Hypoxia Due to Cardiac Arrest Induces a Time-Dependent Increase in Serum Amyloid β Levels in Humans

Amyloid β (Aβ) peptides are proteolytic products from amyloid precursor protein (APP) and are thought to play a role in Alzheimer disease (AD) pathogenesis. While much is known about molecular mechanisms underlying cerebral Aβ accumulation in familial AD, less is known about the cause(s) of brain amyloidosis in sporadic disease. Animal and postmortem studies suggest that Aβ secretion can be up-regulated in response to hypoxia. We employed a new technology (Single Molecule Arrays, SiMoA) capable of ultrasensitive protein measurements and developed a novel assay to look for changes in serum Aβ42 concentration in 25 resuscitated patients with severe hypoxia due to cardiac arrest. After a lag period of 10 or more hours, very clear serum Aβ42 elevations were observed in all patients. Elevations ranged from approximately 80% to over 70-fold, with most elevations in the range of 3–10-fold (average approximately 7-fold). The magnitude of the increase correlated with clinical outcome. These data provide the first direct evidence in living humans that ischemia acutely increases Aβ levels in blood. The results point to the possibility that hypoxia may play a role in the amyloidogenic process of AD

Disease Detection by Ultrasensitive Quantification of Microdosed Synthetic Urinary Biomarkers

The delivery of exogenous agents can enable noninvasive disease monitoring, but existing low-dose approaches require complex infrastructure. In this paper, we describe a microdose-scale injectable formulation of nanoparticles that interrogate the activity of thrombin, a key regulator of clotting, and produce urinary reporters of disease state. We establish a customized single molecule detection assay that enables urinary discrimination of thromboembolic disease in mice using doses of the nanoparticulate diagnostic agents that fall under regulatory guidelines for “microdosing.”National Science Foundation (U.S.). Graduate Research FellowshipNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32CA159496-02)Burroughs Wellcome Fund (Career Award at the Scientific Interface)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)David H. Koch Institute for Integrative Cancer Research at MIT (Frontier Research Program

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

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

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