bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generic modelling to develop thermal yield nomograms for coaxial deep borehole heat exchangers (DBHEs)
Authors: Banks David , Brown Christopher S. , Kolo Isa , Falcone Gioia 
Published: May 2024

Numerical modelling of coaxial deep borehole heat exchangers (DBHEs) can be resource-intensive. Simpler, transparent analytical models and nomograms would be valuable to developers and geologists for evaluating thermal output. In this paper, Beier’s published analytical computational model was used to produce nomograms of geothermal heat yield by systematically varying the DBHE depth and rock thermal conductivity, while assuming two generic simplified DBHE designs, a geothermal gradient of 25°C km
−1
and a fluid circulation rate of 5 l s
−1
. Continuous 25 year heat yields from a 1000 m DBHE range from 27.3 to 54.8 kW for thermal conductivities of 1.6–3.6 W m
−1
K
−1
. For a 3000 m DBHE, they range from 165 to 281 kW. Effective borehole thermal resistance (
R
b,eff
) increases strongly as DBHE depth increases due to internal heat transfer between the upflow and downflow elements. Simulations correspond well with results from industry-standard Earth Energy Designer software for a shallow 200 m coaxial BHE. They modestly underestimate the OpenGeoSys numerical modelled thermal yields by 2–4% for DBHE in the depth range 1000–3000 m. Modelled temperature evolution closely approximates an analytical ‘line heat source’ approach, implying that simpler analytical approaches are plausible for DBHE simulation. Future research should focus on methods for forward quantification of
R
b,eff
.
FASA-DRAM: Reducing DRAM Latency with Destructive Activation and Delayed Restoration
Authors: Du Haitao , Qin Yuhan , Chen Song , Kang Yi 
Published: May 2024

DRAM memory is a performance bottleneck for many applications, due to its high access latency. Previous work has mainly focused on data locality, introducing small but fast regions to cache frequently accessed data, thereby reducing the average latency. However, these locality-based designs have three challenges in modern multi-core systems: (1) inter-application interference leads to random memory access traffic, (2) fairness issues prevent the memory controller from over-prioritizing data locality, and (3) write-intensive applications have much lower locality and evict substantial dirty entries. With frequent data movement between the fast in-DRAM cache and slow regular arrays, the overhead induced by moving data may even offset the performance and energy benefits of in-DRAM caching.
In this article, we decouple the data movement process into two distinct phases. The first phase is Load-Reduced Destructive Activation (LRDA), which destructively promotes data into the in-DRAM cache. The second phase is Delayed Cycle-Stealing Restoration (DCSR), which restores the original data when the DRAM bank is idle. LRDA decouples the most time-consuming restoration phase from activation, and DCSR hides the restoration latency through prevalent bank-level parallelism. We propose FASA-DRAM, incorporating destructive activation and delayed restoration techniques to enable both in-DRAM caching and proactive latency-hiding mechanisms. Our evaluation shows that FASA-DRAM improves the average performance by 19.9% and reduces average DRAM energy consumption by 18.1% over DDR4 DRAM for four-core workloads, with less than 3.4% extra area overhead. Furthermore, FASA-DRAM outperforms state-of-the-art designs in both performance and energy efficiency.
A Hardware Approach For Accelerating Inductive Learning In Description Logic
Authors: Algahtani Eyad 
Published: May 2024

The employment of Machine Learning (ML) techniques in embedded systems has seen constant growth in recent years, especially for black-box ML techniques (such as Artificial Neural Networks (ANNs)). However, despite the successful employment of ML techniques in embedded environments, their performance potential is constrained by the limited computing resources of their embedded computers. Several hardware-based approaches were developed (e.g., using FPGAs and ASICs) to address the constraints of limited computing resources. The scope of this work focuses on improving the performance for Inductive Logic Programming (ILP) on embedded environments. ILP is a powerful logic-based ML technique that uses logic programming to construct human-interpretable ML models, where those logic-based ML models are capable of describing complex and multi-relational concepts. In this work, we present a hardware-based approach that accelerates the hypothesis evaluation task for ILPs in embedded environments that use Description Logic (DL) languages as their logic-based representation. In particular, we target the

\(\mathcal {ALCQ}^{\mathcal {(D)}}\)

language. According to experimental results (through an FPGA implementation), our presented approach has achieved speedups up to 48.7-fold for a disjunction of 32 concepts on 100 M individuals, where the baseline performance is the sequential CPU performance of the Raspberry Pi 4. For role and concrete role restrictions, the FPGA implementation achieved speedups up to 2.4-fold (for MIN cardinality role restriction on 1M role assertions); all FPGA implemented role and concrete role restrictions have achieved similar speedups. In the worst-case scenario, the FPGA implementation achieved either a similar or slightly better performance than the baseline (for all DL operations); the worst-case scenario resulted from using small datasets such as: using conjunction and disjunction on < 100 individuals, and using role and concrete (float/string) role restrictions on < 100,000 assertions.
Does acute heat stress alter lactation performance in postpartum mothers?
Authors: Lefebvre KarLee , Razi Yasamin , Klarner Taryn , Newhouse Ian , Ravanelli Nicholas 
Published: May 2024

Introduction: Heat stress has been shown to acutely decrease lactation performance in various mammalian species, however whether a similar effect is present in humans remains largely unexplored. Objective and hypothesis: The objective of the present study was to determine whether an acute whole-body heat stress reduces lactation performance in postpartum mothers in the proceeding 24 h. Methods: To date, 9 postpartum mothers (32±4 y; 1.6 ±0.1 m; 67±13 kg; 8±3 months postpartum) have participated in the study. During the 24 h period before and after the acute passive heat stress, participants were asked to record their voluntary fluid intake and their milk production defined as the volume of expressed milk and/or breastfeeding volume based on the baby’s weight before and immediately after nursing, accounting for evaporative water losses. The passive heat stress protocol involved participants laying supine while donning a tube-lined garment continuously perfused with 49°C water for 60 minutes. Rectal temperature and heart rate were measured during the passive heat stress intervention to confirm thermal strain, and whole-body sweat losses were calculated as the net difference in body mass following passive heat stress. Results: The 60-minute passive heat stress protocol increased rectal temperature by 0.4±0.3°C, increased heart rate (17±12 BPM), and resulted in a whole-body sweat loss of 278±201 g. The frequency of lactation was similar during the 24 h before (5.4±1.6 times) and 24 h after (5.1±1.1 times, P=0.20) acute passive heat stress. The total volume of human milk production in the 24 h prior to heat stress was not different to the 24 h following heat stress (pre: 327±123 ml, post: 312±148 ml, P=0.33). Maternal fluid intake was higher during the 24 h after passive heat stress (1561±73 ml) in comparison to the 24 h before (1377±244 ml, P=0.05). Conclusion: Preliminary data suggests that an acute bout of whole-body heat stress does not modulate lactation performance in postpartum mothers. This research was supported by Dr. Ravanelli’s Natural Sciences and Engineering Research Council of Canada Discovery Grant (PIN#2022-05096). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Anti-EGFR Antibody–Drug Conjugate Carrying an Inhibitor Targeting CDK Restricts Triple-Negative Breast Cancer Growth
Authors: Cheung Anthony , Chenoweth Alicia M. , Johansson Annelie , Laddach Roman , Guppy Naomi , Trendell Jennifer , Esapa Benjamina , Mavousian Antranik , Navarro-Llinas Blanca , Haider Syed , Romero-Clavijo Pablo , Hoffmann Ricarda M. , Andriollo Paolo , Rahman Khondaker M. , Jackson Paul , Tsoka Sophia , Irshad Sheeba , Roxanis Ioannis , Grigoriadis Anita , Thurston David E. , Lord Christopher J. , Tutt Andrew N. J. , Karagiannis Sophia N. 
Published: May 2024

Abstract

Purpose:
Anti-EGFR antibodies show limited response in breast cancer, partly due to activation of compensatory pathways. Furthermore, despite the clinical success of cyclin-dependent kinase (CDK) 4/6 inhibitors in hormone receptor–positive tumors, aggressive triple-negative breast cancers (TNBC) are largely resistant due to CDK2/cyclin E expression, whereas free CDK2 inhibitors display normal tissue toxicity, limiting their therapeutic application. A cetuximab-based antibody drug conjugate (ADC) carrying a CDK inhibitor selected based on oncogene dysregulation, alongside patient subgroup stratification, may provide EGFR-targeted delivery.

Experimental Design:
Expressions of G1/S-phase cell cycle regulators were evaluated alongside EGFR in breast cancer. We conjugated cetuximab with CDK inhibitor SNS-032, for specific delivery to EGFR-expressing cells. We assessed ADC internalization and its antitumor functions in vitro and in orthotopically grown basal-like/TNBC xenografts.

Results:
Transcriptomic (6,173 primary, 27 baseline, and matched post-chemotherapy residual tumors), single-cell RNA sequencing (150,290 cells, 27 treatment-naïve tumors), and spatial transcriptomic (43 tumor sections, 22 TNBCs) analyses confirmed expression of CDK2 and its cyclin partners in basal-like/TNBCs, associated with EGFR. Spatiotemporal live-cell imaging and super-resolution confocal microscopy demonstrated ADC colocalization with late lysosomal clusters. The ADC inhibited cell cycle progression, induced cytotoxicity against high EGFR-expressing tumor cells, and bystander killing of neighboring EGFR-low tumor cells, but minimal effects on immune cells. Despite carrying a small molar fraction (1.65%) of the SNS-032 inhibitor, the ADC restricted EGFR-expressing spheroid and cell line/patient-derived xenograft tumor growth.

Conclusions:
Exploiting EGFR overexpression, and dysregulated cell cycle in aggressive and treatment-refractory tumors, a cetuximab–CDK inhibitor ADC may provide selective and efficacious delivery of cell cycle–targeted agents to basal-like/TNBCs, including chemotherapy-resistant residual disease.
miR-497 Target Gene Regulatory Network in Angiosarcoma
Authors: Benton Annaleigh , Moriarty Noah M. , Terwilliger Emma , Liu Bozhi , Murphy Ant , Maluvac Hannah , Shu Mae , Gartenhaus Lauren E. , Janson Nimod D. , Pfeffer Claire M. , Utturkar Sagar M. , Parkinson Elizabeth I. , Lanman Nadia A. , Hanna Jason A. 
Published: May 2024

Abstract
Angiosarcoma is a vascular sarcoma that is highly aggressive and metastatic. Because of its rarity, treatment options for patients are limited. Therefore, more research is needed to identify possible therapeutic vulnerabilities. We previously found that conditional deletion of Dicer1 drives angiosarcoma development in mice. Given the role of DICER1 in canonical miRNA biogenesis, this suggests that miRNA loss is important in angiosarcoma development. After testing miRNAs previously suggested to have a tumor-suppressive role in angiosarcoma, miRNA-497-5p (miR-497) suppressed cell viability most significantly. We also found that miR-497 overexpression led to significantly reduced cell migration and tumor formation. To understand the mechanism of miR-497 in tumor suppression, we identified clinically relevant target genes using a combination of RNA-sequencing data in an angiosarcoma cell line, expression data from patients with angiosarcoma, and target prediction algorithms. We validated miR-497 direct regulation of cyclin-D2, cyclin-dependent kinase 6, and vesicle amine transport protein 1 (VAT1). One of these genes, VAT1, is an understudied protein that has been suggested to promote cell migration and metastasis in other cancers. Indeed, we find that pharmacologic inhibition of VAT1 with the natural product neocarzilin A reduces angiosarcoma migration.
Implications: This work supports the potent tumor-suppressive abilities of miR-497 in angiosarcoma, providing evidence for its potential as a therapeutic agent, and provides insight into the mechanisms of tumor suppression through analysis of the target gene regulatory network of miR-497.
Home Health Care Use and Outcomes After Coronary Artery Bypass Grafting Among Medicare Beneficiaries
Authors: Thompson Michael P. , Hou Hechuan , Likosky Donald S. , Pagani Francis D. , Falvey Jason R. , Bowles Kathryn H. , Wadhera Rishi K. , Sterling Madeline R. 
Published: May 2024

BACKGROUND:
Home health care (HHC) has been increasingly used to improve care transitions and avoid poor outcomes, but there is limited data on its use and efficacy following coronary artery bypass grafting. The purpose of this study was to describe HHC use and its association with outcomes among Medicare beneficiaries undergoing coronary artery bypass grafting.

METHODS:
Retrospective analysis of 100% of Medicare fee-for-service files identified 77 331 beneficiaries undergoing coronary artery bypass grafting and discharged to home between July 2016 and December 2018. The primary exposure of HHC use was defined as the presence of paid HHC claims within 30 days of discharge. Hierarchical logistic regression identified predictors of HHC use and the percentage of variation in HHC use attributed to the hospital. Propensity-matched logistic regression compared mortality, readmissions, emergency department visits, and cardiac rehabilitation enrollment at 30 and 90 days after discharge between HHC users and nonusers.

RESULTS:
A total of 26 751 (34.6%) of beneficiaries used HHC within 30 days of discharge, which was more common among beneficiaries who were older (72.9 versus 72.5 years), male (79.4% versus 77.4%), White (90.2% versus 89.2%), and not Medicare-Medicaid dual eligible (6.7% versus 8.8%). The median hospital–level rate of HHC use was 31.0% (interquartile range, 13.7%–54.5%) and ranged from 0% to 94.2%. Nearly 30% of the interhospital variation in HHC use was attributed to the discharging hospital (intraclass correlation coefficient, 0.296 [95% CI, 0.275–0.318]). Compared with non-HHC users, those using HHC were less likely to have a readmission or emergency department visit, were more likely to enroll in cardiac rehabilitation, and had modestly higher mortality within 30 or 90 days of discharge.

CONCLUSIONS:
A third of Medicare beneficiaries undergoing coronary artery bypass grafting used HHC within 30 days of discharge, with wide interhospital variation in use and mixed associations with clinical outcomes and health care utilization.
3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension
Authors: Ichimura Kenzo , Boehm Mario , Andruska Adam M. , Zhang Fan , Schimmel Katharina , Bonham Spencer , Kabiri Angela , Kheyfets Vitaly O. , Ichimura Shoko , Reddy Sushma , Mao Yuqiang , Zhang Tianyi , Wang Gordon X. , Santana Everton J. , Tian Xuefei , Essafri Ilham , Vinh Ryan , Tian Wen , Nicolls Mark R. , Yajima Shin , Shudo Yasuhiro , MacArthur John W. , Woo Y. Joseph , Metzger Ross J. , Spiekerkoetter Edda 
Published: May 2024

BACKGROUND:
Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure.

METHODS:
Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function.

RESULTS:
Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments.

CONCLUSIONS:
3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.
SMYD2-Methylated PPARγ Facilitates Hypoxia-Induced Pulmonary Hypertension by Activating Mitophagy
Authors: Li Yi , Wei Xiang , Xiao Rui , Chen Yongjie , Xiong Tianxin , Fang Ze-Min , Huo Bo , Guo Xian , Luo Hanshen , Wu Xingliang , Liu Liyuan , Zhu Xue-Hai , Hu Qinghua , Jiang Ding-Sheng , Yi Xin 
Published: May 2024

BACKGROUND:
Hyperproliferation of pulmonary arterial smooth muscle cells (PASMCs) and consequent pulmonary vascular remodeling are the crucial pathological features of pulmonary hypertension (PH). Protein methylation has been shown to be critically involved in PASMC proliferation and PH, but the underlying mechanism remains largely unknown.

METHODS:
PH animal models were generated by treating mice/rats with chronic hypoxia for 4 weeks. SMYD2-vTg mice (vascular smooth muscle cell-specific suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 (deformed epidural auto-regulatory factor-1) domain-containing protein 2 transgenic) or wild-type rats and mice treated with LLY-507 (3-cyano-5-{2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]-phenyl}-N-[(3-pyrrolidin-1-yl)propyl]benzamide) were used to investigate the function of SMYD2 (suppressor of variegation, enhancer of zeste, trithorax and myeloid Nervy DEAF-1 domain-containing protein 2) on PH development in vivo. Primary cultured rat PASMCs with SMYD2 knockdown or overexpression were used to explore the effects of SMYD2 on proliferation and to decipher the underlying mechanism.

RESULTS:
We demonstrated that the expression of the lysine methyltransferase SMYD2 was upregulated in the smooth muscle cells of pulmonary arteries from patients with PH and hypoxia-exposed rats/mice and in the cytoplasm of hypoxia-induced rat PASMCs. More importantly, targeted inhibition of SMYD2 by LLY-507 significantly attenuated hypoxia-induced pulmonary vascular remodeling and PH development in both male and female rats in vivo and reduced rat PASMC hyperproliferation in vitro. In contrast, SMYD2-vTg mice exhibited more severe PH phenotypes and related pathological changes than nontransgenic mice after 4 weeks of chronic hypoxia treatment. Furthermore, SMYD2 overexpression promoted, while SMYD2 knockdown suppressed, the proliferation of rat PASMCs by affecting the cell cycle checkpoint between S and G2 phases. Mechanistically, we revealed that SMYD2 directly interacted with and monomethylated PPARγ (peroxisome proliferator-activated receptor gamma) to inhibit the nuclear translocation and transcriptional activity of PPARγ, which further promoted mitophagy to facilitate PASMC proliferation and PH development. Furthermore, rosiglitazone, a PPARγ agonist, largely abolished the detrimental effects of SMYD2 overexpression on PASMC proliferation and PH.

CONCLUSIONS:
Our results demonstrated that SMYD2 monomethylates nonhistone PPARγ and inhibits its nuclear translocation and activation to accelerate PASMC proliferation and PH by triggering mitophagy, indicating that targeting SMYD2 or activating PPARγ are potential strategies for the prevention of PH.
Impacts of Greenland Ice Sheet on Blocking in Idealized Simulations
Authors: Ding Hairu , Dong Li , Liu Kaijun , Lin Ting , Xie Zhiang , Zhang Bo , Wang Xiaoxue 
Published: May 2024

Abstract
As the only remaining ice sheet in the Northern Hemisphere, the Greenland ice sheet (GrIS) plays a crucial role in influencing atmospheric circulations, particularly with its rapid melting under global warming. In this paper, the influences of GrIS topography and surface thermal conditions are investigated by a series of aquaplanet experiments. The results show that the GrIS topography induces stationary waves and favors more blocking events through the generation of negative potential vorticity (PV) anomalies, while it tends to suppress local storm activities through the induced stationary waves. The surface cooling center of the GrIS is found to strengthen the jet streams by enhancing the meridional temperature gradient and thermal wind, while it causes the PV and static stability to increase during near-Greenland blocking days, thereby disfavoring blocking onset. Altogether, the topography and surface thermal effects of GrIS appear to compete with each other so that the net effect would determine the final response. Nevertheless, nonlinearity is found in both GrIS-topography alone and GrIS-surface temperature alone experiments, where nonlinear responses of atmospheric circulation are detected when the GrIS topography height or surface temperature exceeds their critical values, respectively. Hence, through this study, the response of the blocking in the vicinity of Greenland to the combined effects of topography and surface thermal conditions may shed light on comprehending the underlying mechanism of blocking alteration in a changing climate.

Significance Statement
Although there have been numerous observation-based studies showing that the blocking around Greenland has increased over the past few decades, which is a predominant driver in accelerating the Greenland ice sheet (GrIS) melting, the reasons for this change are still unclear. In addition, the impact of GrIS on blocking still needs investigation. Through idealized aquaplanet simulations, this study examines the effect of GrIS’s topography and surface thermal conditions upon blocking onset. It suggests the nonlinearity of the blocking response in the vicinity of Greenland to the combined effects in the variation of the height and surface temperature of GrIS. This study will enhance our understanding of possible changes in blocking due to global warming.