CABO BLANCO: UN SUEÑO HECHO REALIDAD

Me llamo Tommy Åsberg. Soy sueco de nacionalidad. Trabajé 45 años como profesor en un colegio en Estocolmo, la capital de Suecia. Enseñaba Estudios Sociales, Inglés y al final de mi carrera también español básico. Ahora soy pensionado. Voy a contarles por qué he dedicado 22 años de mi vida como presidente de una asociación sueca sin fines de lucro con el nombre Los Amigos de Cabo Blanco

Threshold Receiver Model for Throughput of Wireless Devices with MIMO and Frequency Diversity Measured in Reverberation Chamber

We present a simple theoretical model for the throughput data rate of a wireless LTE device including the improvements of data rate due to diversity in frequency (OFDM) and spatial domains (MIMO) under frequency selective fading. The model is based on defining an ideal threshold receiver for the line-of-sight (LOS) case, corresponding to reception with advanced error-correcting codes. The theoretical throughput model is in agreement with measurements in a reverberation chamber of a commercial LTE device for the 1 x 2 SIMO case, both regarding diversity and MIMO array gains, and it can therefore be used to complement measured results in evaluation of performance of LTE devices

CABO BLANCO: UN SUEÑO HECHO REALIDAD

Me llamo Tommy Åsberg. Soy sueco de nacionalidad. Trabajé 45 años como profesor en un colegio en Estocolmo, la capital de Suecia. Enseñaba Estudios Sociales, Inglés y al final de mi carrera también español básico. Ahora soy pensionado. Voy a contarles por qué he dedicado 22 años de mi vida como presidente de una asociación sueca sin fines de lucro con el nombre Los Amigos de Cabo Blanco

Relationship commitment and value creation in sponsorship relationships

Purpose: The sponsorship industry has evolved considerably in recent years due to the strategic business opportunities that it provides. Despite increased interest in sponsorship, analysis of the relationship between relationship commitment and value creation and of relationship commitment as comprising multiple types or components in the context of sponsorship relationships is lacking. To address these gaps, this paper analyzes relationship commitment (in terms of affective commitment and value-based commitment) as a significant mediating variable, and value creation in the context of sponsorship relationships. Methodology/approach: A questionnaire was sent to Swedish Hockey League sponsors to collect data and to verify the study’s conceptual model and relationships. The response rate for the survey was 19.8%, that is, 122 completed questionnaires out of 616 sent. The respondents represented the most common industries in Sweden, but most of them belonged to the construction, repair, and electronics industries (18.0%), manufacturing and production industry (13.1%), and commerce industry (11.5%). Most sponsoring companies (30.3%) were categorized as medium-sized (50–249 employees). Most respondents (38.5%) had invested EUR 4300–15,000, whereas 11.5% had invested less than EUR 4300. Moreover, we found that most sponsors had been in their sponsorship relationships for more than 10 years (32.8%). Structural equation modeling (SEM) was used for the data analysis. Findings: This study demonstrates that relationship commitment is an important driver of value creation in sponsorship relationships. Furthermore, the various forms of affective commitment and value-based commitment should not be considered merely components or forms but distinct types. Certainly, there is interaction between the two types, but sequentially in such a way that affective commitment is a prerequisite for value-based commitment. This means that a sponsor must have an emotional relationship with the sponsee in order to understand, perceive, and calculate the sponsorship relationship’s future business value in terms of profits and other benefits. This study also finds that value-based commitment is the most significant type of commitment in sponsorship relationships. Research implications: The study demonstrates that shared values, trust, and affective commitment are fundamental conditions for value-based commitment. If the parties agree on how they should behave in the relationship, the rules and objectives that apply lead to the emergence of mutual trust, which in turn makes the parties want to continue the relationship for emotional reasons. But this is not enough for value creation; they must also see that there are future business benefits from the relationship. Therefore, the parties more or less explicitly make calculations. If the calculations indicate that the long-term benefits of the relationship outweigh the short-term sacrifices, they are prepared to invest in the relationship, and this may lead to value creation. In other words, there is both interplay and tension between shared values, trust, and affective commitment, on one hand, and value-based commitment, on the other. Another theoretical contribution is that previous research has considered the links between relationship commitment and value but has ignored the different types of commitment that play key roles in the value-creation process; this study has addressed that oversight. The study demonstrates that affective commitment and value-based commitment have different roles and meanings. Affective commitment indirectly affects value creation, while value-based commitment directly affects value creation. Affective commitment has the role of partial mediator, while value-based commitment has the role of full mediator. Furthermore, they differ in their basic characteristics: affective commitment is an emotional aspect, while value-based commitment is a calculative aspect. Originality/value/contribution: Previous studies have not analyzed the relationship between relationship commitment and value creation. However, this study demonstrates that relationship commitment is an important driver of value creation in sponsorship relationships. Furthermore, most previous research argues that relationship commitment consists of various components or forms that interact in parallel with each other. However, this study demonstrates that the various forms of affective commitment and value-based commitment should not be considered merely components or forms but distinct types. Certainly, there is interaction between the two types, but sequentially in such a way that affective commitment is a prerequisite for value-based commitment. Furthermore, previous studies have consistently noted that affective commitment is the most important component, form, or type of relationship commitment. However, this study finds that value-based commitment is the most significant type of commitment in sponsorship relationships

Reduced WNT5A signaling in melanoma cells favors an amoeboid mode of invasion

Tumor cells invade and spread via either a mesenchymal or an amoeboid mode of migration. Amoeboid tumor cells have a rounded morphology and pronounced RhoA activity. Here, we investigate how WNT5A signaling, a tumor promotor in melanoma, relates to Rho GTPase activity and amoeboid migration. We compared melanoma cells with low (HTB63 cells) and high (WM852 cells) WNT5A expression. HTB63 cells exhibited an amoeboid morphology and had higher RhoA activity but lower invasiveness than WM852 cells in a three-dimensional (3D) collagen matrix. We next explored the relationships between WNT5A, morphology, and invasive behavior. WNT5A knockdown impaired Rho GTPase Cdc42 activity, resulting in reduced invasion of amoeboid and mesenchymal melanoma cells. Interestingly, knockdown of WNT5A or inhibition of its secretion in WM852 cells expressing wild-type BRAF also led to increased RhoA activity via decreased RND3 expression, resulting in predominantly amoeboid morphology. In contrast, such treatments had the opposite effects on RND3 expression and RhoA activity in HTB63 cells expressing the active BRAFV600 mutation. However, treatment of HTB63 cells with a BRAF inhibitor made them respond to WNT5A knockdown in a similar manner as WM852 cells expressing wild-type BRAF. We next found that dual targeting of WNT5A and RhoA more effectively reduced melanoma cell invasion than targeting either protein individually. Taken together, our results suggest that low WNT5A signaling in melanoma cells promotes a rounded amoeboid type of invasion, which quite likely serves as a compensatory response to decreased WNT5A/Cdc42-driven invasion. This phenomenon partially explains the enduring melanoma cell invasion observed after impaired WNT5A signaling and has therapeutic implications. Our results suggest that dual targeting of WNT5A and RhoA signaling is a more effective strategy for controlling the invasion of BRAF wild-type and BRAFV600 mutated melanomas treated with a BRAF inhibitor than targeting either of the proteins individually

Proteomics‐Informed Prediction of Rosuvastatin Plasma Profiles in Patients with a Wide Range of Body Weight

Rosuvastatin is a frequently used probe to study transporter-mediated hepatic uptake. Pharmacokinetic models have therefore been developed to predict transporter impact on rosuvastatin disposition in vivo. However, the interindividual differences in transporter concentrations were not considered in these models, and the predicted transporter impact was compared with historical in vivo data. In this study, we investigated the influence of interindividual transporter concentrations on the hepatic uptake clearance of rosuvastatin in 54 patients covering a wide range of body weight. The 54 patients were given an oral dose of rosuvastatin the day before undergoing gastric bypass or cholecystectomy, and pharmacokinetic (PK) parameters were established from each patient’s individual time-concentration profiles. Liver biopsies were sampled from each patient and their individual hepatic transporter concentrations were quantified. We combined the transporter concentrations with in vitro uptake kinetics determined in HEK293-transfected cells, and developed a semimechanistic model with a bottom-up approach to predict the plasma concentration profiles of the single dose of rosuvastatin in each patient. The predicted PK parameters were evaluated against the measured in vivo plasma PKs from the same 54 patients. The developed model predicted the rosuvastatin PKs within two-fold error for rosuvastatin area under the plasma concentration versus time curve (AUC; 78% of the patients; average fold error (AFE): 0.96), peak plasma concentration (Cmax; 76%; AFE: 1.05), and terminal half-life (t1/2; 98%; AFE: 0.89), and captured differences in the rosuvastatin PKs in patients with the OATP1B1 521T<C polymorphism. This demonstrates that hepatic uptake clearance determined in transfected cell lines, together with proteomics scaling, provides a useful tool for prediction models, without the need for empirical scaling factors

Drug Disposition Protein Quantification in Matched Human Jejunum and Liver From Donors With Obesity

Mathematical models, such as physiologically-based pharmacokinetic models, are used to predict, for example, drug disposition and toxicity. However, populations differ in the abundance of proteins involved in these processes. To improve the building and refinement of such models, they must take into account these interindividual variabilities. In this study, we used global proteomics to characterize the protein composition of jejunum and liver from 37 donors with obesity enrolled in the COCKTAIL study. Liver protein levels from the 37 donors were further compared with those from donors without obesity. We quantified thousands of proteins and could present the expression of several drug-metabolizing enzymes, for the first time, in jejunum, many of which belong to the cytochrome P450 (CYP) (e.g., CYP2U1) and the amine oxidase (flavin-containing) (e.g., monoamine oxidase A (MAOA)) families. Although we show that many metabolizing enzymes had greater expression in liver, others had higher expression in jejunum (such as, MAOA and CES2), indicating the role of the small intestine in extrahepatic drug metabolism. We further show that proteins involved in drug disposition are not correlated in the two donor-matched tissues. These proteins also do not correlate with physiological factors such as body mass index, age, and inflammation status in either tissue. Furthermore, the majority of these proteins are not differently expressed in donors with or without obesity. Nonetheless, interindividual differences were considerable, with implications for personalized prediction models and systems pharmacology

Correlation of body weight and composition with hepatic activities of cytochrome P450 enzymes

Obesity is associated with comorbidities of which pharmacological treatment is needed. Physiological changes associated with obesity may influence the pharmacokinetics of drugs, but the effect of body weight on drug metabolism capacity remains uncertain. The aim of this study was to investigate ex vivo activities of hepatic drug metabolizing CYP enzymes in patients covering a wide range of body weight. Liver biopsies from 36 individuals with a body mass index (BMI) ranging from 18 to 63 kg/m2 were obtained. Individual hepatic microsomes were prepared and activities of CYP3A, CYP2B6, CYP2C8, CYP2D6, CYP2C9, CYP2C19 and CYP1A2 were determined. The unbound intrinsic clearance (CLint,u) values for CYP3A correlated negatively with body weight (r = −0.43, p < 0.01), waist circumference (r = −0.47, p < 0.01), hip circumference (r = −0.51, p < 0.01), fat percent (r = −0.41, p < 0.05), fat mass (r = −0.48, p < 0.01) and BMI (r = −0.46, p < 0.01). Linear regression analysis showed that CLint,u values for CYP3A decreased with 5% with each 10% increase in body weight (r2 = 0.12, β = −0.558, p < 0.05). There were no correlations between body weight measures and CLint,u values for the other CYP enzymes investigated. These results indicate reduced hepatic metabolizing capacity of CYP3A substrates in patients with increasing body weight