Relating crack heating to vibration for vibrothermography

Vibrothermography is an inspection technique that detects cracks by observing vibration induced crack heating. Frictional crack heating in a vibrating specimen is directly linked to the resonant vibrational stress on the crack. In simple geometries we can measure the vibrational mode structure and intuit the dynamic vibrational stress field on the crack. This can be used to establish a relationship between crack heating and vibration, which will be critical for vibrothermography to be accepted as a viable inspection technology. We correlate stress to heating by exciting specimens in a well understood and repeatable resonant vibration mode. Through knowledge of the mode shape, a single point surface velocity measurement is sufficient to calculate the deformed shape of the entire specimen. The loads and stresses within the specimen are calculated from the deformed shape and used to identify the relationship between crack heating and vibration. We explore a simplified case of a bar in third order flexural resonance with a surface crack that heats in response to flexure-induced normal load. Specimens are tuned to resonate in third order flexural bending when excited with a single frequency excitation system. We present an observed relationship between dynamic normal stress, crack size, and crack heating

Characterizing Targeted Therapeutic Delivery and Cellular Dynamics using In Vitro Cancer Disease Models

Cancer is a significant health risk to people living in developed and developing countries, which continues to prove difficult to treat. Common treatment options of cancers include surgical removal, radiation, and chemotherapies, which are often used in combination to improve the likelihood of successful treatment. Such combinatory approaches towards treatment are often taken because each approach is not targeted enough to function perfectly on its own. Being able to delivery therapeutic loads in a more targeted manner to sites of cancer has the capability of improving therapeutic efficiency and improving patient responses. The development of improved therapeutic delivery vehicles and screening systems can help serve the goal of improved targeted therapeutic delivery. The use of microfluidic devices for the study of therapeutic delivery has become popular over the past few decades because of the many benefits that they offer. Specifically, microfluidic devices only require small volumes of therapeutics for testing, which is often ideal because of limited drug supply during screening. Additionally, the high degree of control over channel geometries, ease of fabrication and low cost make microfluidic therapeutic testing devices well suited for higher throughput screening when run together in parallel. The ability to generate shear flow within the microfluidic channels also offers a means of more closely mimicking vascular physiology and conditions that would be experienced during drug delivery in the human body. Lastly, the use of microfluidic in therapeutic testing enables micro-scale data on characteristics such as binding, uptake, cellular permeability and others to be easily collected due to the transparent nature of the devices and ability to facilitate cell cultures. As such, the focus of this dissertation is mainly based around the establishment of microfluidic systems capable of mimicking cancerous environments and testing of various therapeutic vehicles and delivery methods targeted for cancer. In brief, the dissertation demonstrates a few methods of establishing cancerous environments within microfluidic systems of increasing complexity, and how screening of various nanoparticle vehicles and therapeutics is performed.First, a single layer microfluidic device is developed to facilitate the growth of cancer monolayers for the screening of solid lipid nanoparticle drug delivery performance. The device is designed to assist in identifying an optimal ratio of antibody to polymer chains exposed on the surface of the nanoparticles. Improved targeting of nanoparticles to cancer cells is achieved by increasing target specific binding through addition of cancer antibody while reducing non-specific binding through addition of polymer chains on the nanoparticles surface. Conditions for optimal targeting specifically to cancer cells were identified for nanoparticles with 37% of their surface area occupied by polyethelyene glycol (PEG). The cancer cell targeting efficiency for the 37% coated nanoparticles was determined to be a maximum of 81% when a cancer specific antibody was used in conjunction on the nanoparticles surface.Next, to improve the physiological relevance of the microfluidic screening system, a bi-layer setup was fabricated. The nature of the bi-layer device is designed to facilitate the co-culture of cancer and endothelial cells (ECs) in different compartments while still permitting signaling and chemical interactions to occur between the two cell types. The presence of ECs in the device is designed to mimic a blood vessel, as therapeutic delivery within the body relies heavily on the circulatory system from drug transport. As such, understanding the mechanics of therapeutic delivery from mimicked vasculature to cancer is an important consideration. Conditions in the bi-layer system influencing therapeutic transport include endothelial permeability, therapeutic size, system flow rate, and treatment time. Improved therapeutic delivery was achieved using smaller molecules, slower system flow rates, and when the EC monolayer was highly permeabilized. Increased treatment times, resulted in less and less therapeutic transport from the mimicked vessel to the cancer environment as the EC monolayer regained confluency. It was shown that the bi-layer microfluidic system functions to screen therapeutic delivery to a mimicked cancer environment under more physiologically relevant conditions.The next progression with the system was to test nanoparticle delivery and transport from the mimicked vessel to the cancer environment. This was accomplished utilizing the same bi-layer microfluidic setup in conjunction with a range of nanoparticle shapes that were utilized to identify characteristics that facilitate the greatest degree of therapeutic delivery. Specifically, spherical, short rod and long rod/worm-like nanoparticles were tested for their ability to transport therapeutic loads to the cancer environment over the course of 5 day treatments. Optimal nanoparticle shapes for each flow rate varied based on treatment time. Overall, nanoparticle drug delivery should be varied based on the degree of EC permeability which changes with time as the cancer environment is treated.Lastly, to improve the physiological relevance of cancer environments being used, a method for establishing and growing tumor spheroids within the microfluidic devices in an expedited fashion was developed. The ability to perform therapeutic and nanoparticle carrier screening on tumor spheroids as opposed to cancer monolayers provides feedback on efficiency and performance which more closely mimics outcomes observed in animal and clinical testing. In addition, the ability to form tumor spheroids in an expedited manner allows the screening process to be completed in a shorter period of time and with fewer initial cells. The use of convective driven nutrient flow is utilized to achieve such expedited cancer growth in a microfluidic system which also has the potential to facilitate therapeutic screening. The system has been shown to function with adherent and non-adherent cell types where 1.5 to 4.5 times faster growth can be achieved. The ability to cut tumor culturing times from 1 week to 3 days and reducing required cell counts from thousands to tens of cells has the potential to save lives in clinical settings when using patient derived samples

Optimierung mit Taktsignalen angesteuerter Stromschalter in breitbandigen Hochgeschwindigkeitsschaltungen in Bipolar-Technologie

Die vorliegende Arbeit behandelt die Optimierung von mit Taktsignalen angesteuerten Stromschaltern in Bipolar-Technologie im Hinblick auf Ausgangsamplitude, Grenzfrequenz, Flankensteilheit und Tastgradfehler bzw. Gleichanteil. Diese Größen sind bei Taktverteilungsschaltungen sowie allgemein bei mit Taktsignalen angesteuerten Schaltungen entscheidend, um hohe Taktfrequenzen bis möglichst nahe an die Technologiegrenze zu erreichen. Die Besonderheit der vorliegenden Arbeit liegt in der Betrachtung breitbandiger Schaltungen, welche von niedrigen bis hohen Taktfrequenzen eingesetzt werden. Die Arbeit ist zweigeteilt in einen theoretischen und einen experimentellen Teil. Im theoretischen Teil werden analytische Modelle zur Beschreibung der Einflussfaktoren auf die betrachteten Größen vorgestellt. Die Modelle erlauben eine zielführende Schaltungsoptimierung. Sie geben zudem teilweise erstmalig Einblicke in Zusammenhänge, welche bis dato lediglich experimentell oder simulativ beobachtet worden sind. Der experimentelle Teil stellt die Entwicklung zweier Varianten einer Multiplexer-Schaltung vor. Hierfür werden neben dem Anwenden der analytischen Modelle ein spezielles Konzept zur breitbandigen Phasenverschiebung von Taktsignalen und ein darauf basierender Frequenzverdoppler eingesetzt. Beide realisierten Varianten der Multiplexer-Schaltung stellen mit hohen Datenraten bei hohen Ausgangshüben zum Zeitpunkt der jeweiligen Veröffentlichungen einen Rekord auf.The present thesis deals with the optimization of clock-driven current switches in bipolar technology with regard to output amplitude, cut-off frequency, edge steepness and duty cycle error or DC component. These criteria are important in clock distribution circuits as well as generally in circuits driven by clock signals in order to operate at clock frequencies close to the semiconductor technology limit. The peculiarity of the present work lies in the consideration of broadband circuits, which are used at low to high clock frequencies. The thesis is divided into a theoretical and an experimental part. In the theoretical part, analytical models for describing the influencing factors on the considered criteria are presented. By these, dimensioning and optimization of the circuits under investigation can be performed in a fast and target-aiming way. For the first time, the models also provide insights into relationships that have so far only been observed experimentally or by simulation. In the experimental part, two variants of a multiplexer circuit are presented. Besides applying the analytical models, a special concept for a broadband clock phase shifter circuit is proposed and applied in a frequency doubler. Both variants of the multiplexer circuit realized with these methods and circuit concepts form a record at the time of the corresponding publications with their high data rates at high output voltage swings

Toward a Viable Strategy for Estimating Vibrothermographic Probability of Detection

Vibrothermography is a technique for finding cracks and delaminations through infrared imaging of vibration‐induced heating. While vibrothermography has shown remarkable promise, it has been plagued by persistent questions about its reproducibility and reliability. Fundamentally, the crack heating is caused by the vibration, and therefore to understand the heating process we must first understand the vibration process. We lay out the problem and begin the first steps toward relating detectability to the local motion around a crack as well as the crack size. A particular mode, the third‐order free‐free flexural resonance, turns out to be particularly insensitive to the presence of clamping and transducer contact. When this mode is excited in a simple bar geometry the motions of the part follow theoretical calculations quite closely, and a single point laser vibrometer measurement is sufficient to evaluate the motion everywhere. Simple calculations estimate stress and strain anywhere in the bar, and these can then be related to observed crack heating

Identifying Risk Factors of Upper Extremity Injuries in Collegiate Baseball Players: A Pilot Study

Background Repetitive pitching places tremendous forces on the shoulder and elbow which can lead to upper extremity (UE) or lower extremity (LE) overuse injuries. Purpose The purpose of this study was to evaluate pre-season physical measurements in collegiate baseball players and track in-season baseball throwing volume to determine which factors may predict throwing overuse injuries. Study Design Retrospective Cohort study. Methods Baseline preseason mobility, strength, endurance, and perception of function were measured in 17 collegiate baseball pitchers. Participants were then followed during the course of the season to collect rate of individual exposure, estimated pitch volume, and rating of perceived exertion in order to determine if changes in workload contributed to risk of injury using an Acute-to-Chronic Workload ratio (ACWR). Results Participants developing an injury had greater shoulder internal rotator strength (p=0.04) and grip strength in a neutral position (p=0.03). A significant relationship was identified between ACWR and UE injuries (p \u3c 0.001). Athletes with an ACWR above or below 33% were 8.3 (CI95 1.8-54.1) times more likely to suffer a throwing overuse injury occurring to the upper or lower extremity in the subsequent week. Conclusion ACWR change in a positive or negative direction by 33% was the primary predictor of subsequent injury. This finding may assist sports medicine clinicians by using this threshold when tracking pitch volume to ensure a safe progression in workload during a baseball season to reduce the risk of sustaining overuse upper or lower extremity injuries. Level of Evidence 3

Leaf Demography And Phenology In Amazonian Rain Forest: A Census Of 40 000 Leaves Of 23 Tree Species

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116912/1/ecm20047413.pd

Structureâ Property Relationships in Aligned Electrospun Barium Titanate Nanofibers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135366/1/jace14455_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135366/2/jace14455.pd

A Biologic-Device Combination Product Delivering Tumor-Derived Antigens Elicits Immunogenic Cell Death-Associated Immune Responses Against Glioblastoma

Background IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5–6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients. Methods Mouse (m) or human (h) variants of IGV-001 were prepared using GL261 mouse GBM cells or human GBM cells, respectively. BDCs containing vehicle or mIGV-001 were implanted in the flanks of C57BL/6 albino female mice in preventative and therapeutic experiments, optionally in combination with a programmed cell death 1 (PD-1) blocker. Bioactivity of the general approach was also measured against hepatocellular carcinoma Hepa 1–6 cells. Mice were followed for the growth of subsequently implanted or pre-existing tumors and survival. Draining lymph nodes from mice receiving mIGV-001 were immunophenotyped. mIGV-001 and hIGV-001 were analyzed for extracellular ATP and high mobility group box 1 (HMGB1) as indicators of immunogenic cell death (ICD), along with flow cytometric analysis of viability, surface calreticulin, and reactive oxygen species. Stress and cell death-related pathways were analyzed by immunoblotting. Results IGV-001 causes oxidative and endoplasmic reticulum stress in GL261 cells, resulting in a cytotoxic response that enables the release of antigenic material and immunostimulatory, ICD-associated molecules including ATP and HMGB1 from BDCs. Immunophenotyping confirmed that IGV-001 increases the percentage of dendritic cells, as well as effector, and effector memory T cells in BDC-draining lymph nodes. Consistent with these observations, preventative IGV-001 limited tumor progression and extended overall survival in mice intracranially challenged with GL261 cells, a benefit that was associated with an increase in tumor-specific T cells with effector features. Similar findings were obtained in the Hepa 1–6 model. Moreover, therapeutically administered IGV-001 combined with PD-1 delayed progression in GBM-bearing mice. Conclusions These results support treatment with IGV-001 to induce clinically relevant ICD-driven anticancer immune responses in patients with GBM