The effect of nitric oxide surface flux on the foreign body response to subcutaneous implants.

Although the release of nitric oxide (NO) from biomaterials has been shown to reduce the foreign body response (FBR), the optimal NO release kinetics and doses remain unknown. Herein, polyurethane-coated wire substrates with varying NO release properties were implanted into porcine subcutaneous tissue for 3, 7, 21 and 42 d. Histological analysis revealed that materials with short NO release durations (i.e., 24 h) were insufficient to reduce the collagen capsule thickness at 3 and 6 weeks, whereas implants with longer release durations (i.e., 3 and 14 d) and greater NO payloads significantly reduced the collagen encapsulation at both 3 and 6 weeks. The acute inflammatory response was mitigated most notably by systems with the longest duration and greatest dose of NO release, supporting the notion that these properties are most critical in circumventing the FBR for subcutaneous biomedical applications (e.g., glucose sensors).

The Body in Pain: What do people of faith have to say about torture

An examination of why American Protestant churches have a higher likelihood to support torture

Improving Indwelling Glucose Sensor Performance: Porous, Dexamethasone-Releasing Coatings that Modulate the Foreign Body Response

Inflammation and the formation of an avascular fibrous capsule have been identified as the key factors controlling the wound healing associated failure of implantable glucose sensors. Our aim is to guide advantageous tissue remodeling around implanted sensor leads by the temporal release of dexamethasone (Dex), a potent anti-inflammatory agent, in combination with the presentation of a stable textured surface.

First, Dex-releasing polyurethane porous coatings of controlled pore size and thickness were fabricated using salt-leaching/gas-foaming technique. Porosity, pore size, thickness, drug release kinetics, drug loading amount, and drug bioactivity were evaluated. In vitro sensor functionality test were performed to determine if Dex-releasing porous coatings interfered with sensor performance (increased signal attenuation and/or response times) compared to bare sensors. Drug release from coatings monitored over two weeks presented an initial fast release followed by a slower release. Total release from coatings was highly dependent on initial drug loading amount. Functional in vitro testing of glucose sensors deployed with porous coatings against glucose standards demonstrated that highly porous coatings minimally affected signal strength and response rate. Bioactivity of the released drug was determined by monitoring Dex-mediated, dose-dependent apoptosis of human peripheral blood derived monocytes in culture.

The tissue modifying effects of Dex-releasing porous coatings were accessed by fully implanting Tygon® tubing in the subcutaneous space of healthy and diabetic rats. Based on encouraging results from these studies, we deployed Dex-releasing porous coatings from the tips of functional sensors in both diabetic and healthy rats. We evaluated if the tissue modifying effects translated into accurate, maintainable and reliable sensor signals in the long-term. Sensor functionality was accessed by continuously monitoring glucose levels and performing acute glucose challenges at specified time points.

Sensors treated with porous Dex-releasing coatings showed diminished inflammation and enhanced vascularization of the tissue surrounding the implants in healthy rats. Functional sensors with Dex-releasing porous coatings showed enhanced sensor sensitivity over a 21-day period when compared to controls. Enhanced sensor sensitivity was accompanied with an increase in sensor signal lag and MARD score. These results indicated that Dex-loaded porous coatings were able to elicit a favorable tissue response, and that such tissue microenvironment could be conducive towards extending the performance window of glucose sensors in vivo.

The diabetic pilot animal study showed differences in wound healing patters between healthy and diabetic subjects. Diabetic rats showed lower levels of inflammation and vascularization of the tissue surrounding implants when compared to their healthy counterparts. Also, functional sensors treated with Dex-releasing porous coatings did not show enhanced sensor sensitivity over a 21-day period. Moreover, increased in sensor signal lag and MARD scores were present in porous coated sensors regardless of Dex-loading when compared to bare implants. These results suggest that the altered wound healing patterns presented in diabetic tissues may lead to premature sensor failure when compared to sensors implanted in healthy rats.

Big or fast: two strategies in the developmental control of body size.

Adult body size is controlled by the mechanisms that stop growth when a species-characteristic size has been reached. The mechanisms by which size is sensed and by which this information is transduced to the growth regulating system are beginning to be understood in a few species of insects. Two rather different strategies for control have been discovered; one favors large body size and the other favors rapid development.

The Effect of Diet-Induced Obesity and Subsequent Weight Loss on Body Composition, Glucose Clearance, Metabolite Profile and Liver Amp-Activated Protein Kinase in Mice

Obesity, currently an epidemic, is a difficult disease to combat because it is marked by both a change in body weight and an underlying dysregulation in metabolism, making consistent weight loss challenging. We sought to elucidate this metabolic dysregulation resulting from diet-induced obesity (DIO) that persists through subsequent weight loss. We hypothesized that weight gain imparts a change in “metabolic set point” persisting through subsequent weight loss and that this modification may involve a persistent change in hepatic AMP-activated protein kinase (AMPK), a key energy-sensing enzyme in the body. To test these hypotheses, we tracked metabolic perturbations through this period, measuring changes in hepatic AMPK. To further understand the role of AMPK we used AICAR, an AMPK activator, following DIO. Our findings established a more dynamic metabolic model of DIO and subsequent weight loss. We observed hepatic AMPK elevation following weight loss, but AICAR administration without similar dieting was unsuccessful in improving metabolic dysregulation. Our findings provide an approach to modeling DIO and subsequent dieting that can be built upon in future studies and hopefully contribute to more effective long-term treatments of obesity.

Accurate localized resolution of identity approach for linear-scaling hybrid density functionals and for many-body perturbation theory

© 2015 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.A key component in calculations of exchange and correlation energies is the Coulomb operator, which requires the evaluation of two-electron integrals. For localized basis sets, these four-center integrals are most efficiently evaluated with the resolution of identity (RI) technique, which expands basis-function products in an auxiliary basis. In this work we show the practical applicability of a localized RI-variant ('RI-LVL'), which expands products of basis functions only in the subset of those auxiliary basis functions which are located at the same atoms as the basis functions. We demonstrate the accuracy of RI-LVL for Hartree-Fock calculations, for the PBE0 hybrid density functional, as well as for RPA and MP2 perturbation theory. Molecular test sets used include the S22 set of weakly interacting molecules, the G3 test set, as well as the G2-1 and BH76 test sets, and heavy elements including titanium dioxide, copper and gold clusters. Our RI-LVL implementation paves the way for linear-scaling RI-based hybrid functional calculations for large systems and for all-electron many-body perturbation theory with significantly reduced computational and memory cost.

Sea Urchin Body Plan Development and Evolution: An Integrative Transcriptomic Approach

My dissertation work integrates comparative transcriptomics and functional analyses to investigate gene expression changes underlying two significant aspects of sea urchin evolution and development: the dramatic developmental changes associated with an ecologically significant shift in life history strategy and the development of the unusual radial body plan of adult sea urchins.

In Chapter 2, I investigate evolutionary changes in gene expression underlying the switch from feeding (planktotrophic) to nonfeeding (lecithotrophic) development in sea urchins. In order to identify these changes, I used Illumina RNA-seq to measure expression dynamics across 7 developmental stages in three sea urchin species: the lecithotroph Heliocidaris erythrogramma, the closely related planktotroph Heliocidaris tuberculata, and an outgroup planktotroph Lytechinus variegatus. My analyses draw on a well-characterized developmental gene regulatory network (GRN) in sea urchins to understand how the ancestral planktotrophic developmental program was altered during the evolution of lecithotrophic development. My results suggest that changes in gene expression profiles occurred more frequently across the transcriptome during the evolution of lecithotrophy than during the persistence of planktotrophy. These changes were even more pronounced within the GRN than across the transcriptome as a whole, and occurred in each network territory (skeletogenic, endomesoderm and ectoderm). I found evidence for both conservation and divergence of regulatory interactions in the network, as well as significant changes in the expression of genes with known roles in larval skeletogenesis, which is dramatically altered in lecithotrophs. I further explored network dynamics between species using coexpression analyses, which allowed me to identify novel players likely involved in sea urchin neurogenesis and endoderm patterning.

In Chapter 3, I investigate developmental changes in gene expression underlying radial body plan development and metamorphosis in H. erythrogramma. Using Illumina RNA-seq, I measured gene expression profiles across larval, metamorphic, and post-metamorphic life cycle phases. My results present a high-resolution view of gene expression dynamics during the complex transition from pre- to post-metamorphic development and suggest that distinct sets of regulatory and effector proteins are used during different life history phases.

Collectively, my investigations provide an important foundation for future, empirical studies to investigate the functional role of gene expression change in the evolution of developmental differences between species and also for the generation of the unusual radial body plan of sea urchins.

The effects of curcumin (diferuloylmethane) on body composition of patients with advanced pancreatic cancer.

BACKGROUND: Curcumin is a natural product that is often explored by patients with cancer. Weight loss due to fat and muscle depletion is a hallmark of pancreatic cancer and is associated with worse outcomes. Studies of curcumin's effects on muscularity show conflicting results in animal models. METHODS AND RESULTS: Retrospective matched 1:2 case-control study to evaluate the effects of curcumin on body composition (determined by computerized tomography) of 66 patients with advanced pancreatic cancer (22 treated,44 controls). Average age (SEM) was 63(1.8) years, 30/66(45%) women, median number of prior therapies was 2, median (IQR) time from advanced pancreatic cancer diagnosis to baseline image was 7(2-13.5) months (p>0.2, all variables). All patients lost weight (3.3% and 1.3%, treated vs. control, p=0.13). Treated patients lost more muscle (median [IQR] percent change -4.8[-9.1,-0.1] vs. -0.05%[-4.2, 2.6] in controls,p<0.001) and fat (median [IQR] percent change -6.8%[-15,-0.6] vs. -4.0%[-7.6, 1.3] in controls,p=0.04). Subcutaneous fat was more affected in the treated patients. Sarcopenic patients treated with curcumin(n=15) had survival of 169(115-223) days vs. 299(229-369) sarcopenic controls(p=0.024). No survival difference was found amongst non-sarcopenic patients. CONCLUSIONS: Patients with advanced pancreatic cancer treated with curcumin showed significantly greater loss of subcutaneous fat and muscle than matched untreated controls.

The body language: The spontaneous influence of congruent bodily arousal on the awareness of emotional words

Nowadays, the idea of a reciprocal influence of physiological and psychological processes seems to be widely accepted. For instance, current theories of embodied emotion suggest that knowledge about an emotion concept involves simulations of bodily experienced emotional states relevant to the concept. In line with this framework, the present study investigated whether actual levels of physiological arousal interact with the processing of emotional words. Participants performed 2 blocks of an attentional blink task, once after a cycling session (increased arousal) and once after a relaxation session (reduced arousal). Concretely, participants were instructed to detect and report 2 target words (T1 and T2) presented among a series of nonword distractors. T1 and T2 were either neutral, high arousal, or low arousal words. Results revealed that increased physiological arousal led to improved reports of high arousal T2 words, whereas reduced physiological arousal led to improved reports of low arousal T2 words. Neutral T2 remained unaffected by the arousing conditions. These findings emphasize that actual levels of physiological arousal modulate the cognitive access to arousal (in-)congruent emotional concepts and suggest a direct grounding of emotion knowledge in our bodily systems of arousal.

Nations' income inequality predicts ambivalence in stereotype content: How societies mind the gap

Income inequality undermines societies: The more inequality, the more health problems, social tensions, and the lower social mobility, trust, life expectancy. Given people's tendency to legitimate existing social arrangements, the stereotype content model (SCM) argues that ambivalence-perceiving many groups as either warm or competent, but not both-may help maintain socio-economic disparities. The association between stereotype ambivalence and income inequality in 37 cross-national samples from Europe, the Americas, Oceania, Asia, and Africa investigates how groups' overall warmth-competence, status-competence, and competition-warmth correlations vary across societies, and whether these variations associate with income inequality (Gini index). More unequal societies report more ambivalent stereotypes, whereas more equal ones dislike competitive groups and do not necessarily respect them as competent. Unequal societies may need ambivalence for system stability: Income inequality compensates groups with partially positive social images. © 2012 The British Psychological Society.

Ethnomathematical research and drama in education techniques: developing a dialogue in a geometry class of 10th grade students

Ethnomathematical research, together with digital technologies (WebQuest) and Drama-in- Education (DiE) techniques, can create a fruitful learning environment in a mathematics classroom—a hybrid/third space—enabling increased student participation and higher levels of cognitive engagement. This article examines how ethnomathematical ideas processed within the experiential environment established by the Drama-in-Education techniques challenged students‘ conceptions of the nature of mathematics, the ways in which students engaged with mathematics learning using mind and body, and the ̳dialogue‘ that was developed between the Discourse situated in a particular practice and the classroom Discourse of mathematics teaching. The analysis focuses on an interdisciplinary project based on an ethnomathematical study of a designing tradition carried out by the researchers themselves, involving a search for informal mathematics and the connections with context and culture; 10th grade students in a public school in Athens were introduced to the mathematics content via an original WebQuest based on this previous ethnomathematical study; Geometry content was further introduced and mediated using the Drama-in-Education (DiE) techniques. Students contributed in an unfolding dialogue between formal and informal knowledge, renegotiating both mathematical concepts and their perception of mathematics as a discipline.

Molecular dynamics simulation of fractures using an N-body potential

Molecular dynamics has been employed to model the fracture of a twodimensional triangular atomic lattice. The N-body Sutton-Chen potential developed for fcc metals and its extended version (Rafii-Tabar and Sutton) for fcc random binary alloys were used for the interatomic interactions. It is shown that at low temperatures cleavage fractures can occur in both an elemental metal and an alloy. At elevated temperatures the nucleation of dislocations is shown to cause a brittle-to-ductile transition. For the brittle crack propagation in the elemental metal, crack propagation speeds have been computed for different stress rates, and a crack instability found to exist as the speed reaches a critical value of about 32% of the Rayleigh wave speed. For the random alloy, we find that the dislocation movement can be affected by the distorted lattice.

Molecular dynamics simulation of fractures using an N-body potential

Molecular dynamics has been employed to model the fracture of a two dimensional triangular atomic lattice. The N-body Sutton-Chen potential developed for fcc metals and its extended version (Rafii-Tabar and Sutton) for fcc random binary alloys were used for the interatomic interactions. It is shown that at low temperatures cleavage fractures can occur in both an elemental metal and an alloy. At elevated temperatures the nucleation of dislocations is shown to cause a brittle-to-ductile transition. For the brittle crack propagation in the elemental metal, crack propagation speeds have been computed for different stress rates, and a crack instability found to exist as the speed reaches a critical value of about 32% of the Rayleigh wave speed. For the random alloy, we find that the dislocation movement can be affected by the distorted lattice.

The use of evacuation modelling techniques in the design of very large transport aircraft and blended wing body aircraft

Very Large Transport Aircraft (VLTA) pose considerable challenges to designers, operators and certification authorities. Questions concerning seating arrangement, nature and design of recreational space, the number, design and location of internal staircases, the number of cabin crew required and the nature of the cabin crew emergency procedures are just some of the issues that need to be addressed. Other more radical concepts such as blended wing body (BWB) design, involving one or two decks with possibly four or more aisles offer even greater challenges. Can the largest exits currently available cope with passenger flow arising from four or five aisles? Do we need to consider new concepts in exit design? Should the main aisles be made wider to accommodate more passengers? In this paper we demonstrate how computer based evacuation models can be used to investigate these issues through examination of staircase evacuation procedures for VLTA and aisle/exit configuration for BWB cabin layouts.