11 resultados para barrier integrity
em Digital Commons at Florida International University
Resumo:
Professional standards of ethics proclaim the core values of a profession, describe expected professional duties and responsibilities, and provide a framework for ethical practice and ethical decision-making. The purpose of this mixed, quantitative and qualitative, survey study was to examine HRD professionals' perceptions about the AHRD Standards on Ethics and Integrity, how HRD professionals used the Standards for research and decision-making, and the extent to which the Standards provided guidance for ethical decision-making. Through an on-line survey instrument, 182 members of AHRD were surveyed. The open-ended questions were analyzed using thematic analysis to expand on, inform, and support the quantitative findings. The close-ended questions were analyzed with frequency distributions, descriptive statistics, cross tabulations, and Spearman rank correlations. The results showed a significant relationship between (a) years of AHRD membership and level of familiarity with the Standards, (b) years of AHRD membership and use of the Standards for research, and (c) level of familiarity with the Standards and use of the Standards for research. There were no significant differences among scholars, scholar practitioners, practitioners, and students regarding their perceptions about the Standards. The results showed that the Standards were not well known or widely used. Nevertheless, the results indicated overall positive perceptions about the Standards. Seventy percent agreed that the Standards provided an appropriate set of ethical principles and reflected respondents' own standards of conduct. Seventy-eight percent believed that the Standards were important for defining HRD as a profession and 54% believed they were important for developing a sense of belonging to the HRD profession. Fifty-one percent believed the Standards should be enforceable and 61% agreed members should sign the membership application form showing willingness to adhere to the Standards. Seventy-seven percent based work-related ethical decisions on personal beliefs of right and wrong and 56% on established professional values and rules of right and wrong. The findings imply that if the professional standards of ethics are to influence the profession, they should be widely publicized and discussed among members, they should have some binding power, and their use should be encouraged.
Resumo:
This dissertation evaluated the feasibility of using commercially available immortalized cell lines in building a tissue engineered in vitro blood-brain barrier (BBB) co-culture model for preliminary drug development studies. Mouse endothelial cell line and rat astrocyte cell lines purchased from American Type Culture Collections (ATCC) were the building blocks of the co-culture model. An astrocyte derived acellular extracellular matrix (aECM) was introduced in the co-culture model to provide a novel in vitro biomimetic basement membrane for the endothelial cells to form endothelial tight junctions. Trans-endothelial electrical resistance (TEER) and solute mass transport studies were engaged to quantitatively evaluate the tight junction formation on the in-vitro BBB models. Immuno-fluorescence microscopy and Western Blot analysis were used to qualitatively verify the in vitro expression of occludin, one of the earliest discovered tight junction proteins. Experimental data from a total of 12 experiments conclusively showed that the novel BBB in vitro co-culture model with the astrocyte derived aECM (CO+aECM) was promising in terms of establishing tight junction formation represented by TEER values, transport profiles and tight junction protein expression when compared with traditional co-culture (CO) model setups and endothelial cells cultured alone. Experimental data were also found to be comparable with several existing in vitro BBB models built from various methods. In vitro colorimetric sulforhodamine B (SRB) assay revealed that the co-cultured samples with aECM resulted in less cell loss on the basal sides of the insert membranes than that from traditional co-culture samples. The novel tissue engineering approach using immortalized cell lines with the addition of aECM was proven to be a relevant alternative to the traditional BBB in vitro modeling.
Resumo:
The paper examines the nature of qualitative empirical studies published in the AHRD proceedings from 1999-2003 and discusses findings on method, rationale for method, data collection, sampling strategies, and integrity measures.
Resumo:
Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effectivein-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.
Resumo:
Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.
Resumo:
Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.
Resumo:
In this research the integration of nanostructures and micro-scale devices was investigated using silica nanowires to develop a simple yet robust nanomanufacturing technique for improving the detection parameters of chemical and biological sensors. This has been achieved with the use of a dielectric barrier layer, to restrict nanowire growth to site-specific locations which has removed the need for post growth processing, by making it possible to place nanostructures on pre-pattern substrates. Nanowires were synthesized using the Vapor-Liquid-Solid growth method. Process parameters (temperature and time) and manufacturing aspects (structural integrity and biocompatibility) were investigated. Silica nanowires were observed experimentally to determine how their physical and chemical properties could be tuned for integration into existing sensing structures. Growth kinetic experiments performed using gold and palladium catalysts at 1050°C for 60 minutes in an open-tube furnace yielded dense and consistent silica nanowire growth. This consistent growth led to the development of growth model fitting, through use of the Maximum Likelihood Estimation (MLE) and Bayesian hierarchical modeling. Transmission electron microscopy studies revealed the nanowires to be amorphous and X-ray diffraction confirmed the composition to be SiO2 . Silica nanowires were monitored in epithelial breast cancer media using Impedance spectroscopy, to test biocompatibility, due to potential in vivo use as a diagnostic aid. It was found that palladium catalyzed silica nanowires were toxic to breast cancer cells, however, nanowires were inert at 1μg/mL concentrations. Additionally a method for direct nanowire integration was developed that allowed for silica nanowires to be grown directly into interdigitated sensing structures. This technique eliminates the need for physical nanowire transfer thus preserving nanowire structure and performance integrity and further reduces fabrication cost. Successful nanowire integration was physically verified using Scanning electron microscopy and confirmed electrically using Electrochemical Impedance Spectroscopy of immobilized Prostate Specific Antigens (PSA). The experiments performed above serve as a guideline to addressing the metallurgic challenges in nanoscale integration of materials with varying composition and to understanding the effects of nanomaterials on biological structures that come in contact with the human body.
Resumo:
The present study measures the increase in serum carotenoid concentration in 30 healthy individuals after supplementation with a low dose xanthophyll ester (3 and 6 mg of lutein equivalent/per day) when compared to a placebo. Serum levels of carotenoids were measured using HPLC and showed an increase in the concentration of lutein, zeaxanthin and four lutein metabolites proportional to dose. In order to further assess the importance of the end-group structure in carotenoids we have investigated the influence of the end-group type and functionality on the conformational energy barrier. We used the density functional method implemented on GAUSSIAN 98 to calculate the conformational energy curves for rotation of the P-ring or the E-ring relative to short polyene chains around the C6-C7 single bond. A large barrier is observed for the interconversion of conformers in the E-rings (8 kcal/mol) when compared to beta rings (2.3-3 kcal/mol).
Resumo:
Kernel-level malware is one of the most dangerous threats to the security of users on the Internet, so there is an urgent need for its detection. The most popular detection approach is misuse-based detection. However, it cannot catch up with today's advanced malware that increasingly apply polymorphism and obfuscation. In this thesis, we present our integrity-based detection for kernel-level malware, which does not rely on the specific features of malware. ^ We have developed an integrity analysis system that can derive and monitor integrity properties for commodity operating systems kernels. In our system, we focus on two classes of integrity properties: data invariants and integrity of Kernel Queue (KQ) requests. ^ We adopt static analysis for data invariant detection and overcome several technical challenges: field-sensitivity, array-sensitivity, and pointer analysis. We identify data invariants that are critical to system runtime integrity from Linux kernel 2.4.32 and Windows Research Kernel (WRK) with very low false positive rate and very low false negative rate. We then develop an Invariant Monitor to guard these data invariants against real-world malware. In our experiment, we are able to use Invariant Monitor to detect ten real-world Linux rootkits and nine real-world Windows malware and one synthetic Windows malware. ^ We leverage static and dynamic analysis of kernel and device drivers to learn the legitimate KQ requests. Based on the learned KQ requests, we build KQguard to protect KQs. At runtime, KQguard rejects all the unknown KQ requests that cannot be validated. We apply KQguard on WRK and Linux kernel, and extensive experimental evaluation shows that KQguard is efficient (up to 5.6% overhead) and effective (capable of achieving zero false positives against representative benign workloads after appropriate training and very low false negatives against 125 real-world malware and nine synthetic attacks). ^ In our system, Invariant Monitor and KQguard cooperate together to protect data invariants and KQs in the target kernel. By monitoring these integrity properties, we can detect malware by its violation of these integrity properties during execution.^
Resumo:
The impact of ultrasound on improving the performance of a granular iron Permeable Reactive Barrier (PRB) in the degradation of Trichloroethylene (TCE) was evaluated. Two treatment columns made of clear Plexiglas with a height of 1ft and a diameter of 2 inches and filled with granular iron were used. One was fitted with 25Khz ultrasound probes. A solution of TCE was run through at constant flow rate. Samples obtained from the column at different residence times before and after sonication were analyzed for concentrations of TCE and used to generate concentration profiles to obtain rate constants, which were compared. An improvement of 23.4% in the reaction rate of TCE degradation was observed after sonication of the iron media suggesting that ultrasound may contribute to improving the performance of PRBs in the degradation of TCE in contaminated groundwater.
Resumo:
Kernel-level malware is one of the most dangerous threats to the security of users on the Internet, so there is an urgent need for its detection. The most popular detection approach is misuse-based detection. However, it cannot catch up with today's advanced malware that increasingly apply polymorphism and obfuscation. In this thesis, we present our integrity-based detection for kernel-level malware, which does not rely on the specific features of malware. We have developed an integrity analysis system that can derive and monitor integrity properties for commodity operating systems kernels. In our system, we focus on two classes of integrity properties: data invariants and integrity of Kernel Queue (KQ) requests. We adopt static analysis for data invariant detection and overcome several technical challenges: field-sensitivity, array-sensitivity, and pointer analysis. We identify data invariants that are critical to system runtime integrity from Linux kernel 2.4.32 and Windows Research Kernel (WRK) with very low false positive rate and very low false negative rate. We then develop an Invariant Monitor to guard these data invariants against real-world malware. In our experiment, we are able to use Invariant Monitor to detect ten real-world Linux rootkits and nine real-world Windows malware and one synthetic Windows malware. We leverage static and dynamic analysis of kernel and device drivers to learn the legitimate KQ requests. Based on the learned KQ requests, we build KQguard to protect KQs. At runtime, KQguard rejects all the unknown KQ requests that cannot be validated. We apply KQguard on WRK and Linux kernel, and extensive experimental evaluation shows that KQguard is efficient (up to 5.6% overhead) and effective (capable of achieving zero false positives against representative benign workloads after appropriate training and very low false negatives against 125 real-world malware and nine synthetic attacks). In our system, Invariant Monitor and KQguard cooperate together to protect data invariants and KQs in the target kernel. By monitoring these integrity properties, we can detect malware by its violation of these integrity properties during execution.