869 resultados para Target points
Resumo:
The aim of the research was to create a comprehensive city branding process. This was done by identifying the key target groups of the city and considering them in the city branding process. Also key stakeholders were identified and taken into consideration when creating the branding process. As an empirical study, three first stages of the city branding process were implemented for the city of Lappeenranta having "students" as the case target group. An interview with the city officials was conducted, as well as a student survey on the current city image of Lappeenranta. Quantitative research methods were used to analyze the results of the survey. A comprehensive city branding process with eight stages was created in the research. Target groups were considered in the process by identifying the target group dependent stages. The empirical study revealed that the current city image held by the students consists of six dimensions. These dimensions were analyzed from the viewpoint of Lappeenranta with the help of an importance performance analysis.
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Tietojärjestelmät ovat kehittyneet kriittisiksi tekijöiksi yritysten liiketoiminnassa. Niitä on vaikea tai lähes mahdoton korvata. Toisaalta tietojärjestelmät ovat edesauttaneet yrityksiä tehostamaan toimintaansa. Yrityksen toimialalla tai koolla ei nykyään ole merkitystä erilaisten tietoteknisten järjestelmien ja sovellusten hyödyntämisessä. Riskienhallinnan avulla yritys pyrkii ennaltaehkäisemään tunnettuja riskejä. Liiketoiminnan jatkuvuudenhallinta pyrkii puolestaan varautumaan riskin aiheuttamaan liiketoiminnan häiriöön ja siitä toipumiseen. Tietojärjestelmien ollessa korvaamattomia tulee yrityksen kohdistaa resursseja ennaltaehkäiseviin toimiin, lisäksi sen on pyrittävä lyhentämään häiriöstä toipumisen aikaa. Tutkimuksen tarkoituksena oli tunnistaa kohdeyrityksen tietojärjestelmien merkittävimmät riskit, jotka uhkaavat oleellisesti liiketoiminnan jatkuvuutta. Liiketoiminnan jatkuvuuden tarkastelussa hyödynnettiin yrityksen käyttämää suorituskykymittaristoa (Balanced Score Card). Työllä tuetaan yrityksen laatujärjestelmän vaatimuksia liiketoiminnan turvaamisessa. Tutkielma toteutettiin pääasiassa teemahaastatteluiden muodossa, laadullista tutkimusmenetelmää hyödyntäen. Tutkimuksessa todettiin yrityksen tietojärjestelmien ja niiden ylläpidon olevan hyvällä tasolla. Muutamia kriittisiä vikaantumispisteitä kuitenkin havaittiin, joiden pohjalta laadittiin kehitysehdotuksia tietojärjestelmien vikasietoisuuden parantamiseksi liiketoiminnan jatkuvuudenhallinnan näkökannalta.
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PIXE (Particle Induce X-ray Emission spectrometry) was used for analysing stem bark and stem wood of Scots pine, Norway spruce and Silver birch. Thick samples were irradiated, in laboratory atmosphere, with 3 MeV protons and the beam current was measured indirectly using a photo multiplicator (PM) tube. Both point scans and bulk analyses were performed with the 1 mm diameter proton beam. In bulk analyses, whole bark and sectors of discs of the stem wood were dry ashed at 550 ˚C. The ashes were homogenised by shaking and prepared to target pellets for PIXE analyses. This procedure generated representative samples to be analysed, but the enrichment also enabled quantification of some additional trace elements. The ash contents obtained as a product of the sample preparation procedure also showed to be of great importance in the evaluation of results in environmental studies. Spot scans from the pith of pine wood outwards, showed clearly highest concentrations of manganese, calcium and zinc in the first spot irradiated, or 2-3 times higher than in the surrounding wood. For stem wood from the crown part of a pine this higher concentration level was found in the first four spots/mms, including the pith and the two following growth rings. Zinc showed increasing concentrations outwards in sapwood of the pine stem, with the over-all lowest concentrations in the inner half of the sapwood. This could indicate emigration of this element from sapwood being under transformation to heartwood. Point scans across sapwood of pine and spruce showed more distinct variations in concentrations relative to hearth wood. Higher concentrations of e.g. zinc, calcium and manganese were found in earlywood than in denser latewood. Very high concentrations of iron and copper were also seen for some earlywood increments. The ash content of stem bark is up to and order higher than for the stem wood. However, when the elemental concentration in ashes of bark and wood of the same disc were compared, these are very similar – this when trees are growing at spots with no anthropogenic contamination from the atmosphere. The largest difference was obtained for calcium which appeared at two times high concentrations in ashes of bark than in ashes of the wood (ratio of 2). Pine bark is often used in monitoring of atmospheric pollution, where concentrations in bark samples are compared. Here an alternative approach is suggested: Bark and the underlying stem wood of a pine trees are dry ashed and analysed. The elemental concentration in the bark ash is then compared to the concentration of the same element in the wood ash. Comparing bark to wood includes a normalisation for the varying availability of an element from the soil at different sites. When this comparison is done for the ashes of the materials, a normalisation is also obtained for the general and locally different enrichment of inorganic elements from wood to bark. Already a ratio >2 between the concentration in the bark ash and the concentration in the wood ash could indicate atmospheric pollution. For monitoring where bark is used, this way of “inwards” comparison is suggested - instead of comparing to results from analyses of bark from other trees (read reference areas), growing at sites with different soil and, locally, different climate conditions. This approach also enables evaluation of atmospheric pollution from sampling of only relative few individual trees –preferable during forest felling.
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Engelskans dominerande roll som internationellt språk och andra globaliseringstrender påverkar också Svenskfinland. Dessa trender påverkar i sin tur förutsättningarna för lärande och undervisning i engelska som främmande språk, det vill säga undervisningsmålen, de förväntade elev- och lärarroller, materialens ändamålsenlighet, lärares och elevers initiala erfarenheter av engelska och engelskspråkiga länder. Denna studie undersöker förutsättningarna för lärande och professionell utveckling i det svenskspråkiga nybörjarklassrummet i engelska som främmande språk. Utgångsläget för 351 nybörjare i engelska som främmande språk och 19 av deras lärare beskrivs och analyseras. Resultaten tyder på att engelska håller på att bli ett andraspråk snarare än ett traditionellt främmande språk för många unga elever. Dessa elever har också goda förutsättningar att lära sig engelska utanför skolan. Sådan var dock inte situationen för alla elever, vilket tyder på att det finns en anmärkningsvärd heterogenitet och även regional variation i det finlandssvenska klassrummet i engelska som främmande språk. Lärarresultaten tyder på att vissa lärare har klarat av att på ett konstruktivt sätt att tackla de förutsättningar de möter. Andra lärare uttrycker frustration över sin arbetssituation, läroplanen, undervisningsmaterialen och andra aktörer som kommer är av betydelse för skolmiljön. Studien påvisar att förutsättningarna för lärande och undervisning i engelska som främmande språk varierar i Svenskfinland. För att stöda elevers och lärares utveckling föreslås att dialogen mellan aktörer på olika nivå i samhället bör förbättras och systematiseras.
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The growth of breast cancer is regulated by hormones and growth factors. Recently, aberrant fibroblast growth factor (FGF) signalling has been strongly implicated in promoting the progression of breast cancer and is thought to have a role in the development of endocrine resistant disease. FGFs mediate their auto- and paracrine signals through binding to FGF receptors 1-4 (FGFR1-4) and their isoforms. Specific targets of FGFs in breast cancer cells and the differential role of FGFRs, however, are poorly described. FGF-8 is expressed at elevated levels in breast cancer, and it has been shown to act as an angiogenic, growth promoting factor in experimental models of breast cancer. Furthermore, it plays an important role in mediating androgen effects in prostate cancer and in some breast cancer cell lines. We aimed to study testosterone (Te) and FGF-8 regulated genes in Shionogi 115 (S115) breast cancer cells, characterise FGF-8 activated intracellular signalling pathways and clarify the role of FGFR1, -2 and -3 in these cells. Thrombospondin-1 (TSP-1), an endogenous inhibitor of angiogenesis, was recognised as a Te and FGF-8 regulated gene. Te repression of TSP-1 was androgen receptor (AR)-dependent. It required de novo protein synthesis, but it was independent of FGF-8 expression. FGF-8, in turn, downregulated TSP-1 transcription by activating the ERK and PI3K pathways, and the effect could be reversed by specific kinase inhibitors. Differential FGFR1-3 action was studied by silencing each receptor by shRNA expression in S115 cells. FGFR1 expression was a prerequisite for the growth of S115 tumours, whereas FGFR2 expression alone was not able to promote tumour growth. High FGFR1 expression led to a growth advantage that was associated with strong ERK activation, increased angiogenesis and reduced apoptosis, and all of these effects could be reversed by an FGFR inhibitor. Taken together, the results of this thesis show that FGF-8 and FGFRs contribute strongly to the regulation of the growth and angiogenesis of experimental breast cancer and support the evidence for FGF-FGFR signalling as one of the major players in breast cancers.
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Metsäteollisuuden muuttunut toimintaympäristö on saanut kohdeyrityksen pyrkimään asiakaslähtöisempään ja markkinaintegroituneempaan toimintaan. Se, että asiakkaille voidaan luvata, mitä he haluavat ja että lupaukset kyetään pitämään, ovat markkinalähtöisen toiminnan keskeisimpiä tekijöitä. Diplomityön tavoitteena on kuvata metsäteollisuusyrityksen tuotteiden saatavuudenhallinnan nykytilaa tuotannonsuunnittelun, myynnin ja asiakkaiden näkökulmasta. Saatavuudenhallinnalla tarkoitetaan sitä, kuinka myyjä tietää, saako hän myydä asiakkaalle, mitä asiakas haluaa. Työssä käsitellään myös metsäteollisuusyrityksen suunnitteluprosesseja, koska ilman toimivaa myynninsuunnittelua ja operatiivista suunnittelua ei tehokas saatavuudenhallintakaan ole mahdollista. Työssä on esitetty vertailumalleja saatavuudenhallinnan ja suunnitteluprosessien toimivuudesta myös muilta toimialoilta kuten elintarvike- ja metalliteollisuudesta. Työn tuloksena on selkeä kuva saatavuudenhallinnan ja suunnitteluprosessien nykytilasta sekä mihin suuntaan niitä voisi kehittää. Suurimpana ongelmana myyntiprosessissa on pitkän tähtäimen suunnittelun puutteellisuus, minkä johtaa siihen, että asiakastilausten saatavuustarkastelut ovat monimutkaisia ja asiakkaille vastaaminen hidasta. Työssä on esitetty tulevaisuuden tavoitetilamalli, jossa tiedonkulku koko toimitusketjun halki on nopeampaa ja tehokkaampaa sekä toimintatavat yhtenäisiä ja selkeitä. Uusi toimintamalli mahdollistaa nopeammat ja luotettavammat myyntilupaukset sekä ilmoittamisen muutoksista asiakkaalle nykyistä aiemmin ja varmemmin.
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Diplomityön tavoitteena oli selvittää Loviisan ydinvoimalaitoksen höyryturbiinin suoritus-kyvyn mittaamiseen käytettävissä olevia menetelmiä ja mittausjärjestelmiä. Tavoitteena oli selvittää mitkä tekijät aiheuttavat mittauksiin mittausvirheitä ja tutkia turbiineiden nykyisten mittalaitteiden epävarmuudet. Tässä diplomityössä selvitettiin millaisia standardinmukaisia testejä sekä muita varteenotettavia testejä turbiinin suorituskyvyn määrittämiseen on käytetty ja millaisia mittauksia ne vaativat. Lisäksi tutkittiin eri lähteistä millaisia mittalaitteita ja mittausjärjestelmiä voidaan käyttää turbiinin toiminnan mittauksiin. Soveltuvista mittausmenetelmistä esitettiin toimintaperiaatteet ja teoria. Kunnonvalvontaa varten esiteltiin värähtelyiden ja vääntö-momentin mittaamisen periaatteet. Epävarmuuksia arvioitiin mittalaitteiden teoreettisen epävarmuuden ja laitesijoittelun pohjalta. Työssä havaittiin, että suorituskyvyn arvioimiseksi on olemassa useita standardeja, mutta niiden mukaisiin mittauksiin tarvittaisiin nykyistä enemmän mittaustuloksia. Tarkkoja sekä luotettavia mittaustuloksia on haasteellista saada kaksifaasivirtauksesta. Mittalaitevalinnoilla ja mittalaitteiden määrää lisäämällä voidaan mittausten epävarmuutta pienentää. Loviisan ydinvoimalaitokselle ehdotettiin muutamia mittausjärjestelmiä turbiinin suoritus-kyvyn määrittämiseksi. Erityisesti turbiinin sisäiset olosuhteet tulisi määrittää nykyistä tarkemmin. Vääntömomentin mittaaminen olisi hyvä kunnonvalvonnan työkalu.
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Decreasing bone mass during aging predisposes to fractures and it is estimated that every second woman and one in five men will suffer osteoporotic fractures during their lifetime. Bone is an adaptive tissue undergoing continuous remodeling in response to physical and metabolic stimuli. Bone mass decreases through a net negative balance in the bone remodeling process of bone, in which the new bone incompletely replaces the resorbed bone mass. Bone resorption is carried out by the osteoclasts; the bone mineral is solubilized by acidification and the organic matrix is subsequently degraded by proteases. Several classes of drugs are available for prevention of osteoporotic fractures. They act by different mechanisms to increase bone mass, and some of them act mainly as antiresorptives by inhibition of osteoclast formation or their function. Optimally, a drug should act selectively on a specific process, since other processes affected usually result in adverse effects. The purpose of this study was to evaluate whether the osteoclastic vacuolar adenosine trisphosphatases (V-ATPase), which drives the solubilization of bone mineral, can be selectively inhibited despite its ubiquitous cellular functions. The V-ATPase is a multimeric protein composed of 13 subunits of which six possesses two or more isoforms. Selectivity for the osteoclastic V-ATPase could be provided if it has some structural uniqueness, such as a unique isoform combination. The a3 isoform of the 116kDa subunit is inevitable for bone resorption; however, it is also present in, and mainly limited to, the lysosomes of other cells. No evidence of a structural uniqueness of the osteoclastic V-ATPase compared to the lysosomal V-ATPase was found, although this can not yet be excluded. Thus, an inhibitor selective for the a3 isoform would target the lysosomal V-ATPase as well. However, the results suggest that selectivity for bone resorption over lysosomal function can be obtained by two other mechanisms, suggesting that isoform a3 is a valid target. The first is differential compensation; bone resorption depends on the high level of a3 expression, and is not compensated for by other isoforms, while the lower level of a3 in lysosomes of other cells may be partly compensated for. The second mechanism is because the bone resorption process itself is fundamentally different from lysosomal acidification because of the chemistry of bone dissolution and the anatomy of the resorbing osteoclast. By this mechanism, full inhibition of bone resorption is obtained with more than tenfold lower inhibitor concentration than those needed to fully inhibit lysosomal acidification. The two mechanisms are additive. Based on the results, we suggest that bone resorption can be selectively inhibited if VATPase inhibitors that are sufficiently selective for the a3 isoform over the other isoforms are developed.
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This study was carried to evaluate the efficiency of the Bitterlich method in growth and yield modeling of the even-aged Eucalyptus stands. 25 plots were setup in Eucalyptus grandis cropped under a high bole system in the Central Western Region of Minas Gerais, Brazil. The sampling points were setup in the center of each plot. The data of four annual mesurements were colleted and used to adjust the three model types using the age, the site index and the basal area as independent variables. The growths models were fitted for volume and mass of trees. The efficiency of the Bitterlich method was confirmed for generating the data for growth and yield modeling.
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Tässä diplomityössä tutkitaan osaamisen johtamisen järjestelmää strategisesta näkö-kulmasta tietohallintopalveluita tuottavassa organisaatiossa. Tutkimuksen tarkoitukse-na oli kehittää osaamisen johtamisen kokonaisuutta kohdeorganisaation suorituskyvyn kehittämiseksi. Tutkimuksen lähtökohtana ovat organisaation arvot, missio ja visio sekä näiden kautta rakentuva organisaation osaamisen strategia. Osaamisen strategian näkökulmasta tarkastellaan asiantuntijuutta, osaamisen johtamista ja organisaation ydinosaamisia. Teoreettisesta näkökulmasta tutkitaan myös verkostoitumista ja oppi-misen verkostomallin hyödyntämismahdollisuuksia kohdeorganisaatiossa. Empiirinen aineisto kerättiin laadullisella teemahaastattelulla. Tutkimuksessa saatiin selkeä kuva kohdeorganisaation osaamisen johtamisen kokonai-suudesta. Verkostoituminen ja verkostomainen työskentely ovat kohdeorganisaatiossa erittäin suuressa roolissa, joten oppimisen verkostomallia voitaisiin hyödyntää organi-saatiossa tehokkaasti. Tämä edellyttää kuitenkin verkoston johtamista ja tavoitteellista osallistumista verkostoihin sekä asetettujen tavoitteiden mittaamista.
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Olfactory packaging is an emerging technology which uses the aromatic capsules to release various scents. Normally, manufacturers add these aromatic capsules in the printing ink, the label or packaging material itself. When the aromatic capsules meet suitable release triggers, the scents will be released. The common release triggers are external forces, temperature changes, humidity changes and so on. The aim for this Masters of Science Thesis is to understand the aroma printing technology from literature and make market research for this kind of technology. The main target is to collect the current technology principle of aroma packaging and figure out how they are implemented on products with those. In addition, an investigation is made about consumers' attitudes from Chinese and Finnish market through the questionnaire, and the market potential is analyzed as well. The key points researched in this work are: the general attitudes on aroma printing technology, market potential and economic possibilities. This thesis specifies the main technologies used in aroma printing, the solutions of products with aroma packaging and the original results of the questionnaires. It also includes analysis of the acceptance of Chinese and Finnish consumers, what are their opinions of the aroma printing technology and the products packed by aroma printing technology. In addition, various factors which impact the market is discussed in the thesis. At last, some comparisons are made from the point of views of similarities and differences between Chinese and Finnish market.
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Scientific evidence on climate changes at global level has gained increasing interest in the scientific community in general. The impacts of climate change as well as anthropogenic actions may cause errors in hydro-agricultural projects existent in the watershed under study. This study aimed to identify the presence or absence of trend in total annual precipitation series of the watershed of the Mirim Lagoon, state of Rio Grande do Sul-RS / Brazil / Uruguay (Brazilian side) as well as to detect the period in which they occurred. For that, it was analyzed the precipitation data belonging to 14 weather stations. To detect the existence of monotonic trend and change points, it was used the nonparametric tests of Mann-Kendall and Mann-Whitney, the "t" test of Student for two samples of unpaired data (parametric), as well as the technique of progressive mean. The Weather Station 3152014 (Pelotas) presented changes in the trend in the series of annual precipitation in the period from 1953 to 2007. The methodologies that use subdivided series were more efficient in detecting change in trend when compared with the Mann-Kendall test, which uses the complete series (from 1921 to 2007).
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Cells of epithelial origin, e.g. from breast and prostate cancers, effectively differentiate into complex multicellular structures when cultured in three-dimensions (3D) instead of conventional two-dimensional (2D) adherent surfaces. The spectrum of different organotypic morphologies is highly dependent on the culture environment that can be either non-adherent or scaffold-based. When embedded in physiological extracellular matrices (ECMs), such as laminin-rich basement membrane extracts, normal epithelial cells differentiate into acinar spheroids reminiscent of glandular ductal structures. Transformed cancer cells, in contrast, typically fail to undergo acinar morphogenic patterns, forming poorly differentiated or invasive multicellular structures. The 3D cancer spheroids are widely accepted to better recapitulate various tumorigenic processes and drug responses. So far, however, 3D models have been employed predominantly in the Academia, whereas the pharmaceutical industry has yet to adopt a more widely and routine use. This is mainly due to poor characterisation of cell models, lack of standardised workflows and high throughput cell culture platforms, and the availability of proper readout and quantification tools. In this thesis, a complete workflow has been established entailing well-characterised 3D cell culture models for prostate cancer, a standardised 3D cell culture routine based on high-throughput-ready platform, automated image acquisition with concomitant morphometric image analysis, and data visualisation, in order to enable large-scale high-content screens. Our integrated suite of software and statistical analysis tools were optimised and validated using a comprehensive panel of prostate cancer cell lines and 3D models. The tools quantify multiple key cancer-relevant morphological features, ranging from cancer cell invasion through multicellular differentiation to growth, and detect dynamic changes both in morphology and function, such as cell death and apoptosis, in response to experimental perturbations including RNA interference and small molecule inhibitors. Our panel of cell lines included many non-transformed and most currently available classic prostate cancer cell lines, which were characterised for their morphogenetic properties in 3D laminin-rich ECM. The phenotypes and gene expression profiles were evaluated concerning their relevance for pre-clinical drug discovery, disease modelling and basic research. In addition, a spontaneous model for invasive transformation was discovered, displaying a highdegree of epithelial plasticity. This plasticity is mediated by an abundant bioactive serum lipid, lysophosphatidic acid (LPA), and its receptor LPAR1. The invasive transformation was caused by abrupt cytoskeletal rearrangement through impaired G protein alpha 12/13 and RhoA/ROCK, and mediated by upregulated adenylyl cyclase/cyclic AMP (cAMP)/protein kinase A, and Rac/ PAK pathways. The spontaneous invasion model tangibly exemplifies the biological relevance of organotypic cell culture models. Overall, this thesis work underlines the power of novel morphometric screening tools in drug discovery.
The spindle assembly checkpoint as a drug target - Novel small-molecule inhibitors of Aurora kinases
Resumo:
Cell division (mitosis) is a fundamental process in the life cycle of a cell. Equal distribution of chromosomes between the daughter cells is essential for the viability and well-being of an organism: loss of fidelity of cell division is a contributing factor in human cancer and also gives rise to miscarriages and genetic birth defects. For maintaining the proper chromosome number, a cell must carefully monitor cell division in order to detect and correct mistakes before they are translated into chromosomal imbalance. For this purpose an evolutionarily conserved mechanism termed the spindle assembly checkpoint (SAC) has evolved. The SAC comprises a complex network of proteins that relay and amplify mitosis-regulating signals created by assemblages called kinetochores (KTs). Importantly, minor defects in SAC signaling can cause loss or gain of individual chromosomes (aneuploidy) which promotes tumorigenesis while complete failure of SAC results in cell death. The latter event has raised interest in discovery of low molecular weight (LMW) compounds targeting the SAC that could be developed into new anti-cancer therapeutics. In this study, we performed a cell-based, phenotypic high-throughput screen (HTS) to identify novel LMW compounds that inhibit SAC function and result in loss of cancer cell viability. Altogether, we screened 65 000 compounds and identified eight that forced the cells prematurely out of mitosis. The flavonoids fisetin and eupatorin, as well as the synthetic compounds termed SACi2 and SACi4, were characterized in more detail utilizing versatile cell-based and biochemical assays. To identify the molecular targets of these SAC-suppressing compounds, we investigated the conditions in which SAC activity became abrogated. Eupatorin, SACi2 and SACi4 preferentially abolished the tensionsensitive arm of the SAC, whereas fisetin lowered also the SAC activity evoked by lack of attachments between microtubules (MTs) and KTs. Consistent with the abrogation of SAC in response to low tension, our data indicate that all four compounds inhibited the activity of Aurora B kinase. This essential mitotic protein is required for correction of erratic MT-KT attachments, normal SAC signaling and execution of cytokinesis. Furthermore, eupatorin, SACi2 and SACi4 also inhibited Aurora A kinase that controls the centrosome maturation and separation and formation of the mitotic spindle apparatus. In line with the established profound mitotic roles of Aurora kinases, these small compounds perturbed SAC function, caused spindle abnormalities, such as multi- and monopolarity and fragmentation of centrosomes, and resulted in polyploidy due to defects in cytokinesis. Moreover, the compounds dramatically reduced viability of cancer cells. Taken together, using a cell-based HTS we were able to identify new LMW compounds targeting the SAC. We demonstrated for the first time a novel function for flavonoids as cellular inhibitors of Aurora kinases. Collectively, our data support the concept that loss of mitotic fidelity due to a non-functional SAC can reduce the viability of cancer cells, a phenomenon that may possess therapeutic value and fuel development of new anti-cancer drugs.