SToRM: A Model for Unsteady Surface Hydraulics over Complex Terrain

Experimental and Computational Hydraulic

Fish and mammalian glut4 traffic characteristics: an evolutionary perspective on the importance of glut4 protein motifs for trafficking

[eng] Glucose transporters (GLUTs) are extremely important for glucose metabolism. Glucose transporters uptake glucose from blood stream into the cells where it can be metabolized. Among the glucose transporters family, GLUT4, which is solely expressed in muscle and adipose tissues, displays a unique feature as it can change its cellular distribution within minutes in response to insulin to regulate glucose uptake. Therefore, the study of GLUT4 cellular trafficking is fundamental to understand its functioning and to deepen our knowledge on glucose homeostasis. In this work, we utilized a GLUT4 fish variant, brown trout GLUT4, to study GLUT4 trafficking and the role of GLUT4 protein motifs in this process, in 3T3-L1 adipocytes. We observed that, in comparison to mammalian GLUT4 (RatGLUT4), brown trout GLUT4 (BtGLUT4) had a much weaker translocation to the plasma membrane in response to insulin which was in part due to a slower cellular trafficking (exocytosis and endocytosis) and to a poor targeting to the GLUT4 storage vesicles responsible for “holding” GLUT4 inside the cell in the absence of insulin; these vesicles represent the main pool of insulin-responsive GLUT4. In this thesis we also studied the most common GLUT4 endocytic routes. We analyzed the contribution of the clathrin-mediated and the cholesterol-dependent endocytic pathways for RatGLUT4 and BtGLUT4 internalization. We observed that whilst RatGLUT4 internalizes through both the clathrin-mediated and the cholesterol-dependent pathways, BtGLUT4 only utilizes the former. It has been suggested that in adipocytes, the main cholesterol-dependent internalization pathway is the caveolar route. The internalization through this pathway is mediated by plasma membrane structures called caveolae. The formation of these structures is dependent on the caveolin-1 protein. To analyze the role of caveolae in GLUT4 internalization we blocked its formation by knocking down caveolin-1 and observed an increase of RatGLUT4 and BtGLUT4 internalization; however, both GLUT4 isoforms showed less internalization through the clathrin-mediated and cholesterol-dependent pathways in the absence of cavolin-1. Therefore, we suggest that in 3T3-L1 adipocytes caveolin-1 knockdown induces internalization of GLUT4 through alternative pathways. GLUT4 trafficking is regulated by cellular machinery that interacts with GLUT4 protein motifs. To analyze the role of the mammalian N-terminal FQQI8 and C-terminal TELEY502 motifs in GLUT4 trafficking we mutated the corresponding motifs in BtGLUT4 (FQHL8 and TELDY495, respectively) and observed that mutations in the C-terminal had little effect on BtGLUT4 trafficking whereas mutations on the N-terminal (especially FQQL8 mutant) improved BtGLUT4 intracellular retention in the absence of insulin. Furthermore, we verified that FQQL8 mutation increased BtGLUT4 retention in a syntaxin-6-rich compartment, possibly the trans-Golgi network. In addition to studying BtGLUT4 mutants we also analyzed the trafficking of a chimera consisting of a RatGLUT4 backbone with the large cytoplasmic loop of BtGLUT4 (L-GLUT4). We observed that L-GLUT4 possessed higher plasma membrane levels in the absence of insulin and as a result a weaker translocation. Moreover, we observed that this was caused, at least in part, by a reduction in the endocytosis of L-GLUT4 in the absence of insulin. We also analyzed the contribution of the clathrin-mediated and cholesterol-dependent pathways for L-GLUT4 internalization and observed that the loop substitution (L-GLUT4) reduced RatGLUT4 internalization through the cholesterol-dependent route. Moreover, in the absence of insulin and in caveolin-1, L-GLUT4 internalization did not increase as much as that of RatGLUT4. The internalization of L-GLUT4 in the absence of caveolin-1 and insulin occurred through a clathrin-mediated pathway, similarly to BtGLUT4, but it also internalized through a cholesterol-dependent pathway, unlike RatGLUT4 and BtGLUT4. In summary, in this thesis we have contributed to increase the knowledge on GLUT4 trafficking and on the roles of the FQQI8 motif and large cytoplasmic loop in this process, in 3T3-L1 adipocytes.[spa] El transportador de glucosa GLUT4 tiene la capacidad de, en respuesta a insulina, cambiar su localización celular y de esta forma regular el transporte de glucosa. En este trabajo, hemos utilizado una variante de GLUT4 de trucha (BtGLUT4) para estudiar el trafico de GLUT4, así como sus dominios proteicos involucrados en este proceso, en adipocitos 3T3-L1. Hemos observado que en comparación con el GLUT4 de mamíferos (RatGLUT4), el BtGLUT4 tenia una menor capacidad de translocación a la membrana plasmática en respuesta a insulina y que esto se debía a una trafico celular mas lento (exocitosis y endocitosis) y a una peor retención en las vesículas responsables por retener el transportador dentro de la célula en ausencia de insulina. En este trabajo hemos observado que RatGLUT4 ha internalizado por la vía de endocitosis mediada por clatrina y por la vía dependiente de colesterol, mientras que BtGLUT4 solo ha utilizado la primera. Además, hemos inhibido la internalización caveolar, mediante bajada de la expresión de caveolina-1, y hemos observado un aumento de la internalización de RatGLUT4 y BtGLUT4. Con el objetivo de estudiar el papel del dominio FQQI8 (extremo -N) de mamífero en el trafico de GLUT4, hemos mutado la secuencia correspondiente en BtGLUT4 (FQHL8) y hemos observado que mutaciones en este dominio han mejorado la retención intracelular de BtGLUT4 en ausencia de insulina. También hemos estudiado el trafico de una quimera que consiste en la secuencia de RatGLUT4 con el lazo citoplasmático largo de BtGLUT4 (L-GLUT4). Hemos observado que la sustitución del lazo ha aumentado los niveles de RatGLUT4 en superficie en ausencia de insulina y que esto era debido, por lo menos en parte, a una menor endocitosis en ausencia de la hormona. También hemos observado que la sustitución del lazo de RatGLUT4 ha reducido su internalización a través de la vía dependiente de colesterol en ausencia de insulina. Además, en ausencia de caveolina-1 y insulina, la internalización de L-GLUT4 ha aumentado menos que la de RatGLUT4 y ha ocurrido a través de las vías mediada por clatrina y dependiente de colesterol

The role of pH on the biological struvite production in digested sludge dewatering liquors

Struvite production mediated by bacteria has opened up a new route for phosphorus recovery from wastewater streams but its application to digested sludge dewatering liquors is not yet well understood. This study investigates the growth and biological struvite production of selected bacteria in wastewater liquors with pHs between 5.7 to 9.1. The bacterial growth was assessed through flow cytometry. Bacillus pumilus, Halobacterium salinarum and Brevibacterium antiquum remained viable at pHs between 5.7 to 9.1 but B. antiquum was able to grow at pHs between 7.3 to 7.8. Further analysis allowed the identification of crystals as struvite in tests between pH 7.3 to 8.3. All strains were capable of producing struvite at a range of pHs, but the highest production of 135–198 mg/L was observed for pHs between 7.3 to 8.3. At pHs > 8.3, precipitation of struvite and calcium compounds was observed in inoculated and non-inoculated tests. This study demonstrates that biological struvite production can occur at a wide range of pHs, hence significantly different from chemical struvite precipitation that occurs at pH > 8.3, making it a potentially viable process for phosphorus recovery as struvite from wastewater streams and sludge liquors without strict pH control

Understanding the growth of the bio-struvite production Brevibacterium antiquum in sludge liquors

Biological struvite (bio-struvite) production through biomineralization has been suggested as an alternative to chemically derived struvite production to recover phosphorus from wastewater streams. In this study, statistical experimental design techniques were used to find the optimal growth rate (μ) of Brevibacterium antiquum in sludge liquors. Acetate, oleic acid, NaCl, NH4-N, and Ca2+ were shown to affect the growth rate of B. antiquum. The growth rate reached 3.44 1/d when the bacteria were supplemented with 3.0% w/v NaCl and 1124 mg chemical oxygen demand/L as acetate. However, NaCl was found to hinder the biomineralization of bio-struvite. A two-stage experiment demonstrated that bio-struvite was produced in the presence of acetate. Bio-struvite production was confirmed with X-ray spectroscopy and crystal morphology (prismatic, tabular, and twinned crystal habit) through electron microscope analysis. The bio-struvite production was estimated by measuring phosphate content of the recovered precipitates, reaching 9.6 mg P/L as bio-struvite. Overall, these results demonstrated the optimal conditions required to achieve high growth rates as well as bio-struvite production with B. antiquum. The results obtained in this study could be used to develop a process to grow B. antiquum in wastewater streams in mixed cultures and recover phosphorus-rich products such as struvite

A Engenharia cartográfica na UFRGS

A Comunidade Cartográfica está festejando os dez anos do ingresso da primeira turma no Curso de Graduação da Engenharia Cartográfica na Universidade Federal do Rio Grande do Sul. O fortalecimento do Curso de Graduação em Engenharia Cartográfica passa por uma perfeita integração entre o Profissional, Sociedade e Universidade

Historical Perspective and Innovations in Penile Urethroplasty

Penile urethral strictures are common and impact on quality of life and health-care costs. Management of penile urethral strictures is complex and depends on the physical characteristics of the stricture. Contemporary studies show no difference between urethral dilation and internal urethrotomy in terms of long-term outcomes. Overall, long-term success rates range from 20 to 30%. However, their recurrence rate is greater for men with longer strictures, penile urethral strictures, multiple strictures, presence of infection, or history of prior procedures, which make them less cost-effective. Surgical urethroplasty is associated with higher long-term success rates, averaging from 85 to 90%, mostly in virgin or noncomplex cases. Historically, modern urethral reconstruction has evolved from 1950s with the revolutionary introduction of Johanson’s technique for staged urethral reconstruction. Since then, many techniques have been developed and employed for urethroplasty, depending on the location, length, and character of the stricture. Successful management of urethral strictures requires detailed knowledge of anatomy, pathophysiology, proper patient selection, and reconstructive techniques

Causal Entropy and Information Gain for Measuring Causal Control

Artificial intelligence models and methods commonly lack causal interpretability. Despite the advancements in interpretable machine learning (IML) methods, they frequently assign importance to features which lack causal influence on the outcome variable. Selecting causally relevant features among those identified as relevant by these methods, or even before model training, would offer a solution. Feature selection methods utilizing information theoretical quantities have been successful in identifying statistically relevant features. However, the information theoretical quantities they are based on do not incorporate causality, rendering them unsuitable for such scenarios. To address this challenge, this article proposes information theoretical quantities that incorporate the causal structure of the system, which can be used to evaluate causal importance of features for some given outcome variable. Specifically, we introduce causal versions of entropy and mutual information, termed causal entropy and causal information gain, which are designed to assess how much control a feature provides over the outcome variable. These newly defined quantities capture changes in the entropy of a variable resulting from interventions on other variables. Fundamental results connecting these quantities to the existence of causal effects are derived. The use of causal information gain in feature selection is demonstrated, highlighting its superiority over standard mutual information in revealing which features provide control over a chosen outcome variable. Our investigation paves the way for the development of methods with improved interpretability in domains involving causation.Comment: 16 pages. Accepted at the third XI-ML workshop of ECAI 2023. To appear in the Springer CCIS book serie

ADOECIMENTO NO TRABALHO: UM ESTUDO DE CASO

O exercício de uma atividade profissional proporcionaao ser humano fazer parte da vida em sociedade, como membro de uma cultura.Dessa perspectiva, o trabalho confere a possibilidade de construção deidentidade profissional e pessoal. Entretanto, há algumas situações em que otrabalhador adoece. Apresentar e discutir um relato de caso clínico deafastamento do trabalho por adoecimento a partir do referencial teórico daPsicossociologia e a Psicodinâmica do Trabalho constituiu-se como objetivocentral deste estudo

Structural and Functional Evolution of Glucose Transporter 4 (GLUT4): A Look at GLUT4 in Fish

The insulin-responsive glucose transporter GLUT4 was first described in 1988 as a result of studies on the regulation of glucose metabolism by insulin [1]. Soon after the discovery of GLUT4, several groups cloned GLUT4 in the human [2], rat [3,4] and mouse [5]. Since its discovery, GLUT4 has received, together with GLUT1, more experimental attention than any other single membrane transport protein. Structurally, GLUT4 follows the predicted model for class I glucose transporters. GLUT4 has a high affinity for glucose, with a Km of approximately 5 mM [6], and also transports mannose, galactose, dehydroascorbic acid and glucosamine [7-10]. In mammals, GLUT4 is mainly expressed in cardiac and skeletal muscle, brown and white adipose tissue, and brain [6,11,12]. GLUT4 plays a pivotal role in whole body glucose homeostasis, mediating the uptake of glucose regulated by insulin [13,14]. GLUT4 is responsible for the reduction in the postprandial rise in plasma glucose levels [6]. Insulin acts by stimulating the translocation of specific GLUT4-containing vesicles from intracellular stores to the plasma membrane (PM) resulting in an immediate increase in glucose transport [6,15]. The disruption of GLUT4 expression has been extensively associated with pathologies of impaired glucose uptake and insulin resistance such as type 2 diabetes and obesity [13,16-18]..