Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.

The use of non-animal alternatives in the safety evaluations of cosmetics ingredients by the Scientific Committee on Consumer Safety (SCCS)

In Europe, the safety evaluation of cosmetics is based on the safety evaluation of each individual ingredient. Article 3 of the Cosmetics Regulation specifies that a cosmetic product made available on the market is to be safe for human health when used normally or under reasonably foreseeable conditions. For substances that cause some concern with respect to human health (e.g. colorants, preservatives, UV-filters), safety is evaluated at the Commission level by a scientific committee, presently called the Scientific Committee on Consumer Safety (SCCS). According to the Cosmetics Regulations, in the EU, the marketing of cosmetics products and their ingredients that have been tested on animals for most of their human health effects, including acute toxicity, is prohibited. Nevertheless, any study dating from before this prohibition took effect is accepted for the safety assessment of cosmetics ingredients. The in vitro methods reported in the dossiers summited to the SCCS are here evaluated from the published reports issued by the scientific committee of the Directorate General of Health and Consumers (DG SANCO); responsible for the safety of cosmetics ingredients. The number of studies submitted to the SCCS that do not involve animals is still low and in general the safety of cosmetics ingredients is based on in vivo studies performed before the prohibition.

Offdesign operation of kraft recovery boiler

A model to solve heat and mass balances during the offdesign load calculations was created. These equations are complex and nonlinear. The main new ideas used in the created offdesign model of a kraft recovery boiler are the use of heat flows as torn iteration variables instead of the current practice of using the mass flows, vectorizing equation solving, thus speeding up the process, using non dimensional variables for solving the multiple heat transfer surface problem and using a new procedure for calculating pressure losses. Recovery boiler heat and mass balances are reduced to vector form. It is shown that these vectorized equations can be solved virtually without iteration. The iteration speed is enhanced by the use of the derived method of calculating multiple heat transfer surfaces simultaneously. To achieve this quick convergence the heat flows were used as the torn iteration parameters. A new method to handle pressure loss calculations with linearization was presented. This method enabled less time to be spent calculating pressure losses. The derived vector representation of the steam generator was used to calculate offdesign operation parameters for a 3000 tds/d example recovery boiler. The model was used to study recovery boiler part load operation and the effect of the black liquor dry solids increase on recovery boiler dimensioning. Heat flows to surface elements for part load calculations can be closely approximated with a previously defined exponent function. The exponential method can be used for the prediction of fouling in kraft recovery boilers. For similar furnaces the firing of 80 % dry solids liquor produces lower hearth heat release rate than the 65 % dry solids liquor if we fire at constant steam flow. The furnace outlet temperatures show that capacity increase with firing rate increase produces higher loadings than capacity increase with dry solids increase. The economizers, boiler banks and furnaces can be dimensioned smaller if we increase the black liquor dry solids content. The main problem with increased black liquor dry solids content is the decrease in the heat available to superheat. Whenever possible the furnace exit temperature should be increased by decreasing the furnace height. The increase in the furnace exit temperature is usually opposed because of fear of increased corrosion.

Special issue on evolving the e-marketing mindset towards the social web model - Editorial Part 1

Con este proyecto editorial nuestro objetivo es promover un campo de investigación clave en la comercialización de hoy, es decir, la evolución de la mentalidad e-marketing hacia el nuevo modelo de web social.

Is it possible to utilize VIX for a profitable trading strategy of S&P 500 Index?

The goal of this research was to make an overall sight to VIX® and how it can be used as a stock market indicator. Volatility index often referred as the fear index, measures how much it costs for investor to protect his/her S&P 500 position from fluctuations with options. Over the relatively short history of VIX it has been a successful timing coordinator and it has given incremental information about the market state adding its own psychological view of the amount of fear and greed. Correctly utilized VIX information gives a considerable advantage in timing market actions. In this paper we test how VIX works as a leading indicator of broad stock market index such as S&P 500 (SPX). The purpose of this paper is to find a working way to interpret VIX. The various tests are made on time series data ranging from the year 1990 to the year 2010. The 10-day simple moving average strategy gave significant profits from the whole time when VIX data is available. Strategy was able to utilize the increases of SPX in example portfolio value and was able to step aside when SPX was declining. At the times when portfolio was aside of S it was on safety fund like on treasury bills getting an annual yield of 3 percent. On the other side just a static number’s of VIX did not work as indicators in a profit making way.

Infusions of AP5 into the basolateral amygdala impair the formation, but not the expression, of step-down inhibitory avoidance

We evaluated the effects of infusions of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) on the formation and expression of memory for inhibitory avoidance. Adult male Wistar rats (215-300 g) were implanted under thionembutal anesthesia (30 mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Bilateral infusions of AP5 (5.0 µg) were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 mA footshock, 24-h interval between training and the retention test session). Both pre- and post-training infusions of AP5 blocked retention test performance. When given prior to the test, AP5 did not affect retention. AP5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. The results suggest that NMDA receptor activation in the BLA is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. However, the results do not necessarily imply that the role of NMDA receptors in the BLA is to mediate long-term storage of fear-motivated memory within the amygdala.

Dental fear in adolescents' transition to early adulthood

The aims of the study were to assess the validity of a clinical dental fear question (Short Dental Fear Question, SDFQ) and an instrument measuring interaction between adolescents and dental staff (Patient Dental Staff Interaction Questionnaire, PDSIQ). Also, adolescents’ subjective perception of interaction with dental staff, the association with adolescents’ dental fear and sense of coherence as well as a multi-professional small-group intervention model for decreasing high dental fear were assessed. The study sample comprised Finnish adolescents in transition to early adulthood, aged 18–26 years (n = 777, n = 773, n = 5), except for a sample of 15-year-old adolescents (n = 27). Dental fear, sense of coherence (SOC) and the adolescents’ perceived interaction with dental staff were assessed with questionnaires. The principles of fear treatment such as gradual exposure, relaxation, encouragement and cornerstones of the reteaming method based on a solution-focused framework to maintain motivation and peer support were used to decrease fear in the intervention study. The SDFQ was found to be a valid dental fear instrument and the PDSIQ a valid interaction instrument with five factors of interaction retrieved: ‘kind atmosphere and mutual communication’, ‘roughness’, ‘insecurity’, ‘trust and safety’, and ‘shame and guilt’. Highly fearful young adults more often perceived their interaction with dental staff as negative, more often felt insecure and had a weaker sense of coherence compared to their peers with no to moderate dental fear. The results of the intervention study showed that young adults’ high dental fear decreased and their commitment to dental treatment increased. The SDFQ is clinically feasible and informative instrument in measuring dental fear. Knowledge of the level of fear enables dental staff to better consider an adolescent’s fear. Dental staff should be aware that a supportive interaction style, creating trust and safety, is especially beneficial for highly dentally fearful young adults. A weak SOC may affect young adults’ high dental fear in that they would not have enough tools to manage their fear. A multi-professional small therapeutic group seems to increase fearful young adults’ resources for confronting dental treatment.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

Value perceptions of measurement and monitoring system customers

The value that the customer perceives from a supplier’s offering, impacts customer’s decision making and willingness to pay at the time of the purchase, and the overall satisfaction. Thus, for a business supplier, it is critical to understand their customers’ value perceptions. The objective of this thesis is to understand what measurement and monitoring system customers value, by examining their key purchasing criteria and perceived benefits. Theoretical part of this study consists on reviewing relevant literature on organizational buying behavior and customer perceived value. This study employs a qualitative interview research method. The empirical part of this research consisted of conducting 20 in-depth interviews with life science customers in USA and in Europe. Quality and technical features are the most important purchasing criteria, while product-related benefits seem to be the most important perceived benefits. At the marketing of the system, the emphasis should be at which regulations the system complies with, references of supplier’s prior experience, the reliability and usability of the system, and total costs. The benefits that should be emphasized are the better control of customer’s process, and the proof of customer’s product quality

Stigmastadiene and specific extitntion (270 nm) to evaluate the presence of refined oils in virgin olive oil commercialized in Brazil

The increased marketing of olive oil in Brazil has intensified legal requirements to ensure regulation of this product. The measurement of the specific extinction at 270 nm (E 270) and content of stigmastadiene can be used to assess the presence of refined oils in virgin olive oil. During the vegetable oil refining process, compounds with conjugated double bonds are generated from unsaturated fatty acids that absorb at 270 nm and sterols, such as stigmasta-3,5-diene. To compare these parameters, seven samples of extra virgin olive oil and three samples of olive oil (blend of virgin and refined) were analyzed. Among the samples analyzed, four extra virgin samples had levels of stigmastadiene and E 270 higher than expected, among which two were adulterated with seed oil (rich in linoleic acid) and the other two with olive pomace oil. The results demonstrate the higher sensitivity of stigmastadiene to determine the presence of the refined oil in virgin olive oil and good agreement with determining E 270. The latter technique is a simple, quick, and low cost method of determination that can be easily implemented in laboratories to assist in the screening and regulation of olive oils sold in Brazil.

Marketing a Mobile Application in a Highly Competitive Global Marketplace

The purpose of this research was to study the marketing of mobile applications. The main objective was to find out what are the most efficient ways of marketing to increase the sales for a mobile application within a highly competitive marketplace. The marketplaces, app stores, are studied from the perspective of size, ease of entry, competition and customers and their purchasing process. The study also includes research on what are some of the main marketing methods used in mobile app marketing in general. The study consists of two parts, theoretical and empirical research. Theoretical research was done by studying past scientific research on the chosen subjects. As the subject is very new, the research was also extended to other publications from the field of mobile technology. The empirical part was done through interviews and empirical experiments with a case-company, which were used to answer the main objective of this study. These experiments showed that the chosen methods of mobile app marketing, app store optimization, localization and selected social media marketing activities, created the most sales when used together. Positive results were seen also when the activities were conducted by themselves, but together they were able to push the case company to their all time best results. However the key to succeeding and hitting high positions in the app store rankings would most likely require creating a solid marketing strategy, trying out other marketing activities alongside the ones used here, without forgetting to stay on top of mobile technology trends.

The role of personality and situational factors in forgiveness /

This study deals with personality and situational variables that influence forgiveness. The relations between empathy and forgiveness were studied, followed by the examination of the relation of these two variables to the Big Five personality traits, as well as honesty, absorption, the propensity to mystical experiences, and dissociation. Empathy was then tested as a mediating variable between the personality variables and forgiveness. Empathy and forgiveness were then studied in relation to childhood maltreatment. Finally, the effects of six different motivations to forgive were examined in relation to the personality variables. Participants were 142 undergraduate students recruited from the ftrst year psychology class at Brock University; 75% were either 18 or 19 years of age, and 84% were female. All of the variables were measured using self-report questionnaires. The relation between empathy and forgiveness was only partially replicated. In terms of personality, forgiveness was found to be related to honesty, emotionality, and agreeableness. Empathy at least partially mediated the relations between forgiveness and agreeableness, honesty and emotionality. Childhood maltreatment was negatively related to forgiveness, and positively related to openness to experience, absorption, and dissociation from reality, but not to the propensity for mystical experiences. Six different motivations for forgiveness emerged from an exploratory factor analysis. Out of these, Forgiveness to Promote Reconciliation was related to emotionality and dispositional empathy. Religious Forgiveness was related to honesty, emotionality, and mystical experiences. Forgiveness to Feel Better was related to honesty, emotionality, agreeableness, conscientiousness, absorption, mystical experiences, and empathy. Forgiveness to Assert Moral Superiority over the Injurer was negatively related to honesty, empathy, and positively related to extraversion. Forgiveness out of Fear was related to agreeableness. Finally, Altruistic Forgiveness was related to honesty, emotionality, and agreeableness, absorption and the propensity to mystical experiences. Altruistic Forgiveness correlated most highly with all the measures of forgiveness, followed by Forgiveness to Feel better. Altruistic forgiveness was also the motivation for forgiveness that correlated the highest with absorption.

Collective violence : a study of the gendered and socio-economic factors behind early modern Italian and English witch hunts

In this study, I build upon my previous research in which I focus on religious doctrine as a gendered disciplinary apparatus, and examine the witch trials in early modem England and Italy in light of socio-economic issues relating to gender and class. This project examines the witch hunts/trials and early modem visual representations of witches, and what I suggest is an attempt to create docile bodies out of members of society who are deemed unruly, problematic and otherwise 'undesirable'; it is the witch's body that is deemed counternormative. This study demonstrates that it is neighbours and other acquaintances of accused witches that take on the role of the invisible guard of Bantham's Panoptic on. As someone who is trained in the study of English literature and literary theory, my approach is one that is informed by this methodology. It is my specialization in early modem British literature that first exposed me to witch-hunting manuals and tales of the supernatural, and it is for this reason that my research commences with a study of representations of witches and witchcraft in early modem England. From my initial exposure to such materials I proceed to examine the similarities and the differences of the cultural significance of the supernatural vis-a.-vis women's activities in early modem Italy. The subsequent discussion of visual representations of witches involves a predominance of Germanic artists, as the seminal work on the discernment of witches and the application of punishment known as the Malleus Meleficarum, was written in Germany circa 1486. Textual accounts of witch trials such as: "A Pitiless Mother (1616)," "The Wonderful Discovery of the Witchcrafts of Margaret and Philippa Flower (1619)," "Magic and Poison: The Trial ofChiaretta and Fedele (circa 1550)", and the "The Case of Benvegnuda Pincinella: Medicine Woman or Witch (1518),"and witchhunting manuals such as the Malleus Melejicarum and Strix will be put in direct dialogue with visual representations of witches in light of historical discourses pertaining to gender performance and gendered expectations. Issues relating to class will be examined as they pertain to the material conditions of presumed witches. The dominant group in any temporal or geographic location possesses the tools of representation. Therefore, it is not surprising that the physical characteristics, sexual habits and social material conditions that are attributed to suspected witches are attributes that can be deemed deviant by the ruling class. The research will juxtapose the social material conditions of suspected witches with the guilt, anxiety, and projection of fear that the dominant groups experienced in light of the changing economic landscape of the Renaissance. The shift from feudalism to primitive accumulation, and capitalism saw a rise in people living in poverty and therefore an increased dependence upon the good will of others. I will discuss the social material conditions of accused witches as informed by what Robyn Wiegman terms a "minoritizing discourse" (210). People of higher economic standing often blamed their social, medical, and/or economic difficulties on the less fortunate, resulting in accusations of witchcraft.

The meaning of multiple medication use in adults: A qualitative study

Over half of prescribed medications are not taken as prescribed, resulting in health and economic consequences. Using constructivist grounded theory, 15 interviews were conducted to develop a theory on understanding the medication adherence choices of individuals, who were between the ages of 40 to 55, were diagnosed with a chronic condition, and taking three or more medications. The results indicate that participants are engaging in self-management strategies, with massive variance in adherence behaviours. Medications are sacrificed for personal and financial reasons, resonating with feelings of fear for the person’s current situation and future. Individuals are struggling with who they have become to who they once were, which becomes related to their medications. Finally, individuals are citing the impact of their physician; citing barriers to communication and Canada’s health care system. Participants’ experiences provided an understanding of the meanings individuals associate with their medications and how this impacts their decision-making.

A Reading of the conception of man in Hans Jonas’ works: Between Nature and Responsibility. An Environmental Ethics Approach

Hans Jonas is considered one of the principal leaders of the ecological doctrine that fights against the hegemony of technical power upon society. We will study the conception of man in Jonas’ ideology through the lens of nature and of responsibility. He brandishes the specter of disaster (“heuristics of fear”) as a guard against technological excesses. He appeals to a prospective, universal and categorical responsibility to protect nature and to save future generations. Jonas considers responsibility as a method of anticipating the threat to that which is vulnerable, ephemeral, and perishable. Thus, the responsibility that Jonas decrees implies an ethics of conservation. Jonas’ writings aim to procure a new dimension of acting, which necessitates an ethics of foresight and responsibility.