N,N'-Carbonyldiimidazole-mediated functionalization of superparamagnetic nanoparticles as vaccine carrier

Particulates with specific sizes and characteristics can induce potent immune responses by promoting antigen uptake of appropriate immuno-stimulatory cell types. Magnetite (Fe3O4) nanoparticles have shown many potential bioapplications due to their biocompatibility and special characteristics. Here, superparamagnetic Fe3O4 nanoparticles (SPIONs) with high magnetization value (70emug-1) were stabilized with trisodium citrate and successfully conjugated with a model antigen (ovalbumin, OVA) via N,N'-carbonyldiimidazole (CDI) mediated reaction, to achieve a maximum conjugation capacity at approximately 13μgμm-2. It was shown that different mechanisms governed the interactions between the OVA molecules and magnetite nanoparticles at different pH conditions. We evaluated as-synthesized SPION against commercially available magnetite nanoparticles. The cytotoxicity of these nanoparticles was investigated using mammalian cells. The reported CDI-mediated reaction can be considered as a potential approach in conjugating biomolecules onto magnetite or other biodegradable nanoparticles for vaccine delivery.

Optimal allocation of conservation effort among subpopulations of a threatened species: How important is patch quality?

Money is often a limiting factor in conservation, and attempting to conserve endangered species can be costly. Consequently, a framework for optimizing fiscally constrained conservation decisions for a single species is needed. In this paper we find the optimal budget allocation among isolated subpopulations of a threatened species to minimize local extinction probability. We solve the problem using stochastic dynamic programming, derive a useful and simple alternative guideline for allocating funds, and test its performance using forward simulation. The model considers subpopulations that persist in habitat patches of differing quality, which in our model is reflected in different relationships between money invested and extinction risk. We discover that, in most cases, subpopulations that are less efficient to manage should receive more money than those that are more efficient to manage, due to higher investment needed to reduce extinction risk. Our simple investment guideline performs almost as well as the exact optimal strategy. We illustrate our approach with a case study of the management of the Sumatran tiger, Panthera tigris sumatrae, in Kerinci Seblat National Park (KSNP), Indonesia. We find that different budgets should be allocated to the separate tiger subpopulations in KSNP. The subpopulation that is not at risk of extinction does not require any management investment. Based on the combination of risks of extinction and habitat quality, the optimal allocation for these particular tiger subpopulations is an unusual case: subpopulations that occur in higher-quality habitat (more efficient to manage) should receive more funds than the remaining subpopulation that is in lower-quality habitat. Because the yearly budget allocated to the KSNP for tiger conservation is small, to guarantee the persistence of all the subpopulations that are currently under threat we need to prioritize those that are easier to save. When allocating resources among subpopulations of a threatened species, the combined effects of differences in habitat quality, cost of action, and current subpopulation probability of extinction need to be integrated. We provide a useful guideline for allocating resources among isolated subpopulations of any threatened species. © 2010 by the Ecological Society of America.

Using augmented video to test in-car user experiences of context analog HUDs

Automotive interactive technologies represent an exemplar challenge for user experience (UX) designers, as the concerns for aesthetics, functionality and usability add up to the compelling issues of safety and cognitive demand. This extended abstract presents a methodology for the user-centred creation and evaluation of novel in-car applications, involving real users in realistic use settings. As a case study, we present the methodologies of an ideation workshop in a simulated environment and the evaluation of six design idea prototypes for in-vehicle head up display (HUD) applications using a semi-naturalistic drive. Both methods rely on video recordings of real traffic situations that the users are familiar with and/or experienced themselves. The extended abstract presents experiences and results from the evaluation and reflection on our methods.

Multi-parametric hydrogels support 3D in vitro bioengineered microenvironment models of tumour angiogenesis

Tumour microenvironment greatly influences the development and metastasis of cancer progression. The development of three dimensional (3D) culture models which mimic that displayed in vivo can improve cancer biology studies and accelerate novel anticancer drug screening. Inspired by a systems biology approach, we have formed 3D in vitro bioengineered tumour angiogenesis microenvironments within a glycosaminoglycan-based hydrogel culture system. This microenvironment model can routinely recreate breast and prostate tumour vascularisation. The multiple cell types cultured within this model were less sensitive to chemotherapy when compared with two dimensional (2D) cultures, and displayed comparative tumour regression to that displayed in vivo. These features highlight the use of our in vitro culture model as a complementary testing platform in conjunction with animal models, addressing key reduction and replacement goals of the future. We anticipate that this biomimetic model will provide a platform for the in-depth analysis of cancer development and the discovery of novel therapeutic targets.

Transcutaneous bone-anchoring prosthesis with knee replacement: A novel treatment for amputees

Over the last two decades, Transcutaneous Bone-Anchored Prosthesis (TCBAP) has proven to be an effective alternative for prosthetic attachment for amputees, particularly for individuals unable to wear a socket. However, the load transmitted through a typical TCBAP to the residual tibia and knee joint can be unbearable for transtibial amputees with knee arthritis. The aims of this study are (A) to describe the surgical procedure combining TKR with TCBAP for the first time; and (B) to present preliminary data on potential risks and benefits with assessment of clinical and functional outcomes at follow up.

Structural complexity in structural health monitoring: Design of laboratory model and test plan

Many researchers in the field of civil structural health monitoring (SHM) have developed and tested their methods on simple to moderately complex laboratory structures such as beams, plates, frames, and trusses. Fieldwork has also been conducted by many researchers and practitioners on more complex operating bridges. Most laboratory structures do not adequately replicate the complexity of truss bridges. Informed by a brief review of the literature, this paper documents the design and proposed test plan of a structurally complex laboratory bridge model that has been specifically designed for the purpose of SHM research. Preliminary results have been presented in the companion paper.

A comparative study of prognostic model for bearing failure

An effective prognostics program will provide ample lead time for maintenance engineers to schedule a repair and to acquire replacement components before catastrophic failures occur. This paper presents a technique for accurate assessment of the remnant life of machines based on health state probability estimation technique. For comparative study of the proposed model with the proportional hazard model (PHM), experimental bearing failure data from an accelerated bearing test rig were used. The result shows that the proposed prognostic model based on health state probability estimation can provide a more accurate prediction capability than the commonly used PHM in bearing failure case study.

Non-destructive structural integrity assessment of a decommissioned rail wagon system

This paper presents a multi-criteria based approach for nondestructive diagnostic structural integrity assessment of a decommissioned flatbed rail wagon (FBRW) used for road bridge superstructure rehabilitation and replacement applications. First, full-scale vibration and static test data sets are employed in a FE model of the FBRW to obtain the best ‘initial’ estimate of the model parameters. Second, the ‘final’ model parameters are predicted using sensitivity-based perturbation analysis without significant difficulties encountered. Consequently, the updated FBRW model is validated using the independent sets of full-scale laboratory static test data. Finally, the updated and validated FE model of the FBRW is used for structural integrity assessment of a single lane FBRW bridge subjected to the Australian bridge design traffic load.

Reliability and criterion-related validity with a smartphone used in timed-up-and-go test

Background The capacity to diagnosys, quantify and evaluate movement beyond the general confines of a clinical environment under effectiveness conditions may alleviate rampant strain on limited, expensive and highly specialized medical resources. An iPhone 4® mounted a three dimensional accelerometer subsystem with highly robust software applications. The present study aimed to evaluate the reliability and concurrent criterion-related validity of the accelerations with an iPhone 4® in an Extended Timed Get Up and Go test. Extended Timed Get Up and Go is a clinical test with that the patient get up from the chair and walking ten meters, turn and coming back to the chair. Methods A repeated measure, cross-sectional, analytical study. Test-retest reliability of the kinematic measurements of the iPhone 4® compared with a standard validated laboratory device. We calculated the Coefficient of Multiple Correlation between the two sensors acceleration signal of each subject, in each sub-stage, in each of the three Extended Timed Get Up and Go test trials. To investigate statistical agreement between the two sensors we used the Bland-Altman method. Results With respect to the analysis of the correlation data in the present work, the Coefficient of Multiple Correlation of the five subjects in their triplicated trials were as follows: in sub-phase Sit to Stand the ranged between r = 0.991 to 0.842; in Gait Go, r = 0.967 to 0.852; in Turn, 0.979 to 0.798; in Gait Come, 0.964 to 0.887; and in Turn to Stand to Sit, 0.992 to 0.877. All the correlations between the sensors were significant (p < 0.001). The Bland-Altman plots obtained showed a solid tendency to stay at close to zero, especially on the y and x-axes, during the five phases of the Extended Timed Get Up and Go test. Conclusions The inertial sensor mounted in the iPhone 4® is sufficiently reliable and accurate to evaluate and identify the kinematic patterns in an Extended Timed Get and Go test. While analysis and interpretation of 3D kinematics data continue to be dauntingly complex, the iPhone 4® makes the task of acquiring the data relatively inexpensive and easy to use.

Mechanisms underlying the effect of acupuncture on cognitive improvement: A systematic review of animal studies

Acupuncture has been reported to be beneficial in treating cognitive impairment in various pathological conditions. This review describes the effort to understand the signaling pathways that underlie the acupunctural therapeutic effect on cognitive function. We searched the literature in 12 electronic databases from their inception to November 2013, with full text available and language limited to English. Twenty-three studies were identified under the selection criteria. All recruited animal studies demonstrate a significant positive effect of acupuncture on cognitive impairment. Findings suggest acupuncture may improve cognitive function through modulation of signaling pathways involved in neuronal survival and function, specifically, through promoting cholinergic neural transmission, facilitating dopaminergic synaptic transmission, enhancing neurotrophin signaling, suppressing oxidative stress, attenuating apoptosis, regulating glycometabolic enzymes and reducing microglial activation. However, the quality of reviewed studies has room for improvement. Further high-quality animal studies with randomization, blinding and estimation of sample size are needed to strengthen the recognition of group differences.

Importance of animal models in schizophrenia research

Objective This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Method and Results Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Conclusions Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.

Neurodevelopmental animal models of schizophrenia: Effects on prepulse inhibition

Epidemiological studies have shown increased incidence of schizophrenia in patients subjected to different forms of pre- or perinatal stress. However, as the onset of schizophrenic illness does not usually occur until adolescence or early adulthood, it is not yet fully understood how disruption of early brain development may ultimately lead to malfunction years later. In order to elucidate a possible role for neurodevelopmental factors in the pathogenesis of schizophrenia and to highlight potential new treatments, animal models are needed. Prepulse inhibition (PPI) is a model of sensorimotor gating mechanisms in the brain. It is disrupted in schizophrenia patients and the disruption can be reversed with atypical antipsychotics. It has been widely used in animal studies to explore central mechanisms possibly involved in schizophrenia. There has been a recent surge of behavioural and neurochemical animal studies on neurodevelopmental models, particularly on the effects of postweaning isolation, maternal separation and neonatal lesions of the hippocampus. In these models, long lasting alterations in behaviour and/or molecular changes in specific brain regions are observed, comparable to those seen in schizophrenia. The aim of this article is to critically review the available literature on such neurodevelopmental animal models with special focus on the effects on PPI and brain regions that are putatively involved in regulation of PPI.

Comparison of kinematic variables obtained by inertial sensors among stroke survivors and healthy older adults in the Functional Reach Test: cross-sectional study

Background Balance dysfunction is one of the most common problems in people who suffer stroke. To parameterize functional tests standardized by inertial sensors have been promoted in applied medicine. The aim of this study was to compare the kinematic variables of the Functional Reach Test (FRT) obtained by two inertial sensors placed on the trunk and lumbar region between stroke survivors (SS) and healthy older adults (HOA) and to analyze the reliability of the kinematic measurements obtained. Methods Cross-sectional study. Five SS and five HOA over 65. A descriptive analysis of the average range as well as all kinematic variables recorded was developed. The intrasubject and intersubject reliability of the measured variables was directly calculated. Results In the same intervals, the angular displacement was greater in the HOA group; however, they were completed at similar times for both groups, and HOA conducted the test at a higher speed and greater acceleration in each of the intervals. The SS values were higher than HOA values in the maximum and minimum acceleration in the trunk and in the lumbar region. Conclusions The SS show less functional reach, a narrower, slower and less accelerated movement during the FRT execution, but with higher peaks of acceleration and speed when they are compared with HOA.