Quantitative refinement of reaction-based biomodels

In the field of molecular biology, scientists adopted for decades a reductionist perspective in their inquiries, being predominantly concerned with the intricate mechanistic details of subcellular regulatory systems. However, integrative thinking was still applied at a smaller scale in molecular biology to understand the underlying processes of cellular behaviour for at least half a century. It was not until the genomic revolution at the end of the previous century that we required model building to account for systemic properties of cellular activity. Our system-level understanding of cellular function is to this day hindered by drastic limitations in our capability of predicting cellular behaviour to reflect system dynamics and system structures. To this end, systems biology aims for a system-level understanding of functional intraand inter-cellular activity. Modern biology brings about a high volume of data, whose comprehension we cannot even aim for in the absence of computational support. Computational modelling, hence, bridges modern biology to computer science, enabling a number of assets, which prove to be invaluable in the analysis of complex biological systems, such as: a rigorous characterization of the system structure, simulation techniques, perturbations analysis, etc. Computational biomodels augmented in size considerably in the past years, major contributions being made towards the simulation and analysis of large-scale models, starting with signalling pathways and culminating with whole-cell models, tissue-level models, organ models and full-scale patient models. The simulation and analysis of models of such complexity very often requires, in fact, the integration of various sub-models, entwined at different levels of resolution and whose organization spans over several levels of hierarchy. This thesis revolves around the concept of quantitative model refinement in relation to the process of model building in computational systems biology. The thesis proposes a sound computational framework for the stepwise augmentation of a biomodel. One starts with an abstract, high-level representation of a biological phenomenon, which is materialised into an initial model that is validated against a set of existing data. Consequently, the model is refined to include more details regarding its species and/or reactions. The framework is employed in the development of two models, one for the heat shock response in eukaryotes and the second for the ErbB signalling pathway. The thesis spans over several formalisms used in computational systems biology, inherently quantitative: reaction-network models, rule-based models and Petri net models, as well as a recent formalism intrinsically qualitative: reaction systems. The choice of modelling formalism is, however, determined by the nature of the question the modeler aims to answer. Quantitative model refinement turns out to be not only essential in the model development cycle, but also beneficial for the compilation of large-scale models, whose development requires the integration of several sub-models across various levels of resolution and underlying formal representations.

What ethologically based models have taught us about the neural systems underlying fear and anxiety

Classical Pavlovian fear conditioning to painful stimuli has provided the generally accepted view of a core system centered in the central amygdala to organize fear responses. Ethologically based models using other sources of threat likely to be expected in a natural environment, such as predators or aggressive dominant conspecifics, have challenged this concept of a unitary core circuit for fear processing. We discuss here what the ethologically based models have told us about the neural systems organizing fear responses. We explored the concept that parallel paths process different classes of threats, and that these different paths influence distinct regions in the periaqueductal gray - a critical element for the organization of all kinds of fear responses. Despite this parallel processing of different kinds of threats, we have discussed an interesting emerging view that common cortical-hippocampal-amygdalar paths seem to be engaged in fear conditioning to painful stimuli, to predators and, perhaps, to aggressive dominant conspecifics as well. Overall, the aim of this review is to bring into focus a more global and comprehensive view of the systems organizing fear responses.

Co-culture of apoptotic breast cancer cells with immature dendritic cells: a novel approach for DC-based vaccination in breast cancer

A dendritic cell (DC)-based vaccine strategy could reduce the risk of recurrence and improve the survival of breast cancer patients. However, while therapy-induced apoptosis of hepatocellular and colorectal carcinoma cells can enhance maturation and antigen presentation of DCs, whether this effect occurs in breast cancer is currently unknown. In the present study, we investigated the effect of doxorubicin (ADM)-induced apoptotic MCF-7 breast cancer cells on the activation of DCs. ADM-induced apoptotic MCF-7 cells could effectively induce immature DC (iDC) maturation. The mean fluorescence intensity (MFI) of DC maturity marker CD83 was 23.3 in the ADM-induced apoptotic MCF-7 cell group compared with 8.5 in the MCF-7 cell group. The MFI of DC co-stimulatory marker CD86 and HLA-DR were also increased after iDCs were treated with ADM-induced apoptotic MCF-7 cells. Furthermore, the proliferating autologous T-lymphocytes increased from 14.2 to 40.3% after incubated with DCs induced by apoptotic MCF-7 cells. The secretion of interferon-γ by these T-lymphocytes was also increased. In addition, cell-cell interaction between apoptotic MCF-7 cells and iDCs, but not soluble factors released by apoptotic MCF-7 cells, was crucial for the maturation of iDCs. These findings constitute a novel in vitro DC-based vaccine strategy for the treatment of breast cancer by ADM-induced apoptotic MCF-7 cells.

NEW BUSINESS MODELS – Sustainability as a main focus

A business model is a structure frame of an organization that can bring significant benefits and competitive advantage when structured properly. The aim of this paper was to observe and describe development of business models’ and identify factors and elements of a business model that are in a key role from the perspective of an organizational sustainability. One is striving to bring out in this thesis how should truly sustainable business model look like and what are main characteristics of it. Additionally, some recommendations that could be helpful in order to build sustainable and balanced business model in a company are presented in this work. The meaning was to make theoretical and in some extent practical acquaintance with such new business models as open business model and sustainable business model. Long-term sustainability achievement in a company was in a centric role and used as a main criteria when constructing sustainable business model structure. The main research question in this study aims to answer: What a firm should consider in order to develop profitable and sustainable business model? This study is qualitative in nature and it was conducted using content analyze as a main method of this research. The perspective of the target data in this study is an outlook of its producers of how sustainability is reached in an organization throw business model and which practices are important and has to be taken into account. The material was gathered mainly from secondary sources and the theoretical framework was outright built based on secondary data. The secondary data that have been mostly dissertations, academic writings, cases, academic journals and academic books have been analyzed from the point of view of sustainability perspective. As a result it became evident that a structure of a business model and its implementation along with a strategy is often what leads companies to success. However, for the most part, overall business environment decides and delimits how the most optimal business model should be constructed in order to be effective and sustainable. The evaluation of key factors and elements in business model leading organization to sustainability should be examined throw triple bottom line perspective, where key dimensions are environmental, social and economic. It was concluded that dimensions should be evaluated as equal in order to attain total long lasting sustainability, contradicting traditional perspective in business where profit production is seen as only main goal of a business.

Organization of the marketing communication activities after fusion - the integration and the decision making processes

This master’s thesis was made in order to gain answers to the question of how the integration of the marketing communications and the decision making related to it in a geographically dispersed service organization could be improved in a situation where an organization has gone through a merger. The effects of the organizational design dimensions towards the integration of the marketing communications and the decision making related to it was the main focus. A case study as a research strategy offered a perfect frames for an exploratory study and the data collection was conducted by semi-structured interviews and observing. The main finding proved that from the chosen design dimensions, decentralization, coordination and power, could be found specific factors that in a geographically dispersed organization are affecting the integration of the marketing communications negatively. The effects can be seen mostly in the decision making processes, roles and in the division of responsibility, which are affecting the other dimensions and by this, the integration. In a post-merger situation, the coordination dimension and especially the information asymmetry and the information flow seem to have a largest affect towards the integration of the marketing communications. An asymmetric information distribution with the lack of business and marketing education resulted in low self-assurance and at the end in fragmented management and to the inability to set targets and make independent decisions. As conclusions it can be stated, that with the organizational design dimensions can the effects of a merger towards the integration process of the marketing communications to be evaluated.

The new era of customer experience in the omni-channel environment of a communication service provider

This study discusses the evolution of an omni-channel model in managing customer experience. The purpose of this thesis is to expand the current academic literature available on omni-channel and offer suggestions for omni-channel creation. This is done by studying the features of an omni-channel approach into engaging with customers and through the sub-objectives of describing the process behind its initiation as well as the special features communication service providers need to take in consideration. Theories used as a background for this study are related to customer experience, channel management, omni-channel and finally change management. The empirical study of this thesis consists of seven expert interviews conducted in a case company. The interviews were held between March and November 2014. One of the interviewees is the manager of an omni-channel development team, whilst the rest were in charge of the management of the various customer channels of the company. The organization and analysis of the interview data was conducted topically. The use of themes related to major theories on the subject was utilized to create linkages between theory and practice. The responses were also organized in two groups based on the viewpoint to map responses related to the company perspective as well as the customers´ perspective. The findings in this study are that omni-channel is among the best tools for companies to respond to the challenge induced by changing customer needs and preferences, as well as intensifying competitive environment. The omni-channel model was found to promote excellent customer experience and thus to be a source of competition advantage and increasing financial returns by creating an omni-experience for the customer. Through omniexperience customers see all of the transactions with a company presenting one brand and providing ease and effortlessness in every encounter. The processes behind omni-channel formulation were identified as customer experience proclaimed as the most important strategic goal, mapping and establishing a unified brand experience in all (service) channels and empowering the first line personnel as the gate keepers of omniexperience. Further the tools, measurement and supporting strategies were to be in accordance with the omni-channel strategy and the customer needs to become a partner in a two way transaction with the firm. Based on these findings a model for omni-channel creation is offered. Future research is needed to firstly, further test these findings and expand the theoretical framework on omni-channel, as it is quite scarce to date and secondly, to increase the generalizability of the model suggested.

Yliopiston yrittäjämäisyyden sosiaalinen rakentuminen: case Aalto-yliopisto

Keskustelu yrittäjyyden sijoittumisesta yliopistojen tehtäväkenttään on muodostunut 2000-luvun aikana osaksi yhteiskunnallista ja maailmanlaajuista korkeakoulutuksen muutosta. Tämän tutkimuksen tarkoituksena on lisätä ymmärrystä yliopiston yrittäjämäisyyden sosiaalisesta rakentumisesta. Lähestyn yliopiston sisällä tuotettua moniäänistä yrittäjyyspuhetta yliopiston yrittäjämäisyyden todellisuuden representaationa, ja pyrin tekemään siitä selkoa kommunikaatioon kohdistuvan analyysin avulla. Ilmiön empiirinen tarkastelu pohjautuu Aalto-yliopistossa ja sitä edeltäneessä Teknillisessä korkeakoulussa vuosina 2006–2013 kerättyihin tekstiaineistoihin. Aineistojen tulkinta tuottaa monikerroksellista tietoa ilmiöstä niin yksilö- kuin organisaatiotasolla. Tarkastelen tutkimuksessani millaisia merkityksenantoja yrittäjyydelle ja yrittäjämäisyydelle annetaan yliopiston sisällä eri näkökulmista katsottuna, kun yliopisto käy läpi merkittävää organisaatiorakenteellista ja institutionaalista muutosta. Tutkimusasetelman neljä näkökulmaa perustuvat tekniikan alan jatko-opiskelijoiden puheeseen, TKK:n opetussuunnitelmatekstiin, Aalto-yliopiston opettajien puheeseen ja johdon tuottamaan strategiatekstiaineistoon. Tutkimuksen tulosten mukaan käynnissä on ollut akateemisten arvojen ja arvojärjestelmien laajentumisen aika ja tila, jossa yrittäjämäisyys astuu areenalle, mutta sen suppeat tulkinnat eivät tarjoa mahdollisuuksia ruohonjuuritason kiinnittymiseen akateemisesta kulttuurista käsin. Yrittäjyyden ja yrittäjämäisyyden saamat taloudelliskaupalliset merkitykset koetaan uhkaksi, eikä tilannetta helpota yleisesti uuvuttavaksi koettu rakenteellinen ja yhteiskunnallinen yliopiston muutosvaihe. Hallitsevat tarinalinjat kuten puhe kilpailukyvystä ja kilpailutilanteen kovenemisesta tuottavat odotusten viitekehyksen, joilla yliopiston toimintaa raamitetaan ulkoapäin. Yrittäjyyteen laajassa merkityksessä sisältyvät mahdollisuudet jäävät niin ikään hyödyntämättä, ja lukuisat edistämistoiminnot kilpistyvät sosiaalisesti rakentuviin esteisiin. Tässä tutkimuksessa rakentuva laajennettu yliopiston yrittäjämäisyyden viitekehys pyrkii palvelemaan moniäänistymisen tarkoitusta käsitteellisellä tasolla ja avaamaan uusia mahdollisuuksia yliopiston yrittäjämäisyyden edistämiselle.

Critical success factors for improving societal effectiveness of transport sector's R&D

This study investigates societal effectiveness of transport sector’s Research & Development (R&D) operations. In this study effectiveness refers to organization’s capability to produce the intended and desired impacts through its operations. The aim of this study is to identify the motives for evaluating societal effectiveness and recognize the critical success factors for improving effectiveness. The theoretical framework focuses first in the policy context of effectiveness evaluation in public sector and secondly the framework introduces the concept and process of effectiveness evaluation. The empirical part is carried out as a case study, which investigates societal effectiveness of Finnish Transport Agency’s (FTA’s) R&D. The aim is to recognize FTA’s critical success factors for improving R&D operations’ societal effectiveness. Based on these factors, the organization is able to define indicators for measuring effectiveness in the future operations. In this study societal effectiveness is investigated from R&D purchasers’ and R&D end- users’ points of views according to Purchaser-Provider-model. The results indicate that societal effectiveness evaluation is important part of R&D operations, but the implementation of the evaluation as part of daily operations is challenging. Because of limited resources, the organization is forced to strong priorization and therefore R&D tasks are secondary after the operational tasks. Based on the results the critical success factors can be recognized as resources and priorization, clear strategy and objectives, internal communications, cooperation between public and private sector and R&D implementation and dissemination.

New ways to do business plans in multicultural organizations

Business plans are made when establishing new company or when organizations launch new product or services. In this Master Thesis was examined the elements are included in the business plan and emphasized. Business plan is a wide document and can also contain company specific information, the literature review was restricted into three areas which were investigated from the relating literature and articles. The selected areas were Market Segmentation and Targeting, Competitive Environment, and Market Positioning and Strategy. The different business plan models were investigated by interviewing companies who operates in a different industry sectors from each other’s. The models were compared to each other and to the findings from literature. Based on interview results and literature findings, the business plan for fibre based packaging. The created business plan contains three selected areas. It was found that the selected business plan elements can be found from the interviewed companies’ business plans. The market segmentation was done by comparing the market share to known total market size. When analyzing the competitive environment, there was no one selected model in use. The tools to evaluate competitive environment was selected parts from both SWOT analysis and Porter’s five forces model in applicable part. Based on interview results, it can be state that the company or organization should find and built its own model for business plans. In order to receive the benefits for future planning, the company should use the same model for long time.

Vaneritehtaan sisäisen viestinnän kehittäminen

Viestinnän merkitys yritysten menestymisessä on huomattu viimeisten vuosikymmenien aikana ja myös yritysten sisäiseen viestintään kiinnitetään yhä enemmän huomiota. Tutkimukset ovat osoittaneet, että suurin osa organisaatioissa esiintyneistä ongelmista johtuu epäonnistuneesta viestinnästä. Suurin osa kirjallisuudesta keskittyy tarkastelemaan sisäistä viestintää yleisellä tasolla, ottamatta kantaa tarkemmin erilaisten organisaatioiden erityispiirteisiin. Tämän työn tarkoituksen on tarkastella sisäistä viestintää tuotanto-organisaation kontekstissa. Työn tarkoituksena oli tutkia vanerituotantolaitoksen sisäisen viestinnän tilaa ja viestinnän suunnittelua strategisella sekä käytännön tasolla. Työn tuloksena päivitettiin tehtaan sisäinen viestintästrategia tehtaan henkilökunnalle tehdyn kvantitatiivisen tutkimuksen, sekä aikaisempien tutkimusten perusteella. Lisäksi aihetta lähestyttiin havainnoimalla konkreettisia sisäisen viestinnän parantamisen keinoja kolmessa muussa tuotanto-organisaatiossa. Työn tuloksena saatiin arvokasta tietoa tehtaan sisäisen viestinnän tasosta ja kehitysideoita sisäisen viestinnän kehittämiseen. Kyselytutkimuksen tulokset myös tukivat aikaisempien tutkimuksien tuloksia viestinnän tärkeistä elementeistä.

Työnantajamaineen hallinta suomalaisissa suuryrityksissä

Tässä tutkimuksessa tarkastellaan työnantajamainetta ja sen hallintaa organisaation menestystekijänä. Erityislaatuisen osaamisen ollessa yhä voimakkaammin organisaatioiden kilpailukyvyn perusta, sitä keskeisempää yrityksille on saada houkuteltua ja rekrytoitua palvelukseensa lahjakkaita työntekijöitä. Empiirisen tutkimuksen tavoitteena oli selvittää millä tavoin suuret suomalaiset yritykset hallitsevat työnantajamainettaan. Tutkimus toteutettiin kvalitatiivisena monitapaustutkimuksena. Tutkittavia tapauksia olivat Kone Oyj, Wärtsilä Oyj, UPM-Kymmene Oyj sekä OP ryhmä. Empiirinen aineisto kerättiin puolistrukturoitujen haastatteluiden avulla tapausorganisaatioista. Tutkimus osoittaa, että hyvällä työnantajamaineella on olennainen merkitys siinä kuinka vetovoimainen organisaatio on potentiaalisten työntekijöiden keskuudessa. Panostamalla työnantajamaineensa hallintaan, organisaatiot kykenevät houkuttelemaan palvelukseensa lahjakkaimpia ja parhaiten soveltuvia työntekijöitä. Tutkimuksen perusteella työnantajamaineen hallinta on organisaation strategiaan pohjautuvaa jatkuvaa työtä, jota eri organisaatiotahot toteuttavat yhteistyössä. Työnantajamainetta voidaan rakentaa erilaisissa vuorovaikutustilanteissa sidosryhmien kanssa. Nykyisellä henkilöstöllä on tutkimuksen perusteella merkittävä rooli ulkoisen työnantajamaineen hallinnassa.

Strategy and Superior Competence of Growth Company

This thesis is an examination of growth company and it's superior competence and performance which is based on existing theories and research findings. The theory framework is a basis for the processing part of the thesis that is utilized and combined into new thoughts and assumptions. The analysis is focused on the strategy's meaning, the content of strategy, strategy management, strategy planning, strategy tools and methods. The most important finding and discovery were that the strategy and superior competence / performance of successful growth company are rather a continuously improving process and a lifestyle than for example annual strategy project and/or separate strategy seasons.

Towards a contextual understanding of B2B salespeople's selling competencies – An exploratory study among purchasing decision-makers of internationally-oriented technology firms

ABSTRACT Towards a contextual understanding of B2B salespeople’s selling competencies − an exploratory study among purchasing decision-makers of internationally-oriented technology firms The characteristics of modern selling can be classified as follows: customer retention and loyalty targets, database and knowledge management, customer relationship management, marketing activities, problem solving and system selling, and satisfying needs and creating value. For salespeople to be successful in this environment, they need a wide range of competencies. Salespeople’s selling skills are well documented in seller side literature through quantitative methods, but the knowledge, skills and competencies from the buyer’s perspective are under-researched. The existing research on selling competencies should be broadened and updated through a qualitative research perspective due to the dynamic nature and the contextual dependence of selling competencies. The purpose of the study is to increase understanding of the professional salesperson’s selling competencies from the industrial purchasing decision- makers’ viewpoint within the relationship selling context. In this study, competencies are defined as sales-related knowledge and skills. The scope of the study includes goods, materials and services managed by a company’s purchasing function and used by an organization on a daily basis. The abductive approach and ‘systematic combining’ have been applied as a research strategy. In this research, data were generated through semi- structured, person-to-person interviews and open-ended questions. The study was conducted among purchasing decision-makers in the technology industry in Finland. The branches consisted of the electronics and electro-technical industries and the mechanical engineering and metals industries. A total of 30 companies and one purchasing decision-maker from each company were purposively chosen for the sampling. The sample covers different company sizes based on their revenues, their differing structures – varying from public to family companies –that represent domestic and international ownerships. Before analyzing the data, they were organized by the purchasing orientations of the buyers: the buying, procurement or supply management orientation. Thematic analysis was chosen as the analysis method. After analyzing the data, the results were contrasted with the theory. There was a continuous interaction between the empirical data and the theory. Based on the findings, a total of 19 major knowledge and skills were identified from the buyers’ perspective. The specific knowledge and skills from the viewpoint of customers’ prevalent purchasing orientations were divided into two categories, generic and contextual. The generic knowledge and skills apply to all purchasing orientations, and the contextual knowledge and skills depend on customers’ prevalent purchasing orientations. Generic knowledge and skills relate to price setting, negotiation, communication and interaction skills, while contextual ones relate to knowledge brokering, ability to present solutions and relationship skills. Buying-oriented buyers value salespeople who are ‘action oriented experts, however at a bit of an arm’s length’, procurement buyers value salespeople who are ‘experts deeply dedicated to the customer and fostering the relationship’ and supply management buyers value salespeople who are ‘corporate-oriented experts’. In addition, the buyer’s perceptions on knowledge and selling skills differ from the seller’s ones. The buyer side emphasizes managing the subject matter, consisting of the expertise, understanding the customers’ business and needs, creating a customized solution and creating value, reliability and an ability to build long-term relationships, while the seller side emphasizes communica- tion, interaction and salesmanship skills. The study integrates the selling skills of the current three-component model− technical knowledge, salesmanship skills, interpersonal skills− and relationship skills and purchasing orientations, into a selling competency model. The findings deepen and update the content of these knowledges and skills in the B2B setting and create new insights into them from the buyer’s perspective, and thus the study increases contextual understanding of selling competencies. It generates new knowledge of the salesperson’s competencies for the relationship selling and personal selling and sales management literature. It also adds knowledge of the buying orientations to the buying behavior literature. The findings challenge sales management to perceive salespeople’s selling skills both from a contingency and competence perspective. The study has several managerial implications: it increases understanding of what the critical selling knowledge and skills from the buyer’s point of view are, understanding of how salespeople effectively implement the relationship marketing concept, sales management’s knowledge of how to manage the sales process more effectively and efficiently, and the knowledge of how sales management should develop a salesperson’s selling competencies when managing and developing the sales force. Keywords: selling competencies, knowledge, selling skills, relationship skills, purchasing orientations, B2B selling, abductive approach, technology firms

Co-operative acquisitions – the contextual factors and challenges for co-operatives when acquiring an investorowned firm

Mergers and acquisitions (M&As) have been seen as an important strategy in helping organizations to grow, gain access to new markets and resources, increase efficiency, and enable competitiveness in order to fulfil the purpose of the organization. These aspects have made M&As of central interest to academic literature. In co-operative studies mergers especially have been widely studied. The common focus of these studies is that M&As have taken place between organizations of the same form. It is noteworthy that there is a scarcity of literature concerning acquisitions between different organizational types. Moreover, M&As have not been evaluated concerning the organization’s ownership and purpose, which may be significant integration factors. The overall objective of this study is to describe and understand why co-operative organizations use acquisition as a strategic alternative. In more detail – and in order to develop understanding of the background ideals affecting the acquisition decision and the differences of organization ideals in the integration process – this study is based on a qualitative case study approach. By combining interview data gathered from the OPPohjola Group and associating the observations from various streams of research on acquisitions and management with the purpose of co-operation, and examining these issues further, the thesis contributes to the elaboration of theory in the field of the strategic management of co-operatives. The dissertation consists of two parts. The first part introduces the research topic, methods and publications, as well as discussing the overall outcomes. The second part consists of four publications that address the research questions from different viewpoints. The analyses of this dissertation indicate that, from the strategic point of view, the acquisition of an investor-owned firm by a co-operative organization may create competitive advantage for the co-operative. On the other hand, there are differences in and following from the purpose of acquirer and the acquiree that may, in such case, pose several challenges to the integration process.

Choosing the service support model after a merger: Case Are Ltd.

The meaning of information technology (IT) and information systems have increased during the last few years. This is mainly because business is nowadays seen more and more as a service business and IT is one of the key elements to support those business services. Since the meaning of IT services has increased also the meaning of IT service support should be a factor paid more attention to. Especially after a merger and acquisition (M&A) it is more important than ever to consider service support. The purpose of this study is to discover the best practices for choosing a suitable service support model. The research question is How to choose a service support organization model for the ERP service desk function after a merger? A qualitative method is selected as a research method. This thesis includes two parts: a literature review and a case study. Theoretical part compiles an integrated model of previous research on the topic. It consists a collection of academic articles, publications and reports. The empirical part focuses on the issues in the case organization. That part tries to answer the question: what would be the most suitable service support model for the case organization? The empirical part is conducted by interviewing the employees of the case organization. This study finds that even though there are many ways of selecting a service support model it is difficult to define an unambiguous guidelines. However, there are few main objectives that should be taken into account regardless the case. Especially by using ITIL processes it is possible to implement a comprehensive service support and raise overall awareness of the existing service support models. The main functions that need to be taken into account are nature, industry and size of the organization. Also the business strategy, goals and resources need to be considered. These are the same factors that are noticed in the case study as well. The suggestions for the case organization are presented based on the interviews and the literature review.