bluuebunny/crossref_metadata_2025 huggingface dataset:
Network Lifetime Enhancement by Elimination of Spatially and Temporally Correlated RFID Surveillance Data in WSNs
Authors: Dash Lucy , Pattanayak Binod Kumar , Singh Debabrata , Samanta Debabrata , Rimal Yagyanath
Published: September 2022

In wireless sensor networks (WSNs), radio frequency identification (RFID) plays an important role due to its data characteristics which are data simplicity, low cost, simple deployment, and less energy consumption. It consists of a series of tags and readers which collect a huge number of redundant data. It increases system overhead and decreases overall network lifetime. Existing solutions like Time-Distance Bloom Filter (TDBF) algorithm are inapplicable to the large-scale environment. Received Signal Strength (RSS) used in this algorithm is highly dependent on quality of tag and application environment. In this paper, we propose an approach for data redundancy minimization for RFID surveillance data which is a modified version of TDBF. The proposed algorithm is formulated by using the observed time and calculated distance of RFID tags. To overcome these problems, we design our approach to relevantly reduce the spatiotemporal data redundancy in the source level by adding the Received Signal Strength Indicator (RSSI) concept for energy-efficient RFID data communication in wireless sensor network scenario. We introduce in this paper the new improved idea of an existing algorithm which efficiently reduces the rate of data redundancy spatially and temporally. The implemented results overcome the limitations of existing algorithm for data redundancy reduction. Nevertheless, the performance evaluation shows the efficiency of proposed algorithm in terms of time and data accuracy. Furthermore, this algorithm supports multidimensional and large-scale environment suitable for sensor network nowadays.
Automatic Control of Food Machinery Based on Neural Network and Computational Torque Compounding
Authors: Shao Huanxia
Published: September 2022

In order to improve the effect of automatic control of food machinery, this paper combines neural network and computational torque compounding to study the automatic control system of food machinery to improve the effect of automatic control of food machinery. Moreover, this paper studies the problem of strong time-varying nonlinear friction disturbance in the servo motion system, and analyzes the friction nonlinearity at low speed and commutation motion of the system. In addition, this paper introduces the application requirements for the nonlinear friction compensation control method, and proves that the designed controller can maintain the stability of the system under the condition of strong nonlinear time-varying friction through the Lyapunov stability principle. The experimental study shows that the control strategy given in this paper can not only effectively improve the tracking speed of the joints, but also effectively alleviate the later tremor, and the automatic control effect of food machinery based on neural network and computational torque compounding has certain effects.
Research on Multiobjective Optimization of Sponge City Based on SWMM Model
Authors: Luo Jie , Hu Peng , Sun Jie , Yang Ning , Liu Qi , Qin Na , Yuan Yingdong , Xu Guodong
Published: September 2022

With the acceleration of urbanization, the hardened area of the city is increasing, the rainwater runoff is increasing, and the pressure on the urban drainage network is increasing, resulting in urban waterlogging which seriously endangers people's travel safety. SC (sponge city) should take the city as the catchment area, and through the self-regulation of the water system, reduce the consumption of water resources and the discharge of pollutants into the water environment to the maximum extent, meet the production and life of residents to the maximum extent, adapt to the climate change, and serve the ecological balance. Based on SWMM (stormwater management model) model, this study constructed an SC planning and design method based on the coupling of multiobjective optimization and comprehensive evaluation and established a multi-model based on fast classification and non-dominated genetic algorithm (NSGA-II). The results show that compared with the results calculated by other methods, the multiobjective comprehensive optimization model established in this study and the results calculated by the genetic algorithm NSGA-II shorten the optimization period by 1.44%, improve the quality reliability by 9.86%, reduce the total cost by 0.66%, and reduce the environmental impact by 0.93%. The conclusion shows that it reduces the average discharge flow of the discharge port, relieves the drainage pressure of the pipe network, reduces the risk of waterlogging in the city, etc., and it is more suitable for dealing with rainfall events in medium and small return periods.
Intelligent Predictive Maintenance of Dry-Type Transformer Based on Vibration
Authors: Yang Xiaoping , Zhao Xiao , Shen Xianhao , Wang Yang , Xu Ce
Published: September 2022

The normal operation of the transformer is an important guarantee for the safe operation of the whole power network. Usually, the periodic maintenance work increases the workload of the operation and maintenance personnel. In this paper, an intelligent predictive and maintenance system for dry-type transformer based on vibration is proposed to monitor the vibration state of the transformer. The fractional-order Kalman filter and normalization method are used to preprocess the vibration data to reduce noise interference, and then the fault is classified by one-dimensional convolution neural network. On this basis, an improved grey Verhulst model is established to predict the fault time of the transformer. The experimental results show that the classification accuracy of the one-dimensional convolution neural network can reach more than 95%, and the improved grey Verhulst model can predict the fault of the dry-type transformer one week in advance.
A Comprehensive Study on Epidemiology Case Studies Using Computational Analysis
Authors: Lin Xinjiang , Chen Shouping , Akhi Amatul Bushra
Published: September 2022

Health-related issues and occurrences with regard to a particular population are the subject of an epidemiology study. This paper presents the results of a retrospective epidemiological investigation on 15922 hospitalized hand trauma patients from Central China between 2011 and 2020. Gender, age, onset season, injury mechanism, injury environment, injury location, and clinical characteristics are among the characteristics of the data gathered. The study is using computational analysis to draw inferences from the case studies collected in the databases of the hospitals. The types and characteristics of occupational injuries at home and outdoor are compared and analyzed. The purpose of the study is to present the findings from recent case studies for future reference and to recommend useful roles for the industrial sector in the care of patients with hand trauma in order to lower occupational harm. The injuries of preschool children are also analyzed. The incidence rate of hand injuries in infants has been increasing year by year which is directly related to the inefficient growth of children in rural areas. The data are collected from hospitals, then the data analytical tools are applied to draw conclusions. The suggested model is intelligently learned through the application of computational techniques, which are also used to suggest treatments to trauma victims. According to this study, males are more likely than females to sustain hand trauma; occupational injuries are more common than living injuries; males between the ages of 20 and 50 are at an increased risk of suffering an occupational injury. This study showed that the proportion of hand trauma in preschool children was higher (12.27%), and the 2-3-year-old group was the main injury target of preschool children (45.70%). The accidental injuries of newborns and young children can be reduced by government assistance, social support, and tighter monitoring.
Analysis of Modern Public Art Design Integrating Traditional Elements under Interactive Technology
Authors: Liu Liping
Published: September 2022

In order to give full play to the carrier role of modern public art design and inherit the traditional elements whose vitality is gradually losing, this paper analyzes the modern public art design integrating the traditional elements under the interactive technology. Firstly, it analyzes the origin of modern public art design, which is manifested in the rational product of science and technology and the materialized form of cultural aesthetics. Then, it analyzes the current development situation of blindly seeking internationalization, over-reliance on modern tools, and insufficient design education level, and discusses the classification of modern public art integrating traditional elements and the inheritance problems it faces; under the interactive technology, the traditional elements and features are transmitted imperceptibly through a variety of carrier forms to realize the modern public art design integrating the traditional elements. The experimental results show that the resource utilization and benefit of modern public art are increasing exponentially year by year. With the increase of government investment in modern public art design activities, the complete contour map can be obtained by extracting the marked points.
QoS Analysis for Cloud-Based IoT Data Using Multicriteria-Based Optimization Approach
Authors: Jayakumar L. , Chitra R. Jothi , Sivasankari J. , Vidhya S. , Alimzhanova Laura , Kazbekova Gulnur , Kulambayev Bakhytzhan , Kostangeldinova Alma , Devi S. , Teressa Dawit Mamiru
Published: September 2022

This work explains why and how QoS modeling has been used within a multicriteria optimization approach. The parameters and metrics defined are intended to provide a broader and, at the same time, more precise analysis of the issues highlighted in the work dedicated to placement algorithms in the cloud. In order to find the optimal solution to a placement problem which is impractical in polynomial time, as in more particular cases, meta-heuristics more or less approaching the optimal solution are used in order to obtain a satisfactory solution. First, a model by a genetic algorithm is proposed. This genetic algorithm dedicated to the problem of placing virtual machines in the cloud has been implemented in two different versions. The former only considers elementary services, while the latter uses compound services. These two versions of the genetic algorithm are presented, and also, two greedy algorithms, round-robin and best-fit sorted, were used in order to allow a comparison with the genetic algorithm. The characteristics of these two algorithms are presented.
Recognition Method of Volleyball Players’ Spike and Take-Off Action Based on DTW Algorithm
Authors: He Fei , Zhang YongHeng
Published: September 2022

In order to improve the recognition ability of volleyball players’ spike take-off, and thus promote the accuracy of volleyball spike, this article puts forward the recognition technology of volleyball players’ spike take-off based on DTW algorithm combined with image recognition technology. The transmission relation model of detail features of volleyball players’ spike take-off action images is constructed, and the edge contour features of volleyball players’ spike take-off action images are detected and processed by detail wavelet feature decomposition and DWT algorithm. Using prior Atlas knowledge instead of dark primary color, the detailed information and color of the image are obtained. Through the method of filtering and maintaining, the image is guided to filter the details of the input volleyball player’s spike and take-off action image. Sobel operator is used to detect the weak edge information of the animation image. In the edge area, high-order moment feature decomposition and wavelet feature separation are used to enhance the details of the volleyball player’s spike and take-off action image and detect and enlarge the key action feature points, so as to improve the ability of enhancing and identifying the details of the action feature points of the image. The test shows that this method can effectively solve the noise and error in the process of recognizing the spike and take-off action of volleyball players, reduce the recognition error, and improve the ability to accurately locate the spike and take-off force point.
Forward-Solution Noninvasive Computational Arrhythmia Mapping: The VMAP Study
Authors: Krummen David E. , Villongco Christopher T. , Ho Gordon , Schricker Amir A. , Field Michael E. , Sung Kevin , Kacena Katherine A. , Martinson Melissa S. , Hoffmayer Kurt S. , Hsu Jonathan C. , Raissi Farshad , Feld Gregory K. , McCulloch Andrew D. , Han Frederick T.
Published: September 2022

Background:

The accuracy of noninvasive arrhythmia source localization using a forward-solution computational mapping system has not yet been evaluated in blinded, multicenter analysis. This study tested the hypothesis that a computational mapping system incorporating a comprehensive arrhythmia simulation library would provide accurate localization of the site-of-origin for atrial and ventricular arrhythmias and pacing using 12-lead ECG data when compared with the gold standard of invasive electrophysiology study and ablation.

Methods:

The VMAP study (Vectorcardiographic Mapping of Arrhythmogenic Probability) was a blinded, multicenter evaluation with final data analysis performed by an independent core laboratory. Eligible episodes included atrial and ventricular: tachycardia, fibrillation, pacing, premature atrial and ventricular complexes, and orthodromic atrioventricular reentrant tachycardia. Mapping system results were compared with the gold standard site of successful ablation or pacing during electrophysiology study and ablation. Mapping time was assessed from time-stamped logs. Prespecified performance goals were used for statistical comparisons.

Results:

A total of 255 episodes from 225 patients were enrolled from 4 centers. Regional accuracy for ventricular tachycardia and premature ventricular complexes in patients without significant structural heart disease (n=75, primary end point) was 98.7% (95% CI, 96.0%–100%;
P
<0.001 to reject predefined H
0
<0.80). Regional accuracy for all episodes (secondary end point 1) was 96.9% (95% CI, 94.7%–99.0%;
P
<0.001 to reject predefined H
0
<0.75). Accuracy for the exact or neighboring segment for all episodes (secondary end point 2) was 97.3% (95% CI, 95.2%–99.3%;
P
<0.001 to reject predefined H
0
<0.70). Median spatial accuracy was 15 mm (n=255, interquartile range, 7–25 mm). The mapping process was completed in a median of 0.8 minutes (interquartile range, 0.4–1.4 minutes).

Conclusions:

Computational ECG mapping using a forward-solution approach exceeded prespecified accuracy goals for arrhythmia and pacing localization. Spatial accuracy analysis demonstrated clinically actionable results. This rapid, noninvasive mapping technology may facilitate catheter-based and noninvasive targeted arrhythmia therapies.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04559061.
Abstract 002: Reducing Blood Pressure By Decreasing Na/k Pump Activities Using Synchronization Modulation Electric Field
Authors: Wang Lei
Published: September 2022

Na
+
/K
+
-ATPase is essential in maintenance of electrolyte, acid-base and volume homeostasis in kidneys. Increased renal Na/K pump activity has been reported to be associated with elevated blood pressure. Since blood pressure changes are paralleled by alterations in Na/K pump activity, it is proposed that impaired Na
+
/K
+
-ATPase signaling may contribute to imbalanced volume homeostasis and hypertension as well as increased salt sensitivity. Recently, we developed a novel technique called synchronization modulation electric field (SMEF) to electrically modulate the Na/K pump functions. The SMEF first synchronizes the pump molecules so that all the pumps simultaneously extrude Na
+
ions and pump in K
+
ions. Then, by accurately and precisely accelerating or decelerating the pumping rate, SMEF can consequently regulate renal tubular reabsorption and excretion capacity. In this study, we tested the effectiveness of SMEF in the controls of the tubular reabsorption and the regulation of blood pressure in health and hypertensive rat models. In normal SD rats (n=5), urinary flow rates were measured for the left and right kidneys of the same rat. When the SMEF was turned on only on the left kidney with backward modulation at the target frequency of 10 Hz to slow Na/K pumping rate, the urinary flow rate of the left kidney was quickly increased to 5.6±0.3 μl/min/g KW from the basal value of 4±0.4 μl/min/g KW. While the right kidney without SMEF application kept a constant basal urinary flow and Na+ excretion rate. In the Ang II induced hypertensive rat models (n=6), the MAP was gradually lowered by 8 mmHg than the control group when the backward modulation of SMEF was applied, accompanied by an increase of about 13 ml/day in water intake. We then applied the SMEF to the Dahl salt sensitive (SS) rats (n=5). The MAP in control group started to increase after 3-5 days of high salt intake. The SMEF was then applied from 7 days after switching to a high salt diet till the end of the experiments. The MAP quickly reduced by >30 mmHg (from 148 ± 7 to 117 ± 8 mmHg). These data demonstrated that backward modulation of SMEF lowered blood pressure possibly by promoting Na
+
and water excretion. SMEF could be an efficient treatment strategy for salt-sensitive hypertension.
Abstract 004: Pro-angiogenic Effects Of The Thrombospondin-1 Inhibitor Lskl In Preeclampsia Models
Authors: Marc Casandra , Achille Allahnah , Frégeau Geneviève , Hannou Lydia , Vachon Isabelle , Vaillancourt Cathy , Lavoie Julie L , Bertagnolli Mariane
Published: September 2022

Introduction:
Preeclampsia (PE) is characterized by high blood pressure, proteinuria and/or multi-organ damage, reaching 10% of all pregnancies globally. To date, no medication can treat PE. We recently identified an upregulation of the antiangiogenic protein Thrombospondin-1 (THBS1) in human and experimental PE. THBS1 is a main activator of latent TGF-β. We postulate that THBS1-mediated TGF-β activation can contribute to impair placental angiogenesis during PE. In this study, we aim to test the effects of LSKL, an inhibitor of TGF-β activation by THBS1, on angiogenesis in placentas of a mouse model of PE and in human placental endothelial cells exposed to PE-like conditions.

Methods:
Heterozygous female mice overexpressing human angiotensinogen and renin (PE) or C57BL/6 (control) were treated with LSKL or control peptide SLLK (280 μM, sc) at gestational day (GD) 14.5 (n=3 pregnant mouse/group). Placentas (n=4-9/pregnancy) were collected at GD 18.5. Placental expressions of TGF-β1, β2, total/phospho SMAD2 were assessed by western blot and angiogenesis by immunohistochemistry. Endothelial cells were extracted by magnetic sorting from human placentas (n=4) of healthy pregnancies. Cells were treated with LSKL or SLLK (30 μM) under hypoxia (0.5% vs. 8% O
2
) or thrombin (10 u/mL). THBS1 expression in cells was assessed by immunofluorescence. Cell angiogenesis was quantified by the number of closed tubes formed on matrigel (per 15,000 cells, 4h).

Results:
LSKL treatment reduced the expression of TGF-β2 (P<0.01) and phospho-SMAD2 (P<0.05) and significantly improved angiogenesis (P<0.05) in placentas of PE mouse versus control. In cells, both thrombin (P<0.05) and hypoxia (P<0.05) significantly increased THBS1 expression. Thrombin (P<0.01) and hypoxia (P<0.05) significantly impaired cell angiogenesis on matrigel (P<0.01), which was prevented by LSKL treatment (P<0.01). LSKL similarly reduced TGB-β2 (p<0.05) and phospho-SMAD2 (P<0.05) expressions in endothelial cells under thrombin and hypoxia cell exposure.

Conclusion:
Our results describe a significant pro-angiogenic effect of LSKL treatment by regulating THBS1 and TGF-β2 mechanisms in an experimental model of PE and in human placental endothelial cells exposed to PE-like conditions.
Abstract 010: Phosphodiesterase 3a Catalytic-domain Mutants Cause Hypertension With Brachydactyly
Authors: Kayser Charlotte , Bock Andreas , Leeuwen Lisette , Herkert Johanna , Vos Yvonne , Kidd Alexa , Aydin Atakan , Daumke Oliver , Lohse Martin , Luft Friedrich C
Published: September 2022

Mendelian syndromes give great insight into pathogenesis and have implicated salt handling. Hypertension with brachydactyly (HTNB) is unique in that a direct increase in peripheral vascular resistance is produced by activating mutations in phosphodiesterase 3A (PDE3A). A 50 mm Hg blood-pressure elevation by age 50 years causes stroke in untreated persons. Here, we report mutations in the PDE3 catalytic domain found in two new HTNB families. Since structural predictions indicated increased PDE3A cleavage activity, we used Förster resonance energy transfer (FRET) to measure the PDE3-specific cAMP degradation in cytosolic fractions from transfected cells. The newly discovered catalytic-domain PDE3A mutants, R862C and L910P, both showed a shorter transient emission-ratio change upon cAMP addition than PDE3A wildtype, indicating faster cAMP turnover. The V
max
of all experiments were extracted from FRET data and quantitated and analyzed statistically. The mean values V
max
(nM (cAMP)/s) were 143±7 for L910P, 63±3 for R862C and 73±4 for T445N, and 45±3 for WT respectively, (p<0.0001, <0.001, <0.05). We found that all disease-relevant mutations led to a clearly hyperactive PDE3A. The L910P catalytic-domain mutation resulted in the most dramatic increase in cAMP hydrolysis. That mutation also exhibited the most stepwise resistance to milrinone. Recently, we showed that cAMP signaling is organized in nanometer-sized cellular compartments. We suggest that the gain-of-function PDE3 mutations result in unphysiologically larger cAMP nanodomains and thereby dysregulate crucially important cAMP nanoarchitecture. Spatiotemporal cAMP signaling and precise PDE-controlled effector activation, could usher in a site-specific nanomolecular pharmacology.
Abstract 025: RNAseq And Bioinformatics Identify New Pathways In The Thick Ascending Limb (TAL) Involved In Fructose Induced Salt Sensitive Hypertension
Authors: Wu Andrew , Eaton Andrew J , Caceres Paulo , Shrestha-Maskey Puja , Adrianto Indra , Granados-Pineda Jessica , Haque Mohammed Z , Garcia Pedraza Jose A , Ortiz Pablo A
Published: September 2022

Elevated fructose consumption is associated with hypertension in humans. In normal Sprague Dawley rats, a high fructose intake (20% fructose drinking water) induced salt sensitive hypertension. We found that fructose directly stimulates the apical Na/K/2Cl cotransporter NKCC2 in the thick ascending limb (TAL), and when consumed for more than 7 days, increases NKCC2 phosphorylation at Thre 96,101. SPAK and OSR1 kinases are known to phosphorylate NKCC2, but it is not known how fructose activates SPAK or OSR1. We hypothesized that fructose intake activates several signaling cascades in TALs that selectively stimulate SPAK. Using an antibody that recognizes activated SPAK and OSR1 (P-Ser 373 SPAK; Ser325 in OSR1), we found that 20% fructose (14 d) enhanced SPAK/OSR1 phosphorylation by 179±32% (p<0.05). This effect was specific for SPAK because phosphorylation of OSR1, immunoprecipitated from TALs, was not increased by fructose. To study the mechanism of SPAK activation, we isolated TALs from rats on control or 20% fructose diet for (14 d, n=6) and performed RNAseq. Over 12,000 genes were statistically compared and 500 were significantly different (p<0.05). Expression of some of the most highly upregulated genes (PRKRIP1 and SOCS3) was confirmed by Western blot in TALs. However, expression of upstream SPAK activators was unchanged by fructose (WNK1/3/4). We developed a targeted bioinformatics approach that included angiotensin signaling, nitric oxide and lipid metabolism, plus protein-protein interaction networks for SPAK. We identified PRKCQ (PKC Theta), a kinase upstream of SPAK, that was upregulated in TALs by fructose. In fructose fed rats, PRKCQ expression was 31±11% higher than control, as was Phospho-PRKCQ (223±45% increase, p<0.05). We then measured systolic BP (SBP) by telemetry in Dahl SS rats with genetic deletion of SPAK (SPAK KO). In WT Dahl SS rats, 4 weeks of fructose intake increased SBP by 25±4 mmHg (p<0.05), whereas in SPAK KO the increase in SBP was reduced (11±4 mmHg, p<0.05). We concluded that high fructose intake induces several prohypertensive signaling pathways in the TAL that lead to SPAK and NKCC2 activation. We identified PRKCQ as a potential activator of SPAK. Fructose induced hypertension in Dahl SS rats was in part mediated by SPAK.
Abstract 031: Mutagenesis Of The Cleavage Site Of (pro)renin Receptor Abrogates Aldosterone-salt-induced Hypertension And Renal Injury In Mice
Authors: Fu Ziwei , Zheng Huaqing , Yang Tianxin
Published: September 2022

Soluble (pro)renin receptor (sPRR), the extracellular domain of (pro)renin receptor (PRR), is primarily generated by site-1 protease (S1P) and furin. It has been reported that sPRR functions as an important regulator of intrarenal renin contributing to angiotensin II (Ang II)-induced hypertension. Relatively, less is known for the function of sPRR in Ang II-independent hypertension such as mineralocorticoid excess. In the present study, we employed a novel mouse model with mutagenesis of the cleavage site in PRR (termed as Mutant mice) to examine the phenotype during aldosterone (Aldo)-salt treatment. The hypertensive response of Mutant mice to Aldo-salt treatment was blunted (day 12, delta MAP: WT/Aldo-salt 22.4±4.1 mm Hg vs. Mutant/Aldo-salt 11.7±2.5 mm Hg, n=6, p<0.05), in parallel with attenuated response of plasma volume expansion and sodium-water retention. Renal cortical and inner medullary mRNA and protein expression of α-, β-, and γ-subunits of epithelial sodium channel (ENaC) were all increased in WT mice after Aldo-salt treatment but only the increase of α-ENaC in inner medulla was blunted in Mutant mice. The plasma sPRR was increased 1.5-fold after Aldo-salt treatment, which was reduced by 57% in Mutant mice. Moreover, Aldo-salt-induced hypertrophy in the heart and kidney, which were improved in Mutant mice (Heart Weight/Body Weight: WT/Aldo-salt 5.8±0.4 mg/g vs. Mutant/Aldo-salt 4.2±0.3 mg/g; Kidney Weight/Body Weight: WT/Aldo-salt 9.9±0.4 mg/g vs. Mutant/Aldo-salt 7.3±0.4 mg/g, n=6, p<0.01), accompanied with blunted polydipsia and polyuria in Mutant mice. Furthermore, the urinary albumin was increased 8.3-fold after Aldo-salt treatment, which was reduced by 32% in Mutant mice. The mRNA levels of Fibronectin, α-SMA, IL-6, MCP-1 and TGF-β were increased in Aldo-salt/WT mice, which were prevented almost 60% in Aldo-salt/Mutant mice. Together, these results represent strong evidence favoring endogenous sPRR as a mediator of Aldo-salt-induced hypertension and renal injury. Here, we firstly report that sPRR-dependent pathway medicates the Na
+
-retaining action of Aldo in the distal nephron, which opens up a new area for a better understanding of the molecular basis of renal handling of Na
+
balance and blood pressure.
Abstract 038: The Association Of Supine Hypertension Versus Standing Hypotension With Adverse Cardiovascular Events Among Middle-aged Adults
Authors: Earle William , Kondo Jordan , Wood Julia , Turkson-Ocran Ruth-Alma N , Kendrick Karla , Ngo Long H , Cluett Jennifer , Mukamal Ken J , Selvin Elizabeth , Malek Natalie R , Lutsey Pamela L , Coresh Josef , Juraschek Stephen P
Published: September 2022

Background:
Clinical management of orthostatic hypotension (OH) prioritizes the prevention of standing hypotension (HYP), sometimes at the expense of supine hypertension (HTN). It is unclear whether supine HTN is associated with adverse outcomes relative to standing HYP.

Objectives:
To compare supine HTN and standing HYP among middle-aged adults with and without OH.

Methods:
The Atherosclerosis Risk in Communities Study measured supine and standing blood pressure (BP) in adults aged 45-64 between 1987-1989. We defined OH as a positional drop in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg, supine HTN as a BP≥140/≥90 mmHg, and standing HYP as a BP≤105/≤65 mmHg. ARIC participants were followed >30 years. Coronary heart disease (CHD) and mortality were adjudicated; falls and syncope were based on hospital claims. We used adjusted Cox models that included both supine HTN and standing HYP.

Results:
Of 12,580 participants (55% female, 26% Black, mean age 54±6) 5% had OH. Among those without OH (N=11936), 19% had supine HTN and 21% had standing HYP, while among those with OH (N=644), 11% had supine HTN and 34% had standing HYP. Supine HTN was associated with CHD (HR 1.49; 1.36, 1.63), syncope (HR 1.26; 1.15, 1.39), and all-cause mortality (HR 1.47; 1.38, 1.57), while standing HYP was only associated with all-cause mortality (HR 1.08; 1.00, 1.16) and to a lesser extent than supine HTN (P comparing coefficients <0.001) (Table). Associations did not differ for those with OH (P-interactions>0.25).

Conclusion:
Supine HTN was associated with more adverse events than standing HYP, regardless of OH status, questioning conventional practices of prioritizing standing HYP among adults with OH.
Abstract 041: Renal-derived Human Sprr Increases Blood Pressure In Female Mice But Not In Male Mice
Authors: Arthur Gertrude , Poupeau Audrey , Taylor Alexis , Nichols Kellea , Leachman Jacqueline , Hinds Terry , Loria Analia S , Osborn Jeffrey , Yiannikouris Frederique B
Published: September 2022

The soluble prorenin receptor (sPRR) plays an important role in blood pressure regulation. In rodent models, sPRR contributes to Ang II production by increasing renin activity and systolic blood pressure (SBP). However, there is a gap of knowledge concerning the functional role of locally produced human sPRR from the kidney in blood pressure regulation. Therefore, we evaluated the role of renal-derived human sPRR in SBP control.Human sPRR-Myc-tag transgenic mice were bred with mice expressing Hoxb7/Cre to selectively express human sPRR in the collecting duct (RHsPRR). RHsPRR and control (CTL) male and female mice were fed a standard diet for 10 months (n=8-11/group). Body weight was examined weekly and SBP measured by radio-telemetry. Western blot analysis depicted the presence of human sPRR-Myc-tag (28 KDa) in the cortex and medulla of RHsPRR male mice which validated the humanized mouse model. Renal-derived human sPRR did not change body weight in male or female mice (M: CTL: 34±1, RHsPRR: 33±1 g; F: CTL: 28±1, RHsPRR: 30±1 g). Circulating sPRR was also unchanged in male and female mice (M: 3995±643 and 4342±500pg/ml, F: 3479±194 and 3948±238pg/ml). SBP increased significantly in female RHsPRR mice compared to CTL (F: 118.7±2 and 127.2±3 mmHg, P<0.05) but not in male mice (M: 123.8±2 and 119.9±6 mmHg). In female mice, renal-derived human sPRR increased significantly renal AT1R gene expression (F: 1.7±0.5 and 2.6±0.4 2
-ΔΔCT
, P<0.05) and stimulated ERK1/2 (F: 0.3±0.0 and 0.6±0.1 AU, P<0.05) suggesting that human sPRR increases blood pressure in female mice likely via AT1R-ERK1/2 pathway activation. In contrast, in male mice, AT1R-ERK1/2 pathway was not up-regulated and renal ACE2 gene expression was significantly increased in RHsPRR males (M: 1.0±0.2 and 3.3±1.1 2
-ΔΔCT
, P<0.05). Mechanistically, in male mice, our results indicated that the lack of activation of AT1R-ERK1/2 pathway combined with the increase of ACE2 could have prevented RHsPRR-induced increase in SBP. Together, our data highlighted the contribution of renal human sPRR to blood pressure control in a sex-dependent manner and a new mechanism of blood pressure control that involved the renin angiotensin system.
Abstract 043: Prorenin Reduces Spontaneous Firing Rate In Cells Expressing Tyrosine Hydroxylase In The Hypothalamic Paraventricular Nucleus
Authors: Reyes Miriam , Souza Lucas A , Feng Earley Yumei
Published: September 2022

The (pro)renin receptor (PRR) plays essential roles in cardiovascular and metabolic physiology. The tyrosine hydroxylase (TH) neurons in the paraventricular nucleus of the hypothalamus (PVN) have recently emerged as a key metabolic regulator that play functional roles in the regulation of the energy expenditure and metabolism. Using RNAScope in situ hybridization, we found that 95% of TH-containing neurons in the PVN (n=872 cells/3 mice) express the PRR. In this study, we aimed to examine the effects of PRR activation on the firing activity of the TH-containing neurons in the PVN (TH
PVN
). We hypothesized that prorenin activation of the PRR increases firing activity of the TH
PVN
neuron. To test this hypothesis, we performed electrophysiological recordings in loose cell-attached voltage-clamp configuration in PVN slices from mice expressing TdTomato reporter for TH neurons (TH-cre-TdTomato mice). These experiments were carried out to isolate and record spontaneous firing rate (SFR). We abolished all the synaptic transmission by adding a GABA
A
receptor antagonist (picrotoxin, 50 μM), an antagonist of AMPA/kainate receptors (CNQX, 5 μM), and an NMDA receptor antagonist (D-APV, 50 μM) throughout the recording. The cells were discarded if the access resistance was >15 MΩ or fluctuated more than 15%. At the end of the experiments, tetrodotoxin (1 μM) was added to abolish and confirm neuronal activity. The SFR in TH
PVN
neurons was significantly decreased after application of prorenin (PR) (4.9 ± 0.87 and 3.2 ± 1.07 Hz, before and after PR, respectively;
n
= 10,
p
= 0.006, paired
t
-test) indicating that PR reduces spontaneous firing activity of the TH
PVN
neurons. To determine if this effect was due to the prorenin activation of the PRR, we recorded SFR in the presence of PRR antagonist (PRO20). There was no difference in the SFR (5.8 ± 1.58 Hz and 5.9 ± 1.7 Hz,
n
= 5,
p
= 0.903, paired
t
-test) in the TH
PVN
neurons between PRO20 and PRO20+PR group respectively suggesting that PRO20 blocks the effect of PR in reducing SFR in TH
PVN
neurons. Our results showed that the prorenin acts on the PRR to reduce the SFR of the TH
PVN
neurons. We conclude that PRR signaling in the TH
PVN
neurons might play a role in cardiovascular and metabolic regulation by the modulating the TH
PVN
neuronal plasticity.
Abstract 048: Extracellular Endothelial Microvesicles Causative Agents In Hypertension-related Endothelial Dysfunction
Authors: Garcia Vinicius P , Fandl Hannah K , DeSouza Noah M , Berry Auburn R , Greiner Jared J , Stauffer Brian L , DeSouza Christopher A
Published: September 2022

We have previously demonstrated that endothelial cell-derived microvesicles (EMVs) are elevated with hypertension and are associated with endothelial dysfunction. However, it is unknown whether EMVs play a causative role in blood pressure-related endothelial dysfunction. The experimental aim of this study was to determine the effects of EMVs isolated from hypertensive adults on endothelial cell inflammation, apoptosis and nitric oxide (NO) production. Twenty middle-aged adults were studied: 10 normotensive (NT: 8M/2F; 57
+
2 yr; BP: 113/71
+
2/2 mmHg; EMVs: 64
+
10 EMV/μL) and 10 hypertensive (HT: 6M/4F; 56
+
2 yr; 137/82
+
2/2 mmHg; 115
+
17 EMV/μL). All subjects were sedentary, non-smokers, non-medicated and free of overt cardiometabolic diseases. EMVs (CD144+) were identified, sorted and collected from plasma by flow cytometry. Human umbilical vein endothelial cells were cultured and treated with EMVs from either NT or HT adults. EMVs from HT induced significantly greater release of interleukin (IL)-6 (38.9±1.5 vs 31.5±0.9 pg/mL) and IL-8 (38.1±2.7 vs 30.3±1.8 pg/mL) compared with EMVs from NT. Concordantly, HT-related EMVs induced ~25% higher (P<0.05) expression of phosphorylated-NF-kB p65 (Ser536; active NF-kB) (168.5
+
12.1 vs 136.8
+
7.0 AU). HT EMVs induced significantly higher activation of the apoptotic proteins p38-MAPK (26.0
+
4.5 vs 12.4
+
1.2 AU) and caspase-3 (243.1±36.7 vs 150.8±17.0 AU) than NT EMVs. Although total eNOS expression was not significantly altered; active eNOS (pSer1177) (221.02
+
34.8 vs 331.5
+
30.4 AU) and, in turn, NO production (6.2
+
0.4 vs 9.4
+
0.6 υmol/L) were significantly lower (~30%) in the cells treated with EMVs from HT adults. Increased inflammation, apoptosis susceptibility and decreased NO production are central features of endothelial dysfunction. Circulating EMVs represent both a biomarker and mediator of endothelial dysfunction with hypertension.
Abstract 050: Endothelial Cell Mineralocorticoid Receptor Deletion Improves Endothelial Function, Blood Pressure And Fetal Growth In The RUPP Mouse Model Of Preeclampsia
Authors: Moronge Desmond , Ayulo Victor , Connor Gabrielle , Mellott Elisabeth , Jaffe Iris Z , Ogbi Safia , Faulkner Jessica L
Published: September 2022

Preeclampsia (PE) is a hypertensive disorder of pregnancy that causes adverse pregnancy outcomes. Progesterone in pregnancy increases endothelial mineralocorticoid receptor (ECMR) expression, which we showed mediates endothelial function in hypertensive female mice, however, whether ablating endothelial dysfunction in PE improves pregnancy outcomes is unknown. We hypothesized that improving endothelial function via ECMR deletion increases fetal growth and ablates hypertension in the reduced uterine perfusion pressure (RUPP) PE mouse. Pregnant ECMR-intact (WT) and -deficient (KO) mice underwent RUPP or sham surgery on GD13 and sacrificed on GD18 (WT Sham=9, WT RUPP=5, KO Sham=6, KO RUPP=6). Vascular function was measured via wire myography on 2
nd
order mesenteric arteries and thoracic aorta. Systolic blood pressure (BP) was measured by radiotelemetry in a subset of mice. RUPP did not decrease maternal weights in either WT or KO mice (P>0.05) but decreased pup weight (726±20 WT+Sham vs 660±11mg WT+RUPP, *P<0.05) and fetal demise (16±4 vs 28±4% resoprtions/litter, *P<0.05) in WT pregnant mice, however, not in KO mice (710±15 KO+Sham vs 693±19 mg KO+RUPP, P>0.05, and 13±5 vs 28±12% resoprtions/litter, P>0.05), indicating KO protected fetal growth. RUPP reduced endothelial-dependent, acetylcholine-mediated vascular relaxation (10
-9
-3x10
-5
M) in WT, but not KO pregnant mice (*P<0.05, 2-way ANOVA w/ RM), but not aorta ACh-mediated relaxation (P>0.05). Nitric oxide synthase (NOS) inhibitor LNAME ablated differences in ACh-mediated relaxation between WT Sham and WT RUPP (P>0.05), with no differences observed in KO Sham or KO RUPP, in both aorta and mesenteric arteries, indicating RUPP impaired endothelial function via decreasing NOS activity. Preliminary data demonstrates RUPP increased BP on GD15-17 in WT (127±21 mmHg, N=3), however, not in KO pregnant mice (111±4, N=2). RUPP also ablated circadian rhythm in WT, but not KO, pregnant mice from GD15-18. Collectively, these data indicate that ECMR activation induces reduced pup weight, endothelial dysfunction and hypertension in the RUPP model which may lead to clinical studies for consideration of specific MR antagonists as therapeutic options for endothelial dysfunction in PE pregnancies.
Abstract 064: Hypokalemia Induced By Loss Of Kir5.1 Initiates WNK-SPAK/OSR1 Signaling In Dahl Salt-sensitive Rats
Authors: Xu Biyang , Mutig Kerim , Palygin Oleg , Staruschenko Alexander
Published: September 2022

Background:
Hypokalemia promotes Na
+
reabsorption via the Na
+
-Cl
-
(NCC) cotransporter of the distal convoluted tubule (DCT), which reduces the K
+
losses in downstream nephron segments and increases NaCl retention and blood pressure. In dietary K
+
depletion, activation of NCC is mediated by the with no lysine (K) kinase (WNK)-Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1) pathway. Our previous work suggested that deletion of
Kcnj16
(the gene that encodes K
ir
5.1) in Dahl salt-sensitive (SS) rats (SS
Kcnj16-/-
) resulted in hypokalemia with a compensatory increase in expression and activity of NCC. Here, we hypothesized that hypokalemia induced by loss of the K
ir
5.1 subunit initiates WNK-SPAK/OSR1 signaling.

Methods:
8 to 12-week-old male SS
WT
and SS
Kcnj16-/-
rats were separated into 3 groups (N=5 per group) and fed different diets for 3 weeks: SS
WT
(0.4% NaCl); SS
Kcnj16-/-
(0.4% NaCl); SS
Kcnj16-/-
(4% NaCl+2% KCl). At the end of the experiment, kidneys were flushed and processed for Western blot, immunofluorescence, and electron microscopy analysis.

Results:
Electron micrographs exhibited WNK body clusters in SS
Kcnj16-/-
compared to SS
WT
rats. Immunofluorescence staining showed dramatically increased expression of both SPAK and phospho-SPAK (pSPAK) in DCTs of SS
Kcnj16-/-
rats, where pSPAK colocalized with NCC. Similarly, Western blot analysis revealed significantly elevated expression of total SPAK (3.32± 0.18 vs. 1.00 ± 0.19,
P
<0.0001) and pSPAK (2.09 ± 0.51 vs. 1.00 ± 0.19,
P
<0.001) in the kidneys of SS
Kcnj16/-
compared to SS
WT
rats. Moreover, supplementing the SS
Kcnj16-/-
rats with high Na
+
and high K
+
(4% NaCl+2% KCl) reverses the expression and activity of SPAK.

Conclusion:
Our results indicate that hypokalemia resulting from loss of K
ir
5.1 subunit stimulates WNK-SPAK/OSR1 signaling. Furthermore, the fact that dietary K
+
supplementation overturned the altered expression of this pathway implies that plasma K
+
level is responsible for the activation of the WNK-SPAK/OSR1 pathway.
Abstract 068: Genetic Mechanisms Of Cardiac Hypertrophy And Fibrosis In Global
Npr1
Gene-ablated Male And Female Mice
Authors: Ramasamy Chandramohan , Subramanian Umadevi , Pandey Kailash N
Published: September 2022

Genetic ablation of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) in mice triggers cardiac remodeling associated with hypertrophy, fibrosis, and heart failure. The objective of this study was to determine the mechanisms regulating the developments of cardiac hypertrophy and fibrosis in global
Npr1
(encoding NPRA) gene-knockout (KO) mice and whether transforming growth factor-beta 1 (TGF-β1) plays a critical role in this process. Both male and female
Npr1
KO (
Npr1
-/-
, 0-copy), heterozygous (
Npr1
+/-
, 1-copy), and wild-type (WT;
Npr1
+/+
, 2-copy) mice were administered with TGF-β1 receptor antagonist GW788388 (2 mg/kg/day) by intraperitoneal (ip) injection for 28 days. The heart weight/body weight (HW/BW) and tibia length (TL) to BW (TL/BW) ratios were determined. Echocardiography was used to determine the cardiac structure and function. Quantitative polymerase chain reaction (qPCR) and Western blot were used to quantify the hypertrophic and fibrotic markers. HW/BW and TL/BW ratios were significantly higher in
Npr1
KO mice and significantly greater in males than females. The
Npr1
-/-
mice showed significant induction of cardiac hypertrophic marker collagen-1α (3.5-fold) and fibrotic markers, monocyte chemoattractant protein (MCP, 4-fold), connective tissue growth factor (CTGF, 5-fold), alpha-smooth muscle actin (α-SMA, 4-fold) compared with WT mice. The expression of phosphorylated extracellular regulated kinase 1/2 (pERK1/2) was also upregulated in

Npr1
-/-

mice. Left ventricular end-systolic and diastolic dimensions (LVED-s, LEVD-d) and posterior wall thickness (PWT) were significantly increased in male KO mice than female KO mice compared with WT mice. The fractional shortening (FS) was compromised in male KO mice than female KO mice. The Treatment of

Npr1
-/-

mice with GW788388, prevented the development of cardiac hypertrophy and fibrosis compared to vehicle-treatment. The results suggest that the cardiac hypertrophy and fibrosis in
Npr1
-/-
mice is regulated through TGF-β1- SMAD-pathways.
Abstract 072: Distinct And Evolving Chromatin States And Transcription Factors Determine The Development Of The Kidney Vasculature
Authors: Martini Alexandre G , Smith Jason , Medrano Silvia , Sheffiled Nathan , Sequeira Lopez Maria , Gomez Roberto A
Published: September 2022

Differentiation of cells that compose the kidney arterioles is crucial for the formation of a functioning kidney. A group of stromal cells expressing the Forkhead Box D1 (
FoxD1
) transcription factor (TF) will give rise to the metanephric progenitors for the mural cells of the kidneys arteries and arterioles. We investigated the molecular mechanisms that instruct the
FoxD1
progenitors to adopt different cell fates to properly assemble the developing kidney vasculature. We generated FoxD1GC;R26R
mT/mG
mice, where all the
FoxD1
descendant’s cells are labeled with green fluorescent protein (GFP). GFP+ cells were isolated by FACS from kidney cortices and performed either single-cell RNA-Seq (scRNA-Seq) or single-cell Assay for Transposase-Accessible Chromatin (scATAC-Seq
)
at different developmental ages: embryos (E12 and E18) and post-natal (P5 and P30)
.
The integrative analysis of scRNA-Seq and scATAC-Seq identified the
FoxD1
derivative cell populations and their respective accessible chromatin areas over the developmental pathway. Motif analysis revealed the binding sites to putative TFs repertoire for each of the
FoxD1
descendants. Therefore, we generated differentiation trajectories to track the transcriptome and epigenetics changes that occur along the differentiation pathway. At E12, the
FoxD1
progenitor cells harbor open chromatin to bind TFs such as
Zeb1, Maz, Snai2
and
Pbx1
(p_adjusted_value (padj).: 6.7E-40; 3.6E-40; 4.1E-28; 2.5E-5; respectively)
.
The gene expression levels of these TFs were also significant (padj.: 5.7E-68; 6.2E-53; 4.4E-49; 2.6E-47, respectively
)
. All these TFs are strongly correlated to embryogenesis. As development progresses, new open chromatin areas emerge within a different transcriptome. Interestingly, from E18 ahead, all the
FoxD1
decendants exhibited the
Mef2
family of TFs as the highest enriched motifs. At P30, among all the
FoxD1
decendants, the Juxtaglomerular Cells have the highest enrichment score for all the
Mef2
family members (padj.: 0). Thus, as the cells differentiate they acquire distinct chromatin landscapes and TF repertoires. In addition to these unique landscapes
Mef2
family of TFs are prominent for the
FoxD1
descendants differentiation and kidney vascular development.
Abstract 073: Age-Dependent Hypertension-Related Cognitive Impairment And Neuroinflammation In Sprague Dawley Rats Can Be Reversed By An AT
1
R Antagonism
Authors: Nist Kayla M , Wainford Richard D
Published: September 2022

Aim:
We hypothesize paraventricular nucleus (PVN)-specific blood brain barrier (BBB) disruption and neuroinflammation increase hypertension and sympathoexcitation with age, promoting cognitive impairment, that can be attenuated by an Angiotensin II Type 1 Receptor (AT
1
R)-dependent mechanism in the aging Sprague Dawley (SD) rat.

Methods:
In male and female SD rats aged 3, 8 and 16 months old (MO) (N=6/gp) and 16 MO male rats treated with losartan (21 days; sc 3 mg/kg/day), blood pressure (BP; femoral artery cannulation), sympathetic tone to the vasculature (iv hexamethonium) and plasma NE (ELISA) was measured. Memory function was assessed by the novel object recognition task. BBB disruption was assessed via FITC extravasation and IHC/IF was performed for microglia (CD11b/c), astrocytes (GFAP), IL-6 and TNF-α in the PVN.

Results:
Aged male, but not female, SD rats develop HTN, sympathoexcitation, and cognitive impairment. PVN neuroinflammation, proinflammatory cytokine production and BBB disruption increased in male, but not female, rats with age. Losartan significantly lowered BP, reduced sympathoexcitation, attenuated BBB disruption and neuroinflammation, and reversed cognitive impairment in aged male rats.

Conclusions:
Our data suggest there is a potential protective role of female sex steroids in preventing the development of age-dependent HTN which is associated with PVN neuroinflammation. Concurrent with recent clinical findings, we found lowering blood pressure improved cognitive function and, thus, an AT
1
R antagonism represents a new therapeutic modality to improve cognitive performance in hypertensive individuals.