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Hundreds of neurotoxic insecticides are currently in use. However, only a few direct targets have been identified. Here, using Drosophila and the insecticide flonicamid, we identified nicotinamidase (Naam) as a previous unidentified molecular target for an insecticide. Naam is expressed in chordotonal stretch-receptor neurons, and inhibition of Naam by a metabolite of flonicamid, TFNA-AM (4-trifluoromethylnicotinamide), induces accumulation of substrate nicotinamide and greatly inhibits negative geotaxis. Engineered flies harboring a point mutation in the active site show insecticide resistance and defects in gravity sensing. Bees are resistant to flonicamid because of a gene duplication, resulting in the generation of a TFNA-AM-insensitive Naam. Our results, in combination with the absence of genes encoding Naam in vertebrate genomes, suggest that TFNA-AM and potential species-specific Naam inhibitors could be developed as novel insecticides, anthelmintics, and antimicrobials for agriculture and human health.

Background: Echinococcosis is a parasitic zoonotic disease that threatens human health and economic development. In China, 370 counties are endemic for echinococcosis. Qinghai-Tibet Plateau has the most patients and people at risk. Therefore, analyzing the societal factors related to susceptibility to the disease is critical for efficient prevention and control of echinococcosis. Methods: The demographic characteristics and lifestyle of echinococcosis cases were clustered using K-means cluster analysis to determine the main factors of risk of echinococcosis. Results: Middle-aged and young people as well as those with a low education level and herdsmen are at risk of contracting echinococcosis. Nomadism, domestic and feral dogs in the surrounding environment, and drinking heavily polluted natural surface water are the main behavioral risk factors. The cystic echinococcosis (CE) and alveolar echinococcosis (AE) cluster analysis focused on female, middle-aged, and young people, winter settlement and summer nomadism, and domestic and feral dogs in the surrounding environment. There were significant differences in lifestyle between Qinghai-Tibet Plateau cases and non-Qinghai-Tibet-Plateau cases. Conclusion: According to the distribution of cases and CE and AE, this study identified the factors of risk of echinococcosis in the Qinghai-Tibet Plateau and non-Qinghai-Tibet Plateau. Adapted control techniques appropriate for the various epidemic areas should be established to serve as a reference for echinococcosis prevention.

Prediction markets are long known for prediction accuracy. This study systematically explores the fundamental properties of prediction markets, addressing questions about their information aggregation process and the factors contributing to their remarkable efficacy. We propose a novel multivariate utility (MU) based mechanism that unifies several existing automated market-making schemes. Using this mechanism, we establish the convergence results for markets comprised of risk-averse traders who have heterogeneous beliefs and repeatedly interact with the market maker. We demonstrate that the resulting limiting wealth distribution aligns with the Pareto efficient frontier defined by the utilities of all market participants. With the help of this result, we establish analytical and numerical results for the limiting price in different market models. Specifically, we show that the limiting price converges to the geometric mean of agent beliefs in exponential utility-based markets. In risk-measure-based markets, we construct a family of risk measures that satisfy the convergence criteria and prove that the price can converge to a unique level represented by the weighted power mean of agent beliefs. In broader markets with Constant Relative Risk Aversion (CRRA) utilities, we reveal that the limiting price can be characterized by systems of equations that encapsulate agent beliefs, risk parameters, and wealth. Despite the potential impact of traders' trading sequences on the limiting price, we establish a price invariance result for markets with a large trader population. Using this result, we propose an efficient approximation scheme for the limiting price.

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.

Background. Echinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people's health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement. Methods. Report data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering. Results. A total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, s

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.

Contemporary China is dynamic and complex. Recent dramatic changes in the Chinese economy, society, and environment pose numerous challenges for scholars of China. This Handbook will define contemporary China Studies for the social sciences: investigating how we can best study China; exploring the transformations of contemporary China that inform how we study China; presenting the breadth and depth of the China Studies field; and identify future directions for China Studies. In two volumes, the Handbook situates China Studies in history and context. Each chapter in Part One provides an overview and historiography of how scholars have conceptualized the Chinese state, nation, economy and environment, and analyzes trends in terms of different research approaches, types of sources, and trends in the study of these broad concepts. The next five parts cover substantive themes in China Studies, including economic transformations; politics and government; China as a global actor; urbanization and urban development; and Chinese society. In conclusion, the Handbook draws together critical discussions of emerging issues of transdisciplinary approaches to China Studies, the future of Chinese historical Studies, and the future of China in comparative contexts.

Contemporary China is dynamic and complex. Recent dramatic changes in the Chinese economy, society, and environment pose numerous challenges for scholars of China. This Handbook will define contemporary China Studies for the social sciences: investigating how we can best study China; exploring the transformations of contemporary China that inform how we study China; presenting the breadth and depth of the China Studies field; and identify future directions for China Studies. In two volumes, the Handbook situates China Studies in history and context. Each chapter in Part One provides an overview and historiography of how scholars have conceptualized the Chinese state, nation, economy and environment, and analyzes trends in terms of different research approaches, types of sources, and trends in the study of these broad concepts. The next five parts cover substantive themes in China Studies, including economic transformations; politics and government; China as a global actor; urbanization and urban development; and Chinese society. In conclusion, the Handbook draws together critical discussions of emerging issues of transdisciplinary approaches to China Studies, the future of Chinese historical Studies, and the future of China in comparative contexts.

Contemporary China is dynamic and complex. Recent dramatic changes in the Chinese economy, society, and environment pose numerous challenges for scholars of China. This Handbook will define contemporary China Studies for the social sciences: investigating how we can best study China; exploring the transformations of contemporary China that inform how we study China; presenting the breadth and depth of the China Studies field; and identify future directions for China Studies. In two volumes, the Handbook situates China Studies in history and context. Each chapter in Part One provides an overview and historiography of how scholars have conceptualized the Chinese state, nation, economy and environment, and analyzes trends in terms of different research approaches, types of sources, and trends in the study of these broad concepts. The next five parts cover substantive themes in China Studies, including economic transformations; politics and government; China as a global actor; urbanization and urban development; and Chinese society. In conclusion, the Handbook draws together critical discussions of emerging issues of transdisciplinary approaches to China Studies, the future of Chinese historical Studies, and the future of China in comparative contexts.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

Given the vast amount of Chinese and international scholarship on China–Japan relations, this chapter focuses only on the major areas of study, and the key debates. The chapter begins by considering Chinese academic works on Sino-Japanese relations (mainly in the field of IR), followed by an overview of the key international scholarship which encompasses such areas as diplomatic history, economic relations, traditional and non-traditional security issues, and social/cultural relations. It then presents two case studies: the so-called ‘History Issue’, which continues to attract much academic attention, not least because of ongoing debates about interpretations of the past; and the Diaoyu/Senkaku issue which has escalated since 2010 and continues to be a source of tension between the two sides. Throughout, we take note of the recurring themes in the scholarship, which largely revolve around two key topics: the binary of competition versus cooperation; and the history problem. The chapter concludes with a brief consideration of recent and emerging scholarship on China–Japan relations.

This paper studies a class of continuous-time scalar-state stochastic Linear-Quadratic (LQ) optimal control problem with the linear control constraints. Applying the state separation theorem induced from its special structure, we develop the explicit solution for this class of problem. The revealed optimal control policy is a piece-wise affine function of system state. This control policy can be computed efficiently by solving two Riccati equations off-line. Under some mild conditions, the stationary optimal control policy can be also derived for this class of problem with infinite horizon. This result can be used to solve the constrained dynamic mean-variance portfolio selection problem. Examples shed light on the solution procedure of implementing our method., Comment: 30 pages, 6 figures

Incomplete recovery of function and neuropathic pain are common problems after peripheral nerve injury. To develop new treatment strategies for peripheral nerve injuries we investigated whether the neurotrophic factor artemin could improve outcome after sciatic nerve injuries in rats. Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family and exerts neuroprotective effects on sensory neurons as well as influencing behavioural thermal sensitivity. We additionally evaluated if fibrin sealant, which is sometimes used as a nerve glue, had any effects on neuropathic pain-related behaviour. After the sciatic nerve had been transected, 30 animals were randomised to one of three groups: treatment with a fibrin sealant that contained artemin in conjunction with sutures; fibrin sealant with no artemin (sham) in conjunction with sutures; or sutures alone (n=10 in each group). Motor function, sensory function, and autotomy were evaluated from 1 to 12 weeks after injury. Retrograde flourogold tracing 12 weeks after injury showed that the addition of artemin increased the number of regenerating motor neurons. However, it did not improve their performance, as measured by the Sciatic Function Index, compared with sham or suture alone. Animals treated with artemin had a non-significant increase in motor nerve conduction velocity compared with sham. However, artemin did not reverse nerve injury-induced pain behaviour such as cold or heat hypersensitivity. Fibrin sealant in itself did not ameliorate motor performance, or regeneration of motor neurons, or give rise to nerve injury-induced pain behaviour. The results indicate that artemin is of value as a treatment for peripheral nerve injuries, although the effects were limited. As the artemin high-affinity receptor GFRalpha-3 is present in Schwann cells and not in motor neurons, the effect on motor neuron axon regeneration may result from an indirect effect through Schwann cells in the injured nerve.

As neurotransmitter/modulator, adenosine plays an important role in nociceptive processing. Adenosine receptors are G-protein coupled and four receptor subtypes, A1, A2A, A2B and A3 have been identified. It is well established that adenosine and its receptor agonists produce primarily antinociceptive effect in animals and humans. The physiological significance of endogenous adenosine and its receptors in pain modulation, including neuropathic pain (pain after injury or diseases to the nervous system) is, however, less clear. In the first part of this thesis, we have used mice with targeted deletion of adenosine A1 and A3 receptors to explore their individual roles in nociception. In the second part of the thesis, we studied the effect of caffeine, a non-selective antagonist of adenosine receptors, in a rat model of neuropathic pain and explored potential genetic factors in the antinociceptive effect of the adenosine analogue R (-N 6 -2-Phenylisopropyl) adenosine (R-PIA) using inbred mice. To aid these studies, we developed anew method for chronic intrathecal (i.t.) catheterization in mice. A1, but not A3, knock out mice exhibited heat hyperalgesia under normal condition and after carrageenan-induced inflammation, suggesting that the A1 receptor is physiologically active in inhibiting nociceptive input. A1 receptor, on the other hand, does not seem to play a role in localized inflammatory reaction to carrageenan. In contrast, canageenan-induced inflammation was reduced in the periphery in the A3 knock-out mice, which was associated with reduced inflammatory hyperalgesia. This suggests that adenosine A3 receptors play a pro-inflammatory role in peripheral tissues. The antinociceptive effect of i.t. R-PIA was abolished in A1, but not A3, knock-out mice. Further, the antinociceptive effect of i.t., but not systemic, morphine was also reduced in A, knockout mice. These results suggest that the spinal A1 receptor is critical for adenosine analogue-mediated antinociception

As neurotransmitter/modulator, adenosine plays an important role in nociceptive processing. Adenosine receptors are G-protein coupled and four receptor subtypes, A1, A2A, A2B and A3 have been identified. It is well established that adenosine and its receptor agonists produce primarily antinociceptive effect in animals and humans. The physiological significance of endogenous adenosine and its receptors in pain modulation, including neuropathic pain (pain after injury or diseases to the nervous system) is, however, less clear. In the first part of this thesis, we have used mice with targeted deletion of adenosine A1 and A3 receptors to explore their individual roles in nociception. In the second part of the thesis, we studied the effect of caffeine, a non-selective antagonist of adenosine receptors, in a rat model of neuropathic pain and explored potential genetic factors in the antinociceptive effect of the adenosine analogue R (-N 6 -2-Phenylisopropyl) adenosine (R-PIA) using inbred mice. To aid these studies, we developed anew method for chronic intrathecal (i.t.) catheterization in mice. A1, but not A3, knock out mice exhibited heat hyperalgesia under normal condition and after carrageenan-induced inflammation, suggesting that the A1 receptor is physiologically active in inhibiting nociceptive input. A1 receptor, on the other hand, does not seem to play a role in localized inflammatory reaction to carrageenan. In contrast, canageenan-induced inflammation was reduced in the periphery in the A3 knock-out mice, which was associated with reduced inflammatory hyperalgesia. This suggests that adenosine A3 receptors play a pro-inflammatory role in peripheral tissues. The antinociceptive effect of i.t. R-PIA was abolished in A1, but not A3, knock-out mice. Further, the antinociceptive effect of i.t., but not systemic, morphine was also reduced in A, knockout mice. These results suggest that the spinal A1 receptor is critical for adenosine analogue-mediated antinociception

As neurotransmitter/modulator, adenosine plays an important role in nociceptive processing. Adenosine receptors are G-protein coupled and four receptor subtypes, A1, A2A, A2B and A3 have been identified. It is well established that adenosine and its receptor agonists produce primarily antinociceptive effect in animals and humans. The physiological significance of endogenous adenosine and its receptors in pain modulation, including neuropathic pain (pain after injury or diseases to the nervous system) is, however, less clear. In the first part of this thesis, we have used mice with targeted deletion of adenosine A1 and A3 receptors to explore their individual roles in nociception. In the second part of the thesis, we studied the effect of caffeine, a non-selective antagonist of adenosine receptors, in a rat model of neuropathic pain and explored potential genetic factors in the antinociceptive effect of the adenosine analogue R (-N 6 -2-Phenylisopropyl) adenosine (R-PIA) using inbred mice. To aid these studies, we developed anew method for chronic intrathecal (i.t.) catheterization in mice. A1, but not A3, knock out mice exhibited heat hyperalgesia under normal condition and after carrageenan-induced inflammation, suggesting that the A1 receptor is physiologically active in inhibiting nociceptive input. A1 receptor, on the other hand, does not seem to play a role in localized inflammatory reaction to carrageenan. In contrast, canageenan-induced inflammation was reduced in the periphery in the A3 knock-out mice, which was associated with reduced inflammatory hyperalgesia. This suggests that adenosine A3 receptors play a pro-inflammatory role in peripheral tissues. The antinociceptive effect of i.t. R-PIA was abolished in A1, but not A3, knock-out mice. Further, the antinociceptive effect of i.t., but not systemic, morphine was also reduced in A, knockout mice. These results suggest that the spinal A1 receptor is critical for adenosine analogue-mediated antinociception

As neurotransmitter/modulator, adenosine plays an important role in nociceptive processing. Adenosine receptors are G-protein coupled and four receptor subtypes, A1, A2A, A2B and A3 have been identified. It is well established that adenosine and its receptor agonists produce primarily antinociceptive effect in animals and humans. The physiological significance of endogenous adenosine and its receptors in pain modulation, including neuropathic pain (pain after injury or diseases to the nervous system) is, however, less clear. In the first part of this thesis, we have used mice with targeted deletion of adenosine A1 and A3 receptors to explore their individual roles in nociception. In the second part of the thesis, we studied the effect of caffeine, a non-selective antagonist of adenosine receptors, in a rat model of neuropathic pain and explored potential genetic factors in the antinociceptive effect of the adenosine analogue R (-N 6 -2-Phenylisopropyl) adenosine (R-PIA) using inbred mice. To aid these studies, we developed anew method for chronic intrathecal (i.t.) catheterization in mice. A1, but not A3, knock out mice exhibited heat hyperalgesia under normal condition and after carrageenan-induced inflammation, suggesting that the A1 receptor is physiologically active in inhibiting nociceptive input. A1 receptor, on the other hand, does not seem to play a role in localized inflammatory reaction to carrageenan. In contrast, canageenan-induced inflammation was reduced in the periphery in the A3 knock-out mice, which was associated with reduced inflammatory hyperalgesia. This suggests that adenosine A3 receptors play a pro-inflammatory role in peripheral tissues. The antinociceptive effect of i.t. R-PIA was abolished in A1, but not A3, knock-out mice. Further, the antinociceptive effect of i.t., but not systemic, morphine was also reduced in A, knockout mice. These results suggest that the spinal A1 receptor is critical for adenosine analogue-mediated antinociception

Background Human cystic and alveolar echinococcosis are neglected tropical diseases that WHO has prioritized for control in recent years. Both diseases impose substantial burdens on public health and the socio-economy in China. In this study, which is based on the national echinococcosis survey from 2012 to 2016, we aim to describe the spatial prevalence and demographic characteristics of cystic and alveolar echinococcosis infections in humans and assess the impact of environmental, biological and social factors on both types of the disease. Methods We computed the sex-, age group-, occupation- and education level-specific prevalences of cystic and alveolar echinococcosis at national and sub-national levels. We mapped the geographical distribution of echinococcosis prevalence at the province, city and county levels. Finally, by analyzing the county-level echinococcosis cases combined with a range of associated environmental, biological and social factors, we identified and quantified the potential risk factors for echinococcosis using a generalized linear model. Results A total of 1,150,723 residents were selected and included in the national echinococcosis survey between 2012 and 2016, of whom 4161 and 1055 tested positive for cystic and alveolar echinococcosis, respectively. Female gender, older age, occupation at herdsman, occupation as religious worker and illiteracy were identified as risk factors for both types of echinococcosis. The prevalence of echinococcosis was found to vary geographically, with areas of high endemicity observed in the Tibetan Plateau region. Cystic echinococcosis prevalence was positively correlated with cattle density, cattle prevalence, dog density, dog prevalence, number of livestock slaughtered, elevation and grass area, and negatively associated with temperature and gross domestic product (GDP). Alveolar echinococcosis prevalence was positively correlated with precipitation, l