Corrosion of household copper plumbing infrastructure can cause pipe failure and lead to elevated levels of copper in drinking water which can exceed the USEPA health based standard for copper in drinking water of 1.3 mg/L Cu. The purpose of this study was to determine taste thresholds of copper in different types of water, analyze how copper chemistry can affect tasting, determine if common disinfectants influence the taste of copper and evaluate genetic links to copper sensitivity. A one-out-of-five test was used to define thresholds, evaluate disinfectant influences, and examine copper chemistry differences. A difference from control test was used to analyze soluble copper tasting and a one solution test with visual classification was used to discriminate 6-n-propylthiouracil (PROP) taster status. Solutions containing copper sulfate (0.05 – 8 mg/l Cu) were prepared in distilled water, mineral water of varying pH and mineral water with disinfectant added. Geometric mean copper taste thresholds were 0.48 mg Cu/l and 0.41mg Cu/l in distilled and mineral water pH 7.4 respectively. Logistic regression copper taste thresholds were 1.50 mg Cu/l and 1.96 mg Cu/l in distilled and mineral water pH 7.4 respectively. Soluble copper was readily tasted while particulate copper was poorly tasted. Chlorine and chloramines dosed at typical tap water levels had no significant effect on panelists' tasting abilities for water containing 1 mg/l total copper. Geometric mean copper thresholds values did not correlate with (PROP) status so PROP sensitivity would not be a good indicator for copper sensitivity. / Master of Science

The distribution system is the primary cause of taste and odor complaints in drinking water. This research examined the ability of small diameter pipes used in home plumbing to affect drinking water quality. The properties of the materials were investigated in the absence of disinfectant and the presence of either chlorine or chloramines. A panel was trained in flavor profile analysis (FPA) according to Standard Methods 2170B and used to assess the sensory properties of all samples. Chemical analyses were performed to determine disinfectants, total organic carbon (TOC), pH and specific organic contaminants. The first part of this study investigated PEX pipes manufactured by the silane (PEX-b) and peroxide (PEX-a) cross-linking technology, using the utility quick test (UQT) method. Silane PEX-b had a greater effect on water quality properties such as odor, TOC and residual disinfectant demand than peroxide-linked PEX-a. Chemical analysis revealed that PEX pipes can contribute fuel oxygenates such as ETBE (PEX-b) and possibly MTBE (PEX-a) to drinking water. PEX pipes did not contribute any significant trihalomethanes to drinking water. This study showed that the type of PEX used in homes will determine the extent to which drinking water quality is affected. The second part of this study used simulated plumbing rigs to investigate seven different materials under low flow and stagnant conditions; chlorinated polyvinyl chloride, cross-linked polyethylene, polyethylene, epoxy-lined copper, copper, stainless steel, galvanized iron and glass (control). Results showed that these plumbing materials have the potential to affect water quality characteristics such as TOC concentrations, residual disinfectant and odor when newly installed in homes. A high TOC concentration was consistent with the presence of a distinct odor or a high FPA intensity rating. Galvanized iron produced the worst odors that were consistently described as "motor oil". Polyethylene generated more intense plumbing associated odors than PEX or cPVC plastic material. cPVC and copper generated the least odors. Both copper pipe and epoxy-lined copper consumed residual chlorine and chloramines. / Master of Science

The purpose of the problem was to develop a laboratory technique for mass culturing of the aquatic actinomycetes. In order to solve the problem, it was necessary to devise a suitable culture chamber that would nurture the various species in both primary and secondary stages. It was also important to provide an adequate medium for growth of these organisms. Finally, the construction of the culture chambers must provide for a continuous exhaust of the taste and odor compounds so that the production of these components could be correlated with growth stages.

O objetivo desta dissertação é compreender o conceito de padrão moral na filosofia de David Hume. Qual sua importância? O padrão moral regula os juízos morais. Todos os juízos de valor dependem do gosto e de sentimentos de prazer ou desagrado. Mas o que é o gosto? Quais objetos ele julga? Como ele forma juízos? Em moral, o objeto do gosto é o caráter pessoal. O caráter virtuoso causa prazer, o vicioso causa desgosto. Sentimos prazer com um caráter virtuoso porque ele contribui para a felicidade da espécie humana. Sentimos prazer com a felicidade de nossa espécie por causa de um instinto denominado benevolência. Todos nós temos esse instinto, existe uma natureza humana. Alguns juízos de gosto são defectivos, mas o refinamento corrige-os. O padrão moral é instituído pelo refinado gosto de indivíduos que contemplaram a natureza humana. Eles são chamados de moralistas. Moralistas humanizam a humanidade. São essas as principais teses examinadas aqui. / This dissertation aims to comprehend the concept of moral standard in David Humes philosophy. Why is it important? The moral standard regulates moral judgments. All value judgments depend on taste and on sentiments of pleasure or dislike. But what is taste? What objects does it judge? How does it make judgments? The object of taste on morals is personal character. The virtuous character causes pleasure, the vicious character causes disgust. We feel pleasure with a virtuous character, for he promotes the happiness of the human species. We feel pleasure with the happiness of our species because of an instinct denominated benevolence. We all have this instinct, there is a human nature. Some judgments of taste are defective, but refinement corrects them. The moral standard is instituted by the refined taste of individuals who contemplated human nature. They are called moralists. Moralists humanize humanity. These are the principal theses here examined.

Alterações do gosto provocadas pelo uso de derivados de platina têm sido descritos. Contudo, poucos estudos qualificam os gostos prejudicados e se essas alterações derivam exclusivamente da quimioterapia. Objetivo: avaliar as alterações dos gostos doce, azedo, salgado, amargo e umami, em pacientes recebendo quimioterapia com derivados de platina (QTx). Métodos: Foram estudados 43 sujeitos, 21 do grupo estudo e 22 do grupo controle, em dois tempos, antes do início da QTx e uma após dois ciclos de QTx. A ingestão alimentar habitual, Índice de massa corporal e força da preensão palmar por dinamometria e fadiga (através do pictograma da fadiga) foram avaliados para caracterizar o grupo estudado. Foram realizados testes gustativos com Taste Strips, para os 4 gostos e o umami foi estudado comparando por escala Likert a apreciação do gosto, utilizando alimento com e sem glutamato monossódico (GMS). A análise estatística foi realizada com análise de variância (ANOVA) de medidas repetidas, modelo mixto. Adotou-se como nível de significância p<=0,05. Resultados: O salgado e o azedo foram os gostos mais comprometidos no grupo estudo (p=0,001 e 0,05); assim como os receptores ionotrópicos (p=0,02) responsáveis pela identificação desses gostos. Houve diferença entre o T0 e T1 para índice de massa corporal (IMC), dinamometria e impacto nas atividades cotidianas, pelo pictograma da fadiga (p=0,008,0,009 e 0,006 respectivamente).Conclusão: esse achados sugerem que a doença parece exercer um papel importante na alteração de reconhecimento dos gostos, principalmente nos gostos salgado e azedo, identificados pelos receptores ionotrópicos, o que parece relacionar-se com as mudanças alimentares. Os quimioterápicos demostraram uma contribuição para comprometimento da funcionalidade e fadiga / Changes in taste caused by the use of platinum drugs have been described. However, few studies qualify prejudiced tastes and whether these changes are derived exclusively from chemotherapy. Methods: A total of 43 subjects, 21 from the study group and 22 from the control group, were studied in two times, with the aim of evaluating changes in sweet, sour, salty, bitter and umami tastes in patients receiving chemotherapy with platinum drugs (QTx) before the start of QTx, and one after two cycles of QTx. The usual dietary intake, body mass index (BMI) and handgrip strenght by dynamometry and fatigue (through the fatigue pictogram) were evaluated to characterize the group studied. Taste Strips tests were performed for all 4 tastes and umami was studied by comparing Likert\'s taste tasting using monosodium glutamate (GMS) food. Statistical analysis was performed with analysis of variance (ANOVA) of repeated measures, mixed model. It was adopted as significance level p<=0.05. Results: Salty and sour were the most affected tastes in the study group (p = 0.001 and 0.05); as well as the ionotropic receptors (p = 0.02) responsible for identifying these tastes. There was a difference between T0 and T1 for BMI, dynamometry and impact in daily activities, by the fatigue pictogram (p = 0.008,0,009 and 0.006 respectively). Conclusion: these findings suggest that the disease seems to play a role important in altering the recognition of tastes, especially in salty and sour tastes, identified by ionotropic receptors, which seems to be related to dietary changes. The platinun drugs demonstrated a contribution to impairment of functionality and fatigue

Excessive intake of sodium, sugar, fats, and other unhealthy dietary patterns significantly contribute to cardiovascular disease (CVD) risk and, among those with diagnosed CVD, to deleterious outcomes. Taste perception is one of the most important factors influencing dietary intake and there are many factors that can alter it such as medication and genetic variations. Yet there has been relatively little research on influences of taste perception on self-management of CVD and CVD risk. The purpose of this dissertation is to examine the association of various factors and taste perception in order to add to our understanding of what may or may not influence dietary consumption behaviors among persons at-risk for or with diagnosed CVD. The specific aims of this dissertation were to 1) examine the association between dietary sodium consumption and antihypertensive medication regimen in patients with heart failure (HF); 2) examine the associations between variants of the TAS2R38 haplotype and dietary intake patterns of salt, sugar, fat, alcohol and vegetables in community dwelling adults in Appalachia Kentucky with 2 or more CVD risk factors; and 3) examine associations between the TAS2R38 haplotype and salt taste sensitivity and sodium consumption in patients with HF and their family caregivers. Specific aim one was addressed by evaluating whether prescribed diuretic, beta blocker, angiotensin II receptor blockers (ARBs), and angiotensin converting enzyme (ACE) inhibitors predicted sodium consumption as evidenced by sodium density in a sample of patients with HF when controlling for age, gender, ethnicity, smoking status, New York Heart Association (NYHA) class and body mass index (BMI). The results of this study indicate that, among patients with HF, prescribed ACE inhibitor is predictive of higher sodium consumption but not prescribed diuretics, beta blockers and angiotensin receptor blockers. To address specific aim two, a secondary analysis of data of a sample of adults living in rural Appalachia with 2 or more CVD risk factors was conducted. We examined if having one or two PAV haplotypes was predictive of patterns of salt, sugar, fat, alcohol and vegetable consumption, controlling for age, gender, smoking status, BMI, and prescribed ACE and ARB. There were no associations between TAS2R38 haplotype and any of these dietary intake patterns. Specific aim three was addressed in a study to examine the associations between the TAS2R38 haplotype and salt taste sensitivity and sodium consumption as indicated by 24-hour urinary sodium excretion in patients with HF and their family caregivers, controlling for age, gender, ethnicity, smoking status, and fungiform papillae number. Our outcomes indicated that haplotype did not predict salt taste sensitivity but did predict 24-hour urinary sodium excretion, with significantly less levels of urinary sodium excretion among participants who were homozygous for the PAV haplotype compared to those who were heterozygous for the PAV haplotype or homozygous for the AVI haplotype. The results of these studies, separately and in concert, provide greater understanding of influences of taste perception on self-management among people who are at-risk for or who have diagnosed CVD.

The aim of this study was to quantify the density of taste pores on the anterior region of the tongue, in adult males and 8 to 9 year old boys. Earlier studies had shown that, although 8 to 9 year olds were poorer than adults at sensing the tastant sucrose using a whole mouth procedure, localised regions of the tongue in male children were more sensitive than equivalent regions in adults. This study aims to detemine whether the age differences in sensitivity is related to a difference in taste pore density. Two areas of the tongue, for which children had previously been shown to have higher sensitivity than adults, were examined using a videomicrosocpy technique and the number and diameter of taste pores were measured. Children were found to have a greater density of taste pores, however the number of taste pores per papilla were similar in children and adults. It was found to be likely that the greater sensitivity of localised areas on the children's tongue is due to a greater taste pore density. The reduced sensitivity reported using whole mouth stimulation may be due to a reduced capacity to assimilate taste input from the whole mouth or due to different relative contributions to whole-mouth taste from the various receptive fields in the mouth. / Master of Science (Hons)

Die Bittergeschmacksrezeptoren stellen in der Superfamilie der G-Protein-gekoppelten Rezeptoren eine besondere Gruppe dar. Im Menschen können die 25 Rezeptoren eine große Anzahl unterschiedlichster Bittergeschmacksstoffe detektieren. Diese Substanzen können sowohl schädlich, wie etwa Strychnin, als auch der Gesundheit förderliche Arzneistoffe, wie etwa Chloramphenicol sein. Unter den Bittergeschmacksrezeptoren des Menschen gibt es eine Gruppe von drei Rezeptoren, die besonders viele Bitterstoffe detektieren können. Einer von ihnen ist der Rezeptor hTAS2R10. In dieser Arbeit konnte sowohl experimentell als auch durch computergestützte Modellierung gezeigt werden, dass der hTAS2R10 nur eine Bindungstasche besitzt. Das stimmt mit den bisher ausführlich experimentell und in silico untersuchten Rezeptoren hTAS2R1, -R16, -R38 und -R46 überein. Die für die Agonisteninteraktionen nachweislich wichtigen Transmembrandomänen sind in den bisher untersuchten Bittergeschmacksrezeptoren, wie auch im hTAS2R10, die Transmembrandomänen 3, 5, 6 und 7. Die Untersuchungen zeigten, dass die Bindungstasche des hTAS2R10 in der oberen Hälfte des zum extrazellulären Raum gerichteten Bereichs lokalisiert ist. Insbesondere konnte für die untersuchten Agonisten Strychnin, Parthenolid und Denatoniumbenzoat gezeigt werden, dass die Seitenketten der Aminosäuren in Position 3.29 und 5.40 ausgeprägte agonistenselektive Wechselwirkungen eingehen. Weitere Untersuchungen haben ergeben, dass das weitgefächerte Agonistenspektrum des hTAS2R10 zu Lasten der Sensitivität für einzelne Bitterstoffe geht. Der Vergleich wichtiger Positionen im hTAS2R10, hTAS2R46 und mTas2r105 hat deutlich gemacht, dass sich die Bindungsmodi zwischen diesen Rezeptoren unterscheiden. Dies deutet auf eine getrennte evolutionäre Entwicklung der Bindungseigenschaften dieser Rezeptoren hin. Gleichfalls zeigten die Untersuchungen, dass einige Positionen wie z.B. 7.39 die Funktion aller untersuchten Bittergeschmacksrezeptoren prägen, sich jedoch die genaue Bedeutung im jeweiligen Rezeptor unterscheiden kann. Einzelne dieser Positionen konnten auch bei der Agonisteninteraktion des Rhodopsins und des β2-adrenergen Rezeptors beobachtet werden. Die Ergebnisse dieser Arbeit helfen dabei die Wechselwirkungen zwischen Bitterstoffen und den Bittergeschmacksrezeptoren zu verstehen und geben erste Einblicke in die Entwicklung der Rezeptoren in Hinblick auf ihren Funktionsmechanismus. Diese Erkenntnisse können genutzt werden, um Inhibitoren zu entwickeln, die sowohl ein wichtiges Werkzeug in der Rezeptoranalytik wären, als auch dazu genutzt werden könnten, den unerwünschten bitteren Geschmack von Medikamenten oder gesundheitsfördernden sekundären Pflanzenstoffen zu mindern. Damit könnte ein Beitrag zur Gesundheit der Menschen geleistet werden. / In the Superfamily of G protein-coupled receptors the bitter taste receptors form a notable group. The 25 human receptors are able to detect a large group of structurally diverse bitter compounds. These compounds can be toxic – like strychnine – or have beneficial effects on health – like the pharmacological agent chloramphenicol. Three of these bitter taste receptors show a strikingly broad agonist spectrum. One of them is the hTAS2R10. It was shown empirically and by computational modelling that the hTAS2R10 has only one binding pocket. This agrees with the findings of studies on the bitter taste receptors hTAS2R1, -R16, -R38 and -R46. The domains important for agonist interaction in these receptors, as well as in the hTAS2R10, are the transmembrane domains 3, 5, 6 and 7. The results of this thesis show that the binding pocket of the hTAS210 is located in the upper part of the receptor which points into the direction of the extracellular area. Interestingly, it has been shown for the amino acid side chains in the positions 3.29 and 5.40, that they can interact with the analysed agonists strychnine, parthenolide and denatonium benzoate in an agonist-selective way. Further analyses showed that the broad tuning of the hTAS2R10 goes at the expense of the sensitivity to single agonists. The comparison of crucial positions in the hTAS2R10, hTAS2R46 and the mTas2r105 reveal that these receptors differ in their binding mode. These could be evidence that the binding abilities of these receptors evolved independently. However, the results show that some positions, e.g. 7.39, influence the receptor activity in all analysed receptors, but the function of these positions in the receptors could be different. Some of these positions also have an influence on the agonist-receptor interaction of Rhodopsin and the β2-adrenergic receptor. The findings in this thesis contribute to the knowledge about interaction between bitter receptors and bitter compounds. The results also provide insight into the evolvement of receptor functions. These outcomes can be of use for the development of inhibitors which could serve as analytical tools in taste research. Furthermore, such inhibitors could be used to reduce the bitter taste of medicine and healthy plant compounds and thus increase palatability. This could contribute to improve human well-being.

In humans, taste is one of the five senses, and helps in the recognition of nutritionally important and potentially harmful substances. It triggers innate behaviour to accept or reject food. Humans can sense five basic tastes, which are sweet, umami, bitter, salt and sour. The receptors that mediate bitter, sweet and umami tastes belong to the G protein-coupled receptor (GPCR) superfamily. A group of three receptors sense sweet and umami tastes, whereas bitter taste is sensed by 25 bitter taste receptors (referred as T2Rs). T2Rs are activated by structurally diverse natural and synthetic bitter compounds. Many common pharmaceutical compounds are bitter in taste and these are effective ligands for T2Rs. Recent finding of T2Rs in extra-oral tissues suggests these receptors are also involved in various physiological and pathophysiological processes. To understand the structure and function of these receptors, studies directed at elucidating their mechanisms of activation, and identification of novel ligands including bitter blockers (antagonists and inverse agonists), are required. To obtain mechanistic insights into the role of the highly conserved, and receptor specific residues, two bitter taste receptors (T2R1 and T2R4) were targeted. In this study, a combination of molecular, biochemical and pharmacological approaches were used to identify the amino acids and motifs, important for T2Rs to switch from inactive to active state. A hydrogen-bonding network between transmembrane (TM) helices 1-2-7 was identified as important for T2R activation. Alanine-scan mutagenesis of intracellular loops (ICLs) 2 and 3 identified T2R regions important for G protein binding, and receptor activation. A pharmacological method was developed, to screen potential bitter blockers for T2Rs. Using this method, three novel bitter blockers, which include two natural antagonists and one synthetic inverse agonist for T2R4, were discovered. The role of expression tags in enhancing T2R4 expression was also pursued. T2R4 expression on the cell surface was increased 2.5 fold, when its N-terminus was tagged with rhodopsin N-terminal 33 residues (Rho33- T2R4 chimera). In conclusion, work carried out provides novel insights into the mechanisms of T2R activation, and in the discovery of bitter blockers for T2R4.

Long-term memories turn labile with reactivation and undergo a re-stabilization process, termed reconsolidation, involving molecular changes that allow updating of an existing memory trace. Such molecular changes may involve the activation of kinases and expression of proteins related to the increase of synaptic plasticity and memory formation. A kinase reported to have a role in a variety of memory tasks is the extracellular signal-regulated kinase 1/2 (ERK1/2). The downstream activation of ERK targets other regulatory enzymes, transcription factors and cytoskeletal proteins, which allow structural changes in the neuron due to protein synthesis up-regulation. Among the proteins up-regulated by ERK activity is the activity-regulated cytoskeleton-associated protein (ARC), an immediate early gene related to synaptic plasticity. The phase-dependent roles of ERK and ARC have not been examined as part of the molecular mechanisms triggered after a learning experience. In this study I used conditioned taste aversion (CTA) as the learning paradigm and investigated the expression of pERK and ARC in brain regions critical for taste information processing such as the insular cortex and the amygdala. A differential pattern of protein expression was observed in the insular cortex (IC) two hours after taste memory acquisition: pERK activity increased in the aversively conditioned group while ARC increased in the group that received only the novel taste. The central amygdala (CeA) showed a significant increase in pERK, but not ARC activity after CTA training. Immunoblotting experiments performed after memory retrieval in the appetitive group show that pERK continues to signal aversive taste to the IC with ARC exhibiting heightened expression an hour later. An increase in ARC expression 30 minutes after reactivation of the aversive taste was seen in the basolateral amygdala and the CeA exhibited a similar increase at 60 and 90 minutes. Local infusion of ARC antisense oligonucleotides within the IC interfered with the consolidation of safe taste memories, but not with their acquisition. Trace update experiments showed that ARC influences the memory switch from aversive to safe, but not the reverse. Our results indicate that ARC plays a critical role in consolidation and updating of safe taste memories, and the ARC signaling could possibly elicit ERK activation.