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8 result(s) for "Sheng, Yanghui"
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Molecular determinants of response kinetics of mouse M1 intrinsically-photosensitive retinal ganglion cells
Intrinsically-photosensitive retinal ganglion cells (ipRGCs) are non-rod/non-cone retinal photoreceptors expressing the visual pigment, melanopsin, to detect ambient irradiance for various non-image-forming visual functions. The M1-subtype, amongst the best studied, mediates primarily circadian photoentrainment and pupillary light reflex. Their intrinsic light responses are more prolonged than those of rods and cones even at the single-photon level, in accordance with the typically slower time course of non-image-forming vision. The short (OPN4S) and long (OPN4L) alternatively-spliced forms of melanopsin proteins are both present in M1-ipRGCs, but their functional difference is unclear. We have examined this point by genetically removing the Opn4 gene ( Opn4 −/− ) in mouse and re-expressing either OPN4S or OPN4L singly in Opn4 −/− mice by using adeno-associated virus, but found no obvious difference in their intrinsic dim-flash responses. Previous studies have indicated that two dominant slow steps in M1-ipRGC phototransduction dictate these cells’ intrinsic dim-flash-response kinetics, with time constants (τ 1 and τ 2 ) at room temperature of ~ 2 s and ~ 20 s, respectively. Here we found that melanopsin inactivation by phosphorylation or by β-arrestins may not be one of these two steps, because their genetic disruptions did not prolong the two time constants or affect the response waveform. Disruption of GAP (GTPase-Activating-Protein) activity on the effector enzyme, PLCβ4, in M1-ipRGC phototransduction to slow down G-protein deactivation also did not prolong the response decay, but caused its rising phase to become slightly sigmoidal by giving rise to a third time constant, τ 3 , of ~ 2 s (room temperature). This last observation suggests that GAP-mediated G-protein deactivation does partake in the flash-response termination, although normally with a time constant too short to be visible in the response waveform.
Anaplerotic nutrient stress drives synergy of angiogenesis inhibitors with therapeutics targeting tumor metabolism
Tumor angiogenesis is a cancer hallmark, and its therapeutic inhibition has provided meaningful, albeit limited, clinical benefit. While anti-angiogenesis inhibitors deprive the tumor of oxygen and essential nutrients, cancer cells activate metabolic adaptations to diminish therapeutic response. Despite these adaptations, angiogenesis inhibition incurs extensive metabolic stress, prompting us to consider such metabolic stress as an to therapies targeting cancer metabolism. Metabolomic profiling of angiogenesis-inhibited intracranial xenografts showed universal decrease in tricarboxylic acid cycle intermediates, corroborating a state of anaplerotic nutrient deficit or stress. Accordingly, we show strong synergy between angiogenesis inhibitors (Avastin, Tivozanib) and inhibitors of glycolysis or oxidative phosphorylation through exacerbation of anaplerotic nutrient stress in intracranial orthotopic xenografted gliomas. Our findings were recapitulated in GBM xenografts that do not have genetically predisposed metabolic vulnerabilities at baseline. Thus, our findings cement the central importance of the tricarboxylic acid cycle as the nexus of metabolic vulnerabilities and suggest clinical path hypothesis combining angiogenesis inhibitors with pharmacological cancer interventions targeting tumor metabolism for GBM tumors.
The genomic and functional landscapes of developmental plasticity in the American cockroach
Many cockroach species have adapted to urban environments, and some have been serious pests of public health in the tropics and subtropics. Here, we present the 3.38-Gb genome and a consensus gene set of the American cockroach, Periplaneta americana . We report insights from both genomic and functional investigations into the underlying basis of its adaptation to urban environments and developmental plasticity. In comparison with other insects, expansions of gene families in P. americana exist for most core gene families likely associated with environmental adaptation, such as chemoreception and detoxification. Multiple pathways regulating metamorphic development are well conserved, and RNAi experiments inform on key roles of 20-hydroxyecdysone, juvenile hormone, insulin, and decapentaplegic signals in regulating plasticity. Our analyses reveal a high level of sequence identity in genes between the American cockroach and two termite species, advancing it as a valuable model to study the evolutionary relationships between cockroaches and termites. The American cockroach ( Periplaneta americana ) is an hemimetabolous insect with rapid growth, high fecundity, and remarkable tissue-regeneration capability. Here Li et al sequence its 3.38-Gb genome and perform the functional studies, yielding insights into its environmental adaptation and developmental plasticity.
Numerical modelling and theoretical analysis of the acoustic attenuation in bubbly liquids
The propagations of acoustic waves in bubbly liquids have been extensively investigated through experimental and theoretical methods, a computational fluid dynamics (CFD) method was introduced to investigate the acoustic attenuation through bubbles in this study. Numerical 'measurements' of attenuation coefficient (α) and phase velocity (V) were conducted using a homogeneous cavitation model, which were modeled from experimental schemes and compared with the theoretical results. At extremely small bubble volume fraction (β around 10 −11 ), new formulas of the theoretical α (α theo ) were proposed respectively for linear and transient oscillations, and a new formula of the numerical α (α num ) was proposed for transient oscillations. Results showed that α num matched precisely with α theo for linear, nonlinear and transient oscillations. At medium β (around 10 −4 ), the relative difference of α num between the VOF and present methods was less than 1.6%, while it reached 15.4% after replacing the bounded Keller-Miksis equation (KME) in the present method with the KME. However, the traditional theoretical α and V matched precisely with the predictions by the present method with the KME. Thus new theoretical α and V were proposed based on the bounded KME, and the relative differences between α theo and α num were less than 1%. It can be concluded that the bounded KME should be used in both numerical and theoretical predictions.
基于层次任务网络规划的分布式协同地理建模任务分解方法研究
为了有效地实现分布式协同地理建模中的合作规划和资源共享,通过分析分布式协同地理建模中任务分解过程,探讨地理建模任务的功能结构、计算复杂性、组织多方性和时空尺度等分解依据,采用层次任务网络(HTN)规划形式化表达地理建模任务,设计了基于顺序任务分解(OTD)的地理建模任务的递归分解算法,模拟领域专家寻求合作规划地理建模任务的思考方式。以分布式流域水文模型SWAT作为试验案例,开发并实现了地理建模任务HTN规划器,为分布式协同地理建模环境中的任务分解方法提供了新的思路。
颅内转移瘤最新治疗进展和策略
颅内转移瘤亦称脑转移瘤(brain metastases),是临床常见的成人颅内肿瘤,见于10%~40%的癌症患者。随着人口老龄化和影像学检查方法的不断进步,颅内转移瘤的发病率呈逐渐升高之趋势。恶性肿瘤颅内转移的主要途径包括血行转移、邻近部位直接浸润和蛛网膜下隙或淋巴系统转移。
不同水钙处理对甜瓜生长、品质形成及产量的影响
【目的】确定甜瓜适宜的水钙管理模式。【方法】以“亭林雪瓜”为试验材料,设3个灌水量水平,分别为高水W1(220.45 mm)、中水W2(灌水量为W1的2/3,171.05 mm)和低水W3(灌水量为W1的1/2,146.45 mm),2个钙处理水平,分别为喷钙Ca1(总喷钙量为0.68 L/株)和不喷钙Ca0,采用完全随机区组设计,共6个处理,并在果实生长过程中测定了相关的生长生理指标,探究果实生长和糖分积累动态过程及产量品质对不同水钙处理的响应。【结果】雪瓜属高蔗糖积累型甜瓜品种,果径呈单“S”曲线生长,不同水钙处理下果实生长和糖分积累趋势一致。高水条件下果径增长量、果径大小以及果实产量最大,但单株灌溉水生产生产率IWP最低,且高水处理不利于果实糖分累积、降低了果实品质;中水处理下的IWP和果实品质最优,低水处理对果实生长有延缓影响并且降低了果实最终的产量。与不施钙处理相比,施钙处理产量和单果质量及IWP都得到了提高,同时施钙提高了果实硬度,降低了可滴定酸量(其中,单株产量、单果质量从高到低的顺序均为W1Ca1处理>W2Ca1处理>W1Ca0处理>W2Ca0处理>W3Ca1处理>W3Ca0处理,IWP从高到低的顺序为W2Ca1处理>W1Ca1处理> W2Ca0处理>W1Ca0处理>W3Ca1处理>W3Ca0处理)。【结论】不同水钙处理能影响果实生长及糖分积累过程且导致最终产量和品质的差异,中水施钙为甜瓜水钙管理的适宜模式。
社區成年民眾身體活動量、年齡與自評生理心理健康之關聯性
目標:研究欲探索:(1)社區成年民眾身體活動量與自評生理與心理健康的關聯性;以及(2)在不同層級的身體活動量中,年齡與自評健康為線性或U型曲線之關係。方法:研究參與者為社區成年民眾,於教育部體育署舉辦之國民體適能檢測站進行資料收集,包括人口學資料、身體活動量、以及自評生理與心理健康。使用階層迴歸進行統計分析。結果:研究共招募2,212位研究參與者,依照身體活動量區分為高中低三組。控制人口學變項後,高度與中度身體活動量的研究參與者在自評健康(高度Beta = 0.12,中度Beta = 0.20,p值皆小於0.001)、自評生理健康(高度Beta = 0.09,中度Beta = 0.17,p值皆小於0.001)、自評心理健康(高度Beta =0.12,中度Beta = 0.19,p值皆小於0.001)皆顯著高於低度身體活動量者。在三組身體活動量,年齡皆與自評健康為線性正相關,年齡越大分數越高。結論:身體活動與年齡越高,社區成年民眾的自評生理與心理健康越佳。