Search

Indoor positioning is an important component of location-based service. Moreover, it has extensive applications in areas such as the Internet of Things (IoT) and Artificial Intelligence (AI). As a new generation of the mobile communication signal, the introduction of technologies such as multi-carrier, massive multiple-input multiple-output (MIMO), and ultra-dense network (UDN) has enabled 5G NR signal to demonstrate unique technical advantages in the field of indoor positioning. In this paper, for indoor positioning, a subcarrier diversity precision ranging method based on a commercial 5G NR signal is proposed. According to the results of field experiments in the indoor environment, the proposed method significantly improves the ranging precision compared to the Reference Signal Receiving Power (RSRP)-based ranging method. When the diversity ratio is set to 0.25, the 95% cumulative distribution function (CDF) of the overall ranging error is less than 3 meters.

Hai-Yun Zhang,1– 3 Qiu-Meng Xie,1– 3 Cui-Cui Zhao,1– 3 Jia-Feng Sha,1– 3 Ya Ruan,1– 3 Hui-Mei Wu1– 3 1Anhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Geriatric Molecular Medicine of Anhui Province, Hefei, Anhui, People’s Republic of China; 3Key Laboratory of Respiratory Disease Research and Medical Transformation of Anhui Province, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hui-Mei WuAnhui Geriatric Institute, Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaTel +86 551 65120742Email wuhm@ahmu.edu.cnPurpose: CpG-ODN has been found to attenuate allergic airway inflammation in our previous study. Here, we aimed to further investigate whether CpG-ODN exerts such effect via regulating endoplasmic reticulum (ER) stress and revealed the underlying mechanism.Methods: Five-week-old C57BL/6 mice were randomly grouped and treated with or without CpG-ODN or/and SP600125. Meantime, RAW264.7 cells were used to investigate the effect of CpG-ODN on OVA-induced ER stress in vitro. The cellularity of bronchoalveolar lavage fluid (BALF) was classified and counted after Wright–Giemsa staining. HE and PAS staining methods were applied to analyze airway inflammation. The protein levels of IL-4, IL-5, IL-13, p-JNK, JNK, CHOP, XBP1, ATF6α and GRP78 in lung tissues were detected by Western blotting. Correspondingly, the ER stress markers were detected by Western blotting and immunofluorescence in RAW264.7 cells.Results: In OVA-induced allergic airway inflammation, CpG-ODN significantly suppressed inflammatory cells infiltration, goblet cell hyperplasia and the protein expression of Th2 cytokines. Moreover, OVA exposure strongly increased the activation of ER stress with higher protein expressions of CHOP, XBP1, ATF6α and GRP78. However, these OVA-induced increase of ER stress markers were markedly suppressed by CpG-ODN treatment. In addition, exposure to OVA significantly increased the phosphorylation of JNK, which was significantly reduced by CpG-ODN treatment. Remarkably, single treatment of SP600125, an antagonist of JNK, functioned similarly as CpG-ODN in mitigating allergic airway inflammation and suppressing OVA-induced activation of ER stress; however, no significant synergistic effect was evidenced by combined treatment of SP600125 and CpG-ODN. Furthermore, in OVA-stimulated RAW264.7 cells, we also found that OVA stimulation increased the expressions of ER stress markers, and CpG-ODN significantly reduced their expression levels via suppressing the phosphorylation of JNK.Conclusion: These results indicated that CpG-ODN mitigates allergic airway inflammation via suppressing the activation of JNK-medicated ER stress.Keywords: asthma, CpG-ODN, SP600125, endoplasmic reticulum homeostasis

Yuhui Ruan,1 Weisin Chen,2 Chenyang Zhuang,2 Hong Lin2,3 1School of International and Public Affairs, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Institute of Medical Science Popularization, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hong LinDepartment of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaTel +86 13636526656Email lin.hong1@zs-hospital.sh.cnPurpose: This study aimed to elucidate the quality of life of older adults/patients with degenerative lumbar diseases (ODLs) and analyse its association with some of their health-related perceptions.Materials and Methods: This mixed-methods study consisted of a questionnaire survey and an in-depth interview, which was designed within this study. ODLs were recruited from January 12, 2017 to June 27, 2018. The independent sample t-test and grounded theory coding method were employed for data analysis.Results: Of the 125 participants who returned valid questionnaires, 18 were included in the in-depth interviews. ODLs’ quality of life was associated with the following health-related perceptions: “life barriers”, “subjective health status”, and “treatment outcomes” across the domains of physiology, psychology, social relations, and environment.Conclusion: Our findings indicate that ODLs’ quality of life is associated with their health-related perceptions. Thus, to improve older adults’ quality of life, more attention should be paid to enhancing non-medical factors such as their health-related perceptions.Keywords: life barriers, subjective health status, treatment outcomes

BACKGROUND: We used detailed information on patients with diabetes admitted to hospital to determine differences in clinical outcomes before and during the COVID-19 pandemic in the UK. METHODS: The study used electronic patient record data from Imperial College Healthcare NHS Trust. Hospital admission data for patients coded for diabetes was analysed over three time periods: pre-pandemic (31st January 2019-31st January 2020), Wave 1 (1st February 2020-30th June 2020), and Wave 2 (1st September 2020-30th April 2021). We compared clinical outcomes including glycaemia and length of stay. RESULTS: We analysed data obtained from 12,878, 4008 and 7189 hospital admissions during the three pre-specified time periods. The incidence of Level 1 and Level 2 hypoglycaemia was significantly higher during Waves 1 and 2 compared to the pre-pandemic period (25 % and 25.1 % vs. 22.9 % for Level 1 and 11.7 % and 11.5 % vs. 10.3 % for Level 2). The incidence of hyperglycaemia was also significantly higher during the two waves. The median hospital length of stay increased significantly (4.1[1.6, 9.8] and 4.0[1.4, 9.4] vs. 3.5[1.2, 9.2] days). CONCLUSIONS: During the COVID-19 pandemic in the UK, hospital in-patients with diabetes had a greater number of hypoglycaemic/hyperglycaemic episodes and an increased length of stay when compared to the pre-pandemic period. This highlights the necessity for a focus on improved diabetes care during further significant disruptions to healthcare systems and ensuring minimisation of the impact on in-patient diabetes services. SUMMARY: Diabetes is associated with poorer outcomes from COVID-19. However the glycaemic control of inpatients before and during the COVID-19 pandemic is unknown. We found the incidence of hypoglycaemia and hyperglycaemia was significantly higher during the pandemic highlighting the necessity for a focus on improved diabetes care during further pandemics.

Dixing Liu, Jiana Zhong, Weiheng Wen, Yuting Ruan, Zhen Zhang, Jia Sun, Hong Chen Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Hong Chen; Jia SunDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, Guangdong, 510282, People’s Republic of ChinaTel +86 13602759769; +86 13751822925Email chenhong123@smu.edu.cn; sunjia@smu.edu.cnPurpose: Either visceral fat or muscle mass is identified to be correlated with cardiometabolic diseases, especially in type 2 diabetes (T2DM). But, the synergistical effect of visceral fat along with skeletal muscle on the risk of cardiovascular diseases (CVD) in T2DM still remains controversial. Thus, we investigated the relationship between skeletal muscle mass to visceral fat area ratio (SVR) and 10-yr CVD risk scores.Patients and Methods: A total of 291 T2DM patients aged 40– 80 years were enrolled in the current study. SVR was evaluated based on bioelectrical impedance measurements. Both Framingham risk score system and China-PAR risk model were applied to estimate future 10-yr CVD risk in T2DM population.Results: The 10-yr CVD risk scores increased with the decreased SVR tertiles in T2DM (All P< 0.001). SVR value was obviously lower in the high-risk group than that of low- or moderate-risk group (All P< 0.05). However, no significant differences were observed in BMI among different CVD risk groups. Besides, SVR was correlated with Framingham risk score (r=− 0.408; P< 0.001) and China-PAR risk score (r=− 0.336; P< 0.001). HOMA-IR, triglycerides and blood pressure were also inversely related to SVR (All P< 0.05). Furthermore, SVR value was independently correlated with both Framingham 10-yr CVD risk score (β=− 0.074, P=0.047) and China-PAR risk score (β=− 0.100, P=0.004) after adjustment for confounding factors, including age, gender, BMI, FPG, HbA1c, diabetes duration, albumin, creatinine, uric acid, smoking, blood pressure and blood lipid. The linear regression analysis was also conducted for men and women, respectively, indicating that the negative relationship between SVR and 10-yr CVD risk was observed in men but not in women.Conclusion: T2DM populations who have lower SVR value are more likely to increase CVD risk. SVR levels show marked and inverse correlation with estimated 10-yr CVD risk in T2DM, indicating that SVR could be a valuable parameter to assess the risk of CVD events in clinical practice, especially in men.Keywords: type 2 diabetes mellitus, cardiovascular diseases, skeletal muscle mass to visceral fat area ratio, risk assessment

Ran Zheng, Yang Ruan, Yiqun Yan, Zhihao Lin, Naijia Xue, Yaping Yan, Jun Tian, Xinzhen Yin, Jiali Pu, Baorong Zhang Department of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Baorong Zhang; Jiali PuDepartment of Neurology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, People’s Republic of ChinaFax +86-571-87784752Email brzhang@zju.edu.cn; jialipu@zju.edu.cnBackground: Inflammasome-induced neuroinflammation is a key contributor to the pathology of Parkinson’s disease (PD). NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation has been implicated in PD in postmortem human PD brains, indicating it as a potential target for PD treatment. Melatonin, a multitasking molecule, has been found to have anti-inflammatory activities, mediated by silence information regulator 1 (SIRT1). However, whether and how melatonin is involved in inflammasome-induced neuroinflammation in PD pathogenesis remains unclear.Methods: We investigated the potential anti-inflammatory effects of melatonin in vitro and in vivo, using 1-methyl-4-phenylpyridinium (MPP+)-simulated BV2 and primary microglia cell models, and a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine PD model, with or without melatonin treatment. Rotarod, grip strength, and open-field tests were performed to measure the effects of melatonin on MPTP-induced motor disorders. Degeneration of dopaminergic neurons was evaluated by immunofluorescence. Changes in microglia were examined by immunofluorescence and Western blotting, and the expression levels of the involved signaling molecules were assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) was detected using fluorescent probes via flow cytometry.Results: We found that melatonin significantly alleviated motor dysfunction and prevented MPTP-induced neurotoxicity in dopaminergic neurons. Additionally, melatonin reduced MPTP-induced microglial activation and suppressed NLRP3 inflammasome activity, and also inhibited IL-1β secretion. Moreover, in MPP+-primed BV2 cells, melatonin markedly restored the downregulation of SIRT1 and attenuated the activation of the NLRP3 inflammasome. This was reversed by SIRT1 inhibitor treatment.Conclusion: In conclusion, our data demonstrated that melatonin attenuates neuroinflammation by negatively regulating NLRP3 inflammasome activation via a SIRT1-dependent pathway in MPTP-induced PD models. These findings provide novel insights into the mechanism underlying the anti-inflammatory effects of melatonin in PD.Keywords: inflammasomes, melatonin, NLRP3, Parkinson disease, sirtuin 1

Jingjie Hu,&ast; Liuyuan Wang,&ast; Kaili Fan, Wenwei Ren, Qiongzhang Wang, Yiting Ruan, Chengxiang Yuan, Guiqian Huang, Jincai He Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincai He; Guiqian HuangDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel +86 577-555780166; +86 577-555781380Fax +86 577-55578033; +86 577-55578999Email hjc@wmu.edu.cn; huangguiqian123@126.comObjective: Inflammation plays an important role in stroke. Many inflammatory markers in peripheral blood are proved to be associated with stroke severity or prognosis. But few comprehensive models or scales to evaluate the post-stroke depression (PSD) have been reported. In this study, we aimed to compare the level of systemic inflammation markers between PSD and non-PSD patients and explore the association of these inflammatory markers with PSD.Methods: Totally, 432 ischemic stroke patients were consecutively enrolled in the study and received 1 month follow-up. We used the 17-Hamilton Rating Scale to measure depressive symptoms at 1 month after stroke. With the Hamilton Depression Scale score of > 7, patients were diagnosed with PSD. Systemic immune-inflammation index (SII), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and derived neutrophil-to-lymphocyte ratio (dNLR) were calculated from the admission blood work.Results: Finally, 129 patients (30.5%) were diagnosed with PSD at 1 month. PSD patients showed significantly higher levels of SII (501.27 (345.43– 782.58) vs 429.60 (315.64– 570.98), P=0.001), NLR (2.36 (1.77– 3.82) vs 2.17 (1.56– 2.80), P=0.010), dNLR (1.67 (1.30– 2.51) vs 1.54 (1.16– 1.99), P=0.009), PLR (124.65 (95.25– 155.15) vs 109.22 (92.38– 142.03), P=0.015), especially SII at admission as compared to non-PSD patients. In the logistic analysis, SII value (> 547.30) was independently associated with the occurrence of PSD (OR=2.181, 95% CI=1.274– 3.732, p =0.004), better than dNLR (OR=1.833, 95% CI=1.071– 3.137, p =0.027), PLR (OR= 1.822, 95% CI=1.063– 3.122, p =0.029) and NLR (OR =1.728, 95% CI=1.009– 2.958, p =0.046).Conclusion: Increased SII, PLR, dNLR, NLR, particularly SII at admission, are significantly correlated with PSD and may add some prognostic clues to find early discovery of PSD.Keywords: inflammatory markers, post-stroke depression, systemic immune-inflammation index, neutrophil-to-lymphocyte, platelet-to-lymphocyte, derived neutrophil-to-lymphocyte ratio

Hanxin Zhao, Yu Ruan Department of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yu RuanDepartment of Endocrinology and Metabolism, Zhejiang University Affiliated Sir Run Run Shaw Hospital, School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, People’s Republic of ChinaTel +86 571 86006171Email ruanyu2019@zju.edu.cnIntroduction: In recent years, radioactive iodine (RAI) therapy has become a main choice for Graves’ disease. The rapid release of thyroid hormones following RAI may on occasion trigger severe events, such as thyroid storm or heart block. This study presents two cases of possible acute adrenocortical insufficiency precipitated by radioiodine therapy.Case Presentation: Two females aged 65 and 19 years with long-standing Graves’ disease underwent radioiodine treatment at our clinical center. Both patients suffered nausea, fatigue, aggravated palpitation, and relative hypotension thereafter. Laboratory data showed severe thyrotoxicosis with free thyroxine higher than three times the upper limit, while basal serum cortisol (8 AM) was below the lower limit (5.08 μg/dL and 2.08 μg/dL respectively) under stress, indicating a potential relative adrenocortical insufficiency. There was then full recovery after adequate hydrocortisone therapy. As thyrotoxicosis resolved, the levels of basal cortisol were subsequently raised to normal.Conclusion: Post-RAI adrenocortical insufficiency might occur in patients with severe Graves’ disease. Basal serum cortisol might be a cost-effective parameter for the identification of potential patients.Keywords: Graves’ disease, hyperthyroidism, adrenal insufficiency, radioiodine therapy

Chengxiang Yuan,1,* Siyan Chen,1,* Yiting Ruan,1 Yuntao Liu,1 Haoran Cheng,1 Yaying Zeng,1 Yunbin Chen,1 Qianqian Cheng,2 Guiqian Huang,1 Weilei He,1 Jincai He1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jincai HeDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 0577 55579363Email hjc@wmu.edu.cnBackground: Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. Stress hyperglycemia is frequent in patients with acute illness such as stroke. We aimed to explore the association between stress hyperglycemia and HT in AIS patients.Methods: A total of 287 consecutive participants with HT and 285 age- and sex-matched stroke patients without HT were enrolled in this study. Baseline glucose and glycated hemoglobin (HbA1c) levels were collected to measure stress hyperglycemia. The stress hyperglycemia ratio (SHR) was calculated by dividing the fasting plasma glucose at admission with HbA1c. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction type (HI) 1 or 2 or parenchymal hematoma type (PH) 1 or 2.Results: Univariate analysis showed that SHR is significantly higher among patients with HT than those without HT. Compared to the patients in the lower three quartiles of SHR, the incidence of HT was significantly higher among patients with the highest quartile of SHR in total population, diabetic and non-diabetic population. We also observed that patients with the highest SHR quartile were associated with an increased risk of hemorrhagic transformation after adjusted for potential covariates (68.4% versus 39.1%; adjusted odds ratio, 2.320; 95% confidence interval, 1.207– 4.459; P=0.012).Conclusion: The stress hyperglycemia ratio, representing the state of stress hyperglycemia, was significantly associated with an increased risk of hemorrhagic transformation in patients with acute ischemic stroke.Keywords: hyperglycemia, hemorrhagic transformation, acute ischemic stroke, stress hyperglycemia

Pengyu Zhang,1,* Jun Xiao,2,* Yingxin Ruan,3,* Zhenzhen Zhang,1 Xuejun Zhang2 1Department of Blood Transfusion, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin 300060, People’s Republic of China; 2Department of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, People’s Republic of China; 3Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejun ZhangDepartment of Immunology, Key Laboratory of Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People’s Republic of ChinaTel +86 151 2280 0672Email xjzhimmunology@163.comPurpose: The aim of this study was to investigate the monitoring value of serum HER2 in patients with metastatic breast cancer.Patients and Methods: We firstly evaluated the association of serum HER2 levels with tissue HER2 expression and imaging results in 420 breast cancer patients admitted into Tianjin Medical University Cancer Institute and Hospital between April 2016 and December 2018. Secondly, we analyzed serum HER2 levels in breast cancer patients with different metastatic degrees.Results: There is a higher correlation between serum HER2 and tissue HER2 in breast cancer patients with stage III (κ=0.670, p< 0.001) and stage IV (κ=0.464, p< 0.001). Serum HER2 levels were significantly associated with imaging results (κ=0.478, p< 0.001). The ROC curve analysis showed that serum HER2 was superior to other serum markers for predicting metastatic breast cancer. Multinomial logistic regression revealed that the patients with higher serum HER2 levels would be more likely to have breast cancer metastasis.Conclusion: Serum HER2 levels in breast cancer patients can partly reflect tissue HER2 expression and tumor imaging changes, and serum HER2 may be used as a biomarker for evaluating metastatic status in patients with breast cancer.Keywords: serum HER2, breast cancer, tumor metastasis, biomarker

Shasha Lin, 1,* Xiaoqian Luan, 1,* Weilei He, 1,* Yiting Ruan, 1 Chengxiang Yuan, 1 Aiyue Fan, 1 Xiachan Chen, 2 Jincai He 1 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People’s Republic of China; 2Department of Neurology, Wenzhou 325000, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jincai HeDepartment of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, People’s Republic of ChinaTel/Fax +86 577 5557 9363Email hjc@wmu.edu.cnPurpose: Post-stroke depression (PSD) is a frequent comorbidity in patients presenting with acute ischemic stroke. Impaired kidney function has been associated with depression in non-stroke subjects. We would like to evaluate whether the estimated glomerular filtration rate (eGFR) on admission is associated with the development of PSD.Patients and methods: Total of 268 patients with acute ischemic stroke were recruited and completed 1-month follow-up visit. eGFR was calculated from the serum creatinine value, race, age, and sex by using the chronic kidney disease epidemiology collaboration equation (CKD-EPI creatinine equation). The 17-item Hamilton Depression Scale was used to evaluate depression symptoms. Patients with a depression score of ≥ 7 were evaluated using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for diagnosing post-stroke depression at 1 month. Meanwhile, 114 normal control subjects were also recruited.Results: Ninety-three (34.7%) patients were diagnosed as having PSD at 1 month. There was a significant intergroup difference in eGFR levels within 24 hrs after admission (F=13.608, p< 0.001). The levels of eGFR within 24 hrs after admission were significantly lower in both non-PSD patients and PSD patients than in normal controls. In logistic regression, the level of eGFR (< 82mL/min/1.73m 2) was independently associated with increased risk of PSD even after adjusting for confounders (OR=2.328, 95% CI:1.092– 4.965, p=0.029).Conclusion: Reduced eGFR was found to be correlated with the development of PSD and it suggests the need for greater attentions and potential interventions for depression in patients with stroke and with reduced eGFR.Keywords: estimated glomerular filtration rate, eGFR, post-stroke depression, stroke, Depression

Ligen Du,1–3 Enping Chen,2 Ting Wu,4 Yunjun Ruan,1 Saizhu Wu1 1Department of Geriatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; 2Department of Cardiology, The Second People’s Hospital of Longgang District, Shenzhen, Guangdong, China; 3Department of Cardiology, Longgang District People’s Hospital of Shenzhen, Guangdong, China; 4Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, China Purpose: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. Materials and methods: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related β-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagy-related markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. Results: Pretreatment with 10 µM RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated β-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 µM RESV. As compared to the H2O2 treatment group, 10 µM RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. Conclusion: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases. Keywords: oxidative stress, senescence, LC3, p62, p-Rb

Polygenic risk scores (PRSs) have been among the leading advances in biomedicine in recent years. As a proxy of genetic liability, PRSs are utilised across multiple fields and applications. While numerous statistical and machine learning methods have been developed to optimise their predictive accuracy, all of these distil genetic liability to a single number based on aggregation of an individual’s genome-wide alleles. This results in a key loss of information about an individual’s genetic profile, which could be critical given the functional sub-structure of the genome and the heterogeneity of complex disease. Here we evaluate the performance of pathway-based PRSs, in which polygenic scores are calculated across genomic pathways for each individual, and we introduce a software, PRSet, for computing and analysing pathway PRSs. We find that pathway PRSs have similar power for evaluating pathway enrichment of GWAS signal as the leading methods, with the distinct advantage of providing estimates of pathway genetic liability at the individual-level. Exemplifying their utility, we demonstrate that pathway PRSs can stratify diseases into subtypes in the UK Biobank with substantially greater power than genome-wide PRSs. Compared to genome-wide PRSs, we expect pathway-based PRSs to offer greater insights into the heterogeneity of complex disease and treatment response, generate more biologically tractable therapeutic targets, and provide a more powerful path to precision medicine.

Latent variable models have been successfully applied in lossless compression with the bits-back coding algorithm. However, bits-back suffers from an increase in the bitrate equal to the KL divergence between the approximate posterior and the true posterior. In this paper, we show how to remove this gap asymptotically by deriving bits-back coding algorithms from tighter variational bounds. The key idea is to exploit extended space representations of Monte Carlo estimators of the marginal likelihood. Naively applied, our schemes would require more initial bits than the standard bits-back coder, but we show how to drastically reduce this additional cost with couplings in the latent space. When parallel architectures can be exploited, our coders can achieve better rates than bits-back with little additional cost. We demonstrate improved lossless compression rates in a variety of settings, especially in out-of-distribution or sequential data compression.

Histone H3 lysine‐9 di‐methylation (H3K9me2) and lysine‐27 tri‐methylation (H3K27me3) are linked to repression of gene expression, but the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. Here, we report that lysine demethylases 7A (KDM7A) and 6A (UTX) play crucial roles in tumor necrosis factor (TNF)‐α signaling in endothelial cells (ECs), where they are regulated by a novel TNF‐α‐responsive microRNA, miR‐3679‐5p. TNF‐α rapidly induces co‐occupancy of KDM7A and UTX at nuclear factor kappa‐B (NF‐κB)‐associated elements in human ECs. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and are both required for activation of NF‐κB‐dependent inflammatory genes. Chromosome conformation capture‐based methods furthermore uncover increased interactions between TNF‐α‐induced super enhancers at NF‐κB‐relevant loci, coinciding with KDM7A and UTX recruitments. Simultaneous pharmacological inhibition of KDM7A and UTX significantly reduces leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF‐κB‐dependent regulation of genes that control inflammatory responses of ECs.

Aim To compare bolus insulin delivery patterns during closed‐loop home studies in adults with suboptimally [HbA1c 58–86 mmol/mol (7.5%–10%)] and well‐controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. Methods Retrospective analysis of daytime and night‐time insulin delivery during home use of closed‐loop over 4 weeks. Daytime and night‐time controller effort, defined as amount of insulin delivered by closed‐loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. Results Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well‐controlled diabetes. Controller effort during both daytime (P = 0.007) and night‐time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9–10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = –0.21, P = 0.19). Conclusion More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed‐loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality., What's new? Glucose control during hybrid closed‐loop therapy is linked to bolusing behaviour.Closed‐loop users with well‐controlled Type 1 diabetes bolused more frequently without increasing the risk of hypoglycaemia.We highlight the importance of user input and education to gain optimal benefit from hybrid closed‐loop.

Ye Ruan,1 Xueling Xiao,2 Jia Chen,2 Xianhong Li,2 Ann Bartley Williams,3 Honghong Wang2 1Nursing Department, Second Xiangya Hospital, 2Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 3School of Nursing, Yale University, West Haven, CT, USA Aim: The aim of this study was to examine the acceptability and efficacy of interactive short message service (SMS) in improving medication adherence in antiretroviral treatment (ART)-naïve individuals living with HIV/AIDS in Hengyang, Hunan, China.Background: SMS via mobile phone has emerged as a potential tool for improving ART adherence. However, most studies used SMS only as a medication reminder, with few studies exploring the effect of comprehensive, interactive SMS.Patients and methods: In a randomized controlled trial, 100 HIV-positive patients on ART for

Neural network based end-to-end text to speech (TTS) has significantly improved the quality of synthesized speech. Prominent methods (e.g., Tacotron 2) usually first generate mel-spectrogram from text, and then synthesize speech from the mel-spectrogram using vocoder such as WaveNet. Compared with traditional concatenative and statistical parametric approaches, neural network based end-to-end models suffer from slow inference speed, and the synthesized speech is usually not robust (i.e., some words are skipped or repeated) and lack of controllability (voice speed or prosody control). In this work, we propose a novel feed-forward network based on Transformer to generate mel-spectrogram in parallel for TTS. Specifically, we extract attention alignments from an encoder-decoder based teacher model for phoneme duration prediction, which is used by a length regulator to expand the source phoneme sequence to match the length of the target mel-spectrogram sequence for parallel mel-spectrogram generation. Experiments on the LJSpeech dataset show that our parallel model matches autoregressive models in terms of speech quality, nearly eliminates the problem of word skipping and repeating in particularly hard cases, and can adjust voice speed smoothly. Most importantly, compared with autoregressive Transformer TTS, our model speeds up mel-spectrogram generation by 270x and the end-to-end speech synthesis by 38x. Therefore, we call our model FastSpeech., Comment: Accepted by NeurIPS2019

Objective: The increasing prevalence of type 2 diabetes (T2D) and associated morbidity and mortality emphasizes the need for a more complete understanding of the mechanisms mediating glucose homeostasis to accelerate the identification of new medications. Recent reports indicate that the obesity medication lorcaserin, a 5-hydroxytryptamine (5-HT, serotonin) 2C receptor (5-HT2CR) agonist, improves glycemic control in association with weight loss in obese patients with T2D. Here we evaluate whether lorcaserin has an effect on glycemia without body weight loss and how this effect is achieved. Methods: Murine models of common and genetic T2D were utilized to probe the direct effect of lorcaserin on glycemic control. Results: Lorcaserin dose-dependently improves glycemic control in mouse models of T2D in the absence of reductions in food intake or body weight. Examining the mechanism of this effect, we reveal a necessary and sufficient neurochemical mediator of lorcaserin's glucoregulatory effects, brain pro-opiomelanocortin (POMC) peptides. To clarify further lorcaserin's therapeutic brain circuit, we examined the receptor target of POMC peptides. We demonstrate that lorcaserin requires functional melanocortin4 receptors on cholinergic preganglionic neurons (MC4RChAT) to exert its effects on glucose homeostasis. In contrast, MC4RChAT signaling did not impact lorcaserin's effects on feeding, indicating a divergence in the neurocircuitry underpinning lorcaserin's therapeutic glycemic and anorectic effects. Hyperinsulinemic-euglycemic clamp studies reveal that lorcaserin reduces hepatic glucose production, increases glucose disposal and improves insulin sensitivity. Conclusions: These data suggest that lorcaserin's action within the brain represents a mechanistically novel treatment for T2D: findings of significance to a prevalent global disease.

Qiangqiang Ge,1,* Chenghe Wang,2,* Yajun Ruan,1,* Zhong Chen,1 Jihong Liu,1 Zhangqun Ye1 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 2Department of Urology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China *These authors contributed equally tothis work Abstract: Previous research has reported that a particular double-stranded RNA, named dsP53-285, has the capacity to induce expression of the tumor suppressor gene TP53 in chimpanzee cells by targeting its promoter. Usually, it is the wild-type p53 protein, rather than mutants, which exhibits potent cancer-inhibiting effects. In addition, nonhuman primates, such as chimpanzees, share almost identical genome sequences with humans. This prompted us to speculate whether dsP53-285 can trigger wild-type p53 protein expression in human prostate cancer (PCa) cells and consequently suppress cell growth. The human PCa cell lines LNCaP and DU145 were transfected with dsP53-285 for 72hours. Compared with the dsControl and mock transfection groups, expression of both p53 messenger RNA and p53 protein was significantly enhanced after dsP53-285 transfection, and this enhancement was followed by upregulation of p21, which indirectly indicated that dsP53-285 induced wild-type p53 expression. Moreover, overexpression of wild-type p53 mediated by dsP53-285 downregulated the expression of Cyclin D1 and cyclin-dependent kinase 4/6, thereby inducing PCa cell cycle arrest in G0/G1 phase and then inhibiting cell proliferation and clonogenicity. More importantly, dsP53-285 suppressed PCa cells mainly by modulating wild-type p53 expression. In conclusion, our study provides evidence that dsP53-285 can significantly stimulate wild-type p53 expression in the human PCa cell lines LNCaP and DU145 and can exert potent antitumor effects. Keywords: p53, small activating RNA, prostate cancer

The separated silicon-vacancy (SiV) photoluminescent diamond particles were synthesized on a silica optical fiber by hot filament chemical vapor deposition (HFCVD). The effects of the pre-treated method and chamber pressure on the microstructure and photoluminescence of the diamond particles were investigated. The results show that the diamond particles are homogeneously distributed on the surface of the optical fiber. With the chamber pressure increasing from 1.6 kPa to 3.5 kPa, the shape of the particles transforms from flake to circle, while the diamond particles cannot be deposited on the fiber with the pressure further increased to 4.5 kPa. The samples synthesized under 2.5 kPa chamber pressure are composed of diamond particles with size around 200–400 nm, exhibiting stronger SiV photoluminescence with the width of around 6 nm.

Aim: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. Methods: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. Results: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). Conclusion: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.

We aimed to evaluate the relationship between insulin pharmacodynamics and glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy. We retrospectively analysed data from a multicentre randomized control trial involving 32 adults with type 1 diabetes receiving day-and-night closed-loop insulin delivery and sensor-augmented pump therapy over 12 weeks. We estimated time-to-peak insulin action (t$_{max,IA}$) and insulin sensitivity ($_Ix}$) during both interventions, and correlated these with demographic factors and glycaemic outcomes. During both interventions, t$_{max,IA}$ was positively correlated with pre- and post-intervention HbA1c (r = 0.50-0.52, P < .01) and mean glucose (r = 0.45-0.62, P < .05), and inversely correlated with time sensor glucose, which was in target range 3.9 to 10 mmol/L (r = -0.64 to -0.47, P < .05). Increased body mass index was associated with higher t$_{max,I}$ and lower S I (both P < .05). During closed-loop insulin delivery, t$_{max, IA}$, was positively correlated with glucose variability ( P < .05). Faster insulin action is associated with improved glycaemic control during closed-loop insulin delivery and sensor-augmented pump therapy.

The top-quark mass is measured in the all-hadronic top-antitop quark decay channel using proton-proton collisions at a centre-of-mass energy of root s = 8 TeV with the ATLAS detector at the CERN Large Hadron Collider. The data set used in the analysis corresponds to an integrated luminosity of 20.2 fb(-1). The large multi-jet background is modelled using a data-driven method. The top-quark mass is obtained from template fits to the ratio of the three-jet to the dijet mass. The three-jet mass is obtained from the three jets assigned to the top quark decay. From these three jets the dijet mass is obtained using the two jets assigned to the W boson decay. The top-quark mass is measured to be 173.72 +/- 0.55 (stat.) +/- 1.01 (syst.) GeV.

We study online social group dynamics based on how group members diverge in their online discussions. Previous studies mostly focused on the link structure to characterize social group dynamics, whereas the group behavior of content generation in discussions is not well understood. Particularly, we use Jensen-Shannon (JS) divergence to measure the divergence of topics in user-generated contents, and how it progresses over time. We study Twitter messages (tweets) in multiple real-world events (natural disasters and social activism) with different times and demographics. We also model structural and user features with guidance from two socio-psychological theories, social cohesion and social identity, to learn their implications on group discussion divergence. Those features show significant correlation with group discussion divergence. By leveraging them we are able to construct a classifier to predict the future increase or decrease in group discussion divergence, which achieves an area under the curve (AUC) of 0.84 and an F-1 score (harmonic mean of precision and recall) of 0.8. Our approach allows to systematically study collective diverging group behavior independent of group formation design. It can help to prioritize whom to engage with in communities for specific topics of needs during disaster response coordination, and for specific concerns and advocacy in the brand management.

International audience

The iboga alkaloids are a class of naturally occurring and synthetic compounds, some of which modify drug self-administration and withdrawal in humans and preclinical models. Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes and fatalities. hERG blockade as IKr was measured using the whole-cell patch clamp technique in HEK 293 cells. This yielded the following IC50 values: ibogaine manufactured by semisynthesis via voacangine (4.09 ± 0.69 µM) or by extraction from T. iboga (3.53 ± 0.16 µM); ibogaine’s principal metabolite noribogaine (2.86 ± 0.68 µM); and voacangine (2.25 ± 0.34 µM). In contrast, the IC50 of 18-methoxycoronaridine, a product of rational synthesis and current focus of drug development was >50 µM. hERG blockade was voltage dependent for all of the compounds, consistent with low-affinity blockade. hERG channel binding affinities (Ki) for the entire set of compounds, including 18-MC, ranged from 0.71 to 3.89 µM, suggesting that 18-MC binds to the hERG channel with affinity similar to the other compounds, but the interaction produces substantially less hERG blockade. In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion. The apparent structure–activity relationships regarding positions of substitutions on the ibogamine skeleton suggest that the iboga alkaloids might provide an informative paradigm for investigation of the structural biology of the hERG channel.

Although traditional optical fibers are not sensitive to magnetic fields, many applications would benefit from fiber-based magnetometry devices. In this study, a magnetically sensitive optical fiber was demonstrated using doping nanodiamonds containing nitrogen vacancy centers into tellurite glass fibers. The fabrication process provides a robust and isolated sensing platform as the magnetic sensors are fixed in the tellurite glass matrix. Using optically detected magnetic resonance from the doped nanodiamonds, detection of local magnetic fields via side excitation and longitudinal collection were demonstrated. This is an important step towards intrinsically magneto-sensitive fiber devices with future applications in medical magneto-endoscopy and remote mineral exploration sensing.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells.

Tumour necrosis factor alpha (TNFα) is a potent cytokine that signals through nuclear factor kappa B (NFκB) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNFα induces responsive genes to congregate in discrete 'NFκB factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories.

National audience

International audience

To estimate the prevalence of HIV and syphilis and to assess the predictors of unprotected anal intercourse (UAI) among men who have sex with men (MSM) in Beijing, a community-based survey recruited MSM in 2005 through internet advertisement, community outreach, and peer referral. Demographic, sexual, and HIV risk behavioral information were collected. Serospecimens were tested for HIV and syphilis infections. Of the 526 participants, 3.2% were HIV-positive, 11.2% syphilis-positive, 50% and 43.3% had UAI with regular and casual sex partners, respectively. Participants practicing UAI with regular male partners were independently associated with lower monthly income (adjusted odds ratio-AOR, 1.7; 95% CI, 1.0-3.0) and encountering male sex partners at bathhouses, public washrooms, and parks (AOR, 2.2; 95% CI, 1.0-4.9). Participants practicing UAI with casual male partners were associated with encountering male sex partners at bathhouses, publics washrooms, and park (AOR, 3.0; 95% CI, 1.8-5.2) and more male sex partners having receptive anal intercourse (AOR, 1.8; 95% CI, 1.1-2.9), and was inversely associated with receiving money for sex with men (AOR, 0.3; 95% CI, 0.2-0.7). Professional male sex workers were less likely to practice UAI in Beijing, suggesting the benefits of educational outreach to date. Further education, condom promotion, and prevention of sexually transmitted infections should be intensified urgently to combat the rising HIV epidemic among MSM in Beijing.

The properties of large bipolarons in two and three dimensions are investigated by averaging over the relative wavefunction of the two electrons and using the Lee-Low-Pines-Huybrechts variational method. We obtain the ground-state (GS) and excited-state energies of the Fr\"{o}hlich bipolaron for the whole range of electron-phonon coupling constants. Furthermore, we calculate the energies of the first relaxed excited state (RES) and Franck-Condon (FC) excited state of the bipolaron. Compared with the FC state, the first RES has a lower energy. Our results for the GS and RES energies are lower than those obtained before by the Landau-Pekar method in the whole coupling regime., Comment: 19 pages, 5 figures (including 8 parts)

To determine why renal vasoconstriction elicited by periarterial nerve stimulation (RNS) at lower frequencies (< 4 Hz) is resistant to alpha-adrenergic receptor blockade in the rat kidney, we reevaluated the effect of alpha-receptor antagonists on the vasoconstrictor response to norepinephrine (NE) and to RNS and on the release of adrenergic transmitter. The alpha-receptor antagonist prazosin (PZ) at 0.2 and 7 nM reduced the vasoconstrictor response to NE, and 2.4 microM PZ abolished it. PZ (0.2 or 7 nM) reduced RNS-induced vasoconstriction without altering the fractional tritium overflow. PZ (2.4 microM) enhanced fractional tritium overflow and reduced the vasoconstrictor response to RNS at 2-10 Hz, but not at 0.5 or 1 Hz. The effect of 0.2 nM PZ to reduce RNS-induced vasoconstriction was reversed by increasing the concentration to 2.4 microM. Corynanthine (COR; 2.6 microM), a preferential alpha-receptor blocker, or phenoxybenzamine (PBZ; 30 nM) abolished the vasoconstrictor response to NE but only partially reduced response to RNS and enhanced the fractional tritium overflow. Rauwolscine (RW; 2.5 nM), a preferential alpha 2-receptor antagonist, did not alter the vasoconstrictor response to NE but potentiated RNS-induced vasoconstriction and fractional tritium overflow. RW (7.7 microM) inhibited NE-induced vasoconstriction but potentiated the vasoconstrictor response to RNS and fractional tritium overflow. PZ (7 nM) abolished the potentiation by RW and reduced the vasoconstrictor response to RNS. These data suggest that a component of RNS-induced vasoconstriction in the rat kidney is attributable to co-release of a nonadrenergic transmitter with NE. The diminished effect of alpha-receptor antagonists at higher concentrations (e.g., PZ 2.4 microM) to reduce RNS-induced vasoconstriction is caused by their prejunctional action to enhance co-release of the nonadrenergic transmitter.

Pisatin is a fungistatic isoflavonoid produced by garden pea. Field isolates of the ascomycete Nectria haematococca mating population VI (anamorph: Fusarium solani) that are highly virulent on pea have been found to possess the PDA1 gene encoding a pisatin detoxifying activity. Expression of PDA1 is specifically and highly induced by exposure of mycelia to pisatin. A pisatin-responsive DNA-binding activity has previously been identified with properties suggestive of a transcriptional regulator of PDA1. In this study, the sequence determinants for binding this pisatin-responsive factor (PRF) were localized to a 14-bp region through analysis of sequence alterations that reduced PRF binding. Using a homologous in vitro transcription system, a transcriptional activator of PDA1 was shown to be present in mycelial extracts that shared the sequence specificity characteristic of the PRF, indicating function of the DNA-binding protein in transcriptional control. A 70-kDa protein was shown to be a DNA-binding component of PRF by three independent assays for DNA-binding proteins: Southwestern (DNA-protein) blotting, UV-crosslinking, and binding to immobilized DNA. These results characterize a transcriptional activator acting on the PDA1 promoter that is responsive to a host-specific compound and provide insight into the regulation of fungal genes in response to plant flavonoids.

Hydrocarbon leaks in large scale LNG and gas processing and handling facilities present a risk to health and safety, as well as a negative impact on the environment. Existing autonomous leak detection systems rely primarily on point and path detection. This technology requires dispersed gas to physically contact the point sensors or move between two path detectors. Manual leak checks are also performed periodically by checking one component at a time using a flame ionization detector (FID) or optical gas imager, however the size and complexity of these facilities means that smaller leaks may go undetected for extended periods of time and unintended releases may occur when plant personnel are not present. ExxonMobil Research Qatar Ltd. and Providence Photonics LLC have developed the IntelliRed™ Remote Gas Detection system that integrates computer vision algorithms and infrared (IR) optical gas imaging technology to autonomously scan for and identify leaks. The IntelliRed™ system utilizes a unique mid-wave IR (MWIR) imager and a computer vision algorithm that analyzes the video output from the IR imager to determine the presence of hydrocarbon plumes. Most hydrocarbons have strong absorbance peaks in a narrow MWIR region. The algorithm takes advantage of the difference in contrast between a hydrocarbon plume and the background in an IR imager. The algorithm compares sequentially collected IR images and uses a multi-stage confirmation process to model the behavior of the plume and confirm the detection. It has multiple filters that mitigate interferences such as humans, vehicles, and trees. After extended pilot deployments, the IntelliRed™ technology has been qualified and is commercially available for leak detection and environmental applications. An innovative differential infrared (DIR) camera design now offers the possibility of lower detection limits and higher immunity to false alarms for the IntelliRed™ system. The design employs two cooled MWIR sensors with a common optical path. The infrared energy from the scene is divided using a beam splitter, focusing a spatially registered image on each sensor. The spectral filtering for the two sensors is chosen so that one sensor can visualize a hydrocarbon plume while the second sensor cannot. A synchronized system clock for the two sensors ensures that the frames are temporally aligned. The result is a camera which produces both spatially and temporally aligned frames with the plume present in one frame but absent in the other. A differential image is produced by comparing the two sensors frame by frame, providing a robust filter for common interferences such as steam and dust plumes. The DIR camera design requires new computer vision techniques to exploit the information provided by the reference sensor. Results are compared to other autonomous hydrocarbon detection technologies, including single sensor IntelliRed™ technology. New applications enabled by the DIR camera design are discussed, including aerial pipeline surveys. The technology is currently being qualified with DIR based IntelliRed™ pilot deployments underway in Qatar and the United States.

The ball punch test technique was used to evaluate the conventional tensile and impact properties of the tempered martensitic steel EUROFER97 from room temperature down to liquid nitrogen temperature. The testing was carried out on unirradiated material only with small disks, 3 mm in diameter and 0.25 mm in thickness. For comparison, tensile tests were also performed over the same temperature range. Correlations between the load at the plastic bending initiation and the maximum load of the punch tests with the yield stress and the ultimate tensile stress of the tension tests could be established. The temperature dependence of the specific fracture energy of the punch test was used to define a ductile-brittle transition temperature (DBTT) and to correlate this with the DBTT measured from impact Charpy on KLST specimens. The results are compared with other available correlations done in the past on other ferritic steels. (C) 2002 Elsevier Science B.V. All rights reserved.