Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate ear...Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.展开更多
In this research, one-dimensional stratiform a novel dual-model system, cold cloud model （1DSC） coupled to Weather Research and Forecast （WRF） model （WRF-1DSC for short）, was employed to investigate the effects ...In this research, one-dimensional stratiform a novel dual-model system, cold cloud model （1DSC） coupled to Weather Research and Forecast （WRF） model （WRF-1DSC for short）, was employed to investigate the effects of cloud seeding by silver iodide （AgI） on rain enhancement. Driven by changing environmental conditions extracted from the WRF model, WRF-1DSC could be used to assess the cloud seeding effects quantitatively. The employment of WRF- 1DSC, in place of a one-dimen- sional two-moment cloud seeding model applied to a three-dimensional mesoscale cloud-resolving model, was found to result in massive reduction of computational resources. Numerical experiments with WRF-1DSC were conducted for a real stratiform precipitation event ob- served on 4-5 July 2004, in Northeast China. A good agreement between the observed and modeled cloud system ensured the ability of WRF-1DSC to simulate the observed precipitation process efficiently. Sensitivity tests were performed with different seeding times, locations, and amounts. Experimental results showed that the optimum seeding effect （defined as the percentage of rain enhancement or rain enhancement rate） could be achieved through proper seeding at locations of maximum cloud water content when the updraft was strong. The optimum seeding effect was found to increase by 5.61% when the cloud was seeded at 5.5 km above ground level around 2300 UTC 4 July 2004, with the maximum AgI mixing ratio （As） equaling 15 ng kg-1. On the other hand, for an overseeded cloud, a significant reduction occurred in the accumulated precipitation （-12.42%） as Xs reached 100 ng kg^-1. This study demonstrates the potential of WRF- 1DSC in determining the optimal AgI seeding strategy in practical operations of precipitation enhancement.展开更多
An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alp...An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.展开更多
Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input...Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life（Kupers and Ptito,2014）.More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.展开更多
A new Lagrangian—Eulerian coupling model system is developed to study regional air quality. The system consists of mesoscale dynamical meteorological model (MM), Monte—Carlo model (MCM), parameterized model on plane...A new Lagrangian—Eulerian coupling model system is developed to study regional air quality. The system consists of mesoscale dynamical meteorological model (MM), Monte—Carlo model (MCM), parameterized model on planetary boundary layer (PBL) turbulent statistics, dry and wet removal model, and Eulerian nonlinear chemical model (ENCM). The physical, chemical and biological processes on air pollutants are considered comprehensively. 3—D distribution laws tor acidic gaseous pollutants (SO2 and NOx) emitted by Thai Mae Moh Power Plant and the secondary pollutants are studied in detail. The results simulated by the coupling model system are in good agreement with observational concentration data. Key words MM - MCM - ENCM - Coupling model system The authors wish to express their thanks to Prof. Zeng Q. C. for his support to this research and to Dr. Han Z. W. and Zhang M. G. for their help in programming and numerical calculation of IAP, Chinese Academy of Sciences. Thanks are also due to NSTD and EGAT in Thailand for supporting this research.展开更多
A knowledge model with temporal and spatial characteristics for the quantitative design of a cultural pattern in wheat production, using systems analysis and dynamic modeling techniques, was developed for wheat manage...A knowledge model with temporal and spatial characteristics for the quantitative design of a cultural pattern in wheat production, using systems analysis and dynamic modeling techniques, was developed for wheat management, as a decision-making tool in digital farming. The fundamental relationships and algorithms of wheat growth indices and management criteria to cultivars, ecological environments, and production levels were derived from the existing literature and research data to establish a knowledge model system for quantitative wheat management using Visual C^＋＋. The system designed a cultural management plan for general management guidelines and crop regulation indices for timecourse control criteria during the wheat-growing period. The cultural management plan module included submodels to determine target grain yield and quality, cultivar choice, sowing date, population density, sowing rate, fertilization strategy, and water management, whereas the crop regulation indices module included submodels for suitable development stages, dynamic growth indices, source-sink indices, and nutrient indices. Ewluation of the knowledge model by design studies on the basis of data sets of different eco-sites, cultiwrs, and soil types indicated a favorable performance of the model system in recommending growth indices and management criteria under diverse conditions. Practical application of the knowledge model system in comparative field experiments produced yield gains of 2.4% to 16.5%. Thus, the presented knowledge model system overcame some of the difficulties of the traditional wheat management patterns and expert systems, and laid a foundation for facilitating the digitization of wheat management.展开更多
The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent...The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.展开更多
In this paper, the effects of frying time, white egg (0%, 5% and 10% w/w) and chitosan (0%, 0.5% and 1.5% w/w) addition to the batter formulation on the quality of simulated crispy deep-fried Kurdish cheese nugget cru...In this paper, the effects of frying time, white egg (0%, 5% and 10% w/w) and chitosan (0%, 0.5% and 1.5% w/w) addition to the batter formulation on the quality of simulated crispy deep-fried Kurdish cheese nugget crusts was studied by using a deep-fried crust model. Moisture content, oil content, color and hardness of the samples were determined. Crust models were fried at 190℃ for 60, 120 and 180 s. Batter formulations and frying time significantly (p < 0.01) affected moisture, oil content, color and hardness of Crust models. Batter formulation contain 10% white egg was found to be an effective ingredient in decreasing oil content of Crust models. The mean moisture and fat content of Crust models formed with batter contained 10% white egg, fried at 190℃, for 180s were 6.207 ± 0.447 and 5.649 ± 0.394. Batters containing 5% white egg and 1.5% chitosan showed the lowest moisture content and the highest oil content among all the formulations. Crust models containing combination of white egg and chitosan were the darkest. Hardness of samples containing chitosan were the highest, specially for ch1.5 The mean hardness in 60, 120 and 180s of frying in this formulation were 21.518 ± 0.481, 36.871 ± 1.758 and 49.563 ± 1.847 respectively.展开更多
Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurologica...Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.展开更多
Water Quality Model System( WQMS) is an important approach to analyzing aquatic situation and supporting environmental decision. However,the usage and promotion of WQMS is largely limited by amounts of parameters,comp...Water Quality Model System( WQMS) is an important approach to analyzing aquatic situation and supporting environmental decision. However,the usage and promotion of WQMS is largely limited by amounts of parameters,complex conditions and enormous operations. A GIS integrated system of urban water environment coupled with SWMM( storm runoff model),ECOM( hydrodynamic model) and RCA( water quality model) was constructed in this study,with the production and transformation of contaminants in large scale taken into consideration. This integrated system guaranteed an independent calculation and multi-model coupling calculation,including convenient pre-processing,fast and efficient model running and results visualization in different spatial and temporal scales,in the purpose of simplifying the usage and promotion of complex models and providing necessary understanding required in water resource managing and water pollution controlling,and ultimately improving decision making capability. The functionality of the proposed system was illustrated by a case of Wuhan city.展开更多
Resurgence of mycobacterial diseases particularly tuberculosis has caused a renewed interest to unravel the strategies employed by mycobacteria for intracellular survival. In spite of advancement in mycobacterial rese...Resurgence of mycobacterial diseases particularly tuberculosis has caused a renewed interest to unravel the strategies employed by mycobacteria for intracellular survival. In spite of advancement in mycobacterial research, our knowledge about genes and their corresponding functional proteins involved during the interaction of mycobacterium with host’s macrophages is fragmentary. This study pertains to development of a suitable in vitro model using murine macrophages and Mycobacterium bovis BCG to study proteins expressed during macrophage-myco bacterium interactions. Peritoneal macrophages from BALB/c mice were infected with M. bovis BCG and intracellular replication was assessed by {3H} thymi- dine uptake assay which was maximal when macrophage to mycobacterium ratio was 1:10. SDS-PAGE was employed to study the proteins expressed and selected proteins were subjected to mass spectrometry. Seven proteins found to be upregulated during macrophage-mycobacterium interaction were identified by MALDI-TOF. The results indicate that the present in vitro infection model was able to support the growth of M. bovis BCG in murine macrophages and is an ideal model to determine the pattern of functions of gene expression during the interaction of mycobacterium with macrophages. The differentially expressed proteins will help in understanding the mycobacterial molecular basis of adaptation to intracellular macrophage environment.展开更多
The integration of Michaelis-Menten kinetics results in a trancedental equation. The results are not in a form that is readily usable. A more usable form of the model solutions is developed. This was accomplished by u...The integration of Michaelis-Menten kinetics results in a trancedental equation. The results are not in a form that is readily usable. A more usable form of the model solutions is developed. This was accomplished by using Taylor series expansion of dimensionless concentration u in terms of its derivatives. The infinite series expression for dimensionless concentration is given. It can be seen that for times t < , the Taylor series expression evaluated near the origin up to the third derivative is a reasonable representation of the integrated solution. More terms in the Taylor series expression can be added to suit the application. It can vary with the apparent volume, dosage, enzyme concentration, Michaelis constant and the desired accuracy level needed. The single compartment model solution was obtained by the method of Laplace transform. It can be seen from Figure 2 that the dimensionless drug concentration in the compartment goes through a maxima. The curve is convex throughout the absorption and elimination processes. The drug gets completely depleted after a said time. The curve is asymmetrical with a right skew. The systems under absorption with elimination that obey the kinetics that can be represented by a set of reactions in circle were considered. A system of simple reactions in circle was taken into account. The concentration profile of the reactants were obtained by the method of Laplace transforms. The conditions when subcritical damped oscillations can be expected are derived. A model was developed for cases when absorption kinetics exhibit subcritical damped oscillations. The solution was developed by the method of Laplace transforms. The solution for dimensionless concentration of the drug in single compartment for different values of rate constants and dimensionless frequency are shown in Figures 6-9. The drug profile reaches a maximum and drops to zero concen-tration after a said time. The fluctuations in concentration depends on the dimensionless frequency resulting from the subcritical damped oscillations during absorption. At low frequencies the fluctuations are absent. As the frequency is increased the fluctuations in concentration are pronounced. The fre-quency of fluctuations were found to increase with increase in frequency of oscillations during ab-sorption.展开更多
This study examines the issues in development of pharmacokinetic single compartment model for systems that obey free radical copolymerization kinetics. Copolymer composition as a function of reactivity ratios of comon...This study examines the issues in development of pharmacokinetic single compartment model for systems that obey free radical copolymerization kinetics. Copolymer composition as a function of reactivity ratios of comonomers for well mixed case was derived. For some cases, such as DEF-AN, diethyl fumarate and acrylonitrile system multiplicity in composition were found. The analysis is extended to n monomers. State space model expressions are used and the QSSA assumption is stated in state space equation form. Conditions when damped oscillations can be expected are noted. In addition to multiplicity in product composition, an account of reactivity ratios and other instances of multi- plicity were found during the pharmacodynamics of the free radical polymerization reactions. A careful study of initiated case, thermal case, 1 CSTR and 2 CSTRS was undertaken and results were presented. Numerical integration techniques were employed on the desktop computer. Steady state and transient state conversion for initiated case and thermal case for 1 CSTR and 2 CSTRs were calculated and plotted in Figures 7-9 and 12. No multiplicity was found in the thermal case for 1 CSTR in the dynamics of transient monomer conversion. Multiplicity was found in the initiated case for 1 CSTR in the dynamics of transient conversion of monomer. The multiplicity was found in the second CSTR for the case of 2 CSTRs in series. No multiplicity was found in the case of initiator decay.展开更多
Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models ...This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models offer insights, they fall short in presenting a holistic view of complex urban challenges. System dynamics (SD) models that are often utilized to provide holistic, systematic understanding of a research subject, like the urban system, emerge as valuable tools, but data scarcity and theoretical inadequacy pose challenges. The research reviews relevant papers on recent SD model applications in urban sustainability since 2018, categorizing them based on nine key indicators. Among the reviewed papers, data limitations and model assumptions were identified as ma jor challenges in applying SD models to urban sustainability. This led to exploring the transformative potential of big data analytics, a rare approach in this field as identified by this study, to enhance SD models’ empirical foundation. Integrating big data could provide data-driven calibration, potentially improving predictive accuracy and reducing reliance on simplified assumptions. The paper concludes by advocating for new approaches that reduce assumptions and promote real-time applicable models, contributing to a comprehensive understanding of urban sustainability through the synergy of big data and SD models.展开更多
Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most...Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.展开更多
A complex geological environment with faults can be encountered in the process of coal mining.Fault activation can cause instantaneous structure slipping,releasing a significant amount of elastic strain energy during ...A complex geological environment with faults can be encountered in the process of coal mining.Fault activation can cause instantaneous structure slipping,releasing a significant amount of elastic strain energy during underground coal mining.This would trigger strong rockburst disasters.To understand the occurrence of fault-slip induced rockbursts,we developed a physical model test system for fault-slip induced rockbursts in coal mine drifts.The boundary energy storage(BES)loading apparatus and bottom rapid retraction(BRR)apparatus are designed to realize energy compensation and continuous boundary stress transfer of the surrounding rocks for instantaneous fault slip,as well as to provide space for the potential fault slip.Taking the typical fault-slip induced rockburst in the Xinjulong Coal Mine,China,as the background,we conducted a model test using the test system.The deformation and stress in the rock surrounding the drift and the support unit force during fault slip are analyzed.The deformation and failure characteristics and dynamic responses of drifts under fault-slip induced rockbursts are obtained.The test results illustrate the rationality and effectiveness of the test system.Finally,corresponding recommendations and prospects are proposed based on our findings.展开更多
Large-scale new energy grid connection leads to the weakening of the system frequency regulation capability,and the system frequency stability is facing unprecedented challenges.In order to solve rapid frequency fluct...Large-scale new energy grid connection leads to the weakening of the system frequency regulation capability,and the system frequency stability is facing unprecedented challenges.In order to solve rapid frequency fluctuation caused by new energy units,this paper proposes a new energy power system frequency regulation strategy with multiple units including the doubly-fed pumped storage unit(DFPSU).Firstly,based on the model predictive control(MPC)theory,the state space equations are established by considering the operating characteristics of the units and the dynamic behavior of the system;secondly,the proportional-differential control link is introduced to minimize the frequency deviation to further optimize the frequency modulation(FM)output of the DFPSU and inhibit the rapid fluctuation of the frequency;lastly,it is verified on theMatlab/Simulink simulation platform,and the results show that the model predictive control with proportional-differential control link can further release the FM potential of the DFPSU,increase the depth of its FM,effectively reduce the frequency deviation of the system and its rate of change,realize the optimization of the active output of the DFPSU and that of other units,and improve the frequency response capability of the system.展开更多
Accurate satellite data assimilation under all-sky conditions requires enhanced parameterization of scattering properties for frozen hydrometeors in clouds.This study aims to develop a nonspherical scattering look-up ...Accurate satellite data assimilation under all-sky conditions requires enhanced parameterization of scattering properties for frozen hydrometeors in clouds.This study aims to develop a nonspherical scattering look-up table that contains the optical properties of five hydrometeor types—rain,cloud water,cloud ice,graupel,and snow—for the Advanced Radiative Transfer Modeling System(ARMS)at frequencies below 220 GHz.The discrete dipole approximation(DDA)method is employed to compute the single-scattering properties of solid cloud particles,modeling these particles as aggregated roughened bullet rosettes.The bulk optical properties of the cloud layer are derived by integrating the singlescattering properties with a modified Gamma size distribution,specifically for distributions with 18 effective radii.The bulk phase function is then projected onto a series of generalized spherical functions,applying the delta-M method for truncation.The results indicate that simulations using the newly developed nonspherical scattering look-up table exhibit significant consistency with observations under deep convection conditions.In contrast,assuming spherical solid cloud particles leads to excessive scattering at mid-frequency channels and insufficient scattering at high-frequency channels.This improvement in radiative transfer simulation accuracy for cloudy conditions will better support the assimilation of allsky microwave observations into numerical weather prediction models.·Frozen cloud particles were modeled as aggregates of bullet rosettes and the optical properties at microwave range were computed by DDA.·A complete process and technical details for constructing a look-up table of ARMS are provided.·The ARMS simulations generally show agreement with observations of MWTS and MWHS under typhoon conditions using the new look-up table.展开更多
文摘Recently,some of the genetic mechanisms of heart specification have been elucidated in Drosophila .However,genes involved in early cardiogenesis of human remain to be identified.Since the pathways that regulate early cardiac fate determination are conserved between Drosophila and vertebrates,flies can be used as a model test system to explore the genetic basis of cardiogenesis in human.In this project,about 3000 reccieve lethal gene lines were produced by P or EMS mutagenesis.With staining of antibodies against heart precussor cells of Drosophila ,about 200 lines were observed to show heart phenotype.In pilot studies of their function with RNAi technique,the RNAi phenotypes of several genes tested were observed,which were very similar to that of their mutants,showing heart tube defects or no heart precursors formation.Taking advantage of the advanced genetic information available in the Drosophila and human systems,we have identified about 50 human transcripts homologous to the Drosophila heart related gene candidates.Northern blot analysis for some of the human candidates showed that several genes were expressed in both adult and early embryonic tissues,which may help in the evaluation of candidate genes for human cardiogenesis.Our further experiments with transgenic flies generated with wild type and mutant forms of these candidate genes to examine for defects in cardiogenesis or cardiac function are under way.The candidate genes producing cardiac specific defects suggestive of similarities to the heart disease syndromes can then be pursued further as likely disease gene candidates.Such an approach is likely to provide a dramatic reduction of possible candidate genes,or to screen and identify mutations that may generate the disease in human.
基金The financial support for this study by National Natural Science Foundation of China(No.30960242)National Basic Research Program of China(973 program)(No.2012CB720805)Training Project of Young Scientists of Jiangxi Province(Stars of Jing gang)is gratefully acknowledged.
基金supported by the Knowledge Innovation Program of Chinese Academy of Sciences (Grant No. KZCX2-EW-203)the National Basic Research Program of China (Grant No.2013CB430105)the National Department Public Benefit Research Foundation (Grant No.GYHY201006031)
文摘In this research, one-dimensional stratiform a novel dual-model system, cold cloud model （1DSC） coupled to Weather Research and Forecast （WRF） model （WRF-1DSC for short）, was employed to investigate the effects of cloud seeding by silver iodide （AgI） on rain enhancement. Driven by changing environmental conditions extracted from the WRF model, WRF-1DSC could be used to assess the cloud seeding effects quantitatively. The employment of WRF- 1DSC, in place of a one-dimen- sional two-moment cloud seeding model applied to a three-dimensional mesoscale cloud-resolving model, was found to result in massive reduction of computational resources. Numerical experiments with WRF-1DSC were conducted for a real stratiform precipitation event ob- served on 4-5 July 2004, in Northeast China. A good agreement between the observed and modeled cloud system ensured the ability of WRF-1DSC to simulate the observed precipitation process efficiently. Sensitivity tests were performed with different seeding times, locations, and amounts. Experimental results showed that the optimum seeding effect （defined as the percentage of rain enhancement or rain enhancement rate） could be achieved through proper seeding at locations of maximum cloud water content when the updraft was strong. The optimum seeding effect was found to increase by 5.61% when the cloud was seeded at 5.5 km above ground level around 2300 UTC 4 July 2004, with the maximum AgI mixing ratio （As） equaling 15 ng kg-1. On the other hand, for an overseeded cloud, a significant reduction occurred in the accumulated precipitation （-12.42%） as Xs reached 100 ng kg^-1. This study demonstrates the potential of WRF- 1DSC in determining the optimal AgI seeding strategy in practical operations of precipitation enhancement.
基金supported by National Institutes of Health grants AI070827 and CA33266American Cancer Society grant RSG-09-076-01 and the UIC Walter Payton Center GUILD
文摘An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.
基金supported by National Institutes of Health Contracts P30-EY008098 and T32-EY017271-06(BethesdaMD)+14 种基金United States Department of Defense DM090217(ArlingtonVA)Alcon Research Institute Young Investigator Grant(Fort WorthTX)Eye and Ear Foundation(PittsburghPA)Research to Prevent Blindness(New YorkNY)Aging Institute Pilot Seed GrantUniversity of Pittsburgh(PittsburghPA)Postdoctoral Fellowship Program in Ocular Tissue Engineering and Regenerative OphthalmologyLouis J.Fox Center for Vision RestorationUniversity of Pittsburgh and UPMC(PittsburghPA)
文摘Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans.Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life（Kupers and Ptito,2014）.More recent studies explored what happens to the visual pathways in the context of acquired blindness.This is particularly relevant as the majority of diseases that cause vision loss occur in the elderly.
文摘A new Lagrangian—Eulerian coupling model system is developed to study regional air quality. The system consists of mesoscale dynamical meteorological model (MM), Monte—Carlo model (MCM), parameterized model on planetary boundary layer (PBL) turbulent statistics, dry and wet removal model, and Eulerian nonlinear chemical model (ENCM). The physical, chemical and biological processes on air pollutants are considered comprehensively. 3—D distribution laws tor acidic gaseous pollutants (SO2 and NOx) emitted by Thai Mae Moh Power Plant and the secondary pollutants are studied in detail. The results simulated by the coupling model system are in good agreement with observational concentration data. Key words MM - MCM - ENCM - Coupling model system The authors wish to express their thanks to Prof. Zeng Q. C. for his support to this research and to Dr. Han Z. W. and Zhang M. G. for their help in programming and numerical calculation of IAP, Chinese Academy of Sciences. Thanks are also due to NSTD and EGAT in Thailand for supporting this research.
基金Project supported by the National High-Technology Research and Development Program of China (863 Program) (No. 2003AA209030)the National Natural Science Foundation of China (No. 30030090)and the Hi-Tech Research and Development Program of Jiangsu Province (No. BG2004320).
文摘A knowledge model with temporal and spatial characteristics for the quantitative design of a cultural pattern in wheat production, using systems analysis and dynamic modeling techniques, was developed for wheat management, as a decision-making tool in digital farming. The fundamental relationships and algorithms of wheat growth indices and management criteria to cultivars, ecological environments, and production levels were derived from the existing literature and research data to establish a knowledge model system for quantitative wheat management using Visual C^＋＋. The system designed a cultural management plan for general management guidelines and crop regulation indices for timecourse control criteria during the wheat-growing period. The cultural management plan module included submodels to determine target grain yield and quality, cultivar choice, sowing date, population density, sowing rate, fertilization strategy, and water management, whereas the crop regulation indices module included submodels for suitable development stages, dynamic growth indices, source-sink indices, and nutrient indices. Ewluation of the knowledge model by design studies on the basis of data sets of different eco-sites, cultiwrs, and soil types indicated a favorable performance of the model system in recommending growth indices and management criteria under diverse conditions. Practical application of the knowledge model system in comparative field experiments produced yield gains of 2.4% to 16.5%. Thus, the presented knowledge model system overcame some of the difficulties of the traditional wheat management patterns and expert systems, and laid a foundation for facilitating the digitization of wheat management.
基金supported by grants from the Cancer Institutes of the National Institute of HealthCurrent funding comes from CA 83679the Anderson Family Endowed Chair in Medical Education,Research and Patient Care
文摘The prevalent human papillomaviruses(HPVs) infect either cutaneous or mucosal epithelium. Active Infections lead to epithelial hyperprolifeation and are usually cleared in healthy individuals within a year. Persistent infections in the anogenital tracts by certain high-risk genotypes such as HPV-16, HPV-18 and closely related types, can progress to high grade dysplasias and carcinomas in women and men, including cervical, vulva, penile and anal cancers. A significant fraction of the head and neck cancers are also caused by HPV-16. The viral oncogenes responsible for neoplastic conversion are E6 and E7 that disrupt the pathways controlled by the two major tumor suppressor genes, p53 and members of p RB family. Because HPV cannot be propagated in conventional submerged monolayer cell cultures, organotypic epithelial raft cultures that generate a stratified and differentiated epithelium have been used to study the viral life cycle. This article describes several systems to examine aspects of the viral productive phase, along with the advantages and limitations. Animal model systems of HPV carcinogenesis are also briefly described.
文摘In this paper, the effects of frying time, white egg (0%, 5% and 10% w/w) and chitosan (0%, 0.5% and 1.5% w/w) addition to the batter formulation on the quality of simulated crispy deep-fried Kurdish cheese nugget crusts was studied by using a deep-fried crust model. Moisture content, oil content, color and hardness of the samples were determined. Crust models were fried at 190℃ for 60, 120 and 180 s. Batter formulations and frying time significantly (p < 0.01) affected moisture, oil content, color and hardness of Crust models. Batter formulation contain 10% white egg was found to be an effective ingredient in decreasing oil content of Crust models. The mean moisture and fat content of Crust models formed with batter contained 10% white egg, fried at 190℃, for 180s were 6.207 ± 0.447 and 5.649 ± 0.394. Batters containing 5% white egg and 1.5% chitosan showed the lowest moisture content and the highest oil content among all the formulations. Crust models containing combination of white egg and chitosan were the darkest. Hardness of samples containing chitosan were the highest, specially for ch1.5 The mean hardness in 60, 120 and 180s of frying in this formulation were 21.518 ± 0.481, 36.871 ± 1.758 and 49.563 ± 1.847 respectively.
基金This work was supported by Swiss National Science Foundation,grant#31003A_175658 to VLK.
文摘Neuroscience and neurology research is dominated by experimentation with rodents.Around 75%of neurology disease-associated genes have orthologs in Drosophila mel-anogaster,the fruit fly amenable to complex neurological and behavioral investiga-tions.However,non-vertebrate models including Drosophila have so far been unable to significantly replace mice and rats in this field of studies.One reason for this situ-ation is the predominance of gene overexpression(and gene loss-of-function)meth-odologies used when establishing a Drosophila model of a given neurological disease,a strategy that does not recapitulate accurately enough the genetic disease condi-tions.I argue here the need for a systematic humanization approach,whereby the Drosophila orthologs of human disease genes are replaced with the human sequences.This approach will identify the list of diseases and the underlying genes that can be adequately modeled in the fruit fly.I discuss the neurological disease genes to which this systematic humanization approach should be applied and provide an example of such an application,and consider its importance for subsequent disease modeling and drug discovery in Drosophila.I argue that this paradigm will not only advance our un-derstanding of the molecular etiology of a number of neurological disorders,but will also gradually enable researchers to reduce experimentation using rodent models of multiple neurological diseases and eventually replace these models.
基金Science and Technology Program of the Ministry of Housing and Urban-Rural Development(2015-K8-009)
文摘Water Quality Model System( WQMS) is an important approach to analyzing aquatic situation and supporting environmental decision. However,the usage and promotion of WQMS is largely limited by amounts of parameters,complex conditions and enormous operations. A GIS integrated system of urban water environment coupled with SWMM( storm runoff model),ECOM( hydrodynamic model) and RCA( water quality model) was constructed in this study,with the production and transformation of contaminants in large scale taken into consideration. This integrated system guaranteed an independent calculation and multi-model coupling calculation,including convenient pre-processing,fast and efficient model running and results visualization in different spatial and temporal scales,in the purpose of simplifying the usage and promotion of complex models and providing necessary understanding required in water resource managing and water pollution controlling,and ultimately improving decision making capability. The functionality of the proposed system was illustrated by a case of Wuhan city.
文摘Resurgence of mycobacterial diseases particularly tuberculosis has caused a renewed interest to unravel the strategies employed by mycobacteria for intracellular survival. In spite of advancement in mycobacterial research, our knowledge about genes and their corresponding functional proteins involved during the interaction of mycobacterium with host’s macrophages is fragmentary. This study pertains to development of a suitable in vitro model using murine macrophages and Mycobacterium bovis BCG to study proteins expressed during macrophage-myco bacterium interactions. Peritoneal macrophages from BALB/c mice were infected with M. bovis BCG and intracellular replication was assessed by {3H} thymi- dine uptake assay which was maximal when macrophage to mycobacterium ratio was 1:10. SDS-PAGE was employed to study the proteins expressed and selected proteins were subjected to mass spectrometry. Seven proteins found to be upregulated during macrophage-mycobacterium interaction were identified by MALDI-TOF. The results indicate that the present in vitro infection model was able to support the growth of M. bovis BCG in murine macrophages and is an ideal model to determine the pattern of functions of gene expression during the interaction of mycobacterium with macrophages. The differentially expressed proteins will help in understanding the mycobacterial molecular basis of adaptation to intracellular macrophage environment.
文摘The integration of Michaelis-Menten kinetics results in a trancedental equation. The results are not in a form that is readily usable. A more usable form of the model solutions is developed. This was accomplished by using Taylor series expansion of dimensionless concentration u in terms of its derivatives. The infinite series expression for dimensionless concentration is given. It can be seen that for times t < , the Taylor series expression evaluated near the origin up to the third derivative is a reasonable representation of the integrated solution. More terms in the Taylor series expression can be added to suit the application. It can vary with the apparent volume, dosage, enzyme concentration, Michaelis constant and the desired accuracy level needed. The single compartment model solution was obtained by the method of Laplace transform. It can be seen from Figure 2 that the dimensionless drug concentration in the compartment goes through a maxima. The curve is convex throughout the absorption and elimination processes. The drug gets completely depleted after a said time. The curve is asymmetrical with a right skew. The systems under absorption with elimination that obey the kinetics that can be represented by a set of reactions in circle were considered. A system of simple reactions in circle was taken into account. The concentration profile of the reactants were obtained by the method of Laplace transforms. The conditions when subcritical damped oscillations can be expected are derived. A model was developed for cases when absorption kinetics exhibit subcritical damped oscillations. The solution was developed by the method of Laplace transforms. The solution for dimensionless concentration of the drug in single compartment for different values of rate constants and dimensionless frequency are shown in Figures 6-9. The drug profile reaches a maximum and drops to zero concen-tration after a said time. The fluctuations in concentration depends on the dimensionless frequency resulting from the subcritical damped oscillations during absorption. At low frequencies the fluctuations are absent. As the frequency is increased the fluctuations in concentration are pronounced. The fre-quency of fluctuations were found to increase with increase in frequency of oscillations during ab-sorption.
文摘This study examines the issues in development of pharmacokinetic single compartment model for systems that obey free radical copolymerization kinetics. Copolymer composition as a function of reactivity ratios of comonomers for well mixed case was derived. For some cases, such as DEF-AN, diethyl fumarate and acrylonitrile system multiplicity in composition were found. The analysis is extended to n monomers. State space model expressions are used and the QSSA assumption is stated in state space equation form. Conditions when damped oscillations can be expected are noted. In addition to multiplicity in product composition, an account of reactivity ratios and other instances of multi- plicity were found during the pharmacodynamics of the free radical polymerization reactions. A careful study of initiated case, thermal case, 1 CSTR and 2 CSTRS was undertaken and results were presented. Numerical integration techniques were employed on the desktop computer. Steady state and transient state conversion for initiated case and thermal case for 1 CSTR and 2 CSTRs were calculated and plotted in Figures 7-9 and 12. No multiplicity was found in the thermal case for 1 CSTR in the dynamics of transient monomer conversion. Multiplicity was found in the initiated case for 1 CSTR in the dynamics of transient conversion of monomer. The multiplicity was found in the second CSTR for the case of 2 CSTRs in series. No multiplicity was found in the case of initiator decay.
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金sponsored by the U.S.Department of Housing and Urban Development(Grant No.NJLTS0027-22)The opinions expressed in this study are the authors alone,and do not represent the U.S.Depart-ment of HUD’s opinions.
文摘This paper addresses urban sustainability challenges amid global urbanization, emphasizing the need for innova tive approaches aligned with the Sustainable Development Goals. While traditional tools and linear models offer insights, they fall short in presenting a holistic view of complex urban challenges. System dynamics (SD) models that are often utilized to provide holistic, systematic understanding of a research subject, like the urban system, emerge as valuable tools, but data scarcity and theoretical inadequacy pose challenges. The research reviews relevant papers on recent SD model applications in urban sustainability since 2018, categorizing them based on nine key indicators. Among the reviewed papers, data limitations and model assumptions were identified as ma jor challenges in applying SD models to urban sustainability. This led to exploring the transformative potential of big data analytics, a rare approach in this field as identified by this study, to enhance SD models’ empirical foundation. Integrating big data could provide data-driven calibration, potentially improving predictive accuracy and reducing reliance on simplified assumptions. The paper concludes by advocating for new approaches that reduce assumptions and promote real-time applicable models, contributing to a comprehensive understanding of urban sustainability through the synergy of big data and SD models.
基金Deputy for Research and Technology,Kermanshah University of Medical Sciences,Grant/Award Number:4030031。
文摘Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.
基金support from the National Natural Science Foundation of China (Grant Nos.51927807,42077267 and 42277174).
文摘A complex geological environment with faults can be encountered in the process of coal mining.Fault activation can cause instantaneous structure slipping,releasing a significant amount of elastic strain energy during underground coal mining.This would trigger strong rockburst disasters.To understand the occurrence of fault-slip induced rockbursts,we developed a physical model test system for fault-slip induced rockbursts in coal mine drifts.The boundary energy storage(BES)loading apparatus and bottom rapid retraction(BRR)apparatus are designed to realize energy compensation and continuous boundary stress transfer of the surrounding rocks for instantaneous fault slip,as well as to provide space for the potential fault slip.Taking the typical fault-slip induced rockburst in the Xinjulong Coal Mine,China,as the background,we conducted a model test using the test system.The deformation and stress in the rock surrounding the drift and the support unit force during fault slip are analyzed.The deformation and failure characteristics and dynamic responses of drifts under fault-slip induced rockbursts are obtained.The test results illustrate the rationality and effectiveness of the test system.Finally,corresponding recommendations and prospects are proposed based on our findings.
基金supported by the National Natural Science Foundation of China(Project No.52377082)the Scientific Research Program of Jilin Provincial Department of Education(Project No.JJKH20230123KJ).
文摘Large-scale new energy grid connection leads to the weakening of the system frequency regulation capability,and the system frequency stability is facing unprecedented challenges.In order to solve rapid frequency fluctuation caused by new energy units,this paper proposes a new energy power system frequency regulation strategy with multiple units including the doubly-fed pumped storage unit(DFPSU).Firstly,based on the model predictive control(MPC)theory,the state space equations are established by considering the operating characteristics of the units and the dynamic behavior of the system;secondly,the proportional-differential control link is introduced to minimize the frequency deviation to further optimize the frequency modulation(FM)output of the DFPSU and inhibit the rapid fluctuation of the frequency;lastly,it is verified on theMatlab/Simulink simulation platform,and the results show that the model predictive control with proportional-differential control link can further release the FM potential of the DFPSU,increase the depth of its FM,effectively reduce the frequency deviation of the system and its rate of change,realize the optimization of the active output of the DFPSU and that of other units,and improve the frequency response capability of the system.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFB3900400)the National Natural Science Foundation of China(Grant Nos.U2142212 and 42361074)。
文摘Accurate satellite data assimilation under all-sky conditions requires enhanced parameterization of scattering properties for frozen hydrometeors in clouds.This study aims to develop a nonspherical scattering look-up table that contains the optical properties of five hydrometeor types—rain,cloud water,cloud ice,graupel,and snow—for the Advanced Radiative Transfer Modeling System(ARMS)at frequencies below 220 GHz.The discrete dipole approximation(DDA)method is employed to compute the single-scattering properties of solid cloud particles,modeling these particles as aggregated roughened bullet rosettes.The bulk optical properties of the cloud layer are derived by integrating the singlescattering properties with a modified Gamma size distribution,specifically for distributions with 18 effective radii.The bulk phase function is then projected onto a series of generalized spherical functions,applying the delta-M method for truncation.The results indicate that simulations using the newly developed nonspherical scattering look-up table exhibit significant consistency with observations under deep convection conditions.In contrast,assuming spherical solid cloud particles leads to excessive scattering at mid-frequency channels and insufficient scattering at high-frequency channels.This improvement in radiative transfer simulation accuracy for cloudy conditions will better support the assimilation of allsky microwave observations into numerical weather prediction models.·Frozen cloud particles were modeled as aggregates of bullet rosettes and the optical properties at microwave range were computed by DDA.·A complete process and technical details for constructing a look-up table of ARMS are provided.·The ARMS simulations generally show agreement with observations of MWTS and MWHS under typhoon conditions using the new look-up table.
