Early neonatal echocardiographic findings in an experimental rabbit model of congenital diaphragmatic hernia

This study aimed to demonstrate that congenital diaphragmatic hernia (CDH) results in vascular abnormalities that are directly associated with the severity of pulmonary hypoplasia and hypertension. These events increase right ventricle (RV) afterload and may adversely affect disease management and patient survival. Our objective was to investigate cardiac function, specifically right ventricular changes, immediately after birth and relate them to myocardial histological findings in a CDH model. Pregnant New Zealand rabbits underwent the surgical procedure at 25 days of gestation (n=14). CDH was created in one fetus per horn (n=16), and the other fetuses were used as controls (n=20). At term (30 days), fetuses were removed, immediately dried and weighed before undergoing four-parameter echocardiography. The lungs and the heart were removed, weighed, and histologically analyzed. CDH animals had smaller total lung weight (P<0.005), left lung weight (P<0.005), and lung-to-body ratio (P<0.005). Echocardiography revealed a smaller left-to-right ventricle ratio (LV/RV, P<0.005) and larger diastolic right ventricle size (DRVS, P<0.007). Histologic analysis revealed a larger number of myocytes undergoing mitotic division (186 vs 132, P<0.05) in CDH hearts. Immediate RV dilation of CDH hearts is related to myocyte mitosis increase. This information may aid the design of future strategies to address pulmonary hypertension in CDH.

Exercise training prevents increased intraocular pressure and sympathetic vascular modulation in an experimental model of metabolic syndrome

The present study aimed to study the effects of exercise training (ET) performed by rats on a 10-week high-fructose diet on metabolic, hemodynamic, and autonomic changes, as well as intraocular pressure (IOP). Male Wistar rats receiving fructose overload in drinking water (100 g/L) were concomitantly trained on a treadmill for 10 weeks (FT group) or kept sedentary (F group), and a control group (C) was kept in normal laboratory conditions. The metabolic evaluation comprised the Lee index, glycemia, and insulin tolerance test (KITT). Arterial pressure (AP) was measured directly, and systolic AP variability was performed to determine peripheral autonomic modulation. ET attenuated impaired metabolic parameters, AP, IOP, and ocular perfusion pressure (OPP) induced by fructose overload (FT vs F). The increase in peripheral sympathetic modulation in F rats, demonstrated by systolic AP variance and low frequency (LF) band (F: 37±2, 6.6±0.3 vs C: 26±3, 3.6±0.5 mmHg2), was prevented by ET (FT: 29±3, 3.4±0.7 mmHg2). Positive correlations were found between the LF band and right IOP (r=0.57, P=0.01) and left IOP (r=0.64, P=0.003). Negative correlations were noted between KITT values and right IOP (r=-0.55, P=0.01) and left IOP (r=-0.62, P=0.005). ET in rats effectively prevented metabolic abnormalities and AP and IOP increases promoted by a high-fructose diet. In addition, ocular benefits triggered by exercise training were associated with peripheral autonomic improvement.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptorCTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.

Treatment with 1,25(OH)2D3induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma

Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3might be useful as a novel HDAC2 activator in the treatment of asthma.

Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Simulation model of wind turbine gearbox and lubrication system

As increasing efficiency of a wind turbine gearbox, more power can be transferred from rotor blades to generator and less power is used to cause wear and heating in the gearbox. By using a simulation model, behavior of the gearbox can be studied before creating expensive prototypes. The objective of the thesis is to model a wind turbine gearbox and its lubrication system to study power losses and heat transfer inside the gearbox and to study the simulation methods of the used software. Software used to create the simulation model is Siemens LMS Imagine.Lab AMESim, which can be used to create one-dimensional mechatronic system simulation models from different fields of engineering. When combining components from different libraries it is possible to create a simulation model, which includes mechanical, thermal and hydraulic models of the gearbox. Results for mechanical, thermal, and hydraulic simulations are presented in the thesis. Due to the large scale of the wind turbine gearbox and the amount of power transmitted, power loss calculations from AMESim software are inaccurate and power losses are modelled as constant efficiency for each gear mesh. Starting values for simulation in thermal and hydraulic simulations were chosen from test measurements and from empirical study as compact and complex design of gearbox prevents accurate test measurements. In further studies to increase the accuracy of the simulation model, components used for power loss calculations needs to be modified and values for unknown variables are needed to be solved through accurate test measurements.

Spectrally Tuned Lanthanide Photoluminescence for Point-of-Care Testing

Point-of-care (POC) –diagnostics is a field with rapidly growing market share. As these applications become more widely used, there is an increasing pressure to improve their performance to match the one of a central laboratory tests. Lanthanide luminescence has been widely utilized in diagnostics because of the numerous advantages gained by the utilization of time-resolved or anti-Stokes detection. So far the use of lanthanide labels in POC has been scarce due to limitations set by the instrumentation required for their detection and the shortcomings, e.g. low brightness, of these labels. Along with the advances in the research of lanthanide luminescence, and in the field of semiconductors, these materials are becoming a feasible alternative for the signal generation also in the future POC assays. The aim of this thesis was to explore ways of utilizing time-resolved detection or anti-Stokes detection in POC applications. The long-lived fluorescence for the time-resolved measurement can be produced with lanthanide chelates. The ultraviolet (UV) excitation required by these chelates is cumbersome to produce with POC compatible fluorescence readers. In this thesis the use of a novel light-harvesting ligand was studied. This molecule can be used to excite Eu(III)-ions at wavelengths extending up to visible part of the spectrum. An enhancement solution based on this ligand showed a good performance in a proof-of-concept -bioaffinity assay and produced a bright signal upon 365 nm excitation thanks to the high molar absorptivity of the chelate. These features are crucial when developing miniaturized readers for the time-resolved detection of fluorescence. Upconverting phosphors (UCPs) were studied as an internal light source in glucose-sensing dry chemistry test strips and ways of utilizing their various emission wavelengths and near-infrared excitation were explored. The use of nanosized NaYF :Yb3+,Tm3+-particles enabled the replacement of an external UV-light source with a NIR-laser and gave an additional degree of freedom in the optical setup of the detector instrument. The new method enabled a blood glucose measurement with results comparable to a current standard method of measuring reflectance. Microsized visible emitting UCPs were used in a similar manner, but with a broad absorbing indicator compound filtering the excitation and emission wavelengths of the UCP. This approach resulted in a novel way of benefitting from the non-linear relationship between the excitation power and emission intensity of the UCPs, and enabled the amplification of the signal response from the indicator dye.

Dynamic Competitor Analysis Model Of Welding Quality Management Software

Tämä diplomityö arvioi hitsauksen laadunhallintaohjelmistomarkkinoiden kilpailijoita. Kilpailukenttä on uusi ja ei ole tarkkaa tietoa siitä minkälaisia kilpailijoita on markkinoilla. Hitsauksen laadunhallintaohjelmisto auttaa yrityksiä takaamaan korkean laadun. Ohjelmisto takaa korkean laadun varmistamalla, että hitsaaja on pätevä, hän noudattaa hitsausohjeita ja annettuja parametreja. Sen lisäksi ohjelmisto kerää kaiken tiedon hitsausprosessista ja luo siitä vaadittavat dokumentit. Diplomityön teoriaosuus muodostuu kirjallisuuskatsauksesta ratkaisuliike-toimintaan, kilpailija-analyysin ja kilpailuvoimien teoriaan sekä hitsauksen laadunhallintaan. Työn empiriaosuus on laadullinen tutkimus, jossa tutkitaan kilpailevia hitsauksen laadunhallintaohjelmistoja ja haastatellaan ohjelmistojen käyttäjiä. Diplomityön tuloksena saadaan uusi kilpailija-analyysimalli hitsauksen laadunhallintaohjelmistoille. Mallin avulla voidaan arvostella ohjelmistot niiden tarjoamien primääri- ja sekundääriominaisuuksien perusteella. Toiseksi tässä diplomityössä analysoidaan nykyinen kilpailijatilanne hyödyntämällä juuri kehitettyä kilpailija-analyysimallia.

Biomarkkerit sepsiksen diagnostiikassa sekä Kvantitatiivisen prokalsitoniini-immunomäärityksen pystyttäminen ja optimointi point-of-care-ympäristöön

Termiä sepsis käytetään infektion aiheuttamasta yleisestä tulehdusreaktio-oireyhtymästä. Biokemiallinen merkkiaine eli biomarkkeri on aine, joka objektiivisesti mitattuna ja arvioituna toimii indikaattorina erottaen toisistaan normaalit biologiset prosessit ja patogeeniset prosessit. Lisäksi biomarkkeri saattaa osoittaa farmakologisen vasteen lääkehoidolle. Tutkielman kirjallisessa osassa on esitelty ja verrattu toisiinsa jo kliinisessä käytössä olevia sekä lupaavia, vielä tutkimusvaiheessa olevia, sepsiksen biomerkkiaineita. Lisäksi tutkielmassa on tarkasteltu sepsiksen todentamisen, tunnistamisen ja hoidon tulevaisuudennäkymiä. Prokalsitoniini (PCT) on eräs jo kliinisessä käytössä oleva sepsiksen biomerkkiaine. Tutkielman kokeellisessa osassa pystytettiin teho-osastoille suunnattu pikatesti PCT:n mittaamiseen aikaerotteista fluoresenssiteknologiaa hyödyntävälle AQT-järjestelmälle (DHR Finland Oy, Innotrac Diagnostics, Suomi). Järjestelmä mittaa 20–30 minuutissa biomerkkiainepitoisuuden. Tavoitteena oli löytää sopiva vasta-ainepari ja pystyttää kaksipuoleinen immunomääritys, jonka analyyttinen herkkyys on alle 0,02 ng/ml:ssa. Työssä tutkittiin biotinyloidun kokonaisen vasta-aineen ja paikkaspesifisesti biotinyloidun antigeenia sitovan fragmentin (engl. fragment antigen binding, Fab) toimivuutta sitojamolekyylinä. Lisäksi työssä verrattiin kahden eri leimamolekyylin, 9 hampaisen europiumkelaatin sekä Innotracissa kehitetyn tähtikelaatin, toimivuutta PCT-immunomäärityksessä. Vasta-aineiden mahdolliset ristireaktiot testattiin ja määritystä testattiin alustavasti eri näytematriiseissa. Työssä löydettiin 5 vasta-aineparia, joiden analyyttinen herkkyys oli alle 0,02 ng/ml:ssa. Aiemmin testattuja vasta-ainepareja parempi analyyttinen herkkyys johtui todennäköisesti yhden uuden leimavasta-aineen paremmasta affiniteetistä. Tähtikelaatilla leimatulla vasta-aineella analyyttinen herkkyys parani lähes viisinkertaisesti, kun sitä verrattiin 9-hampaisella euroopiumkelaatilla leimatun vasta-aineen määritykseen. Havaittiin myös, että Fab-fragmentilla mitattiin määrityksissä lähes kaksi kertaa suuremmat signaali-taustasuhteet, kun sitä verrattiin kokonaiseen vasta-aineeseen, tietyllä vasta-aineparilla. Tämä johtui luultavasti steeristen esteiden vähenemisestä. Näytematriisilla ei todettu olevan vaikutusta määritykseen, eikä ristireaktioita havaittu. Kehitetyn määrityksen suoriutumista verrattiin markkinoilla olevaan BRAHMS AG:n (Saksa) PCT-määritykseen käyttäen potilasnäytteitä. Korrelaatiokertoimet potilasnäytevertailuissa olivat 0,965–0,989 ja näytteiden mitatuissa pitoisuuksissa oli tasoero.

Model of Big Data Failure: Review of Information System Failure

In the new age of information technology, big data has grown to be the prominent phenomena. As information technology evolves, organizations have begun to adopt big data and apply it as a tool throughout their decision-making processes. Research on big data has grown in the past years however mainly from a technical stance and there is a void in business related cases. This thesis fills the gap in the research by addressing big data challenges and failure cases. The Technology-Organization-Environment framework was applied to carry out a literature review on trends in Business Intelligence and Knowledge management information system failures. A review of extant literature was carried out using a collection of leading information system journals. Academic papers and articles on big data, Business Intelligence, Decision Support Systems, and Knowledge Management systems were studied from both failure and success aspects in order to build a model for big data failure. I continue and delineate the contribution of the Information System failure literature as it is the principal dynamics behind technology-organization-environment framework. The gathered literature was then categorised and a failure model was developed from the identified critical failure points. The failure constructs were further categorized, defined, and tabulated into a contextual diagram. The developed model and table were designed to act as comprehensive starting point and as general guidance for academics, CIOs or other system stakeholders to facilitate decision-making in big data adoption process by measuring the effect of technological, organizational, and environmental variables with perceived benefits, dissatisfaction and discontinued use.

Non-offensive defence : a criteria model of military credibility

Finnish Defence Studies is published under the auspices of the War College, and the contributions reflect the fields of research and teaching of the College. Finnish Defence Studies will occasionally feature documentation on Finnish Security Policy. Views expressed are those of the authors and do not necessarily imply endorsement by the War College.

Model of Big Data Failure: Review of Information System Failure

In the new age of information technology, big data has grown to be the prominent phenomena. As information technology evolves, organizations have begun to adopt big data and apply it as a tool throughout their decision-making processes. Research on big data has grown in the past years however mainly from a technical stance and there is a void in business related cases. This thesis fills the gap in the research by addressing big data challenges and failure cases. The Technology-Organization-Environment framework was applied to carry out a literature review on trends in Business Intelligence and Knowledge management information system failures. A review of extant literature was carried out using a collection of leading information system journals. Academic papers and articles on big data, Business Intelligence, Decision Support Systems, and Knowledge Management systems were studied from both failure and success aspects in order to build a model for big data failure. I continue and delineate the contribution of the Information System failure literature as it is the principal dynamics behind technology-organization-environment framework. The gathered literature was then categorised and a failure model was developed from the identified critical failure points. The failure constructs were further categorized, defined, and tabulated into a contextual diagram. The developed model and table were designed to act as comprehensive starting point and as general guidance for academics, CIOs or other system stakeholders to facilitate decision-making in big data adoption process by measuring the effect of technological, organizational, and environmental variables with perceived benefits, dissatisfaction and discontinued use.