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MOUSE MAMMARY TUMOR VIRUS (MMTV) GENOMIC RNA (gRNA) PACKAGING: SELECTIVE gRNA ENCAPSIDATION IS FACILITATED BY LONG-RANGE INTERACTIONS (LRIs) THAT FACILITATE SPECIFIC GAG BINDING
Get PDFMouse mammary tumor virus (MMTV) is a betaretrovirus that induces breast cancer and sporadically, T-cell lymphomas in mice. MMTV serves as a pertinent model for elucidating the mechanism(s) of oncogenesis and the genetics associated with the development of mammary tumors. Being a rodent retrovirus, MMTV is phylogenetically distant from human and other primate retroviruses; thus, positioning it ideally as a potential vector of choice for human gene therapy. This may circumvent safety concerns such as recombination with other related endogenous human retroviruses. In addition, MMTV is distinct from most other retroviruses, but similar to lentiviruses, in that it has the ability to infect non-dividing cells. Furthermore, MMTV contains multiple steroid responsive promoters, making it not only “switchable” but also “tissue-specific” since they turn on gene expression only in cells with receptors for steroid hormones. These unique features have led to increasing interest in developing MMTV-based vectors for “targeted” and “inducible” human gene therapy, especially for breast tissue. Therefore, it is crucial that the molecular mechanisms of the pertinent aspects of MMTV life cycle be better understood to develop safer, more efficient vectors for gene delivery.Earlier studies have suggested that MMTV harbors sequences known as Packaging Sequences (Psi) responsible for genomic RNA (gRNA) packaging at the 5’ end of its genome. This region has been predicted to assume a higher order structure which was validated biochemically employing hSHAPE (high throughput selective 2\u27 hydroxyl acylation analyzed by primer extension) and shown to have four RNA-RNA long range interactions (LRIs) harboring complementary sequences. Three of these LRIs involve complementary sequences between the U5/Gag (LRIs I-III), while one LRI (LRI-IV) involves complementary sequences within U5/U5 region that are 291 and 190 nucleotides apart, respectively.In addition to Psi, the packaging of gRNA into retroviral particles relies on its specific recognition by the Gag precursor. However, it remains unclear whether the binding of Gag to Psi alone is enough to promote RNA packaging and what role LRIs play in this process. In this study, using MMTV as a model, we investigated the effects of mutations in the four proposed LRIs on the gRNA structure and function. Our findings reveal the presence of an unpredicted extended LRI, and hSHAPE showed that maintaining a Psi structure like the wild type is crucial for efficient RNA packaging. Surprisingly, filter binding assays demonstrated that most mutants, regardless of their packaging capability, exhibited significant binding to Pr77Gag, suggesting that Gag binding to Psi is insufficient for efficient packaging. Further footprinting experiments indicated that efficient RNA packaging is promoted when Pr77 Gag binds to two specific sites within Psi, whereas binding elsewhere in Psi does not lead to efficient packaging. Taken together, these results reveal that the three-dimensional structure of the Psi/Pr77 Gag complex regulates the assembly of viral particles around gRNA, enabling effective discrimination against other viral and cellular RNA species that may also bind Gag efficiently
TACKLING TOXICITY AND HARASSMENT IN ONLINE ENVIRONMENTS THROUGH THE USE OF ARTIFICIAL INTELLIGENCE
Get PDFWith the increase in popularity of online communities, such as social media platforms, online games, and chatroom servers, there is a need to improve chat and content moderation. Platforms have reported an increase in the prevalence of toxic behavior and hate speech. Meanwhile, moderators are reporting difficulties in keeping up with the amount of data to check as well and the type of content they are exposed to, which further harms their own mental health. The main objective of this work is to address the challenges that exist within online communities with the rising prevalence of hate speech. Additionally, some of the burden of reviewing incidents and applying accountability will be lifted off any human moderators. Leveraging the evolution of Large Language Models (LLMs), a Natural Language Processing (NLP)-based solution is prototyped that would monitor chat messages passing through a server and classifying them according to their content. To do this, several LLMs are selected based on the reviewed literature and tested against a dataset containing chat messages sourced from various platforms. The LLM that “behaved” the best is selected to run on a simulated chat server to monitor chat messages and maintain a record of classifications. The results of training and validation showed that DistilBERT performed the best, achieving an accuracy of 95% for binary classification and 75% for six-category classification. After embedding the model into a simulated chatroom’s server and testing it against 1,100 data entries, the binary and six-category accuracies achieved were 98% and 79%, respectively. After retraining, the binary model achieved 98% accuracy with familiar data and 90% for completely new data, while the six-category model achieved 84%. With these results, leveraging LLMs for content moderation shows promise, as presented by the prototype moderator presented in this work. With further optimization and more data, the performance of the model will improve according to the environment it is monitoring
IN VITRO INVESTIGATION OF THE POTENTIAL THERAPEUTIC IMPLICATIONS OF SAFRANAL ON GASTRIC CANCER
Get PDFDespite the fact that gastric cancer patients are indispensable to conventional radiation and chemotherapy, the detrimental side effects of those approaches prompt cancer research to seek new integrative treatments. In this respect, safranal (SAF) stands out as a complementary phytotherapeutic drug with exceptional anticancer properties. Concurring studies have shown that SAF is negatively associated with several cancer types, yet its potential therapeutic impact on gastric cancer remains vastly obscure. Thus, this dissertation sought to investigate SAF\u27s prospective tumoricidal ability and its underlying mechanisms of action on gastric cancer in vitro. Herein, the study evaluated the cytotoxicity of SAF on human adenocarcinoma cell lines (AGS and NCI-N87), focusing on the drug inhibitory activity against AGS migration, colonization, cell cycle, and apoptosis. The results revealed that SAF significantly reduced the viability of both cell lines, disrupting their sustained proliferation and survival ability. Significantly, SAF caused cytological changes in AGS cells by inducing vacuolation and senescence-like morphologies. In addition, treatment with SAF impaired the migration and restricted colonization abilities in AGS cells, eliminating their metastatic movement. Simultaneously, SAF hindered the cell cycle progression by forcing a cycle arrest in the mitotic phase, terminating AGS\u27s sustained proliferative life span. In parallel, treatment with SAF triggered the apoptotic machinery and its associated signal transduction pathways in AGS cells. This study compellingly confirms the efficacy of SAF as a potential anticancer compound and further supports its pharmaceutical application in cancer treatment in the battle against gastric malignancy
TOPOLOGICAL INDICES AND THEIR APPLICATIONS IN DESIGNING DRUGS
Get PDFThis research delves into the use of indices, in the field of drug design with a specific focus on anticancer medications. Topological indices, values derived from representations of chemical structures provide meaningful connections to the physical and chemical characteristics of molecules. These Indices act as tools for predicting behavior playing a vital role in crafting therapeutic drugs. The study primarily delves into topological indices like the Sombor index, Randi´c index, and Atom Bond Connectivity (ABC) index, which are calculated for structures and their relationships with physical properties such as molar volume, refractive index, and flash point are explored using statistical methods like linear regression and correlation analysis. Noteworthy discoveries from this investigation reveal that topological indices can accurately forecast the properties of anticancer medications assisting in optimizing their structures for improved therapeutic e!ectiveness. The thesis not only emphasizes the aspects of these indices but also showcases their practical utility in pharmaceutical sciences by o!ering fresh insights into drug molecule design and analysis. In summary, this research adds to the realm of chemistry by presenting an in-depth examination of how topological indices can be leveraged to predict and control the physicochemical attributes of chemical compounds, for targeted drug development
THE CRIME OF INDECENT ASSAULT IN UAE LAW
Get PDFThe crime of indecent assault is considered one of the serious offenses condemned by UAE law due to its violation of human dignity and ethical and social values. This research focuses on the evolution of legal texts related to this crime, particularly the changes introduced in Federal Decree-Law No. 31 of 2021 concerning crimes and punishments, compared to the UAE Penal Code of 1987. The research also addresses the amendments made to the rules governing this crime, such as raising the age of the victim from 14 to 18 years and abolishing the crime of indecent assault with consent in certain cases .The study highlights that any contact or extension towards the victim’s private areas is considered an indecent assault under the law. It also points out that the degree of breach of modesty plays a crucial role in determining the occurrence and punishment of the crime. Furthermore, the study explores the judicial rulings related to this crime and how they have evolved to align with the social and cultural changes in the UAE. Among the key findings is that indecent assault through surprise, deceit, or trickery occurs only when the victim does not consent to the continuation of the acts against them. The concept of modesty varies across different societal groups, social environments, and values embraced by individuals within the same society. The study recommends that the UAE judiciary should not attribute consent to indecent assault cases falling under the first paragraph of Article 407. It also suggests that the UAE legislator should classify domestic workers as victims of indecent assault under the categories exempt from consent in the second paragraph of Article 407, as they are entrusted to their employers
QUANTUM MARKOV CHAINS RELATED TO CERTAIN LATTICE MODELS
Get PDFA central open problem in quantum field theory is the construction of a general theory of quantum field, this thesis introduces quantum probability and applies it via the construction of quantum Markov chains on different hierarchical lattices (Cayley trees). Furthermore, these trees correspond to the Ising-XY-Model which then the existence of a unique Markov chain can be utilized to detect phase transitions
UTILIZING HYPERSPECTRAL REMOTE SENSING FOR SALINE SOIL ASSESSMENT IN THE EMIRATE OF ABU DHABI, UNITED ARAB EMIRATES
Get PDFThis study presents the application of hyperspectral remote sensing techniques to measure soil salinity. Soil salinity is a major concern in many arid and semi-arid regions, affecting crop productivity and ecosystem health. In most arid and semi-arid areas various levels of salinity can be encountered including sabkhas. Sabkha (salt flat) is a geological feature composed of saline and salt marshes that typically occur in shallow or coastal environments within arid and semi-arid climates. Traditional methods of measuring soil salinity are time-consuming and labor-intensive, making remote sensing techniques an attractive alternative. This study employed a hyperspectral sensor specifically the SVC-XHR-1024i to collect reflectance data over the western region of Abu Dhabi Emirate, a semi-arid area distinguished by scattered sabkhas. Most previous studies have used broad-band multi-spectral data while this study focuses on the use of hyperspectral remote sensing data which is believed to produce better accuracy results. The collected data were then processed to derive spectral indices that are sensitive to soil salinity. Ground truthing was conducted through field sampling and laboratory analysis of soil samples. Laboratory measurements of Electrical Conductivity (EC) of soil water extracts were carried out. The study established a statistical relationship between the EC salinity measurements of the field soil samples and their corresponding spectral reflectance. The study used published spectral salinity indices such as the Near-Shortwave Infrared (NSI), Shortwave Infrared (SWIR), Near-Infrared (NIR), and Visible (VIS) to model salinity levels. The study findings indicate that the NSI-based model has superior predictive capacity for saline soils compared to the SWIR model, with the NIR-SWIR spectral range being optimal for accurate salinity mapping. Specifically, the NSI model demonstrated 71% accuracy as a result of this research. The study highlights the potential of hyperspectral remote sensing as a cost-effective and efficient tool for monitoring soil salinity and identifying areas at risk of salinization, which can inform land management strategies for sustainable agriculture and future land development
DEVELOPING A NEW METHOD FOR BRINE PURIFICATION AND REDUCING SALINITY USING RECYCLED CARBON FIBER
Get PDFBrine water, defined as hot and high salt content water, can be produced in large amounts from water desalination. The potential environmental impacts of brine disposal were evaluated in several studies. Minor variations in water salinity and temperature can significantly influence marine ecosystems. Elevated salinity levels disrupt the osmotic equilibrium between aquatic organisms and their surroundings, which leads to cell dehydration. Various disposal techniques have been implemented recently, including surface water discharge, sewage discharge, deep-well injection, evaporation ponds, and land application. However, these brine disposal techniques are unviable due to their high capital costs and limited applicability. In recent years, carbon fibers have received significant interest because of their strength, high surface area, and ability to resist chemicals and corrosion. In 2022, global carbon fiber consumption will reach 194 kilotons; by 2025, an annual production of 20 kilotons of carbon fiber is expected. Consequently, there is a growing need for better and more effective recycling because of the rising demand for carbon fibers and the associated rise in plastic waste. Three leading technologies have been classified for recycling carbon fibers. Mechanical recycling involves shredding, crushing, or milling carbon fibers into small sizes. The second process is thermal recycling, which requires heat to break down the scrap composite and burn the resin matrix; the carbon fiber then can be recovered. The final recycling technique is chemical recycling; in this technique, chemical solvents must be used to degrade the resin. Usually, this approach results in a clean fiber with high mechanical properties. This research thesis presents a novel method for utilizing carbon fiber waste in rejected brine water desalination. The methodology includes thermally recycling carbon fiber waste, followed by chemical treatment with strong alkaline and acids, and then utilized to purify and treat the rejected brine water. Accordingly, the process focuses on carbon fiber waste utilization, reject brine treatment, and CO2 capture. However, the efficiency of treated carbon for brine treatment can be influenced by many factors, such as the concentration of salts and heavy metals in the brine, the surface area of the recycled carbon fiber, and the contact time. Therefore, it is essential to design the treatment system appropriately and optimize the conditions to achieve the desired level of salts and contaminant removal. As per the obtained findings, surface modification of the recycled fibers showed a significant increase in the surface roughness with the rise of the concentration of the alkaline or acid in the treatment, which can enhance the adsorption rate of brine salts on the surface of the recycled fibers. Furthermore, the lowest recovery percentage achieved was 13.1%, in which recycled carbon fibers were immersed in brine water for 4 hours. However, it increased and reached 92% recovery after reducing the treatment time and treating the surface of the recycled fiber with 3M sodium hydroxide. The presented research is a promising way to utilize waste carbon fiber for brine management and effectively capture CO2
HUMANITARIAN INTERVENTION IN INTERNATIONAL LAW
Get PDFHumanitarian intervention represents a complex and controversial strategy in international relations, with its declared aim being the protection of individuals from severe human rights abuses and humanitarian suffering, particularly in contexts of conflict and crises. Despite the good intentions that may motivate humanitarian interventions, they raise complex questions around sovereignty, ethical responsibility, and unintended consequences. This study explores the issue of whether intervention for the protection of human rights can be considered a legitimate necessity justified by legal grounds and examines the impact of such intervention on state sovereignty and international relations. The study concludes with several findings, most notably that there is a sharp doctrinal divide regarding the legitimacy of humanitarian intervention. This divide stems from the fact that humanitarian intervention has often been stripped of its essence, permitting its politicization and exploitation as a pretext for other purposes. The principle of the responsibility to protect is theoretically positive; however, its practical application has failed in various instances, leading to the emergence of an opposing principle: responsibility while protecting. The study presents several recommendations, including emphasizing that military intervention should not be the first resort, as peaceful conflict resolution mechanisms—such as negotiations, mediation, and humanitarian aid—must be strengthened. Military intervention should only be considered as a last resort after exhausting all other solutions. Additionally, it calls for strengthening the responsibility to protect principle by establishing effective mechanisms for its peaceful implementation and ensuring prompt and effective intervention when there is a genuine threat to human rights. The study also advocates for reforms in the United Nations structure, particularly the Security Council, on matters related to humanitarian intervention, taking into account paragraphs 10 and 11 of the letter dated November 9, 2011, from Brazil’s Permanent Representative to the Secretary-General. These recommendations offer logical and effective solutions for implementing the responsibility to protect
PERFORMANCE OF GEOPOLYMER CONCRETE INCORPORATING RECYCLED AGGREGATES AND GLASS FIBERS
Get PDFThis study aims to investigate the potential use of geopolymer concrete (GC) incorporating recycled concrete aggregates (RCA) and glass fibers (GF) as a sustainable alternative to traditional cement-based concrete. It comprehensively evaluated the impact of RCA and GF on the fresh, physical, mechanical, and durability properties. A blended precursor binder consisting of ground granulated blast furnace slag and fly ash was utilized. To mitigate the challenges associated with the brittle behavior and low crack resistance of GC, mainly when incorporating RCA, two types of GF were used. Type A had a length of 24 mm, while Type B exhibited a length of 45 mm, with a consistent diameter of 0.7 mm. The workability of produced mixes was evaluated using the slump cone test, while the mechanical performance was characterized by compressive strength, tensile strength, and flexural strength. Durability tests such as water absorption, sorptivity, abrasion resistance, ultrasonic pulse velocity, bulk resistivity, and resistance to hydrochloric acid attack were conducted to evaluate the long-term performance of the material and its potential behavior under harsh environmental conditions. Moreover, the shear behavior of GC beams made with RCA and GF was examined through full-scale experimental testing. The results highlighted that 100% RCA led to significant losses in compressive, tensile splitting, flexural, and shear properties. This trend of lowering mechanical properties was observed consistently across all the tested parameters, with each showing a decline as the RCA content increased. Nevertheless, GF incorporation into GC mixes countered the RCA-induced reductions in the mechanical performance to the extent of even exceeding the control mix made with natural aggregates (NA). Notably, the inclusion of GF in RCA-based GC, beyond 1 and 2%, not only offset the negative impacts associated with RCA but also restored literally 95 and 97% of the compressive strength, respectively, of a comparable plain mixture made with NA. This enhancement was consistently observed across all types of GF, highlighting their uniform effectiveness in improving overall characteristics of GC (e.g., compressive strength, tensile strength, modulus of elasticity, etc.). In fact, of the different combinations and volume fractions investigated, the hybrid mix made with both types of GF at a volume fraction of 1% yielded superior performance. Similar findings were noted for the durability of GC upon RCA replacement and GF incorporation. In turn, the full-scale concrete beam testing showed that GF improved the shear and deflection capacity to the extent of potentially replacing steel stirrups, especially with 1% volume fraction of Type B GF. For example, the shear strength improved by 15 and 19% upon the addition of 1 and 2% Type A GF, respectively. Meanwhile, the inclusion of Type B GF at a volume fraction of 0.5 and 1% resulted in 9 and 21% higher shear strength. Notably, the optimal GF-reinforced beam, composed solely of 1% Type B GF, exhibited a shear capacity that was approximately 80% of that achieved by an RCA-based beam reinforced with steel stirrups. The validity of published analytical models to predict the shear capacity of RCA-based GC beams, both with and without GF, was examined