Biotechnology Commons^™

Prediction Of Central Visual Field Measures From Macular Oct Volume Scans With Deep Learning, Vahid Mohammadzadeh, Arvind Vepa, Chuanlong Li, Sean Wu, Leila Chew, Golnoush Mahmoudinezhad, Evan Maltz, Serhat Sahin, Apoorva Mylavarapu, Kiumars Edalati, Jack Martinyan, Dariush Yalzadeh, Fabien Scalzo, Joseph Caprioli, Kouros Nouri-Mahdavi

All Faculty Open Access Publications

Purpose: Predict central 10° global and local visual field (VF) measurements from macular optical coherence tomography (OCT) volume scans with deep learning (DL). Methods: This study included 1121 OCT volume scans and 10-2 VFs from 289 eyes (257 patients). Macular scans were used to estimate 10-2 VF mean deviation (MD), threshold sensitivities (TS), and total deviation (TD) values at 68 locations. A three-dimensional (3D) convolutional neural network based on the 3D DenseNet121 architecture was used for prediction. We compared DL predictions to those from baseline linear models. We carried out 10-fold stratified cross-validation to optimize generalizability. The performance of the …

Changes In Lipid Profiles Of Epileptic Mouse Model, Alicia Johnson, Ryan A. Grove, Deepak Madhavan, Cory Honsinger Thomas Boone, Camila Pereira Braga, Hannah Kyllo, Kaeli Samson, Timothy Simeone, Tomáš Helikar, Corrine K. Hanson, Jiri Adamec

Department of Biochemistry: Faculty Publications

Introduction—Approximately 1% of the world’s population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD’s success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.

Objectives—The …

Liposome Synthesis And Evaluation In The Hek-293 Cell Line, Christine Skibinski

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Liposomes were synthesized using the thin film method. A lyophilized power of egg-derived phosphatidylcholine, stearylamine, and cholesterol were added to ethanol and dried under argon to form a lipid cake. The lipid cake was rehydrated with dPBS and sonicated at 60°C forming a heterogenous batch of liposomes. Our results revealed the average size of the liposomes, determined by Dynamic Light Scattering, was approximately 223.1nm, while demonstrating a weakly positive zeta-potential of 1.9± 8.07mv. Next, we tested the antitumor action of the liposomes in the HEK-293 cell line via an MTT assay. We observed that the liposomes were able to inhibit …

Bola3 And Nfu1 Link Mitoribosome Iron–Sulfur Cluster Assembly To Multiple Mitochondrial Dysfunctions Syndrome, Hui Zhong, Alexandre Janer, Oleh Khalimonchuk, Hana Antonicka, Eric A. Shoubridge, Antoni Barrientos

Department of Biochemistry: Faculty Publications

The human mitochondrial ribosome contains three [2Fe–2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the e xpression of Fe–S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [²Fe–2S] clusters from the GLRX5-BOLA3 node. Additionally, the assembly of the small subunit depends on the mitoribosome biogenesis factor METTL17, recently reported containing a [⁴Fe–4S] cluster, which we …

Plasmid Midiprep: A Method To Purify Plasmids For Recombinant Dna Studies, Adithya Anilkumar, Kyle Doxtater, Samantha Lopez, Sudhir Kotnala, Justin Wendel, Manish Tripathi

Research Colloquium

A fundamental aspect of molecular biology involves exploring the properties and functions of specific genes. The rise of recombinant DNA technology has vastly improved and simplified functional studies by allowing scientists to isolate specific genes using restriction enzymes and plasmids providing greater precision. Plasmids take great significance in downstream studies, which is why quantity and quality of the plasmids purified is important. In this study, we isolated and purified recombinant plasmids in microgram quantities to confirm the yield, quantity, and quality using spectral and size fractionation methods. We also assessed the plasmids for application in downstream studies. We found the …

Factors Influencing Instructors’ Adoption And Continued Use Of Computing Science Technologies: A Case Study In The Context Of Cell Collective, Changsoo Song, Resa M. Helikar, Wendy Smith, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Acquiring computational modeling and simulation skills has become ever more critical for students in life sciences courses at the secondary and tertiary levels. Many modeling and simulation tools have been created to help instructors nurture those skills in their classrooms. Understanding the factors that may motivate instructors to use such tools is crucial to improve students’ learning, especially for having authentic modeling and simulation learning experiences. This study designed and tested a decomposed technology acceptance model in which the perceived usefulness and perceived ease of use constructs are split between the teaching and learning sides of the technology to examine …

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …

Targeting Cellular Signaling Pathways In Cancer By Lactobacilli, Varish Ahmad, Aftab Ahmad, Quazi Muhammad Sajid Jamal

Research Symposium

Purpose: Presenting lactobacilli therapy for cancer treatment targeting cancer signaling Lactobacilli as Probiotic lactic acid bacteria (LAB) are a group of fermentative gram-positive and gram-negative bacteria that produces a large number of intracellular and extracellular metabolites used in the food manufacture industry as well as complementary and alternative medicines against many diseases including cancer.

Description: Some LAB has been found to have inhibitory activity against colon liver cancer, cancer, colorectal cancer, breast cancer, and lung cancer in vivo or in vitro. These fermentative bacteria induced the autophagy cell death either by GRP78 and Beclin-1 or by induction of Bak …

Precise Method To Identify Kinase Drug Targets In Complex Diseases: The First Step Towards Sustainable And Effective Treatment, Hasbanny Irisson, Marzieh Ayati

Research Symposium

Background: Kinases are enzymes that have proven to be important drug targets due to their role in critical biological mechanisms such as phosphorylation. Phosphorylation happens when a kinase catalyzes the transfer of a phosphate group to a protein in a phosphorylated site, which then becomes known as the substrate of the kinase. Any dysregulation of protein phosphorylation causes a wide range of complex diseases including cancer. Thus, discovering the links between kinases and their substrates (i.e. predicting kinase-substrate associations (KSAs)) is crucial in developing effective and sustainable treatments. Presently, less than 5% of phosphorylated sites have an associated kinase, and …

Piperine Encourages Apoptosis In Human Cervical Adenocarcinoma Cells Through Ros Generation, Dna Fragmentation, Caspase-3 Activation And Cell Cycle Arrest, Asif Jafri, Juhi Rais, Sudhir Kumar, Md Arshad

Research Symposium

Background: Cancer is one of the most common destructive diseases and the second leading cause of death in humans. Among cancer, cervical cancer is the second most common malignancy among women globally. Thus, there is a continuous need to search for chemotherapeutic chemicals or naturally occurring drugs to resolve this global health problem. Piperine (1-piperoylpeperdine) is present in the fruits of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). It possesses several pharmacological properties and in the present study we have evaluated its anti-cancer potential on human cervical adenocarcinoma (HeLa) cells.

Methods: The anti-proliferative effect …

Novel Nanoparticle Formulation Of Sabizabulin (Veru-111) For Pancreatic Cancer Treatment, Vivek K. Kashyap, Godwin P. Darkwah, Neeraj Chauhan, Prashanth Kb Nagesh, Anupam Dhasmana, Swati Dhasmana, Qinghui Wang, Duane D. Miller, Wei Li, Bilal B. B. Hafeez, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan

Research Symposium

Background: Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortality in the United States due to very limited therapeutic options. Thus, developing novel therapeutic strategies will help for the management of this disease. We recently identified VERU-111, a novel synthetic molecule which showed potent anti-cancer effect against PanCa via targeting clinically important βIII and βIV tubulin isoforms. In this study, we synthesized and characterized its novel nanoformulation (MNP-VERU) and evaluated its therapeutic effects in vitro and xenograft mouse model.

Methods: MNPs were prepared by chemical precipitation method and loaded with VERU-111 using diffusion method. This formulation was …

Mortaparibplus- A Novel Anticancer Small Molecule Abrogating Mortalin-P53 Interaction In Cancer Cells, Anissa N. Sari, Ahmed Elwakeel, Jaspreet K. Dhanjal, Vipul Kumar, Durai Sundar, Sunil C. Kaul, Renu Wadhwa

Research Symposium

Background. The cessation of tumor cell growth through cell cycle arrest and apoptosis is determined by p53, a tumor suppressor protein. However, the interaction between mortalin-p53 within cytoplasm/nucleus leads to the inactivation of p53 transcriptional activation function. The disruption of mortalin-p53 complex has been suggested as an approach for developing a potential anticancer drug.

Methods. A screening of a high-content chemical library was performed to determine a molecule with mortalin-p53-interaction disrupting characteristics. After four-rounds of visual assays, we discovered a triazole derivative (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole, named Mortaparib^Plus) with a potential ability of disrupting mortalin-p53-complex. In this study, we recruited …

Development Of An Antibiotic Resistance Breaker To Combat Staphylococcus Aureus Pathogenesis Skin Infections Ssis A Multidisciplinary, Gopalakrishnan T Mr

Theses and Dissertations

Problem Statement: Staphylococcus aureus is a highly adaptable and tenacious pathogen known to cause a wide range of infections. The survival characteristics of the pathogen in different host niches are due to their ability to produce various pathogenic determinants. Although there lies the first line of treatment regimens with antibiotics, the pathogen defends at various levels to cause the waves of resistance - a silent pandemic “AMR”.

Notable strategies are through the protective layer, biofilm that enables the inter-/intra species communication (Quorum Sensing; QS) and emerges as a battleground to withstand host-immune response and antibiotic pressure. In parallel, several research …

Transcriptional Pausing Factor M1bp Regulates Cellular Homeostasis By Suppressing Autophagy And Apoptosis In Drosophila Eye, Anuradha Venkatakrishnan Chimata, Hannah Darnell, Akanksha Raj, Madhuri Kango-Singh

Biology Faculty Publications

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BP^RNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway …

Non-Contact Optical Spectroscopy For Tumor-Sensitive Diffuse Reflectance And Fluorescence Measurements On Murine Subcutaneous Tissue Models: Monte Carlo Modeling And Experimental Validations, Zahid Hasan, Pranto Soumik Saha, Madison O. Korfhage, Caigang Zhu

Markey Cancer Center Faculty Publications

Fiber-optic probes are commonly used in biomedical optical spectroscopy platforms for light delivery and collection. At the same time, it was reported that the inconsistent probe- sample contact could induce significant distortions in measured optical signals, which consequently cause large analysis errors. To address this challenge, non-contact optical spectroscopy has been explored for tissue characterizations. However, existing non-contact optical spectroscopy platforms primarily focused on diffuse reflectance measurements and may still use a fiber probe in which the probe was imaged onto the tissue surface using a lens, which serves as a non-contact probe for the measurements. Here, we report a …

Induction Of Ploidy Level On Three Patchouli (Pogostemon Cablin Benth) Cultivars By Colchicine In Vitro, Suseno Amien, Nikkita Putri Darmawan, Daniya Fathya

Jurnal Kultivasi

Patchouli plants produce essential oils and are used as a raw material and fixative agent for perfumes. The most widely cultivated patchouli plant in Indonesia is Aceh patchouli. Sexual propagation in Aceh patchouli plants is impossible as it does not flower. Genetic diversity can be elevated through another method, such as polyploidy induction using colchicine. This research aimed to evaluate the state-of-the-art application of polyploidization techniques as a breeding tool for callus-based explants. A completely randomized design with a factorial pattern was used in this experiment consisting of two factors, patchouli cultivars (Sidikalang, Tapak Tuan, and Lhokseumawe) and colchicine concentration …

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …

Portable Optical Spectroscopic Assay For Non-Destructive Measurement Of Key Metabolic Parameters On In Vitro Cancer Cells And Organotypic Fresh Tumor Slices, Jing Yan, Carlos Frederico Lima Goncalves, Madison O. Korfhage, Zahid Hasan, Teresa Whei-Mei Fan, Xiaoqin Wang, Caigang Zhu

Markey Cancer Center Faculty Publications

To enable non-destructive metabolic characterizations on in vitro cancer cells and organotypic tumor models for therapeutic studies in an easy-to-access way, we report a highly portable optical spectroscopic assay for simultaneous measurement of glucose uptake and mitochondrial function on various cancer models with high sensitivity. Well-established breast cancer cell lines (MCF-7 and MDA-MB-231) were used to validate the optical spectroscopic assay for metabolic characterizations, while fresh tumor samples harvested from both animals and human cancer patients were used to test the feasibility of our optical metabolic assay for non-destructive measurement of key metabolic parameters on organotypic tumor slices. Our optical …

Mirna Regulation Of Skeletal Muscle Hypertrophy, Maslyn Greene

All Dissertations

Muscle tissue is vital to animal survival and economically essential to livestock producers. Reduced muscle growth can occur from various reasons, including genetics, nutrition, and the pre and postnatal environment. Understanding the mechanisms behind muscle growth can aid in developing strategies to increase muscle mass. Several methods to increase muscle mass in livestock animals are currently being pursued, including nutrition, hormonal therapy, and genetic selection. One newly developing avenue is using miRNA technologies to change the expression of protein-coding genes. miRNA are a type of RNA that regulate over half of protein-coding gene expression. Here we evaluate muscle characteristics such …

Investigating The Potential Of A Cell-Based Gene Editing Therapy For Inherited Metabolic Liver Disease, Ilayda Ates

All Dissertations

Inherited metabolic diseases (IMDs) affecting the liver are relatively rare but collectively have a prevalence of 1 in 800 live births. These diseases result from autosomal recessive single-gene mutations, leading to organ dysfunction and potentially fatal consequences if left untreated. One potential therapeutic strategy for IMDs of the liver involves using CRISPR-Cas9-induced loss of function mutations. However, translating this approach into the clinic is limited by the need for safe and effective CRISPR delivery methods. Adeno-associated viral vectors (AAVs), commonly used for CRISPR delivery, are associated with significant safety and efficacy concerns, including risks for immunogenicity, off-target mutagenesis, and genotoxicity …