Detection of patients with functional dyspepsia using wavelet transform applied to their electrogastrogram

The aim of the present study was to develop a classifier able to discriminate between healthy controls and dyspeptic patients by analysis of their electrogastrograms. Fifty-six electrogastrograms were analyzed, corresponding to 42 dyspeptic patients and 14 healthy controls. The original signals were subsampled, filtered and divided into the pre-, post-, and prandial stages. A time-frequency transformation based on wavelets was used to extract the signal characteristics, and a special selection procedure based on correlation was used to reduce their number. The analysis was carried out by evaluating different neural network structures to classify the wavelet coefficients into two groups (healthy subjects and dyspeptic patients). The optimization process of the classifier led to a linear model. A dimension reduction that resulted in only 25% of uncorrelated electrogastrogram characteristics gave 24 inputs for the classifier. The prandial stage gave the most significant results. Under these conditions, the classifier achieved 78.6% sensitivity, 92.9% specificity, and an error of 17.9 ± 6% (with a 95% confidence level). These data show that it is possible to establish significant differences between patients and normal controls when time-frequency characteristics are extracted from an electrogastrogram, with an adequate component reduction, outperforming the results obtained with classical Fourier analysis. These findings can contribute to increasing our understanding of the pathophysiological mechanisms involved in functional dyspepsia and perhaps to improving the pharmacological treatment of functional dyspeptic patients.

MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

Transduction motif analysis of gastric cancer based on a human signaling network

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR,MAPK14, BCL2L1, KRT18,PTPN6, CASP3, TGFBR2,AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Maintenance of the corneal epithelium is carried out by germinative cells of its basal stratum and not by presumed stem cells of the limbus

The purpose of this investigation was to analyze the proliferative behavior of rabbit corneal epithelium and establish if any particular region was preferentially involved in epithelial maintenance. [3H]-thymidine was injected intravitreally into both normal eyes and eyes with partially scraped corneal epithelium. Semithin sections of the anterior segment were evaluated by quantitative autoradiography. Segments with active replication (on) and those with no cell division (off) were intermingled in all regions of the tissue, suggesting that the renewal of the epithelial surface of the cornea followed an on/off alternating pattern. In the limbus, heavy labeling of the outermost layers was observed, coupled with a few or no labeled nuclei in the basal stratum. This suggests that this region is a site of rapid cell differentiation and does not contain many slow-cycling cells. The conspicuous and protracted labeling of the basal layer of the corneal epithelium suggests that its cells undergo repeated cycles of replication before being sent to the suprabasal strata. This replication model is prone to generate label-retaining cells. Thus, if these are adult stem cells, one must conclude that they reside in the corneal basal layer and not the limbal basal layer. One may also infer that the basal cells of the cornea and not of the limbus are the ones with the main burden of renewing the corneal epithelium. No particular role in this process could be assigned to the cells of the basal layer of the limbal epithelium.

Propofol inhibits burn injury-induced hyperpermeability through an apoptotic signal pathway in microvascular endothelial cells

Recent studies have revealed that an intrinsic apoptotic signaling cascade is involved in vascular hyperpermeability and endothelial barrier dysfunction. Propofol (2,6-diisopropylphenol) has also been reported to inhibit apoptotic signaling by regulating mitochondrial permeability transition pore (mPTP) opening and caspase-3 activation. Here, we investigated whether propofol could alleviate burn serum-induced endothelial hyperpermeability through the inhibition of the intrinsic apoptotic signaling cascade. Rat lung microvascular endothelial cells (RLMVECs) were pretreated with propofol at various concentrations, followed by stimulation with burn serum, obtained from burn-injury rats. Monolayer permeability was determined by transendothelial electrical resistance. Mitochondrial release of cytochrome C was measured by ELISA. Bax and Bcl-2 expression and mitochondrial release of second mitochondrial-derived activator of caspases (smac) were detected by Western blotting. Caspase-3 activity was assessed by fluorometric assay; mitochondrial membrane potential (Δψm) was determined with JC-1 (a potential-sensitive fluorescent dye). Intracellular ATP content was assayed using a commercial kit, and reactive oxygen species (ROS) were measured by dichlorodihydrofluorescein diacetate (DCFH-DA). Burn serum significantly increased monolayer permeability (P<0.05), and this effect could be inhibited by propofol (P<0.05). Compared with a sham treatment group, intrinsic apoptotic signaling activation - indicated by Bax overexpression, Bcl-2 downregulation, Δψm reduction, decreased intracellular ATP level, increased cytosolic cytochrome C and smac, and caspase-3 activation - was observed in the vehicle group. Propofol not only attenuated these alterations (P<0.05 for all), but also significantly decreased burn-induced ROS production (P<0.05). Propofol attenuated burn-induced RLMVEC monolayer hyperpermeability by regulating the intrinsic apoptotic signaling pathway.

Evaluation of 99mTc-HYNIC-βAla-Bombesin(7-14) as an agent for pancreas tumor detection in mice

Pancreatic adenocarcinoma is important in oncology because of its high mortality rate. Deaths may be avoided if an early diagnosis could be achieved. Several types of tumors overexpress gastrin-releasing peptide receptors (GRPr), including pancreatic cancer cells. Thus, a radiolabeled peptide derivative of gastrin-releasing peptide (GRP) may be useful as a specific imaging probe. The purpose of the present study was to evaluate the feasibility of using99mTc-HYNIC-βAla-Bombesin(7-14)as an imaging probe for Capan-1 pancreatic adenocarcinoma. Xenographic pancreatic tumor was developed in nude mice and characterized by histopathological analysis. Biodistribution studies and scintigraphic images were carried out in tumor-bearing nude mice. The two methods showed higher uptake by pancreatic tumor when compared to muscle (used as control), and the tumor-to-muscle ratio indicated that99mTc-HYNIC-βAla-Bombesin(7-14)uptake was four-fold higher in tumor cells than in other tissues. Scintigraphic images also showed a clear signal at the tumor site. The present data indicate that99mTc-HYNIC-βAla-Bombesin(7-14)may be useful for the detection of pancreatic adenocarcinoma.

Benchmark of routing protocols regarding green considerations

In Mobile Ad-hoc Networks (MANET) the participating nodes have several roles such as sender, receiver and router. Hence there is a lot of energy consumed by the nodes for the normal working of the network since each node has many different roles. Also in MANET the nodes keep moving constantly and this in turn consumes a lot of energy. Since battery capacity of these nodes is limited it fails to fulfil the high demand of energy. The scarcity of energy makes the energy conservation in mobile ad-hoc networks an important concern. There is several research carried out on the energy consumption of mobile ad-hoc networks these days. Some of this research suggests sleep mode, transmission power control, load balancing etc. In this thesis, we are comparing various proposed energy efficient models for some of the ad-hoc protocols. We compare different energy efficient models for Optimised Linked State Algorithm (OLSR) and Ad-hoc On Demand Distance Vector (AODV). The routing protocols are compared for different parameters such as average remaining energy, number of nodes alive, payload data received and performance with different mobility speed. The simulation results helps in benchmarking the various energy efficient routing models for OLSR and AODV protocols. The benchmarking of the routing protocols can be based on many factors but this thesis concentrates on benchmarking the MANET routing protocols mainly based on the energy efficiency and increased network lifetime.

"Rakkaat poikaiset!". Simon ja Wilhelmina Janssonin perhekirjeet egodokumentteina (1858-1887)

Kustavilainen talonpoikaislaivuri Simon Jansson ja hänen vaimonsa Wilhelmina o.s. Widbom kävivät kolmenkymmenen vuoden ajan kirjeenvaihtoa kouluun ja yliopistoon lähetettyjen poikiensa Waldemar, Evald ja Emil Jahnssonin kanssa. Lähes 150 suomen- ja ruotsinkielistä kirjettä on säilynyt Suomalaisen Kirjallisuuden Seuran kirjallisuusarkistossa ja Turun maakunta-arkistossa. Lähiluvun kautta kirjeistä muodostuu yksityiskohtainen lähde saaristolaisperheen elämäntapaan, arkeen ja työhön sekä saaristoyhteisön sosiaalisen kanssakäymisen muotoihin. Ne kertovat myös ensimmäisen polven oppisivistyneistön synnystä ja niistä resursseista, joita hyödyntäen koulua käymättömät vanhemmat saattoivat kouluttaa lapsensa. Tutkimus liittyy suomalaisten 1800-luvun itseoppineiden kirjoittajien tekstien ja maaseudun kirjallistumisen tutkimukseen. Keskeinen käsite on egodokumentti, jolla tarkoitetaan kirjeitä ja muita tekstejä, joissa kirjoittaja kertoo itse omasta elämästään. Hollantilainen ja ranskalainen egodokumenttien tutkimus on pyrkinyt haastamaan uudenlaisten lähdeaineistojen kautta käsityksiä menneisyydestä sekä nostamaan esiin muun muassa yksilöllisen kokemuksen, kirjoittamisen kulttuurin ja dokumenttien materiaalisuuden. Janssonin perheen kirjeet poikkeavat monin tavoin 1800-luvun säätyläisten kirjeistä. Niiden funktio oli hyvin käytännöllinen ja arkinen, mutta ne olivat myös vanhempien keino tukea perheen yhteistä sosiaalisen nousun projektia. Kustavia koskevan tiheän uutisoinnin kautta ne pyrkivät pitämään kaupunkilaistuvat pojat osana vanhaa yhteisöään. Perheen isä vastasi suurelta osin kirjeenvaihdosta ja siihen liittyvästä huolenpidosta, mikä kertoo sukupuolittuneen työnjaon joustavuudesta saaristossa. Tutkimus osoittaa, ettei isän ammattiin perustuva yliopisto-opiskelijoiden tutkimus ole tavoittanut sitä naisten kautta välittyvää sosiaalista ja kulttuurista pääomaa, joka saattoi olla ratkaiseva perheiden kouluttaessa lapsiaan. Kirjeiden analyysi tarkentaa kuvaa perinteisen talonpoikaispurjehduksen sopeutumisesta vuosisadan loppupuolen uudistuksiin.

Spectral characteristics of bacteriorhodopsin water solution

The object of the study is bacteriorhodopsin. This light-sensitive protein have been selected as perspective substance for optical and optoelectronic applications. Bacteriorhodopsin carries out pumping protons through the cell membrane. Biomolecule converts light into an electric signal when sandwiched between electrodes. These properties were utilized in this research to implement photosensors on the basis of BR layers. These properties were utilized in this research to the bR water solution. According to the absorption spectra and using Kramers – Kronig relation the extinction coefficient has been calculated, as well as the related change of the refractive index value.

The role of keratin intermediate filaments in the colon epithelial cells

Keratins (K) are cytoskeletal proteins mainly expressed in the epithelium and constitute the largest subgroup of intermediate filaments (IFs). Simple epithelial keratins (SEKs) K7-K8 and K18-K20 are the major IF elements in the colon. SEK mutations are known to cause around 30 human diseases, mainly affecting liver and skin. However, so far no strong associations between K8 mutations and the development of human colitis have been found. The keratin contribution to colonic health comes from the K8 knock-out (K8-/-) mouse model, which develops an early chronic inflammation and hyperproliferation in the colon. The aim of this thesis was to investigate how keratins contribute to intestinal health and disease mainly by the experimental analysis using the K8-/- mouse colon and cell culture models. The work described here is divided into three studies. The first study revealed involvement of keratins in Notch1 signaling, which is the master regulator of cell fate in the colon. Immunoprecipitation and immunostaining, both in vitro and in vivo showed that K8 binds and co-localizes with Notch1. Interestingly, overexpression of keratins enhanced Notch1 levels and stabilized Notch intracellular domain (NICD), leading to higher activity of Notch signaling. The dramatic decrease in Notch activity in the K8-/- colon resulted in a differentiation shift towards goblet and enteroendocrine cells. The second study focused on the involvement of keratins in colitis-associated cancer (CAC). Although, the K8-/- inflamed colon did not develop colorectal cancer (CRC) spontaneously, it was dramatically more susceptible to induced CRC in two CRC models: azoxymethane (AOM) and multiple intestinal neoplasia (ApcMin/+). To understand how the loss of K8 contributes to CAC, the epithelial inflammasome signaling pathway was analyzed. The released component of active inflammasome, cleaved caspase-1 and its downstream protein, interleukin (IL)-18, were significantly increased in K8-/- and K8-/-ApcMin/+ colons. The inflammasome pathway has recently been suggested to control the levels of IL-22 binding protein (IL-22BP), which is a negative regulator of IL-22 activity. Interestingly, the activated inflammasome correlated with an upregulation of IL-22 and a complete loss of IL-22BP in the K8-null colons. The activation of IL-22 was confirmed by increased levels of downstream signaling, which is phosphorylated signal transducer and activator of transcription 3 (P-STAT3), a transcription factor promoting proliferation and tissue regeneration in the colon. The objective of the third study, was to examine the role of keratins in colon energy metabolism. A proteomic analysis identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) as the major ownregulated protein in the K8-/- colonocytes. HMGCS2 is the rate-limiting enzyme in ketogenesis, where energy from bacterially produced short chain fatty acids (SCFAs), mainly butyrate, is converted into ketone bodies in colonic epithelium. Lower levels and activity of HMGCS2 in the K8-/- colon resulted in a blunted ketogenesis. The studies upstream from HMGCS2, identified decreased levels of the SCFA-transporter monocarboxylate transporter 1 (MCT1), which led to increased SCFA content in the stool suggesting impaired butyrate transport through the colonic epithelium. Taken together, the results of the herein thesis indicate that keratins are essential regulators of colon homeostasis, in particular epithelial differentiation, tumorigenesis and energy metabolism.

Tuotesuunnittelu direktiiviperustaisesti

Onnistuneen tuotekehitysprojektin läpivieminen vaatii huolellisen alkusuunnittelun ennen varsinaista tuotteen kehityksen aloitusta. Projektin läpiviemiseksi esitetään usein malleja joissa tuotekehitysprojektissa edetään yksi vaihe kerrallaan ja siirrytään seuraavaan vasta, kun edellinen on valmis. Tämän perinteisen mallin rinnalle on tullut DFMA-suunnittelu, jossa murretaan kommunikaatiomuuri suunnittelun ja valmistuksen väliltä ja useita vaiheita tehdään samanaikaisesta. Näin saadaan valmistus- ja kokoonpanoystävällisiä tuotteita, joilla tuotteesta saatava kate voidaan maksimoida samalla kun tuotteen laatua saadaan parannettua. Teknisen kehityksen lisäksi on tuotekehitysprosessissa erottamattomana osana direktiivien asettamien vaatimusten huomioon ottaminen. Jo lähes kaikissa tuotteissa on oltava CE-merkintä. CE-merkinnällä tuotteen valmistaja ottaa täyden vastuun siitä, että tuote täyttää sitä koskevien direktiivien asettamat vaatimukset vaatimustenmukaisuudesta. Direktiivien asettamat vaatimukset on hyvä tiedostaa jo tuotteen suunnittelun alkuvaiheista lähtien, jotta nämä osataan ottaa heti huomioon ja jälkikäteen tehtäviltä muutoksilta vältytään. Teknisten ratkaisujen lisäksi tuotteen dokumentoinnilla on suuri rooli vaatimustenmukaisuuden täyttämisessä. Tuotteesta tulee koota tekninen tiedosto, joka sisältää kaikki tarpeelliset dokumentit, joilla tuotteen vaatimustenmukaisuus voidaan todeta. Teknisen tiedoston vaatimukset on hyvä tiedostaa jo suunnittelun alusta lähtien, jotta tarvittavat dokumentit osataan kerätä projektin aikana tekniseen tiedostoon. Tässä työssä kehitettiin peltier-jäähdytin, jollaiselle asiakkailta saadun palautteen perusteella oli markkinoilla tarve. Jäähdyttimen suunnittelussa käytettiin DFMA:n keinoja yksinkertaistamaan kokoonpanoa. Jäähdyttimelle tehtiin vaatimustenmukaisuustarkastelu, missä tarkasteltiin peltier-jäähdytintä koskevien direktiivien asettamia vaatimuksia ja mitä asioita näiden vaatimusten täyttämiseksi tuli huomioida.