Turbine tip clearance loss mechanisms

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2013.This electronic version was submitted and approved by the author's academic department as part of an electronic thesis pilot project. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from department-submitted PDF version of thesisIncludes bibliographical references (p. 97-98).Three-dimensional numerical simulations (RANS and URANS) were used to assess the impact of two specific design features, and of aspects of the actual turbine environment, on turbine blade tip loss. The calculations were carried out for a subsonic high pressure turbine stage. The loss mechanism examined is that due to tip clearance vortex mixing. The effects examined were three-dimensional blade stacking, downstream transition duct geometry, and unsteadiness due to an upstream nozzle guide vane. Tip leakage loss changes due to three-dimensional blade stacking (bowing or reverse bowing) are verified to be associated with changes in the magnitude of blade tip loading, which create differences in the leakage flow exit velocities. The effect of a downstream diffusing transition duct on tip leakage losses is small; there was a 3.6% increase in tip leakage loss for a 65% increase in duct exit-to-inlet area ratio compared to a constant area duct. For unsteadiness arising from an upstream nozzle guide vane, it is shown that substantial temporal fluctuations in vortex core velocity and loss generation exist. However, the time average tip leakage loss differed less than 5% from the tip leakage loss calculated on a steady flow basis. Based on the computations, the mechanism for tip leakage vortex loss in the three different situations examined appears to be similar to that which is seen for an isolated turbine blade.by Steven Mazur.S.M

CFTR Is a Negative Regulator of NFκB Mediated Innate Immune Response

Dysfunctional CFTR in the airways is associated with elevated levels of NFkappaB mediated IL-8 signaling leading to neutrophil chemotaxis and chronic lung inflammation in cystic fibrosis. The mechanism(s) by which CFTR mediates inflammatory signaling is under debate.We tested the hypothesis that wt-CFTR down-regulates NFkappaB mediated IL-8 secretion. We transiently co-expressed wt-CFTR and IL-8 or NFkappaB promoters driving luciferase expression in HEK293 cells. Wt-CFTR expression in HEK293 cells suppresses both basal and IL1beta induced IL-8, and NFkappaB promoter activities as compared to the control cells transfected with empty vector (p<0.05). We also confirmed these results using CFBE41o- cells and observed that cells stably transduced with wt-CFTR secrete significantly lower amounts of IL-8 chemokine as compared to non-transfected control cells. To test the hypothesis that CFTR must be localized to cell surface lipid rafts in polarized airway epithelial cells in order to mediate the inflammatory response, we treated CFBE41o- cells that had been stably transduced with wt-CFTR with methyl-beta-cyclodextrin (CD). At baseline, CD significantly (p<0.05) induced IL-8 and NFkappaB reporter activities as compared to control cells suggesting a negative regulation of NFkappaB mediated IL-8 signaling by CFTR in cholesterol-rich lipid rafts. Untreated cells exposed to the CFTR channel blocker CFTR-172 inhibitor developed a similar increase in IL-8 and NFkappaB reporter activities suggesting that not only must CFTR be present on the cell surface but it must be functional. We verified these results in vivo by comparing survival, body weight and pro-inflammatory cytokine response to P. aeruginosa LPS in CFTR knock out (CFKO) mice as compared to wild type controls. There was a significant (p<0.05) decrease in survival and body weight, an elevation in IL-1beta in whole lung extract (p<0.01), as well as a significant increase in phosphorylated IkappaB, an inducer of NFkappaB mediated signaling in the CFKO mice.Our data suggest that CFTR is a negative regulator of NFkappaB mediated innate immune response and its localization to lipid rafts is involved in control of inflammation

Sustaining Educational Reforms in Introductory Physics

While it is well known which curricular practices can improve student performance on measures of conceptual understanding, the sustaining of these practices and the role of faculty members in implementing these practices are less well understood. We present a study of the hand-off of Tutorials in Introductory Physics from initial adopters to other instructors at the University of Colorado, including traditional faculty not involved in physics education research. The study examines the impact of implementation of Tutorials on student conceptual learning across eight first-semester, and seven second-semester courses, for fifteen faculty over twelve semesters, and includes roughly 4000 students. It is possible to demonstrate consistently high, and statistically indistinguishable, student learning gains for different faculty members; however, such results are not the norm, and appear to rely on a variety of factors. Student performance varies by faculty background - faculty involved in, or informed by physics education research, consistently post higher student learning gains than less-informed faculty. Student performance in these courses also varies by curricula used - all semesters in which the research-based Tutorials and Learning Assistants are used have higher student learning gains than those semesters that rely on non-research based materials and do not employ Learning Assistants.Comment: 21 pages, 4 figures, and other essential inf

Development of PEGylated PLGA nanoparticle for controlled and sustained drug delivery in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>The mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in CF. The most common mutation, ΔF508-CFTR, is a temperature-sensitive, trafficking mutant with reduced chloride transport and exaggerated immune response. The ΔF508-CFTR is misfolded, ubiquitinated, and prematurely degraded by proteasome mediated- degradation. We recently demonstrated that selective inhibition of proteasomal pathway by the FDA approved drug PS-341 (pyrazylcarbonyl-Phe-Leuboronate, a.k.a. Velcade or bortezomib) ameliorates the inflammatory pathophysiology of CF cells. This proteasomal drug is an extremely potent, stable, reversible and selective inhibitor of chymotryptic threonine protease-activity. The apprehension in considering the proteasome as a therapeutic target is that proteasome inhibitors may affect proteostasis and consecutive processes. The affect on multiple processes can be mitigated by nanoparticle mediated PS-341 lung-delivery resulting in favorable outcome observed in this study.</p> <p>Results</p> <p>To overcome this challenge, we developed a nano-based approach that uses drug loaded biodegradable nanoparticle (PLGA-PEG^PS-341) to provide controlled and sustained drug delivery. The <it>in vitro </it>release kinetics of drug from nanoparticle was quantified by proteasomal activity assay from days 1-7 that showed slow drug release from day 2-7 with maximum inhibition at day 7. For <it>in vivo </it>release kinetics and biodistribution, these drug-loaded nanoparticles were fluorescently labeled, and administered to C57BL6 mice by intranasal route. Whole-body optical imaging of the treated live animals demonstrates efficient delivery of particles to murine lungs, 24 hrs post treatment, followed by biodegradation and release over time, day 1-11. The efficacy of drug release in CF mice (<it>Cftr^-/-</it>) lungs was determined by quantifying the changes in proteasomal activity (~2 fold decrease) and ability to rescue the <it>Pseudomonas aeruginosa </it>LPS (<it>Pa</it>-LPS) induced inflammation, which demonstrates the rescue of CF lung disease in murine model.</p> <p>Conclusion</p> <p>We have developed a novel drug delivery system to provide sustained delivery of CF "correctors" and "anti-inflammatories" to the lungs. Moreover, we demonstrate here the therapeutic efficacy of nano-based proteostasis-modulator to rescue <it>Pa-LPS </it>induced CF lung disease.</p

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported (F(1, 40) = 5.08, p = .03). For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age (F(1, 13) = 6.16, p = 0.28); F(1, 15) = 6.70, p = .021), respectively)

Towards an 'average' version of the Birch and Swinnerton-Dyer Conjecture

The Birch and Swinnerton-Dyer conjecture states that the rank of the Mordell-Weil group of an elliptic curve E equals the order of vanishing at the central point of the associated L-function L(s,E). Previous investigations have focused on bounding how far we must go above the central point to be assured of finding a zero, bounding the rank of a fixed curve or on bounding the average rank in a family. Mestre showed the first zero occurs by O(1/loglog(N_E)), where N_E is the conductor of E, though we expect the correct scale to study the zeros near the central point is the significantly smaller 1/log(N_E). We significantly improve on Mestre's result by averaging over a one-parameter family of elliptic curves, obtaining non-trivial upper and lower bounds for the average number of normalized zeros in intervals on the order of 1/log(N_E) (which is the expected scale). Our results may be interpreted as providing further evidence in support of the Birch and Swinnerton-Dyer conjecture, as well as the Katz-Sarnak density conjecture from random matrix theory (as the number of zeros predicted by random matrix theory lies between our upper and lower bounds). These methods may be applied to additional families of L-functions.Comment: 20 pages, 2 figures, revised first draft (fixed some typos

OpdA, a bacterial organophosphorus hydrolase, prevents lethality in rats after poisoning with highly toxic organophosphorus pesticides

Organophosphorus (OP) pesticides poison more than 3,000,000 people every year in the developing world, mostly through intentional self-poisoning. Advances in medical therapy for OP poisoning have lagged, and current treatment is not highly effective with mortality of up to 40% in even the most advanced Western medical facilities. Administration of a broadly active bacterial OP hydrolase to patients in order to hydrolyze OPs in circulation might allow current therapies to be more effective. The objective of this work was to evaluate the efficacy of a new recombinant bacterial OP hydrolase (OpdA), cloned from Agrobacterium radiobacter, in rat models of two chemically distinct but highly toxic and rapidly acting OP pesticides: dichlorvos and parathion. Without OpdA treatment, median time to death in rats poisoned with 3x LD(50) of dichlorvos or parathion was 6 min and 25.5 min, respectively. Administration of a single dose of OpdA immediately after dichlorvos resulted in 100% survival at 24h, with no additional antidotal therapy. After parathion poisoning, OpdA alone caused only a delay to death. However, an additional two doses of OpdA resulted in 62.5% survival at 24 h after parathion poisoning. In combination with pralidoxime therapy, a single dose of OpdA increased survival to 75% after parathion poisoning. Our results demonstrate that OpdA is able to improve survival after poisoning by two chemically distinct and highly toxic OP pesticides

The puzzling reliability of the Force Concept Inventory

The Force Concept Inventory (FCI) has influenced the development of many research-based pedagogies. However, no data exists on the FCI’s internal consistency or test-retest reliability. The FCI was administered twice to one hundred students during the first week of classes in an electricity and magnetism course with no review of mechanics between test administrations. High Kuder–Richardson reliability coefficient values, which estimate the average correlation of scores obtained on all possible halves of the test, suggest strong internal consistency. However, 31% of the responses changed from test to retest, suggesting weak reliability for individual questions. A chi-square analysis shows that change in responses was neither consistent nor completely random. The puzzling conclusion is that although individual FCI responses are not reliable, the FCI total score is highly reliable

The processing of Holliday junctions by BLM and WRN helicases is regulated by p53.

BLM, WRN, and p53 are involved in the homologous DNA recombination pathway. The DNA structure-specific helicases, BLM and WRN, unwind Holliday junctions (HJ), an activity that could suppress inappropriate homologous recombination during DNA replication. Here, we show that purified, recombinant p53 binds to BLM and WRN helicases and attenuates their ability to unwind synthetic HJ in vitro. The p53 248W mutant reduces abilities of both to bind HJ and inhibit helicase activities, whereas the p53 273H mutant loses these abilities. Moreover, full-length p53 and a C-terminal polypeptide (residues 373-383) inhibit the BLM and WRN helicase activities, but phosphorylation at Ser(376) or Ser(378) completely abolishes this inhibition. Following blockage of DNA replication, Ser(15) phospho-p53, BLM, and RAD51 colocalize in nuclear foci at sites likely to contain DNA replication intermediates in cells. Our results are consistent with a novel mechanism for p53-mediated regulation of DNA recombinational repair that involves p53 post-translational modifications and functional protein-protein interactions with BLM and WRN DNA helicases