Novel biochip platform for nucleic acid analysis

sensor

Novel bead-based platform for direct detection of unlabelled nucleic acids through Single Nucleobase Labelling

Over the last decade, circulating microRNAs have received attention as diagnostic and prognostic biomarkers. In particular, microRNA122 has been demonstrated to be an early and more sensitive indicator of drug-induced liver injury than the widely used biomarkers such as alanine aminotransferase and aspartate aminotransferase. Recently, microRNA122 has been used in vitro to assess the cellular toxicity of new drugs and as a biomarker for the development of a rapid test for drug overdose/liver damage. In this proof-of-concept study, we report a PCR-free and label-free detection method that has a limit of detection (3 standard deviations) of 15 fmoles of microRNA122, by integrating a dynamic chemical approach for "Single Nucleobase Labelling" with a bead-based platform (Luminex®) thereby, in principle, demonstrating the exciting prospect of rapid and accurate profiling of any microRNAs related to diseases and toxicology

Circulating tumor cells criteria (CyCAR) versus standard RECIST criteria for treatment response assessment in metastatic colorectal cancer patients

The use of circulating tumor cells (CTCs) as indicators of treatment response in metastatic colorectal cancer (mCRC) needs to be clarified. The objective of this study is to compare the Response Evaluation Criteria in Solid Tumors (RECIST) with the Cytologic Criteria Assessing Response (CyCAR), based on the presence and phenotypic characterization of CTCs, as indicators of FOLFOX–bevacizumab treatment response. We observed a decrease of CTCs (42.8 vs. 18.2%) and VEGFR positivity (69.7% vs. 41.7%) after treatment. According to RECIST, 6.45% of the patients did not show any clinical benefit, whereas 93.55% patients showed a favorable response at 12 weeks. According to CyCAR, 29% had a non-favorable response and 71% patients did not. No significant differences were found between the response assessment by RECIST and CyCAR at 12 or 24 weeks. However, in the multivariate analysis, RECIST at 12 weeks and CyCAR at 24 weeks were independent prognostic factors for OS (HR: 0.1, 95% CI 0.02–0.58 and HR: 0.35, 95% CI 0.12–0.99 respectively). CyCAR results were comparable to RECIST in evaluating the response in mCRC and can be used as an alternative when the limitation of RECIST requires additional response analysis techniques.This work was supported by Roche Spain and a Ph.D. grant from the University of Granada

YRITYKSEN KASVUSTRATEGIAN SUUNNITTELU

Työ on tehty ulkovalaistuksen asiantuntijayritykselle nimeltä FIXULUX OY, jonka toiminta on käynnistynyt muutamia vuosia sitten. Yritys on vakiinnuttanut asemansa toimialalla ja ajatuksena on kasvattaa ja kehittää liiketoimintaa. Yrityksen päätuotteita ovat valmistajista riippumattomat, puolueettomat valaistussuunnittelu- ja asiantuntijapalvelut kattaen koko ulkovalaistuksen. Työssä kerättiin teoriatietoa liiketoiminnan kehittämisestä ja kasvattamisesta strategisen johtamisen keinoin ja kerätyistä tiedoista koottiin teoriaosuuteen referaatti. Tutkimuksessa selvitettiin mihin asioihin kannattava kasvu mikroyrityksessä voi perustua ja mitkä ovat yrityksen keinot kannattavan kasvun mahdollistamiseksi. Tutkimuksen perusteella mikroyrityksessä kasvu kannattaa perustaa olemassa olevaan osaamiseen, innovaatioihin, asiakaslähtöiseen liiketoimintaan sekä toiminnan sijoittamiseen oikeaan ympäristöön. Yrityksen keinot kannattavan kasvun mahdollistamiseksi ovat tämän tutkimuksen mukaan seuraavat: asiakkuuksien johtaminen, toiminnan ja osaamisen jatkuva kehittäminen, kilpailukykyinen hinnoittelu, ydinliiketoiminnan lähialueelle siirtyminen sekä yritysostot. Teoriapohjaksi on valittu strateginen johtaminen, mutta myös operatiivinen johtaminen nousi tärkeään asemaan työn edetessä. Tässä työssä on hyödynnetty tutkimuksellisen kehitystyön menetelmiä ja lähestymistapana on konstruktiivinen tutkimus. Aineistona on käytetty strategiseen johtamiseen sekä yritystoiminnan kehittämiseen liittyvää kirjallisuutta sekä digitaalisia lähteitä. Konstruktiivisen tutkimuksen päätuloksena tuotettiin kolme kasvuvaihtoehtoa sisältävä palveluliiketoiminnan kasvusuunnitelma. Sisällön perusteella yrityksen johto voi muodostaa oman näkemyksensä, tehdä tarvittavia päätöksiä sekä lähteä kehittämään tarkempaa kasvusuunnitelmaa.This thesis was made as an assignment to an outdoor lighting company called FIXULUX OY which was established a few years ago. The company has established its position in the industry with the idea of expanding and growing its business. The main products of the company are manufacturerindependent and neutral lighting design solutions and expert services throughout all kinds of outdoor lighting. The theory part of this thesis was made by gathering and summarizing information about developing and growing businesses with the help of strategic leadership. Thesis gives answers to questions such as which aspects should be taken into consideration when trying to find profitable growth in a micro sized company and what the means to enable that growth are. Research showed that in a micro sized company growth should be based on existing know-how, innovation, clientbased business and by placing the operations into the right environment. The means to enable profitable growth according to this research are as follows: managing customerships, continuous improvement of operations and know-how, competitive pricing, moving the business close enough to core business areas and business buy-outs. Strategic leadership was selected as the basis of this thesis but approaches from the perspective of operative leadership became equally important once the research progressed. The thesis utilized the research method of development through research with the approach of constructive research. The material used includes literature on strategic leadership and business development as well as digital sources. The main outcome of this thesis is a growth plan for service business including three different approaches for growth. With the help of this content the company management can make up their own opinions, make necessary decisions and start to develop a more precise growth plan

Simultaneous Detection of Drug-Induced Liver Injury Protein and microRNA Biomarkers Using Dynamic Chemical Labelling on a Luminex MAGPIX System

Drug-induced liver injury (DILI) is a potentially fatal adverse event and a leading cause for pre- and post-marketing drug withdrawal. Several multinational DILI initiatives have now recommended a panel of protein and microRNA (miRNA) biomarkers that can detect early liver injury and inform about mechanistic basis. This manuscript describes the development of seqCOMBO, a unique combo-multiplexed assay which combines the dynamic chemical labelling approach and an antibody-dependant method on the Luminex MAGPIX system. SeqCOMBO enables a versatile multiplexing platform to perform qualitative and quantitative analysis of proteins and miRNAs in patient serum samples simultaneously. To the best of our knowledge, this is the first method to profile protein and miRNA biomarkers to diagnose DILI in a single-step assay

miR-122 direct detection in human serum by time-gated fluorescence imaging

A simple method for direct detection of microRNAs (miRs) in human serum without the use of polymerase amplification is presented, achieving low miR-122 concentrations and importantly, discerning effectively single-base sequence mutations. The method is based on the capture of target miRs with synthetic peptide nucleic acid oligomers, dynamic chemical labelling, separation with quaternary amine microplatforms and detection using time-gated fluorescence imaging

Schematic of the assay for miRNA based on combining dynamic labeling of specific single bases and detection using single molecule arrays.

<p>Schematic of the assay for miRNA based on combining dynamic labeling of specific single bases and detection using single molecule arrays.</p

Plot of AEB determined using the assay in Fig 1 against concentration of calibrators for miR-122 (circles) and the same molecule with a single base mismatch at the 9^th position (squares) spiked into buffer.

<p>The sequences of these two molecules are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0179669#pone.0179669.s009" target="_blank">S2 Table</a>. Error bars (±1 s.d.) based on duplicate measurements are smaller than the size of the data point.</p

Dynamic chemistry labeling of biotin into an immobilized abasic PNA probe on a superparamagnetic bead.

<p>Dynamic chemistry labeling of biotin into an immobilized abasic PNA probe on a superparamagnetic bead.</p