Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time ±4 cm pan-and-tilt action. Robot-driven ±60° pivots of an integrated ±185° rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[¹⁸F] fluoro-2-deoxy-ᴅ-glucose (¹⁸F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less¹. In this article, we describe new radiation plans for the treatment of moving lung tumors.     

Frustration‐guided motion planning reveals conformational transitions in proteins

Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics‐inspired motion planning procedure called dCC‐RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration. The constraints balance non‐native contacts and flexibility, and instantaneously redirect the motion towards sterically favorable conformations. On a test set of eight proteins determined in two conformations separated by, on average, 7.5 Å root mean square deviation (RMSD), our pathways reduced the Cα atom RMSD to the goal conformation by 78%, outperforming peer methods. We then applied dCC‐RRT to examine how collective, small‐scale motions of four side‐chains in the active site of cyclophilin A propagate through the protein. dCC‐RRT uncovered a spatially contiguous network of residues linked by steric interactions and collective motion connecting the active site to a recently proposed, non‐canonical capsid binding site 25 Å away, rationalizing NMR and multi‐temperature crystallography experiments. In all, dCC‐RRT can reveal detailed, all‐atom molecular mechanisms for small and large amplitude motions. Source code and binaries are freely available at https://github.com/ExcitedStates/KGS/ .     

Climate warming and heat waves affect reproductive strategies and interactions between submerged macrophytes

Extreme climatic events, such as heat waves, are predicted to increase in frequency and intensity during the next hundred years, which may accelerate shifts in hydrological regimes and submerged macrophyte composition in freshwater ecosystems. Since macrophytes are profound components of aquatic systems, predicting their response to extreme climatic events is crucial for implementation of climate change adaptation strategies. We therefore performed an experiment in 24 outdoor enclosures (400 L) separating the impact of a 4 °C increase in mean temperature with the same increase, that is the same total amount of energy input, but resembling a climate scenario with extreme variability, oscillating between 0 °C and 8 °C above present conditions. We show that at the moderate nutrient conditions provided in our study, neither an increase in mean temperature nor heat waves lead to a shift from a plant‐dominated to an algal‐dominated system. Instead, we show that species‐specific responses to climate change among submerged macrophytes may critically influence species composition and thereby ecosystem functioning. Our results also imply that more fluctuating temperatures affect the number of flowers produced per plant leading to less sexual reproduction. Our findings therefore suggest that predicted alterations in climate regimes may influence both plant interactions and reproductive strategies, which have the potential to inflict changes in biodiversity, community structure and ecosystem functioning.     

动态适应性生态经济区划模型及其应用

提高城市生态经济区划的精确性和动态性,对科学指导城市化发展具有重要的理论意义和应用价值。利用夜间灯光数据与人口密度建立线性模型,探索了以往用行政区域为最小统计单元数据的模拟细化问题;然后通过引入可变参数构建了动态适应性生态经济区划模型,在增强模型动态适应性的同时,将一级区划结果统一划分为生态管控区域、生态优先区域、优化开发区域和重点开发区域4个区域。以广州市增城区为典型案例,通过改进的动态适应性生态经济区划模型,运用GIS将增城区在两种情景下进行了模拟和对比,并提出了政策建议。区划结果符合当地发展特征,也为其他城市与区域的生态经济区划研究提供了科学方法。     

Proteins in Tumor-Derived Plasma Extracellular Vesicles Indicate Tumor Origin

Cancer-derived extracellular vesicles (EVs) promote tumorigenesis, premetastatic niche formation, and metastasis via their protein cargo. However, the proteins packaged by patient tumors into EVs cannot be determined in vivo because of the presence of EVs derived from other tissues. We therefore developed a cross-species proteomic method to quantify the human tumor-derived proteome of plasma EVs produced by patient-derived xenografts of four cancer types. Proteomic profiling revealed individualized packaging of novel protein cargo, and machine learning accurately classified the type of the underlying tumor.     

Can altered muscle synergies control unimpaired gait?

Recent studies have postulated that the human motor control system recruits groups of muscles through low-dimensional motor commands, or muscle synergies. This scheme simplifies the neural control problem associated with the high-dimensional structure of the neuromuscular system. Several lines of evidence have suggested that neurological injuries, such as stroke or cerebral palsy, may reduce the dimensions that are available to the motor control system, and these altered dimensions or synergies are thought to contribute to impaired walking patterns. However, no study has investigated whether impaired low-dimensional control spaces necessarily lead to impaired walking patterns. In this study, using a two-dimensional model of walking, we developed a synergy-based control framework that can simulate the dynamics of walking. The simulation analysis showed that a synergy-based control scheme can produce well-coordinated movements of walking matching unimpaired gait. However, when the dimensions available to the controller were reduced, the simplified emergent pattern deviated from unimpaired gait. A system with two synergies, similar to those seen after neurological injury, could not produce an unimpaired walking pattern. These findings provide further evidence that altered muscle synergies can contribute to impaired gait patterns and may need to be directly addressed to improve gait after neurological injury.     

Masking effect of different durations of forward masker sound on acoustical responses of mouse inferior collicular neurons to probe sound

To study the effects of different durations of forward masker sound on neuronal firing and rate-intensity function (RIF) of mouse inferior collicular (IC) neurons, a tone relative to 5 dB above the minimum threshold (re MT+5 dB) of the best frequency of recorded neurons was used as forward masker sound under free field stimulation condition. The masker durations used were 40, 60, 80, and 100 ms. Results showed that as masker duration was increased, inhibition in neuronal firing was enhanced (P < 0.000 1, n = 41) and the latency of neurons was lengthened (P<0.01, n = 41). In addition, among 41 inhibited IC neurons, 90.2% (37/41) exhibited narrowed dynamic range (DR) when masker sound duration was increased (P < 0.000 1), whereas the DR of 9.8%(4/41) became wider. These data suggest that masking effects of different durations of forward masker sound might be correlated with the amplitude and duration of inhibitory input to IC neurons elicited by the masker sound. __________ Translated from Journal of Central China Normal University (Nat. Sci.), 2005, 39(2): 236–240 [译自: 华中师范大学学报 (自然科学版), 2005, 39(2): 236–240]     

Calibration of Terra/MODIS gross primary production over an irrigated cropland on the North China Plain and an alpine meadow on the Tibetan Plateau

This paper evaluated the MODerate resolution Imaging Spectroradiometer (MODIS) gross primary production (GPP) product (MOD17) by using estimated GPP from eddy‐covariance flux measurements over an irrigated winter wheat and maize double‐cropping field on the North China Plain in 2003–2004, and an alpine meadow on the Tibetan Plateau in 2002–2003. The mean annual GPP from MOD17 accounted for 1/2–2/3 of the surface estimated mean annual GPP for the alpine meadow, but only about 1/5–1/3 for the cropland. This underestimation was partly attributed to low estimates of leaf area index by a MODIS product (MOD15) because it is used to calculate absorbed photosynthetically active radiation in the MOD17 algorithm. The main reason is that the parameter maximum light use efficiency (ε_max) in the MOD17 algorithm was underestimated for the two biomes, especially for the cropland. Contrasted to the default, ε_max was optimized using surface measurements. The optimized ε_max for winter wheat, maize and meadow was 1.18, 1.81 and 0.73 g C/MJ, respectively. By using the surface measurements and optimized ε_max , the MOD17 algorithm significantly improved the accuracy of GPP estimates. The optimum MOD17 algorithm explained about 82%, 68%, and 79% of GPP variance for winter wheat, maize, and meadow, respectively. These results suggest that it is necessary to adjust the MOD17 parameters for the estimation of cropland and meadow GPP, particularly over cropland.