Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

Experimental models of sepsis-induced pulmonary alterations are important for the study of pathogenesis and for potential intervention therapies. The objective of the present study was to characterize lung dysfunction (low PaO2 and high PaCO2, and increased cellular infiltration, protein extravasation, and malondialdehyde (MDA) production assessed in bronchoalveolar lavage) in a sepsis model consisting of intraperitoneal (ip) injection of Escherichia coli and the protective effects of pentoxifylline (PTX). Male Wistar rats (weighing between 270 and 350 g) were injected ip with 10(7) or 10(9) CFU/100 g body weight or saline and samples were collected 2, 6, 12, and 24 h later (N = 5 each group). PaO2, PaCO2 and pH were measured in blood, and cellular influx, protein extravasation and MDA concentration were measured in bronchoalveolar lavage. In a second set of experiments either PTX or saline was administered 1 h prior to E. coli ip injection (N = 5 each group) and the animals were observed for 6 h. Injection of 10(7) or 10(9) CFU/100 g body weight of E. coli induced acidosis, hypoxemia, and hypercapnia. An increased (P < 0.05) cell influx was observed in bronchoalveolar lavage, with a predominance of neutrophils. Total protein and MDA concentrations were also higher (P < 0.05) in the septic groups compared to control. A higher tumor necrosis factor-alpha (P < 0.05) concentration was also found in these animals. Changes in all parameters were more pronounced with the higher bacterial inoculum. PTX administered prior to sepsis reduced (P < 0.05) most functional alterations. These data show that an E. coli ip inoculum is a good model for the induction of lung dysfunction in sepsis, and suitable for studies of therapeutic interventions.

Effect of saline infusion for the maintenance of blood volume on pulmonary gas exchange during temporary abdominal aortic occlusion

We analyzed the effects of saline infusion for the maintenance of blood volume on pulmonary gas exchange in ischemia-reperfusion syndrome during temporary abdominal aortic occlusion in dogs. We studied 20 adult mongrel dogs weighing 12 to 23 kg divided into two groups: ischemia-reperfusion group (IRG, N = 10) and IRG submitted to saline infusion for the maintenance of mean pulmonary arterial wedge pressure between 10 and 20 mmHg (IRG-SS, N = 10). All animals were anesthetized and maintained on spontaneous ventilation. After obtaining baseline measurements, occlusion of the supraceliac aorta was performed by the inflation of a Fogarty catheter. After 60 min of ischemia, the balloon was deflated and the animals were observed for another 60 min of reperfusion. The measurements were made at 10 and 45 min of ischemia, and 5, 30, and 60 min of reperfusion. Pulmonary gas exchange was impaired in the IRG-SS group as demonstrated by the increase of the alveolar-arterial oxygen difference (21 ± 14 in IRG-SS vs 11 ± 8 in IRG after 60 min of reperfusion, P = 0.004 in IRG-SS in relation to baseline values) and the decrease of oxygen partial pressure in arterial blood (58 ± 15 in IRG-SS vs 76 ± 15 in IRG after 60 min of reperfusion, P = 0.001 in IRG-SS in relation to baseline values), which was correlated with the highest degree of pulmonary edema in morphometric analysis (0.16 ± 0.06 in IRG-SS vs 0.09 ± 0.04 in IRG, P = 0.03 between groups). There was also a smaller ventilatory compensation of metabolic acidosis after the reperfusion. We conclude that infusion of normal saline worsened the gas exchange induced by pulmonary reperfusion injury in this experimental model.

High mobility group box 1 as a mediator of endotoxin administration after hemorrhagic shock-primed lung injury

High mobility group box 1 (HMGB1) was discovered as a novel late-acting cytokine that contributes to acute lung injury (ALI). However, the contribution of HMGB1 to two-hit-induced ALI has not been investigated. To examine the participation of HMGB1 in the pathogenesis of ALI caused by the two-hit hypothesis, endotoxin was injected intratracheally in a hemorrhagic shock-primed ALI mouse model. Concentrations of HMGB1 in the lung of the shock group were markedly increased at 16 h (1.63 ± 0.05, compared to the control group: 1.02 ± 0.03; P < 0.05), with the highest concentration being observed at 24 h. In the sham/lipopolysaccharide group, lung HMGB1 concentrations were found to be markedly increased at 24 h (1.98 ± 0.08, compared to the control group: 1.07 ± 0.03; P < 0.05). Administration of lipopolysaccharide to the hemorrhagic shock group resulted in a notable HMGB1 increase by 4 h, with a further increase by 16 h. Intratracheal lipopolysaccharide injection after hemorrhagic shock resulted in the highest lung leak at 16 h (2.68 ± 0.08, compared to the control group: 1.05 ± 0.04; P < 0.05). Compared to the hemorrhagic shock/lipopolysaccharide mice, blockade of HMGB1 at the same time as lipopolysaccharide injection prevented significantly pulmonary tumor necrosis factor-alpha, interleukin-1beta and myeloperoxidase. Lung leak was also markedly reduced at 16 h; blockade of HMGB1 24 h after lipopolysaccharide injection failed to alter lung leak or myeloperoxidase at 48 h. Our observations suggest that HMGB1 plays a key role as a late mediator when lipopolysaccharide is injected after hemorrhagic shock-primed ALI and the kinetics of its release differs from that of one-hit ALI. The therapeutic window to suppress HMGB1 activity should not be delayed to 24 h after the disease onset.

Tietojärjestelmän omistajuuden siirtoprojektin osaamis- ja tarvekartoitus

Tutkimuksen tarkoitus on selventää tietojärjestelmän omistajuuden muutoksessa olevan organisaation osaamisen kartoittamista, määrittämistä ja mittaamista. Yksilön, ryhmän sekä organisaation oppiminen nähdään keskeisenä tekijä organisaation kilpailukyvyn ylläpitämisessä ja kehittämisessä. Aihepiiriä on tutkittu paljon, kuitenkin on edelleen paljon erilaisia näkemyksiä oppimiseen liittyvistä aiheista ja siihen vaikuttavista tekijöistä. Tutkimuksen kohteena ovat myös oppimiseen ja osaamiseen läheisesti liittyvät teemat, innovointi ja muutosjohtaminen, niiltä osin, kun ne vaikuttavat organisatoriseen ja/tai yksilön oppimiseen ja osaamiseen. Tutkimuksen kohteena ovat kaksi julkishallinnon organisaatiota joiden välillä tapahtuu tietojärjestelmien omistajuuden vaihdon yhteydessä kohtuullisen laajamittaista osaamisen siirtoa. Tutkimuksen empiirisessä osassa perehdyttiin organisaation osaamisen hallinnan prosessiin ja sen kehittämismahdollisuuksiin. Organisatoriseen oppimiseen ja osaamiseen vaikuttavat tekijät, niin sisäiset kuin ulkopuoliset, on selvitetty tutkimuksessa. Myös eri tekijöiden vaikutusta organisaation kilpailukykyyn ja kykyyn luoda uutta osaamista ja innovointia on selvitetty tutkimuksessa. Tutkimuksen tulokset ja empiirinen osuus antavat samankaltaisia ratkaisuja osaamiseen, yksilön ja organisaation, oppimisen osalta.

Performance improvement in mediterranean operations using risk management analysis : Case study of Containerships Group Ltd

Emerging markets of Northern Africa and Turkey provide growth opportunities for logistics service companies in the middle of low growth environment of European Union. The purpose of this research is to explore and analyze the risk factors in container shipping industry and third party logistics (3PL) services. The research empirically examined the risk factors, which are related within the interaction between these two parties in emerging markets of Mediterranean area. The previous studies have provided a valuable insight into the operational risks faced by container shipping industries. However, most of these studies have focused on one or several operational risk factors from a single point of view, and no studies have inclusively examined the possible operational risks faced in the container shipping industry from dual perspective of 3PL provider and its customers. A questionnaire has been deployed to collect related data; and the impacts of the risks were then be assessed and ranked using the method of risk mapping. Respondents were located in Turkey, Algeria, Tunisia, and Libya. Research presents the most important risk factors identified, and compares them between 3PL provider and its customers. The research also provide some risk mitigation strategies for the key risk factors, and tried to figure out a common risk picture, which guides the managers in both sides to have a better decisions and as a result, improve the performance of the container shipping operations. Challenge during project execution time was that customers identified vast amount of more risks than what was the case with logistics service operator.

Viimeisimmän finanssikriisin vaikutukset Helsingin Pörssin kulutuspalveluita tuottaviin yrityksiin

Tämän kandidaatintutkielman tarkoituksena on analysoida miten vuonna 2008 alkanut finanssikriisi ja sen aiheuttama taloudellinen epävarmuus ovat vaikuttaneet Nasdaq OMX Helsingin pörssiin listattujen kulutuspalveluita tuottavien yritysten suorituskykyyn. Näiden yritysten suorituskykyä analysoitiin tarkemmin tarkastelemalla kannattavuuden, maksuvalmiuden ja vakavaraisuuden tunnuslukuja aikavälillä 2008-2014. Tutkimuksen tavoitteena oli selvittää, minkälaisia muutoksia suorituskyvyn suhteen tutkitulla aikavälillä oli tapahtunut kulutuspalveluita tuottavien yritysten keskuudessa. Muutoksia analysoitiin sekä kokonaisuutena että yrityskohtaisesti. Lisäksi tutkittiin, miten kulutuspalveluryhmän sisäiset toimialat olivat selviytyneet finanssikriisistä. Käsiteltävää yritysryhmää analysoitiin tunnuslukuanalyysiä hyödyntäen. Saatujen tulosten mukaan finanssikriisillä ei ollut suurta vaikutusta käsiteltävien yritysten maksuvalmiuteen tai vakavaraisuuteen. Kannattavuuden tunnusluvut sen sijaan heikkenivät merkittävästi koko ryhmän osalta finanssikriisin vaikutuksesta. Yrityskohtaiset erot olivat tutkimuksessa melko suuria. Etenkin mediayhtiöiden tunnusluvut heikkenivät merkittävästi tutkitulla aikavälillä. Mediayhtiöiden huonoon suoriutumiseen liittyy finanssikriisin lisäksi muitakin tekijöitä. Median digitalisoituminen on aiheuttanut useille yrityksille ongelmia liiketoiminnan kannattavuuden ylläpitämisessä. Monet tutkituista yrityksistä ovat kuitenkin pystyneet kääntämään liiketoimintansa kannattavampaan suuntaan vuoden 2013 jälkeen. Johtopäätöksenä voidaankin vetää, että viimeisin finanssikriisi oli vaikutuksiltaan merkittävä ja pitkäkestoinen.

NMR studies of the exchange reactions of CH3CN.BX3 with excess CH3CN /|nJoseph Fogelman. -- 260 St. Catharines, Ont. : [s. n.],

Exchange reactions between molecular complexes and excess acid or base are well known and have been extensively surveyed in the literature(l). Since the exchange mechanism will, in some way involve the breaking of the labile donor-acceptor bond, it follows that a discussion of the factors relating to bonding in molecular complexes will be relevant. In general, a strong Lewis base and a strong Lewis acid form a stable adduct provided that certain stereochemical requirements are met. A strong Lewis base has the following characteristics (1),(2) (i) high electron density at the donor site. (ii) a non-bonded electron pair which has a low ionization potential (iii) electron donating substituents at the donor atom site. (iv) facile approach of the site of the Lewis base to the acceptor site as dictated by the steric hindrance of the substituents. Examples of typical Lewis bases are ethers, nitriles, ketones, alcohols, amines and phosphines. For a strong Lewis acid, the following properties are important:( i) low electron density at the acceptor site. (ii) electron withdrawing substituents. (iii) substituents which do not interfere with the close approach of the Lewis base. (iv) availability of a vacant orbital capable of accepting the lone electron pair of the donor atom. Examples of Lewis acids are the group III and IV halides such (M=B, AI, Ga, In) and MX4 - (M=Si, Ge, Sn, Pb). The relative bond strengths of molecular complexes have been investigated by:- (i) (ii) (iii) (iv) (v] (vi) dipole moment measurements (3). shifts of the carbonyl peaks in the IIIR. (4) ,(5), (6) .. NMR chemical shift data (4),(7),(8),(9). D.V. and visible spectrophotometric shifts (10),(11). equilibrium constant data (12), (13). heats of dissociation and heats of reactions (l~), (16), (17), (18), (19). Many experiments have bben carried out on boron trihalides in order to determine their relative acid strengths. Using pyridine, nitrobenzene, acetonitrile and trimethylamine as reference Lewis bases, it was found that the acid strength varied in order:RBx3 > BC1 3 >BF 3 • For the acetonitrile-boron trihalide and trimethylamine boron trihalide complexes in nitrobenzene, an-NMR study (7) showed that the shift to lower field was. greatest for the BB~3 adduct ~n~ smallest for the BF 3 which is in agreement with the acid strengths. If electronegativities of the substituents were the only important effect, and since c~ Br ,one would expect the electron density at the boron nucleus to vary as BF3

Occupational therapist and client experiences of a mental health group

The purpose of this qualitative study was to understand the client and occupational therapist experiences of a mental health group. A secondary aim was to explore the extent to which this group seemed to have reflected a client-centred approach. The topic emerged from personal and professional issues related to the therapist as teacher and to inconsistencies in practice with the profession's client-centred philosophy. This philosophy, the study's frame of reference, was established in terms of themes related to the client-therapist relationship and to client values. Typical practice was illustrated through an extensive literature review. Structured didacticexperiential methods aiming toward skill development were predominant. The interpretive sciences and, to a lesser extent, the critical sciences directed the methodology. An ongoing support group at a community mental health clinic was selected as the focus of the study; the occupational therapist leader and three members became the key participants. A series of conversational interviews, the . core method of data collection, was supplemented by observation, document review, further interviews, and fieldnotes. Transcriptions of conversations were returned to participants for verification and for further reflection. Analysis primarily consisted of coding and organizing data according to emerging themes. The participants' experiences of group, presented as narrative stories within a group session vignette, were also returned to participants. There was a common understanding of the group's structure and the importance of having "air time" within the group; however, differences in perceptions of such things as the importance of the group in members' lives were noted. All members valued the therapeutic aspects of group, the role of group as weekly activity and, to a lesser extent, the learning that came from group. The researcher's perspective provided a critique of the group experience from a client-centred perspective. Some areas of consistency with client-centred practice were noted (e.g., therapist attitudes); however the group seemed to function far from a client-centred ideal. Members held little authority in a relationship dominated by the leaders, and leader agendas rather than member values controlled the session. Possible reasons for this discrepancy ranging from past health care encounters through to co-leader discord emerged. The actual and potential significance of this study was discussed according to many areas of implications: to OT practice, especially client-centred group practice, to theory development, to further areas of research and methodology considerations, to people involved in the group and to my personal growth and development.

I Believe in me, not OCB: Evaluation of Group Function-Based CBT as a Treatment for Obsessive Compulsive Behaviour in Four Children with HFA

Researchers have conceptualized repetitive behaviours in individuals with Autism Spectrum Disorder (ASD) on a continuum oflower-Ievel, motoric, repetitive behaviours and higher-order, repetitive behaviours that include symptoms ofOCD (Hollander, Wang, Braun, & Marsh, 2009). Although obsessional, ritualistic, and stereotyped behaviours are a core feature of ASD, individuals with ASD frequently experience obsessions and compulsions that meet DSM-IV-TR (American Psychiatric Association, 2000) criteria for Obsessive-Compulsive Disorder (OCD). Given the acknowledged difficulty in differentiating between OCD and Autism-related obsessive-compulsive phenomena, the present study uses the term Obsessive Compulsive Behaviour (OCB) to represent both phenomena. This study used a multiple baseline design across behaviours and ABC designs (Cooper, Heron, & Heward, 2007) to investigate if a 9-week Group Function-Based Cognitive Behavioural Therapy (CBT) decreased OCB in four children (ages 7 - 11 years) with High Functioning Autism (HFA). Key treatment components included traditional CBT components (awareness training, cognitive-behavioural skills training, exposure and response prevention) as well as function-based assessment and intervention. Time series data indicated significant decreases in OCBs. Standardized assessments showed decreases in symptom severity, and increases in quality of life for the participants and their families. Issues regarding symptom presentation, assessment, and treatment of a dually diagnosed child are discussed.

Investigating Changes in Parent Knowledge about Obsessive Compulsive Behaviour Following Group Function-Based Cognitive Behavioural Therapy for Children with High Functioning Autism

This study investigated improvements in parent knowledge of effective intervention strategies following participation in a group function-based CBT treatment (GFbCBT) package for children with comorbid OCD and ASD. Nineteen parents of children ages 7-12 years with High Functioning Autism (HFA) participated in the 9-week treatment program. Key components of treatment included psychoeducation and mapping, cognitive-behavioural skills training, function-based interventions and exposure and response prevention (ERP). Treatment sessions also included direct parent education, which followed a behavioural skills training model (Miltenberger, 2008). Parent knowledge (N = 19) was measured pre and post treatment using a vignette about a child demonstrating obsessive-compulsive behaviour. Results of a one-tailed pairwise t-test indicated statistically significant changes (p=.036) in overall parent knowledge following participation in treatment. Statistically significant changes were also found in parents’ ability to generate ERP and function-based intervention strategies. These results provide preliminary evidence that parents benefit from active involvement in the GFbCBT treatment package.

Contribution à l'étude de la construction des concepts scientifiques au cours de l'apprentissage par problèmes en médecine

L’approche d’apprentissage par problèmes (APP) a vu le jour, dans sa forme contemporaine, à la Faculté de médecine de l’Université MacMaster en Ontario (Canada) à la fin des années 1960. Très rapidement cette nouvelle approche pédagogique active, centrée sur l’étudiant et basée sur les problèmes biomédicaux, va être adoptée par de nombreuses facultés de médecine de par le monde et gagner d’autres disciplines. Cependant, malgré ce succès apparent, l’APP est aussi une approche controversée, notamment en éducation médicale, où elle a été accusée de favoriser un apprentissage superficiel. Par ailleurs, les étudiants formés par cette approche réussiraient moins bien que les autres aux tests évaluant l’acquisition des concepts scientifiques de base, et il n’a jamais été prouvé que les médecins formés par l’APP seraient meilleurs que les autres. Pour mieux comprendre ces résultats, la présente recherche a voulu explorer l’apprentissage de ces concepts scientifiques, en tant que processus de construction, chez des étudiants formés par l’APP, à la Faculté de médecine de l’Université de Montréal, en nous appuyant sur le cadre théorique socioconstructivisme de Vygotski. Pour cet auteur, la formation des concepts est un processus complexe de construction de sens, en plusieurs étapes, qui ne peut se concevoir que dans le cadre d’une résolution de problèmes. Nous avons réalisé une étude de cas, multicas, intrasite, les cas étant deux groupes de neuf étudiants en médecine avec leur tuteur, que nous avons suivi pendant une session complète de la mi-novembre à la mi-décembre 2007. Deux grands objectifs étaient poursuivis: premièrement, fournir des analyses détaillées et des matériaux réflectifs et théoriques susceptibles de rendre compte du phénomène de construction des concepts scientifiques de base par des étudiants en médecine dans le contexte de l’APP. Deuxièmement, explorer, les approches de travail personnel des étudiants, lors de la phase de travail individuel, afin de répondre à la question de recherche suivante : Comment la dynamique pédagogique de l’APP en médecine permet-elle de rendre compte de l’apprentissage des concepts scientifiques de base? Il s’agissait d’une étude qualitative et les données ont été recueillies par différents moyens : observation non participante et enregistrement vidéo des tutoriaux d’APP, interview semi-structuré des étudiants, discussion avec les tuteurs et consultation de leurs manuels, puis traitées par diverses opérations: transcription des enregistrements, regroupement, classification. L’analyse a porté sur des collections de verbatim issus des transcriptions, sur le suivi de la construction des concepts à travers le temps et les sessions, sur le role du tuteur pour aider au développement de ces concepts Les analyses suggèrent que l’approche d’APP est, en général, bien accueillie, et les débats sont soutenus, avec en moyenne entre trois et quatre échanges par minute. Par rapport au premier objectif, nous avons effectivement fourni des explications détaillées sur la dynamique de construction des concepts qui s'étend lors des trois phases de l'APP, à savoir la phase aller, la phase de recherche individuelle et la phase retour. Pour chaque cas étudié, nous avons mis en évidence les représentations conceptuelles initiales à la phase aller, co-constructions des étudiants, sous la guidance du tuteur et nous avons suivi la transformation de ces concepts spontanés naïfs, lors des discussions de la phase retour. Le choix du cadre théorique socio constructiviste de Vygotski nous a permis de réfléchir sur le rôle de médiation joué par les composantes du système interactif de l'APP, que nous avons considéré comme une zone proximale de développement (ZPD) au sens élargi, qui sont le problème, le tuteur, l'étudiant et ses pairs, les ressources, notamment l'artefact graphique carte conceptuelle utilisée de façon intensive lors des tutoriaux aller et retour, pour arriver à la construction des concepts scientifiques. Notre recherche a montré qu'en revenant de leurs recherches, les étudiants avaient trois genres de représentations conceptuelles: des concepts corrects, des concepts incomplets et des concepts erronés. Il faut donc que les concepts scientifiques théoriques soient à leur tour confrontés au problème concret, dans l'interaction sociale pour une validation des attributs qui les caractérisent. Dans cette interaction, le tuteur joue un rôle clé complexe de facilitateur, de médiateur, essentiellement par le langage. L'analyse thématique de ses interventions a permis d'en distinguer cinq types: la gestion du groupe, l'argumentation, les questions de différents types, le modelling et les conclusions. Nous avons montré le lien entre les questions du tuteur et le type de réponses des étudiants, pour recommander un meilleur équilibre entre les différents types de questions. Les étudiants, également par les échanges verbaux, mais aussi par la construction collective des cartes conceptuelles initiales et définitives, participent à une co-construction de ces concepts. L'analyse de leurs interactions nous a permis de relever différentes fonctions du langage, pour souligner l'intérêt des interactions argumentatives, marqueurs d'un travail collaboratif en profondeur pour la co-construction des concepts Nous avons aussi montré l'intérêt des cartes conceptuelles non seulement pour visualiser les concepts, mais aussi en tant qu'artefact, outil de médiation psychique à double fonction communicative et sémiotique. Concernant le second objectif, l’exploration du travail personnel des étudiants, on constate que les étudiants de première année font un travail plus approfondi de recherche, et utilisent plus souvent des stratégies de lecture plus efficaces que leurs collègues de deuxième année. Ceux-ci se contentent, en général, des ouvrages de référence, font de simples lectures et s’appuient beaucoup sur les résumés faits par leurs prédécesseurs. Le recours aux ouvrages de référence essentiellement comme source d'information apporte une certaine pauvreté au débat à la phase retour avec peu d'échanges de type argumentatif, témoins d'un travail profond. Ainsi donc, par tout ce soutien qu'elle permet d'apporter aux étudiants pour la construction de leurs connaissances, pour le type d'apprentissage qu'elle offre, l’APP reste une approche unique, digne d’intérêt. Cependant, elle nécessite d'être améliorée par des interventions au niveau du tuteur et des étudiants.

Studies On Chelating Ion-Exchange Resins

Ion-exchange chromatography has emerged as a practical and rapid method of separation and analysis. A review of literature on chelating resins reveals that eventhough investigations on highly selective resins are intensively pursued from early 1940s, such resins are still insufficiently used in analytical chemistry and process technology. This is mainly due to the complexity of their synthesis and high cost. In this context, it is worthwhile to develop novel chelating resins which are specific or at least selective towards a group of metal ions. Synthesis, characterization and analytical applications of two such resins are presented in this thesis.

Investigation on key molecular targets responsible for antidiabetic properties of Symplocos cochinchinensis (Lour.) S. Moore

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia with disturbances in carbohydrate, protein and lipid metabolism resulting from defects in insulin secretion, insulin action or both. Currently there are 387 million people with diabetes worldwide and is expected to affect 592 million people by 2035. Insulin resistance in peripheral tissues and pancreatic beta cell dysfunction are the major challenges in the pathophysiology of diabetes. Diabetic secondary complications (like liver cirrhosis, retinopathy, microvascular and macrovascular complications) arise from persistent hyperglycemia and dyslipidemia can be disabling or even life threatening. Current medications are effective for control and management of hyperglycemia but undesirable effects, inefficiency against secondary complications and high cost are still serious issues in the present prognosis of this disorder. Hence the search for more effective and safer therapeutic agents of natural origin has been found to be highly demanding and attract attention in the present drug discovery research. The data available from Ayurveda on various medicinal plants for treatment of diabetes can efficiently yield potential new lead as antidiabetic agents. For wider acceptability and popularity of herbal remedies available in Ayurveda scientific validation by the elucidation of mechanism of action is very much essential. Modern biological techniques are available now to elucidate the biochemical basis of the effectiveness of these medicinal plants. Keeping this idea the research programme under this thesis has been planned to evaluate the molecular mechanism responsible for the antidiabetic property of Symplocos cochinchinensis, the main ingredient of Nishakathakadi Kashayam, a wellknown Ayurvedic antidiabetic preparation. A general introduction of diabetes, its pathophysiology, secondary complications and current treatment options, innovative solutions based on phytomedicine etc has been described in Chapter 1. The effect of Symplocos cochinchinensis (SC), on various in vitro biochemical targets relevant to diabetes is depicted in Chapter 2 including the preparation of plant extract. Since diabetes is a multifactorial disease, ethanolic extract of the bark of SC (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90 % ethanol) were evaluated by in vitro methods against multiple targets such as control of postprandial hyperglycemia, insulin resistance, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPPxxi IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition, insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F and reduced triglyceride accumulation in 3T3-L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence of bioactives (beta-sitosterol, phloretin 2’glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test (OGTT) to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. Chapter 3 highlights the beneficial effects of hydroethanol extract of Symplocos cochinchinensis (SCE) against hyperglycemia associated secondary complications in streptozotocin (60 mg/kg body weight) induced diabetic rat model. Proper sanction had been obtained for all the animal experiments from CSIR-CDRI institutional animal ethics committee. The experimental groups consist of normal control (NC), N + SCE 500 mg/kg bwd, diabetic control (DC), D + metformin 100 mg/kg bwd, D + SCE 250 and D + SCE 500. SCEs and metformin were administered daily for 21 days and sacrificed on day 22. Oral glucose tolerance test, plasma insulin, % HbA1c, urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, total protein etc. were analysed. Aldose reductase (AR) activity in the eye lens was also checked. On day 21, DC rats showed significantly abnormal glucose response, HOMA-IR, % HbA1c, decreased activity of antioxidant enzymes and GSH, elevated AR activity, hepatic and renal oxidative stress markers compared to NC. DC rats also exhibited increased level of plasma urea and creatinine. Treatment with SCE protected from the deleterious alterations of biochemical parameters in a dose dependent manner including histopathological alterations in pancreas. SCE 500 exhibited significant glucose lowering effect and decreased HOMA-IR, % HbA1c, lens AR activity, and hepatic, renal oxidative stress and function markers compared to DC group. Considerable amount of liver and muscle glycogen was replenished by SCE treatment in diabetic animals. Although metformin showed better effect, the activity of SCE was very much comparable with this drug. xxii The possible molecular mechanism behind the protective property of S. cochinchinensis against the insulin resistance in peripheral tissue as well as dyslipidemia in in vivo high fructose saturated fat diet model is described in Chapter 4. Initially animal were fed a high fructose saturated fat (HFS) diet for a period of 8 weeks to develop insulin resistance and dyslipidemia. The normal diet control (ND), ND + SCE 500 mg/kg bwd, high fructose saturated fat diet control (HFS), HFS + metformin 100 mg/kg bwd, HFS + SCE 250 and HFS + SCE 500 were the experimental groups. SCEs and metformin were administered daily for the next 3 weeks and sacrificed at the end of 11th week. At the end of week 11, HFS rats showed significantly abnormal glucose and insulin tolerance, HOMA-IR, % HbA1c, adiponectin, lipid profile, liver glycolytic and gluconeogenic enzyme activities, liver and muscle triglyceride accumulation compared to ND. HFS rats also exhibited increased level of plasma inflammatory cytokines, upregulated mRNA level of gluconeogenic and lipogenic genes in liver. HFS exhibited the increased expression of GLUT-2 in liver and decreased expression of GLUT-4 in muscle and adipose. SCE treatment also preserved the architecture of pancreas, liver, and kidney tissues. Treatment with SCE reversed the alterations of biochemical parameters, improved insulin sensitivity by modifying gene expression in liver, muscle and adipose tissues. Overall results suggest that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with antiglycation and antioxidant activities.

Information Exchange and Fusion in Dynamic and Heterogeneous Distributed Environments

Context awareness, dynamic reconfiguration at runtime and heterogeneity are key characteristics of future distributed systems, particularly in ubiquitous and mobile computing scenarios. The main contributions of this dissertation are theoretical as well as architectural concepts facilitating information exchange and fusion in heterogeneous and dynamic distributed environments. Our main focus is on bridging the heterogeneity issues and, at the same time, considering uncertain, imprecise and unreliable sensor information in information fusion and reasoning approaches. A domain ontology is used to establish a common vocabulary for the exchanged information. We thereby explicitly support different representations for the same kind of information and provide Inter-Representation Operations that convert between them. Special account is taken of the conversion of associated meta-data that express uncertainty and impreciseness. The Unscented Transformation, for example, is applied to propagate Gaussian normal distributions across highly non-linear Inter-Representation Operations. Uncertain sensor information is fused using the Dempster-Shafer Theory of Evidence as it allows explicit modelling of partial and complete ignorance. We also show how to incorporate the Dempster-Shafer Theory of Evidence into probabilistic reasoning schemes such as Hidden Markov Models in order to be able to consider the uncertainty of sensor information when deriving high-level information from low-level data. For all these concepts we provide architectural support as a guideline for developers of innovative information exchange and fusion infrastructures that are particularly targeted at heterogeneous dynamic environments. Two case studies serve as proof of concept. The first case study focuses on heterogeneous autonomous robots that have to spontaneously form a cooperative team in order to achieve a common goal. The second case study is concerned with an approach for user activity recognition which serves as baseline for a context-aware adaptive application. Both case studies demonstrate the viability and strengths of the proposed solution and emphasize that the Dempster-Shafer Theory of Evidence should be preferred to pure probability theory in applications involving non-linear Inter-Representation Operations.

Ferrocene-Based Pyridylphosphine Ligands – Coordination Chemistry of Group 10, 11 and 12 Metals

English: The present thesis describes the synthesis of 1,1’-ferrocendiyl-based pyridylphosphine ligands, the exploration of their fundamental coordination chemistry and preliminary experiments with selected complexes aimed at potential applications. One main aspect is the synthesis of the bidentate ferrocene-based pyridylphosphine ligands 1-(Pyrid-2-yl)-1’-diphenylphosphinoferrocene, 1-(Pyrid-3-yl)-1’-diphenylphosphinoferrocene and 1-[(Pyrid-2-yl)methyl]-1’-diphenylphosphinoferrocene. A specific feature of these ligands is the ball-bearing like flexibility of the ferrocenebased backbone. An additional flexibility element is the rotation around the C–C single bonds. Consequently, the donor atoms can realise a wide range of positions with respect to each other and are therefore able to adapt to the coordination requirements of different metal centres. The flexibility of the ligand also plays a role in another key aspect of this work, which concerns the coordination mode, i. e. bridging vs. chelating. In addition to the flexibility, also the position of the donor atoms to each other is important. This is largely affected by the position of the pyridyl nitrogen (pyrid-2-yl vs. pyrid-3-yl) and the methylen group in 1-[(Pyrid-2-yl)methyl]-1’-diphenylphosphinoferrocene. Another interesting point is the combination of a soft phosphorus donor atom with a harder nitrogen donor atom, according to the HSAB principle. This combination generates a unique binding profile, since the pi-acceptor character of the P site is able to stabilise a metal centre in a low oxidation state, while the nitrogen sigma-donor ability can make the metal more susceptible to oxidative addition reactions. A P,N-donor combination can afford hemilabile binding profiles, which would be ideal for catalysis. Beyond 1,2-substituted ferrocene derivatives, which are quite successful in catalytic applications, 1,1’-derivatives are rather underrepresented. While a low-yield synthetic pathway to 1-(Pyrid-2-yl)-1’-diphenylphosphinoferrocene was already described in the literature [I. R. Butler, Organometallics 1992, 11, 74.], it was possible to find a new, improved and simplified synthetic pathway. Both other ligands were unknown prior to this work. Satisfactory results in the synthesis of 1-(Pyrid-3-yl)-1’-diphenylphosphinoferrocene could be achieved by working in analogy to the new synthetic procedure for 1-(Pyrid-2-yl)-1’-diphenylphosphinoferrocene. The synthesis of 1-[(Pyrid-2-yl)methyl]-1’-diphenylphosphinoferrocene has been handled by the group of Prof. Petr Stepnicka from Charles University, Prague, Czech Republic. The synthesis of tridentate ligands with an analogous heterodentate arrangement, was investigated briefly as a sideline of this study. The major part of this thesis deals with the fundamental coordination chemistry towards transition metals of the groups 10, 11 and 12. Due to the well-established catalytic properties of analogous palladium complexes, the coordination chemistry towards palladium (group 10) is of particular interest. The metals zinc and cadmium (group 12) are also of substantial importance because they are redox-inert in their divalent state. This is relevant in view of electrochemical investigations concerning the utilisation of the ligands as molecular redox sensors. Also mercury and the monovalent metals silver and gold (group 11) are included because of their rich coordination chemistry. It is essential to answer questions concerning aspects of the ligands’ coordination mode bearing in mind the HSAB principle.