SMRT-mediated co-shuttling enables export of class IIa HDACs independent of their CaM kinase phosphorylation sites

The Class IIa histone deacetylases (HDAC)4 and HDAC5 play a role in neuronal survival and behavioral adaptation in the CNS. Phosphorylation at 2/3 N-terminal sites promote their nuclear export. We investigated whether non-canonical signaling routes to Class IIa HDAC export exist because of their association with the co-repressor Silencing Mediator Of Retinoic And Thyroid Hormone Receptors (SMRT). We found that, while HDAC5 and HDAC4 mutants lacking their N-terminal phosphorylation sites (HDAC4(MUT), HDAC5(MUT)) are constitutively nuclear, co-expression with SMRT renders them exportable by signals that trigger SMRT export, such as synaptic activity, HDAC inhibition, and Brain Derived Neurotrophic Factor (BDNF) signaling. We found that SMRT's repression domain 3 (RD3) is critical for co-shuttling of HDAC5(MUT), consistent with the role for this domain in Class IIa HDAC association. In the context of BDNF signaling, we found that HDAC5(WT), which was more cytoplasmic than HDAC5(MUT), accumulated in the nucleus after BDNF treatment. However, co-expression of SMRT blocked BDNF-induced HDAC5(WT) import in a RD3-dependent manner. In effect, SMRT-mediated HDAC5(WT) export was opposing the BDNF-induced HDAC5 nuclear accumulation observed in SMRT's absence. Thus, SMRT's presence may render Class IIa HDACs exportable by a wider range of signals than those which simply

Offering planning process development: Bridging the Offering Gaps and Consolidating Top Priority Needs in Product Offering

The aim of this Thesis is to study how to manage the front-end of the offering planning process. This includes actual process development and methods to gather and analyze information to achieve the best outcome in customer oriented product offering. Study is carried out in two parts: theoretical part and company related part. Theoretical framework is created introducing different types of approaches to manage product planning processes. Products are seen as platforms and they are broken down to subsystems to show different parts of the development. With the help of the matrix-based approaches product platform related information is gathered and analyzed. In this kind of analysis business/market drivers and cus-tomer/competitor information are connected with product subsystems. This gives possibilities to study product gaps/needs and possible future ideas/scenarios in different customer segments. Company related part consists of offering planning process development in real company environment. Process formation includes documents and tools that guide planning from the information gathering to the prioritization and decision making.

The Musical Offering : Ricercare a 3

Soitinnus: Piano.

The Musical Offering : Sonata a 3

Soitinnus: Piano.

Customer reference marketing in a business to business context

This study focuses on the phenomenon of customer reference marketing in a business tobusiness (B to B) context. Although customer references are generally considered an important marketing and sales tool, the academic literature has paid surprisingly little attention to the phenomenon. The study suggests that customer references could be viewed as important marketing assets for industrial suppliers, and the ability to build, manage and leverage customer reference portfolios systematically constitutes a relevant marketing capability. The role of customer references is examined in the context of the industrial suppliers' shift towards a solution and project orientation and in the light of the on going changes in the project business. Suppliers in several industry sectors are undergoing a change from traditional equipment manufacturing towards project and solution oriented business. It is argued in this thesis that the high complexity, the project oriented nature and the intangible service elements that characterise many contemporary B to B offerings further increase the role of customer references. The study proposes three mechanisms of customer reference marketing: status transfer, validation through testimonials and the demonstration of experience and prior performance. The study was conducted in the context of Finnish B to B process technology and information technology companies. The empirical data comprises 38 interviews with managers of four case companies, 165 customer reference descriptions gathered from six case companies' Web sites, as well as company internal material. The findings from the case studies show that customer references have various external and internal functions that contribute to the growth and performance of B to B firms. Externally, customer references bring status transfer effects from reputable customers, concretise and demonstrate complex solutions, and provide indirect evidence of experience, previous performance, technological functionality and delivered customer value. They can also be leveraged internally to facilitate organisational learning and training, advance offering development, and motivate personnel. Major reference projects create new business opportunities and can be used as a vehicle for strategic change. The findings of the study shed light on the on going changing orientations in the project business environment, increase understanding of the variety of ways in which customer references can be deployed as marketing assets, and provide a framework of the relevant tasks and activities related to building, managing and leveraging a firm's customer reference portfolio. The findings contribute to the industrial marketing research, to the literature on marketing assets and capabilities and to the literature on projects and solutions. The proposed functions and mechanisms of customer reference marketing bring a more thorough and structured understanding about the essence and characteristics of the phenomenon and give a wide ranging view of the role of customer references as marketing assets for B to B firms. The study suggests several managerial implications for industrial suppliers in order to systematise customer reference marketing efforts.

Numerical Investigation of Flow Past a Circular Cylinder and in a Staggered Tube Bundle Using Various Turbulence Models

Transitional flow past a three-dimensional circular cylinder is a widely studied phenomenon since this problem is of interest with respect to many technical applications. In the present work, the numerical simulation of flow past a circular cylinder, performed by using a commercial CFD code (ANSYS Fluent 12.1) with large eddy simulation (LES) and RANS (κ - ε and Shear-Stress Transport (SST) κ - ω! model) approaches. The turbulent flow for ReD = 1000 & 3900 is simulated to investigate the force coefficient, Strouhal number, flow separation angle, pressure distribution on cylinder and the complex three dimensional vortex shedding of the cylinder wake region. The numerical results extracted from these simulations have good agreement with the experimental data (Zdravkovich, 1997). Moreover, grid refinement and time-step influence have been examined. Numerical calculations of turbulent cross-flow in a staggered tube bundle continues to attract interest due to its importance in the engineering application as well as the fact that this complex flow represents a challenging problem for CFD. In the present work a time dependent simulation using κ – ε, κ - ω! and SST models are performed in two dimensional for a subcritical flow through a staggered tube bundle. The predicted turbulence statistics (mean and r.m.s velocities) have good agreement with the experimental data (S. Balabani, 1996). Turbulent quantities such as turbulent kinetic energy and dissipation rate are predicted using RANS models and compared with each other. The sensitivity of grid and time-step size have been analyzed. Model constants sensitivity study have been carried out by adopting κ – ε model. It has been observed that model constants are very sensitive to turbulence statistics and turbulent quantities.

Developing the service offering of an industrial company

The purpose of this thesis was to determine, what kind of service offering the case company should provide to its customers in the Australian market. For this, a model for analysing the competitive environment was developed. In the model, three players were considered: customers, competitors and the case company. Benchmarking was used in identifying competitors’ offerings currently available in the market. Experts inside the case company were consulted for determining the customer need. The competitors’ offerings were analysed on the basis of Pekkarinen et al.’s (2009) framework, dividing the offerings to services supporting the supplier’s product (SSP), supporting the client (SSC), supporting the client’s network (SSN), supporting mutual actions (SSM) and benefit and risk sharing elements. After this, they were compared to the competitive environment in order to identify areas where the case company can differentiate itself from its competitors in the Australian market. On the basis of the company’s key success factors, and the Finnish service concept currently in use, some additional offerings were suggested for the case company in order to further outperform its competitors in the market. Finally, on the basis of the suggested offerings and competitors’ offerings, a service concept was suggested for the case company to introduce in the Australian market.

Ferramenta computacional para dimensionamento de silo unicelular de concreto armado – parte I: silo de seção circular

Silos são construções que, em função de sua finalidade de utilização, estão sujeitos a carregamentos peculiares, tais como pressões horizontais e verticais - estáticas ou dinâmicas, dependendo da fase de operação - atrito nas paredes e cargas térmicas, todos causados pela presença do produto armazenado. Com o objetivo de sistematizar os procedimentos necessários para o dimensionamento de silos unicelulares de concreto armado, um programa computacional denominado SILOS foi desenvolvido, sendo composto por dois módulos: Módulo 1, para silos cilíndricos de seção circular e Módulo 2, para silos prismáticos de seção retangular. Neste artigo (Parte I), são apresentados os procedimentos que compõem o Módulo 1. O Módulo 2 será apresentado em artigo subsequente (Parte II). O programa foi desenvolvido na linguagem DELPHI e pode ser utilizado por profissionais e estudantes da área de Construções Rurais, independentemente da familiaridade do usuário com a linguagem computacional empregada.

Acalasia do esôfago: miotomia com transiluminação

Laparoscopic techniques have provided a new dimension to correct functional disorders of the esophagus, which has stimulated some investigators to recently report the use of laparoscopic cardiomyotomy in the treatment of esophageal achalasia. Now, a new instrument has been added to the current laparoscopic technique to offer a safer and easier method to proceed complete myotomy. After the dissection of the esophagogastric junction, a special catheter is introduced reaching the stomach. lt has an illuminated 10 cm extremity connected to a light source. lts withdrawal allows to visualize every muscle circular fiber by transillumination withan improved view provide by the laparoscopic optic system lens. This condition modifies the operative surgeon s attitude offering a better controlled situation over the procedure. The use of transillumination o fthe esophagogastric junction provides a good identification of the mucosa e submucosa avoiding the risk of esophageal perforation. It also helps to perform a complete myotomy preventing the ocurrence of persistent disphagia in the postoperative period. Cardiomyotomy with parcial fundoplication is possible by videolaparoscopic approach, now made easier with transillumination. This technique is safe and the functional results are similar to those observed in the literature for conventional open procedures, with the obvious advantages of the minimally invasive approach.

Alterações morfométricas da musculatura dos músculos longitudinal e circular de ratos submetidos à criação de piloros no intestino delgado

OBJETIVO: Realizar um estudo morfométrico comparativo da musculatura longitudinal e circular do intestino delgado de ratos submetidos à construção cirúrgica de um e de dois piloros no intestino delgado utilizando-se da técnica de criação de piloros proposta por Rena et al. MÉTODO: Foram utilizados 52 ratos Wistar machos divididos em três grupos. O Grupo A, destacado como controle, composto de 10 animas, cada um forneceu 20mm de segmento de intestino para o estudo. Os animais do Grupo B, composto de 32 animais, foram submetidos à construção de dois piloros, um a 100mm e outro a 150mm da válvula ileocecal e os animais do grupo C, composto de 10 animais, foram submetidos à construção de um piloro a 100mm da mesma. A eutanásia ocorreu no décimo dia. A morfometria das camadas musculares longitudinal e circular acima e abaixo dos piloros foi estudada com utilização do microscópico modelo "Axiostar plus" conectado à câmera "Axioncam Version 5.05.10" com objetiva X5 / 0,12 no o programa "AxioVision 3.1.2.1". RESULTADOS: As alças apresentaram aumento da espessura da camada muscular acima e abaixo do ponto da operação. O estudo morfométrico comparativo das camadas musculares longitudinal e circular mostrou aumento significativo em comparação ao controle, não demonstrando significância entre os grupos B e C. CONCLUSÃO: Os resultados deste estudo revelaram importante aumento de espessura das camadas musculares, porém, menos acentuados que aqueles descritos na literatura quando foram realizados em animais submetidos à estenose fixa. Esses dados indicam que a construção operatória de piloros pela técnica utilizada promove alterações musculares de menor monta, possivelmente, pela função valvular do piloro.

The potential of social networking sites in inpatriate adjustment

People make up one of the most important resources for a corporation and therefore it has to continuously seek an ever more diverse and international workforce. Inpatriation is another way of utilizing foreign expertise in a corporation. An inpatriate refers to a person that is on an international assignment at the headquarters of a corporation, where they have been sent either from a subsidiary abroad or from a third country outside the corporation. Strengthening the social network of the inpatriate and their family contributes to the adjustment process and furthermore the success of the work assignment. As social networking sites are currently the fastest developing personal networking tools in the world, it is interesting to see how they can help in inpatriate adjustment. The objective of this thesis is to explore the potential of social networking sites (SNS) in inpatriate adjustment. The main objective can be divided into three sub objectives: 1. What is SNS used for during the inpatriate assignment? 2. What are the inpatriates’ motivations to use SNS? 3. Could the three facets of adjustment (work, interaction and general) be gained through SNS? This qualitative study utilizes the theme interview data collection method and the thematic analysis approach for analysing the interview data. From the interviews with five Indian inpatriates in Finland the most mentioned uses of SNS were related to participating (sharing opinions, recommendations and discussing things and connecting to friends, family and colleagues) and consuming (collecting information for work and free time), the least mentioned use of SNS was producing (posting videos, photos and updates). An interesting finding was that the five interviewees did not use SNS for purely entertainment motives at all during their assignment. This thesis found that all three facets of adjustment could potentially be gained through SNS.