The imbalanced development among different levels of healthcare facilities has become a major social issue in China's urban healthcare system, which has raised the irrational patient flow ...distribution on the levels of both intra-hospital and inter-healthcare facilities. In this research, we develop a methodology to find the optimal macrolevel patient flow distribution in terms of multidimension inputs and outputs for the two-level healthcare system. The proposed method integrates the discrete-event simulation (DES), the multiobjective optimization and the simulation budget allocation together to comprehensively improve the overall system performances by finding the approximate Pareto patient flow distribution in the hierarchical healthcare system. The multiobjective optimal computing budget allocation (MOCBA) is applied to improve the efficiency, where the nondominated probability is functioned as the fitness measurement to each design. A case study based on the real data is carried out to validate and implement the proposed method. The results of the case study show the recommended Pareto optimal patient flow distribution can improve the overall hierarchical system performances and our methodology are qualified as a quantitative decision tool for decision makers.
The first photocatalytic trichloromethyl radical-triggered annulative reactions of amide-linked 1,7-diynes with polyhalomethanes were established for the flexible assembly of functionalized ...quinolin-2(1H)-ones with generally acceptable yields. With the installation of the aryl group (R
) into the alkynyl moiety,
-center radical-initiated Kharasch-type addition/nucleophilic substitution/elimination cascade to produce quinolin-2(1H)-ones-incorporating
-dihaloalkene, whereas three examples of polyhalogenated quinolin-2(1H)-ones were afforded when amide-linked 1,7-diynes bearing two terminal alkyne units were subjected to BrCX
by exploiting dry acetonitrile as a solvent.
Summary
As a potential cancer therapy, we developed a recombinant adenovirus named Ad-VT, which was designed to express the apoptosis-inducing gene (apoptin) and selectively replicate in cancer cells ...via E1a manipulation. However, how it performs in bladder cancer remains unclear. We examined the antitumor efficacy of Ad-VT in bladder cancers using CCK-8 assays and xenograft models. Autophagy levels were evaluated by western blotting, MDC staining, and RFP-GFP-LC3 aggregates’ analyses. Here, we report the selective replication and antitumor efficacy (viability inhibition and apoptosis induction) of Ad-VT in bladder cancer cells. Using xenograft tumor models, we demonstrate that its effects are tumor specific resulting in the inhibition of tumor growth and improvement of the survival of mice models. Most Importantly, Ad-VT induced a complete autophagy flux leading to autophagic cancer cell death through a signaling pathway involving AMPK, raptor and mTOR. Finally, we suggest that treatment combination of Ad-VT and rapamycin results in a synergistic improvement of tumor control and survival compared to monotherapy. This study suggests that Ad-VT can induce selective autophagic antitumor activities in bladder cancer through the AMPK-Raptor-mTOR pathway, which can be further improved by rapamycin.
Abstract
Bogie frame and body bolster are of vital importance to the reliable operation of the rolling stocks. There are two kinds of test methods for bogie frame and body bolster. One is separate ...test, and the other is joint test. To effectively detect the strength performance of bogie frame and body bolster as well as to improve the test efficiency, we adopted the method of joint test, and designed the test plan according to the standard. The strength test of bogie frame and body bolster is carried out where load analysis is studied and applied. The structural performance of bogie frame and body bolster is evaluated by means of Goodman fatigue limit diagram.
Blockchain as a Service (BaaS) combines features of cloud computing and blockchain, making blockchain applications more convenient and promising. Although current BaaS platforms have been widely ...adopted by both industry and academia, concerns arise regarding their performance, especially in job allocation. Existing BaaS job allocation strategies are simple and do not guarantee load balancing due to the dynamic nature and complexity of BaaS job execution. In this paper, we propose a deep reinforcement learning-based algorithm, Balanced-DRL, to learn an optimized allocation strategy in BaaS based on analyzing the execution process of BaaS jobs and a set of job scale characteristics. Following extensive experiments with generated job request workloads, the results show that Balanced-DRL significantly improves BaaS performance, achieving a 5% to 8% increase in job throughput and a 5% to 20% decrease in job latency.
In this paper, novel (Er1-xYbx)3TaO7 oxides were synthesized via high-temperature sintering method at 1600 °C for 10–15 h. The lattice structure, microstructure, and thermophysical performances were ...studied. Results exhibit that the (Er1-xYbx)3TaO7 oxides have a single fluorite-type lattice and dense microstructure. Because of the phonon scattering caused by Yb2O3 addition, thermal conductivity of (Er1-xYbx)3TaO7 oxides decreases with increasing Yb2O3 content, which is lower than that of 7YSZ. Thermal expansion coefficient of (Er1-xYbx)3TaO7 oxides is elevated with increasing Yb2O3 fraction, which is close to that of 7YSZ. The prepared (Er1-xYbx)3TaO7 oxides also exhibit outstanding crystal-lattice steadiness up to 1200 °C.
Although the room-temperature rechargeable sodium-ion battery has emerged as an attractive alternative energy storage solution for large-scale deployment, major challenges toward practical sodium-ion ...battery technology remain including identification and engineering of anode materials that are both technologically feasible and economical. Herein, an antimony-based anode is developed by incorporating antimony into graphitic carbon matrices using low-cost materials and scalable processes. The composite anode exhibits excellent overall performance in terms of packing density, fast charge/discharge capability and cyclability, which is enabled by the conductive and compact graphitic network. A full cell design featuring this composite anode with a hexacyanometallate cathode achieves superior power output and low polarization, which offers the potential for realizing a high-performance, cost-effective sodium-ion battery.
The human brain undergoes both morphological and functional modifications across the human lifespan. It is important to understand the aspects of brain reorganization that are critical in normal ...aging. To address this question, one approach is to investigate age-related topological changes of the brain. In this study, we developed a brain network model using graph theory methods applied to the resting-state functional magnetic resonance imaging data acquired from two groups of normal healthy adults classified by age. We found that brain functional networks demonstrated modular organization in both groups with modularity decreased with aging, suggesting less distinct functional divisions across whole brain networks. Local efficiency was also decreased with aging but not with global efficiency. Besides these brain-wide observations, we also observed consistent alterations of network properties at the regional level in the elderly, particularly in two major functional networks-the default mode network (DMN) and the sensorimotor network. Specifically, we found that measures of regional strength, local and global efficiency of functional connectivity were increased in the sensorimotor network while decreased in the DMN with aging. These results indicate that global reorganization of brain functional networks may reflect overall topological changes with aging and that aging likely alters individual brain networks differently depending on the functional properties. Moreover, these findings highly correspond to the observation of decline in cognitive functions but maintenance of primary information processing in normal healthy aging, implying an underlying compensation mechanism evolving with aging to support higher-level cognitive functioning.
The newly synthesized compound TGF-β signaling agonist (T74) is a small molecule associated with the TGF-β receptor signaling pathway. Tolerogenic dendritic cells (tDCs) have been used to examine ...immunosuppressive and anti-inflammatory effects in multiple autoimmune disease models. The aim of this study was to investigate whether treatment of DCs with T74 has an antirheumatic effect in a mouse model of collagen-induced arthritis (CIA). Bone marrow-derived cells were obtained from DBA/1J mice and differentiated into DCs. T74-treated DCs (T74-DCs) were generated by treating bone marrow-derived DCs with LPS, type II collagen, and T74. T74-DCs expressed lower levels of surface molecules and inflammatory cytokines associated with antigen presentation and T cell stimulation. The ability of T74-DCs to differentiate effector T cells was lower than that of T74-untreated DCs (NT-DCs), but T74-DCs increased the regulatory T (Treg) cell differentiation in vitro. DBA/1J mice received two subcutaneous (s.c.) injections of type II collagen to establish CIA. Mice then received two s.c. injections of T74-DCs or NT-DCs. Joint inflammation was ameliorated in the paws of T74-DC-treated mice. Additionally, Treg populations in T74-DC-treated mice were higher than in NT-DC-treated or PBS-treated CIA mice. Taken together, these results demonstrate that T74 induces tolerance in DCs, and that T74-mediated DCs exert antirheumatic effects via induction of Tregs.
Objective
Japanese encephalitis (JE) is a critical problem of public health worldwide; however, there is limited data about the clinical features and indicators of outcome in adults with severe ...Japanese encephalitis.
Methods
The clinical manifestations and laboratory study on brain neuroimaging of patients with severe JE were statistically analyzed retrospectively. All patients were followed up for 6 months after discharge. The patients were grouped into good outcome and poor outcome according to the results of the follow-up.
Results
This retrospective study consists of 9 adults with severe JE, including 5 cases with poor outcome, defined as the modified Rankin Scale (mRS) scores of greater than or equal to 4 points, and remained ventilator dependent. Typical clinical manifestations of JE include fever (100%), altered consciousness (100%), headache (66.7%), flaccid weakness (66.7%), and status epilepticus (44.4%). Serological examination revealed that a higher percentage of neutrophils and a lower percentage of lymphocytes at admission may be associated with a poor outcome. Abnormal neuroimaging of the thalamus (85.7%), hippocampal (71.4%), midbrain (28.6%), and basal ganglia (14.3%) was found. 42.9% of patients left severe irreversible disability, and the most prominent were mental symptoms (71.4%) and memory or understanding disorder (57.1%).
Conclusion
Our data suggest that respiratory failure is one of the important causes of early death. Serologic examination, coma, and status epilepticus may indicate a poor outcome for severe JE. Additionally, the hippocampus is the second most common lesion in the adults with severe JE. A large-scale clinical trial is required to further confirm these conclusions.
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