Is there an advantage to be gained from adding digital image cytometry of brush cytology to a standard biopsy protocol in patients with Barrett's esophagus?

BACKGROUND AND STUDY AIMS: The current gold standard in Barrett's esophagus monitoring consists of four-quadrant biopsies every 1-2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett's esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett's esophagus in Switzerland. METHODS: One hundred sixty-four patients with Barrett's esophagus underwent 239 endoscopies with biopsy and brush cytology. DICM was carried out on 239 cytology specimens. Measures of the test accuracy of DICM (relative risk, sensitivity, specificity, likelihood ratios) were obtained by dichotomizing the histopathology results (high-grade dysplasia or adenocarcinoma vs. all others) and DICM results (aneuploidy/intermediate pattern vs. diploidy). RESULTS: DICM revealed diploidy in 83% of 239 endoscopies, an intermediate pattern in 8.8%, and aneuploidy in 8.4%. An intermediate DICM result carried a relative risk (RR) of 12 and aneuploidy a RR of 27 for high-grade dysplasia/adenocarcinoma. Adding DICM to the standard biopsy protocol, a pathological cytometry result (aneuploid or intermediate) was found in 25 of 239 endoscopies (11%; 18 patients) with low-risk histology (no high-grade dysplasia or adenocarcinoma). During follow-up of 14 of these 18 patients, histological deterioration was seen in 3 (21%). CONCLUSION: DICM from brush cytology may add important information to a standard biopsy protocol by identifying a subgroup of BE-patients with high-risk cellular abnormalities.

Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein.

Resistance of human immunodeficiency virus type 1 (HIV-1) to antiretroviral agents results from target gene mutation within the pol gene, which encodes the viral protease, reverse transcriptase (RT), and integrase. We speculated that mutations in genes other that the drug target could lead to drug resistance. For this purpose, the p1-p6(gag)-p6(pol) region of HIV-1, placed immediately upstream of pol, was analyzed. This region has the potential to alter Pol through frameshift regulation (p1), through improved packaging of viral enzymes (p6(Gag)), or by changes in activation of the viral protease (p6(Pol)). Duplication of the proline-rich p6(Gag) PTAP motif, necessary for late viral cycle activities, was identified in plasma virus from 47 of 222 (21.2%) patients treated with nucleoside analog RT inhibitor (NRTI) antiretroviral therapy but was identified very rarely from drug-naïve individuals. Molecular clones carrying a 3-amino-acid duplication, APPAPP (transframe duplication SPTSPT in p6(Pol)), displayed a delay in protein maturation; however, they packaged a 34% excess of RT and exhibited a marked competitive growth advantage in the presence of NRTIs. This phenotype is reminiscent of the inoculum effect described in bacteriology, where a larger input, or a greater infectivity of an organism with a wild-type antimicrobial target, leads to escape from drug pressure and a higher MIC in vitro. Though the mechanism by which the PTAP region participates in viral maturation is not known, duplication of this proline-rich motif could improve assembly and packaging at membrane locations, resulting in the observed phenotype of increased infectivity and drug resistance.

DIGITAL LIBRARY FOR DIGITAL DIVIDE AND ENVIRONMENT OF SCARCE ACCESS TO PRINTED MATERIALS: THE CASE OF UNIVERSITY JEAN PIAGET OF CAPE VERDE

With the failure of the traditional mechanisms of distributing bibliographic materials into developing countries, digital libraries show up as a strong alternative in accomplishing such job, despite the challenges of the digital divide. This paper discusses the challenges of building a digital library (DL) in a developing country. The case of Cape Verde as a digital divide country is analyzed, in terms of current digital library usage and its potentiality for fighting the difficulties in accessing bibliographic resources in the country. The paper also introduces an undergoing project of building a digital library at the University Jean Piaget of Cape Verde.

Designing mobile access to DSpace-based digital libraries

Developing countries face serious problems on building and using digital libraries (DL) due to low computer and Internet penetration rates, lack of financial resources, etc. Thus, since mobile phones are much more used than computers in these countries, they might be a good alternative for accessing DL. Moreover, in the developed world there has been an exponential growth on the usage of mobile phones for data traffic, establishing a good ground for accessing DL on mobile devices. This paper presents a design proposal for making DSpace-based digital libraries accessible on mobile phones. Since DSpace is a popular free and open source DL system used around the world, making it accessible through mobile devices might contribute for improving the global accessibility of scientific and academic publications.

Simultaneous Optical Recording in Multiple Cells by Digital Holographic Microscopy of Chloride Current Associated to Activation of the Ligand-Gated Chloride Channel GABA(A) Receptor.

Chloride channels represent a group of targets for major clinical indications. However, molecular screening for chloride channel modulators has proven to be difficult and time-consuming as approaches essentially rely on the use of fluorescent dyes or invasive patch-clamp techniques which do not lend themselves to the screening of large sets of compounds. To address this problem, we have developed a non-invasive optical method, based on digital holographic microcopy (DHM), allowing monitoring of ion channel activity without using any electrode or fluorescent dye. To illustrate this approach, GABA(A) mediated chloride currents have been monitored with DHM. Practically, we show that DHM can non-invasively provide the quantitative determination of transmembrane chloride fluxes mediated by the activation of chloride channels associated with GABA(A) receptors. Indeed through an original algorithm, chloride currents elicited by application of appropriate agonists of the GABA(A) receptor can be derived from the quantitative phase signal recorded with DHM. Finally, chloride currents can be determined and pharmacologically characterized non-invasively simultaneously on a large cellular sampling by DHM.

Using Digital Video Analysis to Monitor Driver Behavior at Intersections

Commercially available instruments for road-side data collection take highly limited measurements, require extensive manual input, or are too expensive for widespread use. However, inexpensive computer vision techniques for digital video analysis can be applied to automate the monitoring of driver, vehicle, and pedestrian behaviors. These techniques can measure safety-related variables that cannot be easily measured using existing sensors. The use of these techniques will lead to an improved understanding of the decisions made by drivers at intersections. These automated techniques allow the collection of large amounts of safety-related data in a relatively short amount of time. There is a need to develop an easily deployable system to utilize these new techniques. This project implemented and tested a digital video analysis system for use at intersections. A prototype video recording system was developed for field deployment. A computer interface was implemented and served to simplify and automate the data analysis and the data review process. Driver behavior was measured at urban and rural non-signalized intersections. Recorded digital video was analyzed and used to test the system.

Combining digital elevation model analysis and run-out modeling to characterize hazard posed by a potentially unstable rock slope at Turtle Mountain, Alberta, Canada

Turtle Mountain in Alberta, Canada has become an important field laboratory for testing different techniques related to the characterization and monitoring of large slope mass movements as the stability of large portions of the eastern face of the mountain is still questionable. In order to better quantify the volumes potentially unstable and the most probable failure mechanisms and potential consequences, structural analysis and runout modeling were preformed. The structural features of the eastern face were investigated using a high resolution digital elevation model (HRDEM). According to displacement datasets and structural observations, potential failure mechanisms affecting different portions of the mountain have been assessed. The volumes of the different potentially unstable blocks have been calculated using the Sloping Local Base Level (SLBL) method. Based on the volume estimation, two and three dimensional dynamic runout analyses have been performed. Calibration of this analysis is based on the experience from the adjacent Frank Slide and other similar rock avalanches. The results will be used to improve the contingency plans within the hazard area.

Beyond the Net Generation debate: A comparison between digital learners in face-to-face and virtual universities

This paper is based on the hypothesis that the use of technology to support learning is not related to whether a student belongs to the Net Generation, but that it is mainly influenced by the teaching model. The study compares behaviour and preferences towards ICT use in two groups of university students: face-to-face students and online students. A questionnaire was applied to asample of students from five universities with different characteristics (one offers online education and four offer face-to-face education with LMS teaching support).

Error probability in synchronous digital circuits due to power supply noise

This paper presents a probabilistic approach to model the problem of power supply voltage fluctuations. Error probability calculations are shown for some 90-nm technology digital circuits.The analysis here considered gives the timing violation error probability as a new design quality factor in front of conventional techniques that assume the full perfection of the circuit. The evaluation of the error bound can be useful for new design paradigms where retry and self-recoveringtechniques are being applied to the design of high performance processors. The method here described allows to evaluate the performance of these techniques by means of calculating the expected error probability in terms of power supply distribution quality.

Synchronous Digital Hierarchy implementation to a Radio Transmission Node

Kiristyville markkinoille on aina tuotava jotain uutta tarjottavaa ja SDH-kortti on yksi sellainen tuote jonka Nokia Networks julkistaa osaksi uutta Nokia Flexihub Nodea. Tavoitteena on suunnitella VC-12kanavoitu STM-1 kortti yhdistämään ylemmän tason tietoliikenneverkko suuren kapasiteetin radioon. Ennen kuin markkinoilla on valmis tuote, on sen takana valtaisa määrä työtä. Erilaisia dokumentteja on pitänyt tuottaa ja sopimuksia tehdä. Esimerkiksi vaatimusmäärittelyt on oltava selvät, jotta tiedetään mitä tuotteelta halutaan. Tätä ennen on kuitenkin pitänyt ymmärtää miten SDHtoimii ja miten otsikkotavuja käsitellään. Myös erilaiset piirivalinnat aiheuttavat miettimistä, sillä markkinoilla on runsaasti valmiita piirejä SDH signaalinkäsittelyyn. Varma tiedonsiirto on tärkeää puhelinoperaattorille ja siksi joudutaan miettimään varmennuksia ja niiden toteuttamista. Myös synkronointi on tärkeä osa SDH järjestelmää ja sen toteuttaminen hyvin on tärkeää. Hälytykset on otettava huomioon ja mietittävä, miten niiden käsittely saadaan hoidettua järkevästi, ilman että mikään järjestelmän osa ruuhkautuu kohtuuttomasti. Tässä Diplomityössä on tutustuttu SDH-järjestelmään, otsikkotavujen käsittelyyn ja vaatimusmäärittelyihin.

Using digital RNA counting and flow cytometry to compare mRNA with protein expression in acute leukemias.

BACKGROUND: The diagnosis of malignant hematologic diseases has become increasingly complex during the last decade. It is based on the interpretation of results from different laboratory analyses, which range from microscopy to gene expression profiling. Recently, a method for the analysis of RNA phenotypes has been developed, the nCounter technology (Nanostring® Technologies), which allows for simultaneous quantification of hundreds of RNA molecules in biological samples. We evaluated this technique in a Swiss multi-center study on eighty-six samples from acute leukemia patients. METHODS: mRNA and protein profiles were established for normal peripheral blood and bone marrow samples. Signal intensities of the various tested antigens with surface expression were similar to those found in previously performed Affymetrix microarray analyses. Acute leukemia samples were analyzed for a set of twenty-two validated antigens and the Pearson Correlation Coefficient for nCounter and flow cytometry results was calculated. RESULTS: Highly significant values between 0.40 and 0.97 were found for the twenty-two antigens tested. A second correlation analysis performed on a per sample basis resulted in concordant results between flow cytometry and nCounter in 44-100% of the antigens tested (mean = 76%), depending on the number of blasts present in a sample, the homogeneity of the blast population, and the type of leukemia (AML or ALL). CONCLUSIONS: The nCounter technology allows for fast and easy depiction of a mRNA profile from hematologic samples. This technology has the potential to become a valuable tool for the diagnosis of acute leukemias, in addition to multi-color flow cytometry.

FPGA-Based Control Design for Power Electronic Applications

Tehoelektoniikkalaitteella tarkoitetaan ohjaus- ja säätöjärjestelmää, jolla sähköä muokataan saatavilla olevasta muodosta haluttuun uuteen muotoon ja samalla hallitaan sähköisen tehon virtausta lähteestä käyttökohteeseen. Tämä siis eroaa signaalielektroniikasta, jossa sähköllä tyypillisesti siirretään tietoa hyödyntäen eri tiloja. Tehoelektroniikkalaitteita vertailtaessa katsotaan yleensä niiden luotettavuutta, kokoa, tehokkuutta, säätötarkkuutta ja tietysti hintaa. Tyypillisiä tehoelektroniikkalaitteita ovat taajuudenmuuttajat, UPS (Uninterruptible Power Supply) -laitteet, hitsauskoneet, induktiokuumentimet sekä erilaiset teholähteet. Perinteisesti näiden laitteiden ohjaus toteutetaan käyttäen mikroprosessoreja, ASIC- (Application Specific Integrated Circuit) tai IC (Intergrated Circuit) -piirejä sekä analogisia säätimiä. Tässä tutkimuksessa on analysoitu FPGA (Field Programmable Gate Array) -piirien soveltuvuutta tehoelektroniikan ohjaukseen. FPGA-piirien rakenne muodostuu erilaisista loogisista elementeistä ja niiden välisistä yhdysjohdoista.Loogiset elementit ovat porttipiirejä ja kiikkuja. Yhdysjohdot ja loogiset elementit ovat piirissä kiinteitä eikä koostumusta tai lukumäärää voi jälkikäteen muuttaa. Ohjelmoitavuus syntyy elementtien välisistä liitännöistä. Piirissä on lukuisia, jopa miljoonia kytkimiä, joiden asento voidaan asettaa. Siten piirin peruselementeistä voidaan muodostaa lukematon määrä erilaisia toiminnallisia kokonaisuuksia. FPGA-piirejä on pitkään käytetty kommunikointialan tuotteissa ja siksi niiden kehitys on viime vuosina ollut nopeaa. Samalla hinnat ovat pudonneet. Tästä johtuen FPGA-piiristä on tullut kiinnostava vaihtoehto myös tehoelektroniikkalaitteiden ohjaukseen. Väitöstyössä FPGA-piirien käytön soveltuvuutta on tutkittu käyttäen kahta vaativaa ja erilaista käytännön tehoelektroniikkalaitetta: taajuudenmuuttajaa ja hitsauskonetta. Molempiin testikohteisiin rakennettiin alan suomalaisten teollisuusyritysten kanssa soveltuvat prototyypit,joiden ohjauselektroniikka muutettiin FPGA-pohjaiseksi. Lisäksi kehitettiin tätä uutta tekniikkaa hyödyntävät uudentyyppiset ohjausmenetelmät. Prototyyppien toimivuutta verrattiin vastaaviin perinteisillä menetelmillä ohjattuihin kaupallisiin tuotteisiin ja havaittiin FPGA-piirien mahdollistaman rinnakkaisen laskennantuomat edut molempien tehoelektroniikkalaitteiden toimivuudessa. Työssä on myösesitetty uusia menetelmiä ja työkaluja FPGA-pohjaisen säätöjärjestelmän kehitykseen ja testaukseen. Esitetyillä menetelmillä tuotteiden kehitys saadaan mahdollisimman nopeaksi ja tehokkaaksi. Lisäksi työssä on kehitetty FPGA:n sisäinen ohjaus- ja kommunikointiväylärakenne, joka palvelee tehoelektroniikkalaitteiden ohjaussovelluksia. Uusi kommunikointirakenne edistää lisäksi jo tehtyjen osajärjestelmien uudelleen käytettävyyttä tulevissa sovelluksissa ja tuotesukupolvissa.

Sulautetun moniprosessorijärjestelmän suunnittelu sähkömoottorien ohjaus- ja valvontatarpeisiin

Universal Converter (UNICON) –projektin osana suunniteltiin sähkömoottorikäyttöjen ohjaukseen ja mittaukseen soveltuva digitaaliseen signaaliprosessoriin (DSP) pohjautuva sulautettu järjestelmä. Riittävän laskentatehon varmistamiseksi päädyttiin käyttämään moniprosessorijärjestelmää. Prosessorijärjestelmässä käytettävää DSP-piiriä valittaessa valintaperusteina olivat piirien tarjoama prosessointiteho ja moniprosessorituki. Analog Devices:n SHARC-sarjan DSP-piirit täyttivät parhaiten asetetut vaatimukset: Ne tarjoavat tehokkaan käskykannan lisäksi suuren sisäisen muistin ja sisäänrakennetun moniprosessorituen. Järjestelmän mittalaiteluonteisuudesta johtuen keskeinen suunnitteluparametri oli luoda nopeat tiedonsiirtoyhteydet mittausantureilta DSP-järjestelmään. Tämä toteutettiin käyttäen ohjelmointavia FPGA-logiikkapiirejä digitaalimuotoisen mittausdatan vastaanotossa ja esikäsittelyssä. Tiedonsiirtoyhteys PC-tietokoneelle toteutettiin käyttäen erityistä liityntäkorttia DSP-järjestelmän ja PC-tietokoneen välillä. Liityntäkortin päätehtävänä on puskuroida siirrettävä data. Järjestelyllä estetään PC-tietokoneen vaikutus DSP-järjestelmän toimintaan, jotta kyetään takaamaan järjestelmän reaaliaikainen toiminta kaikissa olosuhteissa.

Review of quantitative phase-digital holographic microscopy: promising novel imaging technique to resolve neuronal network activity and identify cellular biomarkers of psychiatric disorders.

Quantitative phase microscopy (QPM) has recently emerged as a new powerful quantitative imaging technique well suited to noninvasively explore a transparent specimen with a nanometric axial sensitivity. In this review, we expose the recent developments of quantitative phase-digital holographic microscopy (QP-DHM). Quantitative phase-digital holographic microscopy (QP-DHM) represents an important and efficient quantitative phase method to explore cell structure and dynamics. In a second part, the most relevant QPM applications in the field of cell biology are summarized. A particular emphasis is placed on the original biological information, which can be derived from the quantitative phase signal. In a third part, recent applications obtained, with QP-DHM in the field of cellular neuroscience, namely the possibility to optically resolve neuronal network activity and spine dynamics, are presented. Furthermore, potential applications of QPM related to psychiatry through the identification of new and original cell biomarkers that, when combined with a range of other biomarkers, could significantly contribute to the determination of high risk developmental trajectories for psychiatric disorders, are discussed.