Search results for: Xiaoyan Zhou

Authors: Lei Zhou, Chao Li, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: Since the first human infection with avian influenza A(H7N9) case was reported in China on 31 March 2013, five epidemics have been observed in China through February 2013 and September 2017. Though the overall mortality rate of H7N9 has remained as high as around 40% throughout the five epidemics, the specific mortality rate in Mainland China varied by provinces. We conducted a descriptive analysis of mortality rates of H7N9 cases to explore the various severity features of the disease and then to provide clues of further analyses of potential factors associated with the severity of the disease. Methods: The data for analysis originated from the National Notifiable Infectious Disease Report and Surveillance System (NNIDRSS). The surveillance system and identification procedure for H7N9 infection have not changed in China since 2013. The definition of a confirmed H7N9 case is as same as previous reports. Mortality rates of H7N9 cases are described and compared by time and location of reporting, age and sex, and genetic features of H7N9 virus strains. Results: The overall mortality rate, the male and female specific overall rates of H7N9 is 39.6% (608/1533), 40.3% (432/1072) and 38.2% (176/461), respectively. There was no significant difference between the mortality rates of male and female. The age-specific mortality rates are significantly varied by age groups (χ²=38.16, p < 0.001). The mortality of H7N9 cases in the age group between 20 and 60 (33.17%) and age group of over 60 (51.16%) is much higher than that in the age group of under 20 (5.00%). Considering the time of reporting, the mortality rates of cases which were reported in the first (40.57%) and fourth (42.51%) quarters of each year are significantly higher than the mortality of cases which were reported in the second (36.02%) and third (27.27%) quarters (χ²=75.18, p < 0.001). The geographic specific mortality rates vary too. The mortality rates of H7N9 cases reported from the Northeast China (66.67%) and Westeast China (56.52%) are significantly higher than that of H7N9 cases reported from the remained area of mainland China. The mortality rate of H7N9 cases reported from the Central China is the lowest (34.38%). The mortality rates of H7N9 cases reported from rural (37.76%) and urban (38.96%) areas are similar. The mortality rate of H7N9 cases infected with the highly pathogenic avian influenza A(H7N9) virus (48.15%) is higher than the rate of H7N9 cases infected with the low pathogenic avian influenza A(H7N9) virus (37.57%), but the difference is not statistically significant. Preliminary analyses showed that age and some clinical complications such as respiratory failure, heart failure, and septic shock could be potential risk factors associated with the death of H7N9 cases. Conclusions: The mortality rates of H7N9 cases varied by age, sex, time of reporting and geographical location in mainland China. Further in-depth analyses and field investigations of the factors associated with the severity of H7N9 cases need to be considered.

Keywords: H7N9 virus, Avian Influenza, mortality, China

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Authors: Yitian Ren, Liyin Shen, Tao Zhou, Xiao Li

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The past urbanization process in China has brought out series of problems, the Chinese government has then positioned small towns in essential roles for implementing the strategy 'The National New-type Urbanization Plan (2014-2020)'. As the connector and transfer station of cities and countryside, small towns are important force to narrow the gap between urban and rural area, and to achieve the mission of new-type urbanization in China. The sustainable development of small towns plays crucial role because cities are not capable enough to absorb the surplus rural population. Nevertheless, there are various types of barriers hindering the sustainable development of small towns, which led to the limited development of small towns and has presented a bottleneck in Chinese urbanization process. Therefore, this paper makes deep understanding of these barriers, thus effective actions can be taken to address them. And this paper chooses the perspective of Southwest China (refers to Sichuan province, Yunnan province, Guizhou province, Chongqing Municipality City and Tibet Autonomous Region), cause the urbanization rate in Southwest China is far behind the average urbanization level of the nation and the number of small towns accounts for a great proportion in mainland China, also the characteristics of small towns in Southwest China are distinct. This paper investigates the barriers of sustainable development of small towns which located in Southwest China by using the content analysis method, combing with the field work and interviews in sample small towns, then identified and concludes 18 barriers into four dimensions, namely, institutional barriers, economic barriers, social barriers and ecological barriers. Based on the research above, questionnaire survey and data analysis are implemented, thus the key barriers hinder the sustainable development of small towns in Southwest China are identified by using fuzzy set theory, those barriers are, lack of independent financial power, lack of construction land index, financial channels limitation, single industrial structure, topography variety and complexity, which mainly belongs to institutional barriers and economic barriers. In conclusion part, policy suggestions are come up with to improve the politic and institutional environment of small town development, also the market mechanism are supposed to be introduced to the development process of small towns, which can effectively overcome the economic barriers, promote the sustainable development of small towns, accelerate the in-situ urbanization by absorbing peasants in nearby villages, and achieve the mission of new-type urbanization in China from the perspective of people-oriented.

Keywords: barrier analysis, sustainable development, small town, Southwest China

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Authors: Ernest Tambo, Ghislaine Madjou, Jeanne Y. Ngogang, Shenglan Tang, Zhou XiaoNong

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Implementing national to community-based 'One Health' surveillance approach for human, animal and environmental consequences mitigation offers great opportunities and value-added in sustainable development and wellbeing. 'One Health' surveillance approach global partnerships, policy commitment and financial investment are much needed in addressing the evolving threats and epidemics crises mitigation in African countries. The paper provides insights onto how China-Africa health development cooperation in promoting “One Health” surveillance approach in response advocacy and mitigation. China-Africa health development initiatives provide new prospects in guiding and moving forward appropriate and evidence-based advocacy and mitigation management approaches and strategies in attaining Universal Health Coverage (UHC) and Sustainable Development Goals (SDGs). Early and continuous quality and timely surveillance data collection and coordinated information sharing practices in malaria and other diseases are demonstrated in Comoros, Zanzibar, Ghana and Cameroon. Improvements of variety of access to contextual sources and network of data sharing platforms are needed in guiding evidence-based and tailored detection and response to unusual hazardous events. Moreover, understanding threats and diseases trends, frontline or point of care response delivery is crucial to promote integrated and sustainable targeted local, national “One Health” surveillance and response approach needs implementation. Importantly, operational guidelines are vital in increasing coherent financing and national workforce capacity development mechanisms. Strengthening participatory partnerships, collaboration and monitoring strategies in achieving global health agenda effectiveness in Africa. At the same enhancing surveillance data information streams reporting and dissemination usefulness in informing policies decisions, health systems programming and financial mobilization and prioritized allocation pre, during and post threats and epidemics crises programs strengths and weaknesses. Thus, capitalizing on “One Health” surveillance and response approach advocacy and mitigation implementation is timely in consolidating Africa Union 2063 agenda and Africa renaissance capabilities and expectations.

Keywords: Africa, one health approach, surveillance, response

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Authors: Sophia Liang Zhou

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For investors, businesses, consumers, and governments, an accurate assessment of future housing prices is crucial to critical decisions in resource allocation, policy formation, and investment strategies. Previous studies are contradictory about macroeconomic determinants of housing price and largely focused on one or two areas using point prediction. This study aims to develop data-driven models to accurately predict future housing market trends in different markets. This work studied five different metropolitan areas representing different market trends and compared three-time lagging situations: no lag, 6-month lag, and 12-month lag. Linear regression (LR), random forest (RF), and artificial neural network (ANN) were employed to model the real estate price using datasets with S&P/Case-Shiller home price index and 12 demographic and macroeconomic features, such as gross domestic product (GDP), resident population, personal income, etc. in five metropolitan areas: Boston, Dallas, New York, Chicago, and San Francisco. The data from March 2005 to December 2018 were collected from the Federal Reserve Bank, FBI, and Freddie Mac. In the original data, some factors are monthly, some quarterly, and some yearly. Thus, two methods to compensate missing values, backfill or interpolation, were compared. The models were evaluated by accuracy, mean absolute error, and root mean square error. The LR and ANN models outperformed the RF model due to RF’s inherent limitations. Both ANN and LR methods generated predictive models with high accuracy ( > 95%). It was found that personal income, GDP, population, and measures of debt consistently appeared as the most important factors. It also showed that technique to compensate missing values in the dataset and implementation of time lag can have a significant influence on the model performance and require further investigation. The best performing models varied for each area, but the backfilled 12-month lag LR models and the interpolated no lag ANN models showed the best stable performance overall, with accuracies > 95% for each city. This study reveals the influence of input variables in different markets. It also provides evidence to support future studies to identify the optimal time lag and data imputing methods for establishing accurate predictive models.

Keywords: linear regression, random forest, artificial neural network, real estate price prediction

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Authors: Liang Zhang, Gang Xu, Yue Wang, Chen Li, Shao Chong Zhou

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Presently, more and more nuclear power plants are facing the issue of life extension. When a nuclear power plant applies for an extension of life, its condition needs to meet the current design standards, which is not fine for all old reactors, typically for seismic design. Seismic-grade equipment in nuclear power plants are now generally placed separately from the non-seismic-grade equipment, but it was not strictly required before. Therefore, it is very important to study whether non-seismic-grade equipment will affect the seismic-grade equipment when dropped down in an earthquake situation, which is related to the safety of nuclear power plants and future life extension applications. This research was based on the cooling water system with the seismic and non-seismic grade equipment installed together, as an example to study whether the non-seismic-grade equipment such as DN50 fire pipes and ventilation pipes arranged above will damage the DN300 pipes and valves arranged below when earthquakes occur. In the study, the simulation was carried out by ANSYS / LY-DYNA, and Johnson-Cook was used as the material model and failure model. For the experiments, the relative positions of objects in the room were restored by 1: 1. In the experiment, the pipes and valves were filled with water with a pressure of 0.785 MPa. The pressure-holding performance of the pipe was used as a criterion for damage. In addition to the pressure-holding performance, the opening torque was considered as well for the valves. The research results show that when the 10-meter-long DN50 pipe was dropped from the position of 8 meters height and the 8-meter-long air pipe dropped from a position of 3.6 meters height, they do not affect the integrity of DN300 pipe below. There is no failure phenomenon in the simulation as well. After the experiment, the pressure drop in two hours for the pipe is less than 0.1%. The main body of the valve does not fail either. The opening torque change after the experiment is less than 0.5%, but the handwheel of the valve may break, which affects the opening actions. In summary, impacts of the upper pipes and ventilation pipes dropdown on the integrity of the DN300 pipes and valves below in a cooling water system of a typical second-generation nuclear power plant under an earthquake was studied. As a result, the functionality of the DN300 pipeline and the valves themselves are not significantly affected, but the handwheel of the valve or similar articles can probably be broken and need to take care.

Keywords: cooling water system, earthquake, integrity, pipe and valve

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Authors: Jianuo Sun, Jinghan Wang, Sirui Zhang, Chenhan Xu, Hongxia Hao, Hong Zhou

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In recent years, the diversification and industrialization of drug-related crimes have posed significant threats to public health and safety globally. The widespread and increasingly younger demographics of drug users and the persistence of drug-impaired driving incidents underscore the urgency of this issue. Drug detection, a specialized forensic activity, is pivotal in identifying and analyzing substances involved in drug crimes. It relies on pharmacological and chemical knowledge and employs analytical chemistry and modern detection techniques. However, current drug detection methods are limited by their inability to perform semi-quantitative, real-time field analyses. They require extensive, complex laboratory-based preprocessing, expensive equipment, and specialized personnel and are hindered by long processing times. This study introduces an alternative approach using nucleic acid aptamers and Aggregation-Induced Emission (AIE) technology. Nucleic acid aptamers, selected artificially for their specific binding to target molecules and stable spatial structures, represent a new generation of biosensors following antibodies. Rapid advancements in AIE technology, particularly in tetraphenyl ethene-based luminous, offer simplicity in synthesis and versatility in modifications, making them ideal for fluorescence analysis. This work successfully synthesized, isolated, and purified an AIE molecule and constructed a probe comprising the AIE molecule, nucleic acid aptamers, and exonuclease for cocaine detection. The probe demonstrated significant relative fluorescence intensity changes and selectivity towards cocaine over other drugs. Using 4-Butoxytriethylammonium Bromide Tetraphenylethene (TPE-TTA) as the fluorescent probe, the aptamer as the recognition unit, and Exo I as an auxiliary, the system achieved rapid detection of cocaine within 5 mins in aqueous and urine, with detection limits of 1.0 and 5.0 µmol/L respectively. The probe-maintained stability and interference resistance in urine, enabling quantitative cocaine detection within a certain concentration range. This fluorescent sensor significantly reduces sample preprocessing time, offers a basis for rapid onsite cocaine detection, and promises potential for miniaturized testing setups.

Keywords: drug detection, aggregation-induced emission (AIE), nucleic acid aptamer, exonuclease, cocaine

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Authors: Qinke Sun, Liang Zhou

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The ‘Dragon-Elephant Debate’ between China and India is an important manifestation of global multipolarity in the 21st century. The two rising powers have carried out economic reforms one after another in the interval of more than ten years, becoming the fastest growing developing country and emerging economy in the world. At the same time, the development differences between China and India have gradually attracted wide attention of scholars. Based on the continuous annual night light data (DMSP-OLS) from 1992 to 2012, this paper systematically compares and analyses the regional development differences between China and India by Gini coefficient, coefficient of variation, comprehensive night light index (CNLI) and hot spot analysis. The results show that: (1) China's overall expansion from 1992 to 2012 is 1.84 times that of India, in which China's change is 2.6 times and India's change is 2 times. The percentage of lights in unlighted areas in China dropped from 92% to 82%, while that in India from 71% to 50%. (2) China's new growth-oriented cities appear in Hohhot, Inner Mongolia, Ordos, and Urumqi in the west, and the declining cities are concentrated in Liaoning Province and Jilin Province in the northeast; India's new growth-oriented cities are concentrated in Chhattisgarh in the north, while the declining areas are distributed in Uttar Pradesh. (3) China's differences on different scales are lower than India's, and regional inequality of development is gradually narrowing. Gini coefficients at the regional and provincial levels have decreased from 0.29, 0.44 to 0.24 and 0.38, respectively, while regional inequality in India has slowly improved and regional differences are gradually widening, with Gini coefficients rising from 0.28 to 0.32. The provincial Gini coefficient decreased slightly from 0.64 to 0.63. (4) The spatial pattern of China's regional development is mainly east-west difference, which shows the difference between coastal and inland areas; while the spatial pattern of India's regional development is mainly north-south difference, but because the southern states are sea-dependent, it also reflects the coastal inland difference to a certain extent. (5) Beijing and Shanghai present a multi-core outward expansion model, with an average annual CNLI higher than 0.01, while New Delhi and Mumbai present the main core enhancement expansion model, with an average annual CNLI lower than 0.01, of which the average annual CNLI in Shanghai is about five times that in Mumbai.

Keywords: spatial pattern, spatial difference, DMSP-OLS, China, India

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Authors: Chao Li, Lei Zhou, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

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Background: In 2016, yellow fever had been first ever discovered in China, soon after the yellow fever epidemic occurred in Angola. After the discovery, China had promptly made the national protocol of control and prevention and strengthened the surveillance on passenger and vector. In this study, a descriptive analysis was conducted to summarize China’s experiences of response towards this import epidemic, in the hope of providing experiences on prevention and control of yellow fever and other similar imported infectious diseases in the future. Methods: The imported cases were discovered and reported by General Administration of Quality Supervision, Inspection and Quarantine (AQSIQ) and several hospitals. Each clinically diagnosed yellow fever case was confirmed by real-time reverse transcriptase polymerase chain reaction (RT–PCR). The data of the imported yellow fever cases were collected by local Centers for Disease Control and Prevention (CDC) through field investigations soon after they received the reports. Results: A total of 11 imported cases from Angola were reported in China, during Angola’s yellow fever outbreak. Six cases were discovered by the AQSIQ, among which two with mild symptom were initiative declarations at the time of entry. Except for one death, the remaining 10 cases all had recovered after timely and proper treatment. All cases are Chinese, and lived in Luanda, the capital of Angola. 73% were retailers (8/11) from Fuqing city in Fujian province, and the other three were labors send by companies. 10 cases had experiences of medical treatment in Luanda after onset, among which 8 cases visited the same local Chinese medicine hospital (China Railway four Bureau Hospital). Among the 11 cases, only one case had an effective vaccination. The result of emergency surveillance for mosquito density showed that only 14 containers of water were found positive around places of three cases, and the Breteau Index is 15. Conclusions: Effective response was taken to control and prevent the outbreak of yellow fever in China after discovering the imported cases. However, though the similar origin of Chinese in Angola has provided an easy access for disease detection, information sharing, health education and vaccination on yellow fever; these conveniences were overlooked during previous disease prevention methods. Besides, only one case having effective vaccination revealed the inadequate capacity of immunization service in China. These findings will provide suggestions to improve China’s capacity to deal with not only yellow fever but also other similar imported diseases in China.

Keywords: yellow fever, first import, China, suggestion

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Authors: Fangjing Zhou, Wen Chen, Brian J. Hall, Yu Wang, Carl Latkin, Li Ling, Joseph D. Tucker

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Background: Economic and social reforms designed to open China to the world has been successful, but also appear to have rapidly laid the foundation for the reemergence of STIs since 1980s. Changes in sexual behaviors, relationships, and norms among Chinese contributed to the STIs epidemic. As the massive population moved during the last 30 years, early coital debut, multiple sexual partnerships, and unprotected sex have increased within the general population. Our objectives were to assess associations between residences location, sexual risk behaviors and sexually transmitted infections (STIs) among adults living in Guangzhou, China. Methods: Stratified cluster sampling followed a two-step process was used to select populations aged 18-59 years in Guangzhou, China. Spatial methods including Geographic Information Systems (GIS) were utilized to identify 1400 coordinates with latitude and longitude. Face-to-face household interviews were conducted to collect self-report data on sexual risk behaviors and diagnosed STIs. Kulldorff’s spatial scan statistic was implemented to identify and detect spatial distribution and clusters of sexual risk behaviors and STIs. The presence and location of statistically significant clusters were mapped in the study areas using ArcGIS software. Results: In this study, 1215 of 1400 households attempted surveys, with 368 refusals, resulting in a sample of 751 completed surveys. The prevalence of self-reported sexual risk behaviors was between 5.1% and 50.0%. The self-reported lifetime prevalence of diagnosed STIs was 7.06%. Anal intercourse clustered in an area located along the border within the rural-urban continuum (p=0.001). High rate clusters for alcohol or other drugs using before sex (p=0.008) and migrants who lived in Guangzhou less than one year (p=0.007) overlapped this cluster. Excess cases for sex without a condom (p=0.031) overlapped the cluster for college students (p<0.001). Conclusions: Short-term migrants and college students reported greater sexual risk behaviors. Programs to increase safer sex within these communities to reduce the risk of STIs are warranted in Guangzhou. Spatial analysis identified geographical clusters of sexual risk behaviors, which is critical for optimizing surveillance and targeting control measures for these locations in the future.

Keywords: cluster analysis, migrant, sexual risk behaviors, spatial distribution

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Authors: Haoming Ma, Guo Yu, Peiru Zhou

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Background: Previous studies show that dysglycemia, mostly hyperglycemia, hypoglycemia and glycemic variability(GV), are associated with excess mortality in critically ill patients, especially those without diabetes. Glycemic variability is an increasingly important measure of glucose control in the intensive care unit (ICU) due to this association. However, there is limited data pertaining to the relationship between different clinical factors and glycemic variability and clinical outcomes categorized by their DM status. This retrospective study of 958 intensive care unit(ICU) patients was conducted to investigate the relationship between GV and outcome in critically ill patients and further to determine the significant factors that contribute to the glycemic variability. Aim: We hypothesize that the factors contributing to mortality and the glycemic variability are different from critically ill patients with or without diabetes. And the primary aim of this study was to determine which dysglycemia (hyperglycemia\hypoglycemia\glycemic variability) is independently associated with an increase in mortality among critically ill patients in different groups (DM/Non-DM). Secondary objectives were to further investigate any factors affecting the glycemic variability in two groups. Method: A total of 958 diabetic and non-diabetic patients with severe diseases in the ICU were selected for this retrospective analysis. The glycemic variability was defined as the coefficient of variation (CV) of blood glucose. The main outcome was death during hospitalization. The secondary outcome was GV. The logistic regression model was used to identify factors associated with mortality. The relationships between GV and other variables were investigated using linear regression analysis. Results: Information on age, APACHE II score, GV, gender, in-ICU treatment and nutrition was available for 958 subjects. Predictors remaining in the final logistic regression model for mortality were significantly different in DM/Non-DM groups. Glycemic variability was associated with an increase in mortality in both DM(odds ratio 1.05; 95%CI:1.03-1.08,p＜0.001) or Non-DM group(odds ratio 1.07; 95%CI:1.03-1.11,p=0.002). For critically ill patients without diabetes, factors associated with glycemic variability included APACHE II score(regression coefficient, 95%CI:0.29,0.22-0.36,p＜0.001), Mean BG(0.73,0.46-1.01,p＜0.001), total parenteral nutrition(2.87,1.57-4.17,p＜0.001), serum albumin(-0.18,-0.271 to -0.082,p＜0.001), insulin treatment(2.18,0.81-3.55,p=0.002) and duration of ventilation(0.006,0.002-1.010,p=0.003).However, for diabetes patients, APACHE II score(0.203,0.096-0.310,p＜0.001), mean BG(0.503,0.138-0.869,p=0.007) and duration of diabetes(0.167,0.033-0.301,p=0.015) remained as independent risk factors of GV. Conclusion: We found that the relation between dysglycemia and mortality is different in the diabetes and non-diabetes groups. And we confirm that GV was associated with excess mortality in DM or Non-DM patients. Furthermore, APACHE II score, Mean BG, total parenteral nutrition, serum albumin, insulin treatment and duration of ventilation were significantly associated with an increase in GV in Non-DM patients. While APACHE II score, mean BG and duration of diabetes (years) remained as independent risk factors of increased GV in DM patients. These findings provide important context for further prospective trials investigating the effect of different clinical factors in critically ill patients with or without diabetes.

Keywords: diabetes, glycemic variability, predictors, severe disease

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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Authors: Haifeng Zhou, Tsungyang Liow, Xiaoguang Tu, Eujin Lim, Chao Li, Junfeng Song, Xianshu Luo, Ying Huang, Lianxi Jia, Lianwee Luo, Kim Dowon, Qing Fang, Mingbin Yu, Guoqiang Lo

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Several Germanium photodetectors (PD) built on silicon micro-disks are fabricated on the standard Si photonics multiple project wafers (MPW) and demonstrated to exhibit very low dark current, satisfactory operation bandwidth and moderate responsivity. Among them, a vertical p-i-n Ge PD based on a 2.0 µm-radius micro-disk has a dark current of as low as 35 nA, compared to a conventional PD current of 1 µA with an area of 100 µm2. The operation bandwidth is around 15 GHz at a reverse bias of 1V. The responsivity is about 0.6 A/W. Microdisk is a striking planar structure in integrated optics to enhance light-matter interaction and construct various photonics devices. The disk geometries feature in strongly and circularly confining light into an ultra-small volume in the form of whispering gallery modes. A laser may benefit from a microdisk in which a single mode overlaps the gain materials both spatially and spectrally. Compared to microrings, micro-disk removes the inner boundaries to enable even better compactness, which also makes it very suitable for some scenarios that electrical connections are needed. For example, an ultra-low power (≈ fJ) athermal Si modulator has been demonstrated with a bit rate of 25Gbit/s by confining both photons and electrically-driven carriers into a microscale volume.In this work, we study Si-based PDs with Ge selectively grown on a microdisk with the radius of a few microns. The unique feature of using microdisk for Ge photodetector is that mode selection is not important. In the applications of laser or other passive optical components, microdisk must be designed very carefully to excite the fundamental mode in a microdisk in that essentially the microdisk usually supports many higher order modes in the radial directions. However, for detector applications, this is not an issue because the local light absorption is mode insensitive. Light power carried by all modes are expected to be converted into photo-current. Another benefit of using microdisk is that the power circulation inside avoids any introduction of the reflector. A complete simulation model with all involved materials taken into account is established to study the promise of microdisk structures for photodetector by using finite difference time domain (FDTD) method. By viewing from the current preliminary data, the directions to further improve the device performance are also discussed.

Keywords: integrated optical devices, silicon photonics, micro-resonator, photodetectors

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Authors: Man-Yu Wong, Siyu Zhou, Zhiqiang Cao

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In quality of life, health service utilization is an important determinant of medical resource expenditures on Colorectal cancer (CRC) care, a better understanding of the increased utilization of health services is essential for optimizing the allocation of healthcare resources to services and thus for enhancing the service quality, especially for high expenditure on CRC care like Hong Kong region. In assessing the association between the health-related quality of life (HRQOL) and health service utilization in patients with colorectal neoplasm, count data models can be used, which account for over dispersion or extra zero counts. In our data, the HRQOL evaluation is a self-reported measure obtained from a questionnaire completed by the patients, misreports and variations in the data are inevitable. Besides, there are more zero counts from the observed number of clinical consultations (observed frequency of zero counts = 206) than those from a Poisson distribution with mean equal to 1.33 (expected frequency of zero counts = 156). This suggests that excess of zero counts may exist. Therefore, we study tests for detecting zero-inflation in models with measurement error in covariates. Method: Under classical measurement error model, the approximate likelihood function for zero-inflation Poisson regression model can be obtained, then Approximate Maximum Likelihood Estimation(AMLE) can be derived accordingly, which is consistent and asymptotically normally distributed. By calculating score function and Fisher information based on AMLE, a score test is proposed to detect zero-inflation effect in ZIP model with measurement error. The proposed test follows asymptotically standard normal distribution under H0, and it is consistent with the test proposed for zero-inflation effect when there is no measurement error. Results: Simulation results show that empirical power of our proposed test is the highest among existing tests for zero-inflation in ZIP model with measurement error. In real data analysis, with or without considering measurement error in covariates, existing tests, and our proposed test all imply H0 should be rejected with P-value less than 0.001, i.e., zero-inflation effect is very significant, ZIP model is superior to Poisson model for analyzing this data. However, if measurement error in covariates is not considered, only one covariate is significant; if measurement error in covariates is considered, only another covariate is significant. Moreover, the direction of coefficient estimations for these two covariates is different in ZIP regression model with or without considering measurement error. Conclusion: In our study, compared to Poisson model, ZIP model should be chosen when assessing the association between condition-specific HRQOL and health service utilization in patients with colorectal neoplasm. and models taking measurement error into account will result in statistically more reliable and precise information.

Keywords: count data, measurement error, score test, zero inflation

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Authors: Liang Zhou, Qinke Sun

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Taking the Yangtze River Economic Belt as an example, using long-term nighttime lighting data from DMSP/OLS from 1992 to 2012, support vector machine classification (SVM) was used to quantitatively extract urban built-up areas of economic belts, and spatial analysis of expansion intensity index, standard deviation ellipse, etc. was introduced. The model conducts detailed and in-depth discussions on the strength, direction, and type of the expansion of the middle and lower reaches of the economic belt and the key node cities. The results show that: (1) From 1992 to 2012, the built-up areas of the major cities in the Yangtze River Valley showed a rapid expansion trend. The built-up area expanded by 60,392 km², and the average annual expansion rate was 31%, that is, from 9615 km² in 1992 to 70007 km² in 2012. The spatial gradient analysis of the watershed shows that the expansion of urban built-up areas in the middle and lower reaches of the river basin takes Shanghai as the leading force, and the 'bottom-up' model shows an expanding pattern of 'upstream-downstream-middle-range' declines. The average annual rate of expansion is 36% and 35%, respectively. 17% of which the midstream expansion rate is about 50% of the upstream and downstream. (2) The analysis of expansion intensity shows that the urban expansion intensity in the Yangtze River Basin has generally shown an upward trend, the downstream region has continued to rise, and the upper and middle reaches have experienced different amplitude fluctuations. To further analyze the strength of urban expansion at key nodes, Chengdu, Chongqing, and Wuhan in the upper and middle reaches maintain a high degree of consistency with the intensity of regional expansion. Node cities with Shanghai as the core downstream continue to maintain a high level of expansion. (3) The standard deviation ellipse analysis shows that the overall center of gravity of the Yangtze River basin city is located in Anqing City, Anhui Province, and it showed a phenomenon of reciprocating movement from 1992 to 2012. The nighttime standard deviation ellipse distribution range increased from 61.96 km² to 76.52 km². The growth of the major axis of the ellipse was significantly larger than that of the minor axis. It had obvious east-west axiality, in which the nighttime lights in the downstream area occupied in the entire luminosity scale urban system leading position.

Keywords: urban space, support vector machine, spatial characteristics, night lights, Yangtze River Economic Belt

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Authors: Shi-Bo Feng, Sheng-Jie Zhang, Jin Zhou

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The relationship between microbial diversity and algal bloom has received considerable attention for decades. Microbes undoubtedly affect annual bloom events and impact the physiology of both partners, as well as shape ecosystem diversity. However, knowledge about interactions and network correlations among broader-spectrum microbes that lead to the dynamics in a complete bloom cycle are limited. In this study, pyrosequencing and network approaches simultaneously assessed the associate patterns among bacteria, archaea, and microeukaryotes in surface water and sediments in response to a natural dinoflagellate (Alexandrium sp.) bloom. In surface water, among the bacterial community, Gamma-Proteobacteria and Bacteroidetes dominated in the initial bloom stage, while Alpha-Proteobacteria, Cyanobacteria, and Actinobacteria become the most abundant taxa during the post-stage. In the archaea biosphere, it clustered predominantly with Methanogenic members in the early pre-bloom period while the majority of species identified in the later-bloom stage were ammonia-oxidizing archaea and Halobacteriales. In eukaryotes, dinoflagellate (Alexandrium sp.) was dominated in the onset stage, whereas multiply species (such as microzooplankton, diatom, green algae, and rotifera) coexistence in bloom collapse stag. In sediments, the microbial species biomass and richness are much higher than the water body. Only Flavobacteriales and Rhodobacterales showed a slight response to bloom stages. Unlike the bacteria, there are small fluctuations of archaeal and eukaryotic structure in the sediment. The network analyses among the inter-specific associations show that bacteria (Alteromonadaceae, Oceanospirillaceae, Cryomorphaceae, and Piscirickettsiaceae) and some zooplankton (Mediophyceae, Mamiellophyceae, Dictyochophyceae and Trebouxiophyceae) have a stronger impact on the structuring of phytoplankton communities than archaeal effects. The changes in population were also significantly shaped by water temperature and substrate availability (N & P resources). The results suggest that clades are specialized at different time-periods and that the pre-bloom succession was mainly a bottom-up controlled, and late-bloom period was controlled by top-down patterns. Additionally, phytoplankton and prokaryotic communities correlated better with each other, which indicate interactions among microorganisms are critical in controlling plankton dynamics and fates. Our results supplied a wider view (temporal and spatial scales) to understand the microbial ecological responses and their network association during algal blooming. It gives us a potential multidisciplinary explanation for algal-microbe interaction and helps us beyond the traditional view linked to patterns of algal bloom initiation, development, decline, and biogeochemistry.

Keywords: microbial community, harmful algal bloom, ecological process, network

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Authors: Ming Zhou, Taeho Park

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Early stage technologies have been particularly challenging to manage due to high degrees of their numerous uncertainties. Most research results directly out of a research lab tend to be at their early, if not the infant stage. A long while uncertain commercialization process awaits these lab results. The majority of such lab technologies go nowhere and never get commercialized due to various reasons. Any efforts or financial resources put into managing these technologies turn fruitless. High stake naturally calls for better results, which make a patenting decision harder to make. A good and well protected patent goes a long way for commercialization of the technology. Our preliminary research showed that there was not a simple yet productive procedure for such valuation. Most of the studies now have been theoretical and overly comprehensive where practical suggestions were non-existent. Hence, we attempted to develop a simple and highly implementable procedure for efficient and scalable valuation. We thoroughly reviewed existing research, interviewed practitioners in the Silicon Valley area, and surveyed university technology offices. Instead of presenting another theoretical and exhaustive research, we aimed at developing a practical guidance that a government agency and/or university office could easily deploy and get things moving to later steps of managing early stage technologies. We provided a procedure to thriftily value and make the patenting decision. A patenting index was developed using survey data and expert opinions. We identified the most important factors to be used in the patenting decision using survey ratings. The rating then assisted us in generating good relative weights for the later scoring and weighted averaging step. More importantly, we validated our procedure by testing it with our practitioner contacts. Their inputs produced a general yet highly practical cut schedule. Such schedule of realistic practices has yet to be witnessed our current research. Although a technology office may choose to deviate from our cuts, what we offered here at least provided a simple and meaningful starting point. This procedure was welcomed by practitioners in our expert panel and university officers in our interview group. This research contributed to our current understanding and practices of managing early stage technologies by instating a heuristically simple yet theoretical solid method for the patenting decision. Our findings generated top decision factors, decision processes and decision thresholds of key parameters. This research offered a more practical perspective which further completed our extant knowledge. Our results could be impacted by our sample size and even biased a bit by our focus on the Silicon Valley area. Future research, blessed with bigger data size and more insights, may want to further train and validate our parameter values in order to obtain more consistent results and analyze our decision factors for different industries.

Keywords: technology management, early stage technology, patent, decision

Procedia PDF Downloads 342

Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li

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Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.

Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry

Procedia PDF Downloads 166

Authors: Dechao Meng, Yongqi Dong, Qiyuan Feng, Zhangzhang Cui, Xiang Hu, Haoliang Huang, Genhao Liang, Huanhua Wang, Hua Zhou, Hawoong Hong, Jinghua Guo, Qingyou Lu, Xiaofang Zhai, Yalin Lu

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Great efforts have been taken to reveal the intrinsic origins of emerging ferromagnetism (FM) in strained LaCoO₃ (LCO) films. However, some macro magnetic performances of LCO are still not well understood and even controversial, such as magnetic anisotropy. Determining and understanding magnetic anisotropy might help to find the true causes of FM in turn. Perpendicular magnetic anisotropy (PMA) was the first time to be directly observed in high-quality LCO films with different thickness. The in-plane (IP) and out of plane (OOP) remnant magnetic moment ratio of 30 unit cell (u.c.) films is as large as 20. The easy axis lays in the OOP direction with an IP/OOP coercive field ratio of 10. What's more, the PMA could be simply tuned by changing the thickness. With the thickness increases, the IP/OOP magnetic moment ratio remarkably decrease with magnetic easy axis changing from OOP to IP. Such a huge and tunable PMA performance exhibit strong potentials in fundamental researches or applications. What causes PMA is the first concern. More OOP orbitals occupation may be one of the micro reasons of PMA. A cluster-like magnetic domain pattern was found in 30 u.c. with no obvious color contrasts, similar to that of LaAlO₃/SrTiO₃ films. And the nanosize domains could not be totally switched even at a large OOP magnetic field of 23 T. It indicates strong IP characters or none OOP magnetism of some clusters. The IP magnetic domains might influence the magnetic performance and help to form PMA. Meanwhile some possible nonmagnetic clusters might be the reason why the measured moments of LCO films are smaller than the calculated values 2 μB/Co, one of the biggest confusions in LCO films.What tunes PMA seems much more interesting. Totally different magnetic domain patterns were found in 180 u.c. films with cluster magnetic domains surrounded by < 110 > cross-hatch lines. These lines were regarded as structure domain walls (DWs) determined by 3D reciprocal space mapping (RSM). Two groups of in-plane features with fourfold symmetry were observed near the film diffraction peaks in (002) 3D-RSM. One is along < 110 > directions with a larger intensity, which is well match the lines on the surfaces. The other is much weaker and along < 100 > directions, which is from the normal lattice titling of films deposited on cubic substrates. The < 110 > domain features obtained from (103) and (113) 3D-RSMs exhibit similar evolution of the DWs percentages and magnetic behavior. Structure domains and domain walls are believed to tune PMA performances by transform more IP magnetic moments to OOP. Last but not the least, thick films with lots of structure domains exhibit different electrical transport behaviors. A metal-to-insulator transition (MIT) and an angular dependent negative magnetic resistivity were observed near 150 K, higher than FM transition temperature but similar to that of spin-orbital coupling related 1/4 order diffraction peaks.

Keywords: structure domain, magnetic anisotropy, magnetic domain, domain wall, 3D-RSM, strain

Procedia PDF Downloads 153

Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

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Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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Authors: Weijing Zhou, Yuting Lei, Francis Nolan

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In the domain of second language acquisition, whenever pronunciation errors or acquisition difficulties are found, researchers habitually attribute them to the negative transfer of the native language or local dialect. To what extent do Mandarin and local dialects affect English phonological acquisition for Chinese learners of English as a foreign language (EFL)? Little evidence, however, has been found via empirical research in China. To address this core issue, the present study conducted phonetic experiments to explore the roles of local dialects and Mandarin in Chinese EFL learners’ acquisition of L2 English consonants. Besides Mandarin, the sole national language in China, Suzhou dialect was selected as the target local dialect because of its distinct phonology from Mandarin. The experimental group consisted of 30 junior English majors at Yangzhou University, who were born and lived in Suzhou, acquired Suzhou Dialect since their early childhood, and were able to communicate freely and fluently with each other in Suzhou Dialect, Mandarin as well as English. The consonantal target segments were all the consonants of English, Mandarin and Suzhou Dialect in typical carrier words embedded in the carrier sentence Say again. The control group consisted of two Suzhou Dialect experts, two Mandarin radio broadcasters, and two British RP phoneticians, who served as the standard speakers of the three languages. The reading corpus was recorded and sampled in the phonetic laboratories at Yangzhou University, Soochow University and Cambridge University, respectively, then transcribed, segmented and analyzed acoustically via Praat software, and finally analyzed statistically via EXCEL and SPSS software. The main findings are as follows: First, in terms of correct acquisition rates (CARs) of all the consonants, Mandarin ranked top (92.83%), English second (74.81%) and Suzhou Dialect last (70.35%), and significant differences were found only between the CARs of Mandarin and English and between the CARs of Mandarin and Suzhou Dialect, demonstrating Mandarin was overwhelmingly more robust than English or Suzhou Dialect in subjects’ multilingual phonological ecology. Second, in terms of typical acoustic features, the average duration of all the consonants plus the voice onset time (VOT) of plosives, fricatives, and affricatives in 3 languages were much longer than those of standard speakers; the intensities of English fricatives and affricatives were higher than RP speakers but lower than Mandarin and Suzhou Dialect standard speakers; the formants of English nasals and approximants were significantly different from those of Mandarin and Suzhou Dialects, illustrating the inconsistent acoustic variations between the 3 languages. Thirdly, in terms of typical pronunciation variations or errors, there were significant interlingual interactions between the 3 consonant systems, in which Mandarin consonants were absolutely dominant, accounting for the strong transfer from L1 Mandarin to L2 English instead of from earlier-acquired L1 local dialect to L2 English. This is largely because the subjects were knowingly exposed to Mandarin since their nursery and were strictly required to speak in Mandarin through all the formal education periods from primary school to university.

Keywords: acquisition of L2 English consonants, role of Mandarin, role of local dialect, Chinese EFL learners from Suzhou Dialect areas

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Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

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The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

Procedia PDF Downloads 152

Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

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Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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Authors: Adil Murtaza, Muhammad Tahir Khan, Awais Ghani, Chao Zhou, Sen Yang, Xiaoping Song

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The morphotropic phase boundary (MPB); a boundary between two different crystallographic symmetries in the composition–temperature phase diagram has been widely studied in ferroelectrics and recently has drawn interest in ferromagnets for obtaining enhanced large field-induced strain. At MPB, the system gets a compressed free energy state, which allows the polarization to freely rotate and hence results in a high magnetoelastic response (e.g., high magnetization, low coercivity, and large magnetostriction). Based on the same mechanism, we designed MPB in a ferromagnetic Tb₁₋ₓNdₓCo₂ system. The temperature-dependent magnetization curves showed spin reorientation (SR); which can be explained by a two-sublattice model. Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb₀.₃₅Nd₀.₆₅Co₂ exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The coercive field (HC) under a low magnetic field and first anisotropy constant (K₁) shows a minimum value at MPB composition of x=0.65. A detailed spin configuration diagram is provided for the Tb₁₋ₓNdₓCo₂ around the composition for the anisotropy compensation; this can guide the development of novel magnetostrictive materials. The anisotropic magnetostriction (λS) first decreased until x=0.8 and then continuously increased in the negative direction with further increase of Nd concentration. In addition, the large ratio between magnetostriction and the absolute values of the first anisotropy constant (λS/K₁) appears at MPB, indicating that Tb₀.₃₅Nd₀.₆₅Co₂ has good magnetostrictive properties. Present work shows an anomalous type of MPB in ferromagnetic materials, revealing that MPB can also lead to a weakening of magnetoelastic behavior as shown in the ferromagnetic Tb₁₋ₓNdₓCo₂ system. Our work shows the universal presence of MPB in ferromagnetic materials and suggests the differences between different ferromagnetic MPB systems that are important for substantial improvement of magnetic and magnetostrictive properties. Based on the results of this study, similar MPB effects might be achieved in other ferroic systems that can be used for technological applications. The finding of magnetic MPB in the ferromagnetic system leads to some important significances. First, it provides a better understanding of the fundamental concept of spin reorientation transitions (SRT) like ferro-ferro transitions are not only reorientation of magnetization but also crystal symmetry change upon magnetic ordering. Second, the flattened free energy corresponding to a low energy barrier for magnetization rotation and enhanced magnetoelastic response near MPB. Third, to attain large magnetostriction with MPB approach two terminal compounds have different easy magnetization directions below Curie temperature Tc in order to accomplish the weakening of magnetization anisotropy at MPB (as in ferroelectrics), thus easing the magnetic domain switching and the lattice distortion difference between two terminal compounds should be large enough, e.g., lattice distortion of R symmetry ˃˃ lattice distortion of T symmetry). So that the MPB composition agrees to a nearly isotropic state along with large ‘net’ lattice distortion, which is revealed in a higher value of magnetostriction.

Keywords: magnetization, magnetostriction, morphotropic phase boundary (MPB), phase transition

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Authors: Weixiao Wei, Chris Shei

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This paper describes Mandate of Heaven as a source of justification for the ruling regime from ancient China approximately three thousand years ago. Initially, the kings of Shang dynasty simply nominated themselves as the sons of Heaven sent to Earth to rule the common people. As the last generation of the kings became corrupted and ruled withbrutal force and crueltywhich directly caused their destruction, the successive kings of Zhou dynasty realised the importance of virtue and the provision of goods to the people. Legitimacy of the ruling regimes became rested not entirely on random allocation of the throne by an unknown supernatural force but on a foundation comprising morality and the ability to provide goods. The latter composite was picked up by the current ruling regime, the Chinese Communist Party, and became the cornerstone of its political legitimacy, also known as ‘performance legitimacy’ where economic development accounts for the satisfaction of the people in place of election and other democratic means of providing legal-rational legitimacy. Under this circumstance, it becomes important as well for the ruling party to use political rhetoric to convince people of the good performance of the government in the economy, morality, and foreign policy. Thus, we see a lot of propaganda materials in both government policy statements and international press conference announcements. The former consists mainly of important speeches made by prominent figures in Party conferences which are not only made publicly available on the government websites but also become obligatory reading materials for university entrance examinations. The later consists of announcements about foreign policies and strategies and actions taken by the government regarding foreign affairsmade in international conferences and offered in Chinese-English bilingual versions on official websites. This documentation strategy creates an impressive image of the Chinese Communist Party that is domestically competent and international strong, taking care of the people it governs in terms of economic needs and defending the country against any foreign interference and global adversities. This political discourse system comprising reading materials fully extractable from government websites also becomes excellent repertoire for teaching and researching in contemporary Chinese language, discourse and rhetoric, Chinese culture and tradition, Chinese political ideology, and Chinese-English translation. This paper aims to provide a detailed and comprehensive description of the current Chinese political discourse system, arguing about its lineage from the rhetorical convention of Mandate of Heaven in ancient China and its current concentration on serving the people in place of election, human rights, and freedom of speech. The paper will also provide guidelines as to how this discourse system and the manifestation of official documents created under this system can become excellent research and teaching materials in applied linguistics.

Keywords: mandate of heaven, Chinese communist party, performance legitimacy, serving the people, political discourse

Procedia PDF Downloads 110

Authors: George Zhou, Yunchan Chen, Candace Chien

Abstract:

Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

Abstract:

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: T. N. Tran Thi, J. Morse, C. Detlefs, P. K. Cook, C. Yıldırım, A. C. Jakobsen, T. Zhou, J. Hartwig, V. Zurbig, D. Caliste, B. Fernandez, D. Eon, O. Loto, M. L. Hicks, A. Pakpour-Tabrizi, J. Baruchel

Abstract:

The ability to grow boron-doped diamond epilayers of high crystalline quality is a prerequisite for the fabrication of diamond power electronic devices, in particular high voltage diodes and metal-oxide-semiconductor (MOS) transistors. Boron and intrinsic diamond layers are homoepitaxially overgrown by microwave assisted chemical vapour deposition (MWCVD) on single crystal high pressure, high temperature (HPHT) grown bulk diamond substrates. Various epilayer thicknesses were grown, with dopant concentrations ranging from 1021 atom/cm³ at nanometer thickness in the case of 'delta doping', up 1016 atom/cm³ and 50µm thickness or high electric field drift regions. The crystalline quality of these overgrown layers as regards defects, strain, distortion… is critical for the device performance through its relation to the final electrical properties (Hall mobility, breakdown voltage...). In addition to the optimization of the epilayer growth conditions in the MWCVD reactor, other important questions related to the crystalline quality of the overgrown layer(s) are: 1) what is the dependence on the bulk quality and surface preparation methods of the HPHT diamond substrate? 2) how do defects already present in the substrate crystal propagate into the overgrown layer; 3) what types of new defects are created during overgrowth, what are their growth mechanisms, and how can these defects be avoided? 4) how can we relate in a quantitative manner parameters related to the measured crystalline quality of the boron doped layer to the electronic properties of final processed devices? We describe synchrotron-based techniques developed to address these questions. These techniques allow the visualization of local defects and crystal distortion which complements the data obtained by other well-established analysis methods such as AFM, SIMS, Hall conductivity…. We have used Grazing Incidence X-ray Diffraction (GIXRD) at the ID01 beamline of the ESRF to study lattice parameters and damage (strain, tilt and mosaic spread) both in diamond substrate near surface layers and in thick (10–50 µm) overgrown boron doped diamond epi-layers. Micro- and nano-section topography have been carried out at both the BM05 and ID06-ESRF) beamlines using rocking curve imaging techniques to study defects which have propagated from the substrate into the overgrown layer(s) and their influence on final electronic device performance. These studies were performed using various commercially sourced HPHT grown diamond substrates, with the MWCVD overgrowth carried out at the Fraunhofer IAF-Germany. The synchrotron results are in good agreement with low-temperature (5°K) cathodoluminescence spectroscopy carried out on the grown samples using an Inspect F5O FESEM fitted with an IHR spectrometer.

Keywords: synchrotron X-ray diffaction, crystalline quality, defects, diamond overgrowth, rocking curve imaging

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Authors: Saul Ngarava, Leocadia Zhou, Nomakhaya Monde

Abstract:

Water crises have the fourth most significant societal impact after weapons of mass destruction, climate change, and extreme weather conditions, ahead of natural disasters. Intricacies between women and water are central to achieving the 2030 Sustainable Development Goals (SDGs). The majority of the 1.2 billion poor people worldwide, with two-thirds being women, and mostly located in Sub Sahara Africa (SSA) and South Asia, do not have access to safe and reliable sources of water. There exist gendered differences in water security based on the division of labour associating women with water. Globally, women and girls are responsible for water collection in 80% of the households which have no water on their premises. Women spend 16 million hours a day collecting water, while men and children spend 6 million and 4 million per day, respectively, which is time foregone in the pursuit of other livelihood activities. Due to their proximity and activities concerning water, women are vulnerable to water insecurity through exposures to water-borne diseases, fatigue from physically carrying water, and exposure to sexual and physical harassment, amongst others. Proximity to treated water and their wellbeing also has an effect on their sensitivity and adaptive capacity to water insecurity. The great distances, difficult terrain and heavy lifting expose women to vulnerabilities of water insecurity. However, few studies have quantified the vulnerabilities and burdens on women, with a few taking a phenomenological qualitative approach. Vulnerability studies have also been scanty in the water security realm, with most studies taking linear forms of either quantifying exposures, sensitivities or adaptive capacities in climate change studies. The current study argues for the need for a water insecurity vulnerability assessment, especially for women into research agendas as well as policy interventions, monitoring, and evaluation. The study sought to identify and provide pathways through which female-headed households were water insecure in South Africa, the 30th driest country in the world. This was through linking the drinking water decision as well as the vulnerability frameworks. Secondary data collected during the 2016 General Household Survey (GHS) was utilised, with a sample of 5928 female-headed households. Principal Component Analysis and Structural Equation Modelling were used to analyse the data. The results show dynamic relationships between water characteristics and water treatment. There were also associations between water access and wealth status of the female-headed households. Association was also found between water access and water treatment as well as between wealth status and water treatment. The study concludes that there are dynamic relationships in water insecurity (exposure, sensitivity, and adaptive capacity) for female-headed households in South Africa. The study recommends that a multi-prong approach is required in tackling exposures, sensitivities, and adaptive capacities to water insecurity. This should include capacitating and empowering women for wealth generation, improve access to water treatment equipment as well as prioritising the improvement of infrastructure that brings piped and safe water to female-headed households.

Keywords: gender, principal component analysis, structural equation modelling, vulnerability, water insecurity

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Authors: Zeyu Zhou, Ziyu Zhao, Xiaochen Yang, Ling AI, Heng Zhai, Stuart Holmes

Abstract:

As a promising sustainable alternative to traditional fossil fuels, fuel cell technology is highly favoured due to its enhanced working efficiency and reduced emissions. In the context of high-temperature fuel cells (operating above 100 °C), the most commonly used proton exchange membrane (PEM) is the Polybenzimidazole (PBI) doped phosphoric acid (PA) membrane. Grafting is a promising strategy to advance PA-doped PBI PEM technology. The existing grafting modification on PBI PEMs mainly focuses on grafting phosphate-containing or alkaline groups onto the PBI molecular chains. However, quaternary ammonium-based grafting approaches face a common challenge. To initiate the N-alkylation reaction, deacidifying agents such as NaH, NaOH, KOH, K2CO3, etc., can lead to ionic crosslinking between the quaternary ammonium group and PBI. Polyvinylpyrrolidone (PVP) is another widely used polymer, the N-heterocycle groups within PVP endow it with a significant ability to absorb PA. Recently, PVP has attracted substantial attention in the field of fuel cells due to its reduced environmental impact and impressive fuel cell performance. However, due to the the poor compatibility of PVP in PBI, few research apply PVP in PA-doped PBI PEMs. This work introduces an innovative strategy to graft PVP onto PBI to form a network-like polymer. Due to the absence of quaternary ammonium groups, PVP does not pose issues related to crosslinking with PBI. Moreover, the nitrogen-containing functional groups on PVP provide PBI with a robust phosphoric acid retention ability. The nuclear magnetic resonance (NMR) hydrogen spectrum analysis results indicate the successful completion of the grafting reaction where N-alkylation reactions happen on both sides of the grafting agent 1,4-bis(chloromethyl)benzene. On one side, the reaction takes place with the hydrogen atoms on the imidazole groups of PBI, while on the other side, it reacts with the terminal amino group of PVP. The XPS results provide additional evidence from the perspective of the element. On synthesized PBI-g-PVP surfaces, there is an absence of chlorine (chlorine in grafting agent 1,4-bis(chloromethyl)benzene is substituted) element but a presence of sulfur element (sulfur element in terminal amino PVP appears in PBI), which demonstrates the occurrence of the grafting reaction and PVP is successfully grafted onto PBI. Prepare these modified membranes into MEA. It was found that during the fuel cell operation, all the grafted membranes showed substantial improvement in maximum current density and peak power density compared to unmodified one. For PBI-g-PVP 30, with a grafting degree of 22.4%, the peak power density reaches 1312 mW cm⁻², marking a 59.6% enhancement compared to the pristine PBI membrane. The improvement is caused by the improved PA binding ability of the membrane after grafting. The AST test result shows that the grafting membranes have better long-term durability and performance than unmodified membranes attributed to the presence of added PA binding sites, which can effectively prevent the PA leaching caused by proton migration. In conclusion, the test results indicate that grafting PVP onto PBI is a promising strategy which can effectively improve the fuel cell performance.

Keywords: fuel cell, grafting modification, PA doping ability, PVP

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Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

Abstract:

Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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