The Role of Snai2/Slug in Diabetes-impaired Wound Healing

Impaired wound healing is a common complication of diabetes mellitus. Advanced glycation end products (AGEs) are a consequence of diabetes and are formed from non-enzymatic reactions between glucose and proteins. The accumulation of AGEs is believed to disrupt wound repair and alter protein function. The epidermal growth factor receptor (EGFR) and a downstream effector, Snai2/Slug, are key regulators of reepithelialization, a vital component of wound healing. Reepithelialization requires keratinocyte proliferation and migration. Therefore, we examined the impact of AGEs on these EGF-stimulated responses. In this dissertation, I present evidence for a critical role of Snai2 in diabetes-impaired wound reepithelialization, extending the knowledge of Snai2 past normal wound repair. A well-studied AGE precursor, glyoxal, was used to model a diabetic environment. Glyoxal decreased EGF-stimulated EGFR activation, leading to impaired keratinocyte proliferation and migration in cell culture and in tissue explants. EGF-stimulated and basal Snai2 protein levels decreased following glyoxal treatment, and this decrease was prevented by the glycation inhibitor, aminoguanidine. Snai2 immunoprecipitated from glyoxal-exposed cells was modified by the AGE product carboxymethyl lysine, identifying Snai2 as an intracellular target of glycation. Furthermore, mice over-expressing Snai2 demonstrated enhanced epithelial outgrowth compared to wild type mice when exposed to glyoxal ex vivo. These data represent a significant breakthrough in the field of diabetes and wound healing as it is the first evidence linking Snai2 down-regulation by pathophysiologic stimuli to impairments in reepithelialization. In addition, few intracellular proteins have been identified as targets of glycation, and this work highlights Snai2 as a novel nuclear protein target with demonstrated relevance to diabetic healing. With this knowledge, we may explore methods to pharmacologically induce Snai2 protein to promote healing of diabetic wounds

Space shuttle: Static aerodynamic characteristics and control effectiveness of the GAC H-33 orbiter at Mach numbers from 0.6 to 4.96

A .003366 scale model of the Grumman H-33 orbiter was tested in the MSFC 14 inch Trisonic Wind Tunnel. Six-component aerodynamic force and moment data was recorded over a Mach number range of 0.6 to 4.96. Both pitch runs and yaw runs at various constant angles of attack were completed. The basic model configuration was investigated. The effects of a component build-up and of various control deflections were obtained. The elevons were deflected symmetrically and asymmetrically to determine elevator and aileron effectiveness. The rudder was tested both flared and unflared and the effects of deflections were determined in the flared case. The model was tested in pitch in two intervals. The first interval was from 0 to 20 deg. Then an adaptor was set to give the sting an offset angle and 20 to 40 deg angle of attack was obtained. Characteristics in sideslip were determined by varying sideslip angle from -4 deg to 10 deg with angle of attack set at 0 deg, 10 deg, 15 deg, and 30 deg

Age-associated reduction of cell spreading induces mitochondrial DNA common deletion by oxidative stress in human skin dermal fibroblasts: implication for human skin connective tissue aging

Abstract Background Reduced cell spreading is a prominent feature of aged dermal fibroblasts in human skin in vivo. Mitochondrial DNA (mtDNA) common deletion has been reported to play a role in the human aging process, however the relationship between age-related reduced cell spreading and mtDNA common deletion has not yet been reported. Results To examine mtDNA common deletion in the dermis of aged human skin, the epidermis was removed from full-thickness human skin samples using cryostat. mtDNA common deletion was significantly elevated in the dermis of both naturally aged and photoaged human skin in vivo. To examine the relationship between age-related reduced cell spreading and mtDNA common deletion, we modulated the shape of dermal fibroblasts by disrupting the actin cytoskeleton. Reduced cell spreading was associated with a higher level of mtDNA common deletion and was also accompanied by elevated levels of endogenous reactive oxygen species (ROS). Boosting cellular antioxidant capacity by using antioxidants was found to be protective against mtDNA common deletion associated with reduced cell spreading. Conclusion mtDNA common deletion is highly prevalent in the dermis of both naturally aged and photoaged human skin in vivo. mtDNA common deletion in response to reduced cell spreading is mediated, at least in part, by elevated oxidative stress in human dermal fibroblasts. These data extend current understanding of the mitochondrial theory of aging by identifying the connection between mtDNA common deletion and age-related reduction of cell spreading.http://deepblue.lib.umich.edu/bitstream/2027.42/112063/1/12929_2015_Article_167.pd

Photonic Crystal Nanobeam Cavity Strongly Coupled to the Feeding Waveguide

A deterministic design of an ultrahigh Q, wavelength scale mode volume photonic crystal nanobeam cavity is proposed and experimentally demonstrated. Using this approach, cavities with Q>10^6 and on-resonance transmission T>90% are designed. The devices fabricated in Si and capped with low-index polymer, have Q=80,000 and T=73%. This is, to the best of our knowledge, the highest transmission measured in deterministically designed, wavelength scale high Q cavities

Charge Ordered RVB States in the Doped Cuprates

We study charge ordered d-wave resonating valence bond states (dRVB) in the doped cuprates, and estimate the energies of these states in a generalized $t-J$ model by using a renormalized mean field theory. The long range Coulomb potential tends to modulate the charge density in favor of the charge ordered RVB state. The possible relevance to the recently observed $4 \times 4$ checkerboard patterns in tunnelling conductance in high $T_c$ cuprates is discussed.Comment: 4 pages, 4 figures, 3 table

Serendipity as a Strategic Advantage?

Who, over the age of 20, hasn\u27t experienced a serendipitous event: unexpected information that yields some unintended but potential value later on? Sitting next to a stranger on a plane who becomes a business partner? Stumbling onto an article in a journal or newspaper that helps tackle a nagging problem? Creating a new drug by accident

Resource Curse or Destructive Creation in Transition Turmoil

This paper explores the “resource curse” problem as a counter-example of creative performance and innovation by examining reliance on capital and physical resources, showing the gap between expectations and ex-post actual performance became clearer under conditions of economic turmoil. The analysis employs the method of logistic regressions with dichotomous response and predictor variables, on a count data sample containing 154 point derived from the transition economy of Vietnam. Performance of analysis has shown significant results. Several findings that have use for economic and business practice follow. First, in a transition period, a typical characteristic of successful firms was their reliance on either capital resources or physical asset endowments, whereas the innovation factor was not significant. Second, poor-performing enterprises exhibited evidence of over reliance on both capital and physical assets. Third, firms that relied on both types of resources tended to downplay creative performance. Fourth, reliance on capital/physical resources and adoption of “creative discipline/innovations” tend to be mutually exclusive. In fact, some evidence suggests that firms face more acute problem caused by the law of diminishing returns in troubled times. The Vietnamese corporate sector’s addiction to resources may contribute to economic deterioration, through a downward spiral of lower efficiency leading to consumption of more resources. The “innovation factor” has not been tapped as a source of economic growth. The absence of innovations and creativity has made the notion of “resource curse” become identical to “destructive creation” implemented by ex-ante resource-rich firms, and worsened the problem of resource misallocation in transition turmoil