Digital Commons Network^™

Effects Of Treatment On Melanoma With Checkpoint Inhibitor, Pembrolizumab (Keytruda ®), Anti-Cd47 Tti-621 (Trillium), And Anti-Sema4d Pepinemab Combination Treatment, Lauren E. Fitzgerald

Seton Hall University Dissertations and Theses (ETDs)

Traditionally, cancer therapies are generally non-specific treatments meant to eradicate cancer cells. This can result in death of healthy tissue, which can significantly affect the overall well-being of the patient during and after treatment. Immunotherapy offers a more targeted approach by using immune cells to specifically identify and kill cancer cells through various neoantigens presented on the surface of the cancer cell. Drugs that target and block PD-(L)1 and CTLA-4, known as checkpoint inhibitors, act to “cut the breaks” on the immune response and keep it actively seeking out and killing cancer cells. Many patients fail on these treatments due …

Detection, Identification, And Metagenomic Characterization Of Cyanobacteria In Barnegat Bay, New Jersey, Roksana M. Rahman

Seton Hall University Dissertations and Theses (ETDs)

Cyanobacterial harmful algal blooms (CHAB), caused by eutrophication, is known to threaten both wildlife and human health. Barnegat Bay, also home to Oyster Creek nuclear power plant, has experienced an elevated levels of nitrogen due to human activity such as recreational activity and urbanization. This has caused an increase of CHAB’s at a more frequent rate within Barnegat Bay. In order to detect possible CHAB causing cyanobacteria, water samples were collected from 12 different locations within Barnegat Bay. Each sample was filtered through a 30- and 0.4-mm polycarbonate filter sequentially. Chelex DNA extraction, polymerase chain reaction (PCR), and gel electrophoresis …

Development Of A Reliable Method To Express And Purify Vaccinia Virus Transcription Factors A7 And D6 In Bacteria, Younghoon Park

Seton Hall University Dissertations and Theses (ETDs)

Poxvirus early genes code for viral products involved in host interaction, immune evasion, replication, and transcription of the viral genome. These viral early genes contain a unique and conserved promoter sequence that is recognized by early transcription factors (ETFs). The working hypothesis is pharmacologically targeting the structure of the poxvirus early promoters can inhibit transcription of poxvirus early genes. Our group has identified unique secondary structure which deviates from a scrambled control near the Vaccinia Virus (VACV) E9L promoter. Targeting these unique structures, which most likely may be G-quadruplexes, with structure specific ligands may distort local DNA structures at the …

Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney

Seton Hall University Dissertations and Theses (ETDs)

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …

A Study Of Exposure To Polycyclic Aromatic Hydrocarbons And Polymorphisms In The Tumor Suppressor Gene, P53, Of Wild Menhaden, Samantha Rose Reed

Seton Hall University Dissertations and Theses (ETDs)

The British Petroleum (BP) Deep Water Horizon Oil spill in the Gulf of Mexico (GOM) caused detrimental effects to wildlife including marine fish populations (Diercks, et al. 2010). The fish were exposed to crude oil which contains polycyclic aromatic hydrocarbons (PAHs). Some PAHs are carcinogens and can damage DNA in key regulatory genes in various species (Milleman, et al. 2015; Nadler, 2017). Menhaden are oily, filter feeding fish and incorporate and retain these lipophilic contaminants at high levels. The objective of the present work was to search for genetic mutations on the tumor suppressor gene, p53, in various organs …

The Rational Design, Synthesis, Characterization, And Biological Evaluation Of Cancer-Targeting Immunostimulatory Peptide-Protein Conjugates And Tripeptides, Keith Smith

Seton Hall University Dissertations and Theses (ETDs)

With the advent of cancer immunotherapy and the rise in applications of synthetic biologics, there has been a steady decline in the incidence of cancer. Despite this trend, there is an anticipated 1.7 million new cancer cases with an estimated 610,000 deaths expected by the end of 2018.2 Therefore, the call for continued efforts in creating more effective treatment options are still in high demand. In this thesis, the rational design of a semi-synthetic cancer-targeting immunostimulatory peptide-protein bioconjugate—using N-succinimidyl carbamate chemistry is described. This bio-orthogonal chemistry approach was used to conjugate the synthetic Pep42, cancer-targeting peptide (CTP) and the immunostimulatory …

Fluorescently Labeled Sirnas And Their Theranostic Applications In Cancer Gene Therapy, Stephen David Kozuch

Seton Hall University Dissertations and Theses (ETDs)

Gene therapy has emerged as a promising precision nano-medicine strategy in the treatment of numerous diseases including cancer. At the forefront of its utility are the applications of short-interfering RNA (siRNA), that silence oncogenic mRNA expression leading to cancer cell death through the RNA interference (RNAi) pathway. Despite the therapeutic potential, siRNAs are limited by poor pharmacological properties, which has hindered their translation into the clinic. Recent studies, however, have highlighted the applications of modified siRNAs, including the use of fluorescent probes and siRNA nanostructures in cancer detection and treatment. The siRNAs reported in this thesis are designed to target …

The Effects Of Cold Plasma Treatment On Sweet Basil (Ocimum Basilicum), Sauvelson Auguste

Seton Hall University Dissertations and Theses (ETDs)

The study discussed herein looks both to continue and to expand upon previous work conducted here at Seton Hall University, which investigated the effect of cold plasma processing on sweet basil and their essential oils. It was found that the application of cold plasma treatment increases plant growth and eugenol concentration, which is an essential oil component and one of the potential natural antioxidants used in food preservation. In this study, we considered methods for increasing the production and harvesting of plants that produce essential oils such as sweet basil (Ocimum basilicum). The study also incorporated more controls …

The Molluscum Contagiosum Virus Mc160 Protein Requires Both Death Effector Domains To Inhibit Mavs- And Tbk1-Induced Interferon Activation, Lissette Bouza

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum Contagiosum Virus (MCV) causes a common persistent, skin infection. Two MCV immune evasion molecules, MCV MC159 and MC160 contain tandem death effector domains (DEDs). DEDs are found in several host proteins including pro-apoptotic proteins Fas-associated Death Domain (FADD) and procaspase-8 and are well characterized in innate immune signaling. MC159 blocks apoptosis induced by both Tumor Necrosis Factor (TNF) and the Fas ligand (FasL) and inhibits activation the host pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (Shisler, 2001; Murao and Shisler 2005). MC160, however, does not inhibit apoptosis, but does dampen TNF-induced NF-κB activation (Shisler, …

Cyclic Urethane: A Versatile Handle For Synthetic Peptide Applications, Hader E. Elashal

Seton Hall University Dissertations and Theses (ETDs)

While peptides have impeccable potential due to their biological and therapeutic abilities, they are inherently limited in clinical practice due to their instability towards proteolysis and poor bioavailability. In the past few years peptidomimetics have emerged as a powerful class of compounds that overcomes the shortcomings associated with peptides. Peptidomimetics essentially mimic a natural peptide or protein in its chemical composition, structure and its ability to perform a biologically relevant role. In addition to increased stability and bioavailability, peptidomimetics can also have increased receptor binding affinity and selectivity, thereby making these mimics lead compounds in the field of drug design …

Correlation Of Environmental Exposure To Polycyclic Aromatic Hydrocarbons And Polymorphisms In The Proto-Oncogene V-Rel Using Wild Atlantic Menhaden, Chelsea Rose Defelice

Seton Hall University Dissertations and Theses (ETDs)

Hurricane Sandy critically damaged the Atlantic coast of New Jersey in the fall of 2012. This was recorded as the largest storm to hit the Atlantic Ocean, which was manifested by its destruction on the homes and communities of those along the coastline. Contamination of surrounding waters due to this natural disaster was of great interest. The re-suspension of land-based pollution is proposed to make these contaminants more bioavailable to coastal species, such as Atlantic menhaden (Brevoortia tyrannus), which are a crucial biomonitoring species through their ecological and economic uses. A proposed increase of body burdens in Atlantic …

Hydraulic Fracturing Fluid Biocide, Tributyl Tetradecyl Phosphonium Chloride, Causes Mitochondrial Dysfunction That Is Enhanced By Sodium Chloride In Chironomus Riparius, Zainab Hussain Alali

Seton Hall University Dissertations and Theses (ETDs)

Tributyl tetradecyl phosphonium chloride (TTPC) is a biocide utilized in the hydraulic fracturing process to extract oil and natural gas from deep underground. This study used 4^th instar Chironomus riparius to investigate the toxicity of TTPC, NaCl, and TTPC+NaCl. Our results show that the 24 h LC₅₀s for TTPC, NaCl, and TTPC+NaCl were 0.57 mg/L, >10,000 mg/L, and 0.32 mg/L, respectively, while the 48 h LC₅₀s for the same treatments were 0.48 mg/L, 9808 mg/L, and 0.22 mg/L, respectively. Additionally, TTPC’s mechanism of action was investigated by measuring the levels of adenosine triphosphate (ATP), superoxide …

Assessing The Effects Of Dual Tasking On Spatiotemporal Parameters Of Gait In Older Adults: Exploring Age And Task Demands, Mohammed Issa Alsaeed

Seton Hall University Dissertations and Theses (ETDs)

The percentage of the senior citizens is expected to be 20% of the US population by 2030. Falls are considered a global problem due to the increased rate of falls and the costs associated with treating impairments resulting from falls. To date, the effects of performing different types of dual tasks among different age groups of the elderly has received less attention. Therefore, this study sought to assess the impact on spatiotemporal parameters of gait when differing age groups of older adults performer dual tasks that require differing motor and cognitive demands.

Three standard measurements were used in this study: …

Effects Of Crude Oil On Tumor Suppressor P53 Polymorphisms In Laboratory-Exposed Atlantic Killifish, Fundulus Heteroclitus, Allison Margaret Nadler

Seton Hall University Dissertations and Theses (ETDs)

Polycyclic aromatic hydrocarbons (PAHs), constituents of crude oil, are implicated as a potent source of adverse toxicological effects on living organisms. To model the effects of PAHs in response to environmental oil spill disasters a species of killifish (Fundulus heteroclitus) was captured and exposed to crude oil in a laboratory-controlled setting. Over a period of 7 days, fish were dosed with crude oil by gavage, culled, and organs were harvested for analysis. Excitation-emission matrix spectroscopy (EEMS) of gall bladder tissue homogenates was used to verify exposure. Effects of PAHs on the p53 gene were evaluated as an indicator …

Mutational Analysis Of The Molluscum Contagiosum Virus Mc160 Protein, Henri Estanbouli

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum Contagiosum Virus (MCV), belongs to a family of large DNA viruses called Poxviridae. MCV causes a common skin infection resulting in benign neoplasms. 122 million cases of MC were reported in 2010. The virus is not primarily lethal, though fatalities have occurred due to secondary bacterial infections. Even with the high volume of reported cases, MCV is very much understudied, and its pathogenicity is not well understood. Thus, with that in mind, a more in-depth understanding of the MCV-host interactions is a priority. Presumably during infection, MCV utilizes immune evasion molecules to inhibit activation of the host pro-inflammatory …

Zinc Chloride Activates Phospho-Akt And Promotes Chondrocyte Maturation In The Atdc5 Chondrogenic Cell Line, Donya T. Burgess

Seton Hall University Dissertations and Theses (ETDs)

Fracture healing is characterized by inflammation, cartilage formation, bone deposition, and remodeling. Endochondral ossification is an important part of callus formation that relies on the maturation of chondrocytes. Early in their maturation these cells express collagen type II alpha 1 chain (COL2A1) and express collagen type X alpha 1 chain (COL10A1) as they mature further and become hypertrophic chondrocytes. Activation of the insulin pathway is considered a primary factor involved in the initiation of chondrogenesis and its progression during bone healing. Insulin mimetics like zinc chloride (ZnCl₂) have been shown to improve bone healing outcomes and enhance bone …

The Effects Of Palmitate On The Expression Of G-Protein Coupled Receptors And Glut Transporters In Neuro2a Cells, Brian Montoya

Seton Hall University Dissertations and Theses (ETDs)

Palmitate (PA) is a saturated fatty acid that has been reported to be elevated in individuals with metabolic syndromes. The effects of fatty acids on the expression of various fatty acid receptors on neuronal cells is unknown, as is the effects of fatty acids on GLUT transporters. In this study, Neuro-2a (N2a) cells were treated with either 300μM of bovine serum albumin (BSA) or 300μM of palmitate conjugated to BSA (PA) at various time points to determine the effect of palmitate on the expression of various fatty acid receptors and GLUT transporters. RNA isolation followed by RT-PCR with primers specific …

Effects Of Direction Time Constraints And Walking Speed On Turn Strategies And Gait Adaptations In Healthy Older And Young Adults, Dennis Torre

Seton Hall University Dissertations and Theses (ETDs)

Hip fractures can be life-threatening, debilitating, and costly. The odds for hip fracture increases from impact of sideways falls. While turning has been strongly associated with hip fracture & sideways falls, the distinction between the risks for walking-turns as opposed to low-velocity in-place turning is not clear. The present study sought to fill a gap as previous research had not compared walking-turn performance in young & healthy older adults at low-fall risk within the same study and response-conditions of speed interacting with direction-cue time constraints. Spatial-temporal variables representative of AP braking/propulsion (i.e. stride-length & speed) & ML stability (left/right H-H …

Development Of Markers For Embryonic Reproductive Competence In Assisted Reproduction, Xin Tao

Seton Hall University Dissertations and Theses (ETDs)

In humans, early embryo development is a complex process that consists of sequential events: oocyte maturation, fertilization, embryonic growth and implantation. Disruption of these highly regulated processes results in reproductive failure and infertility. This study characterizes and describes embryonic aneuploidy, mitochondrial content level and endometrial microbial environment related to reproductive competence, in particular instances in which failure results.

To examine the molecular underpinnings of mammalian gamete and early embryo chromosome segregation, we established a comprehensive chromosomal screening (CCS) method for mice poly bodies, oocytes and embryos by the application of whole genome amplification (WGA) and next generation sequencing (NGS). First, …

Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a condition of inadequate oxygen supply, which can induce cell death. Using human neuronal cells treated with a hypoxia memetic compound, desferoxamine (DFO), a hypoxic cell model system was created. Our lab reported previously that treatment with DFO resulted in the decrease of cell viability. However, there were still surviving neurons. The surviving cells did not exhibit significant morphological changes, as compared to the control cells, under confocal microscopy analysis using annexin-V-FLUOS and propidium iodide staining, indicating that they were not at apoptotic or necrotic stages. These surviving neurons, therefore, developed adaptive responses under hypoxic challenge. Several changes …

The Influence Of Age, Work Experience, Education Level, And Score On A Standardized Pre-Employment Competency Exam On The Outcome Of A Pre-Employment Polygraph Exam, David M. Torres

Seton Hall University Dissertations and Theses (ETDs)

This study examined the influence of age, work experience, education level, and score on a standardized pre-employment competency exam on the outcome of a pre-employment polygraph exam. Due to the strict selection requirements and competitive nature of sensitive government and public safety positions, organizations compete in the costly endeavor to hire qualified applicants efficiently and effectively. As these organizations fail to meet the required hiring levels, their responsibilities in public and national security cannot be carried out. This study was conducted in an effort to reduce the time and financial resources an organization must appropriate on applicants that cannot successfully …

Platelets Prime Hematopoietic-Vascular Niche To Drive Angiocrine-Mediated Liver Regeneration, Koji Shido

Seton Hall University Dissertations and Theses (ETDs)

A critical function for blood vessels is that they secrete paracrine factors necessary for development, homeostasis and repair of the rest of all organs. Among them, the liver is a highly vascular organ, and can undergo regeneration after injury. This liver regeneration process is governed by dynamic interplay between hepatocytes and non-parenchymal cells, liver sinusoidal endothelial cells (LSECs). However, how factors produced from LSECs triggered by injury remains to be defined. Following mouse in vivo liver injury model, activated platelets deploy stromal cell-derived factor 1 and vascular endothelial growth factor A to stimulate CXCR7+ LSECs, orchestrating hepatic regeneration. Upon injection …

Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero

Seton Hall University Dissertations and Theses (ETDs)

Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.

The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and thus the patients have to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

B7h6: A Cancer Biomarker For The Development Of Novel Immunotherapy Approaches, Mariana Phillips

Seton Hall University Dissertations and Theses (ETDs)

Cancer-based immunotherapy has led the evolution of biologics that can stimulate immune responses towards tumor eradication. The synthesis of small to intermediate size molecules with the targeting and effector functions of mAb may represent a novel class of immunotherapeutics that may overcome the limitations of their biological counterparts.Towards this objective, B7H6 has been identified as a protein ligand localized on the cell surface of transformed tumor cells. B7H6 binds specifically to the activating receptor NKp30, constitutively expressed on all resting and active NK cells. Upon ligand:receptor binding, B7H6 triggers NK cell activation and release of chemokines and pro-inflammatory cytokines such …

Characterization Of Zinc And Cadmium Stress Response In Cyanobacterium Synechococcus Sp. Iu 625, Robert Newby Jr

Seton Hall University Dissertations and Theses (ETDs)

The way that cyanobacteria process and interact with heavy metals is an important part of their physiology. Metals like zinc play a role in many essential cell processes; while metals such as cadmium appear to be universally toxic. Little is known about how these metals play a role in the harmful overgrowth of cyanobacteria called blooms. While individual mechanisms have been elucidated, a complete response for metals in cyanobacteria has not yet been proposed. To establish a proposed mechanism of response in cyanobacteria, work was undertaken studying the response to zinc and cadmium in Synechococcus sp. IU 625 (S. IU …

Comparative Evaluation Of The Antibacterial, Anti-Biofilm And Anti-Spore Effects Of Theaflavins And Palmitoyl-Egcg, Gabriella M. Appice

Seton Hall University Dissertations and Theses (ETDs)

Tea, one of the most common beverages, originates from the leaves of the Camellia sinensis plant. Two major groups of tea are fermented black tea and unfermented green tea. Theaflavins (TFs) are the major polyphenols present in black tea, while mono-palmitoyl-epigallocatechin-gallate (pEGCG) is a modified green tea polyphenol. In this study, the antibacterial effects of TF and pEGCG were evaluated against six selected bacteria, Staphylococcus epidermidis, Streptococcus mutans, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Proteus vulgaris, using an antibacterial assay. A viability assay using SYTOX® staining and flow cytometry was also used to determine the effect of these compounds …

Human Neuroblastoma Adaptation To Cobalt Chloride-Induced Hypoxia, Conor Mcauliffe

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a frequent characteristic of the solid tumor microenvironment, which occurs when cancer cells lack adequate access to oxygen. By selecting for cells that can adapt to and grow in low oxygen conditions, tumor hypoxia contributes to a more aggressive and invasive cancer phenotype that portends a poor clinical outcome. While many aspects of the cellular response to hypoxia have been explored, the roles of some factors have not been fully explained. Cell signaling factors, including signal transducer and activator of transcription 3 (STAT3), the mu opioid receptor (MOR), and the delta opioid receptor (DOR), as well as changes …

Transcriptome Approach For Identifying Potential Biomarkers For Endocrine Disruption Due To Crude Oil Exposure Using Killifish (Fundulus Heteroclitus)., Frank J. Zadlock Iv

Seton Hall University Dissertations and Theses (ETDs)

The killifish, Fundulus heteroclitus, is a common fish model in aquatic toxicology. However, little is known in this organism about how endocrine disrupting compounds, (EDCs) including polycyclic aromatic hydrocarbons (PAHs), impact the reproductive status from a molecular standpoint. The objective of this project is to apply high throughput sequencing to F. heteroclitus testes to examine the molecular mechanisms that impair reproduction when exposed to crude oil. First, a crude oil exposure experiment was conducted. Following exposure, semi-quantitative PCR was performed to detect changes in gene expression of the following genes known to respond to EDCs: gonadal aromatase (CYP19a), vitellogenin …

Development Of A Novel Method To Express And Purify Vaccinia Virus Early Transcription Factors A7 And D6 Using Bacteria, Omkar M. Gandbhir

Seton Hall University Dissertations and Theses (ETDs)

The eradication of Smallpox is one of the greatest human achievements. However other poxviruses still exist infecting humans (Molluscum Contagiosum, monkeypox, and Vaccinia) or livestock (cowpox, sheeppox). Though vaccines and anti-virals exist, the side effects are serious, and viral resistance has been detected. The genome amongst poxviruses is highly conserved, early gene promoters maintain a specific critical consensus region that can be targeted for development of novel broad spectrum therapeutics. Using Vaccinia early transcription factors (VETFs) a novel method of expressing and purifying VETF A7 and D6 was developed. A7 and D6 are required for transcription of early genes recruiting …