Objective
Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and ...healthy donors.
Methods
Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed.
Results
Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up‐regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3− Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire.
Conclusion
We established the presence of a specific Tfh cell signature in both circulating and aorta‐infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.
Many of today's data centers experience physical limitations on the power needed to run the data center. The first problem that we study is maximizing the performance (quantified by the reward ...collected for completing tasks by their individual deadlines) of a data center that is subject to total power consumption (of compute nodes and CRAC units) and thermal constraints. The second problem that we study is how to minimize the power consumption in a data center while guaranteeing that the overall performance does not drop below a specified threshold. For both problems, we develop novel optimization techniques for assigning the performance states of cores at the data center level to optimize the operation of the data center. The resource allocation (assignment) techniques in this paper are thermal aware as they consider effects of performance state assignments on temperature and power consumption by the CRAC units. Our simulation studies show that in some cases our assignment technique achieves about 17% average improvement in the reward collected, and about 9% reduction in power consumption compared to an assignment technique that only considers putting a core in the performance state with the highest performance or turning the core off.
Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel ...vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown.
We evaluate mTORC pathway activation in vascular aorta lesions and in T cell homeostasis of patients with LVV.
Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway (S6RP phosphorylation). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. mTORC1 activation was found also in Th1 and Th17 cells both systemically and in inflamed vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNγ+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV.
We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.
•mTORC1 pathway is critical in driving vascular lesions and promoting effector T cells in large vessel vasculitis (LVV).•Targeting mTORC pathway may represent a new therapeutic option in LVV.•The inhibition of the mTORC pathway in LVV may prevent vascular remodeling and stenosis.
mTORC1 pathway has a critical role in driving vascular lesions and promoting effector T cells and suppressing Tregs in large vessel vasculitis (LVV). Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.
We utilize a for-profit aggregator-based residential demand response (DR) approach to the smart grid resource allocation problem. The aggregator entity, using a given set of schedulable residential ...customer assets (e.g., smart appliances), must set a schedule to optimize for a given objective. Here, we consider optimizing for the profit of the aggregator. To encourage customer participation in the residential DR program, a new pricing structure named customer incentive pricing (CIP) is proposed. The aggregator profit is optimized using a proposed heuristic framework, implemented in the form of a genetic algorithm, that must determine a schedule of customer assets and the CIP. To validate our heuristic framework, we simulate the optimization of a large-scale system consisting of 5555 residential customer households and 56 642 schedulable assets using real-pricing data over a period of 24-h. We show that by optimizing purely for economic reasons, the aggregator can enact a beneficial change on the load profile of the overall power system.
Unexpected results of spectral emission and photophysical study of S
2
-excited 4
H
-1-benzopyrane-4-thione (BPT) in water solution were explained by intermolecular hydrogen bonding. There are at ...least two types of BPT-water complexes that participate in the S
2
-fluorescence similarly as in S
0
→ S
2
absorption. They both deactivate with high efficiency in internal conversion S
2
→ S
1
and in intersystem crossing S
1
→ T
1
processes.
Unexpected results of spectral emission and photophysical study of S
2
-excited 4
H
-1-benzopyrane-4-thione (BPT) in water solution were explained by intermolecular hydrogen bonding.
In this paper, the authors examine the problem of designing nominal manipulator Jacobians that are optimally fault tolerant to one or more joint failures. Optimality is defined here in terms of the ...worst-case relative manipulability index. While this approach is applicable to both serial and parallel mechanisms, it is especially applicable to parallel mechanisms with a limited workspace. It is shown that a previously derived inequality for the worst-case relative manipulability index is generally not achieved for fully spatial manipulators and that the concept of optimal fault tolerance to multiple failures is more subtle than previously indicated. Lastly, the authors identify the class of 8-DOF Gough--Stewart platforms that are optimally fault tolerant for up to two joint failures. Examples of optimally fault-tolerant 7- and 8-DOF mechanisms are presented.
The success of an efficient and effective aggregator‐based residential demand response system in the smart grid relies on the day‐ahead customer incentive pricing (CIP) and the load shifting ...protocols. An artificial neural network model is designed to generate the day‐ahead CIP for the aggregator based on historical data. Load scheduling is proposed as a day‐ahead optimization problem that is solved using a blocked sliding window technique using parallel computing. With the assumptions made, the proposed algorithm improved the aggregator performance by reducing the overall simulation time from 275 to 45 min and increasing the aggregator forecast profits and customer savings by 11.85% and 35.99% compared to the previous genetic algorithm‐based approach.
The antimalarial activities of ferrocenic compounds mimicking chloroquine and active upon chloroquine-resistant strains of Plasmodium falciparum were evaluated. Four 7-chloro-4-2-(N,N-substituted ...amino)methylferrocenylmethylaminoquinoline derivatives have been synthesized; one of them, 1a, showed high potent antimalarial activity in vivo on mice infected with Plasmodium berghei N. and Plasmodium yoelii NS. and was 22 times more potent against schizontocides than chloroquine in vitro against a drug-resistant strain of P. falciparum.
Measuring the robustness of a resource allocation Ali, S.; Maciejewski, A.A.; Siegel, H.J. ...
IEEE transactions on parallel and distributed systems,
07/2004, Letnik:
15, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Parallel and distributed systems may operate in an environment that undergoes unpredictable changes causing certain system performance features to degrade. Such systems need robustness to guarantee ...limited degradation despite fluctuations in the behavior of its component parts or environment. This research investigates the robustness of an allocation of resources to tasks in parallel and distributed systems. The main contributions are 1) a mathematical description of a metric for the robustness of a resource allocation with respect to desired system performance features against multiple perturbations in multiple system and environmental conditions, and 2) a procedure for deriving a robustness metric for an arbitrary system. For illustration, this procedure is employed to derive robustness metrics for three example distributed systems. Such a metric can help researchers evaluate a given resource allocation for robustness against uncertainties in specified perturbation parameters.
It is common practice to design a robot's kinematics from the desired properties that are locally specified by a manipulator Jacobian. In this work, the desired property is fault tolerance, defined ...as the post-failure Jacobian possessing the largest possible minimum singular value over all possible locked-joint failures. A mathematical analysis based on the Gram matrix that describes the number of possible planar robot designs for optimally fault-tolerant Jacobians is presented. It is shown that rearranging the columns of the Jacobian or multiplying one or more of the columns of the Jacobian by ±1 will not affect local fault tolerance; however, this will typically result in a very different manipulator. Two examples, one that is optimal to a single joint failure and the second that is optimal to two joint failures, are analyzed. This analysis shows that there is a large variability in the global kinematic properties of these designs, despite being generated from the same Jacobian. It is especially surprising that major differences in global behavior occurs for manipulators that are identical in the working area.
PDF
