The cognitive deficits in patients with HIV profoundly affect the quality of life of people living with this disease and have often been linked to the neuro-inflammatory condition known as HIV encephalitis (HIVE). With the advent of more effective anti-retroviral therapies, HIVE has shifted from a sub-acute to a chronic condition. The neurodegenerative process in patients with HIVE is characterized by synaptic and dendritic damage to pyramidal neurons, loss of calbindin-immunoreactive interneurons and myelin loss. The mechanisms leading to neurodegeneration in HIVE might involve a variety of pathways, and several lines of investigation have found that interference with signaling factors mediating neuroprotection might play an important role. These signaling pathways include, among others, the GSK3β, CDK5, ERK, Pyk2, p38 and JNK cascades. Of these, GSK3β has been a primary focus of many previous studies showing that in infected patients, HIV proteins and neurotoxins secreted by immune-activated cells in the brain abnormally activate this pathway, which is otherwise regulated by growth factors such as FGF. Interestingly, modulation of the GSK3β signaling pathway by FGF1 or GSK3β inhibitors (lithium, valproic acid) is protective against HIV neurotoxicity, and several pilot clinical trials have demonstrated cognitive improvements in HIV patients treated with GSK3β inhibitors. In addition to the GSK3β pathway, the CDK5 pathway has recently been implicated as a mediator of neurotoxicity in HIV, and HIV proteins might activate this pathway and subsequently disrupt the diverse processes that CDK5 regulates, including synapse formation and plasticity and neurogenesis. Taken together, the GSK3β and CDK5 signaling pathways are important regulators of neurotoxicity in HIV, and modulation of these factors might have therapeutic potential in the treatment of patients suffering from HIVE. In this context, the subsequent sections will focus on reviewing the involvement of the GSK3β and CDK5 pathways in neurodegeneration in HIV. 相似文献
Consensus Principal Component Analysis is a multiblock method which is designed to reveal covariant patterns between and within several multivariate data sets. The computation of the parameters of this method namely, block scores, block loadings, global loadings and global scores are based on an iterative procedure. However, very few properties are known regarding the convergence of this iterative procedure. The paper discloses a monotony property of CPCA and exhibits an optimisation criterion for which CPCA algorithm provides a monotonic convergent solution. This makes it possible to highlight new properties of this method of analysis and pinpoint its connection to existing methods such as Generalized Canonical Correlation Analysis and Multiple Co-inertia Analysis. 相似文献
We recently demonstrated that the CAV1 gene was down-regulated, when poorly differentiated thyroid FTC-133 cancer cells formed spheroids under simulated microgravity conditions. Here, we present evidence that the caveolin-1 protein is involved in the inhibition of spheroid formation, when confluent monolayers are exposed to microgravity. The evidence is based on proteins detected in cells and their supernatants of the recent spaceflight experiment: “NanoRacks-CellBox-Thyroid Cancer”. The culture supernatant had been collected in a special container adjacent to the flight hardware incubation chamber and stored at low temperature until it was analyzed by Multi-Analyte Profiling (MAP) technology, while the cells remaining in the incubation chamber were fixed by RNAlater and examined by mass spectrometry. The soluble proteins identified by MAP were investigated in regard to their mutual interactions and their influence on proteins, which were associated with the cells secreting the soluble proteins and had been identified in a preceding study. A Pathway Studio v.11 analysis of the soluble and cell-associated proteins together with protein kinase C alpha (PRKCA) suggests that caveolin-1 is involved, when plasminogen enriched in the extracellular space is not activated and the vascular cellular adhesion molecule (VCAM-1) mediated cell–cell adhesion is simultaneously strengthened and activated PRKCA is recruited in caveolae, while the thyroid cancer cells do not form spheroids. 相似文献
By means of series of tests carried out on simply supported beams of standard rolled sections subjected to bending, fully analytically formulated calculation values were derived for the temperature-dependent stress-strain relationships of structural steel under fire action from normal temperature to 1000 °C.
Systematic series of investigations carried out on frame assemblies made up from rolled sections with high scale accuracy revealed the characteristic parameters influencing the critical temperatures. The analyses showed good-to-excellent agreement both for the temperature-displacement curves and for the critical temperatures, so that the integrity of the stress-strain relationships could also be verified for combined bending and compressive stress states and for stability-endangered assemblies.
The knowledge gained by the of experiment and computation furnished — in generalized terms — a basic concept for the simple and uniform assessment of the resistance to fire action of single elements and whole assemblies of structural steel subject mainly to bending stresses or endangered in stability. This allows the collapse temperatures of uniformly heated systems to be determined as a function of load utilization factor and system slenderness. These major parameters — load utilization factor and system slenderness ratio — are normal temperature design characteristics and can be determined using conventional methods. 相似文献
Process-based biomimetics focuses on the transfer of biological principles to architectural construction. To realise the ICD/ITKE Research Pavilion 2014 -15, presented here by Moritz Doerstelmann, Jan Knippers, Valentin Koslowski, Achim Menges, Marshall Prado, Gundula Schieber and Lauren Vasey of the Institute for Computational Design (ICD) and Institute of Building Structures and Structural Design (ITKE) research team at the University of Stuttgart, sensor-driven robotic fabrication was combined with advanced design computation and simulation. This enabled the construction of an architectural fibre structure on a pneumatic mould, drawing on the complex design of the web of a water spider. 相似文献
Ab initio SCF and semiempirical MINDO/3 and PPP/DCI calculations have been applied to substituted cyclopentamethines which formally resulted from cyclization of streptopentamethines in the α,α′-positions. These compounds exhibit a typical streptopolymethinic charge distribution of the carbon atoms along the cyclized chain, unique molecular geometries, extremely small energy gaps between the lowest excited states S1, T1 and the ground state S0 as well as large electron affinities. With respect to molecular geometry, spectral behaviour and electron affinity substituted cyclopentamethines are closely related to the antiaromatic cyclopentadienyl cation. Depending on the substitution pattern, the one or the other of the two Jahn-Teller distorted geometries of the antiaromatic C5H5⊕ appears to be frozen. 相似文献
RDX products obtained at high heating rates are discussed. RDX was decomposed by combustion in pressurized bomb and by short laser pulse irradiation. 相似文献
Registration of point cloud data containing both depth and color information is critical for a variety of applications, including in-field robotic plant manipulation, crop growth modeling, and autonomous navigation. However, current state-of-the-art registration methods often fail in challenging agricultural field conditions due to factors such as occlusions, plant density, and variable illumination. To address these issues, we propose the NDT-6D registration method, which is a color-based variation of the Normal Distribution Transform (NDT) registration approach for point clouds. Our method computes correspondences between pointclouds using both geometric and color information and minimizes the distance between these correspondences using only the three-dimensional (3D) geometric dimensions. We evaluate the method using the GRAPES3D data set collected with a commercial-grade RGB-D sensor mounted on a mobile platform in a vineyard. Results show that registration methods that only rely on depth information fail to provide quality registration for the tested data set. The proposed color-based variation outperforms state-of-the-art methods with a root mean square error (RMSE) of 1.1–1.6 cm for NDT-6D compared with 1.1–2.3 cm for other color-information-based methods and 1.2–13.7 cm for noncolor-information-based methods. The proposed method is shown to be robust against noises using the TUM RGBD data set by artificially adding noise present in an outdoor scenario. The relative pose error (RPE) increased 14% for our method compared to an increase of 75% for the best-performing registration method. The obtained average accuracy suggests that the NDT-6D registration methods can be used for in-field precision agriculture applications, for example, crop detection, size-based maturity estimation, and growth modeling. 相似文献