Cheminformatic studies of molecular properties and their influence on bioactivity in the context of drug discovery

Molecular shape has long been known to be an important property for the process of molecular recognition. Previous studies postulated the existence of a drug-like shape space that could be used to artificially bias the composition of screening libraries, with the aim to increase the chance of success in Hit Identification. In this work, it was analysed to which extend this assumption holds true. Normalized Principal Moments of Inertia Ratios (NPRs) have been used to describe the molecular shape of small molecules. It was investigated, whether active molecules of diverse targets are located in preferred subspaces of the NPR shape space. Results illustrated a significantly stronger clustering than could be expected by chance, with parts of the space unlikely to be occupied by active compounds. Furthermore, a strong enrichment of elongated, rather flat shapes could be observed, while globular compounds were highly underrepresented. This was confirmed for a wide range of small molecule datasets from different origins. Active compounds exhibited a high overlap in their shape distributions across different targets, making a purely shape­ based discrimination very difficult. An additional perspective was provided by comparing the shapes of protein binding pockets with those of their respective ligands. Although more globular than their ligands, it was observed that binding sites shapes exhibited a similarly skewed distribution in shape space: spherical shapes were highly underrepresented. This was different for unoccupied binding pockets of smaller size. These were on the contrary identified to possess a more globular shape. The relation between shape complementarity and exhibited bioactivity was analysed; a moderate correlation between bioactivity and parameters including pocket coverage, distance in shape space, and others could be identified, which reflects the importance of shape complementarity. However, this also suggests that other aspects are of relevance for molecular recognition. A subsequent analysis assessed if and how shape and volume information retrieved from pocket or respective reference ligands could be used as a pre-filter in a virtual screening approach. ln Lead Optimization compounds need to get optimized with respect to a variety of pararneters. Here, the availability of past success stories is very valuable, as they can guide medicinal chemists during their analogue synthesis plans. However, although of tremendous interest for the public domain, so far only large corporations had the ability to mine historical knowledge in their proprietary databases. With the aim to provide such information, the SwissBioisostere database was developed and released during this thesis. This database contains information on 21,293,355 performed substructural exchanges, corresponding to 5,586,462 unique replacements that have been measured in 35,039 assays against 1,948 molecular targets representing 30 target classes, and on their impact on bioactivity . A user-friendly interface was developed that provides facile access to these data and is accessible at http//www.swissbioisostere.ch. The ChEMBL database was used as primary data source of bioactivity information. Matched molecular pairs have been identified in the extracted and cleaned data. Success-based scores were developed and integrated into the database to allow re-ranking of proposed replacements by their past outcomes. It was analysed to which degree these scores correlate with chemical similarity of the underlying fragments. An unexpectedly weak relationship was detected and further investigated. Use cases of this database were envisioned, and functionalities implemented accordingly: replacement outcomes are aggregatable at the assay level, and it was shawn that an aggregation at the target or target class level could also be performed, but should be accompanied by a careful case-by-case assessment. It was furthermore observed that replacement success depends on the activity of the starting compound A within a matched molecular pair A-B. With increasing potency the probability to lose bioactivity through any substructural exchange was significantly higher than in low affine binders. A potential existence of a publication bias could be refuted. Furthermore, often performed medicinal chemistry strategies for structure-activity-relationship exploration were analysed using the acquired data. Finally, data originating from pharmaceutical companies were compared with those reported in the literature. It could be seen that industrial medicinal chemistry can access replacement information not available in the public domain. In contrast, a large amount of often-performed replacements within companies could also be identified in literature data. Preferences for particular replacements differed between these two sources. The value of combining different endpoints in an evaluation of molecular replacements was investigated. The performed studies highlighted furthermore that there seem to exist no universal substructural replacement that always retains bioactivity irrespective of the biological environment. A generalization of bioisosteric replacements seems therefore not possible. - La forme tridimensionnelle des molécules a depuis longtemps été reconnue comme une propriété importante pour le processus de reconnaissance moléculaire. Des études antérieures ont postulé que les médicaments occupent préférentiellement un sous-ensemble de l'espace des formes des molécules. Ce sous-ensemble pourrait être utilisé pour biaiser la composition de chimiothèques à cribler, dans le but d'augmenter les chances d'identifier des Hits. L'analyse et la validation de cette assertion fait l'objet de cette première partie. Les Ratios de Moments Principaux d'Inertie Normalisés (RPN) ont été utilisés pour décrire la forme tridimensionnelle de petites molécules de type médicament. Il a été étudié si les molécules actives sur des cibles différentes se co-localisaient dans des sous-espaces privilégiés de l'espace des formes. Les résultats montrent des regroupements de molécules incompatibles avec une répartition aléatoire, avec certaines parties de l'espace peu susceptibles d'être occupées par des composés actifs. Par ailleurs, un fort enrichissement en formes allongées et plutôt plates a pu être observé, tandis que les composés globulaires étaient fortement sous-représentés. Cela a été confirmé pour un large ensemble de compilations de molécules d'origines différentes. Les distributions de forme des molécules actives sur des cibles différentes se recoupent largement, rendant une discrimination fondée uniquement sur la forme très difficile. Une perspective supplémentaire a été ajoutée par la comparaison des formes des ligands avec celles de leurs sites de liaison (poches) dans leurs protéines respectives. Bien que plus globulaires que leurs ligands, il a été observé que les formes des poches présentent une distribution dans l'espace des formes avec le même type d'asymétrie que celle observée pour les ligands: les formes sphériques sont fortement sous­ représentées. Un résultat différent a été obtenu pour les poches de plus petite taille et cristallisées sans ligand: elles possédaient une forme plus globulaire. La relation entre complémentarité de forme et bioactivité a été également analysée; une corrélation modérée entre bioactivité et des paramètres tels que remplissage de poche, distance dans l'espace des formes, ainsi que d'autres, a pu être identifiée. Ceci reflète l'importance de la complémentarité des formes, mais aussi l'implication d'autres facteurs. Une analyse ultérieure a évalué si et comment la forme et le volume d'une poche ou de ses ligands de référence pouvaient être utilisés comme un pré-filtre dans une approche de criblage virtuel. Durant l'optimisation d'un Lead, de nombreux paramètres doivent être optimisés simultanément. Dans ce contexte, la disponibilité d'exemples d'optimisations réussies est précieuse, car ils peuvent orienter les chimistes médicinaux dans leurs plans de synthèse par analogie. Cependant, bien que d'un extrême intérêt pour les chercheurs dans le domaine public, seules les grandes sociétés pharmaceutiques avaient jusqu'à présent la capacité d'exploiter de telles connaissances au sein de leurs bases de données internes. Dans le but de remédier à cette limitation, la base de données SwissBioisostere a été élaborée et publiée dans le domaine public au cours de cette thèse. Cette base de données contient des informations sur 21 293 355 échanges sous-structuraux observés, correspondant à 5 586 462 remplacements uniques mesurés dans 35 039 tests contre 1948 cibles représentant 30 familles, ainsi que sur leur impact sur la bioactivité. Une interface a été développée pour permettre un accès facile à ces données, accessible à http:/ /www.swissbioisostere.ch. La base de données ChEMBL a été utilisée comme source de données de bioactivité. Une version modifiée de l'algorithme de Hussain et Rea a été implémentée pour identifier les Matched Molecular Pairs (MMP) dans les données préparées au préalable. Des scores de succès ont été développés et intégrés dans la base de données pour permettre un reclassement des remplacements proposés selon leurs résultats précédemment observés. La corrélation entre ces scores et la similarité chimique des fragments correspondants a été étudiée. Une corrélation plus faible qu'attendue a été détectée et analysée. Différents cas d'utilisation de cette base de données ont été envisagés, et les fonctionnalités correspondantes implémentées: l'agrégation des résultats de remplacement est effectuée au niveau de chaque test, et il a été montré qu'elle pourrait également être effectuée au niveau de la cible ou de la classe de cible, sous réserve d'une analyse au cas par cas. Il a en outre été constaté que le succès d'un remplacement dépend de l'activité du composé A au sein d'une paire A-B. Il a été montré que la probabilité de perdre la bioactivité à la suite d'un remplacement moléculaire quelconque est plus importante au sein des molécules les plus actives que chez les molécules de plus faible activité. L'existence potentielle d'un biais lié au processus de publication par articles a pu être réfutée. En outre, les stratégies fréquentes de chimie médicinale pour l'exploration des relations structure-activité ont été analysées à l'aide des données acquises. Enfin, les données provenant des compagnies pharmaceutiques ont été comparées à celles reportées dans la littérature. Il a pu être constaté que les chimistes médicinaux dans l'industrie peuvent accéder à des remplacements qui ne sont pas disponibles dans le domaine public. Par contre, un grand nombre de remplacements fréquemment observés dans les données de l'industrie ont également pu être identifiés dans les données de la littérature. Les préférences pour certains remplacements particuliers diffèrent entre ces deux sources. L'intérêt d'évaluer les remplacements moléculaires simultanément selon plusieurs paramètres (bioactivité et stabilité métabolique par ex.) a aussi été étudié. Les études réalisées ont souligné qu'il semble n'exister aucun remplacement sous-structural universel qui conserve toujours la bioactivité quel que soit le contexte biologique. Une généralisation des remplacements bioisostériques ne semble donc pas possible.

Reporting a program evaluation: Needs, program plan, intervention, and decisions

The approach to intervention programs varies depending on the methodological perspective adopted. This means that health professionals lack clear guidelines regarding how best to proceed, and it hinders the accumulation of knowledge. The aim of this paper is to set out the essential and common aspects that should be included in any program evaluation report, thereby providing a useful guide for the professional regardless of the procedural approach used. Furthermore, the paper seeks to integrate the different methodologies and illustrate their complementarity, this being a key aspect in terms of real intervention contexts, which are constantly changing. The aspects to be included are presented in relation to the main stages of the evaluation process: needs, objectives and design (prior to the intervention), implementation (during the intervention), and outcomes (after the intervention). For each of these stages the paper describes the elements on which decisions should be based, highlighting the role of empirical evidence gathered through the application of instruments to defined samples and according to a given procedure.

Access Management Research and Awareness Program : Phase IV, 1999

Access management involves balancing the dual roles that roadways must play - through travel and access to property and economic activity. When these roles are not in proper balance, the result is a roadway system that functions sub-optimally. Arterial routes that have a too high driveway density and provide overly extensive access to property have high crash rates and begin to suffer in terms of traffic operations. Such routes become congested, delays increase, and mean travel speeds decline. The Iowa access management research and awareness project has had four distinct phases. Phase I involved a detailed review of the extensive national access management literature so lessons learned elsewhere could be applied in Iowa. In Phase II original case study research was conducted in Iowa. Phase III of the project concentrated on outreach and education about access management. Phase IV of the Iowa access management project extended the work conducted during Phases II and III. The main work products for Phase IV were as follows: 1) three additional before and after case studies, illustrating the impacts of various access management treatments on traffic safety, traffic operations, and business vitality; 2) an access management handbook aimed primarily at local governments in Iowa; 3) a modular access management toolkit with brief descriptions of various access management treatments and considerations; and 4) an extensive outreach plan aimed at getting the results of Phases I through IV of the project out to diverse audiences in Iowa and elsewhere.

Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents.

Dual-energy X-ray absorptiometry (DXA) is the most widely used technical instrument for evaluating bone mineral content (BMC) and density (BMD) in patients of all ages. However, its use in pediatric patients, during growth and development, poses a much more complex problem in terms of both the technical aspects and the interpretation of the results. For the adults population, there is a well-defined term of reference: the peak value of BMD attained by young healthy subjects at the end of skeletal growth. During childhood and adolescence, the comparison can be made only with healthy subjects of the same age, sex and ethnicity, but the situation is compounded by the wide individual variation in the process of skeletal growth (pubertal development, hormone action, body size and bone size). The International Society for Clinical Densitometry (ISCD) organized a Pediatric Position Development Conference to discuss the specific problems of bone densitometry in growing subjects (9-19 years of age) and to provide essential recommendations for its clinical use.

Supply chain integration: studies on linking customer responsiveness and operational efficiency in logistics policy planning

Abstract The research problem in the thesis deals with improving the responsiveness and efficiency of logistics service processes between a supplier and its customers. The improvement can be sought by customizing the services and increasing the coordination of activities between the different parties in the supply chain. It is argued that to achieve coordination the parties have to have connections on several levels. In the framework employed in this research, three contexts are conceptualized at which the linkages can be planned: 1) the service policy context, 2) the process coordination context, and 3) the relationship management context. The service policy context consists of the planning methods by which a supplier analyzes its customers' logistics requirements and matches them with its own operational environment and efficiency requirements. The main conclusion related to the service policy context is that it is important to have a balanced selection of both customer-related and supplier-related factors in the analysis. This way, while the operational efficiency is planned a sufficient level of service for the most important customers is assured. This kind of policy planning involves taking multiple variables into the analysis, and there is a need to develop better tools for this purpose. Some new approaches to deal with this are presented in the thesis.The process coordination context and the relationship management context deal with the issues of how the implementation of the planned service policies can be facilitated in an inter-organizational environment. Process coordination includes typically such mechanisms as control rules, standard procedures and programs, but inhighly demanding circumstances more integrative coordination mechanisms may be necessary. In the thesis the coordination problems in third-party logistics relationship are used as an example of such an environment. Relationship management deals with issues of how separate companies organize their relationships to improve the coordination of their common processes. The main implication related to logistics planning is that by integrating further at the relationship level, companies can facilitate the use of the most efficient coordination mechanisms and thereby improve the implementation of the selected logistics service policies. In the thesis, a case of a logistics outsourcing relationship is used to demonstrate the need to address the relationship issues between the service provider andthe service buyer before the outsourcing can be done.The dissertation consists of eight research articles and a summarizing report. The principal emphasis in the articles is on the service policy planning context, which is the main theme of six articles. Coordination and relationship issues are specifically addressed in two of the papers.

Essays on Innovativeness and its Evaluation in Small and Medium-sized Enterprises

Tutkimus koostuu neljästä artikkelista, jotka käsittelevät suomalaisten pienten ja keskisuurten teollisuusyritysten (PKT-yritysten) innovatiivisuutta, sen attribuutteja (ominaispiirteitä) sekä indikaattoreita. Tutkimuksessa tarkastellaan sekä kirjallisuudessa esitettyjä että PKT-johtajien ja PKT-yritystenkehityshankkeiden rahoituspäätöksiin osallistuvien yritystutkijoiden haastatteluissa esittämiä innovatiivisuuden määritelmiä. Innovatiivisuusindikaattoreista tarkastellaan PKT-yritysten kehittämishankkeille sovellettavia rahoitus- ja arviointikriteerejä sekä yritysten ulkopuolisten rahoittajien että PKT-johtajien näkökulmasta. Erityistä huomiota kohdistetaan sovellettuihin laadullisiin ja ei-numeerisiin innovatiivisuuden arviointikriteereihin. Sekä kirjallisuudessa että kymmenen yritystutkijan ja kuuden esimerkkiyrityksen johtajan haastatteluissa innovaation uutuus yhdistetään innovatiivisuuteen. Muita tärkeitä innovatiivisuuteen liitettyjä ominaisuuksia olivat markkinat, muista yrityksistä erottuminen ja yksilöiden luovuus. Ihmisläheiset ja yksilöihin liittyvät näkökulmat korostuvat yritystutkijoiden ja PKT-johtajien innovatiivisuuden määritelmissä, kun taas kirjallisuudessa annetaan enemmän painoa ympäristölle, tuotteille ja markkinoille. Yritystutkijat pitivät yritykseen ja sen johtajaan liittyviä tekijöitä tärkeinä rahoitettavien kehittämishankkeiden panosten arviointikriteereinä. Tuotteiden kaupallinen menestys oli rahoittajan kannalta tärkein tulostekijä. Tarkastelluissa esimerkkiyrityksissä kehityshankkeista päättäminen ja hankkeiden arviointi on toisaalta intuitiivista ja saattaa olla tiedostamatontakin, koska yritysten kehittämistoiminta on vähäistä. Pienyritysten johtajat korostavat arvioinnissa rahallisiamittareita, vaikka sekä numeerisia että laadullisia kriteereitä sovelletaan. Todennäköisin syy tälle on pienyritysten rajalliset taloudelliset voimavarat. Toinen mahdollinen syy rahoituksellisten tekijöiden painottamiseen on, että tämän päivän ihannejohtaja ymmärretään analyyttiseksi ja mm.rahavirtoja valvovaksi. Kuitenkin innovatiiviset yritysjohtajat pitävät innovaatioiden luomista yhtenä elämän hauskoista puolista. Innovatiiviset esimerkkiyritykset ovat tulevaisuuteen ja kasvuun suuntautuneita strategisella tasolla. Operationaalisella tasolla ne tuottavat keksintöjä ja innovaatioita. Patentteja tarkastelluilla yrityksillä on kuitenkin vähän. Sekä innovatiiviset että vähemmän innovatiiviset esimerkkiyritykset ovat voimakkaasti asiakassuuntautuneita ja erikoistuneita tiettyihin tuotteisiin ja asiakkaisiin. Asiakkaiden tarpeita tyydytetään kehittämällä niitä vastaavia tuotteita. Tästä johtuu, että valtaosa yritysten kehittämistoiminnasta kohdistuu tuotteisiin tai tuotantoon.

Gambling in Spain: update on experience, research and policy

AIMS: To describe the current situation of gambling in Spain, sketching its history and discussing the regulations and legislation currently in force within the framework of the European Union (EU), and to review the epidemiology of gambling in Spain, the self-help groups and professional treatments available, and their potential effectiveness. METHODS: A systematic computerized search was performed in three databases (EMBASE, PubMed and PsychINFO, including articles and chapters) and the reference lists from previous reviews to obtain some of the most relevant studies published up to now on the topic of pathologic gambling in Spain. RESULTS: Similar to other EU countries, Spain has a high prevalence of pathologic gambling, focused on specific culturally bounded types of gambling. Expenditure in online gaming has risen significantly in the last few years, prompting the Spanish government to draft new legislation to regulate gaming. CONCLUSIONS: The gaming industry is expected to be one of the fastest growing sectors in Spain in the coming years owing to the rise of new technologies and the development of online gaming

Towards an Integrative Information Society: Studies on Individuality in Speech and Sign

The flow of information within modern information society has increased rapidly over the last decade. The major part of this information flow relies on the individual’s abilities to handle text or speech input. For the majority of us it presents no problems, but there are some individuals who would benefit from other means of conveying information, e.g. signed information flow. During the last decades the new results from various disciplines have all suggested towards the common background and processing for sign and speech and this was one of the key issues that I wanted to investigate further in this thesis. The basis of this thesis is firmly within speech research and that is why I wanted to design analogous test batteries for widely used speech perception tests for signers – to find out whether the results for signers would be the same as in speakers’ perception tests. One of the key findings within biology – and more precisely its effects on speech and communication research – is the mirror neuron system. That finding has enabled us to form new theories about evolution of communication, and it all seems to converge on the hypothesis that all communication has a common core within humans. In this thesis speech and sign are discussed as equal and analogical counterparts of communication and all research methods used in speech are modified for sign. Both speech and sign are thus investigated using similar test batteries. Furthermore, both production and perception of speech and sign are studied separately. An additional framework for studying production is given by gesture research using cry sounds. Results of cry sound research are then compared to results from children acquiring sign language. These results show that individuality manifests itself from very early on in human development. Articulation in adults, both in speech and sign, is studied from two perspectives: normal production and re-learning production when the apparatus has been changed. Normal production is studied both in speech and sign and the effects of changed articulation are studied with regards to speech. Both these studies are done by using carrier sentences. Furthermore, sign production is studied giving the informants possibility for spontaneous speech. The production data from the signing informants is also used as the basis for input in the sign synthesis stimuli used in sign perception test battery. Speech and sign perception were studied using the informants’ answers to questions using forced choice in identification and discrimination tasks. These answers were then compared across language modalities. Three different informant groups participated in the sign perception tests: native signers, sign language interpreters and Finnish adults with no knowledge of any signed language. This gave a chance to investigate which of the characteristics found in the results were due to the language per se and which were due to the changes in modality itself. As the analogous test batteries yielded similar results over different informant groups, some common threads of results could be observed. Starting from very early on in acquiring speech and sign the results were highly individual. However, the results were the same within one individual when the same test was repeated. This individuality of results represented along same patterns across different language modalities and - in some occasions - across language groups. As both modalities yield similar answers to analogous study questions, this has lead us to providing methods for basic input for sign language applications, i.e. signing avatars. This has also given us answers to questions on precision of the animation and intelligibility for the users – what are the parameters that govern intelligibility of synthesised speech or sign and how precise must the animation or synthetic speech be in order for it to be intelligible. The results also give additional support to the well-known fact that intelligibility in fact is not the same as naturalness. In some cases, as shown within the sign perception test battery design, naturalness decreases intelligibility. This also has to be taken into consideration when designing applications. All in all, results from each of the test batteries, be they for signers or speakers, yield strikingly similar patterns, which would indicate yet further support for the common core for all human communication. Thus, we can modify and deepen the phonetic framework models for human communication based on the knowledge obtained from the results of the test batteries within this thesis.

What happens in the first 200 ms of word reading : ERP studies on visual word recognition with top-down and bottom-up approaches /

In this thesis, three main questions were addressed using event-related potentials (ERPs): (1) the timing of lexical semantic access, (2) the influence of "top-down" processes on visual word processing, and (3) the influence of "bottom-up" factors on visual word processing. The timing of lexical semantic access was investigated in two studies using different designs. In Study 1,14 participants completed two tasks: a standard lexical decision (LD) task which required a word/nonword decision to each target stimulus, and a semantically primed version (LS) of it using the same category of words (e.g., animal) within each block following which participants made a category judgment. In Study 2, another 12 participants performed a standard semantic priming task, where target stimulus words (e.g., nurse) could be either semantically related or unrelated to their primes (e.g., doctor, tree) but the order of presentation was randomized. We found evidence in both ERP studies that lexical semantic access might occur early within the first 200 ms (at about 170 ms for Study 1 and at about 160 ms for Study 2). Our results were consistent with more recent ERP and eye-tracking studies and are in contrast with the traditional research focus on the N400 component. "Top-down" processes, such as a person's expectation and strategic decisions, were possible in Study 1 because of the blocked design, but they were not for Study 2 with a randomized design. Comparing results from two studies, we found that visual word processing could be affected by a person's expectation and the effect occurred early at a sensory/perceptual stage: a semantic task effect in the PI component at about 100 ms in the ERP was found in Study 1 , but not in Study 2. Furthermore, we found that such "top-down" influence on visual word processing might be mediated through separate mechanisms depending on whether the stimulus was a word or a nonword. "Bottom-up" factors involve inherent characteristics of particular words, such as bigram frequency (the total frequency of two-letter combinations of a word), word frequency (the frequency of the written form of a word), and neighborhood density (the number of words that can be generated by changing one letter of an original word or nonword). A bigram frequency effect was found when comparing the results from Studies 1 and 2, but it was examined more closely in Study 3. Fourteen participants performed a similar standard lexical decision task but the words and nonwords were selected systematically to provide a greater range in the aforementioned factors. As a result, a total of 18 word conditions were created with 18 nonword conditions matched on neighborhood density and neighborhood frequency. Using multiple regression analyses, we foimd that the PI amplitude was significantly related to bigram frequency for both words and nonwords, consistent with results from Studies 1 and 2. In addition, word frequency and neighborhood frequency were also able to influence the PI amplitude separately for words and for nonwords and there appeared to be a spatial dissociation between the two effects: for words, the word frequency effect in PI was found at the left electrode site; for nonwords, the neighborhood frequency effect in PI was fovind at the right elecfrode site. The implications of otir findings are discussed.

Studies on Rubber Composition as Passive Acoustic Materials in Underwater Electro Acoustic Tranducer Technology and Their aging Characteristic

The research work has been in the area of compounding and characterization of rubbers for use in under water electro acoustic transducers. The study also covers specific material system such as encapsulation materials, baffle material, seal material, etc. Life prediction techniques of under water rubbers in general have been established with reference to more than one functional property. Ranges of passive materials, besides the active sensing material go into the construction of underwater electro acoustic transducers. Reliability of the transducer is critically dependent on these passive materials. Rubbers are a major class of passive materials. The present work concentrates on these materials. Conventional rubbers are inadequate to meet many of the stringent function specific requirements. There exists a large gap of information in the rubber technology of underwater rubbers, particularly relating to underwater electro acoustic transducers. This study is towards filling up the gaps of information in this crucial area. Water intake into rubber is considered as the single most important issue for the long-term performance of rubbers, especially Neoprene. In this study, the cause and effects of a range of parameters affecting the water absorption by diffusion and permeation have been investigated.

Biochemical Effect of Dicarboxylic Acids on Oxalate Metabolism in Experimental Rats and Studies on Oxalate Degrading Bacteria

The current study is an attempt to find a means of lowering oxalate concentration in individuals susceptible to recurrent calcium oxalate stone disease.The formation of renal stone composed of calcium oxalate is a complex process that remains poorly understood and treatment of idiopathic recurrent stone formers is quite difficult and this area has attracted lots of research workers. The main objective of this work are to study the effect of certain mono and dicarboxylic acids on calcium oxalate crystal growth in vitro, isolation and characterization of oxalate degrading bacteria, study the biochemical effect of sodium glycollate and dicarboxylic acids on oxalate metabolism in experimental stone forming rats and To investigate the effect of dicarboxylic acids on oxalate metabolism in experimental hyperoxaluric rats. Oxalic acid is one of the most highly oxidized organic compound widely distributed in the diets of man and animals, and ingestion of plants that contain high concentration of oxalate may lead to intoxication. Excessive ingestion of dietary oxalate may lead to hyperoxaluria and calcium oxalate stone disease.The formation of calcium oxalate stone in the urine is dependent on the saturation level of both calcium and oxalate. Thus the management of one or both of these ions in individuals susceptible to urolithiasis appears to be important. The control of endogenous oxalate synthesis from its precursors in hyperoxaluric situation is likely to yield beneficial results and can be a useful approach in the medical management of urinary stones. A variety of compounds have been investigated to curtain endogenous oxalate synthesis which is a crucial factor, most of these compounds have not proved to be effective in the in vivo situation and some of them are not free from the toxic effect. The non-operative management of stone disease has been practiced in ancient India in the three famous indigenous systems of medicine, Ayurveda, Unani and Siddha, and proved to be effective.However the efficiency of most of these substances is still questionable and demands further study. Man as well as other mammals cannot metabolize oxalic acid. Excessive ingestion of oxalic acid can arise from oxalate rich food and from its major metabolic precursors, glycollate, glyoxylate and ascorbic acid can lead to an acute oxalate toxicity. Increasedlevels of circulating oxalate, which can result in a variety of diseases including renal failure and oxalate lithiasis. The ability to enzymatically degrade oxalate to less noxious Isubstances, formate and CO2, could benefit a great number of individuals including those afflicted with hyperoxaluria and calcium oxalate stone disease.

Studies on Modified Atmosphere Packaging of Pearl Spot (Etroplussuratensis) With Special Emphasis to Biochemical and Microbiological Parameters

A modified atmosphere may be defined as a packaging or storage of a perishable product in an atmosphere other than that of air. A modified atmosphere (MA) applies to food packaged products changes continuously throughout the storage period. The pearl spot (Etroplus suratensis) is an important brackish water fish belonging to the family Cichlidae. The present work was carried out to see the effect of modified atmosphere packaging on the shelf life fresh pearl spot stored in ice to extent the shelf life. The objectives of the present study are to study the suitability of Thermoformed Trays for modified atmosphere packaging, to standardize the most suitable gas mixture for modified atmosphere packaging pearl spot based on sensory evaluation, to find out the effect of modified atmosphere packaging in comparison to air packaging, to study the biochemical, microbiological, sensory and textural characteristics during storage, to study the safety concern regarding the Clostridium botulinum during modified atmosphere packaging, to find out the most suitable chemical quality indices for modified atmosphere stored pearl spot

Studies on the Characteristics of Vertical Circulation and Equatorial Waves using Indian MST Radar

The aim of the present study is to understand the characteristics and properties of different wave modes and the vertical circulation pattern in the troposphere and lower stratosphere over Indian region using data obtained from the Indian Mesosphere-Stratosphere Troposphere (MST) radar, National Center for Environmental Prediction/National Centres of Atmospheric Research (NCEP/NCAR) reanalysed data and radiosonde observations.Studies on the vertical motion in monsoon Hadley circulation are carried out and the results are discussed . From the analysis of MST radar data, an overall picture of vertical motion of air over Indian region is explained and noted that there exists sinking motion both during winter and summer. Besides, the study shows that there is an anomalous northerly wind in the troposphere over the southern peninsular region during southwest monsoon season.The outcome of the study on intrusion of mid-latitude upper tropospheric trough and associated synoptic-scale vertical velocity over the tropical Indian latitudes are reported and discussed . It shows that there is interaction between north Indian latitudes and tropical easterly region, when there is an eastward movement of Western Disturbance across the country. It explains the strengthening of westerlies and a change of winter westerlies into easterlies in the tropical troposphere and lower stratosphere. The divergence field computed over the MST radar station shows intensification in the downward motion in association with the synoptic systems of the northwest Indian region.

Studies on Electrical and Thermal Properties of Certain Selected Photonic Materials

The present thesis is centered around the study of electrical and thermal properties of certain selected photonic materials.We have studied the electrical conduction mechanism in various phases of certain selected photonic materials and those associated with different phase transitions occurring in them. A phase transition leaves its own impressions on the key parameters like electrical conductivity and dielectric constant. However, the activation energy calculation reveals the dominant factor responsible for conduction process.PA measurements of thermal diffusivity in certain other important photonic materials are included in the remaining part of the research work presented in this thesis. PA technique is a promising tool for studying thermal diffusivities of solid samples in any form. Because of its crucial role and common occurrence in heat flow problems, the thermal diffusivity determination is often necessary and knowledge of thermal diffusivity can intum be used to calculate the thermal conductivity. Especially,knowledge of the thermal diffusivity of semiconductors is important due to its relation to the power dissipation problem in microelectronic and optoelectronic devices which limits their performances. More than that, the thermal properties, especially those of thin films are of growing interest in microelectronics and microsystems because of the heat removal problem involved in highly integrated devices. The prescribed chapter of the present theis demonstrates how direct measurement of thermal diffusivity can be carried out in thin films of interest in a simple and elegant manner using PA techniques. Although results of only representative measurements viz; thermal diffusivity values in Indium, Aluminium, Silver and CdS thin films are given here, evaluation of this quantity for any photonic and / electronic material can be carried out using this technique in a very simple and straight forward manner.