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Store-operated Ca2+ entry (SOCE) triggered by the depletion of endoplasmic reticulum (ER) luminal Ca2+ stores is a major Ca2+ entry pathway in non-excitable cells and is essential in physiological Ca2+ signaling and homeostasis. STIM proteins are sensors of ER luminal Ca2+, which translocate to ER-plasma membrane (PM) junctional regions to activate the family of Orai channels mediating Ca2+ entry. This study is focused on dissecting the mechanism of STIM interacting with Orai. A powerful modifier of SOCE, 2-aminoethoxydiphenyl borate (2-APB) is utilized. First, the action of 2-APB on the mammalian Orai homologues are characterized using the DT40 STIM knockout cells. 50 ìM 2-APB directly activates Orai3 but not Orai1 or Orai2. Second, while it stimulates the STIM2-mediated constitutive Ca2+ entry through Orai, 2-APB also induces the cytosolic STIM C-terminus fragments to translocate to the PM and activate Orai1. These data reveal 50 ìM 2-APB enhances STIM-Orai coupling. Further, this enhanced binding of STIM and Orai leads to a conformational change within the STIM-Orai complex, which is possibly the underlying mechanism for the 50 ìM 2-APB inhibitory effect on SOCE. Finally, six residues (344-349) at the N-terminus of the STIM-Orai activation region (SOAR) prove to be critical for this inhibitory action. These same six amino acid region also constitutes an ancillary Orai binding site within SOAR, in addition to the main polybasic region. The deletion of this ancillary site abolishes the ability of SOAR to bind to and activate Orai1, but can be compensated for by the STIM-Orai binding enhancing effect of 50 ìM 2-APB. The majority of STIM1 is located on the ER membrane, while a small proportion of STIM1 is on the PM. Using an extracellularly applied STIM1 antibody, the PM STIM1 can be aggregated to exert an influence on the ER STIM1. Although the PM STIM1 is not obligatory for STIM1-mediated Orai activation, it nevertheless may have a functional presence in the PM. Lastly, a regulatory link between voltage-gated Ca2+ channels (Cav channels) and the STIM proteins is established. After activation by store depletion, STIM strongly suppresses the Cav1.2 channels. There is a biochemical interaction between STIM1 and the Cav1.2 pore subunit á1C. This inhibitory effect is independent of Orai1 activation. Hence, STIM1 interacts with and reciprocally controls two major Ca2+ channels. / Biochemistry

Since retailing conceptualisation, it has been at the forefront of societal distribution of necessities, goods and experiences. Human beings, the consumers of retail, have daily or multiple times used supermarkets to express their purchase behaviour and elevate their consumer lifes. In the retail space itself the consumer uses their senses of visual, auditory, olfactory and touch to accurately perceive all around them. But there is a group of individuals who face various challenges in the retail experience: people who are visually impaired. For them, the retail experience differs significantly from the norm. Thus, the purpose of this study is to explore how people who are visually impaired experience the retail setting of supermarkets. With an aim to analyse how in-store design and sensory cues can be used to enable and affect supermarkets for the visually impaired. Additionally, the impact of using aids will be explored to facilitate their role in retail experience. Empirical findings were collected with the help of qualitative single case studies with semi structured interviews. In total, one pilot-study was conducted and 15 visually impaired people were interviewed in Sweden. The informants were asked about their retail experience in supermarkets and how in-store design, senses and aids affect their personal experiences. The findings were analysed and coded through thematic analysis and later discussed with various peer-reviewed literature. Conclusively, this thesis found that visually impaired people experience a significant difference from sighted people in supermarkets. Facing numerous challenges and obstacles in their visits. It was found that visually impaired peopleare separated from other customer segments through various inaccessible factors in the retail setting. However, as these factors work as barriers, the research shows that there exist solutions and potential in the supermarket setting, extending through in-store design, sensory cues, and aids. By facilitating and developing the areas, major improvements to customer accessibility can be introduced.

Since the 1800's, technological advances have extended the foundation on which telemedicine could build. With its evolution, telemedicine has proven to be a means of offering effective health care interventions, from a multitude of disciplines. Teledermatology, a specialty application of telemedicine, offers great potential in improving the standard of dermatologic care by bridging the gap between the expert opinion of dermatologists and those without access to basic dermatologic care, particularly in developing nations, where skin disease continues to be a major public health problem. In Honduras, the setting for this study, and other developing nations, technology to support telemedicine is available. Dermatologic disease is among the most common disease presentations in the developing world, which left untreated due to a lack of access to adequate medical care, can progress causing increased morbidity or even death. A potential but untested solution is teledermatology. Teledermatology offers great potential in improving the standard of dermatologic care by bridging the gap between the expert opinion of dermatologists and those without access to basic dermatologic care. The purpose of this study was to evaluate the prevalence and types of dermatologic conditions and the feasibility of a store-and-forward teledermatology system in an underserved area of Honduras, so as to potentially provide more timely diagnosis and treatment, implementation of preventative measures, and offer long term solutions.so as The justification and significance of this study was the potential of store-and-forward teledermatology to improve the standard of dermatologic care by improving access of populations in underserved areas to dermatology specialists through affordable technology. The methodology of this study was primarily case study descriptive. This study was conducted at a public primary care clinic (JMA Clinic) and satellite sites in underserved areas of Francisco Morazán, Honduras. During a four week period in Spring 2011, patients with dermatologic conditions were examined and photos taken of condition. The patient information was sent to 3 U.S. board certified dermatologists, who provided diagnosis and treatment within 24 hours, which allowed the clinic physician sufficient time to review recommendations before patient follow-up. Patients would receive follow-up within 48 hours of initial visit. Diagnostic agreement, image quality, and user satisfaction were evaluated. IRB forms were submitted and clearance given. The data was analyzed with SPSS using descriptive statistics. The primary findings were the types of dermatologic conditions, interobserver agreement, image quality, and patient and physician satisfaction. The findings of this study substantiate the need for dermatologic care, as approximately 1 out of every 5 patients of the JMA Clinic presented with a dermatologic condition. The majority of these patients were children or women in their late 20s and early 30s; many of whom had their condition for more than a year and most had not received prior therapy. The types of dermatologic conditions observed were typical of that seen at a dermatology clinic in the U.S., yet inclusive of tropical and regional differences. Dermatitis, infectious and pigmentary conditions were the most common presentations. The interobserver diagnostic agreement achieved was 78%, and improved when considering differential diagnoses. Image quality received high ratings. Patients and physicians recorded a high level of overall satisfaction. Physicians indicated improved knowledge of teledermatology. Because of the unique environment and circumstances, the results are limited to the setting in which the study occurs. This project was a pilot study limited to 4 weeks of data collection and will be limited in significance by its duration and small sample size with respect to the conclusions that can be drawn about the prevalence and types of dermatologic conditions. This study illustrates that teledermatology is a viable means of providing dermatologic care to those in an underserved area of Honduras, where a lack of or limited access to general healthcare or specialty dermatologic care exists. The data offers insights to draw conclusions and recommendations on the potential for similar models to be implemented in underserved areas throughout Honduras and other similar regions. / Ph. D.

Teleradiology has far-reaching implications for the health of remote and underserved populations. With coordination of radiographic evaluation and diagnosis from a distance, teleradiology has the potential to raise the standard of patient care throughout the world. Perhaps the safest and most cost-effective mode of teleradiology today is telesonography. The current research determined that telesonography improves the standard of care at a rural, government-run primary clinic within the Dominican Republic. The work reported herein is intended to compare the use of telesonography to the current standard of sonographic examination which is referral to government hospital 60km from the clinic. the following research questions were addressed: When compared to the standard of care, (1) To what extent does the use of asynchronous telesonography increase the percentage of received sonographic reports based on the total number of ultrasound referrals (sonographic reports / total number of referrals)? (2) To what extent does the use of asynchronous telesonography increase the rate of successful follow-up visits based on the total number of ultrasound referrals? (3) To what extent does the elapsed time between ultrasound referral and sonographic report delivery decrease with the use of asynchronous telesonography? (4) To what extent does the elapsed time between ultrasound referral and patient follow-up decrease with the use of asynchronous telesonography? Research methodology included randomly assigning 100 patients with clinical indications for sonographic examination into experimental and control groups during a 9-week implementation period. Findings from this study indicate that the implemented telesonography system, along with patient awareness of such a system, while not having an appreciable effect on the time to patient follow-up, provided a 4-fold increase in the proportion of patient follow-ups and a 6-fold increase in the proportion of returned radiological reports, and delivered those reports to the referring physician 6-times faster than in the control group. This study demonstrates the feasibility of utilizing a store-and forward telesonography system within this setting. Additional research focusing on the impact of telesonography on patient outcomes within this setting is recommended. / Ph. D.

The decision to patronize a particular store usually starts with a set of characteristics or attributes that consumers consider important. Consumers then use these attributes to make decisions regarding what store or stores can cater to their particular needs. Past retail and marketing studies have identified several consumer-oriented store attributes such as price, quality, variety, discounts, store reputation and their relationship to store patronage, but these studies overlooked how the physical environment affects retail store patronage. In addition, very few studies have addressed the issue of shopping scenarios and how they affect store patronage. The purpose of this study was to examine the influence of selected environmental dimensions on store patronage using specific apparel shopping scenarios. Data were collected using a random sample of women age 18 and over throughout the United States. The final sample consisted of 151 women. Four hypotheses were formulated and tested using factor analysis, cluster analysis, MANOVA, and Chi-square. The hypotheses tested for differences in (a) importance of environmental dimensions relative to three shopping scenarios, (b) importance of environmental dimensions relative to shopping orientations, (c) perceptions of first store choice relative to shopping orientations, and (d) attitude toward first store choice. Results revealed no difference in importance ratings of two environmental dimension factors, Sensory/Layout (Factor 1) and Music/Aesthetics (Factor 2), for three shopping scenarios (i.e., a dress for a formal social gathering, family gathering, work or community activity). Significant differences were found in the importance ratings of the Sensory/Layout and Music Aesthetics dimension factors across shopping orientation clusters. The clusters were named Decisive Apparel Shoppers (Cluster 1), Confident Apparel Shoppers (Cluster 2), Bargain Apparel Shoppers (Cluster 3), and Appearance Conscious Apparel Shoppers. The Bargain Apparel Shoppers had higher mean scores on the environmental factors than the other shopper groups. With regard to first store choice, the department store was chosen most often as first store choice. Furthermore, differences were found in perception of the environment for first store choice across the shopping orientation clusters. No differences were found for the Ventilation/Sensory factor; however, differences were found for the Signs perception factor. Respondents expressed relatively unfavorable attitudes toward their first store choice. However, of those that expressed an unfavorable attitude, several respondents indicated they were likely to visit their first store choice again. / Ph. D.

Imagine a grocery store that physically helps you to make healthy decisions for you. Your Twinkies, Hoho's, and other processed foods are all available and within sight, but you've got to work for them. In the wake of challenges that Americans face every day, this thesis project is putting a magnifying glass to (hi)stories and the human experience, and promoting change for American suburban and urban grocery stores to be health-fitness machines that we need them to be in order to help those of us on a quest to stay fit and healthy. With the information age pretty much exploding- as we are able to do a search for just about anything on Google, lack of information is not necessarily the problem. While gimmicky short term dieting fads come and go, an architectural model solution can set the foundation and structure to sustain progress. Let's look to the origins of architecture, labyrinths are built of walls, but if we are not careful, we can let them lead us to dead ends. Let's look to the origins of the marketplace, where fresh foods are taken directly from the source. For many of us, the modern American grocery store is the origin of our energy, where we will return again and again. It is our food source. It might be one root of our society's increasing levels of unhealthy weight gain, but also the source of opportunity to challenge the current design of the boxed store. / Master of Architecture

Yes / Abstract Purpose: The best possible way for brick-and-mortar retailers to maximise engagement with personalised shoppers is capitalising on intelligent insights. The retailer operates differently with diversified items and services, but influencing retail atmospheric on personalised shoppers, the perception remains the same across industries. Retail atmospherics stimuli such as design, smell and others create behavioural modifications. The purpose of this study is to explore the atmospheric effects on brick-and- mortar store performance and personalised shopper’s behaviour using cognitive computing based in-store analytics in the context of emerging market. Design/methodology/approach: The data are collected from 35 shoppers of a brick-and-mortar retailer through questionnaire survey and analysed using quantitative method. Findings: The result of the analysis reveals month-on-month growth in footfall count (46%), conversation rate (21%), units per transaction (27%), average order value (23%), dwell time (11%), purchase intention (29%), emotional experience (40%) and a month-on-month decline in remorse (20%). The retailers need to focus on three control gates of shopper behaviour: entry, browsing and exit. Attention should be paid to the cognitive computing solution to judge the influence of retail atmospherics on store performance and behaviour of personalised shoppers. Retail atmospherics create the right experience for individual shoppers and forceful use of it has an adverse impact. Originality/value: The paper focuses on strategic decisions of retailers, the tactical value of personalised shoppers and empirically identifies the retail atmospherics effect on brick-and-mortar store performance and personalised shopper behaviour.

Yes / Ca2+ release from the Golgi apparatus regulates key functions of the organelle, including vesicle trafficking. However, the signaling pathways that control this form of Ca2+ release are poorly understood and evidence of discrete Golgi Ca2+ release events is lacking. Here, we identified the Golgi apparatus as the source of prolonged Ca2+ release events that originate from the nuclear ‘poles’ of primary cardiac cells. Once initiated, Golgi Ca2+ release was unaffected by global depletion of sarcoplasmic reticulum Ca2+, and disruption of the Golgi apparatus abolished Golgi Ca2+ release without affecting sarcoplasmic reticulum function, suggesting functional and anatomical independence of Golgi and sarcoplasmic reticulum Ca2+ stores. Maximal activation of β1-adrenoceptors had only a small stimulating effect on Golgi Ca2+ release. However, inhibition of phosphodiesterase (PDE) 3 or 4, or downregulation of PDE 3 and 4 in heart failure markedly potentiated β1-adrenergic stimulation of Golgi Ca2+ release, consistent with compartmentalization of cAMP signaling within the Golgi apparatus microenvironment. β1-adrenergic stimulation of Golgi Ca2+ release involved activation of both Epac and PKA signaling pathways and CaMKII. Interventions that stimulated Golgi Ca2+ release induced trafficking of vascular growth factor receptor-1 (VEGFR-1) from the Golgi apparatus to the surface membrane. These data establish the Golgi apparatus as a juxtanuclear focal point for Ca2+ and β1-adrenergic signaling, which functions independently from the sarcoplasmic reticulum and the global Ca2+ transients that underlie the primary contractile function of the cell.