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Background: The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations.Methods: A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate.Results: After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population.Conclusions: In this real-world study enrolling non-anticoa

Background: The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refinestroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed toidentify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predictingthromboembolism in non-anticoagulated AF patients following successful ablations. Methods: A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-monthblanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regressionanalysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score wasevaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) andintegrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration bycomparing the predicted risk with the observed annualized event rate. Results: After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide(NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statisticallysignificantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59–0.74 vs. 0.60,95% CI: 0.52–0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identifymore thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibrationcurve showed that the ABC-AF-Stroke score was well calibrated in this population. Conclusions: In this real-world study enrolling non-anticoagulated AF

We develop a diffusion-based approach for various document layout sequence generation. Layout sequences specify the contents of a document design in an explicit format. Our novel diffusion-based approach works in the sequence domain rather than the image domain in order to permit more complex and realistic layouts. We also introduce a new metric, Document Earth Mover's Distance (Doc-EMD). By considering similarity between heterogeneous categories document designs, we handle the shortcomings of prior document metrics that only evaluate the same category of layouts. Our empirical analysis shows that our diffusion-based approach is comparable to or outperforming other previous methods for layout generation across various document datasets. Moreover, our metric is capable of differentiating documents better than previous metrics for specific cases.

Modeling and designing urban building layouts is of significant interest in computer vision, computer graphics, and urban applications. A building layout consists of a set of buildings in city blocks defined by a network of roads. We observe that building layouts are discrete structures, consisting of multiple rows of buildings of various shapes, and are amenable to skeletonization for mapping arbitrary city block shapes to a canonical form. Hence, we propose a fully automatic approach to building layout generation using graph attention networks. Our method generates realistic urban layouts given arbitrary road networks, and enables conditional generation based on learned priors. Our results, including user study, demonstrate superior performance as compared to prior layout generation networks, support arbitrary city block and varying building shapes as demonstrated by generating layouts for 28 large cities., Comment: Accepted by ICCV 2023

Fei Peng,1 Jing Liu,1,2 Yujun Zhang,1,2 Guoyan Zhao,1,2 Deying Gong,1,2 Liu He,1,2 Wensheng Zhang,1,2 Feng Qiu1,2 1Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Feng Qiu; Wensheng Zhang, Email fengqiu@scu.edu.cn; zhang_ws@scu.edu.cnIntroduction: Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.Methods: Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.Results: Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which

Fei Peng,1 Jing Liu,1,2 Yujun Zhang,1,2 Guoyan Zhao,1,2 Deying Gong,1,2 Liu He,1,2 Wensheng Zhang,1,2 Feng Qiu1,2 1Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2National-Local Joint Engineering Research Center of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Feng Qiu; Wensheng Zhang, Email fengqiu@scu.edu.cn; zhang_ws@scu.edu.cnIntroduction: Ropivacaine as a conventional local anesthetic has been used more and more frequently in the treatment of postoperative pain, but its analgesic effect can only last for several hours. In order to fulfill the clinic requirement for long-term analgesia, a long-acting ropivacaine nanocrystal formulation was fabricated through the interaction between ropivacaine and a self-assembling peptide.Methods: Transmission electron microscopy, dynamic light scattering, circular dichroism and fluorescence spectrometry were used to examine the structural changes caused by the interaction between ropivacaine and the peptide. Scanning electron microscopy, dynamic light scattering, Fourier transform infrared spectrometry, X-ray diffraction and optical microscopy were used to characterize the ropivacaine-peptide nanocrystal. In vitro drug release and pharmacokinetics study were conducted to evaluate the slow-release profile of the nanocrystal formulation. A rodent cutaneous trunci muscle reflex model was used to evaluate the nociceptive blockade effects, and histological analysis was used to evaluate the local toxicity. A rodent plantar incisional pain model was used to evaluate the analgesic effect.Results: Soluble ropivacaine monomers interacted with the Q11 peptide through π-π stacking and remolded its self-assembling structure, leading to the formation of drug/peptide nanoparticles which

Jing Wen,1,2 Liu He,1 Xin Du,1 Chang-Sheng Ma1 1Department of Cardiology, Capital Medical University Affiliated Anzhen Hospital; National Clinical Research Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Geriatrics, Beijing Fengtai Hospital, Beijing, People’s Republic of ChinaCorrespondence: Chang-Sheng Ma; Xin Du, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Beijing Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-84005363, Fax +86-10-84005361, Email chshma@vip.sina.com; duxinheart@sina.comBackground: It is uncertain whether the effect of hyperglycemia on mortality among patients with acute coronary syndrome (ACS) could be adjusted by other modifiable risk factors. Greater body mass index (BMI) might enhance the effect of fasting blood glucose (FPG) on cardiovascular mortality in patients with ACS.Methods: We retrospectively enrolled patients admitted for ACS from 2008 to 2017 in Beijing and divided them into three BMI groups (normal weight ≤ 25 kg/m2, overweight 25– 29.9 kg/m2, obese ≥ 30 kg/m2). The relationships between the blood glucose levels and all-cause or cardiovascular mortalities and their heterogeneities across the groups were analyzed using Cox regression models.Results: A total of 8,086 patients were enrolled, with 746 all-cause and 496 cardiovascular mortalities recorded during the follow-up period. Each 1 mmol/L increase in FPG was associated with an increased risk of all-cause mortality across all groups (adjusted hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.02– 1.09 for normal weight patients; adjusted HR: 1.09, 95% CI: 1.05– 1.13 for overweight patients; adjusted HR: 1.12, 95% CI: 1.03– 1.22 for obese patients), and was associated with an increased risk of cardiovascular mortality among overweight (adjusted HR: 1.10, 95% CI: 1.05– 1.14) and obese patients (adjusted HR: 1.15, 95% CI: 1.04– 1.26), wh

Rare information on photodisintegration reactions of nuclei with mass numbers $A \approx 160$ at astrophysical conditions impedes our understanding of the origin of $p$-nuclei. Experimental determination of the key ($p,\gamma$) cross sections has been playing an important role to verify nuclear reaction models and to provide rates of relevant ($\gamma,p$) reactions in $\gamma$-process. In this paper we report the first cross section measurements of $^{160}$Dy($p,\gamma$)$^{161}$Ho and $^{161}$Dy($p,n$)$^{161}$Ho in the beam energy range of 3.4 - 7.0 MeV, partially covering the Gamow window. Such determinations are possible by using two targets with various isotopic fractions. The cross section data can put a strong constraint on the nuclear level densities and gamma strength functions for $A \approx$ 160 in the Hauser-Feshbach statistical model. Furthermore, we find the best parameters for TALYS that reproduce the A $\thicksim$ 160 data available, $^{160}$Dy($p,\gamma$)$^{161}$Ho and $^{162}$Er($p,\gamma$)$^{163}$Tm, and recommend the constrained $^{161}$Ho($\gamma,p$)$^{160}$Dy reaction rates over a wide temperature range for $\gamma$-process network calculations. Although the determined $^{161}$Ho($\gamma$, p) stellar reaction rates at the temperature of 1 to 2 GK can differ by up to one order of magnitude from the NON-SMOKER predictions, it has a minor effect on the yields of $^{160}$Dy and accordingly the $p$-nuclei, $^{156,158}$Dy. A sensitivity study confirms that the cross section of $^{160}$Dy($p$, $\gamma$)$^{161}$Ho is measured precisely enough to predict yields of $p$-nuclei in the $\gamma$-process., Comment: 12 pages,9 figures

Rare information on photodisintegration reactions of nuclei with mass numbers $A \approx 160$ at astrophysical conditions impedes our understanding of the origin of $p$-nuclei. Experimental determination of the key ($p,\gamma$) cross sections has been playing an important role to verify nuclear reaction models and to provide rates of relevant ($\gamma,p$) reactions in $\gamma$-process. In this paper we report the first cross section measurements of $^{160}$Dy($p,\gamma$)$^{161}$Ho and $^{161}$Dy($p,n$)$^{161}$Ho in the beam energy range of 3.4 - 7.0 MeV, partially covering the Gamow window. Such determinations are possible by using two targets with various isotopic fractions. The cross section data can put a strong constraint on the nuclear level densities and gamma strength functions for $A \approx$ 160 in the Hauser-Feshbach statistical model. Furthermore, we find the best parameters for TALYS that reproduce the A $\thicksim$ 160 data available, $^{160}$Dy($p,\gamma$)$^{161}$Ho and $^{162}$Er($p,\gamma$)$^{163}$Tm, and recommend the constrained $^{161}$Ho($\gamma,p$)$^{160}$Dy reaction rates over a wide temperature range for $\gamma$-process network calculations. Although the determined $^{161}$Ho($\gamma$, p) stellar reaction rates at the temperature of 1 to 2 GK can differ by up to one order of magnitude from the NON-SMOKER predictions, it has a minor effect on the yields of $^{160}$Dy and accordingly the $p$-nuclei, $^{156,158}$Dy. A sensitivity study confirms that the cross section of $^{160}$Dy($p$, $\gamma$)$^{161}$Ho is measured precisely enough to predict yields of $p$-nuclei in the $\gamma$-process., Comment: 12 pages,9 figures

Background: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. Results: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. Conclusions: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.

The development of a polarized neuron relies on the selective transport of proteins to axons and dendrites. Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is poorly understood. Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubule-associated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

We present a Photo2Building tool to create a plausible 3D model of a building from only a single photograph. Our tool is based on a prior desktop version which, as described in this paper, is converted into a client-server model, with job queuing, web-page support, and support of concurrent usage. The reported cloud-based web-accessible tool can reconstruct a building in 40 seconds on average and costing only 0.60 USD with current pricing. This provides for an extremely scalable and possibly widespread tool for creating building models for use in urban design and planning applications. With the growing impact of rapid urbanization on weather and climate and resource availability, access to such a service is expected to help a wide variety of users such as city planners, urban meteorologists worldwide in the quest to improved prediction of urban weather and designing climate-resilient cities of the future., Comment: 7 pages, 7 figures, PEARC '20: Practice and Experience in Advanced Research Computing, July 26--30, 2020, Portland, OR, USA

Liu-Jun He,1 Dong-Lin Yang,1 He-Ying Chen,1– 3 Jiu-Hong Huang,1 Ya-Jun Zhang,1 Hong-Xia Qin,1 Juan-Li Wang,1 Dian-Yong Tang,1 Zhong-Zhu Chen1 1National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of China; 2Division of Molecular Nephrology and the Creative Training Center for Undergraduates, The Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3The Undergraduates Class of 2016 Entry the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaCorrespondence: Dong-Lin Yang; Zhong-Zhu ChenNational & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing Engineering Laboratory of Targeted and Innovative Therapeutics, Chongqing Collaborative Innovation Center of Targeted and Innovative Therapeutics, College of Pharmacy & International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing 402160, People’s Republic of ChinaTel/Fax +86-23-61162836Email dlyang@cqwu.edu.cn; 188831382372@163.comBackground: Breast cancer exhibits poor prognosis and high relapse rates following chemotherapy therapeutics. Thus, this study aims to develop effective novel agents regulating the core molecular pathway of breast cancer such as Wnt/β-catenin

Molecular maps of the human brain alone do not inform us of the features unique to humans. Yet, the identification of these features is important for understanding both the evolution and nature of human cognition. Here, we approached this question by analyzing gene expression and H3K27ac chromatin modification data collected in eight brain regions of humans, chimpanzees, gorillas, a gibbon, and macaques. An analysis of spatial transcriptome trajectories across eight brain regions in four primate species revealed 1851 genes showing human-specific transcriptome differences in one or multiple brain regions, in contrast to 240 chimpanzee-specific differences. More than half of these human-specific differences represented elevated expression of genes enriched in neuronal and astrocytic markers in the human hippocampus, whereas the rest were enriched in microglial markers and displayed human-specific expression in several frontal cortical regions and the cerebellum. An analysis of the predicted regulatory interactions driving these differences revealed the role of transcription factors in species-specific transcriptome changes, and epigenetic modifications were linked to spatial expression differences conserved across species.

Background Cardiovascular disease (CVD) is the leading cause of global disease burden. Although stroke was thought to be more prevalent than coronary heart disease (CHD) in Chinese, the epidemic pattern might have been changed in some rural areas nowadays. This study was to estimate up-to-date prevalence of CVD and its risk factors in rural communities of Fangshan District, Beijing, China. Methods A cross-sectional population survey was carried out by stratified cluster sampling. A total of 58,308 rural residents aged over 40 years were surveyed by face-to-face interview and physical examination during 2008 and 2010. The standardized prevalence was calculated according to adult sample data of China's 5th Population Census in 2000, and the adjusted prevalence odds ratio (POR) was calculated for the association of CHD/stroke with its cardiovascular risk factors in multivariate logistic regression models. Results Age- and sex-standardized prevalence was 5.6% for CHD (5.2% in males and 5.9% in females), higher than the counterpart of 3.7% (4.7% in males and 2.6% in females) for stroke. Compared with previous studies, higher prevalence of 7.7%, 47.2%, 53.3% in males and 8.2%, 44.8%, 60.7% in females for diabetes, hypertension and overweight/obesity were presented accordingly. Moreover, adjusted POR (95% confidence interval) of diabetes, obesity, stage 1 and stage 2 hypertension for CHD as 2.51 (2.29 to 2.75), 1.53 (1.38 to 1.70), 1.13 (1.02 to 1.26) and 1.35 (1.20 to 1.52), and for stroke as 2.24 (1.98 to 2.52), 1.25 (1.09 to 1.44), 1.44 (1.25 to 1.66) and 1.70 (1.46 to 1.98) were shown respectively in the multivariate logistic regression models. Conclusions High prevalence of CVD and probably changed epidemic pattern in rural communities of Beijing, together with the prevalent cardiovascular risk factors and population aging, might cause public health challenges in rural Chinese population.

Background Cardiovascular disease (CVD) is the leading cause of global disease burden. Although stroke was thought to be more prevalent than coronary heart disease (CHD) in Chinese, the epidemic pattern might have been changed in some rural areas nowadays. This study was to estimate up-to-date prevalence of CVD and its risk factors in rural communities of Fangshan District, Beijing, China. Methods A cross-sectional population survey was carried out by stratified cluster sampling. A total of 58,308 rural residents aged over 40 years were surveyed by face-to-face interview and physical examination during 2008 and 2010. The standardized prevalence was calculated according to adult sample data of China's 5th Population Census in 2000, and the adjusted prevalence odds ratio (POR) was calculated for the association of CHD/stroke with its cardiovascular risk factors in multivariate logistic regression models. Results Age- and sex-standardized prevalence was 5.6% for CHD (5.2% in males and 5.9% in females), higher than the counterpart of 3.7% (4.7% in males and 2.6% in females) for stroke. Compared with previous studies, higher prevalence of 7.7%, 47.2%, 53.3% in males and 8.2%, 44.8%, 60.7% in females for diabetes, hypertension and overweight/obesity were presented accordingly. Moreover, adjusted POR (95% confidence interval) of diabetes, obesity, stage 1 and stage 2 hypertension for CHD as 2.51 (2.29 to 2.75), 1.53 (1.38 to 1.70), 1.13 (1.02 to 1.26) and 1.35 (1.20 to 1.52), and for stroke as 2.24 (1.98 to 2.52), 1.25 (1.09 to 1.44), 1.44 (1.25 to 1.66) and 1.70 (1.46 to 1.98) were shown respectively in the multivariate logistic regression models. Conclusions High prevalence of CVD and probably changed epidemic pattern in rural communities of Beijing, together with the prevalent cardiovascular risk factors and population aging, might cause public health challenges in rural Chinese population.

Razvijen je novi trodimenzionalno spregnuti dinamički model sustava za rudarenje u dubokom oceanu. Kopač koji se vuče po dnu napravljen je kao 3D model kompaktnog vozila s mehaničkim modelom gusjeničara s elementima u zahvatu, s kojim ne samo da se može ostvariti brza dinamička simulacija nasuprot tradicionalnom 3D modelu sastavljenom od više dijelova, već se može također omogućiti nošenje specijalnog terramehaničkog modela za talog s morskog dna. Cjevovod za kopanje izrađen je kao 3D model diskretnih elemenata s više dijelova koji je podijeljen u krute elemente povezane fleksibilnim konektorima, i može također ostvariti brzu dinamičku simulaciju za tako dugačak cjevovod. Predloženi su i simulirani novi integrirani načini iskapanja za čitav sustav koji pokazuju da se kroz cijeli postupak može dobro održati stabilno sinhronizirano djelovanje čitavog sustava. Dinamička simulacijska analiza data u radu može pružiti važnu teoretsku bazu i tehničku referencu za dizajn konstrukcije, ocjenu djelovanja i kontrolu rada praktičnog sustava iskapanja u dubokom oceanu., A new three-dimensional coupled dynamic model of the deep ocean mining system is developed. The seafloor tracked miner is built as a 3D single-body vehicle model with mesh element track-terrain interaction mechanics model, which not only can realize the fast dynamic simulation in contrast to traditional 3D multi-body model, but also can allow the loading of the seafloor sediment special terramechanics model. The mining pipeline is built as a 3D multi-body discrete element model that is divided into rigid elements linked by flexible connectors, also can realize the fast dynamic simulation for such long pipeline. New integrated mining operation modes for the total system are proposed and simulated, which show that during the whole operation processes, the synchronized stable motion of the total system can be kept well. The dynamic simulation analysis in the paper can provide important theoretical basis and technical reference for structure design, performance evaluation and operation control of the practical deep ocean mining system.

Changes in patterns of antibiotic use in Chinese hospitals before and after intensive nationwide interventions are reported and compared with Chinese national targets and antibiotic use in Swedish hospitals. Chinese data were collected quarterly and yearly from selected patient prescriptions/medical records and medicines inventory control systems from 15 hospitals (2005-2012). Swedish data were extracted from a 2010-point prevalence survey and 2009-2012 sales data from seven university hospitals. An interrupted time series with segmented regression analysis was used to measure changes in patterns of antibiotic use in Chinese hospitals before and after the interventions. Following the 2011 interventions, significant reductions in antibiotic use in Chinese hospitals were seen: the proportion of prescriptions with antibiotics decreased 4.7% (P=0.03) and the proportion of medical records with antibiotic prescription decreased 73% (P=0.04). The proportions of prescriptions and medical records with antibiotics in Chinese hospitals in 2012 were 10% and 50%, respectively, and remained much higher than Swedish hospitals (1.1% in DDD for outpatients and 34% in number of patients for inpatients). Inpatient consumption in Chinese hospitals dropped significantly from 910 DDD/1000 inpatient days in 2008 to 473 in 2012 (588 in Swedish hospitals). Antibiotics are being used less frequently in Chinese hospitals, broad-spectrum antibiotics are still preferred, and overall usage is higher than Sweden. A significant reduction in overall inpatient antibiotic consumption was observed after the interventions. It is not possible to identify whether the-changes have resulted in less inappropriate antibiotic use. Further studies are needed.

Los estudios que se han llevado a cabo en esta tesis se basan en el desarrollo de métodos para la eliminación de contaminantes en aguas mediante procesos en lo que no se utilizan reactivos, lo que proporcionan un valor añadido al tratamiento del agua contaminada. En nuestro caso, los métodos utilizados se centrar en la eliminación de oxoaniones de arsénico y selenio en disoluciones acuosas mediante procesos de adsorción-desorción. Estos procesos caracterizados por la no utilización de reactivos se desarrollaron mediante el estudio de parámetros termodinámicos, como por ejemplo, la temperatura y/o el potencial redox de las disoluciones de estudio. Por tanto, estos métodos no solo nos proporcionarán un ahorro de reactivos en la recuperación del adsorbente, sino que permitirán el reciclado de dicho adsorbente y su reutilización. La capacidad de adsorción del arsenito/arsenato en la esponja cargada con nanoparticulas de óxido de hierro superparamagneticas (SPION) está influenciada por el pH, el tiempo de contacto, la concentración inicial, cantidad de adsorbente, la temperatura y por el potencial redox. La adsorción máxima para el arsenato en el sistema esponja-SPION se ha obtenido en medio ácido (pH 3.6) tras 1 hora a 20ºC, mientras que el equilibrio de desorción se alcanzó a las 2h a 70ºC. Las constantes del equilibrio de adsorcion se determinaron como logK20=4,198 y logK70=1.023 a 20°C y 70°C respectivamente. La disminución de estos valores se relacionan un valor de ∆G negativo, lo que indica un aumento de la adsorción de As(V) cuando la temperatura disminuye. Los valores de ∆H y ∆S calculados son -122,150 kJ mol-1 y 337 J mol-1 K-1 respectivamente, lo que indica que el proceso de adsorción es exotérmico. La oxidación de As(III) a As(V) y el proceso de reducción correspondiente fueron caracterizados para probar el concepto de potencial redox como parámetro clave en estos procesos. La oxidación de As(III) a As(V) mediante dicromato de potasio (tasa de conversión>91%), The studies that have been carried out in the present PhD thesis project are based on the development of methods to remove water pollutants by using reagent-less processes and to provide and added value to the contaminated water treatment. In our case, the methods are related to arsenic or selenium oxyanions removal in aqueous solution. Methods are based on sorption-desorption processes for the indicated oxyanions. Nanostructured materials have been implemented as adsorption substances, being either iron or aluminum oxides the nanoparticles active constituents. Reagent-less processes were developed by using intensive thermodynamic parameters, e.g, temperature and/or redox potential of the target solution. Appropriate tuning of these parameters will allow both process selectivity and regeneration of the adsorption material. Synergic interaction of thermo-tuning with redox variation will provide such results. Thus, this reagentless method could not only provide reagent savings for recovering the adsorbent, but also the adsorbent recycling to be reused will contribute to a-cost efficient process. The results show as follows: The adsorption capacity of arsenate/arsenite on sponge loaded with superparamagnetic iron oxide nanoparticles (SPION) is influenced by pH, contact time, initial concentration, adsorbent dosage, temperature as well as redox potential. The maximum adsorption for arsenate on sponge-SPION was obtained in an acid media (pH 3.6) in 1 hour contact time under 20ºC while desorption equilibrium was achieved with 2 hours under 70ºC. Equilibrium adsorption constants were determined as log K20=4.198 and log K70=1.023 under 20ºC and 70ºC respectively. These values correlate with the decrease of related negative ∆G° values, indicating the adsorption increase of As(V) when temperature decreases. ΔH° and ΔS° were found to be -122.150 kJ mol-1 and 337 J mol-1 K-1 respectively, indicating the adsorption reaction to be exothermic. The oxidation of As (III) to As(V) an

In the uncertain society, people pay insurance on everything, now the trend turns to small animals. The purpose of this study is to understand the differences between two pet insurance markets, where one is developed in UK and the other is in China. Moreover, overview of pet insurance in USA, Sweden and Japan will be attached to set out their perfect operation systems. Based on this analysis, Chinese insurers seek to obtain strategic management experience and coverage setting issue from the international insurance market practitioners. This dissertation collects data by employing online survey and uses SPSS approach to analyse the results. The main findings are China has huge potential to be the next outstanding country of pet insurance sale, however, local insurance companies who sell pet insurance should adjust their present policies and conditions, also the governmental regulatory body (e.g. the China Insurance Regulatory Commission, CIRC) should upgrade relative rules or laws with the development of insurance market.

In the uncertain society, people pay insurance on everything, now the trend turns to small animals. The purpose of this study is to understand the differences between two pet insurance markets, where one is developed in UK and the other is in China. Moreover, overview of pet insurance in USA, Sweden and Japan will be attached to set out their perfect operation systems. Based on this analysis, Chinese insurers seek to obtain strategic management experience and coverage setting issue from the international insurance market practitioners. This dissertation collects data by employing online survey and uses SPSS approach to analyse the results. The main findings are China has huge potential to be the next outstanding country of pet insurance sale, however, local insurance companies who sell pet insurance should adjust their present policies and conditions, also the governmental regulatory body (e.g. the China Insurance Regulatory Commission, CIRC) should upgrade relative rules or laws with the development of insurance market.

In the uncertain society, people pay insurance on everything, now the trend turns to small animals. The purpose of this study is to understand the differences between two pet insurance markets, where one is developed in UK and the other is in China. Moreover, overview of pet insurance in USA, Sweden and Japan will be attached to set out their perfect operation systems. Based on this analysis, Chinese insurers seek to obtain strategic management experience and coverage setting issue from the international insurance market practitioners. This dissertation collects data by employing online survey and uses SPSS approach to analyse the results. The main findings are China has huge potential to be the next outstanding country of pet insurance sale, however, local insurance companies who sell pet insurance should adjust their present policies and conditions, also the governmental regulatory body (e.g. the China Insurance Regulatory Commission, CIRC) should upgrade relative rules or laws with the development of insurance market.

Cas3 is essential for CRISPR-Cas immunity in Escherichia coli and is conserved across Class 1, type I CRISPR-Cas systems. Cas3 is a metal-dependent nuclease and ATP-dependent helicase that is required for CRISPR interference reactions, the stage of immunity in which a Cascade complex delivers crRNA to a complementary sequence in invader DNA to form an R-loop, trigger nuclease degradation of the invader, and stimulate adaptation (“priming”). Cas3 nuclease activity resides in an HD-domain (called Cas3’ here) and Cas3 translocation activity is catalysed by superfamily-2 helicase. The nuclease activity of Cas3 is crucial for interference and a preliminary analysis of its mechanism is presented here. We generated purified E. coli Cas3, Cas3’ and nuclease inactive Cas3’ proteins to study their activities on ssDNA and dsDNA substrates in comparison with similar substrates containing precisely positioned chemical modifications to the DNA backbone or bases. We observed that methyl-phosphonate and abasic DNA modifications had significant inhibitory effects on Cas3’ and Cas3 nuclease activities, and that there were some interesting differences in activities of these two enzymes when confronted with phosphorothioate DNA. This gives clues about the mode of action for Cas3’ and Cas3 when interacting with DNA for catalytic activity. The new work described will form the basis of more detailed kinetic analyses of Cas3’ and Cas3 nuclease activities in future work.

In the uncertain society, people pay insurance on everything, now the trend turns to small animals. The purpose of this study is to understand the differences between two pet insurance markets, where one is developed in UK and the other is in China. Moreover, overview of pet insurance in USA, Sweden and Japan will be attached to set out their perfect operation systems. Based on this analysis, Chinese insurers seek to obtain strategic management experience and coverage setting issue from the international insurance market practitioners. This dissertation collects data by employing online survey and uses SPSS approach to analyse the results. The main findings are China has huge potential to be the next outstanding country of pet insurance sale, however, local insurance companies who sell pet insurance should adjust their present policies and conditions, also the governmental regulatory body (e.g. the China Insurance Regulatory Commission, CIRC) should upgrade relative rules or laws with the development of insurance market.