Advances in Simultaneous Localization and Mapping in Confined Underwater Environments Using Sonar and Optical Imaging.

This thesis reports on the incorporation of surface information into a probabilistic simultaneous localization and mapping (SLAM) framework used on an autonomous underwater vehicle (AUV) designed for underwater inspection. AUVs operating in cluttered underwater environments, such as ship hulls or dams, are commonly equipped with Doppler-based sensors, which---in addition to navigation---provide a sparse representation of the environment in the form of a three-dimensional (3D) point cloud. The goal of this thesis is to develop perceptual algorithms that take full advantage of these sparse observations for correcting navigational drift and building a model of the environment. In particular, we focus on three objectives. First, we introduce a novel representation of this 3D point cloud as collections of planar features arranged in a factor graph. This factor graph representation probabalistically infers the spatial arrangement of each planar segment and can effectively model smooth surfaces (such as a ship hull). Second, we show how this technique can produce 3D models that serve as input to our pipeline that produces the first-ever 3D photomosaics using a two-dimensional (2D) imaging sonar. Finally, we propose a model-assisted bundle adjustment (BA) framework that allows for robust registration between surfaces observed from a Doppler sensor and visual features detected from optical images. Throughout this thesis, we show methods that produce 3D photomosaics using a combination of triangular meshes (derived from our SLAM framework or given a-priori), optical images, and sonar images. Overall, the contributions of this thesis greatly increase the accuracy, reliability, and utility of in-water ship hull inspection with AUVs despite the challenges they face in underwater environments. We provide results using the Hovering Autonomous Underwater Vehicle (HAUV) for autonomous ship hull inspection, which serves as the primary testbed for the algorithms presented in this thesis. The sensor payload of the HAUV consists primarily of: a Doppler velocity log (DVL) for underwater navigation and ranging, monocular and stereo cameras, and---for some applications---an imaging sonar.PhDElectrical Engineering: SystemsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/120750/1/paulozog_1.pd

Synthesis of Disulfonates as DapE Inhibitors Toward the Creation of Novel Antibiotics

In the 21st century, a global antibacterial resistance crisis has risen and is threatening the lives of millions. In addition, it has been determined that antibiotic resistance has added tremendous financial and clinical burdens on the U.S. health care system, patients and their families. The rise of this crisis has in part been attributed to the lack of new drug developments in the field of antibiotics as well as the overuse and misuse of existing medications. A novel bacterial pathway must be discovered and exploited in the fight to combat the antibiotic resistance crisis. DapE is an essential bacterial enzyme in the biosynthetic pathway responsible for the production of meso-diaminopimelic acid (m-DAP) and the amino acid lysine, which are critical to bacterial survival. DapE is an ideal drug target because the human body does not employ the DapE enzyme to manufacture lysine; humans must consume lysine in their diets. Thus, the elimination of mechanism-based toxicity, combined with the discovery of multiple potential inhibitors in our lab for this enzyme, makes DapE a great target to focus on toward the discovery of new antibiotics. This research has proven to be fruitful, but little is known about DapE and its properties. Synthesis of disulfonates will advance our understanding of the DapE enzyme in exploring the impact of a conformational change triggered by substrate binding means for the catalytic mechanism of the DapE enzyme

A Case of Metastatic Squamous Cell Carcinoma in a Patient with Recessive Dystrophic Epidermolysis Bullosa that was Responsive to Pembrolizumab, a Programmed Cell Death Protein 1 Inhibitor

A case of metastatic squamous cell carcinoma in a patient with recessive dystrophic epidermolysis bullosa that was responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. Purpose: Cutaneous squamous cell carcinomas (SCCs) are the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Management of SCCs in these patients is challenging with higher rates of recurrence and lymph nodes metastases. Although surgery is the first-line treatment in the majority of cases, certain clinical situations, such as local recurrence, or regional or distant metastasis, may call for nonsurgical treatment such as chemotherapy. We report the complex management of SCCs in a young female patient with RDEB whose nodal disease responded successfully to programmed cell death protein 1 (PD-1) inhibitor, pembrolizumab. Design: Patient is a 29-year-old female with a long-standing history of RDEB that has been complicated by multifocal and recurrent SCC of the skin. She initially presented in 2015, at the age of 24, for SCC of the skin that was treated with a combination of Mohs micrographic surgery (MMS), wide local excision, and laser-assisted topical delivery of aminolevulinic acid. Over the following 6 months she developed several additional invasive SCCs. Surgical resection was again attempted, however, pathology revealed positive deep and lateral margins at 2 excision sites. Computed tomography (CT) scan at this time revealed bilateral pulmonary nodules and axillary nodes concerning for early metastatic disease. Left axillary node biopsy performed however, was negative for metastatic disease and these were thought to be consistent with a reactive process. Oncology recommended off-label palliative use of cetuximab given her multifocal disease and higher risk of metastasis in RDEB patients. She completed 4 cycles of cetuximab complicated by sepsis due to group G streptococcus, likely from a cutaneous source, as well as a grade 2 EGFR-associated acneiform eruption. After 4 cycles, her CT remained stable and there was no evidence of cutaneous recurrence, so the decision was made to discontinue cetuximab at this time. However, two years following the cessation of cetuximab she developed multiple cutaneous recurrences and a surveillance CT scan showed enlargement of her left axillary lymph nodes to a mass of 3.7 x 4.0 cm in size. Nodal biospy revealed metastatic SCC and molecular testing performed showed that 100% of tumor cells (tumor proportion score) were positive for PD-L1 staining. The decision was made to start pembrolizumab as off label therapy with plans to pursue axillary node excision after she completed treatment. At the completion of 4 cycles of pembrolizumab, a repeat CT scan showed improvement in the enlarged nodes with reduction to 2.2 x 1.4 cm in size and regional lymph node resection was successfully performed. Summary: Pembrolizumab was the first PD-1 inhibitor approved by the FDA for metastatic melanoma. Recently in clinical trials, a new PD-1 inhibitor cemiplimab showed a 50% response rate in the treatment of cutaneous SCC and became the first systemic drug in it’s class to be approved for the treatment of locally advanced or metastatic cutaneous SCC. We report the first case of metastatic SCC in a RDEB patient that responded to treatment with PD-1 inhibitor, pembrolizumab. Conclusion: Immunotherapy with PD-1 inhibitors, such as pembrolizumab may be an alternative treatment modality for SCC in RDEB patients with late stage or metastatic disease. Further larger scale studies are warranted to determine the utility of PD-1 inhibitors in the multimodal management of these high-risk patients.https://scholarlycommons.henryford.com/merf2020caserpt/1131/thumbnail.jp

35224 Identifying a correlation between preceding trauma and development of dermatofibrosarcoma protuberans: A review of the literature

Background: Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic neoplasm that is slow-growing, has low metastatic potential, and is locally infiltrative with a predisposition for recurrence. The development of DFSP can occur spontaneously, but anecdotal evidence suggests a correlation between preceding injury and tumor onset. Methods: A comprehensive literature search was performed using PubMed, Embase, and web of science for articles with unambiguous reporting of DFSP with a history of physical trauma. Of 139 identified articles, 23 (17%) met criteria and were analyzed. Results: In total, 52 patients were reported as having had some form of physical trauma prior to DFSP development, and of these, sex was reported for half (40% men; 60% women). The mean (standard deviation) age at time of diagnosis was 42 (14) years, and lesions ranged from 1 to 20 cm. Involved locations included the trunk (62%), lower extremities (19%), upper extremities (12%), and head/neck (8%). The median (range) time between injury and self-reported lesion was 10 (1-19) years, while the median (range) time between injury and DFSP diagnosis was 10 (2-41) years. Types of injuries reported included tattoos (most common), vaccinations/injections, burns, surgeries, radiation, insect bites, and various levels of minor to blunt force. Discussion: A subset of DFSP cases arise in the setting of prior cutaneous trauma, which may play a role in their pathogenesis. Recognition of this possibility is important to avoid misdiagnosis (i.e., hypertrophic scar or keloid) or delay in diagnosis

Metastatic squamous cell carcinoma in a RDEB patient treated with pembrolizumab

A case of metastatic squamous cell carcinoma in a patient with recessive dystrophic epidermolysis bullosa that was responsive to pembrolizumab, a programmed cell death protein 1 inhibitor. Purpose: Cutaneous squamous cell carcinomas (SCCs) are the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Management of SCCs in these patients is challenging with higher rates of recurrence and lymph nodes metastases. Although surgery is the first-line treatment in the majority of cases, certain clinical situations, such as local recurrence, or regional or distant metastasis, may call for nonsurgical treatment such as chemotherapy. We report the complex management of SCCs in a young female patient with RDEB whose nodal disease responded successfully to programmed cell death protein 1 (PD-1) inhibitor, pembrolizumab. Design: Patient is a 29-year-old female with a long-standing history of RDEB that has been complicated by multifocal and recurrent SCC of the skin. She initially presented in 2015, at the age of 24, for SCC of the skin that was treated with a combination of Mohs micrographic surgery (MMS), wide local excision, and laser-assisted topical delivery of aminolevulinic acid. Over the following 6 months she developed several additional invasive SCCs. Surgical resection was again attempted, however, pathology revealed positive deep and lateral margins at 2 excision sites. Computed tomography (CT) scan at this time revealed bilateral pulmonary nodules and axillary nodes concerning for early metastatic disease. Left axillary node biopsy performed however, was negative for metastatic disease and these were thought to be consistent with a reactive process. Oncology recommended off-label palliative use of cetuximab given her multifocal disease and higher risk of metastasis in RDEB patients. She completed 4 cycles of cetuximab complicated by sepsis due to group G streptococcus, likely from a cutaneous source, as well as a grade 2 EGFR-associated acneiform eruption. After 4 cycles, her CT remained stable and there was no evidence of cutaneous recurrence, so the decision was made to discontinue cetuximab at this time. However, two years following the cessation of cetuximab she developed multiple cutaneous recurrences and a surveillance CT scan showed enlargement of her left axillary lymph nodes to a mass of 3.7 x 4.0 cm in size. Nodal biopsy revealed metastatic SCC and molecular testing performed showed that 100% of tumor cells (tumor proportion score) were positive for PD-L1 staining. The decision was made to start pembrolizumab as off label therapy with plans to pursue axillary node excision after she completed treatment. At the completion of 4 cycles of pembrolizumab, a repeat CT scan showed improvement in the enlarged nodes with reduction to 2.2 x 1.4 cm in size and regional lymph node resection was successfully performed. Summary: Pembrolizumab was the first PD-1 inhibitor approved by the FDA for metastatic melanoma. Recently in clinical trials, a new PD-1 inhibitor cemiplimab showed a 50% response rate in the treatment of cutaneous SCC and became the first systemic drug in it’s class to be approved for the treatment of locally advanced or metastatic cutaneous SCC. We report the first case of metastatic SCC in a RDEB patient that responded to treatment with PD-1 inhibitor, pembrolizumab. Conclusion: Immunotherapy with PD-1 inhibitors, such as pembrolizumab may be an alternative treatment modality for SCC in RDEB patients with late stage or metastatic disease. Further larger scale studies are warranted to determine the utility of PD-1 inhibitors in the multimodal management of these high-risk patients.https://scholarlycommons.henryford.com/merf2020caserpt/1006/thumbnail.jp

Scottish Merchants in Poland 1550-1750

Poland, for the purposes of this study is taken to be metropolitan Poland, that is the areas of the kingdom with Polish speaking people. In the west this area was bordered by the Mark of Brandenburg; in the south-west and south by Habsburg lands; in the south-east by the Ottoman Empire and in the east by Lithuania which did not become united to Poland until the Union Of Lublin in 1596. This study also generally excludes Danzig which, although under the Polish king, was a free city largely inhabited by Germanic peoples. Although this study is concerned with the period circa 1550-1750 it must not be presumed that there were no Scots in Poland before this. The Scots had had trading relations with Poland at least two centuries prior to this and it may reasonably be assumed, although there is no surviving documentary evidence to support this assumption, that once these relations were established Scots, in the form of factors and merchants, went to Poland to advance the trade.

THE DIURNAL AND SEASONAL RADIATIVE EFFECTS OF CIRRUS CLOUDS UTILIZING LARGE AIRBORNE AND SPACE-BORNE LIDAR DATASETS

Cirrus clouds are globally the most common cloud type, however, their radiative impact on the Earth remains a large source of uncertainty in global climate models. Cirrus are unique in that they are absorptive to terrestrial outgoing longwave radiation, while also relatively transmissive to incoming solar radiation. The interactions of this greenhouse and albedo effect determine the sign and magnitude of cirrus radiative effects. Cirrus are microphysically complex, and can exhibit a variety of different ice crystal shapes and sizes depending on the thermodynamic environment in which they form, and their dynamic formation mechanism. Our ability to reliably model cirrus radiative effects is dependent upon accurate observations and parameterizations incorporated into radiative transfer simulations. Laser lidar instruments provide valuable measurements of cirrus clouds unavailable by other radar systems, passive remote sensors, or in-situ instruments alone. In this dissertation I developed and tested an improved calibration technique for the ACATS lidar instrument, and its impact on the direct retrieval of cirrus HSRL optical properties. HSRL retrievals theoretically have reduced uncertainty over those from a standard backscatter lidar. ACATS flew on two field campaigns in 2012 and 2015 where it was unable to consistently calibrate its etalon. It has been operating from the lab in NASA GSFC collecting zenith pointing data of cirrus layers where the improved calibration has resulted in consistent and reliable separation of the particulate and Rayleigh signal components. The diurnal trend of cirrus influence on the global scale has primarily been limited to data provided by satellites in sun-synchronous orbit, which provide only a snapshot of conditions at two times a day. Utilizing data from the CATS lidar aboard the ISS I investigated cirrus at four periods throughout the day in morning, afternoon, evening, and night across all seasons. Cirrus radiative effects were found to have a large latitudinal dependence, and have a greater potential to cool than many studies suggest with their primary warming contributions skewed towards the nighttime hours. Constrained lidar retrievals reduce the assumptions made in retrieving cirrus optical properties. Utilizing the expansive airborne CPL dataset from six flight campaigns I model the radiative effects of over twenty thousand constrained cirrus observations. Mid-latitude cirrus were found to have a mean positive daytime forcing equivalent to that of the CO2 greenhouse effect. However, synoptic cirrus were found to have a greater warming effect than convective cirrus, which were more likely to have a cooling effect