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The goal of this research was to develop a site-targeting nanotherapeutic drug delivery platform for suppression of chronic vascular inflammation and regression associated with debilitating conditions such as pulmonary arterial hypertension (PAH) and diabetic retinopathy (DR). Importantly, loss of endothelium-derived nitric oxide (NO), an endogenous anti-inflammatory and pro-vasculogenic factor that prevents leukocyte-endothelial cell (EC) adhesion and capillary regression, is strongly implicated in chronic inflammation associated with these conditions. Thus, restoring NO levels represents a viable approach for anti-inflammatory therapies. Nitroglycerin (NTG) markedly enhances nitric oxide (NO) bioavailability. However, its ability to mimic the anti-inflammatory and pro-vasculogenic properties of NO remains unknown. Here, the overarching goal was to examine whether (1) NTG can suppress vascular inflammation and regression, (2) a nanotechnological drug delivery approach can be leveraged to simultaneously amplify its anti-inflammatory effects and ameliorate adverse effects associated with conventional high-dose NTG administration, and finally (3) NTG nanoformulation can be modified to selectively deliver NTG to inflamed ICAM-1-expressing vessels. My findings reveal that NTG significantly inhibits monocyte adhesion to inflamed ECs and prevents EC capillary regression in vitro through an increase in endothelial NO and decrease in endothelial ICAM-1 clustering. More importantly, nanoliposomal NTG (NTG-NL) produced an approximately 70-fold increase in NTG drug efficacy when compared with free NTG while preventing excessive mitochondrial superoxide production and loss of arterial vasorelaxation associated with high NTG doses. Finally, to facilitate targeting of NTG-NL to inflamed ICAM-1-expressing vessels, whole ICAM-1 IgG and non-immunogenic anti-ICAM-1 scFv fragment were tethered to the surface of NTG-NL. As a proof-of-concept study whole ICAM-1 IgG-modified NLs demonstrated preferential targeting to inflamed vessel, in vivo. Importantly, however, the translational potential of these NLs lies with the non-immunogenic scFv fragment. The following in vitro studies reveal that NTG-NL modified with anti-ICAM-1 scFv exhibits 6-fold greater binding to inflamed (ICAM-1-expressing) ECs than to normal ECs and achieves superior anti-inflammatory effects. Thus, these findings provide the rationale to examine this novel site-targeting NTG nanotherapeutic as a potentially superior therapy for various vascular inflammation-mediated conditions. Addressing these critical issues related to potential NTG-based therapy forms the central theme of the following dissertation.

Security of information passing through the Internet is threatened by today’s most advanced malware ranging from orchestrated botnets to simpler polymorphic worms. These threats, as examples of zero-day attacks, are able to change their behavior several times in the early phases of their existence to bypass the network intrusion detection systems (NIDS). In fact, even well-designed, and frequently-updated signature-based NIDS cannot detect the zero-day treats due to the lack of an adequate signature database, adaptive to intelligent attacks on the Internet. More importantly, having an NIDS, it should be tested on malicious traffic dataset that not only represents known attacks, but also can to some extent reflect the characteristics of unknown, zero-day attacks. Generating such traffic is identified in the literature as one of the main obstacles for evaluating the effectiveness of NIDS. To address these issues, we introduce RNNIDS that applies Recurrent Neural Networks (RNNs) to find complex patterns in attacks and generate similar ones. In this regard, for the first time, we demonstrate that RNNs are helpful to generate new, unseen mutants of attacks as well as synthetic signatures from the most advanced malware to improve the intrusion detection rate. Besides, to further enhance the design of an NIDS, RNNs can be employed to generate malicious datasets containing, e.g., unseen mutants of a malware. To evaluate the feasibility of our approaches, we conduct extensive experiments by incorporating publicly available datasets, where we show a considerable improvement in the detection rate of an off-the-shelf NIDS (up to 16.67%).

Background: Providing care to a disable relative at home exposes the caregiver to a potentially higher risk of physical and mental problems. We measured health-related quality of life (HRQOL) and its determinants among the caregivers of the Iranian survivors of the Iran-Iraq war (1980–1988) with bilateral lower-limb amputation. Methods: Data were collected from 464 individuals comprising war-related bilateral lower-limb amputees (n=232) and their caregivers (n=232) in January 2015 in Shiraz, Iran. The 36-Item Short-Form Health Survey (SF-36) questionnaire was used to evaluate the caregivers’ QOL. Logistic regression analysis was performed to determine the most significant contributing factors. Results: The mean age of the caregivers and the amputees was 39.4±6.2 and 42.5±6.2 years, respectively. The mean duration of disability was 22.8±3.9 years in the amputees. Most of the caregivers were reported to be in their first marriage. The highest and lowest mean scores of the SF-36 domains in the sample population were observed for physical function (76.65±21.97) and bodily pain (53.54±24.95). QOL in the caregivers was significantly lower than that in a sample of the general Iranian female population (P

The Discovery of Helicobacter pylori in 1982 increased interest in the range of other spiral bacteria that had been seen in Stomach.The power of technologies such as the polymerase chain reaction (PCR) with genus specific primers revealed that many of these bacteria belong to the genus Helicobacter. These non-pylori helicobacters are increasingly being found in human clinical specimens. Non-pylori Helicobacters are Gram-negative, motile, long, tightly coiled, Spiral bacteria ,with three to eight coils, that cause of some gastric problems like gastritis, peptic ulceration and Mcosa-Associated Lymphoid Tissue (MALT) lynphoma in animals and humans. Samples taken during endoscopy were analyzed by rapid urease test, PCR and light microscope(Giemsa and Gram staining). In this study 810 biopsy samples from 270 patients with gastric disorders were collected. Presence of Helicobacters confirmed by a positive urease test and Helicobacter genus specific PCR method utilized. DNA was prepared from biopsies using the Qiamp tissue kit (QIAGEN Inc., Valencia, Calif.) and frozen at -20°C (like gastric samples/biopsies). DNA samples were amplified with 16SrRNA gene primers against Helicobacter species. In gastric biopsy specimen's non-pylori helicobacter spp., have been observed. At the end of the study we found that 71% of urease tests, 0.37% of light microscopic studies (we observed some spiral gram negative bacteria with 2-7 coils) and 0.74% of PCR tests were positive. In analysis with PCR route 2 person (both of them were Male) were infected with H.heilmannii-like organisms( one of them kept a dog for 5 years as a pet).16S rRNA gene amplification was performed on 270 DNA samples and results were positive for H.heilmannii in two cases (275-bp), but negative for H.bizzozeronnii,H.felis and H. Salmonis