Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD) motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP) cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR) nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to androgen stimulation between the 2D and 3D environments. Therefore, we suggest that the presented 3D culture system represents a powerful tool for high throughput prostate cancer drug testing that recapitulates tumor microenvironment. © 2012 Sieh et al.

Ability of modal analysis to detect osseointegration of implants in transfemoral amputees : a physical model study

Owing to the successful use of non-invasive vibration analysis to monitor the progression of dental implant healing and stabilization, it is now being considered as a method to monitor femoral implants in transfemoral amputees. This study uses composite femur-implant physical models to investigate the ability of modal analysis to detect changes at the interface between the implant and bone simulating those that occur during osseointegration. Using electromagnetic shaker excitation, differences were detected in the resonant frequencies and mode shapes of the model when the implant fit in the bone was altered to simulate the two interface cases considered: firm and loose fixation. The study showed that it is beneficial to examine higher resonant frequencies and their mode shapes (rather than the fundamental frequency only) when assessing fixation. The influence of the model boundary conditions on the modal parameters was also demonstrated. Further work is required to more accurately model the mechanical changes occurring at the bone-implant interface in vivo, as well as further refinement of the model boundary conditions to appropriately represent the in vivo conditions. Nevertheless, the ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.

Visual motion perception predicts driving hazard perception ability

PURPOSE: To examine the basis of previous findings of an association between indices of driving safety and visual motion sensitivity and to examine whether this association could be explained by low-level changes in visual function. METHODS: 36 visually normal participants (aged 19 – 80 years), completed a battery of standard vision tests including visual acuity, contrast sensitivity and automated visual fields. and two tests of motion perception including sensitivity for movement of a drifting Gabor stimulus, and sensitivity for displacement in a random-dot kinematogram (Dmin). Participants also completed a hazard perception test (HPT) which measured participants’ response times to hazards embedded in video recordings of real world driving which has been shown to be linked to crash risk. RESULTS: Dmin for the random-dot stimulus ranged from -0.88 to -0.12 log minutes of arc, and the minimum drift rate for the Gabor stimulus ranged from 0.01 to 0.35 cycles per second. Both measures of motion sensitivity significantly predicted response times on the HPT. In addition, while the relationship involving the HPT and motion sensitivity for the random-dot kinematogram was partially explained by the other visual function measures, the relationship with sensitivity for detection of the drifting Gabor stimulus remained significant even after controlling for these variables. CONCLUSION: These findings suggest that motion perception plays an important role in the visual perception of driving-relevant hazards independent of other areas of visual function and should be further explored as a predictive test of driving safety. Future research should explore the causes of reduced motion perception in order to develop better interventions to improve road safety.

Selective reductions using visible light photocatalysts of supported gold nanoparticles

Photocatalytic synthesis using visible light is a desirable chemical process because of its potential to utilize sunlight. Supported gold nanoparticles (Au-NPs) were found to be efficient photocatalysts and the effects of the supports were identified including CeO2, TiO2, ZrO2, Al2O3, and zeolite Y. In particular Au/CeO2 exhibited the high catalytic activity to reduce nitroaromatics to azo compounds, hydrogenate azobenzene to hydroazobenzene, reduce ketones to alcohols, and deoxygenate epoxides to alkenes at ambient temperatures, under irradiation of visible light (or simulated sunlight). The reac-tive efficiency depends on two primary factors: one is the light adsorption of catalysts and another is the driving ability of catalysts corresponding to the reactants. The light absorption by Au-NPs is due to surface plasmon resonance effect or inter-band electron transition; this is related to the reduction ability of the photocatalysts. Irradiation with shorter wavelengths can excite the conduction electrons in Au-NPs to higher energy levels and as a result, induce reduction with more negative reduction potentials. It is known when irradiated with light the Au-NPs can abstract hydrogen from isopropanol forming Au-H species on the Au-NP surface. Hence, we proposed that the active Au-H species will react with the N=O, N=N, C=O double bonds or epoxide bonds, which are weakened by the interaction with the excited electrons in the Au-NPs, and yield the final reductive products. The reacting power of the Au-H species depends on the energy of the excited electrons in Au-NPs: the higher the electronic energy, the stronger the reduction ability of the Au-H species. This finding demonstrates that we can tune the reduction ability of the photocatalysts by manipulating the irradiation wavelength.

Empirical study to identify the key business activities contributing to manufacturing business performance

Purpose: Within the context of high global competitiveness, knowledge management (KM) has proven to be one of the major factors contributing to enhanced business outcomes. Furthermore, knowledge sharing (KS) is one of the most critical of all KM activities. From a manufacturing industry perspective, supply chain management (SCM) and product development process (PDP) activities, require a high proportion of company resources such as budget and manpower. Therefore, manufacturing companies are striving to strengthen SCM, PDP and KS activities in order to accelerate rates of manufacturing process improvement, ultimately resulting in higher levels of business performance (BP). A theoretical framework along with a number of hypotheses are proposed and empirically tested through correlation, factor and path analyses. Design/methodology/approach: A questionnaire survey was administered to a sample of electronic manufacturing companies operating in Taiwan to facilitate testing the proposed relationships. More than 170 respondents from 83 organisations responded to the survey. The study identified top management commitment and employee empowerment, supplier evaluation and selection, and design simplification and modular design as the key business activities that are strongly associated with the business performance. Findings: The empirical study supports that key manufacturing business activities (i.e., SCM, PDP, and KS) are positively associated with BP. The findings also evealed that some specific business activities such as SCMF1,PDPF2, and KSF1 have the strongest influencing power on particular business outcomes (i.e., BPF1 and BPF2) within the context of electronic manufacturing companies operating in Taiwan. Practical implications: The finding regarding the relationship between SCM and BP identified the essential role of supplier evaluation and selection in improving business competitiveness and long term performance. The process of forming knowledge in companies, such as creation, storage/retrieval, and transfer do not necessarily lead to enhanced business performance; only through effectively applying knowledge to the right person at the right time does. Originality/value: Based on this finding it is recommended that companies should involve suppliers in partnerships to continuously improve operations and enhance product design efforts, which would ultimately enhance business performance. Business performance depends more on an employee’s ability to turn knowledge into effective action.

Process for forming alumino-silicate derivatives

A process for the preparation of an amorphous alumino-silicate derivative which involves reacting a solid corresponding starting material with MOH where M is alkali metal or ammonium cation. The solid corresponding starting material may be selected from montmorillonite, kaolin, natural zeolite (e.g., clinoliptolite/heulandite) as well as illite, palygorskite and saponite and additional reactant MX wherein X is halide may be utilized in conjunction with MOH. The invention also includes alumino-silicate derivatives of the general formula M.sub.p Al.sub.q Si.sub.2 O.sub.r (OH).sub.s X.sub.t.uH.sub.2 O as well as alumino-silicate derivatives of the general formula M.sub.p Al.sub.q Si.sub.2 O.sub.r (OH).sub.s.uH.sub.2 O.

Evaluation of plastic deformation ability of Cu/Ni/W metallic multilayers

Plastic deformation behavior of Cu/Ni/Wmetallicmultilayers with individual layer thickness ranging from 5 nm to 300 nm is investigated by nanoindentation testing. The experimental results reveal that the composite still exhibits indentation-induced plastic deformation instability and the loss of strain hardening ability at the nanometer scale even if the composite contains two kinds of layer interfaces (face centered cubic(FCC)/FCC and FCC/ body centered cubic) simultaneously. Plastic deformation behavior of the nanolayered material was evaluated and analyzed.

The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration

Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into various cell types and have been used widely in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with the activation of the PI3K/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functinalities. Biomaterials have been modified in their properties, surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

Binocular rivalry and visuospatial ability in individuals with schizophrenia

Visual abnormalities, both at the sensory input and the higher interpretive levels, have been associated with many of the symptoms of schizophrenia. Individuals with schizophrenia typically experience distortions of sensory perception, resulting in perceptual hallucinations and delusions that are related to the observed visual deficits. Disorganised speech, thinking and behaviour are commonly experienced by sufferers of the disorder, and have also been attributed to perceptual disturbances associated with anomalies in visual processing. Compounding these issues are marked deficits in cognitive functioning that are observed in approximately 80% of those with schizophrenia. Cognitive impairments associated with schizophrenia include: difficulty with concentration and memory (i.e. working, visual and verbal), an impaired ability to process complex information, response inhibition and deficits in speed of processing, visual and verbal learning. Deficits in sustained attention or vigilance, poor executive functioning such as poor reasoning, problem solving, and social cognition, are all influenced by impaired visual processing. These symptoms impact on the internal perceptual world of those with schizophrenia, and hamper their ability to navigate their external environment. Visual processing abnormalities in schizophrenia are likely to worsen personal, social and occupational functioning. Binocular rivalry provides a unique opportunity to investigate the processes involved in visual awareness and visual perception. Binocular rivalry is the alternation of perceptual images that occurs when conflicting visual stimuli are presented to each eye in the same retinal location. The observer perceives the opposing images in an alternating fashion, despite the sensory input to each eye remaining constant. Binocular rivalry tasks have been developed to investigate specific parts of the visual system. The research presented in this Thesis provides an explorative investigation into binocular rivalry in schizophrenia, using the method of Pettigrew and Miller (1998) and comparing individuals with schizophrenia to healthy controls. This method allows manipulations to the spatial and temporal frequency, luminance contrast and chromaticity of the visual stimuli. Manipulations to the rival stimuli affect the rate of binocular rivalry alternations and the time spent perceiving each image (dominance duration). Binocular rivalry rate and dominance durations provide useful measures to investigate aspects of visual neural processing that lead to the perceptual disturbances and cognitive dysfunction attributed to schizophrenia. However, despite this promise the binocular rivalry phenomenon has not been extensively explored in schizophrenia to date. Following a review of the literature, the research in this Thesis examined individual variation in binocular rivalry. The initial study (Chapter 2) explored the effect of systematically altering the properties of the stimuli (i.e. spatial and temporal frequency, luminance contrast and chromaticity) on binocular rivalry rate and dominance durations in healthy individuals (n=20). The findings showed that altering the stimuli with respect to temporal frequency and luminance contrast significantly affected rate. This is significant as processing of temporal frequency and luminance contrast have consistently been demonstrated to be abnormal in schizophrenia. The current research then explored binocular rivalry in schizophrenia. The primary research question was, "Are binocular rivalry rates and dominance durations recorded in participants with schizophrenia different to those of the controls?" In this second study binocular rivalry data that were collected using low- and highstrength binocular rivalry were compared to alternations recorded during a monocular rivalry task, the Necker Cube task to replicate and advance the work of Miller et al., (2003). Participants with schizophrenia (n=20) recorded fewer alternations (i.e. slower alternation rates) than control participants (n=20) on both binocular rivalry tasks, however no difference was observed between the groups on the Necker cube task. Magnocellular and parvocellular visual pathways, thought to be abnormal in schizophrenia, were also investigated in binocular rivalry. The binocular rivalry stimuli used in this third study (Chapter 4) were altered to bias the task for one of these two pathways. Participants with schizophrenia recorded slower binocular rivalry rates than controls in both binocular rivalry tasks. Using a ‘within subject design’, binocular rivalry data were compared to data collected from a backwardmasking task widely accepted to bias both these pathways. Based on these data, a model of binocular rivalry, based on the magnocellular and parvocellular pathways that contribute to the dorsal and ventral visual streams, was developed. Binocular rivalry rates were compared with performance on the Benton’s Judgment of Line Orientation task, in individuals with schizophrenia compared to healthy controls (Chapter 5). The Benton’s Judgment of Line Orientation task is widely accepted to be processed within the right cerebral hemisphere, making it an appropriate task to investigate the role of the cerebral hemispheres in binocular rivalry, and to investigate the inter-hemispheric switching hypothesis of binocular rivalry proposed by Pettigrew and Miller (1998, 2003). The data were suggestive of intra-hemispheric rather than an inter-hemispheric visual processing in binocular rivalry. Neurotransmitter involvement in binocular rivalry, backward masking and Judgment of Line Orientation in schizophrenia were investigated using a genetic indicator of dopamine receptor distribution and functioning; the presence of the Taq1 allele of the dopamine D2 receptor (DRD2) receptor gene. This final study (Chapter 6) explored whether the presence of the Taq1 allele of the DRD2 receptor gene, and thus, by inference the distribution of dopamine receptors and dopamine function, accounted for the large individual variation in binocular rivalry. The presence of the Taq1 allele was associated with slower binocular rivalry rates or poorer performance in the backward masking and Judgment of Line Orientation tasks seen in the group with schizophrenia. This Thesis has contributed to what is known about binocular rivalry in schizophrenia. Consistently slower binocular rivalry rates were observed in participants with schizophrenia, indicating abnormally-slow visual processing in this group. These data support previous studies reporting visual processing abnormalities in schizophrenia and suggest that a slow binocular rivalry rate is not a feature specific to bipolar disorder, but may be a feature of disorders with psychotic features generally. The contributions of the magnocellular or dorsal pathways and parvocellular or ventral pathways to binocular rivalry, and therefore to perceptual awareness, were investigated. The data presented supported the view that the magnocellular system initiates perceptual awareness of an image and the parvocellular system maintains the perception of the image, making it available to higher level processing occurring within the cortical hemispheres. Abnormal magnocellular and parvocellular processing may both contribute to perceptual disturbances that ultimately contribute to the cognitive dysfunction associated with schizophrenia. An alternative model of binocular rivalry based on these observations was proposed.

Pre-service Physical Education teachers and concerns regarding their ability to successfully facilitate school-based physical activity promotion strategies

Regular physical activity (PA) in youth has numerous immediate and long-term health benefits. With several studies indicating low levels of youth PA globally, schools settings have become increasingly critical settings for youth health promotion strategies. The role of physical education (PE) teachers has long been considered central to the facilitation of such strategies. However, PE teachers have a selfreported lack of knowledge, skills, understanding, and competence to successfully implement these strategies. Tertiary education programs are fundamental to adequately preparing, and shaping the attitudes and philosophies of future PE teachers towards their involvement within these programs. The aim of this investigation was to explore the beliefs and perceptions of future secondary school PE teachers, regarding their potential roles in future school-based programs designed to promote student PA. Fifty-seven (21 males and 36 females) pre-service PE teachers completed a series of open-ended survey questions concerning their perceptions towards participating in school-based PA promotion programs both as preservice during practicum, and prospectively as practising teachers. Responses were analysed thematically. Participants responded both positively and enthusiastically to both questions. Concerns regarding time, and the intention or expectation to participate in such programs were also key themes for pre-service and practicing teacher participation respectively. Critically in this study, participants did not identify any limitations which may impact upon their ability to successfully promote youth PA in school settings. This may indicate that participants have misconceptions regarding their ability to fulfil this role, or conversely, the deficiency of current PE teachers regarding school-based PA promotion has been recognised by the tertiary institution, and addressed to adequately prepare its students. School-based PA promotion is an integral element of pre-service PE teacher education, and ongoing professional development of practicing PE teachers. This trend is expected to continue in the future, in order to address ongoing public health concerns.

The ability of YSR DSM-oriented depression scales to predict DSM-IV depression in young adults : a longitudinal study

Background The Achenbach child behaviour checklist (CBCL/YSR) is a widely used screening tool for affective problems. Several studies report good association between the checklists and psychiatric diagnoses; although with varying degrees of agreement. Most are cross-sectional studies involving adolescents referred to mental health services. This paper aims to evaluate the performance of the youth self report (YSR) empirical and DSM-oriented internalising scales in predicting later depressive disorders in young adults. Methods Sample was 2431 young adults from an Australian birth cohort study. The strength of association between the empirical and DSM-oriented scales assessed at 14 and 21 years and structured-interview derived depression in young adulthood (18 to 22 years) were tested using odds ratios, ROC analyses and related diagnostic efficiency tests (sensitivity, specificity, positive and negative predictive values). Results Adolescents with internalising symptoms were twice (OR 2.3, 95%CI 1.7 to 3.1) as likely to be diagnosed with DSM-IV depression by age 21. Use of DSM-oriented depressive scales did not improve the concordance between the internalising behaviour and DSM-IV diagnosed depression at age 14 (ORs ranged from 1.9 to 2.5). Limitations Some loss to follow-up over the 7-year gap between the two waves of follow-up. Conclusion DSM-oriented scales perform no better than the standard internalising or anxious/depressed scales in identifying young adults with later DSM-IV depressive disorder.

Discriminative ability of functional loading tests for adolescent jumper's knee

Objective. To investigate the reliability and validity of five squat-based loading tests that are clinically appropriate for jumper's knee. The loading tests were step up, double leg squat, double leg squat on a 25-degree decline (decline squat), single leg decline squat, and decline hop. Design. Cross-sectional controlled cohort. Subjects without knee pain comprised controls, those with extensor tendon pain comprised the jumper's knee group. Setting. Institutional athlete study group in Australia Participants. Fifty-six elite adolescent basketball players participated in this study, thirteen comprised the jumper's knee group, fifteen athletes formed a control group. Intervention. Each subject performed each loading test for baseline and reliability data on the first testing day. Subjects then performed three days of intensive (6 h daily) basketball training, after which each loading test was reexamined. Main outcome measures. Eleven point interval scale for pain. Results. The tests that best detected a change in pain due to intensive workload were the single leg decline squat and single leg decline hop. This study found that decline tests have better discriminative ability than the standard squat to detect change in jumper's knee pain due to intensive training. The typical error for these tests ranged from 0.3 to 0.5, however, caution should be exercised in the interpretation of these reliability figures due to relatively low scores. Conclusions. The single leg decline squat is recommended in the physical assessment of adolescent jumper's knee. The decline squat was selected as the best clinical test over the decline hop because it was easier to standardise performance.

Improving the ability of guarantors to make a real choice : lenders' practices in taking third party guarantees

This article considers recent cases on guarantees of business loans to identify the lending practices that led the court to set aside the guarantee as against the creditor on the basis that the creditor had engaged in unconscionable conduct. It also explores the role of industry codes of practice in preventing unconscionable conduct, including whether there is a correlation between commitment to an industry code and higher standards of lending practices; whether compliance with an industry code would have produced different outcomes in the cases considered; and whether lenders need to do more than comply with an industry code to ensure their practices are fair and reasonable.