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Articles 331 - 360 of 464
Full-Text Articles in Biomedical Engineering and Bioengineering
Nonlinear Granger Causality And Its Application In Decoding Of Human Reaching Intentions, Mengting Liu
Nonlinear Granger Causality And Its Application In Decoding Of Human Reaching Intentions, Mengting Liu
Doctoral Dissertations
Multi-electrode recording is a key technology that allows the brain mechanisms of decision making, cognition, and their breakdown in diseases to be studied from a network perspective. As the hypotheses concerning the role of neural interactions in cognitive paradigms become increasingly more elaborate, the ability to evaluate the direction of neural interactions in neural networks holds the key to distinguishing their functional significance.
Granger Causality (GC) is used to detect the directional influence of signals between multiple locations. To extract the nonlinear directional flow, GC was completed through a nonlinear predictive approach using radial basis functions (RBF). Furthermore, to obtain …
Performance Of Wavelet Denoising And Automatic Detection Of Action Potentials On Simulated And Real Electrneurographic Recordings, Manikandan Ravi
Performance Of Wavelet Denoising And Automatic Detection Of Action Potentials On Simulated And Real Electrneurographic Recordings, Manikandan Ravi
Bioengineering Theses - Archive
About 1 in 200 people living in the U.S have had an amputation at some stage in their lives. Development of neurally controlled artificial limb prosthesis with the ability to finely control motor activity continues to prove difficult for researchers in the field. One approach is to use the signals obtained from the peripheral nerves by placing an intraneural electrode in the nerve. Since this signal is very noisy, much of the useful information is either lost or buried in the noise even after FIR filtering. Furthermore, there is a need for fast, automated detection of action potentials in order …
Long Gap Peripheral Nerve Reconstruction Using Decellularized Nerve Grafts, Srikanth Vasudevan
Long Gap Peripheral Nerve Reconstruction Using Decellularized Nerve Grafts, Srikanth Vasudevan
Bioengineering Dissertations - Archive
Peripheral nerve injuries that arise as a result of trauma, tumor excision or birth can adversely affect the quality of patient life, leading to lifelong disabilities in some cases. Autologous nerve grafts are the clinical "gold standard" for long gap nerve repair, and allogeneic nerve grafts are considered the next best treatment option. Despite having numerous benefits, autologous nerve grafts are associated with limited supply, longer operation time, risk of infection, painful neuroma formation and most importantly, loss of function at the donor site. Allogeneic nerve grafts require transient immunosuppression, which exposes the patients to risks of infection, toxicity and …
Protoporphyrin Ix (Ppix)-Conjugated Self-Lighting Nanoparticles For Photodynamic Therapy: Synthesis And Characterization, Homa Homayoni
Protoporphyrin Ix (Ppix)-Conjugated Self-Lighting Nanoparticles For Photodynamic Therapy: Synthesis And Characterization, Homa Homayoni
Bioengineering Dissertations - Archive
In Photodynamic therapy (PDT) PDT, cancer destruction relies on applying a photosensitizing drug (PS) followed by light. Absorbed light can activate the PS to transfer energy to existing molecules and substrates or to oxygen to generate singlet oxygen which are highly toxic to cells. Protophorphyrin IX (PpIX) is a photosensitizers (PSs) which has FDA approval and an absorbance near the Soret band which is 10 times stronger than the absorbance in Q-band (600nm). Our goal was to design a modality to eliminate of external blue light in addition to increasing the drug's water dispersion which finally may result in enhancing …
An Investigation Of Concurrent Variations In Blood Oxygen Saturation And Cerebral Blood Flow During Apnea, Jennifer Swittens
An Investigation Of Concurrent Variations In Blood Oxygen Saturation And Cerebral Blood Flow During Apnea, Jennifer Swittens
Bioengineering Theses - Archive
Sleep apnea derived from Greek word "apnoia" which means "without air or temporary interruption in breathing", is a sleep - associated breathing disorder that involves a decrease or complete stop in airflow despite a constant effort to breathe. It is estimated that sleep apnea is prevalent in the US in 18 million people and is approximately 6% of the population.This thesis aims to study the physiological effects of sleep apnea on cerebral blood flow (CBF) and the percentage oxygen saturation (%SaO2), the effect of duration of apnea episode or a breath hold on CBF and %SaO2 and to derive a …
Establishment And Characterization Of An Animal Model Of Distraction Spinal Cord Injury, Jennifer Elisabeth Stearns Bell
Establishment And Characterization Of An Animal Model Of Distraction Spinal Cord Injury, Jennifer Elisabeth Stearns Bell
Bioengineering Dissertations - Archive
Scoliosis corrective surgery requires the application of multidirectional stress forces to the spinal cord, including those of distraction, in addition to the application of fixation rods for correction of the curved spine deformity. If excessive, spine distraction may result in the development of new neurologic deficits, some as severe as permanent paralysis. Intraoperative monitoring is used to alert the surgeon to possible complications; however, the complex nature of spinal cord injury (SCI) involves a primary mechanical insult to the tissue and/or vasculature that may go undetected by monitoring. This is followed by the activation of widespread secondary injury mechanisms. The …
Diffuse Optical Tomography To Study The Ischemic Stroke In Rat Models, Zi-Jing Lin
Diffuse Optical Tomography To Study The Ischemic Stroke In Rat Models, Zi-Jing Lin
Bioengineering Dissertations - Archive
Stroke, including ischemic stroke and hemorrhagic stroke, is the major leading cause of death in the United States. More than 80 percent of stroke patients are diagnosed with ischemic stroke, which usually results from blockage of artery in the brain by thrombosis or arterial embolism. Animal Models, which permit powerful genetic and molecular approaches, provide an essential tool to study and understand the basic processes and potential therapeutic interventions for this disease. Significant efforts have been made to closely mimic the changes that occur in humans during and after stroke using animal models. Recent development on near infrared (NIR) diffuse …
The Pivotal Role Of Fibrocytes On Foreign Body Reactions, David William Baker
The Pivotal Role Of Fibrocytes On Foreign Body Reactions, David William Baker
Bioengineering Dissertations - Archive
Fibrocytes are circulating connective tissue precursor cells that were first described in 1994 by Bucala et al. as mediators of the innate immune response [1]. Recently the notion of a fibrocyte has not only gained widespread acceptance, but these cells have been identified to participate in a number of disease and pathologic states including aberrant wound repair, fibrosis of organs, cardiovascular disease, and even normal aging. Despite these advancements, little was known about the response of these dynamic cells to biomaterial implants and foreign body reactions. The main focus of my thesis work has therefore focused on investigating fibrocyte-mediate responses, …
Noninvasive Assessment Of Tumor Hypoxia Using Oxygen Sensitive Mri In Prostate Tumor Models, Rashmi Reddy Pabhathi Reddy
Noninvasive Assessment Of Tumor Hypoxia Using Oxygen Sensitive Mri In Prostate Tumor Models, Rashmi Reddy Pabhathi Reddy
Bioengineering Theses - Archive
A variety of solid tumors reveal oxygen deficiency as a result of rapid growth and insufficient tumor angiogenesis. Hypoxia in solid tumors appears to speed up malignant progression and metastatic potential of primary tumors thus leading to resistance against anticancer drugs and decreased response to radiotherapy.Of various in vivo non-invasive techniques to assess tumor hypoxia, oxygen-sensitive MRI (BOLD and TOLD) is an attractive and reliable option. Blood Oxygen Level Dependent (BOLD) and Tissue Oxygen Level Dependent (TOLD) MRI offer potential insight into tumor hypoxia. BOLD (Blood Oxygen Level Dependant) contrast MRI which measures R2* (1/T2*) is sensitive to endogenous paramagnetic …
Development Of Non-Invasive Methods For Imaging Inflammatory Response, Yi-Ting Tsai
Development Of Non-Invasive Methods For Imaging Inflammatory Response, Yi-Ting Tsai
Bioengineering Dissertations - Archive
Persistent inflammatory cell reactions are responsible for the pathogenesis of a variety of inflammatory diseases. Although many non-invasive imaging methods have been used in the clinics to monitor the extent of inflammatory responses, almost all of them are based on indirect detection of inflammation-associated anatomical or structure changes of tissues and organs. To fill the gap, our laboratory has focused research efforts on detecting different processes of inflammatory responses. Our results can be summarized in the sequence of inflammatory responses - edema formation, inflammatory cell recruitment, inflammatory product release, and cell death. Shortly after medical device implantation or injury, edema …
Kinetics Analyses Of Interactions Between Oncogenic And Tumor Suppressor Proteins By Quantitative High Resolution Microscopy Methods, Shu-Fen Tseng
Kinetics Analyses Of Interactions Between Oncogenic And Tumor Suppressor Proteins By Quantitative High Resolution Microscopy Methods, Shu-Fen Tseng
Bioengineering Dissertations - Archive
DAB2IP is correlated to the risk of aggressive prostate cancer and loss of DAB2IP not only leads to epithelial-to-mesenchymal transition (EMT), but also makes cells radioresistant. These observations support the notion that improved knowledge of DAB2IP involvement in cellular pathways could be of help to cancer therapy. The goal of this work was to enable the study of how DAB2IP and some of its known key molecular partners interact in the cell by a combination of molecular biology techniques and recently reported quantitative fluorescence microscopy methods. The first part of this work was dedicated on investigating the interaction of DAB2IP …
How Atomic Level Interactions Drive Membrane Fusion: Insights From Molecular Dynamics Simulations, Navendu Bhatnagar
How Atomic Level Interactions Drive Membrane Fusion: Insights From Molecular Dynamics Simulations, Navendu Bhatnagar
Wayne State University Dissertations
This project is focused on identifying the role of key players in the membrane fusion process at the atomic level with the use of molecular dynamics simulations. Membrane fusion of apposed bilayers is one of the most fundamental and frequently occurring biological phenomena in living organisms. It is an essential step in several cellular processes such as neuronal exocytosis, sperm fusion with oocytes and intracellular fusion of organelles to name a few. Membrane fusion is a frequent process in a living organism but is still not fully understood at the atomic level in terms of the role of various factors …
Biom 4110/6110: The Science Of Medicine (Syllabus), Bradford D. Pendley
Biom 4110/6110: The Science Of Medicine (Syllabus), Bradford D. Pendley
Biomedical Engineering Syllabi Archive
Course Description: Integration of fundamental principles from physics, chemistry, biology and mathematics, and applications of these principles to solve problems in medicine.
Mesenchymal Stem Cells As Targeted Cell Vehicles To Deliver Drug-Loaded Nanoparticles For Cancer Therapy, Kytai Truong Nguyen
Mesenchymal Stem Cells As Targeted Cell Vehicles To Deliver Drug-Loaded Nanoparticles For Cancer Therapy, Kytai Truong Nguyen
Bioengineering Faculty Publications - Archive
No abstract provided.
Development Of A Model To Simulate The Single-Limb Stance Phase Of Walking To Determine The Limits Of Stability, Clifford Lee Hancock
Development Of A Model To Simulate The Single-Limb Stance Phase Of Walking To Determine The Limits Of Stability, Clifford Lee Hancock
Bioengineering Theses - Archive
Falls during walking are the primary cause of injuries for older persons and present a high associated cost to society due to the resulting treatment. Hence, the control of balance while moving is an essential issue especially amongst the elderly population. Better understanding of why and how these falls occur could lead to better fall prevention methods, therapies, or devices. These changes could effectively decrease overall emergency room visits, create more room in hospitals for other demands, and decrease medical costs for fall-related disabilities and deaths amongst patients overall. This study attempted to develop an inverted pendulum model of the …
Microfluidic Device For Determining Preferential Cell Migration Toward Extracellular Matrix Proteins, Neil Hall
Microfluidic Device For Determining Preferential Cell Migration Toward Extracellular Matrix Proteins, Neil Hall
Bioengineering Theses - Archive
Extracellular matrix (ECM) proteins interact with cells in bodily microenvironments by influencing their essential cellular processes in growth, survival, migration and repair after injury. In this study, a novel microfluidic device was developed to study preferential interactions of cells with multiple extracellular matrix proteins simultaneously in an unbiased manner. The implementation of PDITC-treated glass and a controlled laminar flow of multiple separated, soluble proteins was used to create an unbiased microenvironment in which ECM proteins are adsorbed on the glass surface in a manner that simultaneously exposes cells to multiple proteins, and allows them to migrate or outgrow toward the …
Recombinant Expression, Purification And Kinetic Characterization Of F₄₂₀-Cofactor Dependent Glucose-6-Phosphate Dehydrogenase From Mycobacterium Tuberculosis, Tijani Osumah
Bioengineering Theses - Archive
The FGD (F₄₂₀-dependent Glucose-6-phosphate dehydrogenase) enzyme is an F₄₂₀ Cofactor (7,8-didemethyl-8-hydroxy-5-deazariboflavin) dependent enzyme found in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is still a prominent cause of illness and death worldwide. Because FGD is not found in humans, makes it a good target for drug development. By understanding the hydride transfer mechanism of the FGD in detail, we can aid in the improvement of drug targeting and development for the treatment of TB. FGD catalyzes the conversion of glucose-6-phosphate to 6-phosophogluconolactone. This project focuses on the purification and kinetic characterization of recombinant FGD using steady-state and pre-steady …
Surface- And Hydrogel-Mediated Delivery Of Nucleic Acid Nanoparticles, Angela K. Pannier, Tatiana Segura
Surface- And Hydrogel-Mediated Delivery Of Nucleic Acid Nanoparticles, Angela K. Pannier, Tatiana Segura
Department of Agricultural and Biological Systems Engineering: Faculty Publications
Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. …
Techniques To Quantify The Size Of Protein Colloids In Amyloid Fiber Formation, Jonathan R. Anson, Chia-Hung Lu, Lingwen Cui, Xiaojing Yang, Shaohua Xu
Techniques To Quantify The Size Of Protein Colloids In Amyloid Fiber Formation, Jonathan R. Anson, Chia-Hung Lu, Lingwen Cui, Xiaojing Yang, Shaohua Xu
Biomedical Engineering and Sciences Faculty Publications
A new method for the analysis of protein colloidal diameter has been developed using three existing protein concentration quantification techniques, absorption at 280 nm, colloidal gold assay, and DC protein assay. Protein colloids are formed in the process of aggregation and are thought to be intermediates in protein self-assembly and formation of amyloid fiber. Deposition of the protein fibers in tissues leads to numerous human diseases including Alzheimer’s. Lysozyme was incubated at pH 2.0, 55°C, an environment conducive to amyloid fiber formation. The protein colloids present in the supernatant of the samples after centrifugation were studied over a time course …
Biomarkers For Brain Disorders Electrochemically Detected By Broderick Probe Microelectrodes/Biosensors, Waqas Saleem, Patricia A. Broderick
Biomarkers For Brain Disorders Electrochemically Detected By Broderick Probe Microelectrodes/Biosensors, Waqas Saleem, Patricia A. Broderick
Publications and Research
Here, we present results from two independent studies carried out using Neuromolecular Imaging (NMI) with miniature BRODERICK PROBE® biosensors. In the first study, we imaged neurotransmitters and neurochemicals in human epilepsy patients intraoperatively during early and late neurodegeneration. In the second study, we imaged neurotransmitters and neurochemicals in an experimental murine model using animals with and without neurodegeneration caused by Parkinson’s disease (PD). We compared our results derived from animals with lesioned group (PD) with non-lesioned group (non-PD), using the same in vivo NMI paradigm. NMI biotechnology enabled neurotransmitters, neuropeptides and neurochemical imaging of dopamine (DA), serotonin (5-HT), homovanillic acid …
Cervical Spine Tolerance And Response In Compressive Loading Modes Including Combined Compression And Lateral Bending, Daniel Toomey
Cervical Spine Tolerance And Response In Compressive Loading Modes Including Combined Compression And Lateral Bending, Daniel Toomey
Wayne State University Dissertations
Injuries in motor vehicle accidents continue to be a serious and costly societal problem. Automotive safety researchers have observed noticeable lateral bending of the anthropomorphic test device (ATD) neck prior to or in conjunction with head impact with the vehicle roof in rollover crash tests. Since there is scant data available about the effects of lateral bending on overall compressive tolerance of the human cervical spine, it is unknown if the presence of lateral bending is important to consider during impacts with the apex of the head. Compressive injury tolerance has historically been reported by identifying the axial force at …
Use Of Focused Ultrasound For Transcranial Sonothrombolysis, Golnaz Ahadi
Use Of Focused Ultrasound For Transcranial Sonothrombolysis, Golnaz Ahadi
Wayne State University Dissertations
Worldwide, stroke is the second most common cause of death. Ischemic stroke remains accountable for the majority of the 20 million devastating stroke events occurring globally each year. Use of transcranial focused ultrasound (FUS) for sonothrombolysis is a new research field for ischemic stroke treatment. If shown to be effective, FUS sonothrombolysis could become a widely available treatment option for the majority of the stroke sufferers that do not qualify or do not have access to current thrombolytic treatment options, such as tPA or neurointerventional methods.
The current study was an in vitro transcranial FUS headsystem investigation for the potential …
Diagnosis Of Systemic Inflammation Using Transendothelial Electrical Resistance And Low-Temperature Co-Fired Ceramic Materials, William L. Mercke
Diagnosis Of Systemic Inflammation Using Transendothelial Electrical Resistance And Low-Temperature Co-Fired Ceramic Materials, William L. Mercke
Theses and Dissertations--Chemical and Materials Engineering
Systemic inflammation involves a complex array of cytokines that can result in organ dysfunction. Mortality remains high despite the vast amount of research conducted to find an effective biomarker. The cause of systemic inflammation can be broad and non-specific; therefore, this research investigates using transendothelial electrical resistance (TEER) measurements to better define systemic inflammatory response syndrome (SIRS)/sepsis within a patient. Results show a difference in TEER measurements between healthy individuals and SIRS-rated patients. This research also displays correlations between TEER measurements and biomarkers currently studied with systemic inflammation (tumor necrosis factor-α, C- reactive protein, procalcitonin). Furthermore, this research also presents …
Nanomaterials For Photo-Based Diagnostic And Therapeutic Applications, Baohong Yuan, Jyothi Unnikrishna Menon, Khanh Vu, Parth V. Jadeja, Kytai Truong Nguyen, Pranjali P. Tambe
Nanomaterials For Photo-Based Diagnostic And Therapeutic Applications, Baohong Yuan, Jyothi Unnikrishna Menon, Khanh Vu, Parth V. Jadeja, Kytai Truong Nguyen, Pranjali P. Tambe
Bioengineering Faculty Publications - Archive
Photo-based diagnosis and treatment methods are gaining prominence due to increased spatial imaging resolution, minimally invasive modalities involved as well as localized treatment. Recently, nanoparticles (NPs) have been developed and used in photo-based therapeutic applications. While some nanomaterials have inherent photo-based imaging capabilities, others including polymeric NPs act as nanocarriers to deliver various fluorescent dyes or photosensitizers for photoimaging and therapeutic applications. These applications can vary from Magnetic Resonance Imaging (MRI) and optical imaging to photothermal therapy (PTT) and chemotherapy. Materials commonly used for development of photo-based NPs ranges from metal-based (gold, silver and silica) to polymer- based (chitosan, dextran, …
Multi-Level Parallelism For Incompressible Flow Computations On Gpu Clusters, Dana A. Jacobsen, Inanc Senocak
Multi-Level Parallelism For Incompressible Flow Computations On Gpu Clusters, Dana A. Jacobsen, Inanc Senocak
Mechanical and Biomedical Engineering Faculty Publications and Presentations
We investigate multi-level parallelism on GPU clusters with MPI-CUDA and hybrid MPI-OpenMP-CUDA parallel implementations, in which all computations are done on the GPU using CUDA. We explore efficiency and scalability of incompressible flow computations using up to 256 GPUs on a problem with approximately 17.2 billion cells. Our work addresses some of the unique issues faced when merging fine-grain parallelism on the GPU using CUDA with coarse-grain parallelism that use either MPI or MPI-OpenMP for communications. We present three different strategies to overlap computations with communications, and systematically assess their impact on parallel performance on two different GPU clusters. Our …
New Microarray Image Segmentation Using Segmentation Based Contours Method, Yuan Cheng
New Microarray Image Segmentation Using Segmentation Based Contours Method, Yuan Cheng
Doctoral Dissertations
The goal of the research developed in this dissertation is to develop a more accurate segmentation method for Affymetrix microarray images. The Affymetrix microarray biotechnologies have become increasingly important in the biomedical research field. Affymetrix microarray images are widely used in disease diagnostics and disease control. They are capable of monitoring the expression levels of thousands of genes simultaneously. Hence, scientists can get a deep understanding on genomic regulation, interaction and expression by using such tools.
We also introduce a novel Affymetrix microarray image simulation model and how the Affymetrix microarray image is simulated by using this model. This simulation …
Microfluidic Devices Applied On Enriching Post –Translational Modified Proteins For Proteomics, Hui Xia
Microfluidic Devices Applied On Enriching Post –Translational Modified Proteins For Proteomics, Hui Xia
Doctoral Dissertations
In this work, microfluidic devices were developed for enriching post-translational modified proteins. Post-translational modifications (PTM) of proteins play essential roles in cellular physiology and disease. The identification of protein substrates and detection of modification site helps understand PTM-mediated regulation in essential biological pathways and functions in various diseases. However, PTM proteins are typically present only at trace levels, making them difficult to identify in mass spectrometry based proteomics. This work study is about the design, fabrication and testing of the microfluidic device for the enrichment of abundant amount of PTMs. Carbonylated protein is used as a representative PTM to illustrate …
Ultrasonication Assisted Layer-By-Layer Technology For The Preparation Of Multi-Functional Anticancer Drugs Paclitaxel And Lapatinib, Xingcai Zhang
Ultrasonication Assisted Layer-By-Layer Technology For The Preparation Of Multi-Functional Anticancer Drugs Paclitaxel And Lapatinib, Xingcai Zhang
Doctoral Dissertations
In this dissertation, ultrasonication assisted Layer-by-Layer (LbL) technology for the preparation of multifunctional poorly water-soluble anticancer drug nanoparticles, paclitaxel and lapatinib, has been developed. Many FDA approved drugs are very low soluble in water; therefore, it is very difficult to load and control their release and targeting efficiently, which greatly confines their application. The development of this method will pave the way for the development and application of those low soluble anticancer drugs.
In the first part of this dissertation, the first approach for powerful ultrasonication, the top-down approach (sonicating bulk drug crystals in polyelectrolyte solution), was successfully applied for …
Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly
Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly
Doctoral Dissertations
Tissue engineered microenvironments were constructed to test the effects glial cells have on calcium information processing, and to mimic conditions in vivo for tumor invasion and residual cancer after resection of tumor. Submaximal, nM, glutamate (GLU) stimuli were applied to the engineered environments, and the resulting calcium dynamic behavior of neuronal cells was measured to help predict and interpret chaotic systems in the experimental realm. Calcium is a key signaling ion which signals through the N-methyl-D-aspartate (NMDA) glutamate receptor on the neuronal membrane. GLU binding to the NMDA receptor (NMDAR) causes a large and dynamic increase in neuronal intracellular calcium. …
Cpg And Interleukin-15 Synergize To Enhance Ifn-Gamma Production By Activated Cd8(+) T Cells, Dustin Cobb, Sigi Guo, Ronald B. Smeltz
Cpg And Interleukin-15 Synergize To Enhance Ifn-Gamma Production By Activated Cd8(+) T Cells, Dustin Cobb, Sigi Guo, Ronald B. Smeltz
Bioelectrics Publications
Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells. Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-gamma by CD8(+) T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-gamma production. The effect of CpG and IL-15 was also evident with CD8(+) T …