Although empirical evidence suggests that interactions occur between serotonin (5- HT) and the hypothalamic-pituitary-interrenal (HPI) axis teleost fish, the mechanisms of serotonergic regulation of the HPI axis require elucidation. The hypothesis that 5-HT regulates the stress response in rainbow trout (Oncorhynchus mykiss) by acting at multiple levels in the HPI axis through tissue-specific 5-HT receptor subtypes was examined. Messenger RNA for 5-HT1A, 5-HT2 and 5-HT4 receptor subtypes was expressed in all HPI axis tissues. Administration of 5-HT in vivo in cannulated trout caused significant increases in plasma cortisol and glucose concentrations. In vitro head kidney preparations revealed a stimulatory effect of 5- HT, acting through the 5-HT4 receptor, on cortisol production. Collectively, these data suggest that 5-HT plays a role in HPI axis activation in rainbow trout, and that at the head kidney level, these effects likely are mediated by the 5-HT4 receptor.

Both cortisol and corticosterone circulate in human plasma however corticosterone has been relatively neglected in human research to date. There is evidence of distinct regulation within different tissues with the transmembrane transporter ABCB1, highly expressed in the brain, exporting cortisol but not corticosterone. This may account for the relative accumulation of corticosterone in the CNS. In contrast, ABCC1, highly expressed in adipose tissue and skeletal muscle, exports corticosterone but not cortisol, suggesting cortisol is the principal glucocorticoid acting in these tissues. We tested the hypotheses that: (i) corticosterone physiology in humans is different to that of cortisol; (ii) inhibition of ABCC1 increases binding of corticosterone to corticosteroid receptors in adipose tissue and skeletal muscle but has no central CNS effect; and (iii) corticosterone is superior to cortisol as a basis for glucocorticoid replacement therapy with fewer metabolic side effects. We compared paired salivary and plasma samples from 10 healthy individuals. Plasma corticosterone showed a similar diurnal variation to cortisol but salivary corticosterone was low and did not correlate with plasma concentrations. A placebo-controlled randomised crossover study was carried out in 14 healthy individuals comparing receptor occupancy of glucocorticoids centrally and peripherally with and without ABCC1 inhibition. Receptor occupancy was assessed through displacement with MR and GR antagonists potassium canrenoate and mifepristone. Centrally, ABCC1 inhibition caused increased activation of the HPA axis after MR and GR antagonism. Peripherally, we were unable to show displacement from adipose tissue or skeletal muscle. A further placebo-controlled randomised crossover study is still ongoing in 16 patients with congenital adrenal hyperplasia, comparing metabolic effects of placebo, cortisol and corticosterone infusions over 6 hours. We present interim data for n=8. ACTH and 17-OHP were suppressed with corticosterone. Metabolic parameters were similar between placebo, cortisol and corticosterone phases. These data suggest corticosterone physiology is distinct compared with cortisol in humans. We have shown ABCC1 inhibition alters the HPA axis after receptor antagonism which suggests ABCC1 may play more of a key role centrally than previously thought. Corticosterone suppresses ACTH and 17-OHP in the short term in congenital adrenal hyperplasia, highlighting the possibility of its use as an alternative glucocorticoid replacement therapy in the future.

Vertebrados exóticos são introduzidos intencionalmente como recurso, como uma alternativa para fins econômicos ou de lazer. Aqueles que se tornam capazes de expandir espontaneamente as novas populações em áreas naturais são conhecidas como invasores e frequentemente estão implicados em efeitos indesejados em populações, comunidades e ecossistemas autóctones. Uma destas espécies é o cervo axis Axis axis, introduzido mundialmente para a caça. Apesar da sua ampla distribuição e utilização, pouco se sabe sobre seus efeitos nas áreas invadidas e em quais regiões esta espécie pode se tornar invasora. Isto dificulta as tomadas de decisão, pois avaliar os efeitos da introdução e prever as áreas em risco de invasão são tarefas fundamentais para estratégias de prevenção, priorização e ações de controle. Assim, esse trabalho teve como objetivos revisar os efeitos do cervo axis em áreas invadidas, utilizando um protocolo de revisão sistemática, e modelar a possível distribuição mundial e regional desta espécie, utilizando variáveis bioclimáticas. Realizamos buscas por estudos sobre efeitos em áreas alóctones em três bancos de dados, utilizando três conjuntos de palavras chaves. Classificamos os estudos que atenderam aos critérios do protocolo segundo o nível de inferência sobre os efeitos em Efeito Demonstrado e Efeito Sugerido. Extraímos os tipos de efeitos relatados e a região de ocorrência. Para a modelagem de distribuição, utilizamos o algoritmo Maxent e variáveis preditoras bioclimáticas. Os pontos de ocorrência utilizados incluem sua distribuição original e três regiões onde a espécie é invasora e das quais foi possível obter ou estimar coordenadas. A revisão sistemática resultou em apenas quatro trabalhos classificados em Efeito Demonstrado, os quais apontam a competição com espécies nativas, alteração da composição florística e faunística e facilitação da entrada de outras espécies invasoras. Os efeitos sugeridos incluem seis trabalhos mostrando a ocorrência de parasitas, um caso de hibridização com outra espécie de cervídeo em cativeiro e um estudo mostrando a degradação das áreas de florestas causada pelo cervo axis em conjunto com outras espécies invasoras. O modelo de distribuição demonstra que amplas extensões da América do Sul, África Central e Sudeste Asiático são suscetíveis à invasão, portanto, nestas áreas deve-se evitar a introdução e controlar a expansão. O sul do Brasil, Uruguai, norte da Argentina e Paraguai são possíveis áreas de ocorrência segundo os modelos bioclimáticos. / Alien vertebrates are intentionally introduced for leisure and economic purposes. Those who become able to expand their populations in the new areas are known as invasive and are often involved in undesirable effects in indigenous populations, communities and ecosystems. The axis deer was introduced worldwide for hunting. Despite its wide distribution and use, little is known about its effects on the invaded areas and regions in which this species can become invasive. This complicates the decision-making because assessing the effects of the introduction and predict areas at risk of invasion are key tasks for prevention strategies, prioritization and control actions. Like this. So, this study aimed to summarize the effects of the axis deer in invaded areas using a systematic review protocol and to model the potential distribution of this species globally and in South America using bioclimatic variables. To summarized the effects we conducted searches for studies on non-native areas in three databases, using three sets of key-words and classified the studies that met the criteria of the protocol according to the level of inference about the effects they investigated. We extracted the types mentioned effects and occurrence region. To model the potential distribution based on bioclimatic variables we used the program Maxent. We used occurrences from the original distribution and three regions where the species is invasive about which geographical coordinates could be obtained or estimated. Four studies demonstrated effects of the axis deer due to competition with native species, changes in the floristic and faunistic composition and facilitation of other invasion processes. Six studies speculated the occurrence of disease transmition, hybridization with other species and difuse degradation of forest areas in combination with other invasive species. The distribution model demonstrated that large extensions of South America, Central Africa and Southeast Asia are susceptible to invasion. In the southern cone of South America Brazil, Uruguay, northern Argentina and Paraguay include extensive areas prone to invasion based on the bioclamatic models.

acase@tulane.edu / Stress is a major determinant of quality of life and chronic stress plays an important contributing role in the occurrence of psychiatric and physiological pathologies. Ascending brainstem noradrenergic afferents provide a critical excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis in response to stress by activating corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN). The stimulatory role of noradrenergic synapses on CRH neurons in the regulation of the HPA axis has long been known, but the cellular mechanisms have been perplexing. We demonstrate a retrograde inter-neuronal communication stimulated by norepinephrine that utilizes a trans-astroglial signaling mechanism to activate upstream neurons and recurrent synaptic inputs. We found that NE activates postsynaptic 1-adrenoceptors in PVN CRH neurons, which triggers a calcium response in astrocytes via the dendritic release of vasopressin. Activated astrocytes stimulate upstream glutamate neurons via ATP release and P2X receptor activation, resulting in the recurrent excitation of the CRH neurons. The NE excitation of CRH neurons is strengthened by simultaneous presynaptic 2-adrenoceptor-mediated suppression of GABA release but is restrained at higher NE concentrations by activation of upstream GABAergic neurons via the same postsynaptic α1-adrenoceptor-mediated retrograde neuronal-glial signaling mechanism. Thus, the NE stimulation of CRH neurons in the PVN is mediated by a novel retrograde signaling mechanism that enlists a trans-neuronal-astroglial circuit to activate upstream glutamate and GABA neurons. This mechanism is stress-sensitive. Acute stress desensitizes this α1-receptor mediated circuit via glucocorticoid receptor-dependent signaling. The desensitization of the excitatory circuit, through which NE exerts its major stimulatory drive to CRH neurons, indicates a cellular mechanism or a target site of negative feedback. Chronic stress desensitized the CRH neurons to both α1 and α2-adrenoceptor activation. Thus, the noradrenergic regulation of CRH neurons was lost entirely following chronic stress, rendering the CRH neurons completely insensitive to this major regulatory input. Our research revealed the cellular mechanisms of the NE regulation of CRH neurons under control, acute stress and chronic stress conditions. It fills an important gap in knowledge concerning the noradrenergic excitatory drive to the CRH neurons and the stress-induced glucocorticoid feedback control of the HPA axis. / 1 / Chun Chen

ABSTRACT Fan cooling is a fairly mainstream and well-developed technology. Vibration may make users feel uncomfortable. Assembly system may produce different noises right after the adverse effect components were destroyed, such as computer crashed or vibration or fan structural damage subsequently affects their fan reliability. Therefore, small vibration resonance amplification can not be overlooked. The researcher applied a 40 * 40 * 48mm fan to solve the problem of resonant vibration. He found the similar results of the natural frequencies of the structure of the fan by experimental and finite element analysis. In order to improve the vibration resonance, he changed the structural of the fans. In different structural designs, the natural frequencies did not change a lot. The natural frequency switched from 3000Hz to 3200Hz. To avoid the resonant frequency of the assemble fan, the researcher changed the number of fan blades and simulated the flow field. Compared the data to the experimental results, the results of the analysis were reasonable. The results showed the performance of the assembly fan did not necessarily need more leaves. The leaf numbers were from 7 (Inlet Fan) & 4 (Outlet Fan) into 5 (Inlet Fan) & 4 (Outlet Fan). Operation speed was changed from 14500 rpm (Inlet & Outlet Fan) to 15500 rpm (Inlet Fan) &11600 rpm (Outlet Fan). Using the fluid flow analysis, he found the change of the leaf number and operation speed of the fan could effectively avoid the resonance frequency and reduce vibration. An impact analysis was also helped to verify the capacity of the anti-impact of the fan. The structure of the fan after the preliminary design has been shaped mostly. By only changing the structural design to avoid excitation of the resonant frequency is difficult to achieve the effective function. To ensure the product stability, it is necessary to deal with the inducing vibration of the fluid flow.

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Thesis (M.S.)--University of Michigan, 1963.

Vertebrados exóticos são introduzidos intencionalmente como recurso, como uma alternativa para fins econômicos ou de lazer. Aqueles que se tornam capazes de expandir espontaneamente as novas populações em áreas naturais são conhecidas como invasores e frequentemente estão implicados em efeitos indesejados em populações, comunidades e ecossistemas autóctones. Uma destas espécies é o cervo axis Axis axis, introduzido mundialmente para a caça. Apesar da sua ampla distribuição e utilização, pouco se sabe sobre seus efeitos nas áreas invadidas e em quais regiões esta espécie pode se tornar invasora. Isto dificulta as tomadas de decisão, pois avaliar os efeitos da introdução e prever as áreas em risco de invasão são tarefas fundamentais para estratégias de prevenção, priorização e ações de controle. Assim, esse trabalho teve como objetivos revisar os efeitos do cervo axis em áreas invadidas, utilizando um protocolo de revisão sistemática, e modelar a possível distribuição mundial e regional desta espécie, utilizando variáveis bioclimáticas. Realizamos buscas por estudos sobre efeitos em áreas alóctones em três bancos de dados, utilizando três conjuntos de palavras chaves. Classificamos os estudos que atenderam aos critérios do protocolo segundo o nível de inferência sobre os efeitos em Efeito Demonstrado e Efeito Sugerido. Extraímos os tipos de efeitos relatados e a região de ocorrência. Para a modelagem de distribuição, utilizamos o algoritmo Maxent e variáveis preditoras bioclimáticas. Os pontos de ocorrência utilizados incluem sua distribuição original e três regiões onde a espécie é invasora e das quais foi possível obter ou estimar coordenadas. A revisão sistemática resultou em apenas quatro trabalhos classificados em Efeito Demonstrado, os quais apontam a competição com espécies nativas, alteração da composição florística e faunística e facilitação da entrada de outras espécies invasoras. Os efeitos sugeridos incluem seis trabalhos mostrando a ocorrência de parasitas, um caso de hibridização com outra espécie de cervídeo em cativeiro e um estudo mostrando a degradação das áreas de florestas causada pelo cervo axis em conjunto com outras espécies invasoras. O modelo de distribuição demonstra que amplas extensões da América do Sul, África Central e Sudeste Asiático são suscetíveis à invasão, portanto, nestas áreas deve-se evitar a introdução e controlar a expansão. O sul do Brasil, Uruguai, norte da Argentina e Paraguai são possíveis áreas de ocorrência segundo os modelos bioclimáticos. / Alien vertebrates are intentionally introduced for leisure and economic purposes. Those who become able to expand their populations in the new areas are known as invasive and are often involved in undesirable effects in indigenous populations, communities and ecosystems. The axis deer was introduced worldwide for hunting. Despite its wide distribution and use, little is known about its effects on the invaded areas and regions in which this species can become invasive. This complicates the decision-making because assessing the effects of the introduction and predict areas at risk of invasion are key tasks for prevention strategies, prioritization and control actions. Like this. So, this study aimed to summarize the effects of the axis deer in invaded areas using a systematic review protocol and to model the potential distribution of this species globally and in South America using bioclimatic variables. To summarized the effects we conducted searches for studies on non-native areas in three databases, using three sets of key-words and classified the studies that met the criteria of the protocol according to the level of inference about the effects they investigated. We extracted the types mentioned effects and occurrence region. To model the potential distribution based on bioclimatic variables we used the program Maxent. We used occurrences from the original distribution and three regions where the species is invasive about which geographical coordinates could be obtained or estimated. Four studies demonstrated effects of the axis deer due to competition with native species, changes in the floristic and faunistic composition and facilitation of other invasion processes. Six studies speculated the occurrence of disease transmition, hybridization with other species and difuse degradation of forest areas in combination with other invasive species. The distribution model demonstrated that large extensions of South America, Central Africa and Southeast Asia are susceptible to invasion. In the southern cone of South America Brazil, Uruguay, northern Argentina and Paraguay include extensive areas prone to invasion based on the bioclamatic models.

Vertebrados exóticos são introduzidos intencionalmente como recurso, como uma alternativa para fins econômicos ou de lazer. Aqueles que se tornam capazes de expandir espontaneamente as novas populações em áreas naturais são conhecidas como invasores e frequentemente estão implicados em efeitos indesejados em populações, comunidades e ecossistemas autóctones. Uma destas espécies é o cervo axis Axis axis, introduzido mundialmente para a caça. Apesar da sua ampla distribuição e utilização, pouco se sabe sobre seus efeitos nas áreas invadidas e em quais regiões esta espécie pode se tornar invasora. Isto dificulta as tomadas de decisão, pois avaliar os efeitos da introdução e prever as áreas em risco de invasão são tarefas fundamentais para estratégias de prevenção, priorização e ações de controle. Assim, esse trabalho teve como objetivos revisar os efeitos do cervo axis em áreas invadidas, utilizando um protocolo de revisão sistemática, e modelar a possível distribuição mundial e regional desta espécie, utilizando variáveis bioclimáticas. Realizamos buscas por estudos sobre efeitos em áreas alóctones em três bancos de dados, utilizando três conjuntos de palavras chaves. Classificamos os estudos que atenderam aos critérios do protocolo segundo o nível de inferência sobre os efeitos em Efeito Demonstrado e Efeito Sugerido. Extraímos os tipos de efeitos relatados e a região de ocorrência. Para a modelagem de distribuição, utilizamos o algoritmo Maxent e variáveis preditoras bioclimáticas. Os pontos de ocorrência utilizados incluem sua distribuição original e três regiões onde a espécie é invasora e das quais foi possível obter ou estimar coordenadas. A revisão sistemática resultou em apenas quatro trabalhos classificados em Efeito Demonstrado, os quais apontam a competição com espécies nativas, alteração da composição florística e faunística e facilitação da entrada de outras espécies invasoras. Os efeitos sugeridos incluem seis trabalhos mostrando a ocorrência de parasitas, um caso de hibridização com outra espécie de cervídeo em cativeiro e um estudo mostrando a degradação das áreas de florestas causada pelo cervo axis em conjunto com outras espécies invasoras. O modelo de distribuição demonstra que amplas extensões da América do Sul, África Central e Sudeste Asiático são suscetíveis à invasão, portanto, nestas áreas deve-se evitar a introdução e controlar a expansão. O sul do Brasil, Uruguai, norte da Argentina e Paraguai são possíveis áreas de ocorrência segundo os modelos bioclimáticos. / Alien vertebrates are intentionally introduced for leisure and economic purposes. Those who become able to expand their populations in the new areas are known as invasive and are often involved in undesirable effects in indigenous populations, communities and ecosystems. The axis deer was introduced worldwide for hunting. Despite its wide distribution and use, little is known about its effects on the invaded areas and regions in which this species can become invasive. This complicates the decision-making because assessing the effects of the introduction and predict areas at risk of invasion are key tasks for prevention strategies, prioritization and control actions. Like this. So, this study aimed to summarize the effects of the axis deer in invaded areas using a systematic review protocol and to model the potential distribution of this species globally and in South America using bioclimatic variables. To summarized the effects we conducted searches for studies on non-native areas in three databases, using three sets of key-words and classified the studies that met the criteria of the protocol according to the level of inference about the effects they investigated. We extracted the types mentioned effects and occurrence region. To model the potential distribution based on bioclimatic variables we used the program Maxent. We used occurrences from the original distribution and three regions where the species is invasive about which geographical coordinates could be obtained or estimated. Four studies demonstrated effects of the axis deer due to competition with native species, changes in the floristic and faunistic composition and facilitation of other invasion processes. Six studies speculated the occurrence of disease transmition, hybridization with other species and difuse degradation of forest areas in combination with other invasive species. The distribution model demonstrated that large extensions of South America, Central Africa and Southeast Asia are susceptible to invasion. In the southern cone of South America Brazil, Uruguay, northern Argentina and Paraguay include extensive areas prone to invasion based on the bioclamatic models.

Located in rural Mount Laurel, Virgina, on the tobacco farm my mother was raised, this house grew from the use of memories as a design tool: my childhood memories not to mimic, rebuild, or remake, but to create new space for new memories. To create a space where, one day, my son could retreat and remember his childhood. / Master of Architecture