bluuebunny/crossref_metadata_2025_split huggingface dataset:
MPU: Memory-centric SIMT Processor via In-DRAM Near-bank Computing
Authors: Xie Xinfeng , Gu Peng , Ding Yufei , Niu Dimin , Zheng Hongzhong , Xie Yuan 
Published: May 2023

With the growing number of data-intensive workloads, GPU, which is the state-of-the-art single-instruction-multiple-thread (SIMT) processor, is hindered by the memory bandwidth wall. To alleviate this bottleneck, previously proposed 3D-stacking near-bank computing accelerators benefit from abundant bank-internal bandwidth by bringing computations closer to the DRAM banks. However, these accelerators are specialized for certain application domains with simple architecture data paths and customized software mapping schemes. For general-purpose scenarios, lightweight hardware designs for diverse data paths, architectural supports for the SIMT programming model, and end-to-end software optimizations remain challenging.To address these issues, we propose Memory-centric Processing Unit (MPU), the first SIMT processor based on 3D-stacking near-bank computing architecture. First, to realize diverse data paths with small overheads, MPU adopts a hybrid pipeline with the capability of offloading instructions to near-bank compute-logic. Second, we explore two architectural supports for the SIMT programming model, including a near-bank shared memory design and a multiple activated row-buffers enhancement. Third, we present an end-to-end compilation flow for MPU to support CUDA programs. To fully utilize MPU’s hybrid pipeline, we develop a backend optimization for the instruction offloading decision. The evaluation results of MPU demonstrate 3.46× speedup and 2.57× energy reduction compared with an NVIDIA Tesla V100 GPU on a set of representative data-intensive workloads.
The release of prolylcarboxypeptidase delays endothelial cell function loss
Authors: Shariat-Madar Zia , Boullard Nicholas , Thrash Caitlin 
Published: May 2023

Prolylcarboxypeptidase (PRCP) is a risk factor for cardiovascular disease. Its functions are well-characterized. It is a critical factor for preserving cellular function by regulating angiotensin, prekallikrein, as well as des-Arg9-bradykinin, induced cell signaling. Several studies, including ours, provide evidence that PRCP levels influence vascular biology. An increased circulating level of PRCP is observed and is implemented in the pathogenesis of several chronic inflammatory diseases. The expression pattern and function of PRCP, a lysosomal serine protease, caused by long-time culture has not been thoroughly investigated. Brefeldin A (0.2 mM), an inhibitor of protein trafficking in the secretory pathway, was ineffective in blocking PRCP release, signifying that PRCP might be secreted via an uncharacterized exocytotic pathway. Cellular senescence, a driving force of age-related dysfunction, can differentially alter the expression of lysosomal enzymes. Here, two structurally distinct lysosomal enzymes, PRCP and SA β-galactosidase, were used to identify their expression pattern during the progression of senescence in endothelial cells. Increased expression of PRCP occurred in parallel to a decline in telomerase reverse transcriptase (hTERT) mRNA levels in the early stages of cellular senescence. However, independent of pH alterations, SA β-galactosidase expression was significantly ( P ≤ 0.5) higher in senescent cells compared to those in early-passage cells. Unlike SA β-galactosidase, expression and activity of PRCP was significantly ( P ≤ 0.5) declined in the later stages of cellular senescence. Our findings support the notion that PRCP potentially has a physiological role in delaying cellular senescence via suppressing reactive oxygen species production, endothelial cell function loss, and may have major implications on endothelial aging. Overhead account, University of Mississippi This is the full abstract presented at the American Physiology Summit 2023 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.
Establishment of acute hypergravity in vivo model
Authors: Endo Yasuhiro , Fujita Masanori , Tandai-Hiruma Megumi , Nakamura Shingo , Ikewaki Katsunori 
Published: May 2023

Introduction: Fighter and acrobatic flight pilots are exposed to short-term cerebral hypoperfusion or cerebral ischemia by hypergravity.　Preventive therapy against hypergravity stress in pilots has been sought in recent years and needs to be developed in animal models as translational research. In this study, we developed acute hypergravity in vivo models, which can be gravity loaded arbitrarily, and the blood pressure, pulse rate, and hemodynamics over time during gravity loading can also be measured. Methods/Results: In this model, 9w male SD rats were anesthetized with sevoflurane (induction 5% for 4 min, maintenance 3%) by inserting catheters in the left femoral and right carotid arteries. After intraperitoneal injection including medetomidine 0.15 mg/kg + midazolam 2 mg/kg + butorphanol 2.5 mg/kg, the rats were loaded with+1Gz~ +5 Gz for 2 minutes by a hypergravity system (Tommy Seiko, Bio Research Center). We connected the system to the femoral catheter, and we used Labchart Software (ADInstruments) to monitor blood pressure and heart date during gravity loading. Then, we used i-stat(Abbot) to measure biomarkers, including lactate acid, via the right carotid catheter from 1min to 10min after gravity-loading Conclusion: Our acute hypergravity model enables us to monitor hemodynamics during gravity loading and measure the dynamics of biomarkers with short half-lives, such as lactic acid. This model applies to the evaluation of the kinetics of hypergravity-induced oxidative stress, including hydroxyl radicals and facilitate translational research. No Conflict of Interest This is the full abstract presented at the American Physiology Summit 2023 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.
Loss of GPR19 drives obesity-related cardiac dysfunction in mice
Authors: Mushala Bellina , Xie Bingxian , McMahon Brenda , Thapa Dharendra , Jurczak Michael , Scott Iain 
Published: May 2023

Background: Obesity is the second leading cause of preventable death in the United States and serves as a fundamental risk factor for cardiovascular disease. Dysregulated energy metabolism in hearts from obese subjects constrains cardiac contractile function under conditions of increased workload. G protein-coupled receptor (GPCR) signaling cascades play a key role in cardiovascular homeostasis, and are potential therapeutic targets to alleviate obesity-induced cardiac dysfunction. GPR19 is a poorly characterized class A orphan GPCR that is differentially expressed in several peripheral tissues, including robust expression in the heart. Recent reports from our group implicate GPR19 in a novel signaling pathway regulating mitochondrial energy metabolism in cardiac cells. However, evidence of its pathophysiological relevance in systemic or tissue-specific homeostasis has yet to be elucidated. Hypothesis: We hypothesize that GPR19 signaling mediates nutrient signaling and cardiac energy metabolism to preserve myocardial contractile function in diet-induced obesity. Methods: We used novel whole-body GPR19 knockout mice and subjected them to metabolic cage, echocardiography, and isolated perfused working heart analysis. This preliminary characterization was designed to understand the systemic effects of GPR19 depletion on cardiac and whole-body physiology under low-fat and high-fat fed conditions. Results: We report that GPR19 KO mice exhibit sex-dependent changes in both body and heart weight, increased energy expenditure, decreased physical activity, and markers of altered cardiac hemodynamics and energy metabolism. Conclusion: These findings define a new role for the GPR19 signaling pathway in the regulation of cardiac metabolic homeostasis, and thus highlight it as a potential target for therapeutic interventions in obesity-induced cardiovascular dysfunction. The project described was supported by NIGMS T32GM133332 and NHLBI R01HL147861. This is the full abstract presented at the American Physiology Summit 2023 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.
Emodin protects lipopolysaccharide-induced myocardial injury and mitochondrial dysfunction via PI3K/AKT signaling pathway based on Network Pharmacology
Authors: Liu Yanru , Liu Hanqiong , Sun Wenwen , Li Tao , Lin Bohan , Liu Wei , Zhang Hao , Shi Liang 
Published: May 2023

Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. Cardiac dysfunction is a significant manifestation of sepsis and it is associated with the prognosis of the disease. It is assumed that damage to myocardial mitochondrial function is one of the main causes of cardiac dysfunction in septic patients, and the repair of myocardial mitochondrial function may alleviate cardiac dysfunction in septic patients. Emodin has been discovered to serve a variety of pharmacological effects, including anti-tumor, anti-inflammatory, antioxidant, and anti-apoptotic properties. In this study, we investigated the potential protective effect of Emodin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation. The model of myocardial injury induced by LPS was established and divided into three groups: the control group, the lipopolysaccharide (LPS) group, and the LPS+Emodin group. The apoptosis rate, reactive oxygen species (ROS), mitochondrial permeability transition pore(MPTP), and mitochondrial membrane potential (MMP) were determined in LPS-induced sepsis Cardiacmyocytes treated with different concentrations of Emodin. In addition, the degree of myocardial mitochondrial damage was evaluated by electron microscopy. Signal pathway-related proteins were determined by Western blotting in vitro. And then, network pharmacology screening revealed TP53, CASP3, ILB, MYC, TNF, PTGS2, and PPARG as the critical overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 10 enriched biological processes and signaling pathways associated with the therapeutic effects of emodin on sepsis. The results show the PI3K-AKT pathway is mainly involved in the emodin-sepsis myocardial injury network. Meanwhile, Emodin has been demonstrated to protect the myocardium from LPS-induced myocardial injury in vitro, and moderate doses of Emodin showed the most prominent effect. Emodin alleviates mitochondrial damage by reducing apoptosis and inhibiting oxidative stress and ameliorates protecting LPS-induced myocardial injury and mitochondrial dysfunction through the PI3K-AKT pathway. This provides a feasible strategy for preventing and treating myocardial injury and mitochondrial dysfunction in sepsis. This study was supported by the Science and Technology Bureau of Zhengjiang (Grant No.SH2022068 and SH2022042). This is the full abstract presented at the American Physiology Summit 2023 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.
A novel mouse model for an inducible gene-modification in the renal thick ascending limb
Authors: Bourqui Laurent , Winter Denise V. , Odermatt Alex , Loffing-Cueni Dominique , Loffing Johannes 
Published: May 2023

The thick ascending limb (TAL) is critical for the renal control of fluid and ion homeostasis. The function of the TAL depends on the activity of the bumetanide-sensitive Na-K-2Cl co-transporter NKCC2, which is highly abundant in the luminal membrane of TAL cells. The TAL function is regulated by various hormonal and non-hormonal factors. However, many of the underlying signal transduction pathways remain elusive. Here, we describe the characterization of a novel gene-modified mouse model for an inducible and specific Cre/Lox-mediated gene modification in the TAL. In these mice, a tamoxifen-dependent Cre (CreERT2) was inserted into the 3’ UTR of the Slc12a1 gene, which encodes NKCC2 (Slc12a1-CreERT2). Although this gene-modification strategy reduced endogenous NKCC2 expression at the mRNA and protein level, the lowered NKCC2 abundance was not associated with an altered urinary fluid and ion excretion. Likewise, the renal response to loop-diuretics or water restriction was similar in wildtype (wt) and in Slc12a1-CreERT2wt/tg mice. Immunohistochemistry on kidneys from Slc12a1-CreERT2 mice revealed strong Cre expression exclusively in TAL cells but not in any other nephron portion. Cross-breeding of these mice with the mT/mG reporter mouse line showed a very low recombination rate (0.22%) at baseline, but a complete recombination (100%) after repeated tamoxifen administration. The achieved recombination encompassed the entire TAL and included also the macula densa. Thus, the new Slc12a1-CreERT2wt/tg mouse line allows an inducible and very efficient gene-targeting in the TAL and hence promises to be a powerful tool to advance our understanding of the regulation of TAL function. The research of Johannes Loffing is supported by the Swiss National Science Foundation (310030_143929/1) and the Swiss National Centre for Competence in Research “Kidney.CH” This is the full abstract presented at the American Physiology Summit 2023 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.
Constitutive Loss of Ptpn2 in Mice Causes Features of Anemia Including Iron Deficiency
Authors: Lei Hillmin , Shawki Ali , Spalinger Marianne , Canale Vinicius , Santos Alina , Chatterjee Pritha , Crawford Meli’sa , Manz Salomon , Scharl Michael , McCole Declan 
Published: May 2023

Background: Anemia is the most frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and is associated with the risk of Crohn’s disease. Anemia significantly impairs quality of life, increases hospitalization rates, and increases medical care costs of IBD patients. Iron deficiency is the most frequent cause of anemia in IBD; however, the mechanisms involved are still poorly understood. Here, we investigated the role of the IBD risk gene, protein tyrosine phosphatase non-receptor type 2 ( PTPN2), in regulating iron homeostasis. Methods: Constitutive Ptpn2 wild type (WT), heterozygous (Het), and knockout (KO) 3-week-old mice were analyzed for serum iron content, complete blood count parameters, and intestinal and extraintestinal non-heme iron. Protein and RNA from duodenal epithelial cells (DECs) were assayed by western blotting and qPCR. Localization of the brush border ferrous iron transporter, DMT1, and the ferrous iron absorption driver, NHE3, in duodenal tissue was determined by immunohistochemistry (IHC). Results: Ptpn2-KO mice had reduced i) serum iron ( p=0.0007; n=10); ii) serum iron carrier transferrin saturation ( p=0.0077; n=8); iii) hemoglobin ( p=0.0002; n=5); iv) hematocrit ( p=0.0023; n=5); v) intestinal non-heme iron: duodenum ( p=0.0128; n=10) and jejunum ( p=0.0006; n=8); and vi) extraintestinal tissue non-heme iron: liver ( p=0.0014; n=10), spleen ( p=0.04; n=10), kidney ( p=0.0004; n=7), and gastrocnemius muscle ( p=0.0436; n=9) vs. Ptpn2-WT and Het mice. This indicated that loss of Ptpn2 causes characteristics of anemia including decreased serum iron and tissue iron storage and impaired intestinal iron homeostasis. DEC gene expression of the intracellular iron storage molecule ferritin ( Fth1) was reduced ( p=0.048; n=4) while the basolateral cellular iron importer transferrin receptor 1 ( Tfrc1) was significantly increased ( p=0.0048; n=5) in Ptpn2-KO mice. Reduced FTH1 protein expression ( p=0.007; n=12) and increased TFRC1 protein expression ( p=0.0021; n=8) in DECs of Ptpn2-KO mice was confirmed by western blot, indicating cellular iron deficiency. DMT1 (n=6) and NHE3 (n=8) protein expression in DECs was unaltered, whereas IHC showed reduced apical membrane DMT1 and NHE3 in the duodenal epithelium of Ptpn2-KO mice (n=6), suggesting a possible mechanism of impaired intestinal non-heme iron uptake. Conclusions: Loss of Ptpn2 in mice causes features of anemia including iron deficiency associated with mislocalization of DMT1 and reduced apical membrane expression of NHE3. These findings identify a critical role for PTPN2 in regulating systemic iron homeostasis. This is the full abstract presented at the American Physiology Summit 2023 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.
Establishing the reproducibility of mitochondrial capacity using near-infrared spectroscopy
Authors: Landers-Ramos Rian , Dietz Grace , Chartier Gregory , Knuth Nicolas 
Published: May 2023

Near infrared spectroscopy (NIRS) has been used as a valid measure of skeletal muscle oxidative capacity. Some studies have indicated non-uniform measures of NIRS-derived measures of oxygen consumption within a specific muscle bed. Thus, determining standardization of protocols and reproducibility of NIRS-derived muscle oxidative capacity is critical to ensure trusted responses. OBJECTIVE: Establish the reproducibility of NIRS-derived skeletal muscle oxidative capacity within the medial gastrocnemius muscle. We hypothesized that assessments of mitochondrial capacity using NIRS would yield strong intra- and inter-day reproducibility. METHODOLOGY: Ten healthy adults (30 ± 11 years old) participated in two visits to the lab scheduled 2-7 days apart. For each visit, a NIRS device was placed on the belly of the medial gastrocnemius muscle of the subject’s dominant leg, and electrical stimulation pads were placed directly above and below the NIRS device. A pneumatic cuff capable of rapid inflation was placed on the same leg proximal to the tibiofemoral joint. Laying supine, electrical stimulation was applied for 30s followed immediately by 6 rapid arterial occlusions lasting 5s each with 5s recovery between occlusions. The protocol was repeated three times for a total of four tests, and a physiological calibration was performed to correct for changes in blood volume. Differences in oxygenated and deoxygenated hemoglobin (Hbdiff) were collected continuously using NIRS. Recovery rate constants (min-1) following electrical stimulation were derived from analyses of Hbdiff signals to estimate skeletal muscle oxidative capacity. Location of the device was marked, and the protocol was repeated 2-7 days later. Coefficient of variation (CV%) and intraclass correlation coefficients (ICC) was used to determine intra- and inter-day reproducibility of results. RESULTS: The average recovery rate constant for oxygen consumption was 2.09 ± 0.24 min-1 on Day 1 and 2.07 ± 0.25 min-1 on Day 2 (p=0.91). Day 1 CV and ICC for four repeated trials was 11.9% and 0.888, respectively. Day 2 CV and ICC was 12.1 % and 0.700, respectively. Inter-day CV was 10.1% and inter-day ICC was 0.881. CONCLUSIONS: The intra- and inter-day CV and ICC for mitochondrial capacity measures of the medial gastrocnemius indicated good reproducibility using NIRS. These data support the use of NIRS to reliably assess mitochondrial capacity in younger adults. Supported by Towson University (TU) School of Emerging Technology, TU Summer Undergraduate Research Institute, and the APS John F. Perkins Research Enhancement Award This is the full abstract presented at the American Physiology Summit 2023 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.
Human physiology undergraduates display low baseline subjective and objective understanding of cardiovascular health disparities in LGBTQ+ populations
Authors: Moreira Jesse , Streed Carl , Silva Vanessa , Fetterman Jessica 
Published: May 2023

Introduction: Cardiovascular disease (CVD) is known to disproportionately burden lesbian, gay, bisexual, transgender, queer, (LGBTQ+) communities. Few physiology classrooms, however, incorporate population-specific mechanisms of CVD, including Minority Stress and associated psychological/physiological sequelae, when discussing disease mechanisms. Hypothesis: We hypothesized that baseline student measures of understanding regarding LGBTQ+ CVD burden and mechanisms would be low. Methods: Students enrolled in an undergraduate senior-level Cardiovascular Pathophysiology course were surveyed using Qualtrics. Likert-scale questions assessed agreement with understanding of LGBTQIA2S+ health disparity presence and mechanism. Open-ended prompts evaluated objective ability to explain understanding of CVD mechanisms in LGBTQ+ populations. Results: Of the 45 survey respondents, 12 (27.3%) identified as cisgender men, 30 (68.2%) identified as cisgender women, and 2 (4.5%) identified as non-binary. Regarding self-reported race/ethnicity, 7 respondents (15.9%) identify as Latine/Hispanic, 23 (48.9%) as White, 21 (44.7%) as Asian, 2 (4.25%) as Middle Eastern, and 1 (2.15%) preferred not to disclose. For sexuality, 32 (66.67%) identified as Straight/Heterosexual, 5 (10%) as lesbian/gay, 6 (13%) as bisexual, 1 (2%) as asexual, and 4 (8%) as queer. The majority of respondents (66%) reported “no previous” or “minimal previous” exposure to CVD disparity in LGBTQIA2S+ populations. Median Likert score (1-5, 1 representing high disagreement and 5 high agreement) for agreement with understanding that LGBTQ+ individuals face specific health disparities was 5.0 (interquartile range (IQR) 25%-75%: 4-5), median Likert score for agreement with understanding the mechanisms of LGBTQ+ health disparities was 2.0 (IQR 25%-75%: 2-4), and median Likert score for student agreement with understanding of how to intervene in LGBTQ+ specific health disparities was 3.0 (IQR 25%-75%: 2-4). The majority of students (70%) responded “I do not know” to the open-response prompt regardingthe mechanisms associating CVD with psychosocial stress in LGBTQ+ populations. Conclusion: Undergraduate students are aware of the CVD burden in LGBTQ+ populations, but lack understanding of the mechanisms behind the increased CVD risk or how to intervene. Curricularreform addressing LGBTQ+ specific CVD mechanismsand the biology ofpsychosocial stress is neededto foster understanding and creatediversely-educated future clinicians and scientists. This is the full abstract presented at the American Physiology Summit 2023 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.