A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y

The effects of the alpha-diketone derivatives 2,3- and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG2 and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the alpha-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exposures. Flow cytometry was also used to study the effects of the three isomers on the cell cycle of the SH-SY5Y line only. With 2,5-hexanedione, the mean MTT IC50 decreased more than 10-fold from 4 to 48 hr. The toxicities of both alpha-diketones were similar, with a more than 18-fold increase in sensitivity of the SH-SY5Y at 24 hr compared to that of 4 hr. With flow cytometry at 48 hr, SH-SY5Y apoptosis with 2,5-hexanedione rose throughout the concentration range evaluated (0-30 mM) while 2,3- and 3,4-hexanediones showed apoptosis over the concentration range 1-1.6 mM, with 3,4-hexanedione being the more potent compared to the 2,3-isomer. At 1.6 mM nearly all the cells had entered apoptosis in the presence of the 3,4-isomer, (94.9 ± 1.4%) but only 57.5 ±4.1% of the 2,3-isomer-treated cells had reached that stage. The 2,3-and 3,4-isomers in diets alone may not pose a serious threat to human health. Further studies may be necessary to evaluate the effects of other dietary components on their toxicity. These alpha-diketones also display a degree of toxic selectivity towards neuroblastoma cells, which may have therapeutic implications.

Influence of QT correction on temporal and amplitude features for human identification via ECG

Identification of humans via ECG is being increasingly studied because it can have several advantages over the traditional biometric identification techniques. However, difficulties arise because of the heartrate variability. In this study we analysed the influence of QT interval correction on the performance of an identification system based on temporal and amplitude features of ECG. In particular we tested MLP, Naive Bayes and 3-NN classifiers on the Fantasia database. Results indicate that QT correction can significantly improve the overall system performance. © 2013 IEEE.

The challenges of representing human behaviour in simulation models:some case examples from supply chain, evacuation modelling and rail disruption

As more of the economy moves from traditional manufacturing to the service sector, the nature of work is becoming less tangible and thus, the representation of human behaviour in models is becoming more important. Representing human behaviour and decision making in models is challenging, both in terms of capturing the essence of the processes, and also the way that those behaviours and decisions are or can be represented in the models themselves. In order to advance understanding in this area, a useful first step is to evaluate and start to classify the various types of behaviour and decision making that are required to be modelled. This talk will attempt to set out and provide an initial classification of the different types of behaviour and decision making that a modeller might want to represent in a model. Then, it will be useful to start to assess the main methods of simulation in terms of their capability in representing these various aspects. The three main simulation methods, System Dynamics, Agent Based Modelling and Discrete Event Simulation all achieve this to varying degrees. There is some evidence that all three methods can, within limits, represent the key aspects of the system being modelled. The three simulation approaches are then assessed for their suitability in modelling these various aspects. Illustration of behavioural modelling will be provided from cases in supply chain management, evacuation modelling and rail disruption.

Managing human resources in Asia-Pacific

Given the enormous economic and developmental changes being experienced by nations in the Asia-Pacific region, and the related movement of people between and across countries, it is critical that we better understand the HRM policies and practices of these nations. The latest instalment in the Global HRM series, Managing Human Resources in Asia-Pacific (2E) presents the HRM situations in a number of South-East Asian and Pacific Rim countries, highlighting the growth of the personnel and HR function, the dominant HRM system(s) in the area, the influence of different factors on HRM, and the challenges faced by HR functions in these nations. This edition extends its coverage to Cambodia, Fiji, Indonesia, and the Philippines; a new chapter discusses HR research challenges in the region, such as the transferability of western constructs, problems with data collection, and the emergence of MNEs from Asia Pacific. © 2014 Taylor & Francis.

Nicotine exposure reduces cell viability but induces anti-inflammatory effects in human cystic fibrosis bronchial epithelial cells

Background: Mouse models of cystic fibrosis (CF) fail to truly represent the respiratory pathology. We have consequently developed human airways cell culture models to address this. The impact of cigarette smoke within the CF population is well documented, with exposure being known to worsen lung function. As nicotine is often perceived to be a less harmful component of tobacco smoke, this research aimed to identify its effects upon viability and inflammatory responses of CF (IB3-1) and CF phenotype corrected (C38) bronchial epithelial cells. Methods: IB3-1 and C38 cell lines were exposed to increasing concentrations of nicotine (0.55-75μM) for 24 hours. Cell viability was assessed via Cell Titre Blue and the inflammatory response with IL-6 and IL-8 ELISA. Results: CF cells were more sensitive; nicotine significantly (P<0.05) reduced cell viability at all concentrations tested, but failed to have a marked effect on C38 viability. Whilst nicotine induced anti-inflammatory effects in CF cells with a significant reduction in IL-6 and IL-8 release, it had no effect on chemokine release by C38 cells. Conclusion: CF cells may be more vulnerable to inhaled toxicants than non-CF cells. As mice lack a number of human nicotinic receptor subunits and fail to mimic the characteristic pathology of CF, these data emphasise the importance of employing relevant human cell lines to study a human-specific disease.

Sustainability Challenges of Phosphorus and Food: Solutions from Closing the Human Phosphorus Cycle

The Green Revolution has led to a threefold growth in food production in the last 50 to 75 years, but increases in crop production have required a concurrent increase in the use of inorganic phosphorus as fertilizer. A sustainable phosphorus supply is not assured, though, and food production depends on mineral phosphorus supplies that are nonrenewable and are being depleted. Phosphorus is effectively a nonsubstitutable necessity for all life. Because mineral phosphorus deposits are not distributed evenly, future phosphorus scarcity may have national security implications. Some projections show economically viable mineral reserves becoming depleted within a few decades. Phosphorus-induced food shortages are therefore a possibility, particularly in developing countries where farmers are more vulnerable to volatile fertilizer prices. Sustainable solutions to such future challenges exist, and involve closing the loop on the human phosphorus cycle. We review the current state of knowledge about human phosphorus use and dependence and present examples of these sustainable solutions.

Living on both sides of the fence: A phenomenological study of human resource development professionals as downsizing survivors and strategic human resource development facilitators

This phenomenological study explored how HR professionals who identified themselves as facilitators of strategic HRD (SHRD) perceived the experience of being an organizational agent-downsizing survivor. Criterion and snowball sampling were used to recruit 15 participants for this study. A semi-structured interview guide was used to interview participants. Creswell's (2007) simplified version of Moustakas's (1994) Modification of the Stevick-Colaizzi-Keen Method of Analysis of Phenomenological Data was used to analyze the data. Four main themes and corresponding sub-themes emerged from an inductive data analysis. The four main themes were a) the emotionality of downsizing, b) feeling responsible, c) choice and control, and d) possibilities for growth. Participants perceived downsizing as an emotional organizational change event that required them to manage their own emotions while helping others do the same. They performed their roles within an organizational atmosphere that was perceived as chaotic and filled with apprehension, shock, and a sense of ongoing loss, sadness and grieving. They sometimes experienced guilt and doubt and felt deceptive for having to keep secrets from others when planning for downsizing. Participants felt a strong sense of responsibility to protect employees emotionally, balance employee and organizational interests, and try to ensure the best outcomes for both. Often being there for others meant that they put on their games faces and took care of themselves last. Participants spoke of the importance of choosing one's attitude, being proactive rather than reactive, and finding ways to regain control in the midst of organizational crisis. They also perceived that although downsizing was emotionally difficult to go through that it provided possibilities for self, employee, and organizational growth.

Identification of characteristic volatile organic compounds released during the decomposition process of human remains and analogues

The manner in which remains decompose has been and is currently being researched around the world, yet little is still known about the generated scent of death. In fact, it was not until the Casey Anthony trial that research on the odor released from decomposing remains, and the compounds that it is comprised of, was brought to light. The Anthony trial marked the first admission of human decomposition odor as forensic evidence into the court of law; however, it was not "ready for prime time" as the scientific research on the scent of death is still in its infancy. This research employed the use of solid-phase microextraction (SPME) with gas chromatography-mass spectrometry (GC-MS) to identify the volatile organic compounds (VOCs) released from decomposing remains and to assess the impact that different environmental conditions had on the scent of death. Using human cadaver analogues, it was discovered that the environment in which the remains were exposed to dramatically affected the odors released by either modifying the compounds that it was comprised of or by enhancing/hindering the amount that was liberated. In addition, the VOCs released during the different stages of the decomposition process for both human remains and analogues were evaluated. Statistical analysis showed correlations between the stage of decay and the VOCs generated, such that each phase of decomposition was distinguishable based upon the type and abundance of compounds that comprised the odor. This study has provided new insight into the scent of death and the factors that can dramatically affect it, specifically, frozen, aquatic, and soil environments. Moreover, the results revealed that different stages of decomposition were distinguishable based upon the type and total mass of each compound present. Thus, based upon these findings, it is suggested that the training aids that are employed for human remains detection (HRD) canines should 1) be characteristic of remains that have undergone decomposition in different environmental settings, and 2) represent each stage of decay, to ensure that the HRD canines have been trained to the various odors that they are likely to encounter in an operational situation.

Student Independent Projects Environmental Studies 2011: The Humber River Basin Human Values Project: Designing a Sampling Strategy for a Pilot Survey in the Corner Brook Area

Sustainability can be indicated by a number of factors. Populations need to be aged evenly, ensuring a healthy equilibrium. Job opportunities must be numerous and of wide varieties to balance incomes from different employment sectors. Regions must also sustain vital natural resources in the area which are directly related to a place being self-sustaining. These indicators prove to be true, especially in Newfoundland, where people have struggled to remain in the small traditional communities that they consider being there 'home.' The population of Corner Brook and the surrounding areas can be stratified according to the values people hold to their special place. Even though people in western Newfoundland hold strong ties to their home, some parts of the region even though people in western Newfoundland hold strong ties to their home, some parts of the region struggle with employment, low incomes, out-migration, and dependency on declining natural resources. The aim of this paper is to present the process of designing a sample strategy for a human values pilot survey conducted in the city of Corner Brook. It will present a theoretical background over the period 2002-2006 to be used for sampling strategy.

Brands, Close Relationships, and Consumer Well-Being

Consumers have relationships with other people, and they have relationships with brands similar to the ones they have with other people. Yet, very little is known about how brand and interpersonal relationships relate to one another. Even less is known about how they jointly affect consumer well-being. The goal of this research, therefore, is to examine how brand and interpersonal relationships influence and are influenced by consumer well-being. Essay 1 uses both empirical methods and surveys from individuals and couples to investigate how consumer preferences in romantic couples, namely brand compatibility, influences life satisfaction. Using traditional statistical techniques and multilevel modeling, I find that the effect of brand compatibility, or the extent to which individuals have similar brand preferences, on life satisfaction depends upon power in the relationship. For high power partners, brand compatibility has no effect on life satisfaction. On the other hand, for low power partners, low brand compatibility is associated with decreased life satisfaction. I find that conflict mediates the link between brand compatibility and power on life satisfaction. In Essay 2 I again use empirical methods and surveys to investigate how resources, which can be considered a form of consumer well-being, influence brand and interpersonal relations. Although social connections have long been considered a fundamental human motivation and deemed necessary for well-being (Baumeister and Leary 1995), recent research has demonstrated that having greater resources is associated with weaker social connections. In the current research I posit that individuals with greater resources still have a need to connect and are using other sources for connection, namely brands. Across several studies I test and find support for my theory that resource level shifts the preference of social connection from people to brands. Specifically, I find that individuals with greater resources have stronger brand relationships, as measured by self-brand connection, brand satisfaction, purchase intentions and willingness to pay with both existing brand relationships and with new brands. This suggests that individuals with greater resources place more emphasis on these relationships. Furthermore, I find that resource level influences the stated importance of brand and interpersonal relationships, and that having or perceiving greater resources is associated with an increased preference to engage with brands over people. This research demonstrates that there are times when people prefer and seek out connections with brands over other people, and highlights the ways in which our brand and interpersonal relationships influence one another.

IL-10-producing Regulatory B Cell Development in Human Autoimmune Disease

B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of costimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of “regulatory B cells” has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported with interleukin-10 (IL-10) being the most studied. IL-10-producing regulatory B cells predominantly localize within a rare CD1dhiCD5+ B cell subset in mice and the CD24hiCD27+ B cell subset in adult humans. This specific IL-10-producing subset of regulatory B cells have been named “B10 cells” to highlight that the regulatory function of these rare B cells is primarily mediated by IL-10, and to distinguish them from other regulatory B cell subsets that regulate immune responses through different mechanisms. B10 cells have been studies in a variety of animal models with autoimmune disease and clinical settings of human autoimmunity. There are many unsolved questions related to B10 cells including their surface phenotype, their origin and development in vivo, and their role in autoimmunity.

In Chapter 3 of this dissertation, the role of the B cell receptor (BCR) in B10 cell development is highlighted. First, the BCR repertoire of mouse peritoneal cavity B10 cells is examined by single cell sequencing; peritoneal cavity B10 cells have clonally diverse germline BCRs that are predominantly unmutated. Second, mouse B10 cells are shown to have higher frequencies of λ+ BCRs compared to non-B10 cells which may indicate the involvement of BCR light chain editing early in the process of B10 cell development in vivo. Third, human peripheral blood B10 cells are examined and are also found to express higher frequencies of λ chains compared to non-b10 cells. Therefore, B10 cell BCRs are clonally diverse and enriched for unmutated germline sequences and λ light chains.

In Chapter 4 of this dissertation, B10 cells are examined in the healthy developing human across the entire age range of infancy, childhood and adolescence, and in a large cohort of children with autoimmunity. The study of B10 cells in the developing human documents a massive transient expansion during middle childhood when up to 30% of blood B cells were competent to produce IL-10. The surface phenotype of pediatric B10 cells was variable and reflective of overall B cell development. B10 cells down-regulated CD4+ T cell interferon-gamma (IFN-γ) production through IL-10-dependent pathways and IFN-γ inhibited whereas interleukin-21 (IL-21) promoted B cell IL-10 competency in vitro. Children with autoimmunity had a contracted B10 cell compartment, along with increased IFN-γ and decreased IL-21 serum levels compared to age-matched healthy controls. The decreased B10 cell frequencies and numbers in children with autoimmunity may be partially explained by the differential regulation of B10 cell development by IFN-γ and IL-21 and alterations in serum cytokine levels. The age-related changes of the B10 cell compartment during normal human development provide new insights into immune tolerance mechanisms involved in inflammation and autoimmunity.

These studies collectively demonstrate that BCR signals are the most important early determinant of B10 cell development in vivo, that human B10 cells are not a surface phenotype defined developmental B cell subset but a functionally defined regulatory B cell subset that regulates CD4+ T IFN-γ production through IL-10-dependent pathways and that human B10 cell development can be regulated by soluble factors in vivo such as the cytokine milieu. The findings of these studies provide new insights into immune tolerance mechanisms involved in human autoimmunity and the potent effects of IL-21 on human B cell IL-10 competence in vitro open new horizons in the development of autologous B10 cell-based therapies as an approach to treat human autoimmune disease in the future.

Influence of Increased Human Presence in the Mills River Basin on Water Availability and Drought

Periods of drought and low streamflow can have profound impacts on both human and natural systems. People depend on a reliable source of water for numerous reasons including potable water supply and to produce economic value through agriculture or energy production. Aquatic ecosystems depend on water in addition to the economic benefits they provide to society through ecosystem services. Given that periods of low streamflow may become more extreme and frequent in the future, it is important to study the factors that control water availability during these times. In the absence of precipitation the slower hydrological response of groundwater systems will play an amplified role in water supply. Understanding the variability of the fraction of streamflow contribution from baseflow or groundwater during periods of drought provides insight into what future water availability may look like and how it can best be managed. The Mills River Basin in North Carolina is chosen as a case-study to test this understanding. First, obtaining a physically meaningful estimation of baseflow from USGS streamflow data via computerized hydrograph analysis techniques is carried out. Then applying a method of time series analysis including wavelet analysis can highlight signals of non-stationarity and evaluate the changes in variance required to better understand the natural variability of baseflow and low flows. In addition to natural variability, human influence must be taken into account in order to accurately assess how the combined system reacts to periods of low flow. Defining a combined demand that consists of both natural and human demand allows us to be more rigorous in assessing the level of sustainable use of a shared resource, in this case water. The analysis of baseflow variability can differ based on regional location and local hydrogeology, but it was found that baseflow varies from multiyear scales such as those associated with ENSO (3.5, 7 years) up to multi decadal time scales, but with most of the contributing variance coming from decadal or multiyear scales. It was also found that the behavior of baseflow and subsequently water availability depends a great deal on overall precipitation, the tracks of hurricanes or tropical storms and associated climate indices, as well as physiography and hydrogeology. Evaluating and utilizing the Duke Combined Hydrology Model (DCHM), reasonably accurate estimates of streamflow during periods of low flow were obtained in part due to the model’s ability to capture subsurface processes. Being able to accurately simulate streamflow levels and subsurface interactions during periods of drought can be very valuable to water suppliers, decision makers, and ultimately impact citizens. Knowledge of future droughts and periods of low flow in addition to tracking customer demand will allow for better management practices on the part of water suppliers such as knowing when they should withdraw more water during a surplus so that the level of stress on the system is minimized when there is not ample water supply.

WAKING (TO) THINKING BEING: A STUDY OF EDUCATION, METAPHYSICS, MIND, AND LANGUAGE

This dissertation articulates the basic aims and achievements of education. It recognizes language as central to thinking, and philosophy and education as belonging profoundly to one another. The first step is to show that although philosophy can no longer claim to dictate the foundations of knowledge or of disciplines of inquiry, it still offers an exceptionally general level of self-understanding. Education is equally general and faces a similar crisis of self-identity, of coming to terms with reality. Language is the medium of thought and the repository of historical mind; so a child’s acquisition of language is her acquisition of rational freedom. This marks a metaphysical change: no longer merely an animal, she comes to exercise her powers of rationality, transcending her environment by seeking and expressing reasons for thinking and doing. She can think about herself in relation to the universe, hence philosophize and educate others in turn. The discussion then turns to the historical nature of language. The thinking already embedded in language always anticipates further questioning. Etymology serves as a model for philosophical understanding, and demonstrates how philosophy can continue to yield insights that are fundamental, but not foundational, to human life. The etymologies of some basic educational concepts disclose education as a leading out and into the midst of Being. The philosophical approach developed in previous chapters applies to the very idea of an educational aim. Discussion concerning the substantiality of educational ideals results in an impasse: one side recommends an open-­ended understanding of education’s aims; the other insists on a definitive account. However, educational ideals exhibit a conceptual duality: the fundamental achievements of education, such as rational freedom, are real; but how we should understand them remains an open question. The penultimate chapter investigates philosophical thinking as the fulfillment of rational freedom, whose creative insights can profoundly transform our everyday activities. That this transformative self-understanding is without end suggests the basic aims of education are unheimlich. The dissertation concludes with speculative reflection on the shape and nature of language, and with the suggestion that through education reality awakens to itself.

Humanism is a violence typical of the beasts. Philosozing with a Hammer, using Levinas and Derrida, the Measure of the Human and the Human as a measure

Levinas’s reflections arose as a critique of traditional philosophy which, since it was based on presence and identity, leads to the exclusion of the other. Instead of an onto-logical thought the Lithuanian proposes that the ipseity of the human being be constituted by alterity, and that it be so ethically, because the subject is sub-ject, that is, that which upholds, responsibility. In an attempt to take the obligatory attention to the otherness of the other even further, Derrida would develop a radical critique of the Levinasian posture. Deconstruction of every trace of ipseity and sovereignty in the relationship with the other, the reading that we have done of the work of Derrida opts for a no definable understanding of the human. That is why every de-limitation of an ethical field as a properly human implies a brutal violence that the levinasian humanism of the other tried to exceed.

The visibility of the world and the invisibility of the soul. Phenomenological structure of the human perception

The essay intends to demonstrate the need to postulate an (invisible) spiritual reality in the human being as a condition of possibility of the world’s visibility. For that purpose, it employs the phenomenological method. It describes the structure of human sensitive perception. This description firstly presents the world’s structure (first distance). Secondly, it manifests the importance of the body as a border element between the soul and the world and as an organ by means of which the soul structures the world. It is the second distance the distance between the body and the world. But, thirdly, the description states that, no matter how intimately the soul interpenetrates the body and requires it to know the world, the soul is not the body. It is the third distance or the primordial distance between the soul and everything else (including the body itself).