Policy inconsistencies may arise between safety and utility policies due to their opposite objectives. In this work we provide a formal examination of policy inconsistencies resolution for the ...coexistence of static separation-of-duty (SSoD) policies and strict availability (SA) policies. Firstly, we reduce the complexity of reasoning about policy inconsistencies by static pruning technique and minimal inconsistency cover set. Secondly, we present a systematic methodology for measuring safety loss and utility loss, and evaluate the safety-utility tradeoff for each choice. Thirdly, we present two prioritized-based resolutions to deal with policy inconsistencies based on safety-utility tradeoff. Finally, experiments show the effectiveness and efficiency of our approach.
A disintegrin and metalloprotease 12 (ADAM12), an essential transmembrane protein with metalloprotease, cell binding and intracellular signal‑regulating capabilities, has been reported to play a ...crucial role in various types of cancers. However, the biological function of ADAM12 in gastric cancer (GC) remains unclear. Bioinformatic and experimental analyses were used to determine the expression level and prognostic value of ADAM12 in GC. The level of DNA methylation and the competing endogenous RNA (ceRNA) network was identified using MethSurv, Starbase3.0, miRNet2.0 and experimental analyses. Then, the co‑expression profiles of ADAM12 were determined and subjected to enrichment analysis using the LinkedOmics database. The protein‑protein interaction network and the docking model of ADAM12 were constructed using the GeneMANIA, STRING, and HDOCK webservers. The role of ADAM12 in tumor metastasis and immune infiltration was investigated using
assays and TIMER database exploration. It was found that ADAM12 was overexpressed and was correlated with a poor prognosis of GC patients. In addition, the aberrant DNA methylation status and ceRNA regulation may contribute to the upregulation of ADAM12 in GC. Moreover, the enrichment analysis revealed that ADAM12 is involved in multiple vital biological functions and pathways, such as 'macrophage activation', 'extracellular matrix binding' and 'ECM‑receptor interaction'. Subsequently, the protein‑protein interaction network and molecular docking model demonstrated that follistatin like 3 (FSTL3) is a potential binding partner of ADAM12. Finally, it was demonstrated that ADAM12 promotes tumor metastasis, immune infiltration and M2 macrophage polarization in GC. In summary, these results highlight the potential of ADAM12 to be used as a therapeutic target for GC.
Malignant gliomas manifest frequent tumor recurrence after surgical resection and/or other treatment because of their nature of invasiveness and dissemination. The recognized brain tumor-tracking ...property of neural progenitor/stem cells opened the possibility of targeting malignant brain tumors using neural progenitor/stem cells. We and others have previously shown that fetal neural progenitor/stem cells can be used to deliver therapeutic molecules to brain tumors. Our recent work has further shown that gene delivery by bone marrow-derived neural progenitor/stem cells achieves therapeutic effects in a glioma model. In this study, we isolate and characterize bone marrow-derived neural progenitor/stem cells, which also express the chemokine receptor chemokine CXC receptor 4 (CXCR4). We show that CXCR4 is required for their chemotaxis and extracellular matrix invasion against a gradient of glioma soluble factors. Furthermore, beta-galactosidase-labeled bone marrow-derived neural progenitor/stem cells implanted in the contralateral side of the brain were shown to track gliomas as early as day 1 and increased through days 3 and 7. Intracranial glioma tracking by bone marrow-derived neural progenitor/stem cells is significantly inhibited by preincubation of bone marrow-derived neural progenitor/stem cells with a blocking anti-CXCR4 antibody, suggesting a CXCR4-dependent tracking mechanism. Glioma tracking bone marrow-derived neural progenitor/stem cells were found to express progenitor/stem cell markers, as well as CXCR4. Although bromodeoxyuridine incorporation assays and proliferating antigen staining indicated that tumor tracking bone marrow-derived neural progenitor/stem cells were mostly nonproliferating, these cells survive in the local tumor environment with little apoptosis. Elucidating the molecular mechanism of brain tumor tracking by adult source stem cells may provide basis for the development of future targeted therapy for malignant brain tumors.
The blood-brain tumor barrier (BTB) significantly limits the delivery of chemotherapeutics to brain tumors. Nitric oxide (NO) is involved in the regulation of cerebral vascular permeability. We ...investigated the effects of NO donors, L-arginine and hydroxyurea, on BTB permeability in 9L gliosarcoma-bearing Fischer rats.
The rats implanted with 9L gliosarcoma were dosed orally with hydroxyurea and L-arginine. BTB permeability, defined by the unidirectional transport constant, Ki, for 14Csucrose was measured. The expression of neural and endothelial NO synthase (NOS) in tumors and normal brain tissue was examined. Further, the levels of NO, L-citrulline, and cGMP in the tumor and normal brain tissue were measured.
Oral administration of l-arginine or hydroxyurea significantly increased BTB permeability when compared with the nontreated control. The selective effects were abolished by iberiotoxin, an antagonist of calcium-dependent potassium (KCa) channel that is a cGMP pathway effector. The expression of endothelial NOS, but not neural NOS, was higher in tumor vessels than in those of normal brain. Moreover, the levels of NO, L-citrulline, a byproduct of NO formation from L-arginine, and cGMP were enhanced in the tumor tissue by oral administration of L-arginine and/or hydroxyurea.
Oral administration of L-arginine or hydroxyurea selectively increased tumor permeability, which is likely mediated by alteration in cGMP levels. The findings suggest that use of oral NO donors may be a strategy to enhance the delivery of chemotherapeutics to malignant brain tumors.
Since the 1950s, hypoxia has been recognized as a crucial characteristic of cancer cells and their microenvironment. Indeed, hypoxia promotes the growth, survival, and metastasis of cancer cells. In ...the early 1990s, we found that as many phenomena in hypoxia can occur through hypoxia-inducible factor-1α (HIF1α). HIF1α is known as an angiogenesis converter in hypoxia, which promotes tumorigenesis, development, immune escape, recurrence, etc; This page goes into great detail on how HIF1α is activated during hypoxia and how the 2 signaling channels interact. It specifically emphasizes the significance of reactive oxygen species, the function of the PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade, and outlines the similarities between the 2 important factors (reactive oxygen species and PI3K/the serine/threonine kinase Akt/mammalian target of rapamycin cascade), nuclear factor κB, for HIF1α Important implications, in an effort to offer fresh views for the treatment of head and neck squamous cell carcinoma and HIF1α research.
Metal halide perovskite light-emitting diodes (PeLEDs) have shown enormous potential in the field of display. Recently, the economical and practical polyvinylpyrrolidone (PVP) has been widely used in ...perovskite-based optoelectronic devices. However, its comprehensive and complex effects are still lack of in-depth research. In this work, PVP interlayer is experimentally evidenced to play a multi-function role of passivating interface defects between hole transport layer (HTL) and emissive layer (EML), inhibiting grain boundary defects of EML, balancing hole/electron mobilities, and supporting as a hydrophilic interlayer to improve the wettability in PeLEDs. As a result, the hydrophobic poly-TPD HTL based 3D CsPbBr3, quasi-2D PEA2 CsPbBr35PbBr4 and 3D CsPb(Cl0.3Br0.7)3 PeLEDs are successfully demonstrated with the assistance of PVP buffer layer, yielding the optimized luminance, external quantum efficiency, current efficiency and T50 lifetime of 45,582 cd m−2, 2.78%, 8.4 cd A−1 and 2400 s for CsPbBr3 PeLED, 14,074 cd m−2, 5.50%, 17.6 cd A−1 and 7260 s for PEA2 CsPbBr35PbBr4 PeLED, 774 cd m−2, 0.40%, 0.47 cd A−1 and 330 s for 3D CsPb(Cl0.3Br0.7)3 PeLED, respectively. This work provides a deep insight of PVP buffer layer into various HTLs and multi-colored PeLEDs for the first time, which helps to enhance the key optoelectronic performance for PeLEDs.
•The effects of PVP layer on PeLEDs are explored for the first time.•The PVP-based PeLEDs exhibit superior optoelctronic properties.•The blue PeLED shows high EL stability and ultra-narrow FWHM.•This methods has versatility in various HTLs and perovskite EMLs.
Previous studies on solid organ transplantation have reported that a low time in therapeutic range (TTR) of tacrolimus increases the risk of poor outcomes. However, the reproducibility of the ...findings in liver transplantation has not yet been confirmed. The TTR, coefficient of variation (CV) and standard deviation (SD) were calculated for 207 adult liver transplant patients from the date of transplantation until the first episode of acute rejection (AR), graft loss, acute kidney injury (AKI), biliary complications, infection or the last follow‐up. Kaplan–Meier curves, log‐rank tests and Cox regression analyses were performed. Sixty‐one (29.5%) patients reached the composite endpoint of AR, biliary complications and graft loss. The log‐rank test indicated that the low TTR group had an increased risk of the composite endpoint (P < 0.001), AKI (P < 0.001) and infection (P < 0.001). Multivariate Cox regression analyses revealed that a 10% decrease in TTR was associated with an increased hazard for composite endpoint (hazard ratio HR: 1.185, P = 0.010), AKI (HR: 1.355, P < 0.001) and infection (HR: 1.357, P < 0.001). Unexpectedly, SD and CV demonstrated no association with the above‐mentioned inferior outcomes. Compared with SD and CV, the TTR of tacrolimus was more correlated with inferior outcomes and may be a novel indicator for predicting the prognosis of liver transplantation.
PDF
