Improving Pile Foundation Models for use in Bottom-fixed Offshore Wind Turbine Applications

AbstractPerforming a dynamic analysis of an offshore wind turbine with an aero-elastic solver relies on the inclusion of a model to represent the behavior of the piled foundations. The most commonly used solution is the p-y method, which was developed for offshore oil and gas applications and has been extended to the offshore wind energy industry. There are several shortcomings with this method, however, which can affect the accuracy of wind turbine simulations. These shortcomings are identified and explained in this work. More advanced pile foundations models which account for many nonlinear behaviors ignored by the traditional p-y method have been developed in the past for applications unrelated to offshore wind turbines. These models can nevertheless be applied to offshore wind turbine simulations and are discussed herein. A proposed method for incorporating these so called ‘dynamic p-y’ models into wind turbine simulations is laid out and discussed

IMPROVED METHODS FOR THE ANALYSIS OF SINGLE-CELL RNA-SEQUENCING AND IMAGING DATA

Two key challenges in the analysis of single cell RNA-seq (scRNA-seq) data are excess zeros due to “drop-out” events and substantial overdispersion due to stochastic and systematic differences. Association analysis of scRNA-seq data is further confronted with the possible dependency introduced by measuring multiple single cells from the same biological sample. To address these three challenges, the first chapter of this work proposes TWO-SIGMA: a TWO-component SInGle cell Model-based Association method for differential expression analysis of scRNA-seq data. The first component models the drop-out probability with a mixed-effects logistic regression, and the second component models the (conditional) mean read count with a mixed-effects negative binomial regression. Simulation studies and real data analysis show advantages in type-I error control and power enhancement over alternative approaches including MAST and a zero-inflated negative binomial model without random effects. The second chapter of this dissertation expands the first to Gene set testing (GST). Here, we propose TWO-SIGMA-Geneset to conduct competitive gene set testing, in which the genes in a given set are compared to the remaining collection of genes. Previous work has demonstrated that inter-gene correlation can substantially inflate type-I error. We provide an adjustment for inter-gene correlation, which is estimated using the residuals from the gene-level TWO-SIGMA model. Simulation studies show that type-I error is well controlled in a variety of representative scenarios, with or without inter-gene correlation present. Power is improved over state-of-the-art methods, including CAMERA, for a variety of scenarios consistent with real single-cell RNA-seq data. Finally, the third chapter of this work studies chromosomal interactions at the single-cell level. First, we discuss the Hi-C technology for analyzing genome-wide chromosomal interactions. In particular, we focus on peak calling, in which the aim is to separate interactions between loci that are due to random chance from interactions that are not random. Second, we discuss state-of-the-art methods for single-cell imaging. We then show an example of a way to combine information from Hi-C and imaging data from Drosophilia embryos for peak calling using the Cauchy Combination Test. We conclude by discussing potential future research in this context.Doctor of Philosoph

Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

We demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure

C16-Ceramide Analog Combined with Pc 4 Photodynamic Therapy Evokes Enhanced Total Ceramide Accumulation, Promotion of DEVDase Activation in the Absence of Apoptosis, and Augmented Overall Cell Killing

Because of the failure of single modality approaches, combination therapy for cancer treatment is a promising alternative. Sphingolipid analogs, with or without anticancer drugs, can improve tumor response. C16-pyridinium ceramide analog LCL30, was used in combination with photodynamic therapy (PDT), an anticancer treatment modality, to test the hypothesis that the combined treatment will trigger changes in the sphingolipid profile and promote cell death. Using SCCVII mouse squamous carcinoma cells, and the silicone phthalocyanine Pc 4 for PDT, we showed that combining PDT with LCL30 (PDT/LCL30) was more effective than individual treatments in raising global ceramide levels, as well as in reducing dihydrosphingosine levels. Unlike LCL30, PDT, alone or combined, increased total dihydroceramide levels. Sphingosine levels were unaffected by LCL30, but were abolished after PDT or the combination. LCL30-triggered rise in sphingosine-1-phosphate was reversed post-PDT or the combination. DEVDase activation was evoked after PDT or LCL30, and was promoted post- PDT/LCL30. Neither mitochondrial depolarization nor apoptosis were observed after any of the treatments. Notably, treatment with the combination resulted in augmented overall cell killing. Our data demonstrate that treatment with PDT/LCL30 leads to enhanced global ceramide levels and DEVDase activation in the absence of apoptosis, and promotion of total cell killing

Increased R2* in the Caudate Nucleus of Asymptomatic Welders

Welding has been associated with neurobehavioral disorders. Welding fumes contain several metals including copper (Cu), manganese (Mn), and iron (Fe) that may interact to influence welding-related neurotoxicity. Although welding-related airborne Fe levels are about 10-fold higher than Mn, previous studies have focused on Mn and its accumulation in the basal ganglia. This study examined differences in the apparent transverse relaxation rates [R2* (1/T2*), estimate of Fe accumulation] in the basal ganglia (caudate nucleus, putamen, and globus pallidus) between welders and controls, and the dose–response relationship between estimated Fe exposure and R2* values. Occupational questionnaires estimated recent and lifetime Fe exposure, and blood Fe levels and brain magnetic resonance imaging (MRI) were obtained. Complete exposure and MRI R2* and R1 (1/T1: measure to estimate Mn accumulation) data from 42 subjects with welding exposure and 29 controls were analyzed. Welders had significantly greater exposure metrics and higher whole-blood Fe levels compared with controls. R2* in the caudate nucleus was significantly higher in welders after controlling for age, body mass index, respirator use, caudate R1, and blood metals of Cu and Mn, whereas there was no difference in R1 values in the basal ganglia between groups. The R2* in the caudate nucleus was positively correlated with whole-blood Fe concentration. This study provides the first evidence of higher R2* in the caudate nucleus of welders, which is suggestive of increased Fe accumulation in this area. Further studies are needed to replicate the findings and determine the neurobehavioral relevance

Editor’s Highlight: Lower Fractional Anisotropy in the Globus Pallidus of Asymptomatic Welders, a Marker for Long-Term Welding Exposure

Introduction: Welding fumes contain several metals including manganese (Mn), iron (Fe), and copper (Cu) that at high exposure may co-influence welding-related neurotoxicity. The relationship between brain accumulation of these metals and neuropathology, especially in welders with subclinical exposure levels, is unclear. This study examined the microstructural integrity of basal ganglia (BG) regions in asymptomatic welders using diffusion tensor imaging (DTI). Methods: Subjects with (n = 43) and without (age- and gender-matched controls; n = 31) history of welding were studied. Occupational questionnaires estimated short-term (HrsW; welding hours and E90; cumulative exposure, past 90 days) and long-term (YrsW; total years welding and ELT; cumulative exposure, lifetime) exposure. Whole blood metal levels (Mn, Fe, and Cu) were obtained. Brain MRI pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and Fe accumulation in BG [caudate, putamen, and globus pallidus (GP)]. DTI was used to assess BG microstructural differences, and related with exposure measurements. Results: When compared with controls, welders had significantly lower fractional anisotropy (FA) in the GP. In welders, GP FA values showed non-linear relationships to YrsW, blood Mn, and PI. GP FA decreased after a critical level of YrsW or Mn was reached, whereas it decreased with increasing PI values until plateauing at the highest PI values. GP FA, however, did not show any relationship with short-term exposure measurements (HrsW, E90), blood Cu and Fe, or R2* values. Conclusion: GP FA captured microstructural changes associated with chronic low-level Mn exposure, and may serve as a biomarker for neurotoxicity in asymptomatic welders

T1 Relaxation Rate (R1) Indicates Nonlinear Mn Accumulation in Brain Tissue of Welders With Low-Level Exposure

Although the essential element manganese (Mn) is neurotoxic at high doses, the effects of lower exposure are unclear. MRI T1-weighted (TIW) imaging has been used to estimate brain Mn exposure via the pallidal index (PI), defined as the T1W intensity ratio in the globus pallidus (GP) versus frontal white matter (FWM). PI may not, however, be sensitive to Mn in GP because Mn also may accumulate in FWM. This study explored: (1) whether T1 relaxation rate (R1) could quantify brain Mn accumulation more sensitively; and (2) the dose-response relationship between estimated Mn exposure and T1 relaxation rate (R1). Thirty-five active welders and 30 controls were studied. Occupational questionnaires were used to estimate hours welding in the past 90 days (HrsW) and lifetime measures of Mn exposure. T1W imaging and T1-measurement were utilized to generate PI and R1 values in brain regions of interest (ROIs). PI did not show a significant association with any measure of Mn and/or welding-related exposure. Conversely, in several ROIs, R1 showed a nonlinear relationship to HrsW, with R1 signal increasing only after a critical exposure was reached. The GP had the greatest rate of Mn accumulation. Welders with higher exposure showed significantly higher R1 compared either with controls or with welders with lower exposure. Our data are additional evidence that Mn accumulation can be assessed more sensitively by R1 than by PI. Moreover, the nonlinear relationship between welding exposure and Mn brain accumulation should be considered in future studies and policies

The Grizzly, October 19, 1999

Homecoming 1999 Hit Ursinus This Past Weekend • Handicap Accessibility On Ursinus College Campus • Adding to the Arts Program? • Reimert: A Suite Housing Experience • Baked to Perfection at Brew Moon • Opinion: Don\u27t They Have Anything Better to do?; Letters to the Editors; Guns Don\u27t Kill People, People Kill People • Modernized Version of Antigone High in Energy, Mediocre in Quality • Bears Fight off Gettysburg Bullets Gridiron • Hockey Battles with Holy Cross and Davis & Elkins; A Close Call and a Win • Two Near Misses for Men\u27s Soccer • Bishop Takes Top Honors at Moravianhttps://digitalcommons.ursinus.edu/grizzlynews/1449/thumbnail.jp

Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice

Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable to control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL-6 levels, expression of pro-inflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice, and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus non-obese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression