The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator o...The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.展开更多
The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to...The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.展开更多
Purpose: This study describes a machine-learning approach utilizing patients' anatomical changes to predict parotid mean dose changes in fractionated radiotherapy for head-and-neck cancer, thereby facilitating pla...Purpose: This study describes a machine-learning approach utilizing patients' anatomical changes to predict parotid mean dose changes in fractionated radiotherapy for head-and-neck cancer, thereby facilitating plan adaptation decisions. Methods: Parotid mean dose changes during treatment sessions are assumed to correlate with patients’ anatomical changes, quantified by 65 geometrical features in four sets. SET1 is the parotid volumetric changes;SET2 is the distance changes from the parotid to the PTV;SET3 is the length of beam path changes between the parotid and skin near the neck;SET4 is the distance changes from the parotid to the two bony landmarks—the dens of the C2 and tip of the basilar part of the occipital bone. The introduced landmarks in SET4 are used as surrogates for the PTV in SET2 due to PTV’s unavailability at the simulation stage. Signed Euclidean distance is applied to quantify the distance and beam path length. A decision tree classifier to predict an x% increase in parotid mean dose is developed. In a study involving 18 patients (36 parotids) previously treated with adaptive radiotherapy, a leave-one-out cross-validation combined with enumerating 4 combinations of the 65 geometrical features is used to find a feature subset maximizing classifier’s accuracy. The classifier’s accuracy, with and without SET2’s PTV features inclusion, is evaluated to determine the SET4’s bony landmark surrogate feasibility. Results: Under x = 5% (or x = 10%) parotid mean dose increase: without SET2’s PTV features inclusion, one beam path feature from SET3 and one bony landmark feature from SET4 yield maximal accuracy of 86.1%, which is a 30.5% (19.4%) improvement over prevalence = 55.6% (66.7%);TPR = 87.5% (75%), TNR = 85% (91.7%), PPV = 82.3% (81.8%) and NPV = 89.5% (88%). With SET2’s PTV features inclusion, accuracy increases from 86.1% to 91.6%. Conclusion: Under the current 18 enrolled patients’ data, we found that the introduced SET4’s bony landmarks are feasible surrogates for the SET2�展开更多
Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and ro...Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and routines related to diabetes management. Technology can support daily diabetes self-management activities including blood glucose monitoring, exercising, healthy eating, taking medication, monitoring for complications, and problem-solving. This article describes an integrative review conducted to evaluate the types of technology being used to facilitate diabetes self-management and the effect of that technology on self-management and diabetes outcomes for adults living with type 2 diabetes mellitus. A literature review was conducted by searching Medline, Pub Med, and Psych INFO databases using the search terms: diabetes self-management, technology, type 2 diabetes, smartphones, cell phones, and diabetes mellitus covering the years from 2008-2013. Articles relying on secondary data(editorials, systematic reviews) and articles describing study protocol only were excluded. Fourteen studies including qualitative, quasiexperimental, and randomized controlled trial designs were identified and included in the review. The review found that technological interventions had positive impacts on diabetes outcomes including improvements in hemoglobin A1 C levels, diabetes self-management behaviors, and diabetes self-efficacy. Results indicate that technological interventions can benefit people living with diabetes when used in conjunction with diabetes care delivered by healthcare providers.展开更多
Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon ...Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (^+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months;amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.展开更多
区域一体化快速发展背景下,如何系统谋划区域综合交通运输规划,使经济、土地/空间及交通与环境协调发展,是实现区域可持续发展亟需深入研究的课题。因此,本文统筹考虑经济、土地/空间及交通和环境要素的动态交互关系,提出大区域综合货...区域一体化快速发展背景下,如何系统谋划区域综合交通运输规划,使经济、土地/空间及交通与环境协调发展,是实现区域可持续发展亟需深入研究的课题。因此,本文统筹考虑经济、土地/空间及交通和环境要素的动态交互关系,提出大区域综合货运整体规划模型的设计与开发方法。利用PECAS(Production,Exchange and Consumption Allocation System)理论框架分析生产者、消费者、交换商品、土地(空间)和运输方式之间的交互关系,并通过PECAS的集计经济流表设计模型结构,构建相应的宏观经济预测、社会经济活动空间分配、空间开发以及交通运输需求预测这4个模块,模拟区域社会经济活动增长及其空间分布与土地/空间开发及综合交通需求时变等特征之间的互动耦合关系。在社会经济发展目标、土地空间和环境等约束条件下,通过构建空间经济模型和综合交通一体化网络分配模型,实现面向多货品和多方式的综合货运整体规划建模方法,以辅助区域产业布局、土地利用与综合交通系统的整体规划。本文以长江经济带为研究案例,基于相关数据构建相应的大区域综合货运整体规划模型,分析评估2012—2035年模型预测结果。结果显示,预测得到的综合交通年平均日货运量拟合优度超过85%,分担率误差低于1%,验证了本文建模方法的有效性。展开更多
The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at differe...The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.展开更多
In the last two or three decades,physical activity(PA) has gained increasing recognition as being essential for maintaining good health and improving quality of life for all ages.Children have traditionally been activ...In the last two or three decades,physical activity(PA) has gained increasing recognition as being essential for maintaining good health and improving quality of life for all ages.Children have traditionally been active in both free play and organized sports.However,there has been a recent decline in the PA levels among children for various reasons.This lifestyle change has resulted in increased obesity accompanied by a rise in diabetes and cardiovascular risk among otherwise healthy children.These lifestyle changes have been shown to be even more a problem when the child is already affected by a chronic disease.Due to medical limitations and contraindications,much care must be taken to make certain that these children are involved in the appropriate volume and intensity of exercise.The type of activity must also be given careful consideration to avoid undue risk for the child who may have problems such as poor balance,limited strength,poor vision,or cognitive disability.Further complications are either caused or exacerbated by lack of sufficient PA.The priority beyond concern for safety should be focused on ensuring the highest quality of life possible.The purpose of this review is to examine how PA can benefit children with selected chronic health conditions.展开更多
基金supported by National Institutes of Health(NIH)/National Cancer Institute(NCI)grants(R01 CA186662 and R01 CA214019 to RZ).The content is solely the responsibility of the authors,and does not necessarily represent the official views of the National Institutes of Health.supported by American Cancer Society(ACS)grant RSG-15-009-01-CDDsupported by funds for the Robert L.Boblitt Endowed Professor in Drug Discovery and research funds from the College of Pharmacy and the University of Houston+3 种基金supported by grants from the National Nature Science Foundation(81630086,81427805,81672763,31401611,and 81502122)the Key Research Program(ZDRW-ZS-2017-1)the Strategic Priority Research Program(XDA12020319)of the Chinese Academy of Sciencesthe Science and Technology Commission of Shanghai Municipality(16391903700 and 14391901800).
文摘The p53 tumor suppressor plays a major role in controlling the initiation and development of cancer by regulating cell cycle arrest,apoptosis,senescence,and DNA repair.The MDM2 oncogene is a major negative regulator of p53 that inhibits the activity of p53 and reduces its protein stability.MDM2,p53,and the p53-MDM2 pathway represent welldocumented targets for preventing and/or treating cancer.Natural products,especially those from medicinal and food plants,are a rich source for the discovery and development of novel therapeutic and preventive agents against human cancers.Many natural product-derived MDM2 inhibitors have shown potent efficacy against various human cancers.In contrast to synthetic small-molecule MDM2 inhibitors,the majority of which have been designed to inhibit MDM2-p53 binding and activate p53,many natural product inhibitors directly decrease MDM2 expression and/or MDM2 stability,exerting their anticancer activity in both p53-dependent and p53-independent manners.More recently,several natural products have been reported to target mutant p53 in cancer.Therefore,identification of natural products targeting MDM2,mutant p53,and the p53-MDM2 pathway can provide a promising strategy for the development of novel cancer chemopreventive and chemotherapeutic agents.In this review,we focus our discussion on the recent advances in the discovery and development of anticancer natural products that target the p53-MDM2 pathway,emphasizing several emerging issues,such as the efficacy,mechanism of action,and specificity of these natural products.
文摘The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.
文摘Purpose: This study describes a machine-learning approach utilizing patients' anatomical changes to predict parotid mean dose changes in fractionated radiotherapy for head-and-neck cancer, thereby facilitating plan adaptation decisions. Methods: Parotid mean dose changes during treatment sessions are assumed to correlate with patients’ anatomical changes, quantified by 65 geometrical features in four sets. SET1 is the parotid volumetric changes;SET2 is the distance changes from the parotid to the PTV;SET3 is the length of beam path changes between the parotid and skin near the neck;SET4 is the distance changes from the parotid to the two bony landmarks—the dens of the C2 and tip of the basilar part of the occipital bone. The introduced landmarks in SET4 are used as surrogates for the PTV in SET2 due to PTV’s unavailability at the simulation stage. Signed Euclidean distance is applied to quantify the distance and beam path length. A decision tree classifier to predict an x% increase in parotid mean dose is developed. In a study involving 18 patients (36 parotids) previously treated with adaptive radiotherapy, a leave-one-out cross-validation combined with enumerating 4 combinations of the 65 geometrical features is used to find a feature subset maximizing classifier’s accuracy. The classifier’s accuracy, with and without SET2’s PTV features inclusion, is evaluated to determine the SET4’s bony landmark surrogate feasibility. Results: Under x = 5% (or x = 10%) parotid mean dose increase: without SET2’s PTV features inclusion, one beam path feature from SET3 and one bony landmark feature from SET4 yield maximal accuracy of 86.1%, which is a 30.5% (19.4%) improvement over prevalence = 55.6% (66.7%);TPR = 87.5% (75%), TNR = 85% (91.7%), PPV = 82.3% (81.8%) and NPV = 89.5% (88%). With SET2’s PTV features inclusion, accuracy increases from 86.1% to 91.6%. Conclusion: Under the current 18 enrolled patients’ data, we found that the introduced SET4’s bony landmarks are feasible surrogates for the SET2�
文摘Technology can be used to supplement healthcare provider diabetes care by providing both educational and motivational support. Education can be provided using technology allowing patients to learn new practices and routines related to diabetes management. Technology can support daily diabetes self-management activities including blood glucose monitoring, exercising, healthy eating, taking medication, monitoring for complications, and problem-solving. This article describes an integrative review conducted to evaluate the types of technology being used to facilitate diabetes self-management and the effect of that technology on self-management and diabetes outcomes for adults living with type 2 diabetes mellitus. A literature review was conducted by searching Medline, Pub Med, and Psych INFO databases using the search terms: diabetes self-management, technology, type 2 diabetes, smartphones, cell phones, and diabetes mellitus covering the years from 2008-2013. Articles relying on secondary data(editorials, systematic reviews) and articles describing study protocol only were excluded. Fourteen studies including qualitative, quasiexperimental, and randomized controlled trial designs were identified and included in the review. The review found that technological interventions had positive impacts on diabetes outcomes including improvements in hemoglobin A1 C levels, diabetes self-management behaviors, and diabetes self-efficacy. Results indicate that technological interventions can benefit people living with diabetes when used in conjunction with diabetes care delivered by healthcare providers.
文摘Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (^+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months;amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.
文摘区域一体化快速发展背景下,如何系统谋划区域综合交通运输规划,使经济、土地/空间及交通与环境协调发展,是实现区域可持续发展亟需深入研究的课题。因此,本文统筹考虑经济、土地/空间及交通和环境要素的动态交互关系,提出大区域综合货运整体规划模型的设计与开发方法。利用PECAS(Production,Exchange and Consumption Allocation System)理论框架分析生产者、消费者、交换商品、土地(空间)和运输方式之间的交互关系,并通过PECAS的集计经济流表设计模型结构,构建相应的宏观经济预测、社会经济活动空间分配、空间开发以及交通运输需求预测这4个模块,模拟区域社会经济活动增长及其空间分布与土地/空间开发及综合交通需求时变等特征之间的互动耦合关系。在社会经济发展目标、土地空间和环境等约束条件下,通过构建空间经济模型和综合交通一体化网络分配模型,实现面向多货品和多方式的综合货运整体规划建模方法,以辅助区域产业布局、土地利用与综合交通系统的整体规划。本文以长江经济带为研究案例,基于相关数据构建相应的大区域综合货运整体规划模型,分析评估2012—2035年模型预测结果。结果显示,预测得到的综合交通年平均日货运量拟合优度超过85%,分担率误差低于1%,验证了本文建模方法的有效性。
文摘The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years.
文摘In the last two or three decades,physical activity(PA) has gained increasing recognition as being essential for maintaining good health and improving quality of life for all ages.Children have traditionally been active in both free play and organized sports.However,there has been a recent decline in the PA levels among children for various reasons.This lifestyle change has resulted in increased obesity accompanied by a rise in diabetes and cardiovascular risk among otherwise healthy children.These lifestyle changes have been shown to be even more a problem when the child is already affected by a chronic disease.Due to medical limitations and contraindications,much care must be taken to make certain that these children are involved in the appropriate volume and intensity of exercise.The type of activity must also be given careful consideration to avoid undue risk for the child who may have problems such as poor balance,limited strength,poor vision,or cognitive disability.Further complications are either caused or exacerbated by lack of sufficient PA.The priority beyond concern for safety should be focused on ensuring the highest quality of life possible.The purpose of this review is to examine how PA can benefit children with selected chronic health conditions.