14 research outputs found
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Linear instability for incompressible inviscid fluid flows : two classes of perturbations
textOne approach to examining the stability of a fluid flow is to linearize the
evolution equation at an equilibrium and determine (if possible) the stability
of the resulting linear evolution equation. In this dissertation, the space of
perturbations of the equilibrium flow is split into two classes and growth of
the linear evolution operator on each class is analyzed. Our classification of
perturbations is most naturally described in V.I. Arnold’s geometric view of
fluid dynamics. The first class of perturbations we examine are those that
preserve the topology of vortex lines and the second class is the factor space
corresponding to the first class. In this dissertation we establish lower bounds
for the essential spectral radius of the linear evolution operator restricted to
each class of perturbations.Mathematic
Introduction to the Special Issue on Teaching Inquiry (Part II): Implementing Inquiry
We provide an introduction to the special issue on Teaching Inquiry, through its motivation and themes, focusing here on Part II: Implementing Inquiry
Introduction to the Special Issue on Teaching Inquiry (Part I): Illuminating Inquiry
We provide an introduction to the special issue on Teaching Inquiry, through its motivation and themes. We focus here on Part I: Illuminating Inquiry
Linear instability criteria for ideal fluid flows subject to two subclasses of perturbations
In this paper we examine the linear stability of equilibrium solutions to
incompressible Euler's equation in 2- and 3-dimensions. The space of
perturbations is split into two classes - those that preserve the topology of
vortex lines and those in the corresponding factor space. This classification
of perturbations arises naturally from the geometric structure of
hydrodynamics; our first class of perturbations is the tangent space to the
co-adjoint orbit. Instability criteria for equilibrium solutions are
established in the form of lower bounds for the essential spectral radius of
the linear evolution operator restricted to each class of perturbation.Comment: 29 page
Minimal residual disease in Myeloma: Application for clinical care and new drug registration
The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes
DHX34 and NBAS form part of an autoregulatory NMD circuit that regulates endogenous RNA targets in human cells, zebrafish and Caenorhabditis elegans
The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs harboring premature termination codons but also regulates the abundance of cellular RNAs. We sought to identify transcripts that are regulated by two novel NMD factors, DHX34 and neuroblastoma amplified sequence (NBAS), which were identified in a genome-wide RNA interference screen in Caenorhabditis elegans and later shown to mediate NMD in vertebrates. We performed microarray expression profile analysis in human cells, zebrafish embryos and C. elegans that were individually depleted of these factors. Our analysis revealed that a significant proportion of genes are co-regulated by DHX34, NBAS and core NMD factors in these three organisms. Further analysis indicates that NMD modulates cellular stress response pathways and membrane trafficking across species. Interestingly, transcripts encoding different NMD factors were sensitive to DHX34 and NBAS depletion, suggesting that these factors participate in a conserved NMD negative feedback regulatory loop, as was recently described for core NMD factors. In summary, we find that DHX34 and NBAS act in concert with core NMD factors to co-regulate a large number of endogenous RNA targets. Furthermore, the conservation of a mechanism to tightly control NMD homeostasis across different species highlights the importance of the NMD response in the control of gene expression
Philip MorrisonLINEAR INSTABILITY FOR INCOMPRESSIBLE INVISCID FLUID FLOWS: TWO CLASSES OF
I am indebted to several people for their help and support leading up to the completion of this dissertation. First, I wish to thank Boris Kunin for convincing me to become a mathematician and for the countless hours of discussion that prepared me for graduate school in mathematics. I would also like to thank Misha Vishik, not only for introducing me to some very interesting mathematics, but also for his dedication as my advisor. Misha always encouraged me to be my own mathematician and kept me from making any terrible mistakes along the way. Several other members of the department here at UT have graciously shared their time and wisdom to provided me with support both academic and non-academic throughout my graduate career. I especially wish to thank Irene Gamba, Karen Uhlenbeck and Bill Beckner. My fellow graduate students have been excellent collegues – in particular I would like to thank Tim Blass for all of the helpful mathematical discussions. I am grateful to my dad for his enthusiastic encouragement of all my scientific pursuits, and to my mom for showing me what it is to be a woman totally confident in her intellectual abilities. I am also grateful to Brian, Pippa, Adri and Brandy for being truly amazing friends. Finally, I would like to v express deepest gratitude to Mike for his patience and understanding, which have made it possible for me to pursue a career in mathematics. vi LINEAR INSTABILITY FOR INCOMPRESSIBL
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Increased Risk of Monoclonal Gammopathy of Undetermined Significance in US Military Service Members: A Case-Control Study of 1,068 Service Members Deployed to Either Europe or Iraq, with or without Reported Burn Pit and Toxic Smoke Exposure
Background:Monoclonal Gammopathy of Undetermined Significance (MGUS) is a plasma cell disorder which may lead to and in all cases precedes multiple myeloma (MM). Although, the etiology of MGUS is unknown, multiple studies have shown an association between MGUS and pesticide exposure (Kachuri et al, Int. J. Cancer 2013). Furthermore, soldiers and First Responders may be at higher risk of developing MGUS as evidenced by a 2.4-fold increased risk for MGUS in Vietnam Veterans exposed to Agent Orange (Landgren et al, JAMA Oncol. 2015) and a 1.8-fold higher risk in World Trade Center (9/11 attacks)-exposed fire fighters compared to reference populations (Landgren et al, JAMA Oncol. 2018). US Service Members deployed to the Southwest Asia theater of military operations (e.g., Iraq and Afghanistan) may have been exposed to various airborne hazards including smoke and fumes from open burn pits (chemical, paint, munitions, petroleum, plastic, rubber, medical, human, and food waste), oil well fires, and aircraft fuel/exhaust. Researchers are currently investigating the long-term consequences from these exposures. We were motivated to determine whether US Service Members deployed to Iraq were at increased risk of developing MGUS. Methods: Serum samples and clinical data (N=1,068) were attained from the Armed Forces Health Surveillance Division (AFHSD), the central epidemiologic health registry and biorepository for the US Military after IRB exemptions were granted. A total of 534 US Service Members who deployed to Iraq between January 1, 2005 and June 30, 2007 and reported burn pit exposure, smoke, burning trash, etc. on their post-deployment health assessment form (exposed cases) were matched 1:1 to 534 Members deployed to Germany (matched controls) who were never deployed to Southwest Asia and denied toxic exposure. All cases were deployed ≥ 6 months, were ≥ 35 years old at time of deployment, remained in the military ≥ 10 years and had serum available in the AFHSD repository 10 years after deployment. Matched criteria included deployment year (+/- 10 years), age (+/- 3 years), sex, service branch, military rank, and occupation category. The 10-year post-deployment samples underwent laboratory testing to screen for monoclonal protein by immunofixation (IFE) using pentavalent antisera with positive samples confirmed and typed using IFE gels (Sebia) and for serum free light chains (sFLC; Sebia) performed on the DYNEX Agility platform. IFE-positive samples underwent serum protein electrophoresis (SPEP) quantification by capillary electrophoresis (Sebia). Results:The median age of exposed Service Members was 37 years (range: 35-52) and 37 years (range: 35-55) for controls (Table 1). In both cohorts, the frequency of White (64.8%), Black (18.7%), Hispanic (7.5%), and male (89%) patients were the same as was the distribution of military occupation, rank, and service branch. The median number of days deployed for exposed vs controls was 243 and 852, respectively. There was no statistically significant difference between burn pit exposed and controls in the combined prevalence of MGUS (IFE+ monoclonal protein) and light chain (LC) MGUS (abnormal sFLC ratio), 6.7% (95% Confidence Interval (CI): 4.8-9.2%) vs 5.4% (95% CI: 3.7-7.7%), respectively (p=0.22). Similarly, there was no difference in prevalence when assessing IFE+ or sFLC+ cases separately (Table 2). The prevalence of MGUS or LC-MGUS for all 1,068 Service Members was 6.1% (95% CI: 4.7-7.7%). Conclusion:In our cohort of 534 Service Members deployed to Iraq and exposed to burn pits and other airborne toxic hazards (cases) there was no statistically significant difference in the prevalence of MGUS compared to 534 deployed to Germany (matched controls). Interestingly, the overall prevalence of MGUS/LC-MGUS in this combined deployed population was 6.1%. When taking into account that the median age at deployment was 37 years and samples were attained 10 years later (approximately at an age of 47 years), the observed prevalence is 3-fold higher than that reported in the Icelandic iStopMM study (2% in the 41-50 -year age group). Future studies are needed to further elucidate causes for the increased prevalence of MGUS/LC-MGUS in deployed US Military Service Members. This contents is the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of the US Government nor endorsement of commercial products mentioned