Objectives The objective of the present study was to investigate the usefulness of time-frequency analysis (TFA) of olfactory-induced EEG change with a low-cost, portable olfactometer in the clinical investigation of smell function. Materials & methods A total of 78 volunteers participated. The study was composed of three parts where olfactory stimuli were presented using a custom-built olfactometer. Part I was designed to optimize the stimulus as well as the recording conditions. In part II EEG-power changes after olfactory/trigeminal stimulation were compared between healthy participants and patients with olfactory impairment. In Part III the test-retest reliability of the method was evaluated in healthy subjects. Results Part I indicated that the most effective paradigm for stimulus presentation was cued stimulus, with an interstimulus interval of 18-20s at a stimulus duration of 1000ms with each stimulus quality presented 60 times in blocks of 20 stimuli each. In Part II we found that central processing of olfactory stimuli analyzed by TFA differed significantly between healthy controls and patients even when controlling for age. It was possible to reliably distinguish patients with olfactory impairment from healthy individuals at a high degree of accuracy (healthy controls vs anosmic patients: sensitivity 75%; specificity 89%). In addition we could show a good test-retest reliability of TFA of chemosensory induced EEG-power changes in Part III. Conclusions Central processing of olfactory stimuli analyzed by TFA reliably distinguishes patients with olfactory impairment from healthy individuals at a high degree of accuracy. Importantly this can be achieved with a simple olfactometer.

El marketing sensorial es considerado como una estrategia de mercadeo que intenta estimular nuestros sentidos. La mayoría de las marcas peruanas ahora tratan de conquistar a los consumidores y retenerlos ya que cada día son más exigentes. Lo que la mayoría de las veces hacen es enfocar la atención que sus clientes le dan a sus sentidos teniendo en cuenta que el sentido del olfato se caracteriza por tener un alto nivel de recordación. Esto a su vez hace que de cierta manera la marca trate de ganarse un lugar en la mente de los consumidores. Teniendo en cuenta esto, se procederá a analizar el marketing olfativo en la tienda Desigual en Lima para posicionarse en la mente del consumidor de 22 a 29 años en el segundo semestre del año 2020. Se desarrollará de manera cualitativa, ya que se buscará; de alguna manera, comprender al consumidor y cómo percibe el marketing olfativo al momento de buscar la experiencia dentro de la tienda. / Sensory marketing is a marketing strategy that stimulate our senses. Nowadays most of the Peruvian brands try to retain the consumers, who become more demanding every day. What the brands do most is focus on their clients sense attention taking into account the sense of smell, that its characterized by having a high level of memory. This means that the brand is already positioned in the consumer's mind. Taking this into account, we will proceed to analyze the olfactory marketing of the Desigual brand in Lima for people between 22 and 27 years old in the second semester of the year 2020. It will be developed qualitatively, as it will be sought; in some way, understand the consumer and how he perceives olfactory marketing when looking for the experience with in the store. / Trabajo de investigación

A great degree of interindividual variability has been established in measures of psychophysical olfactory performance and odor awareness in both children and adults. Previous studies have suggested the possibility that one of the factors that might contribute to this variability might be the degree of odor exposure in everyday contexts. In the present study, we hypothesized that children exposed to a greater variety of odors on a more frequent basis would exhibit higher odor identification and odor awareness scores. We have found an effect of odor exposure on the children's olfactory knowledge as reflected in their reports of olfactory behavior, but not olfactory abilities. In so doing, we replicated some of the previous findings in the literature of female over male advantage in the olfactory domain. Namely, we report that girls showed a more profound understanding of their olfactory environment and a greater degree of olfaction-oriented behavior, which was not accounted for by a gender difference in verbal fluency. Nevertheless, girls did not outperform boys on either of the measures of olfactory performance. Semi-longitudinal and longitudinal studies in verbally proficient children, employing both self- and parental reports of children's odor exposure and repeated olfactory testing, might...

The main body of the thesis deals with selected factors underlying the considerable variability in human olfactory abilities and some odour awareness-related measures, addressed in samples ranging in age from middle childhood to young adulthood. The thesis consists of two parts. The first part (Chapter 1), first presents the major advances and developments that brought about something of a renaissance of scientific interest in the human sense of smell, including the recent proliferation of psychophysical studies, both basic research and clinical. Next, an outline of olfactory psychophysical measures and related olfactory abilities that are of relevance to the studies presented in this thesis is provided. Subsequently, the selected factors contributing to interindividual differences in olfactory abilities, that have been addressed by this thesis, are reviewed, namely the effect of sex (or gender), which is approached from a developmental perspective, childhood gender nonconformity, and personality. Finally, intraindividual fluctuations in olfactory performance are also mentioned in brief. Next, the focus shifts to odour awareness by first introducing the various approaches that can be adopted to get closer to the real-life context as opposed to laboratory setting (where most olfactory studies continue to be...

The main body of the thesis deals with selected factors underlying the considerable variability in human olfactory abilities and some odour awareness-related measures, addressed in samples ranging in age from middle childhood to young adulthood. The thesis consists of two parts. The first part (Chapter 1), first presents the major advances and developments that brought about something of a renaissance of scientific interest in the human sense of smell, including the recent proliferation of psychophysical studies, both basic research and clinical. Next, an outline of olfactory psychophysical measures and related olfactory abilities that are of relevance to the studies presented in this thesis is provided. Subsequently, the selected factors contributing to interindividual differences in olfactory abilities, that have been addressed by this thesis, are reviewed, namely the effect of sex (or gender), which is approached from a developmental perspective, childhood gender nonconformity, and personality. Finally, intraindividual fluctuations in olfactory performance are also mentioned in brief. Next, the focus shifts to odour awareness by first introducing the various approaches that can be adopted to get closer to the real-life context as opposed to laboratory setting (where most olfactory studies continue to be...

This study aimed to elucidate the role of smell diaries in Olfactory training (OT) and probe gender differences in intensity ratings and measured olfactory function throughout the OT course. Fifty olfactory loss patients (36 women and 14 men) undergoing OT rated odor intensities on a daily basis for at least 12 weeks. They exhibited significant improvement in measured olfactory function after OT; gender had no significant effect. As for the diaries, women rated odors with higher intensities than men, and ratings from women increased with time while men rated odors at the same level. Across all patients, there was a weak positive correlation between ratings and psychophysical test scores (r = 0.30, p = .04). Throughout the OT course, the increase in odor intensity ratings was more pronounced in women than it was in men (F[1, 44] = 7.9, p = .007). However, this gender-related difference was not found for measured olfactory function, suggesting pronounced gender-differentiated behaviors in terms of self-ratings of olfactory function.

Evidence suggests that postural stability may benefit from olfactory exposure, but whether this effect is different for hyposmic and healthy subjects remains unknown and little attention has been paid to the hedonic valence of odors in this context. Forty-five participants aged between 23 and 64 years were invited to this study, of whom 32 had normal olfactory function 13 exhibited olfactory deficits. Movement measurements were performed with the “Unterberger stepping test.” Participants walked in place with stretched arms for 8 periods of 30 s each, separated by intervals of approximately 15 s. During each of these 30-s blocks one of the three odor conditions was presented to them: (a) pleasant odor, (b) unpleasant odor, and (c) odorless control. Both participants with normosmia and impaired olfaction moved to the left and right sides more when exposed to the unpleasant odor as compared to pleasant odor exposure or no odor. When smelling pleasant odors, participants presented shorter maximal anterior/posterior sway than during no odor exposure, but it was similar when smelling unpleasant odor. The study demonstrated strong effects of odors on postural stability with pleasant odors limiting and unpleasant enhancing postural sways. Practical Applications Odors affect postural stability. Although we fail to demonstrate that postural stability measurements can be applied as a supporting method in smell dysfunction diagnosis, the current study opens prospects for further explorations of the relationship between olfactory and vestibular systems. These efforts may eventually lead to practical solutions supporting postural balance in patients suffering from conditions adversely affecting the vestibular system.

Small intestine neuroendocrine tumors (SI-NETs) and lung carcinoids (LCs) are relatively indolent tumors, which originate from neuroendocrine (NE) cells of the diffuse NE system. Metastases can spread before diagnosis. Thus, potential cures become unavailable, which entitles new biomarker development. Indeed, we aimed at developing Ma2 autoantibodies and olfactory receptor 51E1 (OR51E1) as potential novel biomarkers and exploring other candidate protein markers in patients’ serum. First, we established a sensitive, specific and reliable anti-Ma2 indirect ELISA to distinguish SI-NET patients from healthy controls. We detected longer progression-free and recurrence-free survivals in patients expressing low anti-Ma2 titers. Moreover, a high anti-Ma2 titer was more sensitive than chromogranin A for the risk of recurrence after radical operation of SI-NET patients. We then investigated OR51E1 expression in SI-NETs and LCs. OR51E1 mRNA expression, analyzed by quantitative real-time PCR, was high in microdissected SI-NET cells, in LC cell lines and in frozen LC specimens. Immunohistochemistry (IHC) showed abundant OR51E1 protein expression in SI-NETs. OR51E1 co-expressed with vesicular-monoamine-transporter-1 in the majority of normal and neoplastic enterochromaffin cells. Furthermore, the study on LCs revealed that OR51E1, somatostatin receptor (SSTR) 2, SSTR3, and SSTR5 are expressed in 85%, 71%, 25% and 39% of typical carcinoids (TCs), whereas in 86%, 79%, 43% and 36% of atypical carcinoids (ACs). Based on the proposed IHC scoring system, in the LC cases, where all SSTR subtypes were absent, membrane OR51E1 expression was detected in 10 out of 17 TCs and 1 out of 2 ACs. Moreover, higher OR51E1 scores were detected in 5 out of 6 OctreoScan-negative LC lesions. In addition, the last presented study used a novel suspension bead array, which targeted 124 unique proteins, by using Human Protein Atlas antibodies, to profile biotinylated serum samples from SI-NET patients and healthy controls. We showed 9 proteins, IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP as significant contributors to tumor classification. In conclusion, we proposed Ma2 autoantibodies as a sensitive circulating marker for SI-NET recurrence; OR51E1 as a candidate therapeutic target for SI-NETs; whereas as a novel diagnostic marker for LCs and 9 serum proteins as novel potential SI-NET markers. / 小肠神经内分泌肿瘤(SI-NET)和肺类癌(LC)是起源于不同神经内分泌细胞的生长缓慢的肿瘤。肿瘤往往于诊断前已经转移。这导致目前缺乏有效的治疗方法，同时也使得对于新的生物标记物的研发变得有意义。因此，我们在本论文中分别研究了Ma2自身抗体(抗Ma2)，以及潜在的新型生物标记物嗅觉受体51E1(OR51E1)。我们还探讨了患者血清中的其他候选蛋白标记物。 首先，我们建立了一个灵敏特异而可靠的抗Ma2间接酶联免疫吸附试验，用以区分SI-NET患者组和健康对照组。在表达低滴度抗Ma2的患者中，我们检测到了较长的病情无恶化存活率以及肿瘤无复发存活率。此外，高滴度抗Ma2比嗜铬粒蛋白A更为灵敏地检测到了SI-NET患者根治手术后复发的风险。     接下来，我们研究了SI-NET和LC患者肿瘤中的OR51E1受体蛋白的表达。我们用实时定量PCR技术检测到了OR51E1信使核糖核酸在显微切除的SI-NET肿瘤细胞中，以及在LC细胞系和冷冻LC标本中的高度表达。免疫组化结果显示出OR51E1蛋白在SI-NET肿瘤组织中的高度表达。OR51E1与囊泡单胺转运蛋白1在大多数正常和肿瘤的肠嗜铬细胞中可共表达。 另外，我们针对LC患者的研究显示，OR51E1受体蛋白以及促生长素抑制素受体(SSTR)2，SSTR3和SSTR5分别在85％，71％，25％和39％的典型性肺类癌(TC)，以及86％，79％，43％和36的非典型性肺类癌(AC)中表达。基于我们我提出的免疫组化结果得分系统，在无SSTR表达的LC中，OR51E1蛋白在17个TC中的10个以及2个AC中的1个中呈细胞膜表达。而且，在6个OctreoScan显象呈阴性的LC中，有5个OR51E1免疫组化得分很高。     此外，在本论文最后的一项研究中，我们采用了一种新型的悬浮磁珠阵列技术，通过使用来自于人类蛋白质图谱项目的针对124种独特蛋白质的抗体，对SI-NET患者和健康对照组的用生物素标记过的血清样本进行了分析。结果显示，通过利用9种蛋白，即IGFBP2，IGF1，SHKBP1，ETS1，STX2，IL1α，MAML3，EGR3和XIAP，我们可以显著的对肿瘤进行分类。     综上所述，我们提出Ma2自身抗体可作为一个体液中灵敏的生物标记物用以暗示SI-NET肿瘤的复发; OR51E1受体蛋白可作为一个在SI-NET治疗中所能用及的候选生物靶分子，并在LC中作为一种新型的潜在生物标记物。此外，我们在SI-NET患者血清中检测到了9种新的候选标记物蛋白。

<p>Ovim se istraživanjem na primeru osnovnih predikata (glagola) percepcije ruskog i srpskog jezika odgovara na pitanja vezana za sistemske odnose u oblasti leksike, klasifikaciju jezičkih jedinica, definisanje leksema, međusobnu zavisnost značenja leksema i njihovih morfolo&scaron;kih i sintaksičkih obeležja. Osnovni predikati (glagoli) percepcije ruskog i srpskog jezika pozicioniraju se unutar semantičkih paradigmi, zasnovanih na interakciji diferencijalnih i zajedničkih komponenata značenja svojih članova. Članovi paradigmi izdvajaju se na osnovu kriterijuma određenih u skladu s principima organizacije centra i periferije leksičkog sistema. Pozicioniranje izdvojenih predstavnika vizuelne, auditivne, olfaktorne, gustativne i taktilne percepcije, kao i njihovih vidskih korelata, rezultira utvrđivanjem strukture paradigmi i smerova semantičke derivacije u njima.</p> / <p>This dissertation focuses on systemic relationships among the basic predicates (verbs) of perception in Russian and Serbian. It investigates issues related to the lexicon, the classification of linguistic units, the relationships between the meanings of lexemes and their morphological and syntactic features, as well as the definition of the main members of the analysed lexico-semantic group. The basic predicates of perception in Russian and Serbian are positioned within the semantic paradigms, based on the interaction of differential and general components of meaning of their members. The members of the paradigms are selected based on criteria established in accordance with the principle of the organization of lexical systems into core and periphery. The positioning of the selected representatives of visual, auditory, olfactory, gustative and tactile perception, as well as their aspectual correlates, results in determining the structure of the paradigms and the directions of semantic derivation in them.</p>

La neurogenèse persiste à l’âge adulte dans deux régions du système nerveux central (SNC) des mammifères : la zone sous-ventriculaire (SVZ) du cerveau antérieur et la zone sous-granulaire (SGZ) de l’hippocampe. Cette neurogenèse est possible grâce à la capacité de prolifération des cellules souches présentes dans les niches de la SVZ et la SGZ, mais en vieillissant, le cerveau subit une diminution dramatique du nombre de cellules souches neurales adultes (CSNa), une diminution de la prolifération cellulaire et une altération des niches de neurogenèse. Cependant, une importante question reste sans réponse : comment la perte tardive des CSNa est temporellement reliée aux changements de l’activité de prolifération et de la structure de la principale niche de neurogenèse (la SVZ)? Afin d’avoir un aperçu sur les événements initiaux, nous avons examiné les changements des CSNa et de leur niche dans la SVZ entre le jeune âge et l’âge moyen. La niche de la SVZ des souris d’âge moyen (12 mois) subit une réduction de l’expression des marqueurs de plusieurs sous-populations de précurseurs neuraux en comparaison avec les souris jeunes adultes (2 mois). Anatomiquement, cela est associé avec des anomalies cytologiques, incluant une atrophie générale de la SVZ, une perte de la couche de cellules sousépendymaires par endroit et l’accumulation de gouttelettes lipidiques de grande taille dans l’épendyme. Fonctionnellement, ces changements sont corrélés avec une diminution de l’activité de la SVZ et une réduction du nombre de nouveaux neurones arrivant aux bulbes olfactifs. Pour déterminer si les CSNa de la SVZ ont subi des changements visibles, nous avons évalué les paramètres clés des CSNa in vivo et in vitro. La culture cellulaire montre qu’un nombre équivalent de CSNa ayant la capacité de former des neurosphères peut être isolé du cerveau du jeune adulte et d’âge moyen. Cependant, à l’âge moyen, les précurseurs neuraux semblent moins sensibles aux facteurs de croissance durant leur différenciation in vitro. Les CSNa donnent des signes de latence in vivo puisque leur capacité d’incorporation et de rétention du BrdU diminue. Ensemble, ces données démontrent que, tôt dans le processus du vieillissement, les CSNa et leur niche dans la SVZ subissent des changements significatifs, et suggèrent que la perte de CSNa liée au vieillissement est secondaire à ces événements. / Neurogenesis persists throughout the adulthood in two regions of the mammalian central nervous system (SNC): the sub-ventricular zone (SVZ) of the forebrain and the sub-granular zone (SGZ) of the hippocampus. Neurogenesis is possible due to the proliferation capacity of stem cells present within both the SVZ and SGZ niches, but with aging, the forebrain undergoes a drastic reduction in its number of adult neural stem cells (aNSCs), a decrease of cell proliferation and an alteration of the neurogenic niches. However, a key unresolved question remains: how the onset of aNSC loss is temporally related to changes of proliferating activity and to structural alterations within the principal stem cell niche (the SVZ)? To gain insights into the initial events leading to aging-associated aNSC loss, we investigated the changes occurring to aNSCs and the SVZ niche between young adulthood and middle-age. The SVZ niche of middle-aged mice (12-months-old) was found to display reduced expression of markers for multiple neural precursor sub-populations when compared to young adult mice (2-months-old). Anatomically, this was associated with significant cytological aberrations, including an overall atrophy of the SVZ, loss of sub-ependymal cells, and accumulation of large lipid droplets within the ependyma. Functionally, these changes correlated with diminished SVZ activity and reduced number of newly born neurons reaching the principal target tissue: the olfactory bulbs. To determine whether changes were evident at the level of the SVZ stem cells, we evaluated key in vitro and in vivo parameters of aNSCs. Tissue culture experiments showed that equal numbers of neurosphere-forming aNSCs could be isolated from young adult and middle-aged forebrains. However, at middle-age, neural precursors seemed to be less sensitive to growth factors during their in vitro differentiation and displayed signs of increased quiescence in vivo. Collectively, these findings demonstrate that, with early aging, aNCS and their SVZ niche go through significant changes, and suggest that aging-associated aNSC loss is secondary to these events.