The great novelist and poet Johann Wolfgang von Goethe (1749 – 1832) arguably made his most significant contribution to the artistic world with his literary masterpiece Faust I. Goethe’s love of music and melody is evident throughout all of Faust, particularly in the expressive poetry of the character of Gretchen, whose meaningful words gave inspiration to a variety of musical manifestations, especially in German Lied. This document serves as a performance guide for vocalists. It provides vital information on the setting and arrangement of the poetry within the musical settings, the background and significance of the composer and his works, and the organization of the music. The examination of each piece will involve assessment of musical phrasing, tessitura, and overall vocal complexity in eight German Lieder settings of Gretchen’s soliloquy “Ach neige, du Schmerzenreiche” from Goethe’s Faust. The suggestions within the investigations are based on examination of pedagogical practices as well as personal experience and discoveries made while singing and performing these pieces. Through an investigation of each piece, the singer will be able to attain a successful understanding of the framework and approach to the music and poetry, and thereby achieve awareness of accurate performance practice. This document examines in order of composition, the settings by Bettina von Arnim, Franz Schubert (including the completed fragment as arranged by Benjamin Britten), Conrad Kreutzer, Bernhard Klein, Johann Loewe, Robert Schumann, Hugo Wolf, and Fredric Joseph Kroll. Because this document serves to investigate only German Lieder settings, it will not examine the choral works of Hans Pfitzner, Antoni Radziwill, Julius Röntgen, Giuseppe Verdi’s Italian setting “Deh, pietoso, oh Addolorata,” nor Richard Wagner’s Melodram. This document will also very briefly discuss the lost and inaccessible settings of Gretchen’s prayer, including those of Carl Debrois van Bruyck, Edmund von Freyhold, Moritz Hauptmann, Justus Lecerf, Leopold Lenz, Louis Schlottmann, and Hans Sommer.

The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the “cholinergic anti-inflammatory pathway”. Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Analytical Chemistry Candidate: Ivo Vrobel Supervisors: Prof. RNDr. Petr Solich, CSc; Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague Prof. Seppo Auriola, MSc.(Chem.) Marko Lehtonen; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Eastern Finland in Kuopio Title of master's thesis: LC-MS/MS analysis of acetylcholine in brain microdialysis samples Novel fast and simple LC-MS/MS method of ACh quantification in brain microdialysis samples utilizing stable-isotope-labeled IS was developed. The chromatographic step is based on revered-phase mode of pentafluorophenylpropyl (PFPP) column. The satisfactory retention of ACh is achieved with highly aqueous mobile phase containing 0.05% of the ion-pairing agent TFA and 4% of ACN in 4 min analytical run. Ionization of ACh and IS with low background noise and tolerant towards use of TFA was performed with atmospheric pressure thermospray ionization (APTSI). The selectivity of ACh and IS detection was obtained by SRM modes of MS/MS in the linear ion trap mass analyzer. The performance of developed method was cross validated to the validated method used in the laboratory for ACh measurements. The set of microdialysis...

Since its beginnings in 1974, the Automated Clearing House (ACH) network has grown into one of the largest, safest, and most efficient payment systems in the world. An ACH transaction is an electronic funds transfer between bank accounts using a batch processing system. Currently, the ACH Network moves almost $43 trillion and 25 billion electronic financial transactions each year. With the increasing movement toward an electronic, interconnected and mobile infrastructure, it is critical that electronic payments work safely and efficiently for all users. ACH transactions carry sensitive data, such as a consumer's name, account number, tax identification number, account holder name, address, or social security number. ACH fraud consists of the theft of funds through the Automated Clearing House financial transaction network (Accounts Receivable & Order-to-Cash Network, 2012). If the transactions are intercepted by fraudulent activities, either during transit or during rest, the sensitive customer data can be used to steal the transferred funds, which can cause financial and reputational damage to ACH network participants and consumers. Even though the National Automated Clearing House Association (NACHA) requires ACH participants to use commercially reasonable encryption and authentication procedures, the risks associated with employee error or negligence, physical theft, and insider theft of data remain substantial. The ACH network that handles 40 billion transactions annually has consumer and corporate financial information. As the ACH network emerges as a prominent payment channel, proactive steps must be taken to guarantee consumer safety. The primary research question “How can opportunities to commit ACH fraud by insiders be inhibited by masking sensitive data in the ACH transactions life cycle?” is addressed employing design science research methodology with special focus on this specific question: Will use of Multi-step tokens in life cycle of ACH transactions lower the risk of sensitive data exposure? To demonstrate the extent to which the Multi-step tokens in the life cycle of ACH transactions lower the risk of sensitive data exposure, the following two sub-questions will be answered: • How to model and simulate sensitive data exposure risk in current ACH transaction life cycle? • How to model and simulate sensitive data exposure risk in the multi-step tokenized ACH transaction life cycle? The research findings through proof of concept simulations confirm that sensitive consumer personal identifiable information shared in ACH network can be made more secure from insider threat opportunities by multi-step tokenization of ACH data. In the to-be system, the real account number will not be used to post the actual financial transaction. Only tokenized account number will be used by RDFI (Receiving Depository Financial Institution) to post the financial transaction. Even if the ODFI (Originating Depository Financial Institution) initiate the financial transaction using real account number, RDFI will reject the transaction back to the originator to resend the transaction using the token value. For the same account number, RDFI will have different token values based on SEC (Standard Entry Class) code, origin, ODFI, transaction type etc. The account token value will be generated only if ODFI sends a token request separately to RDFI in a multi-step manner. The research findings suggest that multi-step tokenization can be used to generate and validate unique transaction path as a function of the transaction origin number, originating depository financial institution, Standard Entry class, Receiving depository financial institution and account number. Even if the account or token value gets misplaced, the data will be of no use to the person having the information. The cipher can be further strengthened by including additional unique ACH data elements. The findings stem from proof of concept development and testing of conceptual, empirical and simulated models of current ACH network, insider breach scenarios, and multi-step tokenized systems. The study findings were augmented by running different model scenarios and comparing the outputs for breaches, network traffic and costs. The study findings conclude with an implementation proposal of the findings in the ACH network and opportunities for further research on the topic.

No description available.

<p>Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder.</p><p>Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter ³H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the ³H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons.</p><p>Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death.</p><p>Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered.</p><p>Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.</p>

Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disease with unknown ethiology. The aim of this study was to increase understanding of the pathophysiological mechanisms of dying motor neurons and wasting muscle tissue in this particular disorder. Quantitative receptor autoradiographic methodology was applied on cervical spinal cord sections from patients with ALS to evaluate the specific binding of the acetylcholine transporter 3H-vesamicol in motor neurons. Despite a significant reduction of the number of ventral motor neurons in ALS, the 3H-vesamicol binding was not reduced in ALS compared to control cases, which suggests an increased metabolic activity in remaining motor neurons. Motor neurons dying in ALS might go through apoptosis (programmed cell death), so immunohistochemical and TUNEL techniques were applied on thoracic spinal cord from ALS patients to evaluate the possibility of an apoptotic process. The increased Bax expression indicates an apoptotic process and further, motor neurons were TUNEL-positive, indicating DNA degradation caused by programmed cell death. Muscle biopsies were obtained from ALS patients, and mRNA levels for the neurotrophic factors GDNF and BDNF were measured and compared to control subjects. GDNF levels were increased in muscle tissue in ALS whereas BDNF levels were unaltered. Levels of GDNF and BDNF were also measured in cerebrospinal fluid from ALS patients and controls using ELISA methodology. Levels of BDNF were unaltered in ALS cornpared to controls. GDNF however was not detectable in controls whereas 12 out of 15 ALS patients had measurab1e levels of GDNW. A marked upregulation of endogenous GDNF and GDNF mRNA in ALS CSF and muscle respectively is of special interest in relation to clinical trials where GDNF is administered to this group of patients.

No description available.

Foreign investments in SADC are regulated by Annex 1 of the SADC Protocol on Finance and Investments (SADC FIP), as well as the laws of SADC Member States. At present, SADC faces the challenge that this regime for the regulation of foreign investments is unstable, unsatisfactory and unpredictable. Furthermore, the state of the rule of law in some SADC Member States is unsatisfactory. This negatively affects the security of foreign investments regulated by this regime. The main reasons for this state of affairs are briefly explained below. The regulatory regime for foreign investments in SADC is unstable, due to recent policy reviews and amendments of key regulatory instruments that have taken place. Major developments in this regard have been the suspension of the SADC Tribunal during 2010, the amendment of the SADC Tribunal Protocol during 2014 to bar natural and legal persons from access to the Tribunal, and the amendment of Annex 1 during 2016 to remove investor access to international investor-state arbitration, better known as investor-state dispute settlement (ISDS). The regulation of foreign investments in SADC has been unsatisfactory, among others because some SADC Member States have failed or neglected to harmonise their investment laws with both the 2006 and the 2016 Annex 1. Furthermore, SADC Member States such as Angola, Democratic Republic of Congo (DRC), Malawi, Mauritius, Seychelles, Eswatini, Tanzania, Zambia, and Zimbabwe have multiple Regional Economic Community (REC) memberships. This places these Member States in a position whereby they have conflicting interests and treaty obligations. Finally, the future of the regime for the regulation of foreign investments in SADC is unpredictable, due to regional integration efforts such as the recent formation of the COMESA-EAC-SADC Tripartite Free Zone (T-FTA) and the African Continental Free Trade Area (AfCFTA). The T-FTA is entitled to have its investment protocol, while the AfCFTA investment protocol will be negotiated from 2018 until 2020. These developments entail that the 2016 Annex 1 will soon be replaced by an investment protocol at either the T-FTA or AfCFTA levels, thereby ushering a new regime for the regulation of foreign investments in SADC. The unknown nature of the future regulations create uncertainty and instability among foreign investors and host states alike. This study analyses the regulation of foreign investments in terms of Annex 1 and selected laws of SADC Member States. In the end, it makes the three findings mentioned above. In order to address these findings, the study makes four recommendations. The first is that foreign investments in SADC must be regulated at African Union (AU) level, by means of an AfCFTA investment protocol (which incidentally is now the case). Secondly, investor-state disputes must be referred to the courts of a host state, optional ISDS, the African Court of Justice and Human Rights (ACJ&HR) or other agreed forum. Thirdly, an African Justice Scoreboard (AJS) must be established. The AJS will act as a gateway to determine whether an investor-state dispute shall be referred to the courts of a host state, ISDS, the ACJ&HR or other forums. Fourthly, the office of an African Investment Ombud (AIO) must be created. The AIO shall facilitate the early resolution of investor-state disputes, so as to reduce the number of disputes that may end-up in litigation or arbitration. / Mercantile Law / LL. D.

This thesis is developed as a proposal for heating for a primary school and kindergarten in the region of Brno-countryside. For the insulated building, a combination of heating and air-conditioning is proposed. The concept is designed so that the air-conditioning preheats the exterior air and the heating system warms the incoming air to a comfortable temperature. For the required thermal performance, sources of heat (for gas and pellets) and a layout solution for the boiler room is designed. Drainage of combustion products is proposed for both solutions. The project solution is per the extent of the construction permit. The theoretical part is linked with the practical part through the condensation boilers, their function and division, and drainage of combustion products. The experiment for the given topic was conducted on the drainage of combustion products. The pressure loss of the reverse knob was determined in relation to the flow rate of air in the condensation boilers as this loss is essential in assessing the drainage of combustion products.