The Design and development of secure password synchronization and querting system for the enterprise networks /

Organizations that run large computer networks should also provide maintenance for the computers on these networks. Nowadays, it is a common practice to outsource this maintenance task to specialized service firms. These service firms may not be considered trustworthy. Therefore, the local administrator password of a local machine that a maintenance technician needs to access should be changed periodically. Consequently, the technician needs a way to learn the current local administrator password of each computer. In this thesis, a secure password synchronization and querying system is presented. In this system, the local administrator passwords of computers are changed periodically in synchronization with a server managing the system. The maintenance technicians can learn the current password of a computer by querying the server. For synchronization and querying mechanisms, we propose three secure protocols that employ symmetric and asymmetric encryption techniques. Moreover, in this thesis, the proposed protocols are implemented as a software product and the performance of the system is evaluated by simulating the system. The average of the number of successful synchronizations stays constant when the number of computers is increased from 3,000 to 20,000 in the simulation. An increase in the number of computers doesn't change the behavior of the system. In addition, it is shown that the system can be configured to survive under rough network conditions. The implementation details and the performance evaluation of the system are presented in the thesis

Design and implementation of a low-latency origin and relay for media-over-quic transport

The Media-over-QUIC Transport (MOQT) is an emerging application-layer protocol designed for low-latency media ingestion and distribution. It is applicable in both browser scenarios (i.e., HTTP/3WebTransport) and non-browser settings (i.e., raw QUIC) and geared towards diverse applications, including live streaming, cloud gaming, remote desktop, video conferencing and eSports. One of the primary goals of MOQT is to allow implementers to develop a highly scalable low-latency media delivery solution. This research delves into exploring the design and implementation of a Media-over-QUIC origin and relay

Apoptotic rate and metallothionein levels in the tissues of cadmium- and copper-exposed rats

It is well known that cadmium (Cd) has toxic and carcinogenic effects in rodents and humans, but the effects of Cd on apoptosis are still not clear. Although some studies have shown that Cd has apoptotic potential, other studies have shown that Cd can be antiapoptotic. Parameters such as sensitivity of the exposed organism or cells and the exposure conditions should be important in delineating the effect of Cd on apoptosis. In the present study, we aimed to determine the apoptotic index (AI) of Sprague-Dawley rat tissues that are loaded at a lower Cd concentration than the critical concentration (50 mu g/g) for its toxic effects. Metallothionein (NIT) levels of tissues were also determined and the experiments repeated with copper (Cu)-exposed rats. We detected decreases in the apoptotic index in liver and lung tissues of Cd-exposed groups accompanied with an increase in MT levels. Also, decreases of Al were detected in the liver tissues of Cu-exposed groups. These findings indicate that Cd can suppress apoptosis in vivo. The possible role of NIT expression on the suppression of apoptosis and the importance of free-Cd ion concentration on switching antiapoptotic effects to proapoptotic effects are also discussed

Dephosphorylation of Ikaros by a specific phosphatase regulates its function in chromatin remodeling (136.9)

Abstract Ikaros encodes a zinc finger protein essential for lymphoid development. Ikaros localizes to pericentromeric heterochromatin (PC-HC) where it recruits target genes, resulting in their activation or repression via chromatin remodeling. Ikaros' function is controlled by post-translational modification. Our previous studies show that phosphorylation of Ikaros by CK2 kinase controls its PC-HC localization, and its ability to bind the upstream regulatory region (URE) and regulate expression of TdT during thymocyte differentiation. Here, we demonstrate, by co-immunoprecipitation, that Ikaros interacts in vivo with a specific phosphatase for which it is a substrate. Mutational analysis identified specific residues essential for Ikaros-phosphatase interaction. Mutant Ikaros protein with disrupted phosphatase interaction undergoes CK-2-mediated hyperphosphorylation that inhibits its ability to bind the TdT URE, and its PC-HC localization. Alanine mutations at the CK2-phosphorylated residues restore both Ikaros' DNA-binding ability and PC-HC localization, regardless of its ability to interact with the phosphatase. We propose a model whereby the regulation of TdT expression by Ikaros is controlled by CK2 kinase and interaction with a specific phosphatase and that the balance of these two signal transduction pathways is essential for normal T cell differentiation. Supported by NIH K22CA111392 (SD)</jats:p

Determinants of the Green Supplier Selection

AbstractGreen consideration has been one of the most crucialissues for environmental protection due to increasing consumption level, and ill effect of the industrial developments, as well. For overcoming the negative impacts of the industrial processes, supplier selection can be seen as an important part of the green supply chain management concept due to its long term effects. On the other hand, many companies bestow a privilege on their partners if they have green consideration thanks to the positive perception of the customers.In this paper, a literature review is done for expressing what criteria effect the decision environment to build a better relationship with partners, and a criteria list for green supplier selection for textile industry is proposed in a hierarchic structure which is useful to integrate multicriteria decision analysis. The proposed criteria list is formed by eight main criteria and thirty one sub-criteria which consists green and also non-green criteria what are cost, delivery, quality, service, strategic alliance, pollution control, green product and environmental management

The novel mesityloxy substituted metallo-phthalocyanine dyes with long fluorescence lifetimes and high singlet oxygen quantum yields

The synthesis of novel peripheral or non-peripheral tetra-mesityloxy substituted metal-free, zinc and indium phthalocyanines, which are highly soluble in organic solvents, has been achieved. The phthalocyanines have been characterized by UV-vis, IR, MALDI-TOF Mass, 1H NMR, 13C NMR spectroscopies and elemental analysis. On their spectroscopic, photochemical and photophysical properties, the effects of the substituent position and the variety of central metal ions in phthalocyanine cavity are also investigated. Photodegradation, singlet oxygen and fluorescence quantum yields, and fluorescence lifetimes in dimethylformamide for the phthalocyanines are described. These properties of the compounds are very useful for photodynamic therapy applications and their high singlet oxygen quantum yields are very important for Type II mechanisms. The phthalocyanines can be appropriate candidates as Type II photosensitizers. © 2015 Elsevier B.V. All rights reserved

Identification of O-GlcNAc Modification Targets in Mouse Retinal Pericytes: Implication of p53 in Pathogenesis of Diabetic Retinopathy

Abstract Hyperglycemia is the primary cause of the majority of diabetes complications, including diabetic retinopathy (DR). Hyperglycemic conditions have a detrimental effect on many tissues and cell types, especially the retinal vascular cells including early loss of pericytes (PC). However, the mechanisms behind this selective sensitivity of retinal PC to hyperglycemia are undefined. The O-linked b-N-acetylglucosamine (O-GlcNAc) modification is elevated under hyperglycemic condition, and thus, may present an important molecular modification impacting the hyperglycemia-driven complications of diabetes. We have recently demonstrated that the level of O-GlcNAc modification in response to high glucose is variable in various retinal vascular cells. Retinal PC responded with the highest increase in O-GlcNAc modification compared to retinal endothelial cells and astrocytes. Here we show that these differences translated into functional changes, with an increase in apoptosis of retinal PC, not just under high glucose but also under treatment with O-GlcNAc modification inducers, PUGNAc and Thiamet-G. To gain insight into the molecular mechanisms involved, we have used click-It chemistry and LC-MS analysis and identified 431 target proteins of O-GlcNAc modification in retinal PC using an alkynyl-modified GlcNAc analog (GlcNAlk). Among the O-GlcNAc target proteins identified here 115 of them were not previously reported to be target of O-GlcNAc modification. We have identified at least 34 of these proteins with important roles in various aspects of cell death processes. Our results indicated that increased O-GlcNAc modification of p53 was associated with an increase in its protein levels in retinal PC. Together our results suggest that post-translational O-GlcNAc modification of p53 and its increased levels may contribute to selective early loss of PC during diabetes. Thus, modulation of O-GlcNAc modification may provide a novel treatment strategy to prevent the initiation and progression of DR

Abstract 1403: ROS metabolism and autophagy as potential targets to improve head and neck cancer treatment

Abstract Introduction: Cancer cells exhibit a high degree of plasticity to adapt the rapidly changing tumor microenvironment (TME), in part by altering cellular metabolic pathways at a faster and more efficient pace than normal cells. Cancer cell plasticity, with genetic and epigenetic alterations, promote the diversity of cancer cells contributing to heterogeneity within the tumor. Head and neck cancer (HNC) is a notable example of this diversity; HNC tumors harbor cells with a wide genetic and metabolic heterogeneity, including cancer stem cells (CSC). Despite current treatment approaches, more than 40% of HNC patients have disease recurrence. Thus, we developed a multimodal approach to effectively prevent the development of radio/drug-resistance. Experimental Procedures: Nuclear-localized mkate2 expressing HNC cell numbers detected for every 6 hours by using IncuCyte S3 instrument. Apoptotic cells detected via NucView 488 Caspase-3 substrate and ROS levels determined using CellROX green simultaneously with cell numbers in the IncuCyte S3 instrument. Synergy scores calculated according to viability in SynergyFinder 2.0 web-application. Results: Our preliminary data profiling of metabolic regulators as radiosensitizer indicate that auranofin (AUR, thioredoxin reductase inhibitor) and buthionine sulfoximine (BSO, γ-glutamylcysteine synthetase inhibitor), given in combination with radiation (RT+AUR+BSO): 1) significantly inhibit proliferation in HNC cell lines, 2) increase ROS accumulation, and 3) reduce the surviving fraction of cells in colony forming assays compared to individual/dual agent applications. Furthermore, we added an autophagy inhibitor, SAR405, in our treatment regimen because of the crosstalk between ROS levels and autophagy. Human (FaDu and UM-SCC-47) and murine (MOC1 and MOC2) HNC cell were treated with +/-AUR+/-BSO+/-SAR405 and high-throughput combinatorial screening of cell numbers obtained over time. The combination of AUR+BSO+SAR405 registered a higher synergy score than the double combinations. Furthermore, as compared to single or double drug applications, the AUR+BSO+SAR405 group had a greater apoptotic cell rate and ROS levels. Conclusion: We present here a high-throughput method to screen multi-drug synergy. Multi-modal approach is important to prevent recurrence by providing a broader effect on heterogenous cancer cells in tumor. Moreover, multi-drug combinations allow usage of lower doses of drugs effectively, hence lowers the treatment-related adverse effects. This approach indicated the possibility of HNC treatment by increasing the ROS levels beyond the containable threshold which is consistent with the recent findings about the alterations in redox metabolism, particularly upregulation in thioredoxin and glutathione pathways, in many cancer types. In vivo experiments are ongoing to evaluate the potential of this combination for clinical studies. Citation Format: Zafer Gurel, Qianyun Luo, Michael S. Luy, Randall J. Kimple. ROS metabolism and autophagy as potential targets to improve head and neck cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1403.</jats:p

Regulation of chromatin remodeling during thymocyte differentiation (88.5)

Abstract The Ikaros gene encodes a DNA-binding protein that functions as a master regulator of lymphoid development. Ikaros protein interacts with histone deacetylation complex and represses transcription of its target genes via chromatin remodeling. We have previously reported that Ikaros’ activity and protein stability is regulated by CK2 kinase (Popescu et al. J Biol Chem 2009 284:13869). We studied the effect of CK2-mediated phosphorylation on Ikaros function in primary thymocytes. Ikaros proteins with phosphomimetic mutations at CK2 phosphorylation sites 1) lose the ability to associate with Sin3a, a component of the NuRD histone deacetylase, as indicated by co-immunoprecipitation assays and 2) fail to repress genes involved in thymocyte differentiation as indicated by luciferase reporter assay. The introduction of phosphoresistant mutations at five N-terminal CK2 phosphorylation sites on the Ikaros protein restored Ikaros’ association with Sin3a, as well as wild-type levels of repressor activity. The treatment of primary thymocytes with CK2 kinase inhibitors resulted in increased levels of Ikaros protein and increased Ikaros’ DNA-binding affinity to the promoter regions of its target genes, as measured by quantitative chromatin immunoprecipitation. These results demonstrate that CK2 kinase regulates thymocyte differentiation by controlling Ikaros’ association with chromatin remodeling complexes and its ability to repress the transcription of developmentally regulated genes.</jats:p