Chemical genetic manipulation of interferon regulatory factor 1 (IRF-1) using synthetic biology

Interferon regulatory factor 1 (IRF-1), the founding member of IRF family, is a nuclear transcription factor first described as a transcription factor that binds to the upstream region of interferon induced genes following viral infection. In addition, IRF-1 has been reported to be involved in cell growth regulation, induction of apoptosis, immune responses, post-transcriptional modification, and cell transformation by oncogenes. Thus, IRF-1 shows accumulative evidence supporting the theory that IRF-1 functions as a tumour suppressor. However, we still lack the knowledge in the regulation and function behind IRF-1 and many other tumour suppressors due to the lack of synthetic tools that can aid in understanding the mechanism of cancer biology. Here we described the creation of synthetic tools that can be applied to study the role of a transcription factor(s) in cancer biology. Firstly, we described the creation, using recombineering technology, of universal bacterial artificial chromosome (BAC) targeting vector. This targeting vector, carry a cre-conditioned STOP cassette that can be targeted at a desired specific area. The resulted targeting vector can aid the generation of mice models with a conditioned knock-in subtle mutation(s). The resulted cre-conditioned mice models are an essential tool for any outstanding research project in cancer biology. Secondly, we described the development of Flp-In System™ from Invitrogen; the system can ease the generation of isogenic stable mammalian expression cell lines. Using this system, we created two isogenic stable cell lines expressing wild-type IRF-1 and a mutant that abolish IRF-1 DNA binding ability (W11R). Both cell lines were investigated using microarray analysis revealing new IRF-1 target genes. We reported the up-regulation of expected standard interferon regulatory genes such as, interleukin-24 (IL-24) and interferon regulatory factor-2 binding protein-2 (IRF2BP2) and the up-regulation of standard apoptotic genes such as, early growth response-1 (EGR-1) and prostate transmembrane protein, androgen induced-1 (PMEPA1) confirming the role of IRF-1 as a tumour suppressor. However, we also reported the up-regulation of secreted phosphoprotein-1 (SPP1) and SH3 and PX domains-2A (SH3PXD2A) which are matricellular protein produced by cancer cells playing a role in cellular adhesion, invasion, tumour growth progression and metastasis. Thus, we proposed a new biological role of IRF-1 in cellular movement. Thirdly, we described the development of a synthetic stable reporter cell line which can report IRF-1 transcriptional activity; such reporter cell line can be used once large scale screening is needed. The created stable reporter cell line was used to screen a kinase inhibitor library which has revealed C3 as an IRF-1 modifier. The newly identified IRF-1 modifier regulates IRF-1 transcriptional activity by inhibiting platelet-derived growth factor receptor (PDGFR) and/or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase. Finally, we validated the synthetic Flp-In System™ by testing the system using a novel oncoprotein model. We have developed a stable cell line that overexpresses an oncoprotein named Anterior Gradient 2 (AGR-2). We have found that AGR-2 can attenuate IRF-1 protein levels dependent of p53. In addition, AGR-2 has been identified as a cellular survivor factor during unfolding protein response. In conclusion, this study descried the creation and the validation of synthetic tools: synthetic cassette for cre-conditioned mice creation, the Flp-In System™ for isogenic stable cell line creation, and IRF-1 reporter cell line for high throughput screening. All synthetic tools were validated and used to investigate IRF-1, a transcription factor that plays a role in cancer and immune system

Internet protocol MANET vs named data MANET: A critical evaluation

Many researches have been done in the field of mobile networking, specifically in the field of ad-hoc networks.The major aim of these networks is the delivery of data to a given node at the destination, irrespective of its location.Mobile Ad-hoc Network (MANET) employs the traditional TCP/IP structure to provide end-to-end communication between nodes (we named this type of architecture is IP-MANET).However, due to their mobility and the limited resource in wireless networks, each layer in the TCP/IP model requires redefinition or modifications to function efficiently in MANET. Named Data MANET (NDMANET) architecture is a recently emerging research area. The in-network chunk-based caching feature of NDN is beneficial in coping with the mobility and intermittent connectivity challenges in MANETs.In the natural disaster field, MANET is considered a challenging task because of the unpredictable changes in the network topology due to the absence of any centralized control.The goals of this paper have two ways: first, this study provides a performance comparison of IP-MANET to ND-MANET in terms of throughput, delay, and packet loss.While the second contribution is to identify which architecture has an impact on the natural disaster (i.e., Flooding disaster) in rural areas and suggests which one may perform better.For experimental purposes, our analyses IP-MANET and ND-MANET by extensive simulations in the NS 3 simulator under a number of different network scenarios, and show that how number of nodes and variety packets size affect their performance

Sequence analysis of the VSX1 and SOD1 genes in families with Keratoconus and a review of the literature

AbstractObjectiveKeratoconus (KC) is a non-inflammatory disorder of the cornea in which the cornea becomes thin and conical, inducing myopia and irregular astigmatism and resulting in mild to marked impairment of vision. The present study was designed to screen two candidate KC genes to identify pathogenic sequence variants responsible for KC in Saudi families.MethodsPeripheral blood samples from members of five Saudi families with KC from the Northern region were collected. Genomic DNA was isolated, and bidirectional sequencing was performed of all coding exons of VSX1 and SOD1 genes using Sanger sequencing.ResultsAll five of the KC families showed a pattern of autosomal recessive inheritance. Phenotyping of these families was performed by a senior ophthalmologist. Sequence analysis of the VSX1 and SOD1 genes failed to reveal any pathogenic sequence variant that could account for KC in the affected individuals.ConclusionOur failure to detect sequence variants in two of the known KC associated genes triggers an interest in other known KC candidate genes, including miR-184, DOCK9, IL1RN and SLC4A11. Future genotyping with dense SNP arrays followed by exome sequencing in these families will be a useful approach to identify the gene(s) underlying KC in this Saudi cohort, which may be different from those reported elsewhere

Investment in ICT in Developing Countries: the effect of FDI: Evidences from Sultanate of Oman

Foreign direct investment (FDI) is a crucial tool developing the economy of any country if it is employed in a proper manner. Moreover, foreign direct investment has many effects; and one of them is thriving the information and communication technology (ICT) sector as a pivotal sector which includes four sub-sectors according to the World Bank (ICT Service Exports, ICT Goods Imports, High-Technology Exports and ICT Goods Exports). Hence, the aim of this paper is to identify the influence of foreign direct investment in thriving the sub-sectors of information and communication technology, as one of the drivers to develop the economy. To accomplish this purpose the statistical data on direct foreign investment and exports and imports of information and communication technology about Sultanate of Oman were collected from 2000-2014 published by the World Bank. descriptive statistics and Simple regression model were used to analyze the collected data and test the hypotheses of the study. The findings show that the planning for foreign direct investment is ad-hoc, therefore there should be a obvious view of how to exploit foreign direct investment in economy development, especially in transferring of information and communication technology. The paper contributed to the literature by being the first study that attempted to interpret the role of foreign direct investment  on exports and imports of information and communication technology in Sultanate of Oman.  Keywords: Foreign direct investment (FDI), ICT, High-Technology Exports, ICT Goods, ICT Service Exports, ICT Goods Imports, Oman. JEL Classifications: F14, N

Performance analysis of reactive and proactive routing protocols in MANET

In the artificial disaster field, Mobile Ad-hoc Network (MANET) routing is considered a challenging task because of the unpredictable changes in the network topology due to the absence of any centralized control. This routing has led to the development of several different routing protocols for MANET.Thus, it is hard to decide which of these protocols act better than the others.The objectives of this study are of two folds.First, this study provides a performance comparison of MANET routing protocols in terms of delay, packet lost, throughput, jitter, packet delivery ratio (PDR), and normalized routing load (NRL). Second, this study identifies whether MANET routing protocol has an impact on the artificial disaster and suggests which protocols may perform better.For experimental purposes, Network Simulator 2 (NS-2) was used.High density nodes were created in a 1000×1000m location area, and each node was assigned a CBR traffic load.Random Waypoint Mobility mode was used to be implemented with varying pause time and the number of connections.The simulation results show that Destination Sequence Distance Vector (DSDV) protocol provides better throughput and PDR with less jitter, delay and NRL for low or high-traffic load and mobility.However, DSDV still has performance limitations with packet loss parameter. Additionally, the results obtained show that DSDV gives a great improvement for using network resources, especially when the number of connections is high with low mobility. Hence, DSDV is considered as a better routing protocol that is used in the artificial disaster and emergency recovery application

Vitamin D serum level predicts stroke clinical severity, functional independence, and disability—A retrospective cohort study

BackgroundStroke is a leading cause of mortality and disability and one of the most common neurological conditions globally. Many studies focused on vitamin D as a stroke risk factor, but only a few focused on its serum level as a predictor of stroke initial clinical severity and recovery with inconsistent results. The purpose of this study was to assess the relationship between serum vitamin D levels and stroke clinical severity at admission and functional independence and disability at discharge in Saudi Arabia.MethodologyA retrospective cohort study of adult ischemic stroke patients who had their vitamin D tested and admitted within 7 days of exhibiting stroke symptoms at King Abdulaziz Medical City (KAMC) Jeddah, Saudi Arabia. Based on vitamin D level, the patients were categorized into normal [25(OH)D serum level ≥ 75 nmol/L], insufficient [25(OH)D serum level is 50–75 nmol/L], and deficient [25(OH)D serum level ≤ 50 nmol/L]. The primary outcome was to assess the vitamin D serum level of ischemic stroke patients’ clinical severity at admission and functional independence at discharge. The National Institute of Health Stroke Scale (NIHSS) was used to assess the clinical severity, whereas the modified Rankin scale (mRS) was used to assess functional independence and disability.ResultsThe study included 294 stroke patients, out of 774, who were selected based on the inclusion and exclusion criteria. The mean age of the participants was 68.2 ± 13.4 years, and 49.3% were male. The patients’ distribution among the three groups based on their vitamin D levels is: normal (n = 35, 11.9%), insufficient (n = 66, 22.5%), and deficient (n = 196, 65.6%). After adjusting for potential covariates, regression analysis found a significant inverse relationship of NIHSS based on 25(OH)D serum level (beta coefficient: −0.04, SE: 0.01, p = 0.003). Patients with deficient serum vitamin D level also had significantly higher odds of worse functional independence in mRS score [OR: 2.41, 95%CI: (1.13–5.16), p = 0.023] when compared to participants with normal vitamin D level.ConclusionLow vitamin D levels were associated with higher severity of stroke at admission and poor functional independence and disability at discharge in patients with acute ischemic stroke. Further randomized clinical and interventional studies are required to confirm our findings

Channel Estimation for LTE downlink

In LTE system, supporting high mobile user speed is one of the key of requirements. However, the channel variation in different mobility scenarios is a significant challenge to achieving this goal. The channel estimation is required at the receiver part to satisfy the good performance with channel variation. In this master thesis, I use the different estimators to estimate the channel at the LTE Downlink system with different scenarios. The LS block fading estimator use at low mobility where the channel is statistic during one subframe. When the user speed more than 20 km/h the LS block estimation degrade in MSE and throughput performance. The LS fast fading outperforms the LS block fading at the velocity more than 25 km/h. LS estimation can be simply implemented with low computational complexity, however the MSE performance is not satisfactory at the high mobility. The LMMSE method is optimum in minimizing the MSE of the channel estimates and in throughput performance.However, the algorithm contains matrix inverse operation and other complex operations which causes high computational complexity. To compatible between these different estimators with good performance and low complexity, the proposed method is used. This method combines three different type channel estimations which is termed Hybrid Linear Mean Square Error ( HLMSE). This proposed estimator is a hybrid of the Least Square (LS) estimator block for low mobility , LS fast fading estimator for moderate mobility and Linear Minimum Mean Square Error (LMMSE) estimator for high mobility. The performance of the HLMSE estimator compared with LS in terms of throughput and Mean Square Error(MSE) outperforms the LS in both throughput and MSE. The complexity of the HLMSE can be controlled by channel variation, which depends on mobility

An observational mechanism for detection of distributed denial-of-service attacks

<p>This study proposes a continuous mechanism for detecting distributed denial of service (DDoS) attacks from network traffic data. The mechanism aims to systematically organise traffic data and prepare them for DDoS attack detection using convolutional deep-learning neural networks. The proposed mechanism contains ten phases covering activities, including data preprocessing, feature selection, data labelling, model building, model evaluation, DDoS detection, attack pattern identification, alert creation, notification delivery, and periodical data sampling. The evaluation results suggested that the detection model built based on convolutional deep-learning neural networks and relevant network traffic features provided 97.2% detection accuracy. The study designed a holistic mechanism that considers the systematic network traffic data management for continuous monitoring and good performance of DDoS attack detection. The proposed mechanism could provide a solution for network traffic data management and enhance the existing methods for DDoS attack detection. In addition, it generally contributes to the cybersecurity body of knowledge.</p&gt