Depressed cardiac autonomic modulation in patients with chronic kidney disease

Introduction: A dysfunctional autonomic nervous system (ANS) has also been recognized as an important mechanism contributing to the poor outcome in CKD patients, with several studies reporting a reduction in heart rate variability (HRV). Objective: Evaluate the sympathovagal balance in patients with chronic kidney disease on conservative treatment. Methods: In a cross-sectional study, patients with CKD stages 3, 4 and 5 not yet on dialysis (CKD group) and age-matched healthy subjects (CON group) underwent continuous heart rate recording during two twenty-minute periods in the supine position (pre-inclined), followed by passive postural inclination at 70° (inclined period). Power spectral analysis of the heart rate variability was used to assess the normalized low frequency (LFnu), indicative of sympathetic activity, and the normalized high frequency (HFnu), indicative of parasympathetic activity. The LFnu/HFnu ratio represented sympathovagal balance. Results: After tilting, CKD patients had lower sympathetic activity, higher parasympathetic activity, and lower sympathovagal balance than patients in the CON group. Compared to patients in stage 3, patients in stage 5 had a lower LFnu/HFnu ratio, suggesting a more pronounced impairment of sympathovagal balance as the disease progresses. Conclusion: CKD patients not yet on dialysis have reduced HRV, indicating cardiac autonomic dysfunction early in the course of CKD.

Modulation of TGF-β signaling by Hypoxia

A tumor is a fast-growing malignant tissue. This creates areas inside the tumor that are distant from local blood vessels to be able to get enough oxygen. This hypoxic condition activates a transcription factor called hypoxia inducible factor (HIF). HIF responses help a cell to adapt to decreased oxygen by activating glycolytic and angiogenesis pathways and by regulating apoptotic responses. Hypoxia drives the upregulation of a growth factor called transforming growth factor beta (TGF-beta). Similar to a hypoxia response, TGF is an important regulator of cell fate. TGF-β and HIF pathways regulate partially overlapping target genes. This regulation can also be cooperative. The TGF-beta signal is initiated by activation of plasma membrane receptors that then activate effector proteins called small mothers against decapentaplegic (Smad) homologs. In healthy tissue, TGF-β keeps cell proliferation and growth under control. During cancer progression, TGF-beta has shown a dual role, whereby it inhibits initial tumor formation but, conversely, in an existent tumor, TGF-beta drives malignant progression. Along with HIF and TGF-beta also protein dephosphorylation is an important regulatory mechanism of cell fate. Protein dephosphorylation is catalyzed by protein phosphatases such as Protein phosphatase 2A (PP2A). PP2A is a ubiquitous phosphatase that can exist in various active forms. PP2A can specifically regulate TGF-beta signaling either by enhancing or inhibiting the receptor activity. This work demonstrates that during hypoxia, PP2A is able to fine-tune TGF-beta signal by specifically targeting Smad3 effector in a Smad7-dependent manner. Inactivation of Smad3 in hypoxia leads to malignant conversion of TGF-beta signaling.

Adoption and Usability of Online Pharmacies for Purchasing Prescription Medicines

The study examines customers’ perceptions of purchasing prescription medicine from online pharmacies. The main purpose is to find determinants affecting the adoption of online pharmacies, and to consider the role of usability in the adoption process. The theoretical part of the paper provides the overlook on adoption constructs and their relations. In addition, usability factors used in prior studies are presented, as well as how they have been connected to IS adoption research. The specialties of Finnish pharmacy business and the requirements set to online pharmacies are also discussed. The empirical part of the study is conducted with the qualitative approach. Four respondents were interviewed and observed while they tried online pharmacies. The data gathered indicates respondents’ initial beliefs toward the service, perceptions of the usability, and the changes in the perceptions and beliefs after using online pharmacies. The results indicate that usability factors and adoption determinants are interrelated. Usability influences perceived ease of use, which affects both perceived usefulness and behavioral intention. Regulations restrict the design of online pharmacies, which has affect on the both the perceived ease of use and perceived usefulness, and thus the whole adoption process.

Corporate social responsibility in online retail – Perceptions from online discussions on Amazon

Online retail has experienced substantial growth due to the increased utilization of digital technologies. The growth in the industry has created numerous multinational corporations, which serve customers all around the world. As a result, the online retailers’ efforts in sustainability have been more often in publicity. Corporate Social Responsibility (CSR), the efforts going beyond the company’s interest in order to bring social good, have been discussed in the academic community for decades. While the various effects of CSR in retail and business generally have been realized, the research aims to make a contribution by examining the concept from the viewpoint of online retail by focusing on interaction at online discussion forums. The main research question asks: What is the role of online retailer CSR in the online discussion forum context? In order to answer this question, additional three sub-research questions are suggested: 1) What elements of CSR are relevant in the online retailer context? 2) How are discussion forums used in communication regarding CSR and online retail by different discusser types? 3) What kind of company perceptions and consumer behavior appear in online discussions of Amazon’s CSR? The study is qualitative of nature, using the content analysis research method to examine posts found from four different public online discussion forums. A qualitative, interpretative analysis was used, although quantitative measures regarding discussion posts were also presented. The analysis contains a coding process, where attributes are attached to discussion posts. As a result of the process, specific patterns can be indicated in order to categorize the posts. As the research uses Amazon as the case company, the case study method is also adopted. In the online retail context, ethics regarding the online retailer’s tax and labor policies are found as most relevant elements. Customers, using discussion forums to share their experiences and opinions regarding online retailer CSR efforts, are realized as the most prominent stakeholder. The research also highlights the role of online retailer employees providing details on internal business practices. However, the not realize the possibility to participate in discussions. Most discussion posts refer either to a positive, negative or mixed reaction towards CSR efforts, it is suggested that the concept is relevant also in online retail. Although online retailer CSR efforts are somewhat linked to company perceptions, the concept has a minimal role in consumer behavior. In online retail, CSR efforts can reduce the risk of being involved in discussions related to controversies. In addition, online retailer CSR efforts should communicate how the retailer contributes locally.

Corporate social responsibility in online retail – Perceptions from online discussions on Amazon

Online retail has experienced substantial growth due to the increased utilization of digital technologies. The growth in the industry has created numerous multinational corporations, which serve customers all around the world. As a result, the online retailers’ efforts in sustainability have been more often in publicity. Corporate Social Responsibility (CSR), the efforts going beyond the company’s interest in order to bring social good, have been discussed in the academic community for decades. While the various effects of CSR in retail and business generally have been realized, the research aims to make a contribution by examining the concept from the viewpoint of online retail by focusing on interaction at online discussion forums. The main research question asks: What is the role of online retailer CSR in the online discussion forum context? In order to answer this question, additional three sub-research questions are suggested: 1) What elements of CSR are relevant in the online retailer context? 2) How are discussion forums used in communication regarding CSR and online retail by different discusser types? 3) What kind of company perceptions and consumer behavior appear in online discussions of Amazon’s CSR? The study is qualitative of nature, using the content analysis research method to examine posts found from four different public online discussion forums. A qualitative, interpretative analysis was used, although quantitative measures regarding discussion posts were also presented. The analysis contains a coding process, where attributes are attached to discussion posts. As a result of the process, specific patterns can be indicated in order to categorize the posts. As the research uses Amazon as the case company, the case study method is also adopted. In the online retail context, ethics regarding the online retailer’s tax and labor policies are found as most relevant elements. Customers, using discussion forums to share their experiences and opinions regarding online retailer CSR efforts, are realized as the most prominent stakeholder. The research also highlights the role of online retailer employees providing details on internal business practices. However, the not realize the possibility to participate in discussions. Most discussion posts refer either to a positive, negative or mixed reaction towards CSR efforts, it is suggested that the concept is relevant also in online retail. Although online retailer CSR efforts are somewhat linked to company perceptions, the concept has a minimal role in consumer behavior. In online retail, CSR efforts can reduce the risk of being involved in discussions related to controversies. In addition, online retailer CSR efforts should communicate how the retailer contributes locally.

Path Analysis of Online Users Using Clickstream Da-ta: Case Online Magazine Website

This paper explores behavioral patterns of web users on an online magazine web-site. The goal of the study is to first find and visualize user paths within the data generated during collection, and to identify some generic behavioral typologies of user behavior. To form a theoretical foundation for processing data and identifying behavioral ar-chetypes, the study relies on established consumer behavior literature to propose typologies of behavior. For data processing, the study utilizes methodologies of ap-plied cluster analysis and sequential path analysis. Utilizing a dataset of click stream data generated from the real-life clicks of 250 ran-domly selected website visitors over a period of six weeks. Based on the data collect-ed, an exploratory method is followed in order to find and visualize generally occur-ring paths of users on the website. Six distinct behavioral typologies were recog-nized, with the dominant user consuming mainly blog content, as opposed to editori-al content. Most importantly, it was observed that approximately 80% of clicks were of the blog content category, meaning that the majority of web traffic occurring in the site takes place in content other than the desired editorial content pages. The out-come of the study is a set of managerial recommendations for each identified behavioral archetype.

Jätteiden kemiallisten ominaisuuksien spektrometriset online-mittausmenetelmät

Tässä diplomityössä käsiteltiin spektrometrisia online-mittausmenetelmiä jätteiden kemiallisten ja fysikaalisten ominaisuuksien määrittämiseksi. Tavoitteena oli selvittää, mitä ominaisuuksia menetelmillä voidaan mitata ja kuinka luotettavia tuloksia mittauksilla saadaan. Diplomityössä suoritettiin kirjallisuuskatsaus, jossa käsiteltiin kolmen spektrometrisen menetelmän soveltuvuutta reaaliaikaisiin jätemittauksiin. Työn empiirisessä osassa FPXRFanalysaattorilla mitattiin neljän eri jätenäytteen alkuainepitoisuuksia. Mittauksen tarkoituksena oli selvittää, mitä alkuaineita menetelmällä voidaan mitata. FPXRF-analysaattorilla saatuja tuloksia verrattiin ICP-MS-menetelmällä saatuihin tuloksiin regressioanalyysin avulla. Työssä todettiin, että FPXRF-analysaattori sopii parhaiten kaliumin, kalsiumin, ja raudan pitoisuuksien määrittämiseen. Lisäksi lyijyn, sinkin, kromin, kloorin, kuparin, kadmiumin, arseenin, fosforin, molybdeenin ja vanadiinin määrittäminen on mahdollista, mutta tarkan pitoisuuden saamiseksi laboratoriomenetelmien käyttö voi olla tarpeen. Tutkituista jätenäytteistä menetelmä soveltui parhaiten tuhkalle ja kompostille niiden fyysisten ominaisuuksien, kuten homogeenisuuden ja kosteuspitoisuuden takia. Biojätteelle menetelmä soveltui huonosti. FPXRF-analysaattorin luotettavuuteen vaikuttaa näytteen kosteuspitoisuus, homogeenisuus, partikkelikoko, mittaustapa ja laitteen kalibrointi. Työssä tarkastelluilla menetelmillä ei voida tällä hetkellä täysin korvata laboratorioanalyyseja. FPXRF-analysaattoria voidaan kuitenkin käyttää kvalitatiiviseen tai semikvantitatiiviseen haitta-aineiden analysointiin, millä voidaan vähentää kalliiden laboratorioanalyysien tarvetta.

Real-time adaptive control of ultra-fast laser scribing process with spectrometer online monitoring

There exist several researches and applications about laser welding monitoring and parameter control but not a single one have been created for controlling of laser scribing processes. Laser scribing is considered to be very fast and accurate process and thus it would be necessary to develop accurate turning and monitoring system for such a process. This research focuses on finding out whether it would be possible to develop real-time adaptive control for ultra-fast laser scribing processes utilizing spectrometer online monitoring. The thesis accurately presents how control code for laser parameter tuning is developed using National Instrument's LabVIEW and how spectrometer is being utilized in online monitoring. Results are based on behavior of the control code and accuracy of the spectrometer monitoring when scribing different steel materials. Finally control code success is being evaluated and possible development ideas for future are presented.

Collaborative reflection : supporting one practitioner's development of online learning communities /

This is a study of one participant's reflective practice as she worked to develop online communities in a face-to-face science course. Her process of reflective practice was examined in order to address factors that influenced her learning path, and the benefits and challenges of collaborative action research. These research goals were pursued using a collaborative action research methodology, initially chosen for its close match with Schon's (1983) model of reflective practice. The participant's learning fit vnth Mezirow's (1991) model of transformative learning. She began with beliefs that matched her goals, and she demonstrated significant learning in three areas. First, she demonstrated instrumental learning around the constraints of workload and time, and achieving online learning community indicators. Second, she demonstrated communicative learning that helped her to see her own needs for feedback and communication more clearly, and how other process partners had been a support to her. Third, her emancipatory learning saw her revisiting and questioning her goals. It was through the reflective conversation during the planned meetings and the researcher's reframing and interrogation of that reflection that the participant was able to clarify and extend her thinking, and in so doing, critically reflect on her practice as she worked to develop online learning communities. In this way, the collaborative action research methodology was an embodiment of co-constructivism through collaborative reflective practice. Schon's (1983) model of reflective practice positions a lone practitioners moving through cycles ofplan-act-observe-reflect. The results fi"om this study suggest that collaboration is an important piece of the reflective practice model.

Online problem-based learning : perceptions of nursing educators /

A qualitative study was conducted to detennine 5 nursing educators' perceptions about the online application of a problem-based learning strategy in undergraduate nursing education. The question asked in the study was: Can the essential elements of face-to-face problem-based learning be supported in an online format? The data for this study came from 2 individual tape-recorded interviews with each of the 5 participants over a 3-month period and from a researchjournaI. The educators felt that student-centered learning and critical thinking could be supported within an online format. However, they noted that challenges could exist in terms of developing tutor roles, fostering student self-direction, facilitating group process and connections, and incorporating a nursing philosophy of online learning. The importance of tailoring an online problem-based learning course to reflect educators' philosophies and values in nursing emerged as an important theme from the interview responses. Overall, the participants suggested that an ideal environment would blend both face-to-face and online elements and that fewer elements would be offered in the first 2 years of the nursing program. They described a hybrid model of problem-based learning in which the online component could be used to support face-to-face sessions.

Perceptions of some teachers about the similarities and/or differences in teaching online versus in a classroom environment /

The introduction of computer and communications technology, and particularly the internet, into education has opened up some new possibilities for teaching and learning. Courses designed and delivered in an online environment offer the possibility of highly interactive and individually focussed teaching and learning experiences. However, online courses also present new challenges for both teachers and students. A qualitative study was conducted to explore teachers' perceptions about the similarities and differences in teaching in the online and face-to-face (F2F) environments. Focus group discussions were held with 5 teachers; 2 teachers were interviewed in depth. The participants, 3 female and 2 male, were full-time teachers from a large College of Applied Arts & Technology in southern Ontario. Each of them had over 10 years of F2F teaching experience and each had been involved in the development and teaching of at least one online course. i - -; The study focussed on how teaching in the online environment compares with teaching in the F2F environment, what roles teachers and students adopt in each setting, what learning communities mean online and F2F and how they are developed, and how institutional policies, procedures, and infrastructure affect teaching and learning F2F and online. This study was emic in nature, that is the teachers' words determine the themes identified throughout the study. The factors identified as affecting teaching in an online environment included teacher issues such as course design, motivation to teach online, teaching style, role, characteristics or skills, and strategies. Student issues as perceived by the teachers included learning styles, role, and characteristics or skills. As well, technology issues such as a reliable infrastructure, clear role and responsibilities for maintaining the infrastructure, support, and multimedia capability affected teaching online. Finally, administrative policies and procedures, including teacher selection and training, registration and scheduling procedures, intellectual property and workload policies, and the development and communication of a comprehensive strategic plan were found to impact on teaching online. The teachers shared some of the benefits they perceived about teaching online as well as some of the challenges they had faced and challenges they perceived students had faced online. Overall, the teachers feh that there were more similarities than differences in teaching between the two environments, with the main differences being the change from F2F verbal interactions involving body language to online written interactions without body language cues, and the fundamental reliance on technology in the online environment. These findings support previous research in online teaching and learning, and add teachers' perspectives on the factors that stay the same and the factors that change when moving from a F2F environment to an online environment.

The role of cyclic nucleotides in modulation of crayfish neuromuscular junctions by a neuropeptide /

DF2, a heptapeptide, is a member of the family of FMRFamide-like peptides and has been shown to increase the amount of transmitter released at neuromuscular junctions of the crayfish, Procambarus clarkit Recent evidence has shown that protein kinase C (PKC), calcium/calmodulin-dependent protein kinase II (CaMKII) and the cAMPdependent protein kinase (PKA) play a role in the neuromodulatory pathway of DF2. The involvement of these kinases led to the prediction that a G-protein-coupled receptor (GPCR) is activated by DF2 due to the role that each kinase plays in traditional GPCR pathways seen in other organisms and in other cells. G-proteins can also act on an enzyme that generates cyclic guanosine monophosphate (cGMP) which mediates its effects through a cGMP-dependent protein kinase (PKG). This thesis addresses the question of whether or not DF2's effects on synaptic transmission in crayfish are mediated by the cyclic nucleotides cAMP and cGMP. The effects of DF2 on synaptic transmission were examined using deep abdominal extensor muscles of the crayfish Procambarus clarkii. An identified motor neuron was stimulated, and excitatory post-synaptic potentials (EPSPs) were recorded in abdominal extensor muscle LI . A number of activators and inhibitors were used to determine whether or not cAMP, PKA, cGMP and PKG mediate the effect of this peptide. Chemicals that are known to activate PKA (Sp-cAMPS) and/or PKG (8-pCPTcGMP) mimic and potentiate DF2's effect by increasing EPSP amplitude. Inhibitors of either PKA (Rp-cAMPS) or PKG (Rp-8-pCPT-cGMPS) block a portion of the increase in EPSP amplitude induced by the peptide. When both kinase inhibitors are applied simultaneously, the entire effect of DF2 on EPSPs is blocked. The PKG inhibitor blocks the effects of a PKG activator but does not alter the effect of a PKA activator on EPSP amplitude. Thus, the PKG inhibitor appears to be relatively specific for PKG. A trend in the data suggests that the PKA inhibitor blocks a portion of the response elicited by the PKG activator. Thus, the PKA inhibitor may be less specific for PKA. Phosphodiesterase inhibitors, which are known to inhibit the breakdown of cAMP (IBMX) and/or cGMP (mdBAMQ), potentiate the effect of the peptide. These results support the hypothesis that cAMP and cGMP, acting through their respective protein kinase enzymes, mediate the ability of DFi to increase transmitter output.

Cortical and autonomic modulation of attentional control /

Whereas the role of the anterior cingulate cortex (ACC) in cognitive control has received considerable attention, much less work has been done on the role of the ACC in autonomic regulation. Its connections through the vagus nerve to the sinoatrial node of the heart are thought to exert modulatory control over cardiovascular arousal. Therefore, ACC is not only responsible for the implementation of cognitive control, but also for the dynamic regulation of cardiovascular activity that characterizes healthy heart rate and adaptive behaviour. However, cognitive control and autonomic regulation are rarely examined together. Moreover, those studies that have examined the role of phasic vagal cardiac control in conjunction with cognitive performance have produced mixed results, finding relations for specific age groups and types of tasks but not consistently. So, while autonomic regulatory control appears to support effective cognitive performance under some conditions, it is not presently clear just what factors contribute to these relations. The goal of the present study was, therefore, to examine the relations between autonomic arousal, neural responsivity, and cognitive performance in the context of a task that required ACC support. Participants completed a primary inhibitory control task with a working memory load embedded. Pre-test cardiovascular measures were obtained, and ontask ERPs associated with response control (N2/P3) and error-related processes (ERN/Pe) were analyzed. Results indicated that response inhibition was unrelated to phasic vagal cardiac control, as indexed by respiratory sinus arrhythmia (RSA). However, higher resting RSA was associated with larger ERN ampUtude for the highest working memory load condition. This finding suggests that those individuals with greater autonomic regulatory control exhibited more robust ACC error-related responses on the most challenging task condition. On the other hand, exploratory analyses with rate pressure product (RPP), a measure of sympathetic arousal, indicated that higher pre-test RPP (i.e., more sympathetic influence) was associated with more errors on "catch" NoGo trials, i.e., NoGo trials that simultaneously followed other NoGo trials, and consequently, reqviired enhanced response control. Higher pre-test RPP was also associated with smaller amplitude ERNs for all three working memory loads and smaller ampUtude P3s for the low and medium working memory load conditions. Thus, higher pretest sympathetic arousal was associated with poorer performance on more demanding "catch" NoGo trials and less robust ACC-related electrocortical responses. The findings firom the present study highlight tiie interdependence of electrocortical and cardiovascular processes. While higher pre-test parasympathetic control seemed to relate to more robust ACC error-related responses, higher pre-test sympathetic arousal resulted in poorer inhibitory control performance and smaller ACC-generated electrocortical responses. Furthermore, these results provide a base from which to explore the relation between ACC and neuro/cardiac responses in older adults who may display greater variance due to the vulnerabihty of these systems to the normal aging process.

Aspects of the hemes and modulation of hydrogen donors in catalases from bovine liver, yeast, and escherichia coli

Catalase is the enzyme which decomposes hydrogen peroxide to water and oxygen. Escherichia coli contains two catalases. Hydroperoxidase I (HPI) is a bifunctional catalase-peroxidase. Hydroperoxidase II (HPII) is only catalytically active toward H202. Expression of the genes encoding these proteins is controlled by different regimes. HPJI is thought to be a hexamer, having one heme d cis group per enzymatic subunit. HPII wild type protein and heme containing mutant proteins were obtained from the laboratory of P. Loewen (Univ. of Manitoba). Mutants constructed by oligonucleotidedirected mutagenesis were targeted for replacement of either the His128 residue or the Asn201 residue in the vicinity of the HPII heme crevice. His128 is the residue thought to be analogous to the His74 distal axial ligand of the heme in the bovine liver enzyme, and Asn201 is believed to be a residue critical to the function of the enzyme because of its role in orienting and interacting with the substrate molecule. Investigation of the nature of the hemes via absorption spectroscopy of the unmodified catalase proteins and their derived pyridine hemochromes showed that while the bovine and Saccharomyces cerevisiae catalase enzymes are protoheme-containing, the HPII wild type protein contains heme d, and the mutant proteins contain either solely protoheme, or heme d-protoheme mixtures. Cyanide binding studies supported this, as ligand binding was monophasic for the bovine, Saccharomyces cerevisiae, and wild type HPII enzymes, but biphasic for several of the HPII mutant proteins. Several mammalian catalases, and at least two prokaryotic catalases, are known to be NADPH binding. The function of this cofactor appears to be the prevention of inactivation of the enzyme, which occurs via formation of the inactive secondary catalase peroxide compound (compound II). No physiologically plausible scheme has yet been proposed for the NADPH mediation of catalase activity. This study has shown, via fluorescence and affinity chromatography techniques, that NADPH binds to the T (Typical) and A (Atypical) catalases of Saccharomyces cerevisiae, and that wild type HPII apparently does not bind NADPH. This study has also shown that NADPH is unlike any other hydrogen donor to catalase, and addresses its features as a unique donor by proposing a mechanism whereby NADPH is oxidized and catalase is protected from inactivation via the formation of protein radical species. Migration of this radical to a position close to the NADPH is also proposed as an adjunct hypothesis, based on similar electron migrations that are known to occur within metmyoglobin and cytochrome c peroxidase when reacted with H202. Validation of these hypotheses may be obtained in appropriate future experiments.