Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of the published in vitro and in vivo work supporting the development as an anti-cancer agent, from in vitro experiments to animal model studies ending with a summary of the clinical trial results and trials underway is presented. In addition some potential non-oncology applications are explored and the potential mode of action of Seliciclib in these areas is described. Finally the authors argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division

Recent data about insulin signaling system and insulin resistance states

Insulin is the key hormone regulating glucose homeostasis and has many cellular effects on metabolism, growth, and differentiation. Its action is mediated through a specific cell surface receptor. The first step following insulin binding consists of receptor autophosphorylation and stimulation of its tyrosine kinase activity. Among the multiple substrates the insulin receptor substrate-1 is the major cytoplasmic substrate. It binds several Src homology 2 proteins through its multiple tyrosine phosphorylation sites: phosphatidylinositol 3-kinase, the Ras guanine nucleotide-releasing complex growth factor receptor-bound protein-2/son of sevenless protein, the tyrosine phosphatase Syp, and the adapter protein Nek. Insulin receptor substrate-1 is essential for many, but not all of the insulin biological responses. Recently, a primary alternative substrate, insulin receptor substrate-2, was purified and cloned. Numerous biochemical abnormalities of the insulin signaling system lead to insulin resistance. The recent data about the molecular mechanisms of insulin action may provide new insights into the pathophysiology and therapy of diabetes mellitus and other insulin resistance states.Biomedical Reviews 1996; 5: 47-55

Signal transduction in keratinocyte proliferation and differentiation

Keratinocytes, a key cellular component for both homeostasis and pathology of the skin, secrete a number of growth factors and cytokines, and their proliferation and differentiation are stimulated by a variety of biological factors. The major mechanism by which keratinocytes respond to extracellular signals is change in protein phosphorylation. In this review, we focus on factors known to influence keratinocyte proliferation and differentiation, such as epidermal growth factor family, nerve growth factor, transforming growth factor-β, insulin-like growth factor-1, keratinocyte growth factor, hepatocyte growth factor, cytokines. A hypothesis for a dual role of epidermal growth factor in keratinocyte proliferation and differentiation is proposed.Biomedical Reviews 1997; 8: 73-85

Advocating the need of a systems biology approach for personalised prognosis and treatment of B-CLL patients

The clinical course of B-CLL is heterogeneous. This heterogeneity leads to a clinical dilemma: can we identify those patients who will benefit from early treatment and predict the survival? In recent years, mathematical modelling has contributed significantly in understanding the complexity of diseases. In order to build a mathematical model for determining prognosis of B-CLL one has to identify, characterise and quantify key molecules involved in the disease. Here we discuss the need and role of mathematical modelling in predicting B-CLL disease pathogenesis and suggest a new systems biology approach for a personalised therapy of B-CLL patients

Branding Tourist Destinations on the Example of Central Istria

Destinacija je nerijetko isključivi razlog putovanja. Nju čine određeni elementi među kojima su najizraženiji oni poput atrakcija destinacije, usluga, imiđa, cijene, pristupačnosti i sl. Turizam je u Hrvatskoj, zbog njezinih prirodnih bogatstava, vrlo perspektivna grana djelatnosti. Ipak, turistička ponuda ne sastoji se samo od prirodnih ljepota, gastronomske ponude destinacije i smještajnih kapaciteta. Sve navedeno jesu elementi ponude, međutim, za stvaranje profita ključni su gosti. Da bi se gosta privuklo da posjeti određenu destinaciju, mora mu se pružiti adekvatna prezentacija osnovnih informacija o toj destinacije i dati mu razlog zbog kojeg bi trebao odabrati upravo određenu destinaciju. U novije doba sve je veća raznolikost u turističkoj potražnji, odnosno povećava se broj potreba gostiju koje treba zadovoljiti. Brendiranjem destinacije ista postaje prepoznatljiva i promovirana kroz različite kanale turističkog tržišta. Upravo je taj segment aktivnosti potreban i središnjoj Istri kako bi se razvila u što poželjniju turističku destinaciju. To je razlog provođenja ovog istraživanja o brendiranju turističke destinacije središnje Istre čiji je cilj saznati realno stanje turizma u središnjoj Istri, ali i uvidjeti pozitivne aspekte koji se mogu postignuti kvalitetnim brendiranjem. Istraživanje je provedeno među renomiranim i najkvalitetnijim turističkim djelatnicima središnje Istre, podijeljenim u pet različitih sektora.Destination is often the main reason for travelling. It unifies certain elements among which the most prominent ones are attraction, service, image, price, accessibility, etc. Tourism in Croatia, due to its natural resources, is a very promising branch of activity. However, the tourist offer does not only consist of natural beauty, the destination, gastronomic offer and accommodation capacities. All of this makes part of the offer, however the key for making profit are guests. To attract a guest to visit a particular destination, an adequate presentation oft he destination basic information should be provided and, furthermore give reason to choose a particular destination. Nowadays there is a growing diversity in tourist demand, respectively the number of guests needs that need to be satisfy is increasing. By branding the destination, it becomes recognizable and promoted through various tourist market channels. This is the activity segment needed in Central Istria to develop it into a more desirable tourist destination. This is the main reason for carrying out this research about branding the tourist destination of Central Istria, which aim is to find out the real state of tourism in Central Istria, as well as to realize the positive aspects that can be achieved by quality branding. The research was conducted among the renowned and best tourist employees of Central Istria, divided into five different sectors

Branding Tourist Destinations on the Example of Central Istria

Destinacija je nerijetko isključivi razlog putovanja. Nju čine određeni elementi među kojima su najizraženiji oni poput atrakcija destinacije, usluga, imiđa, cijene, pristupačnosti i sl. Turizam je u Hrvatskoj, zbog njezinih prirodnih bogatstava, vrlo perspektivna grana djelatnosti. Ipak, turistička ponuda ne sastoji se samo od prirodnih ljepota, gastronomske ponude destinacije i smještajnih kapaciteta. Sve navedeno jesu elementi ponude, međutim, za stvaranje profita ključni su gosti. Da bi se gosta privuklo da posjeti određenu destinaciju, mora mu se pružiti adekvatna prezentacija osnovnih informacija o toj destinacije i dati mu razlog zbog kojeg bi trebao odabrati upravo određenu destinaciju. U novije doba sve je veća raznolikost u turističkoj potražnji, odnosno povećava se broj potreba gostiju koje treba zadovoljiti. Brendiranjem destinacije ista postaje prepoznatljiva i promovirana kroz različite kanale turističkog tržišta. Upravo je taj segment aktivnosti potreban i središnjoj Istri kako bi se razvila u što poželjniju turističku destinaciju. To je razlog provođenja ovog istraživanja o brendiranju turističke destinacije središnje Istre čiji je cilj saznati realno stanje turizma u središnjoj Istri, ali i uvidjeti pozitivne aspekte koji se mogu postignuti kvalitetnim brendiranjem. Istraživanje je provedeno među renomiranim i najkvalitetnijim turističkim djelatnicima središnje Istre, podijeljenim u pet različitih sektora.Destination is often the main reason for travelling. It unifies certain elements among which the most prominent ones are attraction, service, image, price, accessibility, etc. Tourism in Croatia, due to its natural resources, is a very promising branch of activity. However, the tourist offer does not only consist of natural beauty, the destination, gastronomic offer and accommodation capacities. All of this makes part of the offer, however the key for making profit are guests. To attract a guest to visit a particular destination, an adequate presentation oft he destination basic information should be provided and, furthermore give reason to choose a particular destination. Nowadays there is a growing diversity in tourist demand, respectively the number of guests needs that need to be satisfy is increasing. By branding the destination, it becomes recognizable and promoted through various tourist market channels. This is the activity segment needed in Central Istria to develop it into a more desirable tourist destination. This is the main reason for carrying out this research about branding the tourist destination of Central Istria, which aim is to find out the real state of tourism in Central Istria, as well as to realize the positive aspects that can be achieved by quality branding. The research was conducted among the renowned and best tourist employees of Central Istria, divided into five different sectors

Percursos e Memórias Acadêmicas e Profissionais

Memorial presented at the Master in Technological and Professional EducationMemorial presented at the Master in Technological and Professional EducationMemorial apresentado no Mestrado em Educação Tecnológica e Profissiona

Gestão da segurança no manuseio e operação com explosivos e acessórios de detonação em pedreiras

Monografia apresentada ao Setor de Pós-graduação da Universidade do Extremo Sul Catarinense- UNESC, para a obtenção do título de especialista em Engenharia de Segurança do Trabalho.O presente trabalho tem como objetivo a elaboração de procedimentos técnico-operacionais, concernentes ao recebimento, ao manuseio e à detonação com o emprego de explosivos e seus acessórios, em mina a céu aberto – pedreiras. Os dados obtidos para análise e realização deste, foram levantados de literaturas correlatas afins, arquivos, fotos (in loco), assim como de informações da Unidade de Extração de Basalto, localizada em Rio Maior, Município de Urussanga-SC., cuja qual faz parte das unidades de mineração da Empresa SBM – Sul Brasileira de Mineração – durante o período de 2014 a 2015, pertencente ao Grupo SETEP Construções S.A. A metodologia aplicada consistiu no acompanhamento e participação direta no denominado ciclo operacional de lavra, correspondente às etapas de perfuração, carregamento e detonação, registrando-se situações e eventuais dificuldades das atividades, correlacionado-as com as Normas Regulamentadoras vigentes no País e demais referências bibliográficas inerentes ao setor. A segurança nas operações com explosivos são de extrema importância, devido ao seu elevado grau de risco, que pode acarretar em acidentes, em sua maioria, graves, por algum ato ou condição insegura, resultante do descumprimento aos procedimentos e/ou normas implementadas à execução do trabalho de lavra. Com a criação de um procedimento padrão e modelo, à etapa de carregamento e detonação, sem dúvidas, elevar-se-á a segurança da atividade e, principalmente, dos colaboradores envolvidos nesse tipo de trabalho