Growth Factor Gradient Formation and Release from PEG Microspheres for Nerve Regeneration.

Many biological processes depend on concentration gradients in signaling molecules. Thus, introduction of spatial patterning of proteins, while retaining activity and releasability, will be critical for the field of regenerative medicine. In particular, the area of nerve regeneration is in need of innovations to improve outcomes. Only about 25% of surgical patients with peripheral nerve damage (~200,000 surgical interventions performed each year) regain full motor function with less than 3% regaining sensation. The use of nerve guidance conduits (NGC’s) which are filled with biomimetic scaffolds is one treatment being explored. These scaffolds, however, lack the spatial patterning of proteins found in native tissue. Glial-cell line derived neurotrophic factor (GDNF), a potent stimulator of axon regeneration, is one such protein that, if contained within the scaffold and conformed to a particular concentration profile, could greatly enhance neural regeneration. The object of this work is to utilize poly(ethylene glycol) (PEG) microspheres to accomplish this spatial patterning of GDNF and apply it to NGC’s. First, an approach utilizing the controllability of the PEG microsphere’s density (buoyancy) was explored. By creating the microspheres under varying conditions, incubation time and temperature, the cross-linking and, thus, the swelling rate of the microspheres could be controlled. This created microspheres of different densities that, upon centrifugation, would orient themselves within a scaffold, creating a gradient in the different microsphere types. GDNF loaded into a batch of microspheres would thusly be oriented within the scaffold along with that particular microsphere batch. Through this, gradients in GDNF were created. Heparin was also added to the microspheres to allow for reversible binding of GDNF. Next, gradients in reversibly bound GDNF were formed through sequential centrifugation of microsphere batches. For instance, a layer of GDNF loaded microspheres were formed into a scaffold followed by a layer of microspheres without GDNF on top of them. This created an initial step gradient in GDNF that, given time to release, would form a linear concentration gradient. Gradients formed by this method were visualized by fluorescent confocal microscopy and compared to Fickian models. Some conditions yielded profiles more linear than the model predictions, which persisted for over a week. Lastly, the sequential gradient formation was modified and applied to NGC’s. Before the scaffolds were ready for in vivo implantation, functionalities such as cell initiated degradability, cell adhesion, and inter-microsphere cross-linking were added. A plasmin degradable peptide sequence (GCGGVRNGGK) was incorporated into the microspheres. CLICK agents, laminin, and heparin (via a new binding chemistry) were attached to the microspheres to add inter-microsphere cross-linking, add cell adhesion, and heparin binding functionalities, respectively. GDNF gradient formation and activity retention were confirmed with these fully functionalized microspheres. Microsphere scaffolds with linear gradients in GDNF were then formed in silicone tubes which were transplanted into rats with severed sciatic nerves

The Uncertain Future of Australia’s Pacific Solution

The plight of a refugee is one that many of us will never understand. However, the ugly truth is that there is a global rise in the number of displaced persons seeking asylum. By the end of 2015, the number of displaced persons surpassed post World War II numbers, prompting developed nations around the world to enforce, amend, or implement policies targeted at controlling the flood of refugees at their borders. This Comment examines the policies of Australia, a nation that has had strict immigration policies in place for decades. Specifically, it discusses the Australian stance on refugee migration and how such policy reconciles with human rights obligations imposed by international treaties

Take it to the Bridge: The Arts of Interfaith Peacebuilding

This writing argues that the arts go beyond dialogue to affect and enhance interfaith peacebuilding, understanding, and cooperation. My research focuses on the three Abrahamic Faiths, Judaism, Christianity, and Islam, with an in-depth analysis of music and peacebuilding amidst Jews and Arabs in Israel. Specifically, I discuss the use of music as a bridge of understanding between cultures and share examples of other types of art as well. This research also adds to the limited amount of theory, analysis, and writing in the subject area of peacebuilding and the arts. Section One introduces the terms and ideas surrounding the topics of interfaith, peacebuilding, identity, diversity, pluralism, and unity. Section Two includes a literature review conducted in this area of study. I also share art and interviews from artists who create peacebuilding art and music. In Section Three, I describe the qualitative research method “Portraiture” and how I used it as a framework for my fieldwork during summer 2013 in Israel. Images and information from Jewish and Arab artists, musicians, and activists serve as visual references in this section. Section Four includes a historical theological perspective of interfaith peacebuilding. I analyze the theology of Nicholas of Cusa (1401-1463), whose writings explore a medieval understanding of interfaith peacebuilding and cooperation. Specifically, I focus on his ideas surrounding concepts of God, interreligious relationships, and music. In Section Five, I describe my musical artifact and how my fieldwork and research are expressed in this artifact. Section Six includes details of the songwriting, production, and overall process involved in the creation of my artifact. Finally, Section Seven, includes information on further areas for research and offers my concluding thoughts and reflections

Diesel engine fuel injection monitoring using acoustic measurements and independent component analysis

Air-borne acoustic based condition monitoring is a promising technique because of its intrusive nature and the rich information contained within the acoustic signals including all sources. However, the back ground noise contamination, interferences and the number of Internal Combustion Engine ICE vibro-acoustic sources preclude the extraction of condition information using this technique. Therefore, lower energy events; such as fuel injection, are buried within higher energy events and/or corrupted by background noise. This work firstly investigates diesel engine air-borne acoustic signals characteristics and the benefits of joint time-frequency domain analysis. Secondly, the air-borne acoustic signals in the vicinity of injector head were recorded using three microphones around the fuel injector (120° apart from each other) and an Independent Component Analysis (ICA) based scheme was developed to decompose these acoustic signals. The fuel injection process characteristics were thus revealed in the time-frequency domain using Wigner-Ville distribution (WVD) technique. Consequently the energy levels around the injection process period between 11 and 5 degrees before the top dead center and of frequency band 9 to 15 kHz are calculated. The developed technique was validated by simulated signals and empirical measurements at different injection pressure levels from 250 to 210 bars in steps of 10 bars. The recovered energy levels in the tested conditions were found to be affected by the injector pressure settings

International migration and adverse birth outcomes: role of ethnicity, region of origin and destination

Background: The literature on international migration and birth outcomes shows mixed results. This study examined whether low birth weight (LBW) and preterm birth differed between non-migrants and migrant subgroups, defined by race/ethnicity and world region of origin and destination. Methods: A systematic review and meta-regression analyses were conducted using three-level logistic models to account for the heterogeneity between studies and between subgroups within studies. Results: Twenty-four studies, involving more than 30 million singleton births, met the inclusion criteria. Compared with US-born black women, black migrant women were at lower odds of delivering LBW and preterm birth babies. Hispanic migrants also exhibited lower odds for these outcomes, but Asian and white migrants did not. Sub-Saharan African and Latin-American and Caribbean women were at higher odds of delivering LBW babies in Europe but not in the USA and south-central Asians were at higher odds in both continents, compared with the native-born populations. Conclusions: The association between migration and adverse birth outcomes varies by migrant subgroup and it is sensitive to the definition of the migrant and reference groups

The application of δ13C, TOC and C/N geochemistry to reconstruct Holocene relative sea levels and paleoenvironments in the Thames Estuary, UK

We examined the use of δ13C, TOC and C/N geochemistry of sedimentary organic matter to reconstruct former sea levels and paleoenvironments in the absence of suitable microfossil data. The modern distribution of δ13C, TOC and C/N of 33 vegetation and 74 surface sediment samples collected from four coastal wetlands in the Thames Estuary and Norfolk, UK are described. The δ13C, TOC and C/N geochemistry of sediments varied in relation to the input of in situ vascular vegetation versus allochthonous particulate organic matter and algae, which was controlled primarily by tidal inundation. We reviewed published and unpublished studies to produce an English database of vegetation (n = 257) and sediment (n = 132) δ13C, TOC and C/N geochemistry. Four elevation-dependent environments in the database had statistically distinct δ13C, TOC and C/N values: (1) tidal flat/low marsh (δ13C: −24.9 ± 1.2‰; TOC: 3.6 ± 1.7%; C/N: 9.9 ± 0.8); (2) middle marsh/high (δ13C: −26.2 ± 1.0‰; TOC: 9.8 ± 6.7%; C/N: 12.1 ± 1.8); (3) reed swamp (δ13C: −27.9 ± 0.7‰: TOC: 36.5 ± 11.5%; C/N: 13.9 ± 1.2); and (4) fen carr (δ13C: −29.0 ± 0.6‰; TOC: 41.6 ± 5.7%; C/N: 17.4 ± 3.1). The δ13C, TOC and C/N geochemistry database was applied to a Holocene sediment core collected from the Thames Estuary to produce three new sea-level index points and one limiting date, illustrating the utility of δ13C, TOC and C/N values to reconstruct Holocene relative sea levels