Kulttuuriteon ja flopin välimaastossa

Kirjallisuusarvostelu

Contribution of matrix vesicles and alkaline phosphatase to ectopic bone formation

Endochondral calcification involves the participation of matrix vesicles (MVs), but it remains unclear whether calcification ectopically induced by implants of demineralized bone matrix also proceeds via MVs. Ectopic bone formation was induced by implanting rat demineralized diaphyseal bone matrix into the dorsal subcutaneous tissue of Wistar rats and was examined histologically and biochemically. Budding of MVs from chondrocytes was observed to serve as nucleation sites for mineralization during induced ectopic osteogenesis, presenting a diameter with Gaussian distribution with a median of 306 ± 103 nm. While the role of tissue-nonspecific alkaline phosphatase (TNAP) during mineralization involves hydrolysis of inorganic pyrophosphate (PPi), it is unclear how the microenvironment of MV may affect the ability of TNAP to hydrolyze the variety of substrates present at sites of mineralization. We show that the implants contain high levels of TNAP capable of hydrolyzing p-nitrophenylphosphate (pNPP), ATP and PPi. The catalytic properties of glycosyl phosphatidylinositol-anchored, polidocanol-solubilized and phosphatidylinositol-specific phospholipase C-released TNAP were compared using pNPP, ATP and PPi as substrates. While the enzymatic efficiency (k cat/Km) remained comparable between polidocanol-solubilized and membrane-bound TNAP for all three substrates, the k cat/Km for the phosphatidylinositol-specific phospholipase C-solubilized enzyme increased approximately 108-, 56-, and 556-fold for pNPP, ATP and PPi, respectively, compared to the membrane-bound enzyme. Our data are consistent with the involvement of MVs during ectopic calcification and also suggest that the location of TNAP on the membrane of MVs may play a role in determining substrate selectivity in this micro-compartment.

Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 µg) or Dextran (200 µg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (µg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7%). IPC inhibited VE (38.8%) and VP (54%) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3%; NM: 64%). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants.

Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

Whole-body vibration decreases the proliferativeb response of TCD4+ cells in elderly individuals with knee osteoarthritis

The aim of this study was to investigate the effect of adding whole-body vibration (WBV; frequency = 35 to 40 Hz; amplitude = 4 mm) to squat training on the T-cell proliferative response of elderly patients with osteoarthritis (OA) of the knee. This study was a randomized controlled trial in which the selected variables were assessed before and after 12 weeks of training. Twenty-six subjects (72 ± 5 years of age) were divided into three groups: 1) squat training with WBV (WBV, N = 8); 2) squat training without WBV (N = 10), and 3) a control group (N = 8). Women who were ≥60 years of age and had been diagnosed with OA in at least one knee were eligible. The intervention consisted of 12 uninterrupted weeks of squatting exercise training performed 3 times/week. Peripheral blood mononuclear cells were obtained from peripheral blood collected before and after training. The proliferation of TCD4+ and TCD8+ cells was evaluated by flow cytometry measuring the carboxyfluorescein succinimidyl ester fluorescence decay before and after the intervention (∆). The proliferative response of TCD4+ cells (P = 0.02, effect size = 1.0) showed a significant decrease (23%) in the WBV group compared to the control group, while there was no difference between groups regarding the proliferative response of TCD8+ cells (P = 0.12, effect size = 2.23). The data suggest that the addition of WBV to squat exercise training might modulate T-cell-mediated immunity, minimizing or slowing disease progression in elderly patients with OA of the knee.

Chronic granulomatous disease: why an inflammatory disease?

Chronic granulomatous disease is a primary immunodeficiency caused by mutations in the genes encoding subunits of the phagocytic NADPH oxidase system. Patients can present with severe, recurrent infections and noninfectious conditions. Among the latter, inflammatory manifestations are predominant, especially granulomas and colitis. In this article, we systematically review the possible mechanisms of hyperinflammation in this rare primary immunodeficiency condition and their correlations with clinical aspects.

Comparison of Model-Based Flow Rate Estimation Methods in Frequency-Converter-Driven Pumps and Fans

Fluid handling systems such as pump and fan systems are found to have a significant potential for energy efficiency improvements. To deliver the energy saving potential, there is a need for easily implementable methods to monitor the system output. This is because information is needed to identify inefficient operation of the fluid handling system and to control the output of the pumping system according to process needs. Model-based pump or fan monitoring methods implemented in variable speed drives have proven to be able to give information on the system output without additional metering; however, the current model-based methods may not be usable or sufficiently accurate in the whole operation range of the fluid handling device. To apply model-based system monitoring in a wider selection of systems and to improve the accuracy of the monitoring, this paper proposes a new method for pump and fan output monitoring with variable-speed drives. The method uses a combination of already known operating point estimation methods. Laboratory measurements are used to verify the benefits and applicability of the improved estimation method, and the new method is compared with five previously introduced model-based estimation methods. According to the laboratory measurements, the new estimation method is the most accurate and reliable of the model-based estimation methods.

Alhaisen volatiliteetin sekä korkean idiosynkraattisen riskin anomaliat Suomen osakemarkkinoilla institutionaalisen sijoittajan näkökulmasta

Alhaisen volatiliteetin anomalian mukaan sijoittajan on mahdollista saada korkeaa tuottoa alhaisella riskillä, mikä on sijoitusstrategina mielenkiintoinen, koska modernin rahoitusteorian mukaan korkeat tuotot saavutetaan vain riskiä kasvattamalla. Tässä tutkielmassa selvitettiin alhaisen volatiliteetin ja korkean idiosynkraattisen riskin anomalioiden olemassaoloa Suomen osakemarkkinoilla sekä institutionaalisen sijoittajan mahdollisuuksia hyödyntää tutkittuja anomalioita. Tutkimusaineisto large cap -osakkeilla vuosilta 2000-2013 osoittaa, että sijoittamalla alhaisen volatiliteetin osakkeisiin sijoittaja on pystynyt voittamaan absoluuttisella tuotolla mitattuna OMXH CAP-indeksin, muttei saavuttamaan riskikorjattuja ylituottoja. Alhaisen volatiliteetin osakkeiden suoriutumista on selitetty useilla tekijöillä kuten sijoittajien irrationaalisella käyttäytymisellä näiden suosiessa korkean volatiliteetin osakkeita painaen alas samalla näiden tuottopotentiaalia. Toiseksi, alhaisen volatiliteetin yrityksillä on vahvat fundamentit, joiden myötä liikevoitto sekä tulos pysyvät vahvoina, joka näkyy puolestaan hyvinä osaketuottoina. Lisäksi, institutionaaliselle sijoittajalle muodostuu esteitä sijoittaa vain alhaisen volatiliteetin osakkeisiin, mikä osaltaan estää anomalian pois pyyhkiytymisen. Idiosynkraattisen riskin anomaliaa ei voitu todentaa käytettäessä FF3-mallin residuaaleja. Anomaliaa tutkittiin historiallista sekä EGARCH-mallilla ennustettua idiosynkraattista riskiä käyttäen.

Value added KPI service delivery with quality function deployment: Multiple case study in asset & real estate management

The aim of this study is to investigate value added service concept for an asset and real estate management case company. The initial purpose was to recognize the most value adding key performance indicators (KPIs) information delivered for its customers, real estate investors with value added service. The multiple case study strategy included two focus group interviews with five case interviews in total. Additionally, quality function deployment (QFD) was used in order to form up the service process. The study starts with introduction and methodology explaining the demand for the thesis study. The subsequent chapter presents the theoretical background on real estate management KPIs in four main points of views and quality function deployment from the service development point of view. The chapter also defines research gap for the case study. According to the case study interviews, the most favored KPIs to deliver for the clients are income maturity of lease agreements and leasing activity. These KPIs and quality characteristics are translated into the QFD. In total, the service QFD explains the service planning, process control, and action plan phases.

Sodan sumu ja kitka sodankäynnin yleisissä periaatteissa

Tämän Pro Gradu -tutkielman tarkoitus oli selvittää, mitä sodan sumu ja kitka käsitteinä tarkoittavat. Lisäksi haluttiin selvittää, miten sodan sumua ja kitkaa voidaan vähentää yleisten taktisten periaatteiden avulla. Tutkimuksen tarkoituksena ei ole antaa yleispätevää määritelmää sodan sumusta ja kitkasta, vaan antaa käytettyjen lähteiden perusteella esimerkkejä sodan sumun ja kitkan määritelmistä. Tämä tutkimus on luonteeltaan laadullinen tutkimus. Tutkimus otteena käytetään hermeneuttista ajattelua. Tutkimuskeinona käytetään asiakirja tutkimusta ja sisällönanalyysiä, perehtymällä erilaisiin kirjallisiin lähteisiin ja analysoimalla sekä tekemällä johtopäätöksiä niistä. Sodan sumun ja kitkan määrittelemiseen käytetään käsiteanalyysiä. Tutkimuksen pääkysymys on: Mitä sodan sumu ja kitka tarkoittavat ja miten niitä voidaan vähentää sodankäynnin yleisten periaatteiden avulla? Alakysymyk-set ovat: 1) Miten sodan sumu ja kitka määritellään Clausewitzin Sodankäynnistä teoksen mukaan? 2) Miten sodan sumu ja kitka määritellään muissa lähteissä? 3) Miten sodan sumua ja kitkaa voidaan vähentää sodankäynnin yleisten periaatteiden avulla? Sodan sumun ja kitkan määrittelyssä käytettiin eri lähteistä saatavia määritelmiä. Näistä määritelmistä koottiin yhteen keskeiset asiat ja luotiin viisi erilaista määritelmää sodan sumusta ja kitkasta. Näistä Clausewitzin ja Barry Wattsin mallit pohjautuvat suoraan heidän omiin teoksiinsa, koska he ovat analysoineet käsitteitä syvällisesti. Kolme muuta mallia muodostuivat useiden lähteiden synteesistä. Sodan yleisten periaatteiden osalta käsittelyyn otettiin kaksikymmentäkolme periaatetta. Näiden avulla tarkasteltiin Clausewitzin sodan yleisen kitkan vähentämistä. Tutkimus osoitti Clausewitzin sodan yleisen kitkan olevan käyttökelpoinen käsite nykyaikana. Suuria eroja ei ollut löydettävissä sodan sumun ja kitkan määritelmien väliltä. Sodankäynnin yleisten periaatteiden avulla voidaan vähentää sodan yleistä kitkaa, erityisesti fyysisten ja henkisten rasitusten sekä epävarmuuden osalta.