1,721,065 research outputs found
An extracellular domain of the insulin receptor ß-subunit with regulatory function on protein-tyrosine kinase
Anti-insulin receptor monoclonal antibody MA-10 inhibits insulin receptor autophosphorylation of purified rat liver insulin receptors without affecting insulin binding (Cordera, R., Andraghetti, G., Gherzi, R., Adezati, L., Montemurro, A., Lauro, R., Goldfine, I. D., and De Pirro, R. (1987) Endocrinology 121, 2007-2010). The effect of MA-10 on insulin receptor autophosphorylation and on two insulin actions (thymidine incorporation into DNA and receptor down-regulation) was investigated in rat hepatoma Fao cells. MA-10 inhibits insulin-stimulated receptor autophosphorylation, thymidine incorporation into DNA, and insulin-induced receptor down-regulation without affecting insulin receptor binding. We show that MA-10 binds to a site of rat insulin receptors different from the insulin binding site in intact Fao cells. Insulin does not inhibit MA-10 binding, and MA-10 does not inhibit insulin binding to rat Fao cells. Moreover, MA-10 binding to down-regulated cells is reduced to the same extent as insulin binding. In rat insulin receptors the MA-10 binding site has been tentatively localized in the extracellular part of the insulin receptor beta-subunit based on the following evidence: (i) MA-10 binds to insulin receptor in intact rat cells; (ii) MA-10 immunoprecipitates isolated insulin receptor beta-subunits labeled with both [35S]methionine and 32P; (iii) MA-10 reacts with rat insulin receptor beta-subunits by the method of immunoblotting, similar to an antipeptide antibody directed against the carboxyl terminus of the insulin receptor beta-subunit. Moreover, MA-10 inhibits autophosphorylation and protein-tyrosine kinase activity of reduced and purified insulin receptor beta-subunits. The finding that MA-10 inhibits insulin-stimulated receptor autophosphorylation and reduces insulin-stimulated thymidine incorporation into DNA and receptor down-regulation suggests that the extracellular part of the insulin receptor beta-subunit plays a role in the regulation of insulin receptor protein-tyrosine kinase activity
Role of proline 193 in the insulin receptor post-translational processing
Aims/hypothesis. A point mutation, P193L, in the insulin receptor alpha subunit, has been previously identified in a patient affected by an extreme form of insulin resistance due to reduced insulin binding. In our study we investigated the cellular mechanisms by which P193L substitution causes a reduction of insulin receptor numbers on the cell surface.Methods. Mutated insulin receptors have been generated and expressed in COS1 cells. Transcription as well as translation of P193L insulin receptor have been measured and compared with wild type insulin receptorResults. P193L insulin receptor is normally transcribed and progresses to the step of insulin proreceptor, which does not proceed to dimerization, resulting in the accumulation of the 210 kDa form. These findings suggest that the P193L insulin proreceptor is retained in the endoplasmic reticulum, where several molecular chaperones drive the folding of protein precursors. Therefore the interaction between mutated insulin receptor precursor and two endoplasmic reticulum resident chaperones (GRP78 and calnexin) were investigated. P193L insulin proreceptor co-immunoprecipitates with greater amounts of GRP78 and its interaction with calnexin is greatly delayed compared with wild type insulin receptor precursor, Co-transfection of wild type and mutated insulin receptors causes a considerable reduction of cell surface wild type insulin receptors,Conclusion/interpretation. P193 is critical for insulin propeceptor folding. The monomeric form of P193L insulin proreceptor is retained in the endoplasmic reticulum by a calnexin and GRP78 mediated mechanism that reduces mature insulin receptor expression on the cell surface
The economic burden of severe hypoglycemia: Two sides of the same coin. Comment on G. Veronese and Coll. Costs associated with emergency care and hospitalization for severe hypoglycemia
LUTI Model for the Metropolitan Area of Santander
This article presents a land use and transport interaction model (LUTI model) to simulate the overall equilibrium of an urban
system. The proposed system of integrated models combines random utility theory with hedonic regression techniques and a transport model
with equilibrium between supply and demand to estimate the location of population, economic activities, and average real estate prices in
different zones within an urban system. The LUTI model was applied to the metropolitan area of Santander (Spain) to check its base year
goodness of fit and therefore its ability to predict the impacts of introducing different transport policies. In the case of Santander, the property
price and population/economic activity location submodels showed sensitivity to the different accessibility and transport characteristics of
each zone, and the model as a whole provided a good degree of fit
Lanino: due volti per San Magno
Il presente contributo esamina due disegni di Bernardino Lanino – una testa maschile e una femminile della Biblioteca Reale di Torino – ponendoli in relazione al ciclo di affreschi nella basilica di San Magno a Legnano. Tale rapporto è discusso sulla base di un’inedita campagna fotografica e nell’ambito degli studi per un volume monografico dedicato alla basilica, a cura di Pietro C. Marani, di prossima pubblicazione
Modelling the spatial interactions between workplace and residential location
The use of Multinomial Logit (MNL) models specification for the simulation of residential
location have been often criticised due to the Independence of Irrelevant Alternatives
hypothesis (IIA) which does not allow for the existence of spatial correlation between residential
zones. Moreover, it is not clear when and to what extent the influence of the workplace
zone and accessibility to employment affect the residential location choices made by
households; in other word, whether the residing choice is conditional to the workplace, or
vice versa; or if such choices (residence and work place) are joint.
In this paper, Nested Logit (NL) and Cross-Nested Logit models of residential location
choice are specified and compared to MNL, to investigate the existence of spatial correlation
between different locations. Furthermore, different assumptions are tested, considering
the choice of residential zone and the joint choice of residential zone and work place
zone.
The models were estimated for the urban area of Santander (Spain). The results indicate
that the inclusion in the model specification, of the spatial correlation between zones fit
the data significantly better. Home-work journey times were a statistically significant factor
in household location choice, whereas accessibility to employment had the correct sign
but it was not statistically significant
Prediction of Diabetes Remission at Long Term Following Biliopancreatic Diversion
Importance In obese patients with type 2 diabetes (T2DM), the marked weight loss following bariatric surgery is accompanied in a consistent number of cases by T2DM resolution or control. The clinical need of preoperative parameters reliable in predicting a positive metabolic outcome at long term followingthe operation has then emerged. Observation A cohort of 135 consecutive T2DM patients with a wide range of body mass index (BMI) at more than 5 years following biliopancreatic diversion (BPD) was considered.The 5-year-T2DM resolution, defined as glycosylated hemoglobin (HbA1C) lower than 6.5% without antidiabetic therapy, was related to demographic, anthropometric, and biochemical findings prior to the operation. The long-term metabolic outcome was positively related to baseline BMI values and negatively with the preoperative use of insulin. Conclusion BMI and insulin therapy at the time of surgery are associated with the probability of T2DM long lasting remission and could be used as solid predictors before surgery. In the overweight and non morbidly obese diabetic patients, bariatric surgery is less efficient in determining long term T2DM resolution than in their morbid obese counterparts
Art and technology as tools for creating inclusive and sharing spaces
Digital Art was born at the turn of the 1960s and 1970s within science and technology laboratories at universities in the United States, and then came to Europe.
It is during these years of experimentation that the movement evolved into the multiple fields of practice and languages that still characterize it today.
Despite more than fifty years of activity and research, Digital Art only began to attract attention from a wider audience in the new millennium, moving out of a niche context (Galansino & Tabacchi, 2022).
The event that led to the change and the (re)discovery of Digital Art was in fact a Christie's auction, when Mike Winkelmann's work made of NFTs was sold for $69.3 million. It was only on March 11, 2021 (Galansino & Tabacchi, 2022). As is happens very often with contemporary art, if an artwork is sold by an auction house, such as Christie's and Sotheby's, which carry the status, quality, and potential buyers, then the artwork obtains added value and extensive media coverage (Thompson, 2017).
In recent years, the art world has shifted its focus towards Digital Art resulting in a significant increase in the sales of NFTs works, the creation of the metaverse, and other related developments.
Using digital technologies and interactive media, the phenomenon has challenged traditional concepts of artwork, artist, and audience (Paul, 2015) and, not least, the definition of appropriate spaces for the production and enjoyment of works.
In recent decades, Digital Art has undergone significant changes due to the use of constantly evolving tools and technologies.
It is defined as fluid art, constantly changing precisely because the technologies and society in which it operates are also constantly changing (Paul, 2015).
Digital artists have always searched and created art in "wrong places”, outside the art world, but rather on the web, in laboratories, in scientific and technological research facilities (Quaranta, 2010).
As the place of investigation changes, the artist's tools, stimuli, means of production inevitably change.
Additionally, the places of creation, preservation and display of digital works may change as well.
Thanks to the powerful connectivity of the Internet, artists are now able to create and foster genuine communities by way of networking. This often involves a system where the artwork can be exchanged freely, without the need for monetary transactions. These exchanges are typically facilitated through websites, email lists, and other alternative spaces.
This new paradigm marks a departure from traditional art sales practices and enables artists to connect with each other and a wider audience in a more open, collaborative, and inclusive way.
Digital Art was born with the idea of being characterized by free and accessible sharing to everyone. This characteristic represents the anti-institutional spirit of the internet.
However, it is worth noting that this spirit is ephemeral and reflects the aesthetics and technologies of the internet itself (Tribe & Jana, 2006).
It raises the question of what has caused the recent surge of interest in the digital world among the artistic and cultural communities. This growth has resulted in the establishment of more research and dissemination centers, festivals, and museums.
Over the past few years, there has been a significant shift in the art world, with many traditional institutions embracing the digital medium.
As a result, numerous art galleries have emerged, serving as a bridge between the public and digital art. These galleries aim to showcase works that explore the intersection of technology and art, often featuring interactive installations, digital sculptures, and immersive experiences.
The rise of these galleries has enabled artists working in digital media to reach a wider audience, while also providing visitors with an opportunity to engage with cutting-edge artworks that challenge their perceptions and expand their horizons.
This paper aims to provide a comprehensive overview of the contemporary artistic and digital landscape as it is about the physical spaces where works of art are created, produced, and shared.
Mapping research centers, production facilities, and other community hubs in Europe, the purpose is to explore how physical spaces can aid in the design and execution of projects, as well as foster community building while engaging with the local area and various user groups, such as Young Adults. The goal is to create inclusive spaces that promote cultural participation, becoming an intersection between creativity, art, innovation, and technology for the benefit of the local community.
As part of the research, a series of interviews were conducted with artists, curators, and professionals who specialize in the field of digital culture.
The purpose of these interviews is to gain a comprehensive understanding of the various approaches and needs that arise during the different stages of conception, prototyping, and creation of Digital Art.
The contribution proposes an analysis of the contemporary digital art scene, starting from historical research that can illustrate the key moments of Digital Art, from its inception to the very recent developments.
Helped by the mapping of major international research and dissemination centers, the aim is to better understand how artists and their works are involved within these institutions with the goal of establishing common guidelines that can help in the enjoyment of internal spaces dedicated to the creation of their art.
The proposal aims to investigate new types of spaces related to the creation of digital art with particular attention to the predisposition of these places to transform into inclusive and sharing spaces by going to create on the one hand a virtual and global network, but, using space, also a physical and local platform, stimulating experimentation, interaction and continuous updating.
A double level of community between real and virtual that can stimulate the public both interest in art and in science and technology.
To support this research, interviews will be conducted with artists, curators, and professionals working in the field of digital culture
Una evaluación de las relaciones entre las condiciones de transporte y los precios inmobiliarios mediante el uso de modelos hedónicos espaciales
En la presente ponencia se especifica un modelo hedónico de regresión lineal múltiple (MLR), un modelo hedónico autoregresivo espacial (SAR), un modelo hedónico autoregresivo espacial en el término de error (SEM) y un modelo hedónico espacial Durbin (SDM) para estimar los precios inmobiliarios de una serie de viviendas. Los cuatro tipos de modelos han sido aplicados al área metropolitana de Santander (Cantabria, España) con el objetivo de obtener una estimación de los impactos provocados en el precio de los inmuebles por cambios en las condiciones de transporte. Se comparará además la bondad de ajuste de los distintos modelos y se contrastarán una serie de hipótesis metodológicas sobre el rendimiento de las especificaciones que consideran la existencia de relaciones espaciales entre observaciones.
En el caso de Santander, el uso de modelos que consideran la dependencia espacial entre observaciones permitió ofrecer un mayor grado de ajuste en un escenario donde se detectó una fuerte correlación espacial en los residuos de los modelos MLR derivados, seguramente, de problemas de especificación. El modelo SEM combinado con una matriz de vecindad con contigüidad tipo reina ofreció un buen ajuste a los datos a la vez que presentó parámetros significativos y signos teóricamente coherentes. Este modelo permitió estimar incrementos medios de más del 1% por cada línea adicional de bus presente en las cercanías de los inmuebles, así como reducciones del 1% en el precio de éstos por cada minuto adicional de tiempo de viaje al centro urbano. La cercanía a estaciones de tren supuso sin embargo una reducción en el precio de los inmuebles lo que seguramente se debió a las externalidades negativas derivadas de este tipo de equipamientos
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