Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons

There is growing interest in the potential beneficial effects of flavonoids in the aging and diseased brain. We have investigated the potential of the flavanone hesperetin and two of its metabolites, hesperetin-7-O-beta-D-glucuronide and 5-nitro-hesperetin, to inhibit oxidative stress-induced neuronal apoptosis. Exposure of cortical neurons to hydrogen peroxide led to the activation of apoptosis signal-regulating kinase 1 via its de-phosphorylation at Ser963, the phosphorylation of c-jun N-terminal kinase and c-Jun (Ser73) and the activation of caspase 3 and caspase 9. Whilst hesperetin glucuronide failed to exert protection, both hesperetin and 5-nitro-hesperetin were effective at preventing neuronal apoptosis via a mechanism involving the activation/phosphorylation of both Akt/protein kinase B and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Protection against oxidative injury and the activation of Akt and ERK1/2 followed a bell-shaped response and was most apparent at 100 nmol/L concentrations. The activation of ERK1/2 and Akt by flavanones led to the inhibition of the pro-apoptotic proteins, apoptosis signal-regulating kinase 1, by phosphorylation at Ser83 and Bad, by phosphorylation at both Ser136 and Ser112 and to the inhibition of peroxide-induced caspase 9 and caspase 3 activation. Thus, flavanones may protect neurons against oxidative insults via the modulation of neuronal apoptotic machinery.

Effect of chymosin and salt reduction on the quality of ultrafiltrated white-salted cheese

This study demonstrated that both chymosin and salt-in-moisture (SM) were important factors for proteolysis in the manufacture of ultrafiltrated white-salted cheese, with significant effects on water-soluble nitrogen and nitrogen soluble in trichloroacetic acid. In contrast, the levels of free amino acids were not significantly affected by chymosin and salt treatments. The cheeses made using high levels of chymosin with low SM had lower levels of residual α(s1)- and β-casein at the end of ripening. On texture profile analysis, the hardness and fracturability of the cheeses significantly increased with SM and decreased during ripening. Increases in chymosin significantly contributed to the overall weakening of the structure throughout ripening. Bitter flavour was detected after 12 weeks in the cheese made with the higher chymosin level and lower SM, which could be the result of accumulation of γ-casein fractions. The sensory data indicated that the hedonic responses for low chymosin with low SM cheeses were good and acceptable in flavour, which may be due to the moderate levels of proteolysis products.

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

Visible-near infrared spectroscopy sensor for predicting curd and whey composition during cheese processing

The potential of visible-near infrared spectra, obtained using a light backscatter sensor, in conjunction with chemometrics, to predict curd moisture and whey fat content in a cheese vat was examined. A three-factor (renneting temperature, calcium chloride, cutting time), central composite design was carried out in triplicate. Spectra (300–1,100 nm) of the product in the cheese vat were captured during syneresis using a prototype light backscatter sensor. Stirring followed upon cutting the gel, and samples of curd and whey were removed at 10 min intervals and analyzed for curd moisture and whey fat content. Spectral data were used to develop models for predicting curd moisture and whey fat contents using partial least squares regression. Subjecting the spectral data set to Jack-knifing improved the accuracy of the models. The whey fat models (R = 0.91, 0.95) and curd moisture model (R = 0.86, 0.89) provided good and approximate predictions, respectively. Visible-near infrared spectroscopy was found to have potential for the prediction of important syneresis indices in stirred cheese vats.

Internal rents and corporate property management: a study into the use of internal rents in UK corporate organisations

Research in the late 1980s showed that in many corporate real estates users were not fully aware of the full extent of their property holdings. In many cases, not only was the value of the holdings unknown, but there was uncertainty over the actual extent of ownership within the portfolio. This resulted in a large number of corporate occupiers reviewing their property holdings during the 1990s, initially to create a definitive asset register, but also to benefit from an more efficient use of space. Good management of corporately owned property assets is of equal importance as the management of other principal resources within the company. A comprehensive asset register can be seen as the first step towards a rational property audit. For the effective, efficient and economic delivery of services, it is vital that all property holdings are utilised to the best advantage. This requires that the property provider and the property user are both fully conversant with the value of the property holding and that an asset/internal rent/charge is made accordingly. The advantages of internal rent charging are twofold. Firstly, it requires the occupying department to “contribute” an amount to the business equivalent to the open market rental value of the space that it occupies. This prevents the treating of space as a free good and, as individual profit centres, each department will then rationalise its holdings to minimise its costs. The second advantage is from a strategic viewpoint. By charging an asset rent, the holding department can identify the performance of its real estate holdings. This can then be compared to an internal or external benchmark to help determine whether the company has adopted the most efficient tenure pattern for its properties. This paper investigates the use of internal rents by UK-based corporate businesses and explains internal rents as a form of transfer pricing in the context of management and responsibility accounting. The research finds that the majority of charging organisations introduced internal rents primarily to help calculate true profits at the business unit level. However, less than 10% of the charging organisations introduced internal rents primarily to capture the return on assets within the business. There was also a sizeable element of the market who had no plans to introduce internal rents. Here, it appears that, despite academic and professional views that internal rents are beneficial in improving the efficient use of property, opinion at the business and operational level has not universally accepted this proposition.

The parental overprotection scale: associations with child and parental anxiety

Background: Parental overprotection has commonly been implicated in the development and maintenance of childhood anxiety disorders. Overprotection has been assessed using questionnaire and observational methods interchangeably; however, the extent to which these methods access the same construct has received little attention. Edwards, 2008 and Edwards et al., 2010 developed a promising parent-report measure of overprotection (OP) and reported that, with parents of pre-school children, the measure correlated with observational assessments and predicted changes in child anxiety symptoms. We aimed to validate the use of the OP measure with mothers of children in middle childhood, and examine its association with child and parental anxiety. Methods: Mothers of 90 children (60 clinically anxious, 30 non-anxious) aged 7–12 years completed the measure and engaged in a series of mildly stressful tasks with their child. Results: The internal reliability of the measure was good and scores correlated significantly with observations of maternal overprotection in a challenging puzzle task. Contrary to expectations, OP was not significantly associated with child anxiety status or symptoms, but was significantly associated with maternal anxiety symptoms. Limitations: Participants were predominantly from affluent social groups and of non-minority status. Overprotection is a broad construct, the use of specific sub-dimensions of behavioural constructs may be preferable. Conclusions: The findings support the use of the OP measure to assess parental overprotection among 7–12 year-old children; however, they suggest that parental responses may be more closely related to the degree of parental rather than child anxiety.

Ion acceleration at both the interior and exterior Alfvén waves associated with the magnetopause reconnection site: Signatures in cusp precipitation

We present evidence for the acceleration of magnetospheric ions by reflection off two Alfvén waves, launched by the reconnection site into the inflow regions on both sides of the reconnecting magnetopause. The “exterior” wave stands in the inflow from the magnetosheath and is the magnetopause, in the sense that the majority of the field rotation occurs there. The other, “interior” wave stands in the inflow region on the magnetospheric side of the boundary. The population reflected by the interior wave is the more highly energized of the two and appears at low altitudes on open field lines, immediately equatorward of the cusp precipitation. In addition, we identify the population of magnetosheath ions transmitted across the exterior Alfvén wave, as well as a population of magnetospheric ions which are accelerated, after transmission through the interior wave, by reflection off the exterior wave. The ion populations near the X line are modeled and, with allowance for time-of-flight effects, are also derived from observations in the dayside auroral ionosphere. Agreement between observed and theoretical spectra is very good and the theory also explains the observed total fluxes and average energies of the precipitations poleward of the open/closed field line boundary. The results offer a physical interpretation of all the various classifications of precipitation into the dayside ionosphere (central plasma sheet, dayside boundary plasma sheet, void, low-latitude boundary layer, cusp, and mantle) and allow the conditions in both the magnetosphere and the magnetosheath adjacent to the X line to be studied.

All for the good

The Guise of the Good thesis has received much attention since Anscombe's brief defence in her book Intention. I approach it here from a less common perspective - indirectly, via a theory explaining how it is that moral behaviour is even possible. After setting out how morality requires the employment of a fundamental test, I argue that moral behaviour involves orientation toward the good. Immoral behaviour cannot, however, involve orientation to evil as such, given the theory of evil as privation. There must always be orientation to good of some kind for immorality even to be possible. Evil can, nevertheless, be intended, but this must be carefully understood in terms of the metaphysic of good and evil I set out. Given that metaphysic, the Guise of the Good is a virtual corollary.

Strategy Method (and payment cards)

Payment cards are a useful device to measure subjects’ preferences for a good and especially their willingness to pay for it. Together with some other similar elicitation methods, payment cards are especially appropriate for both hypothetical and incentive-compatible valuations of a good; a property which has prompted many researchers to use them in studies comparing stated and revealed valuations. The Strategy Method (hereafter SM) is a method based on a similar principle as that of payment cards, but is aimed at eliciting a subject’s full profile of responses to each of the strategies available to the rival(s).

Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation

Background: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson’s disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. Results: All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Conclusions: Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.

Whose peace? Local ownership and UN peacebuilding

In recent years, there has been an increasing emphasis on the participation of national actors in United Nations peace operations, reflecting what has become a near orthodox commitment to ‘local ownership.’ Advocates of local ownership assert that it: (1) increases the legitimacy of UN peacebuilding efforts; (2) increases the sustainability of peacebuilding activities after the departure of the UN; and (3) increases democratic governance in post-conflict states. While such thinking about local ownership has informed UN peacebuilding policy to a large extent, the UN has, to date, assumed these positive benefits without critically examining the causal mechanisms that allegedly produce them, specifying the conditions under which this correlation holds, or providing convincing evidence for these assertions. Moreover, exactly what local ownership is, what is being owned, and who local ‘owners’ are remain unclear. Indeed a closer examination of ownership’s relation with legitimacy, sustainability, and democratization reveal a plethora of contradictions that imply that local ownership may in fact decrease the UN’s ability to deliver peacekeeping results. Crucially, however, the UN persists in adopting a local ownership approach to peacebuilding, suggesting that it does so because it is normatively appropriate rather than operationally effective.

Poly-bagging predictors for classification modelling for credit scoring

Credit scoring modelling comprises one of the leading formal tools for supporting the granting of credit. Its core objective consists of the generation of a score by means of which potential clients can be listed in the order of the probability of default. A critical factor is whether a credit scoring model is accurate enough in order to provide correct classification of the client as a good or bad payer. In this context the concept of bootstraping aggregating (bagging) arises. The basic idea is to generate multiple classifiers by obtaining the predicted values from the fitted models to several replicated datasets and then combining them into a single predictive classification in order to improve the classification accuracy. In this paper we propose a new bagging-type variant procedure, which we call poly-bagging, consisting of combining predictors over a succession of resamplings. The study is derived by credit scoring modelling. The proposed poly-bagging procedure was applied to some different artificial datasets and to a real granting of credit dataset up to three successions of resamplings. We observed better classification accuracy for the two-bagged and the three-bagged models for all considered setups. These results lead to a strong indication that the poly-bagging approach may promote improvement on the modelling performance measures, while keeping a flexible and straightforward bagging-type structure easy to implement. (C) 2011 Elsevier Ltd. All rights reserved.

MACHINE VISION FOR AUTOMATICVISUAL INSPECTION OF WOODENRAILWAY SLEEPERS USING UNSUPERVISED NEURAL NETWORKS

The motivation for this thesis work is the need for improving reliability of equipment and quality of service to railway passengers as well as a requirement for cost-effective and efficient condition maintenance management for rail transportation. This thesis work develops a fusion of various machine vision analysis methods to achieve high performance in automation of wooden rail track inspection.The condition monitoring in rail transport is done manually by a human operator where people rely on inference systems and assumptions to develop conclusions. The use of conditional monitoring allows maintenance to be scheduled, or other actions to be taken to avoid the consequences of failure, before the failure occurs. Manual or automated condition monitoring of materials in fields of public transportation like railway, aerial navigation, traffic safety, etc, where safety is of prior importance needs non-destructive testing (NDT).In general, wooden railway sleeper inspection is done manually by a human operator, by moving along the rail sleeper and gathering information by visual and sound analysis for examining the presence of cracks. Human inspectors working on lines visually inspect wooden rails to judge the quality of rail sleeper. In this project work the machine vision system is developed based on the manual visual analysis system, which uses digital cameras and image processing software to perform similar manual inspections. As the manual inspection requires much effort and is expected to be error prone sometimes and also appears difficult to discriminate even for a human operator by the frequent changes in inspected material. The machine vision system developed classifies the condition of material by examining individual pixels of images, processing them and attempting to develop conclusions with the assistance of knowledge bases and features.A pattern recognition approach is developed based on the methodological knowledge from manual procedure. The pattern recognition approach for this thesis work was developed and achieved by a non destructive testing method to identify the flaws in manually done condition monitoring of sleepers.In this method, a test vehicle is designed to capture sleeper images similar to visual inspection by human operator and the raw data for pattern recognition approach is provided from the captured images of the wooden sleepers. The data from the NDT method were further processed and appropriate features were extracted.The collection of data by the NDT method is to achieve high accuracy in reliable classification results. A key idea is to use the non supervised classifier based on the features extracted from the method to discriminate the condition of wooden sleepers in to either good or bad. Self organising map is used as classifier for the wooden sleeper classification.In order to achieve greater integration, the data collected by the machine vision system was made to interface with one another by a strategy called fusion. Data fusion was looked in at two different levels namely sensor-level fusion, feature- level fusion. As the goal was to reduce the accuracy of the human error on the rail sleeper classification as good or bad the results obtained by the feature-level fusion compared to that of the results of actual classification were satisfactory.

Professional and Non-Professional Written Travel Texts – Do They Have Common Features? : A Comparative Investigation on Travel Texts on Trysil, Norway

This study aims to investigate possible distinctions between professional and non-professional written travel texts all treating the same destination: the Norwegian ski resort Trysil. The study will investigate to what extent the different texts correlate with the genre of travel texts, as the travel texts are treated as personal narratives, and how they conform to a given structure for narratives and with guidelines for professional writers. Furthermore, the investigation aims to explore to what extent there are similarities and differences between the texts regarding the given structure. The texts will first be analysed and organized separately by macrorules and a news schema that are constructed specifically for these sorts of texts, in order to reveal their discourse structure, and then compared to each other. As the discourse structure of the different texts is revealed, it is seen that there are certain differences between the two different text types. Finally, seen that the text types differ in their structure, this study will show that despite the fact that journalists write stories, and that non-professional written stories are narratives, they do not share the same structure, and are constructed in different ways.

Exploring self-rated health among adolescents : a think-aloud study

BACKGROUND: Despite extensive use of self-rated health questions in youth studies, little is known about what such questions capture among adolescents. Hence, the aim of this study was to explore how adolescents interpret and reason when answering a question about self-rated health. METHODS: A qualitative study using think-aloud interviews explored the question, "How do you feel most of the time?", using five response options ("Very good", "Rather good", "Neither good, nor bad", "Rather bad", and "Very bad"). The study involved 58 adolescents (29 boys and 29 girls) in lower secondary school (7th grade) and upper secondary school (12th grade) in Sweden. RESULTS: Respondents' interpretations of the question about how they felt included social, mental, and physical aspects. Gender differences were found primarily in that girls emphasized stressors, while age differences were reflected mainly in the older respondents' inclusion of a wider variety of influences on their assessments. The five response options all demonstrated differences in self-rated health, and the respondents' understanding of the middle option, "Neither good, nor bad", varied widely. In the answering of potential sensitive survey questions, rationales for providing honest or biased answers were described. CONCLUSIONS: The use of a self-rated health question including the word 'feel' captured a holistic view of health among adolescents. Differences amongst response options should be acknowledged when analyzing self-rated health questions. If anonymity is not feasible when answering questions on self-rated health, a high level of privacy is recommended to increase the likelihood of reliability.