2,103 research outputs found
The development of liposome encapsulated calcium phosphates for bone regeneration
University of Technology, Sydney. Faculty of Science.Osteoporosis, a degenerative bone disorder, is one of the leading causes of morbidity in the
elderly. Proper nutrition plays a role in the prevention and treatment of osteoporosis. Intake
of calcium and Vitamin D are some of the most important nutritional factors, and
supplementation remains the gold standard and first line of treatment for low bone mineral
density and osteoporosis. Supplementation can prevent bone loss and reduce fracture risk.
This work set about to produce, characterise and encapsulate for direct delivery to the bone
various micro and nano sized calcium based mineral compounds which may be beneficial to
bone health, using the precipitation method and biomimetic processes.
Calcium phosphate mineral was produced and characterised, including hydroxyapatite (Hap),
dicalcium phosphate dihydrate (DCPD), as well as multiphase and substituted calcium
phosphates using biomimetic process. Standard simulated body Fluid (SBF) solution was
modified, creating a high carbonate solution which better mimics the bone environment, and
produces precipitates more similar to bone than traditional low carbonate SBF, as confirmed
using Fourier Tansform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD).
The use of liposomes as a delivery vesicle for the calcium mineral was evaluated usmg
FTIR, XRD, Electron Dispersive Spectroscopy, Mass Spectrometry Transmission and
Scanning Electron Microscopy, and X-Ray Mapping. The calcium mineral from aqueous
solutions and prepared HAp and DCPD was incorporated into the liposome.
Functional groups were synthesised based on a published structure used to target the bone
marrow macrophage, and incorporation into liposomes was confitmed using Nuclear
Magnetic Resonance Spectroscopy and FTIR. Preliminary cell culture studies showed no
direct effect on osteoblast like Mg63 or Saos-2 cells or osteoclast resorption, measured by
bone collagen release.
Macrophage response was explored using U93 7 cell line. Expression of TNF-a and IL-1 ,
markers of inflammation, increased with liposome treatments compared to the negative control
but decreased compared the positive control. The Mg63 cells given U937 supematants showed
liposomes increased OPG production, but this was regardless of mineralisation.
The calcium based mineral compounds were produced, characterised, successfully
encapsulated using liposomes and functionalised to improve uptake at the bone site . This
shows the potential to deliver calcium to the bone, however further work to inhibit
inflammation and increase the calcium dose to elicit greater cell response is required before
this approach can be developed as a treatment option
Collecting genetic material from beef cattle (2005)
The beef cattle industry has long awaited the development of genetic tests to assist producers in breeding selection and management and to improve the marketability of cattle. Currently, there are only a handful of genetic tests commercially available for beef cattle. Beef producers interested in using genetic testing to improve their breeding stock need to know how to collect and store various genetic materials for testing.New February 2005 -- Extension website
Design Novel Dual Agonists for Treating Type-2 Diabetes by Targeting Peroxisome Proliferator-Activated Receptors with Core Hopping Approach
Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses
Needle in a haystack? A comparison of eDNA metabarcoding and targeted qPCR for detection of the great crested newt (Triturus cristatus)
Environmental DNA (eDNA ) analysis is a rapid, cost‐effective, non‐invasive biodiversity monitoring tool which utilises DNA left behind in the environment by organisms for species detection. The method is used as a species‐specific survey tool for rare or invasive species across a broad range of ecosystems. Recently, eDNA and “metabarcoding” have been combined to describe whole communities rather than focusing on single target species. However, whether metabarcoding is as sensitive as targeted approaches for rare species detection remains to be evaluated. The great crested newt Triturus cristatus is a flagship pond species of international conservation concern and the first UK species to be routinely monitored using eDNA . We evaluate whether eDNA metabarcoding has comparable sensitivity to targeted real‐time quantitative PCR (qPCR ) for T. cristatus detection. Extracted eDNA samples (N = 532) were screened for T. cristatus by qPCR and analysed for all vertebrate species using high‐throughput sequencing technology. With qPCR and a detection threshold of 1 of 12 positive qPCR replicates, newts were detected in 50% of ponds. Detection decreased to 32% when the threshold was increased to 4 of 12 positive qPCR replicates. With metabarcoding, newts were detected in 34% of ponds without a detection threshold, and in 28% of ponds when a threshold (0.028%) was applied. Therefore, qPCR provided greater detection than metabarcoding but metabarcoding detection with no threshold was equivalent to qPCR with a stringent detection threshold. The proportion of T. cristatus sequences in each sample was positively associated with the number of positive qPCR replicates (qPCR score) suggesting eDNA metabarcoding may be indicative of eDNA concentration. eDNA metabarcoding holds enormous potential for holistic biodiversity assessment and routine freshwater monitoring. We advocate this community approach to freshwater monitoring to guide management and conservation, whereby entire communities can be initially surveyed to best inform use of funding and time for species‐specific surveys
Approximation of the critical buckling factor for composite panels
This article is concerned with the approximation of the critical buckling factor for thin composite plates. A new method to improve the approximation of this critical factor is applied based on its behavior with respect to lamination parameters and loading conditions. This method allows accurate approximation of the critical buckling factor for non-orthotropic laminates under complex combined loadings (including shear loading). The influence of the stacking sequence and loading conditions is extensively studied as well as properties of the critical buckling factor behavior (e.g concavity over tensor D or out-of-plane lamination parameters). Moreover, the critical buckling factor is numerically shown to be piecewise linear for orthotropic laminates under combined loading whenever shear remains low and it is also shown to be piecewise continuous in the general case. Based on the numerically observed behavior, a new scheme for the approximation is applied that separates each buckling mode and builds linear, polynomial or rational regressions for each mode. Results of this approach and applications to structural optimization are presented
Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study
Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD
The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease
The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra
Leone, and Guinea – countries ravaged by extreme poverty, deforestation and
mining-related disruption of livelihoods and ecosystems, and bloody civil wars in
the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded
in the legacy of colonialism and its creation of enduring inequalities within African
nations and globally, via neoliberalism and the Washington Consensus. Recent
experiences with new and emerging diseases such as SARS and various strains of
HN influenzas have demonstrated the effectiveness of a coordinated local and
global public health and education-oriented response to contain epidemics. To what
extent is international assistance to fight Ebola strengthening local public health and
medical capacity in a sustainable way, so that other emerging disease threats, which
are accelerating with climate change, may be met successfully? This chapter
considers the wide-ranging socio-political, medical, legal and environmental factors
that have contributed to the rapid spread of Ebola, with particular emphasis on the
politics of the global and public health response and the role of gender, social
inequality, colonialism and racism as they relate to the mobilization and
establishment of the public health infrastructure required to combat Ebola and other
emerging diseases in times of climate change
Bilateral Assessment of Functional Tasks for Robot-assisted Therapy Applications
This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks
Polynomial-sized Semidefinite Representations of Derivative Relaxations of Spectrahedral Cones
We give explicit polynomial-sized (in and ) semidefinite
representations of the hyperbolicity cones associated with the elementary
symmetric polynomials of degree in variables. These convex cones form a
family of non-polyhedral outer approximations of the non-negative orthant that
preserve low-dimensional faces while successively discarding high-dimensional
faces. More generally we construct explicit semidefinite representations
(polynomial-sized in , and ) of the hyperbolicity cones associated with
th directional derivatives of polynomials of the form where the are symmetric
matrices. These convex cones form an analogous family of outer approximations
to any spectrahedral cone. Our representations allow us to use semidefinite
programming to solve the linear cone programs associated with these convex
cones as well as their (less well understood) dual cones.Comment: 20 pages, 1 figure. Minor changes, expanded proof of Lemma
Circulating microRNAs Reveal Time Course of Organ Injury in a Porcine Model of Acetaminophen-Induced Acute Liver Failure
Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of acute liver failure, are lacking. MicroRNAs are short, non-coding strands of RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global microRNA and specific microRNA species into the plasma using a porcine model of acetaminophen-induced acute liver failure. Pigs were induced to acute liver failure with oral acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global microRNA concentrations increased 4h prior to acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic DNA (P<0.0001). MiR122 increased around the time of onset of acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after acute liver failure (P<0.0001) and was associated with increasing creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002)
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