bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Compressive Strength of Concrete and Rock Using an Elementary Instance‐Based Learning Algorithm
Authors: Hsieh Shun-Chieh
Published: April 2021

The use of machine learning techniques to predict material strength is becoming popular. However, not much attention has been paid to instance‐based learning (IBL) algorithms. Therefore, in order to predict material strength, as the direct method by conducting tests is time‐consuming and expensive and experimental errors are inevitable, an indirect method based on elementary instance‐based learning algorithm was proposed. The standard k‐nearest neighbors (k-NN) with cross‐validation were utilized to develop compressive strength prediction models for some concretes and rocks by considering indirect parameters such as physical and mechanical parameters. Results on applying this method to datasets from literature studies show that the values of RMSE for k-NN are modest, indicating adequacy to predict compressive strength with comprehensive range values of predictors. Additionally, the R2‐values of the k-NN models were high. In other words, the models were able to explain the variance in compressive strength for data with a wide range of input values.
Grouped Secret Sharing Schemes Based on Lagrange Interpolation Polynomials and Chinese Remainder Theorem
Authors: Miao Fuyou , Yu Yue , Meng Keju , Xiong Yan , Chang Chin-Chen
Published: April 2021

In a

t
,
n

threshold secret sharing (SS) scheme, whether or not a shareholder set is an authorized set totally depends on the number of shareholders in the set. When the access structure is not threshold, (t,n) threshold SS is not suitable. This paper proposes a new kind of SS named grouped secret sharing (GSS), which is specific multipartite SS. Moreover, in order to implement GSS, we utilize both Lagrange interpolation polynomials and Chinese remainder theorem to design two GSS schemes, respectively. Detailed analysis shows that both GSS schemes are correct and perfect, which means any authorized set can recover the secret while an unauthorized set cannot get any information about the secret.
Spatiotemporal Variations of Drought in the Arid Region of Northwestern China during 1950–2012
Authors: Huang Wenjun , Yang Jianjun , Liu Yang , Yu Entao
Published: April 2021

There are water resource shortages and frequent drought disasters in the arid region of northwestern China (ARNC). The purpose of this study is to understand the spatiotemporal variations of the droughts in this region and to further estimate future changes. Multiple drought indexes such as the standardized precipitation index (SPI), the standardized precipitation evapotranspiration index (SPEI), and the self-calibrated Palmer drought severity index (SC-PDSI) are used to investigate the temporal and spatial characteristics of the ARNC drought from 1950 to 2012. Our results indicate the following: (1) The drought indexes exhibit significant increasing trends, and the highest drought frequency occurred in the 1960s, followed by a decreasing trend during the next few decades. All four seasons exhibit a wet trend, with a higher drought frequency in summer than in the other seasons. (2) The changes of the drought indexes in the ARNC also exhibit distinct spatial variations, with a wet trend in the subregions of North Xinjiang (NXJ), the Tianshan Mountains (TS), South Xinjiang (SXJ), and the Qilian Mountains (QL), but with a dry trend in the subregions of the Hexi Corridor (HX) and the western part of Inner Mongolia (WIM). (3) There was a major climate variability in the ARNC that occurred in the 1980s, and there were dry and wet climate oscillation periods of 8a, 17a, and >20a.
Factors Affecting Social Support Status of People Living with HIV/AIDS at Selected Hospitals of North Shewa Zone, Amhara Region, Ethiopia
Authors: Basha Elyas Admasu , Derseh Behailu Tariku , Wubetu Abate Dargie , Engidaw Nigus Alemnew , Gizachew Kefyalew Dagne
Published: April 2021

Background. Globally, millions of people are affected by human immunodeficiency virus (HIV). Acquired immunodeficiency was linked with psychosocial problems, whereby stigma and discrimination are the most common. Therefore, this study was aimed at assessing the level of the social support problem in people living with human immunodeficiency virus (PLHIV) and factors associated with it at selected hospitals of North Shewa Zone, Amhara Region, Ethiopia. Method. An institution-based cross-sectional study design was employed. A total of 422 PLHIV were involved in the study. A multidimensional perceived social support scale (MPSSS) for the measurement of social support problems was implemented. Systematic random sampling was used to recruit the study population after selecting study areas by lottery methods. Multivariate logistic regression analyses were performed via SPSS software. The statistical association was declared at a p value of less than 0.05 in the final model. Result. The prevalence of poor social support among study participants was 12.6%. Poor adherence to their antiretrovirus drugs was highly associated with poor social support (AOR = 2.06, 95% CI: 1.36, 3.13). Moreover, psychological distress (AOR = 4.67, 95% CI: 2.02, 10.81) and perceived stigma (AOR = 1.78, 95% CI: 1.18, 2.70) were positively associated. Conclusion. The burden of poor social support is increasingly affecting the lives of PLHIV. Poor social support in PLHIV is more magnified by poor adherence, having psychological distress, and perceived stigma.
IRS‐2/Akt/GSK‐3β/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity
Authors: Wang Lei , Duan Jialin , Jia Na , Liu Meiyou , Cao Shanshan , Weng Yan , Zhang Wei , Cao Jinyi , Li Ruili , Cui Jia , Wang Jingwen
Published: April 2021

Chronic hyperlipidemia leads to pancreatic β‐cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; however, its protective effects against lipotoxicity‐induced β‐cell oxidative stress and dysfunction are not clear. This study was designed to investigate the effects of CHS against lipotoxicity‐induced β‐cell injuries and its possible mechanism involved. High‐fat (HF) diet and a low dose of streptozotocin‐ (STZ‐) induced type 2 diabetes mellitus (T2DM) model in vivo and βTC3 cells subjected to 0.5 mM palmitate (PA) to imitate the lipotoxic model in vitro were performed. Pancreatic functions, ROS, and antioxidant protein measurements were performed to evaluate the effects of CHS on cell injuries. Protein expression levels were measured by Western blotting. Furthermore, siRNA‐targeted Nrf2, PI3K/Akt inhibitor (LY294002), or GSK‐3β inhibitor (LiCl) was used to investigate the crosstalk relationships between proteins. As the results showed, CHS treatment inhibited apoptosis, promoted insulin release, and reduced oxidative stress. CHS treatment significantly increased the expression of Nrf2 in the cytoplasm and nuclear protein. The antioxidative and benefit effects of CHS were inhibited by siNrf2. The phosphorylation of IRS‐2, PI3K, Akt, and GSK‐3β was markedly increased by CHS which were inhibited by PA. In addition, inhibition of PI3K/Akt or GSK‐3β with specific inhibitors dramatically abrogated the protective effects of CHS, revealing that the IRS‐2/Akt/GSK‐3β signaling axis was involved in the protective effects of CHS. These results demonstrate that CHS protected βTC3 cells against PA‐induced oxidative stress and cell dysfunction through Nrf2 by the IRS‐2/Akt/GSK‐3β‐mediated pathway.
Low-Intensity Ultrasound Causes Direct Excitation of Auditory Cortical Neurons
Authors: Qi Xiaofei , Lyu Kexin , Meng Long , Li Cuixian , Zhang Hongzheng , Niu Lili , Lin Zhengrong , Zheng Hairong , Tang Jie
Published: April 2021

Cochlear implantation is the first-line treatment for severe and profound hearing loss in children and adults. However, deaf patients with cochlear malformations or with cochlear nerve deficiencies are ineligible for cochlear implants. Meanwhile, the limited spatial selectivity and high risk of invasive craniotomy restrict the wide application of auditory brainstem implants. A noninvasive alternative strategy for safe and effective neuronal stimulation is urgently needed to address this issue. Because of its advantage in neural modulation over electrical stimulation, low-intensity ultrasound (US) is considered a safe modality for eliciting neural activity in the central auditory system. Although the neural modulation ability of low-intensity US has been demonstrated in the human primary somatosensory cortex and primary visual cortex, whether low-intensity US can directly activate auditory cortical neurons is still a topic of debate. To clarify the direct effects on auditory neurons, in the present study, we employed low-intensity US to stimulate auditory cortical neurons in vitro. Our data show that both low-frequency (0.8 MHz) and high-frequency (>27 MHz) US stimulation can elicit the inward current and action potentials in cultured neurons. c-Fos staining results indicate that low-intensity US is efficient for stimulating most neurons. Our study suggests that low-intensity US can excite auditory cortical neurons directly, implying that US-induced neural modulation can be a potential approach for activating the auditory cortex of deaf patients.
Drying Kinetics and Quality of Whole, Halved, and Pulverized Tiger Nut Tubers (Cyperus esculentus)
Authors: Abano Ernest Ekow , Akanson Joshua , Kizzie-Hayford Nazir
Published: April 2021

The objective of this study was to provide the optimum drying conditions to produce high-quality dried tiger nuts using hot-air drying. For this, we evaluated the effect of the whole, halved, and pulverized tiger nuts and air temperature (50 to 70°C) on the drying kinetics and quality of tiger nuts. The drying process generally followed a constant rate in the first 3 hours and a falling regime. We found the optimum drying conditions for tiger nuts to be crushed before convective hot-air drying at a temperature of 70°C. At this optimum condition, the predicted drying time, vitamin C content, reducing sugars, browning, brightness, redness, and yellowness was 780 min, 22.9 mg/100 mg dry weight, 157.01 mg/100 g dry weight, 0.21 Abs unit, 56.97, 1.6, and 17.0, respectively. The tiger nut’s reducing sugars increased from the 130.8 mg/100 dry weight in the raw tiger nuts to between 133.11 and 158.18 mg/100 dry weight after drying. The vitamin C degradation rate was highest in the uncut tiger nuts (32-35%) while in the halved and the pulverized samples, it was between 12 and 17%. The crushed samples’ effective moisture removal increased between 5.6- and 6.75-fold at the different air temperatures than that of the intact tiger nuts. The activation energy was 18.17 kJ/mol for the unbroken, 14.78 kJ/mol for the halved, and 26.61 kJ/mol for the pulverized tiger nut samples. The model

MR
=
0.997
 
exp

−
0.02

t

1.266

+
0.0000056
t

was the most suitable thin-layer drying model among the models examined for convective hot-air drying of tiger nuts. It is advisable to crush tiger nut before hot-air drying to produce better-quality flour for making milk beverages, cakes, biscuits, bread, porridge, and tiger nut-based breakfast cereals.
Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts
Authors: Fuhrman Barbara J. , Moore Steven C. , Byrne Celia , Makhoul Issam , Kitahara Cari M. , Berrington de González Amy , Linet Martha S. , Weiderpass Elisabete , Adami Hans-Olov , Freedman Neal D. , Liao Linda M. , Matthews Charles E. , Stolzenberg-Solomon Rachael Z. , Gaudet Mia M. , Patel Alpa V. , Lee I-Min , Buring Julie E. , Wolk Alicja , Larsson Susanna C. , Prizment Anna E. , Robien Kim , Spriggs Michael , Check David P. , Murphy Neil , Gunter Marc J. , Van Dusen Harold L. , Ziegler Regina G. , Hoover Robert N.
Published: April 2021

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31–39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89–0.94), liver cancer (HR = 0.92; 95% CI, 0.85–0.99), melanoma (HR = 0.95; 95% CI, 0.93–0.98), bladder cancer (HR = 0.96; 95% CI, 0.93–0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96–0.99), lung (HR = 0.98; 95% CI, 0.96–0.99), and breast (HR = 0.98; 95% CI, 0.93–0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis.

Significance:

Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.
Circulating Tumor Cell Chromosomal Instability and Neuroendocrine Phenotype by Immunomorphology and Poor Outcomes in Men with mCRPC Treated with Abiraterone or Enzalutamide
Authors: Brown Landon C. , Halabi Susan , Schonhoft Joseph D. , Yang Qian , Luo Jun , Nanus David M. , Giannakakou Paraskevi , Szmulewitz Russell Z. , Danila Daniel C. , Barnett Ethan S. , Carbone Emily A. , Zhao Jimmy L. , Healy Patrick , Anand Monika , Gill Audrey , Jendrisak Adam , Berry William R. , Gupta Santosh , Gregory Simon G. , Wenstrup Richard , Antonarakis Emmanuel S. , George Daniel J. , Scher Howard I. , Armstrong Andrew J.
Published: April 2021

Purpose:

While the detection of AR-V7 in circulating tumor cells (CTC) is associated with resistance to abiraterone or enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), it only accounts for a minority of this resistance. Neuroendocrine (NE) differentiation or chromosomal instability (CIN) may be additional mechanisms that mediate resistance.

Experimental Design:

PROPHECY was a multicenter prospective study of men with high-risk mCRPC starting abiraterone or enzalutamide. A secondary objective was to assess Epic CTC CIN and NE phenotypes before abiraterone or enzalutamide and at progression. The proportional hazards (PH) model was used to investigate the prognostic importance of CIN and NE in predicting progression-free survival and overall survival (OS) adjusting for CTC number (CellSearch), AR-V7, prior therapy, and clinical risk score. The PH model was utilized to validate this association of NE with OS in an external dataset of patients treated similarly at Memorial Sloan Kettering Cancer Center (MSKCC; New York, NY).

Results:

We enrolled 118 men with mCRPC starting on abiraterone or enzalutamide; 107 were evaluable on the Epic platform. Of these, 36.4% and 8.4% were CIN positive and NE positive, respectively. CIN and NE were independently associated with worse OS [HR, 2.2; 95% confidence interval (CI), 1.2–4.0 and HR 3.8; 95% CI, 1.2–12.3, respectively] when treated with abiraterone/enzalutamide. The prognostic significance of NE positivity for worse OS was confirmed in the MSKCC dataset (n = 173; HR, 5.7; 95% CI, 2.6–12.7).

Conclusions:

A high CIN and NE CTC phenotype is independently associated with worse survival in men with mCRPC treated with abiraterone/enzalutamide, warranting further prospective controlled predictive studies to inform treatment decisions.
First-in-Human Phase I Study of ABBV-085, an Antibody–Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors
Authors: Demetri George D. , Luke Jason J. , Hollebecque Antoine , Powderly John D. , Spira Alexander I. , Subbiah Vivek , Naumovski Louie , Chen Chris , Fang Hua , Lai Dominic W. , Yue Huibin , Polepally Akshanth R. , Purcell James W. , Robinson Randy , Sharma Padmanee , Allison James P. , Tolcher Anthony , Villalobos Victor M.
Published: April 2021

Purpose:

Leucine-rich repeat containing 15 (LRRC15) is expressed on stromal fibroblasts in the tumor microenvironment of multiple solid tumor types and may represent an interesting target for therapy, particularly in patients with sarcomas where LRRC15 is also expressed by malignant cells. ABBV-085 is a monomethyl auristatin-E antibody–drug conjugate that targets LRRC15 and showed antineoplastic efficacy in preclinical experiments. Herein, we report findings of ABBV-085 monotherapy or combination therapy in adult patients with sarcomas and other advanced solid tumors.

Patients and Methods:

This first-in-human phase I study (NCT02565758) assessed ABBV-085 safety, pharmacokinetics/pharmacodynamics, and preliminary antitumor activity. The study consisted of two parts: dose escalation and dose expansion. ABBV-085 was administered by intravenous infusion at 0.3 to 6.0 mg/kg every 14 days.

Results:

In total, 85 patients were enrolled; 45 patients received the recommended expansion dose of 3.6 mg/kg ABBV-085 monotherapy, including 10 with osteosarcoma and 10 with undifferentiated pleomorphic sarcoma (UPS). Most common treatment-related adverse events were fatigue, nausea, and decreased appetite. The overall response rate for patients with osteosarcoma/UPS treated at 3.6 mg/kg was 20%, including four confirmed partial responses. No monotherapy responses were observed for other advanced cancers treated at 3.6 mg/kg. One patient treated with ABBV-085 plus gemcitabine achieved partial response.

Conclusions:

ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.
Lipid Testing, Lipid-Modifying Therapy, and PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Eligibility in 27 979 Patients With Incident Acute Coronary Syndrome
Authors: Sarak Bradley , Savu Anamaria , Kaul Padma , McAlister Finlay A. , Welsh Robert C. , Yan Andrew T. , Goodman Shaun G.
Published: April 2021

Background:

While registry-based studies have shown that as many as 1 in 2 patients with stable atherosclerotic cardiovascular disease would be eligible for PCSK9i (proprotein convertase subtilisin-kexin type 9 inhibitor) therapy, this has not been studied in a large population-based postacute coronary syndrome (ACS) cohort.

Methods:

We examined lipid testing performed in hospital or within 90 days of discharge and lipid-lowering therapies dispensed within 90 days of discharge in patients surviving for at least 1 year after their first ACS between 2012 and 2018 in the province of Alberta, Canada. We estimated the proportion of patients eligible for PCSK9i and the expected benefits of treatment.

Results:

Of the 27 979 patients (median age 64.0 years, 29.3% female, 28.0% diabetic), 3750 (13.4%) did not have lipid testing in-hospital or within 90 days postdischarge. Untested patients were more likely to be older, female, from rural areas, to have more comorbidities, to already be on cardioprotective therapies, to present with unstable angina, and were less likely to have invasive interventions (all
P
<0.0001). Of the 24 229 tested, 18 767 (77.5%) had at least one lipid value above guideline-recommended threshold (LDL [low-density lipoprotein] ≥1.8 mmol/L [70 mg/dL] and non-HDL [high-density lipoprotein] ≥2.6 mmol/L [100 mg/dL]), of which 7284 (38.8%) did not have repeat testing within the year after discharge. Lipid testing in hospital was associated with higher rates of initiation or escalation of statin therapy within 90 days of their ACS (adjusted odds ratio, 2.13 [95% CI, 1.97–2.30). In total, 9592 patients (39.6% of the tested cohort) would be eligible for PCSK9i use, which could result in 184 fewer cardiovascular events over 3.4 years, including cardiovascular death, nonfatal ACS (myocardial infarction or unstable angina requiring hospitalization), and ischemic stroke.

Conclusions:

Within 90 days of incident ACS, ≈80% of patients did not meet guideline-recommended lipid thresholds and more than one-third would potentially be eligible for PCSK9i.
Trends of Coronary Artery Bypass Grafting Performance in a Cohort of Hospitals in China Between 2013 and 2018
Authors: Li Xi , Gu Dachuan , Wang Xianqiang , Diao Xiaolin , Chen Sipeng , Ma Hanping , Zhang Heng , Zhao Yan , Zheng Zhe
Published: April 2021

Background:

China has witnessed a rapid increase in the volume of coronary artery bypass grafting (CABG) but substantial gaps in the performance for CABG across the nation. The present study aimed to investigate the change in CABG performance after years of quality improvement measures in a national registry in China.

Methods:

The study included 66 971 patients who underwent isolated CABG in a cohort of 74 tertiary hospitals in China between January 2013 and December 2018. Data were collected from the Chinese Cardiac Surgery Registry. Outcomes were in-hospital mortality and postoperative length of stay. Five process measures for surgical technique and secondary prevention were also analyzed. We described the changes in the overall performance and interhospital heterogeneity across the years.

Results:

The in-hospital mortality declined from 0.9% in 2013 to 0.6 in 2018, with a risk-adjusted odds ratio of 0.66 (95% CI, 0.46–0.93;
P
<0.001). The standard mean difference for risk-standardized mortality rate between hospitals in the lowest and highest quartile narrowed from 1.63 in 2013 to 1.35 in 2018. The median (interquartile range) hospital-level rate of using arterial graft increased from 93.9% (86.0%–97.8%) to 94.6% (83.3%–99.2%), but the difference was not statistically significant. Meanwhile, the rate of free from blood transfusion increased from 17.0% (2.6%–32.0%) to 34.1% (8.8%–52.9%). The hospital-level rate of prescribing β-blockers at discharge significantly increased from 82.8% (66.7%–90.3%) to 91.1% (82.1%–97.1%), statin from 75.8% (55.7%–88.9%) to 88.9% (75.0%–96.0%), and aspirin from 90.3% (83.9%–95.2%) to 95.3% (88.9%–98.1%).

Conclusions:

In the Chinese Cardiac Surgery Registry, there were notable improvements in the treatment process related to CABG and decline of in-hospital mortality with reduced interhospital heterogeneity.
Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases
Authors: Sahoo Susmita , Adamiak Marta , Mathiyalagan Prabhu , Kenneweg Franziska , Kafert-Kasting Sabine , Thum Thomas
Published: April 2021

Exosomes are small membrane-bound vesicles of endocytic origin that are actively secreted. The potential of exosomes as effective communicators of biological signaling in myocardial function has previously been investigated, and a recent explosion in exosome research not only underscores their significance in cardiac physiology and pathology, but also draws attention to methodological limitations of studying these extracellular vesicles. In this review, we discuss recent advances and challenges in exosome research with an emphasis on scientific innovations in isolation, identification, and characterization methodologies, and we provide a comprehensive summary of web-based resources available in the field. Importantly, we focus on the biology and function of exosomes, highlighting their fundamental role in cardiovascular pathophysiology to further support potential applications of exosomes as biomarkers and therapeutics for cardiovascular diseases.
Upregulation of Piezo1 (Piezo Type Mechanosensitive Ion Channel Component 1) Enhances the Intracellular Free Calcium in Pulmonary Arterial Smooth Muscle Cells From Idiopathic Pulmonary Arterial Hypertension Patients
Authors: Liao Jing , Lu Wenju , Chen Yuqin , Duan Xin , Zhang Chenting , Luo Xiaoyun , Lin Ziying , Chen Jiyuan , Liu Shiyun , Yan Han , Chen Yilin , Feng Huazhuo , Zhou Dansha , Chen Xu , Zhang Zizhou , Yang Qifeng , Liu Xinyi , Tang Haiyang , Li Jing , Makino Ayako , Yuan Jason X.-J. , Zhong Nanshan , Yang Kai , Wang Jian
Published: April 2021

Emerging studies have reported the mechanosensitive Piezo1 (piezo type mechanosensitive ion channel component 1) plays essential roles in regulating the vascular tone through mechanistic actions on intracellular calcium homeostasis. However, the specific roles of Piezo1 in pulmonary vessels remain incompletely understood. We aim to investigate whether and how Piezo1 regulates the intracellular calcium homeostasis in human pulmonary arterial smooth muscle cells (PASMCs) under normal and pulmonary arterial hypertension (PAH) conditions. Cultured human PASMCs isolated from both control donors and idiopathic PAH patients were used as cell models. Fura-2 based intracellular calcium imaging was performed to measure the intracellular free calcium concentration ([Ca
2+
]
i
). Results showed that activation of Piezo1 by Yoda1 increases [Ca
2+
]
i
by inducing both intracellular calcium release from internal calcium stores through the intracellular (intra-) Piezo1 localized at the subcellular organelles, including endoplasmic reticulum/sarcoplasmic reticulum, mitochondria, and nucleus; as well as extracellular calcium influx through the plasma membrane-localized Piezo1 in a mechanism independent of the store-operated calcium entry. Moreover, the Piezo1-mediated increase of [Ca
2+
]
i
is linked to increased contraction and proliferation of PASMCs. Yoda1 induces dose-dependent vasocontraction in endothelium-denuded rat intrapulmonary arteries. Significant upregulation and increased activity of Piezo1 were observed in idiopathic PAH-PASMCs versus donor-PASMCs, contributing to the increased [Ca
2+
]
i
and excessive proliferation of idiopathic PAH-PASMCs. In summary, Piezo1 mediates the increase of [Ca
2+
]
i
by triggering both intracellular calcium release and extracellular influx. The enhanced Piezo1 expression and activity accounts, at least partially, for the abnormally elevated [Ca
2+
]
i
and proliferation in idiopathic PAH-PASMCs.
CRISPR/Cas9 Mediated Deletion of the Angiotensinogen Gene Reduces Hypertension: A Potential for Cure?
Authors: Sun Hualing , Hodgkinson Conrad P. , Pratt Richard E. , Dzau Victor J.
Published: April 2021

Hypertension is a major contributor to the global burden of disease. Unfortunately, hypertension is controlled in less than one-fifth of patients worldwide due to either failure to treat or lack of compliance to medication. An ideal therapy would be administered one time only and yield lifelong blood pressure control. We investigated our hypothesis that CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat–associated 9)-mediated disruption of a key gene in the renin-angiotensin system, AGT (angiotensinogen), specifically in the liver, would result in sustained and possibly lifelong reduction in blood pressure. We demonstrated in vitro that the CRISPR/Cas9 system led to a significant reduction in AGT expression in hepatocytes. Delivery of the CRISPR/Cas9 system into the liver via the hepatocyte-targeting adeno-associated virus 8 reduced both AGT expression (40% decrease) and circulating AGT levels (30% decrease). In the SHR (spontaneously hypertensive rat) model of hypertension, CRISPR/Cas9-mediated loss of AGT expression reduced blood pressure in adult animals with established hypertension and prevented the spontaneous development of hypertension in young SHR. Moreover, reductions in blood pressure were prolonged and sustained up to 1 year of follow-up. In addition, the partial disruption of the hepatic AGT gene was sufficient to control hypertension but did not affect the homeostatic response to cardiovascular stress such as sodium depletion and furosemide. In summary, we have demonstrated that targeting the CRISPR/Cas9 system to hepatic AGT results in sustained reduction of blood pressure and is a potential therapy to achieve sustained and possibly lifelong control of human hypertension.
Multistability and Rare Spontaneous Transitions in Barotropic β-Plane Turbulence
Authors: Simonnet Eric , Rolland Joran , Bouchet Freddy
Published: April 2021

We demonstrate that turbulent zonal jets, analogous to Jovian ones, which are quasi stationary, are actually metastable. After extremely long times, they randomly switch to new configurations with a different number of jets. The genericity of this phenomenon suggests that most quasi-stationary turbulent planetary atmospheres might have many climates and attractors for fixed values of the external forcing parameters. A key message is that this situation will usually not be detected by simply running the numerical models, because of the extremely long mean transition time to change from one climate to another. To study such phenomena, we need to use specific tools: rare-event algorithms and large-deviation theory. With these tools, we make a full statistical mechanics study of a classical barotropic beta-plane quasigeostrophic model. It exhibits robust bimodality with abrupt transitions. We show that new jets spontaneously nucleate from westward jets. The numerically computed mean transition time is consistent with an Arrhenius law showing an exponential decrease of the probability as the Ekman dissipation decreases. This phenomenology is controlled by rare noise-driven paths called instantons. Moreover, we compute the saddles of the corresponding effective dynamics. For the dynamics of states with three alternating jets, we uncover an unexpectedly rich dynamics governed by the symmetric group of permutations, with two distinct families of instantons, which is a surprise for a system where everything seemed stationary in the hundreds of previous simulations of this model. We discuss the future generalization of our approach to more realistic models.
On the Momentum Flux of Vertically-Propagating Orographic Gravity Waves Excited in Nonhydrostatic Flow over Three-dimensional Orography
Authors: Xu Xin , Li Runqiu , Teixeira Miguel A. C. , Lu Yixiong
Published: April 2021

This work studies nonhydrostatic effects (NHE) on the momentum flux of orographic gravity waves (OGWs) forced by isolated three-dimensional orography. Based on linear wave theory, an asymptotic expression for low horizonal Froude number ( where (U, V) is the mean horizontal wind, γ and a are the orography anisotropy and half-width and N is the buoyancy frequency) is derived for the gravity wave momentum flux (GWMF) of vertically-propagating waves. According to this asymptotic solution, which is quite accurate for any value of Fr, NHE can be divided into two terms (NHE1 and NHE2). The first term contains the high-frequency parts of the wave spectrum that are often mistaken as hydrostatic waves, and only depends on Fr. The second term arises from the difference between the dispersion relationships of hydrostatic and nonhydrostatic OGWs. Having an additional dependency on the horizontal wind direction and orography anisotropy, this term can change the GWMF direction. Examination of NHE for OGWs forced by both circular and elliptical orography reveals that the GWMF is reduced as Fr increases, at a faster rate than for two-dimensional OGWs forced by a ridge. At low Fr, the GWMF reduction is mostly attributed to the NHE2 term, whereas the NHE1 term starts to dominate above about Fr = 0.4. The behavior of NHE is mainly determined by Fr, while horizontal wind direction and orography anisotropy play a minor role. Implications of the asymptotic GWMF expression for the parameterization of nonhydrostatic OGWs in high-resolution and/or variable-resolution models are discussed.
Relationship between Boreal Summer Circulation Trend and Destructive Stationary–Transient Wave Interference in the Western Hemisphere
Authors: Kim Dong Wan , Lee Sukyoung
Published: April 2021

This study examines the role of the latent heating in exciting the upper-level circulation anomaly, which destructively interferes with the climatological stationary wave in the Western Hemisphere during boreal summer. This destructive interference pattern closely resembles the circulation trend that is known to be responsible for surface heat extreme trends. To investigate the mechanism behind this circulation anomaly, daily stationary–transient wave interference and related meteorological variables are analyzed using reanalysis data for the period of 1979–2017. Numerical model simulations forced by reanalysis heating anomalies indicate that the destructive interference pattern is most effectively excited by latent heating anomalies over the North Pacific Ocean and eastern Canada. The North Pacific heating anomaly drives circulation anomalies that not only resemble the destructive interference pattern, but also transport moisture into eastern Canada. The resulting latent heating over eastern Canada drives circulation that further reinforces the destructive interference pattern, which includes a prominent high pressure system over Greenland. Tropical heating also plays a role in driving the destructive interference pattern. On intraseasonal time scales, the destructive interference pattern is preceded by suppressed Indo–western Pacific heating and enhanced North American monsoon heating. On decadal time scales, both heating centers have strengthened, but the trend of the North American monsoon heating was greater than that of the Indo–western Pacific heating. These uneven heating trends help to explain the resemblance between the destructive interference pattern and the circulation trend over the Western Hemisphere.
A single column simulation-based decomposition of the tropical upper tropospheric warming
Authors: Wang Yuwei , Huang Yi
Published: April 2021

An atmospheric global climate model (GCM) and its associated single-column model are used to study the tropical upper tropospheric warming and elucidate how different processes drive this warming. In this modeling framework, on average the direct radiative process accounts for 13% of the total warming. The radiation increases the atmospheric lapse rate and triggers more convection, which further produces 74% of the total warming. The rest 13% is attributable to the circulation adjustment. The relative importance of these processes differs in different regions. In the deep tropics, the radiative-convective adjustment produces the most significant warming and accounts for almost 100% of the total warming. In the subtropics, the radiative-convective adjustment accounts for 73% of the total warming and the circulation adjustment plays a more important role than in the deep tropics, especially at the levels above 200 hPa. When the lateral boundary conditions, i.e. the temperature and water vapor advections, are held fixed in single-column simulations, the tropospheric relative humidity significantly increases in the radiative-convective adjustment in response to the surface warming. This result, in contrast to the relative humidity conservation behavior in the GCM, highlights the importance of circulation adjustment in maintaining the constant relative humidity. The tropical upper tropospheric warming in both the full GCM and the single-column simulations is found to be less strong than the warming predicted by reference moist adiabats. This evidences that the sub-moist-adiabat warming occurs even without the dilution effect of the large-scale circulation adjustment.
Atlantic Multidecadal Oscillation Drives Interdecadal Pacific Variability via Tropical Atmospheric Bridge
Authors: An Xiaohe , Wu Bo , Zhou Tianjun , Liu Bo
Published: April 2021

The interdecadal Pacific oscillation (IPO) and Atlantic multidecadal oscillation (AMO), two leading modes of decadal climate variability, are not independent. It was proposed that ENSO-like sea surface temperature (SST) variations play a central role in the Pacific responses to the AMO forcing. However, observational analyses indicate that the AMO-related SST anomalies in the tropical Pacific are far weaker than those in the extratropical North Pacific. Here, we show that SST in the North Pacific is tied to the AMO forcing by convective heating associated with precipitation over the tropical Pacific, instead of by SST there, based on an ensemble of pacemaker experiments with North Atlantic SST restored to the observation in a coupled general circulation model. The AMO modulates precipitation over the equatorial and tropical southwestern Pacific through exciting an anomalous zonal circulation and an interhemispheric asymmetry of net moist static energy input into the atmosphere. The convective heating associated with the precipitation anomalies drives SST variations in the North Pacific through a teleconnection, but it remarkably weakens the ENSO-like SST anomalies through a thermocline damping effect. This study has implications that the IPO is a combined mode generated by both AMO forcing and local air–sea interactions, but the IPO-related global warming acceleration/slowdown is independent of the AMO.
A Statistical Method for Generating Temporally Downscaled Geochemical Tracers in Precipitation
Authors: Finkenbiner Catherine E. , Good Stephen P. , Allen Scott T. , Fiorella Richard P. , Bowen Gabriel J.
Published: April 2021

Sampling intervals of precipitation geochemistry measurements are often coarser than those required by fine-scale hydrometeorological models. This study presents a statistical method to temporally downscale geochemical tracer signals in precipitation so that they can be used in high-resolution, tracer-enabled applications. In this method, we separated the deterministic component of the time series and the remaining daily stochastic component, which was approximated by a conditional multivariate Gaussian distribution. Specifically, statistics of the stochastic component could be explained from coarser data using a newly identified power-law decay function, which relates data aggregation intervals to changes in tracer concentration variance and correlations with precipitation amounts. These statistics were used within a copula framework to generate synthetic tracer values from the deterministic and stochastic time series components based on daily precipitation amounts. The method was evaluated at 27 sites located worldwide using daily precipitation isotope ratios, which were aggregated in time to provide low resolution testing datasets with known daily values. At each site, the downscaling method was applied on weekly, biweekly and monthly aggregated series to yield an ensemble of daily tracer realizations. Daily tracer concentrations downscaled from a biweekly series had average (+/- standard deviation) absolute errors of 1.69‰ (1.61‰) for δ2H and 0.23‰ (0.24‰) for δ18O relative to observations. The results suggest coarsely sampled precipitation tracers can be accurately downscaled to daily values. This method may be extended to other geochemical tracers in order to generate downscaled datasets needed to drive complex, fine-scale models of hydrometeorological processes.
Validating the Land-Atmosphere Coupling Behavior in Weather and Climate Models Using Observationally-Based Global Products
Authors: Abdolghafoorian Abedeh , Dirmeyer Paul A.
Published: April 2021

The interactions between land and atmosphere (with terrestrial and atmospheric coupling segments) play a significant role in weather and climate. A predominant segment of land-atmosphere (L-A) feedbacks is the coupling between soil moisture (SM) and surface heat fluxes, the terrestrial coupling leg. The lack of high-quality long-term globally distributed observations, however, has hindered a robust, realistic identification of the terrestrial leg strength on a global scale. This exploratory study provides insight into how SM signals are translated into surface flux signals through the construction of a global depiction of the terrestrial leg from several recently developed global, gridded, observationally- and satellite-based data sets. The feasibility of producing global gridded estimates of L-A coupling metrics is explored. Five weather and climate models used for subseasonal to seasonal forecasting are confronted with the observational estimates to discern discrepancies that may affect their ability to predict phenomena related to L-A feedbacks, such as drought or heat waves. The terrestrial feedback leg from observations corroborates the “hot spots” of L-A coupling found in modeling studies, but the variances in daily time series of surface fluxes differ markedly. Better agreement and generally higher confidence are seen in metrics using latent heat flux than sensible heat flux. Observational metrics allow for clear stratification of model fidelity that is consistent across seasons, despite observational uncertainty. The results highlight the impact of SM on partitioning available surface energy and illustrate the potential of global observationally-based data sets for the assessment of such relationships in weather and climate models.
A Nearshore Oceanic Front Induced By Wave Streaming
Authors: Wang Peng , McWilliams James C. , Uchiyama Yusuke
Published: April 2021

Coastal fronts impact cross-shelf exchange of materials, such as plankton and nutrients, which are important to the ecosystems in continental shelves. Here using numerical simulation we demonstrate a nearshore front induced by wave streaming. Wave streaming is a bottom Eulerian current along the surface wave direction, and it is caused by the wave bottom dissipation. Wave streaming drives a Lagrangian overturning circulation in the inner shelf and pumps up deep and cold water into the overturning circulation. The water inside the overturning circulation is quickly mixed and cooled because of the wave streaming-enhanced viscosity. However, the offshore water outside the overturning circulation remains stratified and warmer. Hence, a front develops between the water inside and outside the overturning circulation. The front is unstable and generates submesoscale shelf eddies, which lead the offshore transport across the front. This study presents a new mechanism for coastal frontogenesis.
Deep-learning-based precipitation observation quality control
Authors: Sha Yingkai , Gagne David John , West Gregory , Stull Roland
Published: April 2021

We present a novel approach for the automated quality control (QC) of precipitation for a sparse station observation network within the complex terrain of British Columbia, Canada. Our QC approach uses Convolutional Neural Networks (CNNs) to classify bad observation values, incorporating a multi-classifier ensemble to achieve better QC performance. We train CNNs using human QC’d labels from 2016 to 2017 with gridded precipitation and elevation analyses as inputs. Based on the classification evaluation metrics, our QC approach shows reliable and robust performance across different geographical environments (e.g., coastal and inland mountains), with 0.927 Area Under Curve (AUC) and type I/type II error lower than 15%. Based on the saliency-map-based interpretation studies, we explain the success of CNN-based QC by showing that it can capture the precipitation patterns around, and upstream of the station locations. This automated QC approach is an option for eliminating bad observations for various applications, including the pre-processing of training datasets for machine learning. It can be used in conjunction with human QC to improve upon what could be accomplished with either method alone.
A Progress Report on the Development of the High-Resolution Rapid Refresh Ensemble
Authors: Kalina Evan A. , Jankov Isidora , Alcott Trevor , Olson Joseph , Beck Jeffrey , Berner Judith , Dowell David , Alexander Curtis
Published: April 2021

The High-Resolution Rapid Refresh Ensemble (HRRRE) is a 36-member ensemble analysis system with 9 forecast members that utilizes the Advanced Research version of the Weather Research and Forecasting (ARW-WRF) dynamic core and the physics suite from the operational Rapid Refresh/High-Resolution Rapid Refresh deterministic modeling system. A goal of HRRRE development is a system with sufficient spread among members, comparable in magnitude to the random error in the ensemble mean, to represent the range of possible future atmospheric states. HRRRE member diversity has traditionally been obtained by perturbing the initial and lateral boundary conditions of each member, but recent development has focused on implementing stochastic approaches in HRRRE to generate additional spread. These techniques were tested in retrospective experiments and in the May 2019 Hazardous Weather Testbed Spring Experiment (HWT-SE). Results show a 6%–25% increase in the ensemble spread in 2-m temperature, 2-m mixing ratio, and 10-m wind speed when stochastic parameter perturbations are used in HRRRE (HRRRE-SPP). Case studies from HWT-SE demonstrate that HRRRE-SPP performed similar to or better than the operational High-Resolution Ensemble Forecast system, version 2 (HREFv2), and the nonstochastic HRRRE. However, subjective evaluations provided by HWT-SE forecasters indicated that overall, HRRRE-SPP predicted lower probabilities of severe weather (using updraft helicity as a proxy) compared to HREFv2. A statistical analysis of the performance of HRRRE-SPP and HREFv2 from the 2019 summer convective season supports this claim, but also demonstrates that the two systems have similar reliability for prediction of severe weather using updraft helicity.
How material deprivation impacted economic stress across European countries during the great recession. A lesson on social comparisons
Authors: Kley Stefanie
Published: April 2021

The development of a common standard of consumption is one goal of the ongoing harmonization of the EU member states’ economies. As a result, the degree to which household deprivation affects people’s economic stress should converge. Based on comparison theory, such convergence could be one indicator for Europe growing together (‘Europeanization’). The association between deprivation and economic stress is tested across and between 28 EU countries with EU-SILC data. Moreover, it is examined whether this association changed between 2007 and 2015, as the great recession starting in 2008 affected European countries differently. The results show that, given a certain level of household deprivation, people judge their situation differently across Europe. Whereas economic stress levels are higher in relatively poor countries, the deprivation-stress link is stronger in rich countries. Across-time comparisons suggest no decline in the extent to which a country’s deprivation level moderated the effect of household deprivation on economic stress. The findings support the persistence of national reference groups against which individuals judge their own economic situation.
The Nexus of Trade Openness, Institutions and Economic Growth: An Empirical Investigation of BRICS Countries
Authors: Sheikh Mehraj Ahmad , Malik Mushtaq Ahmad
Published: April 2021

The empirical limits of this study lie in investigating the nexus between trade openness, institutional quality and economic growth in emerging BRICS countries. Having nascent institutions, the study aims to analyse their role in determining the trade–growth relationship. Using endogeneity expunging GMM technique, the empirical evidence shows—first, imports play a crucial part in augmenting growth. While exports and overall trade openness do show a positive impact, they lack the statistical significance. Second, institutional infrastructure shows an indirect effect by augmenting the economic performance when complemented with higher imports. These countries stand to gain more from imports with improved institutional infrastructure.

JEL Codes: F10, O4, C23