Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells

Recall responses by memory CD8 T cells are impaired in the absence of CD4 T cells. Although several mechanisms have been proposed, the molecular basis is still largely unknown. Using a local influenza virus infection in the respiratory tract and the lung of CD4[superscript −/−] mice, we show that memory CD8 T cell impairment is limited to the lungs and the lung-draining lymph nodes, where viral Ags are unusually persistent and abundant in these mice. Persistent Ag exposure results in prolonged activation of the AKT–mTORC1 pathway in Ag-specific CD8 T cells, favoring their development into effector memory T cells at the expense of central memory T cells, and inhibition of mTORC1 by rapamycin largely corrects the impairment by promoting central memory T cell development. The findings suggest that the prolonged AKT–mTORC1 activation driven by persistent Ag is a critical mechanism underlying the impaired memory CD8 T cell development and responses in the absence of CD4 T cells.National Institutes of Health (U.S.) (Grant AI69208)Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology (SMART). Infectious Disease Research Program)Ivan R. Cottrell Professorship and Research FundNational Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Support (Core) Grant P30-CA14051

Inhomogeneous microstructure and fatigue crack propagation of thick-section high strength steel joint welded using double-sided hybrid fiber laser-arc welding

The inhomogeneous microstructure and fatigue crack propagation of 30 mm thick-section high strength steel welded joint by double-sided hybrid fiber laser-arc welding were investigated in detail. The results indicated that the average effective grain size of the laser zone was only 1/2 of that of the arc zone, due to the faster cooling rate of the laser resource. The base metal consisted of massive polygonal ferrites and small granular carbides, while fine grained region, the coarse grained region and weld metal were all composed of martensite with a high dislocation density. Compared with the arc zone, the percentage of grain boundaries with high misorientation angle increased 24% for the laser zone, as the average grain size of the laser zone was smaller than that of the arc zone. The results also revealed that the fatigue crack propagation resistance of the welded joint was higher than that of the base metal. Meanwhile, a significant increase in the fatigue crack propagation resistance of the laser zone occurred, as compared with the arc zone, due to the refined grains and the high proportion of the grain boundaries with high misorientation angle (>15°) in the laser zone

Draft genome sequence of the Tibetan antelope

The Tibetan antelope (Pantholops hodgsonii) is endemic to the extremely inhospitable high-altitude environment of the Qinghai-Tibetan Plateau, a region that has a low partial pressure of oxygen and high ultraviolet radiation. Here we generate a draft genome of this artiodactyl and use it to detect the potential genetic bases of highland adaptation. Compared with other plain-dwelling mammals, the genome of the Tibetan antelope shows signals of adaptive evolution and gene-family expansion in genes associated with energy metabolism and oxygen transmission. Both the highland American pika, and the Tibetan antelope have signals of positive selection for genes involved in DNA repair and the production of ATPase. Genes associated with hypoxia seem to have experienced convergent evolution. Thus, our study suggests that common genetic mechanisms might have been utilized to enable high-altitude adaptation

Intracellular Water Exchange for Measuring the Dry Mass, Water Mass and Changes in Chemical Composition of Living Cells

We present a method for direct non-optical quantification of dry mass, dry density and water mass of single living cells in suspension. Dry mass and dry density are obtained simultaneously by measuring a cell’s buoyant mass sequentially in an H[subscript 2]O-based fluid and a D[subscript 2]O-based fluid. Rapid exchange of intracellular H[subscript 2]O for D[subscript 2]O renders the cell’s water content neutrally buoyant in both measurements, and thus the paired measurements yield the mass and density of the cell’s dry material alone. Utilizing this same property of rapid water exchange, we also demonstrate the quantification of intracellular water mass. In a population of E. coli, we paired these measurements to estimate the percent dry weight by mass and volume. We then focused on cellular dry density – the average density of all cellular biomolecules, weighted by their relative abundances. Given that densities vary across biomolecule types (RNA, DNA, protein), we investigated whether we could detect changes in biomolecular composition in bacteria, fungi, and mammalian cells. In E. coli, and S. cerevisiae, dry density increases from stationary to exponential phase, consistent with previously known increases in the RNA/protein ratio from up-regulated ribosome production. For mammalian cells, changes in growth conditions cause substantial shifts in dry density, suggesting concurrent changes in the protein, nucleic acid and lipid content of the cell.National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874)National Institutes of Health (U.S.) (Center for Cell Division Process Grant P50GM6876)National Institutes of Health (U.S.) (Contract R01CA170592)United States. Army Research Office (Institute for Collaborate Biotechnologies Contract W911NF-09-D-0001

Robust Visual Tracking Based on Fusional Multi-Correlation-Filters with a High-Confidence Judgement Mechanism

Visual object trackers based on correlation filters have recently demonstrated substantial robustness to challenging conditions with variations in illumination and motion blur. Nonetheless, the models depend strongly on the spatial layout and are highly sensitive to deformation, scale, and occlusion. As presented and discussed in this paper, the colour attributes are combined due to their complementary characteristics to handle variations in shape well. In addition, a novel approach for robust scale estimation is proposed for mitigatinge the problems caused by fast motion and scale variations. Moreover, feedback from high-confidence tracking results was also utilized to prevent model corruption. The evaluation results for our tracker demonstrate that it performed outstandingly in terms of both precision and accuracy with enhancements of approximately 25% and 49%, respectively, in authoritative benchmarks compared to those for other popular correlation- filter-based trackers. Finally, the proposed tracker has demonstrated strong robustness, which has enabled online object tracking under various scenarios at a real-time frame rate of approximately 65 frames per second (FPS)

Research on a new omnidirectional mobile platform with heavy loading and flexible motion

This article presents an omnidirectional mobile platform with six mecanum wheels, which provide better carrying capacity than traditional four-wheel platform. Omnidirectional mobile platform with six mecanum wheels can withstand heavier load than the omnidirectional mobile platform with four mecanum wheels, which was used to transport large equipments used in marine and aerospace. Due to the small size, omnidirectional mobile platform with six mecanum wheels move more flexibly and reach desired position and pose easier in narrow workspace, compared with omnidirectional mobile platform with eight mecanum wheels whose disadvantage of large size offsets the advantage of zero turning radius. The kinematic model of the omnidirectional mobile platform with six mecanum wheel is established and verified through four kinds of motion state by the simulation (the omnidirectional mobile platform with six mecanum wheels moving along the Z axis, the X axis, the direction of which angle between positive X is 45 degrees, and the omnidirectional mobile platform with six mecanum wheels rotating around the geometric center). The states of one wheel in failure have been analyzed in this article, taking into account the research levels of omnidirectional mobile platform with six mecanum wheels in the presence. The motion features of the platform with six mecanum wheels and four mecanum wheels are analyzed when certain wheels are locked-up or followed-up based on the force analysis of the wheels, and it proves that the platform with six mecanum wheels moves more stable than the platform with four mecanum wheels. In the presence of wheel failure, the platform still can move to the target location with gesture, due to its redundancy. This study contributes to the research of omnidirectional mobile platform with normal or failure mecanum wheels

Investigation of Guidewire Deformation in Blood Vessels Based on an SQP Algorithm

This paper proposes a solution to the simulated deformation of guidewires when they come in contact with the blood vessel in an interventional surgery simulation training system. Starting from the principle of minimum energy, the guidewire is evenly dispersed into a rigid light bar articulation model. A sequential quadratic programming (SQP) algorithm is used to nonlinearly optimize the deflection angle of each light bar. When the elastic potential energy of the guidewire reaches a minimum, we can get the guidewire deformation we want to solve. The method proposed in this paper avoids necessity of delving into contact deformation caused by the contact force between the guidewire and the blood vessel wall, while solving the problem of the deformation of the guidewire due to the pose of the contact points. We use an ABAQUS (finite element software) simulation to verify that this solution has a theoretical simulation accuracy of 5.11%, and the designed experiments prove that the actual simulation accuracy is about 11%. Moreover, we also simulated the bending stress state of the guidewire by using the deflection angle of each bar. In addition, in order to achieve the most suitable simulation results, we discuss the discrete density of the guidewire model from the perspective of algorithm time consumption and simulation accuracy