New insights into small molecules inhibitors and protein-protein interactions of VirB8 : a critical conserved component of the type IV secretion system.

Les systèmes bactériens de sécrétion de type IV (T4SS) sont constitués d’un ensemble de 8 à 12 protéines conservées. Ces dernières sont utilisées lors de la translocation de protéines, la translocation de complexes ADN-protéines mais aussi pour le transport de ces derniers au travers de la membrane cellulaire. Les T4SS, en tant que facteurs de virulence pour beaucoup de pathogènes comme Brucella suis, sont donc d’excellents modèles cibles pour le développement de médicaments d’antivirulence. Ces médicaments, en privant le pathogène de son facteur essentiel de virulence : le T4SS, constituent une alternative ou encore une amélioration des traitements antibiotiques utilisés actuellement. VirB8, un facteur d’assemblage conservé dans le T4SS, forme des dimères qui sont importants pour la fonction des T4SS dans ces pathogènes. De par ses interactions multiples, VirB8 est un excellent modèle pour l’analyse des facteurs d’assemblage mais aussi en tant que cible de médicaments qui empêcheraient son interaction avec d’autres protéines et qui, in fine, désarmeraient les bactéries en les privant de leur fonctions essentielles de virulence. À ce jour, nous savons qu’il existe un équilibre monomère-dimère et un processus d’homodimerization de VirB8 dont l’importance est vitale pour la fonctionnement biologique des T4SSs. En se basant sur des essais quantitatifs d’interaction, nous avons identifié (i) des sites potentiels d’interaction avec d’autres protéines VirB du T4SS mais aussi (ii) isolé des petites molécules inhibitrices afin de tester la fonction protéique de VirB8. Afin de déterminer les acides aminés importants pour l’hétérodimérization de VirB8 avec VirB10, nous avons effectué des expériences de mutagenèse aléatoire, de phage display et d’arrimage moléculaire in silico. Ces expériences ont démontré l’importance de trois acides aminés localisés sur le feuillet β : R160, S162, T164 et I165. Ces derniers seraient importants pour l’association de VirB8 avec VirB10 étant donné que leur mutagenèse entraine une diminution de la formation du complexe VirB8-VirB10. L’objectif actuel de notre projet de recherche est de pouvoir mieux comprendre mais aussi d’évaluer le rôle de VirB8 dans l’assemblage du T4SS. Grace à un méthode de criblage adaptée à partir de la structure de VirB8, nous avons pu identifié une petite molécule inhibitrice BAR-068, qui aurait un rôle prometteur dans l’inhibition du T4SS. Nous avons utilisé la spectroscopie par fluorescence, l’essai à deux hybrides, le cross-linking et la cristallographie afin de déterminer le mécanisme d'interaction existant entre VirB8 et BAR-068. Ces travaux pourraient permettre de nombreuses avancées, notamment en termes de compréhension des mécanismes d’inhibition du T4SS. Notre objectif ultime est de pouvoir caractériser la séquence d’évènements essentiels à l’assemblage et au fonctionnement du T4SS. De manière globale, notre projet de recherche permettrait de révéler les grands principes d’assemblage des protéines membranaires, les processus de sécrétion de protéines chez les bactéries mais aussi de proposer une nouvelle stratégie lors du développement de drogues antimicrobiennes.

Introducing "Critical Essays": Leigh Hunt and theatrical criticism in the early nineteenth century

The years 1801 to 1808 saw the emergence of Leigh Hunt as a public figure on the London literary scene, first with the publication of his collection of poetry, "Juvenilia", and then with his work as theater critic for "The News" between 1805 and 1807. [...]

Studies on development of MgB2 superconductor with improved in-field critical current density

National Institute for Interdisciplinary Science and Technology

Effect of Improving Energy Efficiency on System Reliability

In the present scenario of energy demand overtaking energy supply top priority is given for energy conservation programs and policies. Most of the process plants are operated on continuous basis and consumes large quantities of energy. Efficient management of process system can lead to energy savings, improved process efficiency, lesser operating and maintenance cost, and greater environmental safety. Reliability and maintainability of the system are usually considered at the design stage and is dependent on the system configuration. However, with the growing need for energy conservation, most of the existing process systems are either modified or are in a state of modification with a view for improving energy efficiency. Often these modifications result in a change in system configuration there by affecting the system reliability. It is important that system modifications for improving energy efficiency should not be at the cost of reliability. Any new proposal for improving the energy efficiency of the process or equipments should prove itself to be economically feasible for gaining acceptance for implementation. In order to arrive at the economic feasibility of the new proposal, the general trend is to compare the benefits that can be derived over the lifetime as well as the operating and maintenance costs with the investment to be made. Quite often it happens that the reliability aspects (or loss due to unavailability) are not taken into consideration. Plant availability is a critical factor for the economic performance evaluation of any process plant.The focus of the present work is to study the effect of system modification for improving energy efficiency on system reliability. A generalized model for the valuation of process system incorporating reliability is developed, which is used as a tool for the analysis. It can provide an awareness of the potential performance improvements of the process system and can be used to arrive at the change in process system value resulting from system modification. The model also arrives at the pay back of the modified system by taking reliability aspects also into consideration. It is also used to study the effect of various operating parameters on system value. The concept of breakeven availability is introduced and an algorithm for allocation of component reliabilities of the modified process system based on the breakeven system availability is also developed. The model was applied to various industrial situations.

E-marketing motivators,inhibitors and critical success factors: A study of small and medium tourism enterprises (SMTES) in Mauritius and Andaman islands, India

Information and Communication Technologies (ICTs) have a dramatic impact on the tourism industry because they force this sector as a whole to rethink the way in which it organises its business . In the light of such rethinking within the tourism industry, this study has focussed on the Small and Medium Tourism Enterprises (SMTEs) in two island destinations, namely Mauritius and Andaman Islands, India.Suggestions. The findings conceming SMTEs in Mauritius and Andaman Islands have been compared to make some destination-specific inferences. The relevance of the findings has been discussed with reference to the SMTEs in the two destinations as well as the possible acceptability in other comparable settings. Suggestions have been made for further research in SMTEs’ use of the Internet for marketing function.

Disorder-induced critical phenomena in magnetically glassy Cu-Al-Mn alloys

Measurements of magnetic hysteresis loops in Cu-Al-Mn alloys of different Mn content at low temperatures are presented. The loops are smooth and continuous above a certain temperature, but exhibit a magnetization discontinuity below that temperature. Scaling analysis suggest that this system displays a disorder-induced phase transition line. Measurements allow one to determine the critical exponents ß=0.03±0.01 and ß¿=0.4±0.1, which coincide with those reported recently in a different system, thus supporting the existence of universality for disorder-induced critical points.

Benthic ecology of selected prawn culture fields and ponds near Cochin

The thesis on the"Benthic ecology of selected prawn culture fields and ponds near Cochin” was taken up with a view to provide information on the qualitative and quantitative distribution of benthos and their relationships to prawnproduction of different culture ecosystems and to the physico-chemical parameters influencing their production. A two-year observation was carried out in nine selected prawn culture systems including perennial ponds (stations 1 to 4) seasonal fields (stations 5 to 7) and contiguous canals (stations 8 and 9) during December 1988 to November 1989. All macro- and meiobenthic organisms contributing to the faua were identified and their abundance, distribution, diversity, biomass and trophic relationships between benthos and prawns were studied. The environmental variables studied were temperature pH, salinity, dissolved oxygen, alkalinity, nitrite-nitrogen, nitrate-nitrogen, amonianitrogen, phosphate and silicate of bottom water and organic carbon and texture of the soil The thesis is presented in 4 Chapters. Chapter I presents an’ INTRODUCTION to the topic of study and a review of relevant works to bring an awareness to the present status of research in benthos and benthic ecology. Chapter 11, MATERIALS AND MTHODS, includes the techniques of sampling, preservation of samples and methods of analyses of various physico-chemical factors and area covered under the study is also given in this chapter. Chapter III, HYDROGRAPHY deals with the results of investigation and discussion onthe physico-chemical parameters of water and Chapter IV, SEDIMENT covers the sedimentoloical characteristics of the different culture systems followed by a detailed discussion. Chapter V, BOTTOM FAUNA presents an account on the various aspects of benthos and benthic ecology and the details of prawn production. A discussion on the overall assessment of interrelations between abiotic and biotic factors is given in Chapter VI, DISCUSSION. A critical evaluation of the implication of benthic production on prawn production under culture conditions and trophic relationships are also included in this chapter. An executive SUMMARY of the observations made during this study is presented in the final section of the thesis .

A critical study of major construction projects in kerala vis-a-vis effectiveness in project implementation

Chapter 1 presents a brief note on the state at which the construction industry stands at present, bringing into focus the significance of the critical study. Relevance of the study, area of investigation and objectives of the study are outlined in this chapter. The 2nd chapter presents a review of the literature on the relevant areas. In the third chapter an analysis on time and cost overrun in construction highlighting the major factors responsible for it has been done. A couple of case studies to estimate loss to the nation on account of delay in construction have been presented in the chapter. The need for an appropriate estimate and a competent contractor has been emphasised for improving effectiveness in the project implementation. Certain useful equations and thoughts have been formulated on this area in this chapter that can be followed in State PWD and other Govt. organisations. Case studies on project implementation of major projects undertaken by Government sponsored/supported organizations in Kerala have been dealt with in Chapter 4. A detailed description of the project of Kerala Legislature Complex with a critical analysis has been given in this chapter. A detailed account of the investigations carried out on the construction of International Stadium, a sports project of Greater Cochin Development Authority is included here. The project details of Cochin International Airport at Nedumbassery, its promoters and contractors are also discussed in Chapter 4. Various aspects of implementation which led the above projects successful have been discussed in chapter 5. The data collected were analysed through discussion and perceptions to arrive at certain conclusions. The emergence of front-loaded contract and its impact on economics of the project execution are dealt with in this chapter. Analysis of delays in respect of the various project narrated in chapter 3 has been done here. The root causes of the project time and overrun and its remedial measures are also enlisted in this chapter. Study of cost and time overrun of any construction project IS a part of construction management. Under the present environment of heavy investment on construction activities in India, the consequences of mismanagement many a time lead to excessive expenditure which are not be avoidable. Cost consciousness, therefore has to be keener than ever before. Optimization in investment can be achieved by improved dynamism in construction management. The successful completion of coristruction projects within the specified programme, optimizing three major attributes of the process - quality, schedule and costs - has become the most valuable and challenging task for the engineer - managers to perform. So, the various aspects of construction management such as cost control, schedule control, quality assurance, management techniques etc. have also been discussed in this fifth chapter. Chapter 6 summarises the conclusions drawn from the above criticalr1 of rhajor construction projects in Kerala.

IA Critical Study of the Impact of Institutional Finance on Agriculture in Selected Villages of Ernakulam Revenue District

Vast changes have taken place in the field of institutional rural credit in India since the nationalisation of nineteen commercial banks in 1969. The supply of institutional finance to cultivators amounted to 63.2 percent of the total credit in 1981 compared to 31.2 percent in 1971. Insti tutionalisation of agricultural credit envisaged two objectives in general. One was to emancipate cultivators and farmers from the clutches of indigenous financiers and money lenders. The second was to make farmers financially capable of adopting the new technology or improved practices in agriculture so as to increase their agricultural production and thereby contributing to the development of agriculture in India. Though vast literature on Institutional Credi t and agriculture is available, no indepth and serious work examining thoroughly the cause of credit diversion has been undertaken so far. The present study is an attempt to fill up this gap. The study will be helpful to lending insti tutions, viz. Co-ope:r-atives, Commercial banks and various other insti tutional agencies in connection with their lending activity_ Also, the study will help government in .formulating proper policies that will insure a preferential treatment in favour of the most needy category of farmers and cultivators with respect to agricultural credit disbursement

Criminal justice system in pondicherry - a comparative critical study of the past and the presen

The Union Territory of Pondicherry prior to its merger with the Indian Union was a French Colony. The erstwhile territory of Pondicherry along with its hamlets, namely, KARAIKKAL, MAHE and YANAM was administered by the French Regime. Before it was established by French in 1 6 74 A.D. it was part of Vijayanagara Empire. Prior to this, Pondicherry was a part of the Kingdom of Chola and Pallava Kings. During French Regime, the laws which were in force in France in relation to administration of civil and criminal justice were extended to the erstwhile Territory of Pondicherry. Thus while Pondicherry stood influenced by the Inquisitorial system since the beginning of the 18th century, the neighboring states forming part of the Indian Union since Independence came under the Influence of the British system, viz. accusatorial system. The territory of Pondicherry, for administrative reasons, came to be merged with the Indian Union in the early 60's. Following the merger, the Indian administration sought to extent its own laws from time to time replacing erstwhile French Laws, however, subject to certain savings. Thus the transitional period witnessed consequential changes in the administration of the territory, including the sphere of judicial system. Since I 963, the Union Territory of Pondicherry was brought under the spell of the Indian Legal System The people in Pondicherry ' thus have had the benefit of experiencing both the svstems. Their experiences will be of much help to those who undertake comparative studies in law. The plus and minus points of the respective systems help one to develop a detachment that helps independent evaluation of the svstents. The result of these studies could be relevant in revitalising our criminal systems.The present system is evaluated in the light of the past system. New dimensions are added by way' of an empirical study also.

Quantum critical effects in mean-field glassy systems

We consider the effects of quantum fluctuations in mean-field quantum spin-glass models with pairwise interactions. We examine the nature of the quantum glass transition at zero temperature in a transverse field. In models (such as the random orthogonal model) where the classical phase transition is discontinuous an analysis using the static approximation reveals that the transition becomes continuous at zero temperature.