MHC/Peptide-Specific Interaction of the Humoral Immune System: A New Category of Antibodies.

Abs bind to unprocessed Ags, whereas cytotoxic CD8(+) T cells recognize peptides derived from endogenously processed Ags presented in the context of class I MHC complexes. We screened, by ELISA, human sera for Abs reacting specifically with the influenza matrix protein (IMP)-derived peptide58-66 displayed by HLA-A*0201 complexes. Among 653 healthy volunteers, blood donors, and women on delivery, high-titered HLA-A*0201/IMP58-66 complex-specific IgG Abs were detected in 11 females with a history of pregnancies and in 1 male, all HLA-A*0201(-). These Abs had the same specificity as HLA-A*0201/IMP58-66-specific cytotoxic T cells and bound neither to HLA-A*0201 nor the peptide alone. No such Abs were detected in HLA-A*0201(+) volunteers. These Abs were not cross-reactive to other self-MHC class I alleles displaying IMP58-66, but bound to MHC class I complexes of an HLA nonidentical offspring. HLA-A*0201/IMP58-66 Abs were also detected in the cord blood of newborns, indicating that HLA-A*0201/IMP58-66 Abs are produced in HLA-A*0201(-) mothers and enter the fetal blood system. That Abs can bind to peptides derived from endogenous Ags presented by MHC complexes opens new perspectives on interactions between the cellular and humoral immune system.

Study of Johnsons Glacier (Livingston Island, Antarctica) by means of shallow ice cores and their tephra and by analysis of 137Cs content

With the aim of monitoring the dynamics of the Livingston Island ice cap, the Departament de Geodinàmica i Geofísica of the Universitat de Barcelona began ye a r ly surveys in the austral summer of 1994-95 on Johnsons Glacier. During this field campaign 10 shallow ice cores were sampled with a manual ve rtical ice-core drilling machine. The objectives were: i) to detect the tephra layer accumulated on the glacier surface, attributed to the 1970 Deception Island pyroclastic eruption, today interstratified; ii) to verify wheter this layer might serve as a reference level; iii) to measure the 1 3 7Cs radio-isotope concentration accumulated in the 1965 snow stratum; iv) to use the isochrone layer as a mean of verifying the age of the 1970 tephra layer; and, v) to calculate both the equilibrium line of the glacier and average mass balance over the last 28 years (1965-1993). The stratigr a p hy of the cores, their cumulative density curves and the isothermal ice temperatures recorded confi rm that Johnsons Glacier is a temperate glacier. Wi n d, solar radiation heating and liquid water are the main agents controlling the ve rtical and horizontal redistribution of the volcanic and cryoclastic particles that are sedimented and remain interstratified within the g l a c i e r. It is because of this redistribution that the 1970 tephra layer does not always serve as a ve ry good reference level. The position of the equilibrium line altitude (ELA) in 1993, obtained by the 1 3 7Cs spectrometric analysis, varies from about 200 m a.s.l. to 250 m a.s.l. This indicates a rising trend in the equilibrium line altitude from the beginning of the 1970s to the present day. The va rying slope orientation of Johnsons Glacier relative to the prevailing NE wind gives rise to large local differences in snow accumulation, which locally modifies the equilibrium line altitude. In the cores studied, 1 3 7Cs appears to be associated with the 1970 tephra laye r. This indicates an intense ablation episode throughout the sampled area (at least up to 330 m a.s.l), which probably occurred synchronically to the 1970 tephra deposition or later. A rough estimate of the specific mass balance reveals a considerable accumulation gradient related to the increase with altitude.

Preparation and phytotoxicity of sorgoleone analogues

3,5-Dimethoxybenzylic alcohol was converted into the 2-acetoxy-5-methoxy-3-(pent-1-yl)-1,4-benzoquinone (12), in seven steps, with an overall yield of 14.6%. The natural quinone sorgoleone (1) was isolated from Sorghum bicolor and converted into the corresponding quinone (13) having a saturated side chain. The selective effects of these compounds (1, 12 and 13), at the dose of 5.6 mug of a.i./ g of substrate, on the growth of Cucumis sativus, Lactuca sativa, Desmodium tortuosum, Hyptis suaveolens and Euphorbia heterophylla were evaluated. All three compounds caused some inhibition on the root growth of the test plants (0.0-69.19%) with the aerial parts less affected. The results showed that the triene unit of the sorgoleone side chain is not essential for the phytotoxicity and also the synthetic quinone was as active as the natural product.

Problematic Internet use in British adolescents: An exploration of the addictive symptomatology

Research into online addictions has increased substantially over the last decade, particularly amongst youth. This study adapted the Problematic Internet Entertainment Use Scale for Adolescents [PIEUSA] for use with a British population. The adapted scale was used to (i) validate the instrument for English-speaking adolescent samples, (ii) estimate the prevalence of adolescent online problem users and describe their profile, and (iii) assess the accuracy of the scale"s classification of symptomatology. A survey was administered to 1097 adolescents aged between 11 and 18 years. The results indicated that (i) reliability of the adapted scale was excellent; factor validity showed unidimensionality, and construct validity was adequate. The findings also indicated that (ii) prevalence of online problem users was 5.2% and that they were more likely to younger males that engaged in online gaming for more than two hours most days. The majority of online problem users displayed negative addictive symptoms, especially"loss of control" and"conflict". The adapted scale showed (iii) very good sensitivity, specificity, and classification accuracy, and was able to clearly differentiate between problem and non-problem users. The results suggest certain differences between adolescent and adult online problem users based in the predominance of slightly different psychological components.

Characterizing Propionibacterium freudenreichii ssp. shermanii JS and Lactobacillus rhamnosus LC705 as a new probiotic combination: basic properties of JS and pilot in vivo assessment of the combination

Characterizing Propionibacterium freudenreichii ssp. shermanii JS and Lactobacillus rhamnosus LC705 as a new probiotic combination: basic properties of JS and pilot in vivo assessment of the combination Each candidate probiotic strain has to have the documentation for the proper identification with current molecular tools, for the biological properties, for the safety aspects and for the health benefits in human trials if the intention is to apply the strain as health promoting culture in the commercial applications. No generalization based on species properties of an existing probiotic are valid for any novel strain, as strain specific differences appear e.g. in the resistance to GI tract conditions and in health promoting benefits (Madsen, 2006). The strain evaluation based on individual strain specific probiotic characteristics is therefore the first key action for the selection of the new probiotic candidate. The ultimate goal in the selection of the probiotic strain is to provide adequate amounts of active, living cells for the application and to guarantee that the cells are physiologically strong enough to survive and be biologically active in the adverse environmental conditions in the product and in GI tract of the host. The in vivo intervention studies are expensive and time consuming; therefore it is not rational to test all the possible candidates in vivo. Thus, the proper in vitro studies are helping to eliminate strains which are unlikely to perform well in vivo. The aims of this study were to characterize the strains of Propionibacterium freudenreichii ssp. shermanii JS and Lactobacillus rhamnosus LC705, both used for decades as cheese starter cultures, for their technological and possible probiotic functionality applied in a combined culture. The in vitro studies of Propionibacterium freudenreichii ssp. shermanii JS focused on the monitoring of the viability rates during the acid and bile treatments and on the safety aspects such as antibiotic susceptibility and adhesion. The studies with the combination of the strains JS and LC705 administered in fruit juices monitored the survival of the strains JS and LC705 during the GI transit and their effect on gut wellbeing properties measured as relief of constipation. In addition, safety parameters such as side effects and some peripheral immune parameters were assessed. Separately, the combination of P. freudenreichii ssp. shermanii JS and Lactobacillus rhamnosus LC705 was evaluated from the technological point of view as a bioprotective culture in fermented foods and wheat bread applications. In this study, the role ofP. freudenreichii ssp. shermanii JS as a candidate probiotic culture alone and in a combination with L. rhamnosus LC705 was demonstrated. Both strains were transiently recovered in high numbers in fecal samples of healthy adults during the consumption period. The good survival through the GI transit was proven for both strains with a recovery rate from 70 to 80% for the JS strain and from 40 to 60% for the LC705 strain from the daily dose of 10 log10 CFU. The good survival was shown from the consumption of fruit juices which do not provide similar matrix protection for the cells as milk based products. The strain JS did not pose

Salmonella enterica– Mechanisms of fluoroquinolone and macrolide resistance

Salmonella enterica – Fluorokinoloni- ja makrolidiresistenssimekanisimit Vakavia salmonellainfektioita on pitkään hoidettu fluorokinoloniantibiooteilla, kuten siprofloksasiinilla. Fluorokinolonien runsas käyttö niin ihmisillä kuin eläimilläkin on kuitenkin johtanut fluorokinoloniresistenttien salmonellakantojen lisääntymiseen. Vuoteen 2002 asti kaikki matalan tason fluorokinoloniresistenssiä ilmentävät salmonellakannat olivat resistenttejä nalidiksiinihapolle, joka on vanha ensimmäisen polven kinoloniantibiootti jota ei enää käytetä infektioiden hoidossa. Vuonna 2003 havaitsimme aivan uudentyyppisen resistenssifenotyypin salmonelloissa. Kaikki uuden fenotyypin kannat osoittivat matalaa fluorokinoloniresistenssiä (MIC ≥0.125 mg/L), mutta useat kannat olivat yllättäen aikaisempaa herkempiä nalidiksiinihapolle (MIC ≤32 mg/L). Ilmiöllä on suuri merkitys salmonellan antibioottiherkkyyksien määrittämisessä, sillä jos kanta on ollut nalidiksiinihapolle herkkä, sitä on pidetty herkkänä myös fluorokinoloneille. Väitöskirjatyössä määritettiin vuosina 2003–2007 Suomessa kerättyjen kotimaisten ja ulkomaalaisten S. enterica -kantojen fluorokinoloniresistenssiä sekä tutkittiin uuden salmonellafenotyypin epidemiologiaa ja resistenssimekanismeja. Lisäksi tutkittiin salmonellan hoidossa mahdollisesti käyttökelpoisen makrolidiantibioottijohdannaisen, atsitromysiinin tehoa salmonelloihin ja erityisesti matalaa fluorokinoloniresistenssiä ilmentäviin kantoihin. Tutkimuksessa havaittiin, että matalaa fluorokinoloniresistenssiä osoittavien salmonellakantojen määrä vähenee. Lasku oli voimakkainta Kaakkois-Aasiasta tuoduissa kannoissa. Uusi resistenssifenotyyppi on plasmidivälitteinen ja qnr-geenit olivat ainoa plasmidivälitteinen kinoloniresistenssimekanismi, joka kannoista löydettiin. Myöskään kromosomaalisten gyrA, gyrB ja parE -geenien QRDR-alueelta ei löydetty fluorokinoloniresistenssiä aiheuttavia mutaatioita. Transformaatiolla osoitettiin qnr-plasmidien olevan siirtyviä ja uusi resistenssifenotyyppi saatiin ilmennettyä myös herkässä vastaanottajakannassa. Nämä tulokset osoittavat, että vaikka S. enterican qnr-fenotyyppi on toistaiseksi levinnyt pääasiassa Kaakkois-Aasiaan, se siirtyy helposti bakteerista toiseen ja tulee todennäköisesti aiheuttamaan hoito-ongelmia myös muualla maailmassa. Uudentyyppinen qnr-fenotyyppi voi olla vaikea havaita perinteisellä herkkyysmäärityksellä. Siksi laboratorioissa tulisi aina määrittää sekä siprofloksasiiniettä nalidiksiinihappoherkkyydet. Atsitromysiinin osoitettiin olevan herkkyysmääritysten mukaan tehokas salmonelloja kohtaan mukaanlukien matala-asteista fluorokinoloniresistenssiä ilmentävät bakteerikannat.

Surgical Treatment of Colorectal Cancer. Controversial Issues

Aims: This study was carried out to evaluate surgical treatment of colorectal cancer (CRC) with special interest in present status and controversial issues: stenting as a palliative procedure for metastasized CRC (I), duration of thromboprophylaxis after the surgical treatment of CRC (II), treatment of the increasing population of elderly people (III) and the quality of life (QoL) after surgery for rectal cancer with special reference to pelvic floor dysfunction (IV). Materials and methods: The material consisted of patients with CRC operated on at Turku University Hospital between 2003 and 2008. In study II the data was collected retrospectively from electronic archives. In other studies the follow-up data was collected at postoperative control visits. In study IV the RAND-36 standardized questionnaire and additional questions assessing urinary, sexual and anorectal dysfunction were used. Results: The results of the current study showed that self-expanding metallic stents provided an alternative to palliative surgery in the treatment of obstructive CRC. Low molecular heparin given s.c. for a median of 11 days until hospital discharge seemed to provide sufficient thromboprophylaxis after surgery. With preoperative selection elderly patients with rectal cancer were suitable for major surgery for rectal cancer with morbidity and mortality rates comparable to those in younger patients. There was no difference between preoperative and one year postoperative general QoL for operated rectal cancer patients. Postoperative pelvic dysfunction was associated with an impaired QoL in some dimensions. Conclusions: Many individual factors regarding the patient and the disease must be taken into account when making treatment decisions in CRC to ensure successful treatment of CRC, patient satisfaction and QoL.

Enhanced photocatalytic activity of TiO2 films by modification with polyethylene glycol

Titanium dioxide porous thin films on the Anatase phase were deposited onto glass slides by the sol-gel method assisted with polyethylene glycol (PEG). The dip-coated films were characterized using scanning electron microscopy (SEM), thermogravimetric analysis (TGA and DTG), UV-visible spectroscopy and X-ray diffraction (XRD). The photocatalytic activity of the films was determined by means of methyl-orange oxidation tests. The resultant PEG-modified films were crack-free and developed a porous structure after calcination at 500 °C. Photo-oxidation tests showed the dependency of catalytic activity of the films on the number of layers (thickness) and porosity, i.e. of the interfacial area.

An undergraduate level experiment on the synthesis of Au nanoparticles and their size-dependent optical and catalytic properties

The synthesis of gold nanoparticles (Au NPs) 15, 26, and 34 nm in diameter, followed by the investigation of their size-dependent optical and catalytic properties, is described herein as an undergraduate level experiment. The proposed experiment covers concepts on the synthesis, stabilization, and characterization of Au NPs, their size-dependent optical and catalytic properties at the nanoscale, chemical kinetics, and the role of a catalyst. The experiment should be performed by groups of two or three students in three lab sessions of 3 h each and organized as follows: i) synthesis of Au NPs of different sizes and investigation of their optical properties; ii) evaluation of their catalytic activity; and iii) data analysis and discussion. We believe that this activity enables students to integrate these multidisciplinary concepts in a single experiment as well as to become introduced/familiarized with an active research field and current literature in the areas of nanoparticle synthesis and catalysis.

Conductometric determination of propranolol hydrochloride in pharmaceuticals

In this paper the conductometric titration of propranolol hydrochloride in pharmaceutical formulations using silver nitrate as titrant is proposed. The method was based on the formation of an insoluble salt (AgCl(s)) between the chloride of propranolol hydrochloride molecule and Ag(I) ions of the titrant AgNO3. The effect of the PROP-AgNO3 concentrations and the interval of time between the successive additions of the titrant on the shape of the titration curve were studied. The obtained recoveries for four samples ranged from 96.8 to 105%. The proposed method was successfully applied in the determination of propranolol hydrochloride in several pharmaceutical formulations, with results in close agreement at a 95 % confidence level with those obtained using official spectrophotometric method.

Bisphosphonate Inhibition of Prostate Cancer Cell Invasion, Migration and Cytoskeletal Organization

Metastatic bone lesions are commonly associated with prostate cancer affecting approximately 60-80% of the patients. The progression of prostate cancer into an advanced stage is a complex process and its molecular mechanisms are poorly understood. So far, no curative treatment is available for advanced stages of prostate cancer. Bisphosphonates (BPs) are synthetic pyrophosphate analogues, which are used as therapeutics for various metabolic bone diseases because of their ability to inhibit osteoclastic bone resorption. Nitrogen-containing bisphosphonates block the function of osteoclasts by disturbing the vesicular traffic and the mevalonate pathway -related enzymes, for example farnesyl diphosphate synthase, which is involved in post-translational isoprenylation of small GTPases. In addition, the anti-proliferative, anti-invasive and pro-apoptotic effects of nitrogen-containing bisphosphonates on various cancer cell lines have been reported. The aim of this thesis work was to clarify the effects of bisphosphonates on prostate cancer cells, focusing on the mechanisms of adhesion, invasion and migration. Furthermore, the role of the mevalonate pathway and prenylation reactions in invasion and regulation of the cytoskeleton of prostate cancer cells were examined. Finally, the effects of alendronate on cytoskeleton- and actin-related proteins in prostate cancer cells were studied in vitro and in vivo. The results showed that the nitrogen-containing bisphosphonate alendronate inhibited the adhesion of prostate cancer cells to various extracellular matrix proteins and migration and invasion in vitro. Inhibition of invasion and migration was reversed by mevalonate pathway intermediates. The blockage of the prenylation transferases GGTase I and FTase inhibited the invasion, migration and actin organization of prostate cancer cells. The marked decrease of cofilin was observed by the prenylation inhibitors used. Inhibition of GGTase I also disrupted the regulation of focal adhesion kinase and paxillin. In addition, alendronate disrupted the cytoskeletal organization and decreased the level of cofilin in vitro and in vivo. The decrease of the cofilin level by alendronate could be one of the key mechanisms behind the observed inhibition of migration and invasion. Based on the effects of nitrogen-containing bisphosphonates on tumor cell invasion and cytoskeletal organization, they can be suggested to be developed as therapeutics for inhibiting prostate cancer metastasis.

The Use of Radiostereometric Analysis in Fractures of the Distal Radius: From Phantom Models to Clinical Application

Radiostereometric analysis (RSA) is a highly accurate method for the measurement of in vivo micromotion of orthopaedic implants. Validation of the RSA method is a prerequisite for performing clinical RSA studies. Only a limited number of studies have utilised the RSA method in the evaluation of migration and inducible micromotion during fracture healing. Volar plate fixation of distal radial fractures has increased in popularity. There is still very little prospective randomised evidence supporting the use of these implants over other treatments. The aim of this study was to investigate the precision, accuracy, and feasibility of using RSA in the evaluation of healing in distal radius fractures treated with a volar fixed-angle plate. A physical phantom model was used to validate the RSA method for simple distal radius fractures. A computer simulation model was then used to validate the RSA method for more complex interfragmentary motion in intra-articular fractures. A separate pre-clinical investigation was performed in order to evaluate the possibility of using novel resorbable markers for RSA. Based on the validation studies, a prospective RSA cohort study of fifteen patients with plated AO type-C distal radius fractures with a 1-year follow-up was performed. RSA was shown to be highly accurate and precise in the measurement of fracture micromotion using both physical and computer simulated models of distal radius fractures. Resorbable RSA markers demonstrated potential for use in RSA. The RSA method was found to have a high clinical precision. The fractures underwent significant translational and rotational migration during the first two weeks after surgery, but not thereafter. Maximal grip caused significant translational and rotational interfragmentary micromotion. This inducible micromotion was detectable up to eighteen weeks, even after the achievement of radiographic union. The application of RSA in the measurement of fracture fragment migration and inducible interfragmentary micromotion in AO type-C distal radius fractures is feasible but technically demanding. RSA may be a unique tool in defining the progress of fracture union.

Travels through Sweden, Finland, and Lapland, to the North Cape, in the years 1798 and 1799 : by Joseph Acerbi. In two volumes. Illustrated with seventeen elegant engravings. Vol. I[-II].

Vol. I: Portrait of Joseph Acerbi. Painted by P. Violet, engr. by P. W. Tomkins.

Travels through Sweden, Finland, and Lapland, to the North Cape, in the years 1798 and 1799 : by Joseph Acerbi. In two volumes. Illustrated with seventeen elegant engravings. Vol. I[-II].

Vol. I: Portrait of Joseph Acerbi. Painted by P. Violet, engr. by P. W. Tomkins.

Reflexive model of research-based theatre – processing innovation at the crossroads of theatre, reflection and practice-based innovation activities

Contemporary organisations have to embrace the notion of doing ‘more with less’. This challenges knowledge production within companies and public organisations, forcing them to reorganise their structures and rethink what knowledge production actually means in the context of innovation and how knowledge is actually produced among various professional groups within the organisation in their everyday actions. Innovations are vital for organisational survival, and ‘ordinary’ employees and customers are central but too-often ignored producers of knowledge for contemporary organisations. Broader levels of participation and reflexive practices are needed. This dissertation discusses the missing links between innovation research conducted in the context of industrial management, arts, and culture; applied drama and theatre practices (specifically post-Boalian approaches); and learning – especially organising reflection – in organisational settings. This dissertation (1) explores and extends the role of research-based theatre to organising reflection and reflexive practices in the context of practice-based innovation, (2) develops a reflexive model of RBT for investigating and developing practice-based organisational process innovations in order to contribute to the development of a tool for innovation management and analysis, and (3) operationalises this model within private- and publicsector organisations. The proposed novel reflexive model of research-based theatre for investigating and developing practice-based organisational process innovations extends existing methods and offers a different way of organising reflection and reflexive practices in the context of general innovation management. The model was developed through five participatory action research processes conducted in four different organisations. The results provide learning steps – a reflection path – for understanding complex organisational life, people, and relations amid renewal and change actions. The proposed model provides a new approach to organising and cultivating reflexivity in practice-based innovation activities via research-based theatre. The results can be utilised as a guideline when processing practice-based innovation within private or public organisations. The model helps innovation managers to construct, together with their employees, temporary communities where they can learn together through reflecting on their own and each others’ experiences and to break down assumptions related to their own perspectives. The results include recommendations for practical development steps applicable in various organisations with regard to (i) application of research-based theatre and (ii) related general innovation management. The dissertation thus contributes to the development of novel learning approaches in knowledge production. Keywords: practice-based innovation, research-based theatre, learning, reflection, mode 2b knowledge production