bluuebunny/crossref_metadata_2025 huggingface dataset:
Encompassing geoheritage's multiple voices, multiple venues and multi-disciplinarity
Authors: Clary Renee M. , Pyle Eric J. , Andrews William
Published: April 2024

Geoheritage is recognized globally as a critical concept that celebrates unique geological sites, their history and scientific value, educational potential and geotourism opportunities. Importantly, geoheritage encompasses a wide range of geodiversity, which exists in a variety of scales – from local outcrops to internationally recognized UNESCO sites – and within a continuum of scientific value, historical merit, indigenous meaning, educational potential and geotourism possibilities. We celebrate a selected example of geoheritage sites across the world that have been noticed, recognized and utilized. The breadth and geodiversity of some of these sites indicate we should broaden our geoheritage definition and include historical collections and largely inaccessible sites. Notably, all geoscientists and educators must remain diligent to ensure the sustainability of these sites so that future generations can enjoy our geological and cultural heritage.
Toward Practical Superconducting Accelerators for Machine Learning Using U-SFQ
Authors: Gonzalez-Guerrero Patricia , Huch Kylie , Patra Nirmalendu , Popovici Thom , Michelogiannakis George
Published: April 2024

Most popular superconducting circuits operate on information carried by ps-wide, μV-tall, single flux quantum (SFQ) pulses. These circuits can operate at frequencies of hundreds of GHz with orders of magnitude lower switching energy than complementary-metal-oxide-semiconductors (CMOS). However, under the stringent area constraints of modern superconductor technologies, fully-fledged, CMOS-inspired superconducting architectures cannot be fabricated at large scales. Unary SFQ (U-SFQ) is an alternative computing paradigm that can address these area constraints. In U-SFQ, information is mapped to a combination of streams of SFQ pulses and in the temporal domain. In this work, we extend U-SFQ to introduce novel building blocks such as a multiplier and an accumulator. These blocks reduce area and power consumption by 2

\(\times\)

and 4

\(\times\)

compared with previously proposed U-SFQ building blocks and yield at least 97% area savings compared with binary approaches. Using these multiplier and adder, we propose a U-SFQ Convolutional Neural Network (CNN) hardware accelerator capable of comparable peak performance with state-of-the-art superconducting binary approach (B-SFQ) in 32

\(\times\)

less area. CNNs can operate with 5–8 bits of resolution with no significant degradation in classification accuracy. For 5 bits of resolution, our proposed accelerator yields 5

\(\times\)

to 63

\(\times\)

better performance than CMOS and 15

\(\times\)

to 173

\(\times\)

better area efficiency than B-SFQ.
True Contraction Decomposition and Almost ETH-Tight Bipartization for Unit-Disk Graphs
Authors: Bandyapadhyay Sayan , Lochet William , Lokshtanov Daniel , Saurabh Saket , Xue Jie
Published: April 2024

We prove a structural theorem for unit-disk graphs, which (roughly) states that given a set

\(\mathcal{D}\)

of

\(n\)

unit disks inducing a unit-disk graph

\(G_{\mathcal{D}}\)

and a number

\(p\in[n]\)

, one can partition

\(\mathcal{D}\)

into

\(p\)

subsets

\(\mathcal{D}_{1},\dots,\mathcal{D}_{p}\)

such that for every

\(i\in[p]\)

and every

\(\mathcal{D}^{\prime}\subseteq\mathcal{D}_{i}\)

, the graph obtained from

\(G_{\mathcal{D}}\)

by contracting all edges between the vertices in

\(\mathcal{D}_{i}\backslash\mathcal{D}^{\prime}\)

admits a tree decomposition in which each bag consists of

\(O(p+|\mathcal{D}^{\prime}|)\)

cliques. Our theorem can be viewed as an analog for unit-disk graphs of the structural theorems for planar graphs and almost-embeddable graphs proved recently by Marx et al. [SODA ’22] and Bandyapadhyay et al. [SODA ’22]. By applying our structural theorem, we give several new combinatorial and algorithmic results for unit-disk graphs. On the combinatorial side, we obtain the first Contraction Decomposition Theorem for unit-disk graphs, resolving an open question in the work by Panolan et al. [SODA ’19]. On the algorithmic side, we obtain a new algorithm for bipartization (also known as odd cycle transversal) on unit-disk graphs, which runs in

\(2^{O(\sqrt{k}\log k)}\cdot n^{O(1)}\)

time, where

\(k\)

denotes the solution size. Our algorithm significantly improves the previous slightly subexponential-time algorithm given by Lokshtanov et al. [SODA ’22] which runs in

\(2^{O(k^{27/28})}\cdot n^{O(1)}\)

time. We also show that the problem cannot be solved in

\(2^{o(\sqrt{k})}\cdot n^{O(1)}\)

time assuming the Exponential Time Hypothesis, which implies that our algorithm is almost optimal.
D
2
Comp: Efficient Offload of LSM-tree Compaction with Data Processing Units on Disaggregated Storage
Authors: Ding Chen , Zhou Jian , Lu Kai , Li Sicen , Xiong Yiqin , Wan Jiguang , Zhan Ling
Published: April 2024

LSM-based key-value stores suffer from sub-optimal performance due to their slow and heavy background compactions. The compaction brings severe CPU and network overhead on high-speed disaggregated storage. This article further reveals that data-intensive compression in compaction consumes a significant portion of CPU power. Moreover, the multi-threaded compactions cause substantial CPU contention and network traffic during high-load periods. Based on the above observations, we propose fine-grained dynamical compaction offloading by leveraging the modern Data Processing Unit (DPU) to alleviate the CPU and network overhead. To achieve this, we first customized a file system to enable efficient data access for DPU. We then leverage the Arm cores on the DPU to meet the burst CPU and network requirements to reduce resource contention and data movement. We further employ dedicated hardware-based accelerators on the DPU to speed up the compression in compactions. We integrate our DPU-offloaded compaction with RocksDB and evaluate it with NVIDIA’s latest Bluefield-2 DPU on a real system. The evaluation shows that the DPU is an effective solution to solve the CPU bottleneck and reduce data traffic of compaction. The results show that compaction performance is accelerated by 2.86 to 4.03 times, system write and read throughput is improved by up to 3.2 times and 1.4 times respectively, and host CPU contention and network traffic are effectively reduced compared to the fine-tuned CPU-only baseline.
Psychology-Guided Environment Aware Network for Discovering Social Interaction Groups from Videos
Authors: Yu Jiaqi , Yang Jinhai , Yang Hua , Pan Renjie , Lai Pingrui , Zhai Guangtao
Published: April 2024

Social interaction is a common phenomenon in human societies. Different from discovering groups based on the similarity of individuals’ actions, social interaction focuses more on the mutual influence between people. Although people can easily judge whether or not there are social interactions in a real-world scene, it is difficult for an intelligent system to discover social interactions. Initiating and concluding social interactions are greatly influenced by an individual’s social cognition and the surrounding environment, which are closely related to psychology. Thus, converting the psychological factors that impact social interactions into quantifiable visual representations and creating a model for interaction relationships poses a significant challenge. To this end, we propose a Psychology-Guided Environment Aware Network (PEAN) that models social interaction among people in videos using supervised learning. Specifically, we divide the surrounding environment into scene-aware visual-based and human-aware visual-based descriptions. For the scene-aware visual clue, we utilize 3D features as global visual representations. For the human-aware visual clue, we consider instance-based location and behaviour-related visual representations to map human-centred interaction elements in social psychology: distance, openness, and orientation. In addition, we design an environment aware mechanism to integrate features from visual clues, with a Transformer to explore the relation between individuals and construct pairwise interaction strength features. The interaction intensity matrix reflecting the mutual nature of the interaction is obtained by processing the interaction strength features with the interaction discovery module. An interaction constrained loss function composed of interaction critical loss function and smoothFβloss function is proposed to optimize the whole framework to improve the distinction of the interaction matrix and alleviate class imbalance caused by pairwise interaction sparsity. Given the diversity of real-world interactions, we collect a new dataset named Social Basketball Activity Dataset (Soical-BAD), covering complex social interactions. Our method achieves the best performance among social-CAD, social-BAD, and their combined dataset named Video Social Interaction Dataset (VSID).
The Question of HIV Vaccine: Why Is a Solution Not Yet Available?
Authors: Libera Martina , Caputo Valeria , Laterza Giulia , Moudoud Louiza , Soggiu Alessio , Bonizzi Luigi , Diotti Roberta A.
Published: April 2024

Ever since its discovery, human immunodeficiency virus type 1 (HIV‐1) infection has remained a significant public health concern. The number of HIV‐1 seropositive individuals currently stands at 40.1 million, yet definitive treatment for the virus is still unavailable on the market. Vaccination has proven to be a potent tool in combating infectious diseases, as evidenced by its success against other pathogens. However, despite ongoing efforts and research, the unique viral characteristics have prevented the development of an effective anti‐HIV‐1 vaccine. In this review, we aim to provide an historical overview of the various approaches attempted to create an effective anti‐HIV‐1 vaccine. Our objective is to explore the reasons why specific methods have failed to induce a protective immune response and to analyze the different modalities of immunogen presentation. This trial is registered with NCT05414786, NCT05471076, NCT04224701, and NCT01937455.
Coupled Insights into Structural, Electronic, and Optical Properties of GeTMS3(TM=Sc, Fe, Zn) Sulfide Perovskite across Different Phases: Ab Initio Study
Authors: Bakeer Anwar M. , Mahmoud Nada T. , Shaltaf Riad
Published: April 2024

The structural stability analysis of various phases of GeTMS3(TM=Sc, Fe, Zn) sulfide perovskite has been conducted utilizing the WIEN2k package. This investigation leverages density functional theory (DFT) within the full potential linearized augmented plane wave (FP‐LAPW) method, employing GGA‐mBJ potentials. The focus of this study has encompassed the computation of structural, magnetic, and optical attributes across distinct GeTMS3 phases. These materials have been identified as promising contenders for applications in photovoltaics and spintronics. The study reveals the stability of various phases, with the orthorhombic phase proving energetically favorable for GeScS3 and GeZnS3, and the tetragonal phase for GeFeS3. Magnetic analyses indicate favorable ferromagnetic behavior in GeFeS3 and nonmagnetic characteristics in GeScS3 and GeZnS3. Furthermore, electronic examinations unveil semimetallic and semiconducting behaviors in GeScS3 and GeZnS3 in the tetragonal, respectively, with GeFeS3 exhibiting a half‐metallic nature in the orthorhombic phase. Optical properties illustrate their potential as light harvesters, displaying characteristics suitable for energy conversion applications. This study contributes to a deeper understanding of sulfide perovskite properties, offering insights into potential applications in diverse technological fields.
Litterfall-Associated Carbon Deposition and Vertical Profiles of Soil Organic Carbon in Different Land-Use Systems
Authors: Teramage Mengistu T. , Bassango Biruk , Sime Getachew
Published: April 2024

Litterfall is one of the major inputs for soil nutrients. Understanding the connection of litterfall and soil organic carbon (SOC) as the part of ecological processes is a key step towards carbon sequestration as a climate change mitigation strategy. Yet, it remains inadequate to support by empirical pieces of evidence particularly in tropical ecosystems. In this study, litter traps were used to monitor the monthly organic carbon deposition over a year through litterfall, and soil samples were collected vertically up to 30 cm depth to define the SOC depth distribution in three different land use types located at Wondo Genet district, southern Ethiopia. The results were interpreted by deploying both the carbon stratification ratio (CSR) and carbon flow balance ratio (CFBR) as ecological indicators. The results revealed that both the annual litterfall amount and associated organic carbon input in plantation forest (958.4 ± 112 g·m−2·yr−1; 391.4 ± 112 g·C·m−2·yr−1) were higher than those in the homegarden (183.5.4 ± 26 g·m−2·yr−1; 67.4 ± 10 g·C·m−2·yr−1), conceivably due to few litter contributors (trees) present in the homegarden. The CSR of the homegarden (1.3 ± 0.01) was found between the ratio obtained for crop (1.2 ± 0.01) and plantation forest (1.4 ± 0.01), indicating that it is definitely a combination of pure plantation forest and crop system. The CFBR was higher in plantation forest (3.4 yr−1) than in soil of homegarden (0.77 yr−1), implying the net accumulation of soil carbon over time in the latter system. Hence, homegardens could be considered as a system of climate-smart practice with multiple-biogeochemistry pathways, which simultaneously address the social-absolute needs. Given the current tendency of transforming homegarden agroforestry to monoculture types owing to economical drivers, such indicators can dictate of making rational decisions related to land use planning and soil fertility management.
Gangliosides as Therapeutic Targets for Neurodegenerative Diseases
Authors: Inci Orhan Kerim , Basırlı Hande , Can Melike , Yanbul Selman , Seyrantepe Volkan
Published: April 2024

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.
Biogas Production Optimization in the Anaerobic Codigestion Process: A Critical Review on Process Parameters Modeling and Simulation Tools
Authors: Kelif Ibro Mohammed , Ramayya Ancha Venkata , Beyene Lemma Dejene
Published: April 2024

Many operational parameters, either discretely or collectively, can influence the biodegradation performance towards enhancing biogas yield and quality. Among the operating parameters, organic loading rate (OLR), inoculum-substrate ratio, and carbon-nitrogen ratio (C/N) are the most critical parameters in the optimization and enhancement of biogas yield. Optimization of the biogas production processes depends on the ability of anaerobic microorganisms to respond to variations in operational parameters such as pH, redox potential, and intermediate products to enhance the biogas yield. This review article focuses on the role of process parameters, kinetic models, artificial intelligence, Aspen Plus (AP), and anaerobic digestion model no. 1 (ADM1) in optimizing biogas yield via an anaerobic codigestion (AcoD) process. The review showed that biomaterials codigestion upgraded biogas yield to the extent of 400%, and organic removal efficiency reached up to 90% compared to a single substrate. In addition, the current work has verified that the kinetic model is the most effective tool for signifying that the hydrolysis phase is the rate-limiting step, whereas AP is the most effective tool in the design and optimization of the AcoD process parameters. The reviewed kinetic and AI models show strong correlation values ranging from 0.931 to 0.9991 and 0.8700 to 0.9998, respectively. The AcoD system involves complex chemical reactions, but AP might have limitations in representing such complex chemical processes with nonideal behavior and complicated reaction mechanisms. The design and optimization of AcoD with reliable input parameters are highly limited or nonexistent. The AcoD process design with AP opens fresh research opportunities, including improved efficiency, finding appropriate retention time, and saving time, as well as finding the optimum biogas yield. This review article gives an insightful understanding of AcoD process parameter optimization and valuable strategies for policy development enhancing sustainability in the biogas sector.
Survey of Connectivity Restoration in 3D Wireless Ad Hoc/Sensor Networks
Authors: Chen Hongsheng , Wu Chunhui , Wu Mou , Xu Bin , Fan Ping
Published: April 2024

Wireless ad hoc/sensor networks (WASN) have seen increased application in three-dimensional (3D) environments, such as underwater and aerial scenarios. However, WASN may be fragmented or unable to connect continuously due to the harsh surrounding environment or high mobility. Therefore, restoring the network connectivity and transmit data in real time is very important. This paper focuses on the critical task of restoring network connectivity in 3D WASN, a complex issue given that existing connectivity restoration algorithms for two-dimensional environments are not directly applicable or become overly complicated in 3D contexts. We present a comprehensive analysis of the current research landscape, summarizing key findings related to various aspects of 3D WASN connectivity restoration. These aspects include the application environment (underwater, in the sky, and recovery disaster), opportunities for restoration (active, passive, and active/passive), implementation strategies (clustering and sleep scheduling), and resource constraints (node deployment and movement control). Our study also proposes a classification of connectivity restoration solutions for 3D WASN, identifying existing gaps and suggesting potential future research directions. By providing specific insights and a structured overview of the field, we aim to contribute to the ongoing development of robust and resilient 3D WASN.
Exploring the Mechanism of Echinatin against Cervical Cancer Based on Network Pharmacology
Authors: Chen Hu , Wang Jinlei
Published: April 2024

Cervical cancer significantly impacts women’s health due to its high mortality rate and increasing prevalence among younger individuals, thereby posing a severe threat. Echinatin is the primary active component of licorice in traditional Chinese medicine. However, studies on its use in cervical cancer treatment are limited. In our study, 198 targets of Echinatin were identified by some databases. Among these, 40 core targets related to cervical cancer were selected. Enrichment analyses revealed that Echinatin operated through genes associated with cell cycle, apoptosis, senescence, and various cancer‐related signaling pathways. Differential expression of intersecting targets was verified in the GEO database, and molecular docking also indicated a strong binding capacity between active compounds and identified targets. Moreover, the results of western blot provided further evidence at the protein level. Echinatin hindered the proliferation, migration, and invasion of HeLa and SiHa cells while increasing their apoptosis. This study predicted the potential targets and beneficial effects of Echinatin in cervical cancer treatment, which provides a new avenue for further research into the molecular mechanisms underlying the role of Echinatin in cervical cancer treatment.
A Retrospective Analysis of Polymer Selection Using Solvent Casting: Formulation and DoE Optimization of the Amorphous Solid Dispersion of Amoxicillin Trihydrate by a Spray Drying Method
Authors: Borkhataria Chetan , Chauhan Hardik , Mistry Bhargavi , Kalaria Manisha , Katbamana Rachana , Patel Kalpesh
Published: April 2024

Background. Amoxicillin trihydrate possesses poor solubility, compressibility, and flow behavior. Amorphous solid dispersion prepared by spray drying could solve all three problems at the same time. Objective. To prepare amorphous solid dispersion after screening of polymers by solvent casting method using a spray drying method. Methods. The solvent casting method was used to screen polymers, PVP/VA S‐630, PVP K30, Soluplus, PEG 4000, HPMC AS, and HPMC HP55, in 1 : 1 and 2 : 3 ratios and followed by spray drying after polymer selection. Results. The dissolution performance of the formulation improved with time. The optimum feed rate and feed concentration were found to have an impact on the flow properties and particle size of spray‐dried formulations, and they were selected as independent variables in a 32 full factorial statistical design. The ANOVA and regression analysis suggest that the developed regression model has a significant overall fit to the data and can explain a substantial proportion of the variability in the dissolution at 10 minutes. The optimized batch was selected based on the decisive factors of minimum and maximum values of response variables. Overall, the optimized batch demonstrated improved characteristics in terms of percentage yield (32.81%), dissolution at 10 min (49.70%), and angle of repose at 31.42°. Conclusion. This study provides valuable insights into optimizing formulation strategies for preserving the amorphous state of drugs and contributes to the development of stable pharmaceutical formulations.
Catalytic Degradation Efficacy of Silver Nanoparticles Fabricated Using Actinidia deliciosa Peel Extract
Authors: Kassem Agha Maya , Maatouk Batoul , Mhanna Rami , El-Dakdouki Mohammad H.
Published: April 2024

The preparation of metallic nanoparticles using green synthetic approaches and its application toward the efficient degradation of environmentally hazardous dyes constitutes an attractive alternative to currently employed methods. In the current report, the green synthesis of silver nanoparticles (AgNPs) was successfully achieved using Actinidia deliciosa (kiwifruit) peel aqueous extract as a bioreducing agent under optimized synthesis conditions. The experimental parameters were optimized in terms of reactant ratio, reaction temperature, and reaction time. The biogenic nanoparticles exhibited SPR absorption band at λmax 480 nm. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images revealed quasispherical monodisperse nanoparticles which were 36 nm in diameter. The hydrodynamic diameter of the nanoparticles was 106 nm as determined by dynamic light scattering, and the highly negative ζ-potential (−34 mV) supported its superior colloidal stability. Energy dispersive X-ray confirmed that silver is a major constituent of the nanoparticles. X-ray diffraction (XRD) diffractograms confirmed the crystallinity of the nanoparticles and its face-centered cubic (fcc) lattice structure. The functional groups in the plant’s phytochemicals facilitating the reduction of Ag+ ions and stabilization of the formed AgNPs were identified by fourier transform infrared (FTIR) spectroscopy. In specific, the bands in the FTIR spectra at 3,412, 1,618, 1,419, and 1,237 cm−1 suggested the presence of phenolic compounds. Phytochemical analysis by colorimetric assays revealed that the kiwifruit peel extract was rich in phenolic compounds. When evaluated in the catalytic degradation of organic dyes, the biosynthesized AgNPs induced instant and complete discoloration of the methylene blue dye when 1.6 mg of nanoparticles was used. At a lower dose of AgNPs (0.4 mg), 80% degradation of the dye occurred after 3 hr of treatment. The degradation reaction followed second-order kinetics with a rate constant of 0.01083 mM−1s−1. The current study highlights the immense potential of the prepared nanoparticles as efficient catalysts for the degradation of hazardous organic dyes such as methylene blue and presents an intriguing argument for investigating the catalytic efficiency of the biogenic AgNPs for the degradation of other structurally different dye pollutants.
Performance Evaluation of Onboard Processing Capability Reduction in Cooperative Vehicles Using 5G and Artificial Intelligence
Authors: Palacios-Morocho Elizabeth , Inca Saúl , Monserrat Jose F.
Published: April 2024

Fifth-generation (5G) technology is one of the keys to the Industrial Revolution known as Industry 4.0 as it provides faster connectivity and allows a greater number of devices to be connected simultaneously. In the transport sector, newly produced vehicles are equipped with various sensors and applications to help drivers perform safe maneuvers. However, moving from semiautonomous to fully autonomous vehicles to cooperating systems remains a major challenge. Many researchers have focused on artificial intelligence (AI) techniques and the ability to share information to achieve this cooperative behavior. This information can be made up of different data, which can be obtained from different sensors such as laser imaging detection and ranging (LiDAR), radar, camera, global positioning system (GPS), or data related to the current speed, acceleration, or position. The combination of the different shared data is performed depending on the approach of each navigation algorithm. This data fusion will allow a better understanding of the environment but will overload the network, as the traffic generated will be massive. Therefore, this paper addresses the challenge of achieving this cooperation between vehicles from the point of view of network requirements and computational capacity. In addition, this study contributes to advancing theory into real-world practice by examining the performance of cooperative navigation algorithms in the midst of the migration of computational resources from onboard vehicle equipment to the cloud. In particular, it investigates the transition from a cooperative navigation algorithm based on a decentralized architecture to a semidecentralized one as computationally demanding processes previously performed onboard are performed in the cloud. Additionally, the paper discusses the indispensable role of 5G in fulfilling the escalating demands for high throughput and low latency in these services, particularly as the number of vehicles increases. The results of the tests show that the AI acting alone cannot achieve optimal performance, even using 100% of the computational capacity of the onboard equipment in the vehicle. However, a system that integrates 5G and AI-based joint decisions can achieve better performance, reduce the computational resources consumed in the vehicle, and increase the efficiency of collaborative choices by up to 83.3%.
Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: April 2024

Purpose:

TGFβ signaling is implicated in the progression of most cancers, including esophageal adenocarcinoma (EAC). Emerging evidence indicates that TGFβ signaling is a key factor in the development of resistance toward cancer therapy.

Experimental Design:

In this study, we developed patient-derived organoids and patient-derived xenograft models of EAC and performed bioinformatics analysis combined with functional genetics to investigate the role of SMAD family member 3 (SMAD3) in EAC resistance to oxaliplatin.

Results:

Chemotherapy nonresponding patients showed enrichment of SMAD3 gene expression when compared with responders. In a randomized patient-derived xenograft experiment, SMAD3 inhibition in combination with oxaliplatin effectively diminished tumor burden by impeding DNA repair. SMAD3 interacted directly with protein phosphatase 2A (PP2A), a key regulator of the DNA damage repair protein ataxia telangiectasia mutated (ATM). SMAD3 inhibition diminished ATM phosphorylation by enhancing the binding of PP2A to ATM, causing excessive levels of DNA damage.

Conclusions:

Our results identify SMAD3 as a promising therapeutic target for future combination strategies for the treatment of patients with EAC.
Metabolic Signaling in Cancer Metastasis
Authors: Krieg Sarah , Fernandes Sara Isabel , Kolliopoulos Constantinos , Liu Ming , Fendt Sarah-Maria
Published: April 2024

Metastases, which are the leading cause of death in patients with cancer, have metabolic vulnerabilities. Alterations in metabolism fuel the energy and biosynthetic needs of metastases but are also needed to activate cell state switches in cells leading to invasion, migration, colonization, and outgrowth in distant organs. Specifically, metabolites can activate protein kinases as well as receptors and they are crucial substrates for posttranslational modifications on histone and nonhistone proteins. Moreover, metabolic enzymes can have moonlighting functions by acting catalytically, mainly as protein kinases, or noncatalytically through protein–protein interactions. Here, we summarize the current knowledge on metabolic signaling in cancer metastasis.

Significance:

Effective drugs for the prevention and treatment of metastases will have an immediate impact on patient survival. To overcome the current lack of such drugs, a better understanding of the molecular processes that are an Achilles heel in metastasizing cancer cells is needed. One emerging opportunity is the metabolic changes cancer cells need to undergo to successfully metastasize and grow in distant organs. Mechanistically, these metabolic changes not only fulfill energy and biomass demands, which are often in common between cancer and normal but fast proliferating cells, but also metabolic signaling which enables the cell state changes that are particularly important for the metastasizing cancer cells.
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects
Authors: Menachem Assaf , Alteber Zoya , Cojocaru Gady , Fridman Kfir Tal , Blat Dan , Leiderman Olga , Galperin Moran , Sever Lital , Cohen Nadav , Cohen Keren , Granit Roy Z. , Vols Sandra , Frenkel Masha , Soffer Liron , Meyer Karin , Menachem Keren , Galon Tilleman Hadas , Morein Dina , Borukhov Itamar , Toporik Amir , Perpinial Shahor Michal , Tatirovsky Evgeny , Mizrachi Aviram , Levy-Barda Adva , Sadot Eran , Strenov Yulia , Eitan Ram , Jakobson-Setton Ariella , Yanichkin Natalia , Ferre Pierre , Ophir Eran
Published: April 2024

Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment (TME) in response to IFNγ upregulation in a negative feedback mechanism. In this study, we found that IL18 is upregulated in the TME compared with the periphery across multiple human tumors and most of it is bound to IL18BP. Bound IL18 levels were largely above the amount required for T-cell activation in vitro, implying that releasing IL18 in the TME could lead to potent T-cell activation. To restore the activity of endogenous IL18, we generated COM503, a high-affinity anti-IL18BP that blocks the IL18BP:IL18 interaction and displaces precomplexed IL18, thereby enhancing T- and NK-cell activation. In vivo, administration of a surrogate anti-IL18BP, either alone or in combination with anti-PD-L1, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, the anti-IL18BP induced pronounced TME-localized immune modulation including an increase in polyfunctional nonexhausted T- and NK-cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL18BP using an Ab is a promising approach to harness cytokine biology for the treatment of cancer.
Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: April 2024

Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the β1+β2-agonist isoproterenol and administering β1 or β1+β2 antagonists prior to exercise revealed these effects to be β2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, β2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies.

Significance:

Exercise mobilizes effector γδ T-cells to blood via β2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.
Serial Excision Technique to Reduce Cicatricial Alopecia
Authors: Benez Marcela , Alves Ana Luísa , Emmels Lucas , Dornelas Adriana , Loda Guillermo
Published: April 2024

Introduction: Cicatricial alopecia (CA) poses a challenge for dermatologists due to irreversible hair follicle damage. While pharmacological treatments offer limited efficacy, surgical interventions aim to improve aesthetic outcomes. This article explores the serial excision technique (SET) as a viable option for stable cases of inflammatory CA. Case Report/Case Presentation: Three adult females with different forms of CA underwent staged surgeries to correct CA patches. Procedures included different incision and closure methods based on individual characteristics such as age, type and extent of alopecia, location, and tissue mobility in the scarred area. Discussion: CA significantly impacts patients’ quality of life, demanding comprehensive treatment approaches. SET emerges as an encouraging possibility for stable cases, providing notable cosmetic improvements and enhancing patients’ well-being. This technique offers cost-effective benefits with potential standalone efficacy or in combination with hair transplantation, providing promising outcomes for individuals with CA.
Imágenes de la vanguardia poética latinoamericana en la Guerra Civil Española
Authors: Miranda Julia
Published: April 2024

En este trabajo se estudian los cambios poéticos en algunos escritores de la vanguardia latinoamericana que participaron en la Guerra Civil Española. Las nuevas formas se fundamentaron en las modalidades de la poesía popular, en formas didácticas y de ilusión de comunicabilidad, en combinación con los elementos ya consolidados de las poéticas vanguardistas. En este sentido, el propósito de este trabajo es exponer las interrelaciones que se produjeron entre ciertos imaginarios poéticos de la Guerra Civil Española y los imaginarios sociales del poeta en ese contexto. Mediante la selección del imaginario del escombro y su análisis, se argumenta que la imagen del poeta actuante, sólida desde un comienzo, presenta fisuras al enfrentarse a los daños producidos por los bombardeos en las ciudades.
Discordance Between Very Low‐Density Lipoprotein Cholesterol and Low‐Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort
Authors: Seehusen Kristina E. , Remaley Alan T. , Sampson Maureen , Meeusen Jeffrey W. , Larson Nicholas B. , Decker Paul A. , Killian Jill M. , Takahashi Paul Y. , Roger Véronique L. , Manemann Sheila M. , Lam Reyna , Bielinski Suzette J.
Published: April 2024

Background

Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low‐density lipoprotein cholesterol (VLDL‐C) and lipid discordance could be contributors to the residual risk of ASCVD.

Methods and Results

Cardiovascular disease–free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low‐density lipoprotein cholesterol (LDL‐C) and VLDL‐C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow‐up. The association of LDL‐C and VLDL‐C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL‐C and VLDL‐C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL‐C (per 10‐mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05–1.09];
P
<0.001]) after adjustment for traditional risk factors. The interaction between LDL‐C and VLDL‐C was not statistically significant (
P
=0.11). Discordant individuals with high VLDL‐C and low LDL‐C experienced the highest rate of incident ASCVD events, 16.9 per 1000 person‐years, during follow‐up.

Conclusions

VLDL‐C and lipid discordance are associated with a greater risk of ASCVD and can be estimated from clinically ordered lipid panels to improve ASCVD risk assessment.
Usefulness of Heart Failure Categories Based on Left Ventricular Ejection Fraction
Authors: Christersson Malin , Gustafsson Stefan , Lampa Erik , Almstedt Matilda , Cars Thomas , Bodegård Johan , Arefalk Gabriel , Sundström Johan
Published: April 2024

Background

Heart failure guidelines have recently introduced a narrow category with mildly reduced left ventricular ejection fraction (LVEF) (heart failure with mildly reduced ejection fraction; LVEF 41%–49%) between the previous categories of reduced (heart failure with reduced ejection fraction; LVEF ≤40%) and preserved (heart failure with preserved ejection fraction; LVEF ≥50%) ejection fraction. Grouping of continuous measurements into narrow categories can be questioned if their variability is high.

Methods and Results

We constructed a cohort of all 9716 new cases of chronic heart failure with an available LVEF in Stockholm, Sweden, from January 1, 2015, until December 31, 2020. All values of LVEF were collected over time, and patients were followed up until death, moving out of Stockholm, or end of study. Mixed models were used to quantify within‐person variance in LVEF, and multistate Markov models, with death as an absorbing state, to quantify the stability of LVEF categories. LVEF values followed a normal distribution. The SD of the within‐person variance in LVEF over time was 7.4%. The mean time spent in any LVEF category before transition to another category was on average <1 year for heart failure with mildly reduced ejection fraction. Probabilities of transitioning between categories during the first year were substantial; patients with heart failure with mildly reduced ejection fraction had a probability of <25% of remaining in that category 1 year later.

Conclusions

LVEF follows a normal distribution and has considerable variability over time, which may impose a risk for underuse of efficient treatment. The heart failure with mildly reduced ejection fraction category is especially inconstant. Assumptions of a patient's current LVEF should take this variability and the normal distribution of LVEF into account.
Speaking “Mouth to Mouth” (Num 12:8)
Authors: Berman Joshua
Published: April 2024

The phrase פה אל פה אדבר בו in Num 12:8a is generally taken to mean to speak with Moses “face to face.” However, commentators have noted that this understanding presents grammatical difficulties. In this study I propose a new understanding of the idiom and argue that it refers to oral transmission, from one speaking agent to the next in a linear chain. This idiomatic use of the phrase “mouth to mouth” is found in ancient Egyptian texts and widely across many cultures. This understanding of the idiom פה אל פה is animated further by a re-examination of four pieces of textual data: a) the meaning of the phrase בכל ביתי נאמן הוא in Num 12:7, and specifically an interpretation widespread in rabbinic commentary, but absent from modern exegesis; b) the meanings and diffusion of the prepositional verb דבר ב; c) the morphologies of various פה-פה expressions found in 2 Kings, Jeremiah, and Ezra; d) the structural and thematic similarities of Num 11 and Num 12.
Species Diversity of the Leafhopper Tribe Paralimnini Distant (Hemiptera: Cicadellidae: Deltocephalinae) from Pakistan, with Description of Two New Genera
Authors: Naveed Hassan , Hassan Muhammad Asghar , Zhang Yalin , Chen Keping
Published: April 2024

Paralimnini Distant, 1908, is a notable leafhopper tribe that exhibits a wide distribution across all biogeographical regions, namely the Palearctic, Nearctic, Afrotropical, Oriental, Neotropical, and Australian regions. Among these, the Oriental region demonstrates the highest diversity of Paralimnini, with a significant portion of this diversity remaining unexplored according to recent investigations. This study focuses on examining 10 species under seven genera of the Paralimnini leafhopper tribe found in Pakistan. A comprehensive morphological study is conducted, which includes the description of two new genera, Paralimnolus gen. nov. and Lalianlus gen. nov., with P. bicolor sp. nov. and L. bifurcates sp. nov. within the tribe. The study meticulously describes and provides illustrations of all the taxa based on careful observations of specimens obtained from Pakistan. Additionally, the study furnishes an updated checklist and a key to facilitate the identification of known and new Pakistani genera belonging to the tribe Paralimnini. The present findings shed light on the diversity and distribution patterns of the Paralimnini tribe in Pakistan, particularly emphasizing the junction of the Oriental and Palearctic regions in the northern parts, as these parts of the country serve as a significant reservoir of undocumented species. The thorough documentation and available identification resources provided in this study serve as valuable references for future investigations and contribute to our knowledge of the leafhopper fauna in Pakistan.
Dual Stratification on the Double Diffusive Magnetohydrodynamics Flow of Nanofluids with Dissipation Effects-Revised Buongiorno Model
Authors: Suriyakumar P. , kumar S. Suresh , Al-Mdallal Qasem M. , Ganesh N. Vishnu
Published: April 2024

We analyze the effects of double stratification and dissipation on the hydro magnetic free convection flow of nanofluids over a vertical plate in this work. Considered two different kinds of nanofluids, such as copper and alumina–water nanofluids. By employing the similarity transformation,
partial differential equations are converted into non-linear ordinary differential equations, which can be numerically computed with MATLAB. In practical situations where the heat and mass transfer mechanisms run simultaneously, the analysis of natural convection in the influence of double
stratification is a fundamentally interesting and important problem, because of its broad range of engineering applications. These applications include the rejection of heat into the environment, such as lakes, rivers, and seas; the storage of thermal energy, such as solar ponds; and the transmission
of heat from thermal sources, such as the condensers of power plants. To highlight the impact of double stratification and dissipation on the hydromagnetic free convective flow of nanofluid over a vertical plate, a wide variety of parameter values are used. The numerical outcomes for the different
parameters of velocity, temperature, volume fraction, and concentration are obtained and displayed graphically. The skin friction coefficient and reduced Nusselt number are also determined numerically and tabulated.
Effect of Three Types of Gravity Modulation on Rivlin Ericksen Nanofluid Saturated in Porous Medium with Internal Heating
Authors: Ismail  , Bhadauria B. S.
Published: April 2024

In this paper, authors have studied the Rivlin-Ericksen elastico-viscous nanofluid thermal instability with internal heating under three types of gravity modulation in a horizontal layer of porous medium using both linear and nonlinear ways. Linear stability analysis is done using normal
mode approach, whereas nonlinear stability analysis is done using truncated Fourier series method. The results demonstrate that the internal heating, modified diffusivity ratio, and concentration Rayleigh number advance the initiation of convective motion in the system. On the other hand,
Darcy number stabilize the system. To understand the behaviour of mass/heat transfer in the system two different approaches viz Mathematica NDSolve and Runge-Kutta-Fehlberg method (RKF-45) are used, and it is found that the rate of heat/mass transfer is exactly the same in both cases. In comparison
to other gravity modulation profiles, day-night gravity modulation profile accelerates mass/heat transfer more quickly than the other two types of gravity modulation profiles. Steady state graph has demonstrated, convection occurs earlier when internal heating and amplitude values are increased.
Moreover, it is also observed that heat/mass transport is very much affected by the variation of kinematic viscoelasticity parameter.