Hybridized polymer matrix composites

The extent to which graphite fibers are released from resin matrix composites that are exposed to fire and impact conditions was determined. Laboratory simulations of those conditions that could exist in the event of an aircraft crash and burn situation were evaluated. The effectiveness of various hybridizing concepts in preventing this release of graphite fibers were also evaluated. The baseline (i.e., unhybridized) laminates examined were prepared from commercially available graphite/epoxy, graphite/polyimide, and graphite/phenolic materials. Hybridizing concepts investigated included resin fillers, laminate coatings, resin blending, and mechanical interlocking of the graphite reinforcement. The baseline and hybridized laminates' mechanical properties, before and after isothermal and humidity aging, were also compared. It was found that a small amount of graphite fiber was released from the graphite/epoxy laminates during the burn and impact conditions used in this program. However, the extent to which the fibers were released is not considered a severe enough problem to preclude the use of graphite reinforced composites in civil aircraft structure. It also was found that several hybrid concepts eliminated this fiber release. Isothermal and humidity aging did not appear to alter the fiber release tendencies

Lecturing and other face-to-face teaching – too much or too little? An assessment based on student feedback and fail rates

Institutes of higher learning are tending to reduce the amount of face-to-face teaching that they offer, and particularly through the traditional pedagogical method of lecturing. There is ongoing debate about the educational value of lectures as a teaching approach, in terms of both whether they facilitate understanding of subject material and whether they augment the student educational experience. In this study, student evaluation of teaching scores plus academic outcome (percentage of students who fail) was assessed for 236 course units offered by a science faculty at an Australian university over the course of one year. These measures were related to the degree to which lectures and other face-to-face teaching were used in these units, controlling for factors such as class size, school and year level. An information-theoretic model selection approach was employed to identify the best models and predictors of student assessments and fail rates. All the top models of student feedback included a measure reflecting amount of face-to-face teaching, with the evaluation of quality of teaching being higher in units with higher proportions of lectures. However, these models explained only 12–20% of the variation in student evaluation scores, suggesting that many other factors come into play. By contrast, units with fewer lectures have lower failure rates. These results suggest that moving away from lectures and face-to-face teaching may not harm, and indeed may improve the number of students who pass the subject, but that this may be incurred at the expense of greater dissatisfaction in students\u27 learning experience

The transcription factors Egr2 and Egr3 are essential for the control of inflammation and antigen-induced proliferation of B and T cells

This article is available open access under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/3.0/). Copyright @ 2012 Elsevier Inc.Lymphocytes provide optimal responses against pathogens with minimal inflammatory pathology. However, the intrinsic mechanisms regulating these responses are unknown. Here, we report that deletion of both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also impaired antigen receptor-induced proliferation of B and T cells. Egr2- and Egr3-defective B and T cells had hyperactive signal transducer and activator of transcription-1 (STAT1) and STAT3 while antigen receptor-induced activation of transcription factor AP-1 was severely impaired. We discovered that Egr2 and/or Egr3 directly induced expression of suppressor of cytokine signaling-1 (SOCS1) and SOCS3, inhibitors of STAT1 and STAT3, and also blocked the function of Batf, an AP-1 inhibitor, in B and T cells. Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation.Arthritis Research U

Early growth response gene 2 (Egr-2) controls the self-tolerance of T cells and prevents the development of lupuslike autoimmune disease

© 2008 Zhu et al. This article is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).Maintaining tolerance of T cells to self-antigens is essential to avoid autoimmune disease. How self-reactive T cells are kept functionally inactive is, however, unknown. In this study, we show that early growth response gene 2 (Egr-2), a zinc-finger transcription factor, is expressed in CD44(high) T cells and controls their proliferation and activation. In the absence of Egr-2, CD44(high), but not CD44(low) T cells, are hyperreactive and hyperproliferative in vivo. The accumulation of activated CD4(+)CD44(high) T cells leads to the development of a late onset lupuslike autoimmune disease characterized by the accumulation of interferon (IFN)-gamma and interleukin (IL)-17-producing CD4(+) T cells, loss of tolerance to nuclear antigens, massive infiltration of T cells into multiple organs and glomerulonephritis. We found that the expression of cyclin-dependent kinase inhibitor p21cip1 was impaired in Egr-2-deficient T cells, whereas the expression of IFN-gamma and IL-17 in response to T cell receptor ligation was significantly increased, suggesting that Egr-2 activates the expression of genes involved in the negative regulation of T cell proliferation and inflammation. These results demonstrate that Egr-2 is an intrinsic regulator of effector T cells and controls the expansion of self-reactive T cells and development of autoimmune disease.The Biotechnology and Biological Sciences Research Council, the Medical Research Council and the Wellcome Trust

The Obesity Epidemic: From the Environment to Epigenetics – Not Simply a Response to Dietary Manipulation in a Thermoneutral Environment

The prevalence of obesity continues to increase particularly in developed countries. To establish the primary mechanisms involved, relevant animal models which track the developmental pathway to obesity are required. This need is emphasized by the substantial rise in the number of overweight and obese children, of which a majority will remain obese through adulthood. The past half century has been accompanied with unprecedented transitions in our lifestyle. Each of these changes substantially contributes to enhancing our capacity to store energy into adipose tissues. The complex etiology of adiposity is critical as a majority of models investigating obesity utilize a simplistic high-fat/low-carbohydrate diet, fed over a short time period to comparatively young inbred animals maintained in fixed environment. The natural history of obesity is much more complex involving many other mechanisms and this type of challenge may not be the optimal experimental intervention. Such processes include changes in adipose tissue composition with time and the transition from brown to white adipose tissue. Brown adipose tissue, due its unique ability to rapidly produce large amounts of heat could have a pivotal role in energy balance and is under epigenetic regulation mediated by the histone H3k9-specific demethylase Jhdma2a. Furthermore, day length has a potential role in determining endocrine and metabolic responses in brown fat. The potential to utilize novel models and interventions across a range of animal species in adipose tissue development may finally start to yield sustainable strategies by which excess fat mass can, at last, be avoided in humans

Aging of the inceptive cellular population: the relationship between stem cells and aging

The average life expectancy worldwide has about doubled and the global population has increased six fold over the past century. With improving health care in the developed world there is a proportional augmentation in the treatment necessary for elderly patients occasioning the call for increased research in the area of aging and age-related diseases. The manifestation of this research has been focalized on the causative cellular processes and molecular mechanisms involved. Here we will discuss the efforts of this research in the area of stem cells, delving into the regulatory mechanisms and how their de-regulation could be attributed to aging and age-related diseases

The placenta, maternal diet and adipose tissue development in the newborn

Background: A majority of adipose tissue present in the newborn possess the unique mitochondrial protein, uncoupling protein (UCP1). It is thus highly metabolically active and capable of producing 300 times more heat per unit mass than any other organ in the body. The extent to which maternal obesity and/or an obesogenic diet impacts on placental function thereby resetting the relative distribution of different types of fat in the fetus is unknown. Summary: Developmentally the majority (if not all) fat in the fetus can be considered as classical brown fat, in which UCP1 is highly abundant. In contrast, beige (or recruitable) fat which possess 90% less UCP1 may only appear after birth, as a majority of fat depots undergo a pronounced transformation that is usually accompanied by the loss of UCP1. The extent to which this process can be modulated in a depot-specific manner and/or changes in the maternal metabolic environment remain unknown. Key Messages: An increased understanding of the mechanism by which offspring born to mothers possess excessive adipose tissue could enable sustainable interventions designed to promote the abundance of UCP1 possessing adipocytes. Ultimately, this would increase their energy expenditure and improve glucose homeostasis in these individuals

Effect of maternal cold exposure and nutrient restriction on insulin-like growth factor sensitivity in adipose tissue of newborn sheep

Adipose tissue mass in the newborn is determined in part by insulin-like growth factor (IGF)s, which are dependent on the maternal nutritional and metabolic environment during late gestation. The present study was designed to determine whether maternal cold exposure (CE) commencing in mid gestation could modulate some of the adaptive effects of nutrient restriction in late gestation on adipose tissue endocrine sensitivity in the resulting offspring. Twenty eight pregnant sheep were entered into the study and were either shorn, i.e. cold exposed, from 70 days gestation (term = 147 days), or remained unshorn, and were fed either their total calculated metabolisable energy (ME) requirements for body weight and pregnancy from 110 days gestation or 50% of this amount (n=7 per group). Adipose tissue was sampled from the offspring at one day of age and the mRNA abundance for IGF-I, II their receptors (R) and GH secretagogue receptor-1a (GHSR-1a) were determined. CE mothers produced larger offspring with more perirenal adipose tissue, an adaptation prevented by maternal nutrient restriction. Nutrient restriction in unshorn mothers increased IGF-I and IIR mRNA abundance. The mRNA abundances for IGF-I, II and IIR in adipose tissue were reduced by CE, adaptations independent of maternal food intake, whereas CE plus nutrient restriction increased GHSR-1a mRNA. In conclusion, maternal nutrient restriction with or without CE has very different effects on IGF sensitivity of adipose tissue and may act to ensure adequate fat stores are present in the newborn in the face of very different maternal endocrine and metabolic environments

Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females

Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR. A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT prevalence and activity measured by other modalities. Consistent assessment of this uniquely metabolic tissue is fundamental to the discovery of potential therapeutic strategies against metabolic disease