconfigurability. This LMMF-based antenna has good prospects for applications in the fields of flexible electronics and transparent electronics.
Iterative Approximation of Common Fixed Points for Edge-Preserving Quasi-Nonexpansive Mappings in Hilbert Spaces along with Directed Graph
Authors: Dewangan Kiran , Gurudwan Niyati , Ahmad Junaid , Aloqaily Ahmad , Mlaiki Nabil
Published: April 2023

We present iterative approximation results of an iterative scheme for finding common fixed points of edge-preserving quasi-nonexpansive self-maps in Hilbert spaces along with directed graph. We obtain weak as well as strong convergence of our scheme under various assumptions. That is, we impose several possible mild conditions on the domain, on the mapping, or on the parameters involved in our scheme to prove convergence results. We support numerically our main outcome by giving an example. Eventually, an application is provided for solving a variational inequality problem. Our result are new/generalized some recently announced results of the literature.
Numerical Simulation of High Efficiency Environment Friendly CuBi2O4-Based Thin-Film Solar Cell Using SCAPS-1D
Authors: Sarker Kushal , Sumon Md. Shamsujjoha , Orthe Mst. Farzana , Biswas Sunirmal Kumar , Ahmed Md. Mostak
Published: April 2023

In this research work, a copper bismuth oxide- (CuBi2O4-) based thin-film solar cell has been proposed for the lead and toxic-free (Al/ITO/TiO2/CuBi2O4/Mo) structure simulated in SCAPS-1D software. The main aim of this work to make an ecofriendly and highly efficient thin-film solar cell. The absorber layer CuBi2O4, buffer layer TiO2, and the electron transport layer (ETL) ITO have been used in this simulation. The performance of the suggested photovoltaic devices was quantitatively evaluated using variations in thickness such as absorber, buffer, defect density, operating temperature, back contact work function, series, shunt resistances, acceptor density, and donor density. The absorber layer thickness is fixed at 2.0 μm, the buffer layer at 0.05 μm, and the electron transport layer at 0.23 μm, respectively. The CuBi2O4 absorber layer produces a solar cell efficiency of 31.21%, an open-circuit voltage (

V

oc

) of 1.36 V, short-circuit current density (

J

sc

) of 25.81 mA/cm2, and a fill factor (FF) of 88.77%, respectively. It is recommended that the proposed CuBi2O4-based structure can be used as a potential for thin-film solar cells that are both inexpensive and highly efficient.
Anticataract Effect of the Aqueous Extract of the Flowers of Aspilia africana in Murine Model of Diabetic and Age-Related Cataracts
Authors: Frema Amanfo Adwoa , Kyei Samuel , Duah Boakye Yaw , Osei Akoto Clement , Kwaku Addo Justice , Oduro Yeboah Kofi , Osafo Newman
Published: April 2023

Background. The use of Aspilia africana in traditional medicine for the management of ocular diseases has been reported in India and some indigenous communities of Africa. The aim of this study was to investigate the aqueous extract of the flowers of A. africana (AAE) as an anticataract remedy using murine models of diabetic and senile cataracts. Methods. Preliminary phytochemical screening of the extract, in vitro antioxidant assays, and in vitro aldose reductase inhibitory activity were performed. For anticataract investigations of the extracts, diabetic cataract was induced by galactose administration in 3-week-old Sprague Dawley rats. The evaluation of experimentally induced age-related cataract was performed by administering sodium selenite to 10-day-old rat pups. Results. The phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, glycosides, and saponins. In vitro aldose reductase inhibitory property of the extract on rat lenses revealed that the AAE inhibited the enzyme activity with IC50 of 12.12 µg/ml. For the anticataract investigations, 30, 100, and 300 mg·kg−1AAE-treated rats recorded significantly low (

p
≤
0.0001

) cataract scores compared to the negative control rats, indicating a delay in cataractogenesis from the second week of treatment in the galactose-induced cataractogenesis. Similarly, the treatment with AAE caused a significant reduction (

p
≤
0.0001

) in cataract scores compared to the negative control rats in the selenite-induced cataractogenesis. Markers of lens transparency, such as aquaporin 0, alpha-A crystallin, and total lens proteins and lens glutathione levels, were significantly preserved (

p
≤
0.05
–
0.0001

) in each cataract model after AAE treatment. Conclusion. The study established the anticataract potential of the aqueous extract of flowers of A. africana in murine models, hence giving scientific credence to its folkloric use in the management of cataract.
Data Protection of Accounting Information Based on Big Data and Cloud Computing
Authors: Li Xiaohua
Published: April 2023

With the rapid development of Internet technology, mankind has entered the era of big data. The Internet records all kinds of information, and the amount of information generated in the future is in a state of explosive growth. With the development of enterprises, the data of accounting information have grown, and its security has also been threatened. Once the accounting information is leaked, it will have a great impact on the company. Therefore, it is very necessary to protect accounting information data. This paper aims to study how to protect accounting information data based on big data and cloud computing. Based on this, this paper proposes an attribute-based encryption method based on big data and cloud computing and analyzes the ABE scheme of a single authority and multiple authorities. The multiauthority ABE scheme can effectively solve the problems of low computational efficiency, poor security performance, and high time overhead in the single-authority ABE scheme. The experimental results of this paper show that, under the single-authority ABE scheme in the information data protection of enterprise A, the confidentiality of data is 54% at the highest and 46% at the lowest, which is generally not very high. In the information data protection of the multiauthority ABE scheme in enterprise A, the highest data confidentiality is 86% and the lowest is 79%. The highest is 32% more than the single-authority ABE scheme. The lowest is also 33% more than that. Generally speaking, the confidentiality of its data is very high. In terms of reliability, integrity, and effectiveness, the single-authority ABE scheme is not as good as the multiauthority ABE scheme. It shows that the multiauthority ABE scheme proposed in this paper has a powerful information data security protection function and can be effectively applied to accounting information data protection.
Experimental Study on Freezing Strength of Soil-Concrete Lining Interface in Cold Regions
Authors: Fuping Zhang , Jianguo Shang , Wenting Geng , Pengfei He
Published: April 2023

The lining of water conveyance canals in cold regions is usually subjected to serious damage, such as spalling, bulging, and fracture, due to the harsh natural environment. The main causes of these types of damage are the normal frost-heaving force and tangential frost-heaving force (adfreeze force) acting on the liner plate. In this study, the adfreeze forces between the foundation soil and liner plate were studied using the direct shear test, considering the effects of the initial water content, test temperature, and compactness. The results show that the increase of the water content, the increase of the temperature, and the decrease of the compactness increased the interfacial peak shear displacement, and they all varied in the range of 0.3–1.6 mm. With the decrease of the initial water content of the soil sample, the increase of the test temperature, and the decrease of the compactness, the peak shear stress decreased significantly with the amplitude between 51 and 87%. The interfacial cohesion decreased significantly with the increase of the initial water content, the increase of the temperature, and the decrease of the compactness. The interfacial friction angle had no apparent variation pattern. At room temperature, the interfacial friction angle decreased significantly with the increase of the water content. When the water content was 30%, the interfacial friction angle was almost lost completely, which can easily lead to the sliding loss of the foundation soil and further damage, such as the instability of the lining.
Figure S6 from Proteostasis Modulation in Germline Missense von Hippel Lindau Disease
Authors: Chittiboina Prashant , Mandal Debjani , Bugarini Alejandro , Asuzu David T. , Mullaney Dustin , Mastorakos Panagiotis , Stoica Stefan , Alvarez Reinier , Scott Gretchen , Maric Dragan , Elkahloun Abdel , Zhuang Zhengping , Chew Emily Y. , Yang Chunzhang , Linehan Marston , Lonser Russell R.
Published: April 2023

Figure S6
Figure S4 from Proteostasis Modulation in Germline Missense von Hippel Lindau Disease
Authors: Chittiboina Prashant , Mandal Debjani , Bugarini Alejandro , Asuzu David T. , Mullaney Dustin , Mastorakos Panagiotis , Stoica Stefan , Alvarez Reinier , Scott Gretchen , Maric Dragan , Elkahloun Abdel , Zhuang Zhengping , Chew Emily Y. , Yang Chunzhang , Linehan Marston , Lonser Russell R.
Published: April 2023

Figure S4
Figure S2 from Proteostasis Modulation in Germline Missense von Hippel Lindau Disease
Authors: Chittiboina Prashant , Mandal Debjani , Bugarini Alejandro , Asuzu David T. , Mullaney Dustin , Mastorakos Panagiotis , Stoica Stefan , Alvarez Reinier , Scott Gretchen , Maric Dragan , Elkahloun Abdel , Zhuang Zhengping , Chew Emily Y. , Yang Chunzhang , Linehan Marston , Lonser Russell R.
Published: April 2023

Figure S2
Figure S4 from Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: April 2023

On-treatment changes in NK-cell lineage markers in injected and noninjected lesions
Data from Expression and therapeutic targeting of Trop-2 in treatment resistant prostate cancer
Authors: Sperger Jamie M. , Helzer Kyle T. , Stahlfeld Charlotte N. , Jiang Dawei , Singh Anupama , Kaufmann Katherine R. , Niles David J. , Heninger Erika , Rydzewski Nicholas R. , Wang Liguo , Wang Liewei , Yang Rendong , Ren Yanan , Engle Jonathan W. , Huang Peng , Kyriakopoulos Christos E. , Slovin Susan F. , Soule Howard R. , Zhao Shuang G. , Kohli Manish , Tagawa Scott T. , Cai Weibo , Dehm Scott M. , Lang Joshua M.
Published: April 2023

Abstract
PURPOSE. Men with metastatic castration-resistant prostate cancer (mCRPC) frequently develop resistance to androgen receptor signaling inhibitor (ARSI) treatment; therefore, new therapies are needed. Trophoblastic cell-surface antigen (Trop-2) is a transmembrane protein identified in prostate cancer and overexpressed in multiple malignancies. Trop-2 is a therapeutic target for antibody drug conjugates (ADCs). Experimental Design. Trop-2 gene (TACSTD2) expression and markers of treatment resistance from prostate biopsies were analyzed using data from four previously curated cohorts of mCRPC (n = 634) and the PROMOTE study (dbGaP accession phs001141.v1.p1, n = 88). EpCAM or Trop-2 positive circulating tumor cells were captured from peripheral blood for comparison of protein (n=15) and gene expression signatures of treatment resistance (n=40). We assessed the efficacy of Trop-2 targeting agents in a mouse xenograft model generated from prostate cancer cell lines. RESULTS. We demonstrated TACSTD2 is expressed in mCRPC from luminal and basal tumors but at lower levels in patients with neuroendocrine prostate cancer. Patients previously treated with ARSI showed no significant difference in TACSTD2 expression, whereas patients with detectable AR-V7 expression showed increased expression. We observed that Trop-2 can serve as a cell surface target for isolating circulating tumor cells, which may serve as a predictive biomarker for ADCs. We also demonstrated that prostate cancer cell line xenografts can be targeted specifically by labeled anti-Trop-2 agents in vivo. CONCLUSION. These results support further studies on Trop-2 as a therapeutic and diagnostic target for mCRPC.
Data from Proteostasis modulation in germline missense von Hippel Lindau disease
Authors: Chittiboina Prashant , Mandal Debjani , Bugarini Alejandro , Asuzu David T. , Mullaney Dustin , Mastorakos Panagiotis , Stoica Stefan , Alvarez Reinier , Scott Gretchen , Maric Dragan , Elkahloun Abdel , Zhuang Zhengping , Chew Emily Y. , Yang Chunzhang , Linehan Marston , Lonser Russell R.
Published: April 2023

Abstract
Purpose: Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation/progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in pre-clinical models. We asked if short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in germline missense VHL patients. Experimental Design: We administered oral vorinostat to seven subjects (aged 46.0±14.5 years) and then removed symptomatic hemangioblastomas surgically (clinicaltrials.gov identifier NCT02108002). Results: Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared to untreated hemangioblastomas from same patients. We found transcriptional suppression of downstream HIF effectors. Mechanistically, vorinostat prevented Hsp90 recruitment to mutated pVHL in-vitro. The effects of vorinostat on the Hsp90-pVHL interaction, pVHL rescue, and transcriptional repression of downstream HIF effectors was independent of the location of the missense mutation on the VHL locus. We confirmed a neoplastic stromal cell-specific effect in suppression of pro-tumorigenic pathways with single nucleus transcriptomic profiling. Conclusions: We found that oral vorinostat treatment in VHL patients with germline missense mutations has a potent biologic effect that warrants further clinical study. These results provide biologic evidence to support the use of proteostasis modulation for the treatment of syndromic solid tumors involving protein misfolding.
Data from Proteostasis Modulation in Germline Missense von Hippel Lindau Disease
Authors: Chittiboina Prashant , Mandal Debjani , Bugarini Alejandro , Asuzu David T. , Mullaney Dustin , Mastorakos Panagiotis , Stoica Stefan , Alvarez Reinier , Scott Gretchen , Maric Dragan , Elkahloun Abdel , Zhuang Zhengping , Chew Emily Y. , Yang Chunzhang , Linehan Marston , Lonser Russell R.
Published: April 2023

AbstractPurpose:
Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL.
Patients and Methods:
We administered oral vorinostat to 7 subjects (ages 46.0 ± 14.5 years) and then removed symptomatic hemangioblastomas surgically (ClinicalTrials.gov identifier NCT02108002).
Results:
Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared with untreated hemangioblastomas from same patients. We found transcriptional suppression of downstream hypoxia-inducible factor (HIF) effectors. Mechanistically, vorinostat prevented Hsp90 recruitment to mutated pVHL in vitro. The effects of vorinostat on the Hsp90–pVHL interaction, pVHL rescue, and transcriptional repression of downstream HIF effectors was independent of the location of the missense mutation on the VHL locus. We confirmed a neoplastic stromal cell–specific effect in suppression of protumorigenic pathways with single-nucleus transcriptomic profiling.
Conclusions:
We found that oral vorinostat treatment in patients with germline missense VHL mutations has a potent biologic effect that warrants further clinical study. These results provide biologic evidence to support the use of proteostasis modulation for the treatment of syndromic solid tumors involving protein misfolding. Proteostasis modulation with vorinostat rescues missense mutated VHL protein. Further clinical trials are needed to demonstrate tumor growth arrest.
Supplementary Figure 1 from Anti–PD-1 and Extended Half-life IL2 Synergize for Treatment of Murine Glioblastoma Independent of Host MHC Class I Expression
Authors: Tritz Zachariah P. , Ayasoufi Katayoun , Wolf Delaney M. , Owens Carley A. , Malo Courtney S. , Himes Benjamin T. , Fain Cori E. , Goddery Emma N. , Yokanovich Lila T. , Jin Fang , Hansen Michael J. , Parney Ian F. , Wang Chensu , Moynihan Kelly D. , Irvine Darrell J. , Wittrup K. Dane , Diaz Marcano Rosa M. , Vile Richard G. , Johnson Aaron J.
Published: April 2023

Supplemental Figure 1
Data from EBV-upregulated B7-H3 inhibits NK cell–mediated antitumor function and contributes to nasopharyngeal carcinoma progression
Authors: Chen Haiwen , Duan Xiaobing , Deng Xiaohong , Huang Yingping , Zhou Xiang , Zhang Shanshan , Zhang Xiao , Liu Pingjuan , Yang Chaopin , Liu Guojun , Ren Qinqin , Xiong Yan , Zhu Bo , Zhang Jiexia , Xiang Tong
Published: April 2023

Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus (EBV)-associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV+ NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell–based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV-positive NPC tissues and found that EBV infection–induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection–induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti–PD-L1 treatment restored NK cell–mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. Based on our findings, we conclude that EBV infection can inhibit NK cell–mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell–based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.
FIGURE 4 from Uncovering the Protective Neurologic Mechanisms of Hypofractionated FLASH Radiotherapy
Authors: Alaghband Yasaman , Allen Barrett D. , Kramár Eniko A. , Zhang Richard , Drayson Olivia G.G. , Ru Ning , Petit Benoit , Almeida Aymeric , Doan Ngoc-Lien , Wood Marcelo A. , Baulch Janet E. , Ballesteros-Zebadua Paola , Vozenin Marie-Catherine , Limoli Charles L.
Published: April 2023

FLASH irradiation protects against reductions in LTP after CONV irradiation, 6 months after irradiation. A, Extended novel object recognition testing, 4 months after irradiation. Female mice that exposed to FLASH-RT performed significantly better than those who received CONV-RT (n = 15–16/treatment). B, TBS applied to the Schaffer collaterals produced a robust increase in fEPSP slope (as percent of baseline) in control and FLASH irradiated female mice but reduced in CONV mice 6 months after exposure. C, Levels of potentiation in the fEPSP slope maintained 1 hour after TBS was reduced significantly in the hippocampus of CONV-RT mice, but not in control or FLASH irradiated mice. Data were analyzed using a one-way ANOVA followed by Bonferroni multiple comparison test (n = 10–11/treatment). *, P ≤ 0.05: ***, P ≤ 0.001; ****, P ≤ 0.0001.
Data from A Very Long-acting Exatecan and Its Synergism with DNA Damage Response Inhibitors
Authors: Fontaine Shaun D. , Carreras Christopher W. , Reid Ralph R. , Ashley Gary W. , Santi Daniel V.
Published: April 2023

Exatecan (Exa) is a very potent inhibitor of topoisomerase I and anticancer agent. It has been intensively studied as a single agent, a large macromolecular conjugate and as the payload component of antigen-dependent antibody–drug conjugates. The current work describes an antigen-independent conjugate of Exa with polyethylene glycol (PEG) that slowly releases free Exa. Exa was conjugated to a 4-arm 40 kDa PEG through a β-eliminative cleavable linker. Pharmacokinetic studies in mice showed that the conjugate has an apparent circulating half-life of 12 hours, which reflects a composite of both the rate of renal elimination (half-life ∼18 hours) and release of Exa (half-life ∼40 hours). Remarkably, a single low dose of 10 μmol/kg PEG-Exa—only approximately 0.2 μmol/mouse—caused complete suppression of tumor growth of BRCA1-deficient MX-1 xenografts lasting over 40 days. A single low dose of 2.5 μmol/kg PEG-Exa administered with low but efficacious doses of the PARP inhibitor talazoparib showed strong synergy and caused significant tumor regression. Furthermore, the same low, single dose of PEG-Exa administered with the ATR inhibitor VX970 at doses of the DNA damage response inhibitor that do not affect tumor growth show high tumor regression, strong synergy, and synthetic lethality.
Significance:
A circulating conjugate that slowly releases Exa is described. It is efficacious after a single dose and synergistic with ATR and PARP inhibitors.
A Very Long-acting Exatecan and Its Synergism with DNA Damage Response Inhibitors
Authors: Fontaine Shaun D. , Carreras Christopher W. , Reid Ralph R. , Ashley Gary W. , Santi Daniel V.
Published: April 2023

Exatecan (Exa) is a very potent inhibitor of topoisomerase I and anticancer agent. It has been intensively studied as a single agent, a large macromolecular conjugate and as the payload component of antigen-dependent antibody–drug conjugates. The current work describes an antigen-independent conjugate of Exa with polyethylene glycol (PEG) that slowly releases free Exa. Exa was conjugated to a 4-arm 40 kDa PEG through a β-eliminative cleavable linker. Pharmacokinetic studies in mice showed that the conjugate has an apparent circulating half-life of 12 hours, which reflects a composite of both the rate of renal elimination (half-life ∼18 hours) and release of Exa (half-life ∼40 hours). Remarkably, a single low dose of 10 μmol/kg PEG-Exa—only approximately 0.2 μmol/mouse—caused complete suppression of tumor growth of BRCA1-deficient MX-1 xenografts lasting over 40 days. A single low dose of 2.5 μmol/kg PEG-Exa administered with low but efficacious doses of the PARP inhibitor talazoparib showed strong synergy and caused significant tumor regression. Furthermore, the same low, single dose of PEG-Exa administered with the ATR inhibitor VX970 at doses of the DNA damage response inhibitor that do not affect tumor growth show high tumor regression, strong synergy, and synthetic lethality.

Significance:

A circulating conjugate that slowly releases Exa is described. It is efficacious after a single dose and synergistic with ATR and PARP inhibitors.
Blood Purification with oXiris© in Critically Ill Children with Vasoplegic Shock
Authors: Morin Luc , Charbel Ramy , Cousin Vladimir L , Marais Clémence , Claude Caroline , Barreault Simon , Durand Philippe , Miatello Jordi , Tissières Pierre
Published: April 2023

Introduction: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients’ condition. This study aimed to assess the vaso-inotropic support evolution over time in pediatric patients with vasoplegic shock treated with oXiris©. Methods: All patients aged below 18 years admitted at the Paris Saclay University Quaternary Pediatric Intensive Care Unit with vasoplegic shock and acute kidney injury and treated with oXiris© between October 2017 and January 2020 were included. The vaso-inotropic score and the 28-day mortality were assessed. Improvement under treatment was defined as a 50% decrease in the vaso-inotropic score following 24 h of oXiris© therapy. Results: Eleven pediatric patients aged 2–15 years and weighing 11–60 kg were admitted with vasoplegic shock and acute kidney injury. They received thirteen sessions of oXiris© therapy for septic shock (N = 7) and liver failure (N = 6). Eight patients did not improve their condition during the session, and five ultimately died (37.5% survival). Five patients improved, decreasing their inotropic support by >50% in 24 h. Among them, four survived (80%). Conclusion: Hemofiltration and extracorporeal blood purification with oXiris© can be used in pediatric patients with vasoplegic shock with rapid improvement in hemodynamics in selected patients.