17 research outputs found
Synergistic development of an engineered biodegradable theranostic probe and lymph node organ-on-a-chip to study nanoparticle-lymphatic interactions
No full textThe lymphatic system plays a vital role in controlling immune response. Despite this, cancer often reshapes the lymphatic microenvironment and metastasizes into lymph nodes. Theranostic (therapeutic + diagnostic) nanoparticles have been used in a variety of applications, including the detection and treatment of cancer metastases in lymph nodes. However, accumulation in the liver remains a major concern with any nanoparticle-based intervention. We have developed biodegradable nanoparticles made of biliverdin, an endogenous fluorophore that results from the breakdown of hemoglobin. We demonstrated the degradation of biliverdin nanoparticles (BVNPs) in the presence of biliverdin reductase, as well as the use of BVNPs in photoacoustic imaging of sentinel lymph nodes. Fundamental studies on BVNPs demonstrated shifts in their spectral properties as a response to various stimuli, including pH changes, metal chelation, and UV irradiation. BVNPs loaded with doxorubicin (Dox-BVNPs) were used for treatment of triple-negative breast cancer. BVNPs were further modified via metal chelation for use as a magnetic resonance imaging contrast agent. Finally, hybrid biliverdin-silica particles were developed for use in fluorescence imaging in the near-infrared I and II windows. At the same time, microfluidic models were created to recapitulate the lymph node tissue microenvironment. We first developed a lymphatic vessel on-a-chip that achieved long-term culture of primary human lymphatic endothelial cells (HLECs) under gravity-driven flow. We then developed a lymphatic system on-a-chip, comprised of multiple units that each model the lymph node subscapsular sinus, high endothelial venules, and lymph nodules. This device allows for the exploration of transport of nanoparticles, cancer cells, and immune cells to and from lymph nodes.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2022-08-01The student, Parinaz Fathi, accepted the attached license on 2020-05-27 at 09:47.The student, Parinaz Fathi, submitted this Dissertation for approval on 2020-05-27 at 10:25.This Dissertation was approved for publication on 2020-06-17 at 15:05.DSpace SAF Submission Ingestion Package generated from Vireo submission #15422 on 2020-10-02 at 15:48:56Made available in DSpace on 2020-10-07T22:48:04Z (GMT). No. of bitstreams: 3
FATHI-DISSERTATION-2020.pdf: 27458256 bytes, checksum: 17880d1a44e4f24438dde7e96a8dad85 (MD5)
LICENSE.txt: 4210 bytes, checksum: b2f6e6970694ac3bc3e89296ed220a44 (MD5)
PROQUEST_LICENSE.txt: 4556 bytes, checksum: 6a4f7aaef7517e37ebe8556f98fcbadc (MD5)
Previous issue date: 2020-06-17Embargo set by: Seth Robbins for item 116284
Lift date: 2022-10-07T22:48:14Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 116284
Lift date: 2022-10-07T22:50:13Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemAuthor requested closed access (OA after 2yrs) in Vireo ETD systemLimite
Personalized absorbable gastrointestinal stents for intestinal fistulae and perforations
No full textGastrointestinal (GI) tract perforations and obstructions are relatively frequent surgical emergencies, are potentially life-threatening, and can occur from several different sources. In general, treatment requires urgent surgical repair or resection and at times can lead to further complications. Currently available stents are non-absorbable, are manufactured in a narrow size range, and/or are limited to usage in locations that are accessible for endoscopic removal post-healing. The use of 3D-printed bioresorbable polymeric stents will provide patients with a stent that can prevent leakage, is tailored specifically to their geometry, will degrade with time to eliminate the need for further surgeries for stent removal post-healing, and will be usable in locations that are not endoscopically accessible. This project focused on the characterization of polycaprolactone-polydioxanone (PCL-PDO) composites for use in a bioresorbable gastrointestinal stent. Dynamic Mechanical Analysis (DMA) tests were conducted to separately analyze the effects of composition, the filament formation process, and physiological temperature on the PCL-PDO material properties. The proposed stent design was then modelled using computer-aided design, and Finite Element Analysis (FEA) was used to simulate the effects of physiologically relevant forces on stent integrity. The presence of hydrolysable ester bonds was confirmed using FTIR spectroscopy, and composite morphology was examined with scanning electron microscopy. In vitro studies were used to evaluate the biocompatibility of the polymer composite, finding that the PCL:PDO filament had no negative impact on cell viability over a period of 48 hours, and in fact was conducive to cell proliferation over a period of 3 days. PCL-PDO stents were then 3D-printed and placed in vivo in a pig model, and histological evaluation was used to determine the safety of these stents. Further analyses were conducted through stent placement in ex vivo pig intestines.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-12-01The student, Parinaz Fathi, accepted the attached license on 2017-12-08 at 10:42.The student, Parinaz Fathi, submitted this Thesis for approval on 2017-12-08 at 10:49.This Thesis was approved for publication on 2017-12-12 at 09:02.DSpace SAF Submission Ingestion Package generated from Vireo submission #11917 on 2018-03-13 at 10:37:57Made available in DSpace on 2018-03-13T17:35:52Z (GMT). No. of bitstreams: 3
FATHI-THESIS-2017.pdf: 1901157 bytes, checksum: 828764aaf1e79b24190fd0d4a52cddd8 (MD5)
Draft_120817 - Dept review.docx: 9783017 bytes, checksum: ec2fc5cebde3a443185ba7e4e3eb3273 (MD5)
LICENSE.txt: 4210 bytes, checksum: 111b8b43508f67df5ce0c0280e807410 (MD5)
Previous issue date: 2017-12-12Embargo set by: Seth Robbins for item 105490
Lift date: 2020-03-13T17:36:05Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 105490 on 2020-03-14T09:15:16Z
Affordance Theory in XR Design : A Designer’s Perspective
No full textThis thesis explores the application of Affordance Theory in creating virtual learning environments, particularly in the context of the Agile XR project. The author, an experienced spatial designer with a decade and a half of expertise, concentrates on redesigning the user-friendliness and immersion of a virtual world called Dana’s Mind. In implementing the Affordance Theory, the author orientates to two significant literatures, The Ecological Approach to Visual Perception (Gibson,1979) and The Design of Everyday Things (Norman, 2013). Affordance Theory can be separated into two views.
Gibson’s perspective highlights the significance of environmental clues in indicating potential actions, regarding objects not just as static entities but as invitations for action. Expand upon this concept by introducing the concept of “perceived affordances,” highlighting the significance of making these signals clear in design to improve user comprehension without relying on instruction manuals.
This study utilizes a first-person study methodology, where the author actively participates in Dana’s Mind, carefully documenting their encounters and findings. The study is enhanced by feedback from teachers who participated in the Agile XR project, which offers significant insights into user interactions. Subsequent redesign combines theoretical ideas and practical feedback to keep the original design’s style while improving user-centric aspects.
In terms of the study's research participation, this study utilizes a dual-method approach: the author evaluates the revised virtual area, replicating their first experience, while eight other individuals give extra opinions through a survey. Findings emphasize the influence of Affordance Theory on user engagement and highlight its function in establishing a consistent and user-friendly virtual learning environment.
This study suggests that Affordance Theory is a highly effective tool for designers, serving as an advantage in XR design for online education and optimizing the user interface of virtual elements to be intuitive and user-friendly, guaranteeing a smooth and effortless experience for students and teachers. The paper claims that Affordance Theory is crucial for improving XR design, which transforms online learning spaces into settings where navigation is efficient and intuitively simple
A Survey On Hybrid Routing Protocols In MANETS
No full textMobile Ad hoc NETwork (MANET) is a collection of mobile nodes that are arbitrarily located so that the interconnections between nodes are dynamically changing. A routing protocol is used to find routes between mobile nodes to facilitate communication wi thin the network. The main goal of such an ad hoc network routing protocol is to establish correct and efficient route between a pair of mobile nodes. Route should be discovered and maintained with a minimum of overhead and bandwidth consumption. There are number of routing protocols were proposed for ad hoc networks. T he objective of this paper is to create a taxonomy of the ad hoc hybrid routing protocols, and to survey and comp are each type of hybrid protocols. We try to show the requirements considered by the different hybrid protocols, the resource limitations under which they operate, and the design decisions made by the author
Deletion of Glucocorticoid Receptors in Forebrain GABAergic Neurons Alters Acute Stress Responding and Passive Avoidance Behavior in Female Mice
No full textThe glucocorticoid receptor (GR) is critically involved in regulation of stress responses [inhibition of the hypothalamic-pituitary-adrenal (HPA) axis], emotional behavior and cognition via interactions with forebrain corticolimbic circuity. Work to date has largely focused on GR actions in forebrain excitatory neurons; however, recent studies suggest a potential role mediated by interneurons. Here, we targeted GR deletion in forebrain GABAergic neurons, including the cortical interneurons, using a Dlx5/6-Cre driver line to test the role of forebrain interneuronal GR in HPA axis regulation and behavior. Our data indicate that GR deletion in GABAergic neurons causes elevated corticosterone stress responsiveness and decreased cross-over latencies in a passive avoidance task in females, but not males. Dlx5/6-Cre driven gene deletion caused loss of GR in interneurons in the prefrontal cortex (PFC) and hippocampus, but also in select diencephalic GABAergic neurons (including the reticular thalamic nucleus and dorsomedial hypothalamus). Our data suggest that GR signaling in interneurons is differentially important in females, which may have implications for GR-directed therapies for stress-related affective disease states
Code authorship attribution using content-based and non-content-based features
No full textMachine learning approaches are widely used in natural language analysis. Previous research has shown that similar techniques can be applied in the analysis of computer programming (artificial) languages. In this thesis, we focus on identifying the authors of computer programs by using machine learning techniques. We extend these techniques to determine which features capture the writing style of authors in the classification of a computer program according to the author's identity. We then propose a novel approach for computer program author identification. In this method, program features from the text documents are combined with authors' sociological features (gender and region) to develop the classification model. Several experiments have been conducted on two datasets composed of computer programs written in C++, and the results are encouraging. According to the experimental results, the author's identity can be predicted with a accuracy rate
Diet-Induced Obese Mice Retain Endogenous Leptin Action
No full textSummaryObesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice
Measures of a Sustainable Commute as a Predictor of Happiness
No full textabstract: The ways in which we travel—by what mode, for how long, and for what purpose—can affect our sense of happiness and well-being. This paper assesses the relationships between measures of the sustainability of transportation systems in U.S. metropolitan areas and subjective well-being. Associations between self-reported happiness levels from the Gallup Healthways Well-being Index and commute data were examined for 187 core-based statistical areas (CBSA). We also supplement this quantitative analysis through brief case studies of high- and low-performing happiness cities. Our quantitative results indicate that regions with higher commute mode shares by non-automobile modes generally had higher well-being scores, even when controlling for important economic predictors of happiness. We also find that pro-sustainable transportation policies can have implications for population-wide happiness and well-being. Our case studies indicate that both high and low scoring happiness cities demonstrate a dedicated commitment to improving sustainable transportation infrastructure. Our study suggests that cities that provide incentives for residents to use more sustainable commute modes may offer greater opportunity for happiness than those that do not.The final version of this article, as published in Sustainability, can be viewed online at: http://www.mdpi.com/2071-1050/9/7/121
Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress
No full textOrganismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regional Glp1r knockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally, Glp1r knockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention
