Influence of distal ileum exclusion on hepatic and renal functions in presence of extrahepatic cholestasis

OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney functional changes secondary to extrahepatic cholestasis.METHODS: We studied 24 rats, divided into three groups with eight individuals each: Group 1 (control), Group 2 (ligation of the hepatic duct combined with internal biliary drainage), and Group 3 (bile duct ligation combined with internal biliary drainage and exclusion of the terminal ileum). Animals in Group 1 (control) underwent sham laparotomy. The animals of groups 2 and 3 underwent ligation and section of the hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we associated the exclusion of the last ten centimeters of the terminal ileum and carried out an ileocolic anastomosis. After four weeks of monitoring, blood was collected from all animals of the three groups for liver and kidney biochemical evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline phosphatase, cGT, creatinine and urea).RESULTS: there were increased values of ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p < 0.05).CONCLUSION: ileal exclusion worsened liver and kidney functions in the murine model of extrahepatic cholestasis, being disadvantageous as therapeutic procedure for cholestatic disorders.

Transcriptional and Epigenetic Regulation of Human CD4+ T Helper Lineage Specification

Activated T helper (Th) cells have ability to differentiate into functionally distinct Th1, Th2 and Th17 subsets through a series of overlapping networks that include signaling and transcriptional control and the epigenetic mechanisms to direct immune responses. However, inappropriate execution in the differentiation process and abnormal function of these Th cells can lead to the development of several immune mediated diseases. Therefore, the thesis aimed at identifying genes and gene regulatory mechanisms responsible for Th17 differentiation and to study epigenetic changes associated with early stage of Th1/Th2 cell differentiation. Genome wide transcriptional profiling during early stages of human Th17 cell differentiation demonstrated differential regulation of several novel and currently known genes associated with Th17 differentiation. Selected candidate genes were further validated at protein level and their specificity for Th17 as compared to other T helper subsets was analyzed. Moreover, combination of RNA interference-mediated downregulation of gene expression, genome-wide transcriptome profiling and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq), combined with computational data integration lead to the identification of direct and indirect target genes of STAT3, which is a pivotal upstream transcription factor for Th17 cell polarization. Results indicated that STAT3 directly regulates the expression of several genes that are known to play a role in activation, differentiation, proliferation, and survival of Th17 cells. These results provide a basis for constructing a network regulating gene expression during early human Th17 differentiation. Th1 and Th2 lineage specific enhancers were identified from genome-wide maps of histone modifications generated from the cells differentiating towards Th1 and Th2 lineages at 72h. Further analysis of lineage-specific enhancers revealed known and novel transcription factors that potentially control lineage-specific gene expression. Finally, we found an overlap of a subset of enhancers with SNPs associated with autoimmune diseases through GWASs suggesting a potential role for enhancer elements in the disease development. In conclusion, the results obtained have extended our knowledge of Th differentiation and provided new mechanistic insights into dysregulation of Th cell differentiation in human immune mediated diseases.

Calculation of breed direct and maternal genetic fractions and breed specific direct and maternal heterozygosity for crossbreeding data

Teaching, research, and herd breeding applications may require calculation of breed additive contributions for direct and maternal genetic effects and fractions of heterozygosity associated with breed specific direct and maternal heterosis effects. These coefficients can be obtained from the first NB rows of a pseudo numerator relationship matrix where the first NB rows represent fractional contributions by breed to each animal or group representing a specific breed cross. The table begins with an NB x NB identity matrix representing pure breeds. Initial animals or representative crosses must be purebreds or two-breed crosses. Parents of initial purebreds are represented by the corresponding column and initial two-breed cross progeny by the two corresponding columns of the identity matrix. After that, usual rules are used to calculate the NB column entries corresponding to breeds for each animal. The NB entries are fractions of genes expected to be contributed by each of the pure breeds and correspond to the breed additive direct fractions. Entries in the column corresponding to the dam represent breed additive maternal fractions. Breed specific direct heterozygosity coefficients are entries of an NB x NB matrix formed by the outer product of the two NB by 1 columns associated with sire and dam of the animal. One minus sum of the diagonals represents total direct heterozygosity. Similarly, the NB x NB matrix formed by the outer product of columns associated with sire of dam and dam of dam contains breed specific maternal heterozygosity coefficients. These steps can be programmed to create covariates to merge with data. If X represents these coefficients for all unique breed crosses, then the reduced row echelon form function of MATLAB or SAS can be used on X to determine estimable functions of additive breed direct and maternal effects and breed specific direct and maternal heterosis effects

Gene Regulation in The Human Immune System. Gene Expression Signatures of Th2 Cell Differentiation, Type 1 Diabetes, and Intrauterine Immune Adaptation

The human immune system is constantly interacting with the surrounding stimuli and microorganisms. However, when directed against self or harmless antigens, these vital defense mechanisms can cause great damage. In addition, the understanding the underlying mechanism of several human diseases caused by aberrant immune cell functions, for instance type 1 diabetes and allergies, remains far from being complete. In this Ph.D. study these questions were addressed using genome-wide transcriptomic analyses. Asthma and allergies are characterized by a hyperactive response of the T helper 2 (Th2) immune cells. In this study, the target genes of the STAT6 transcription factor in naïve human T cells were identified with RNAi for the first time. STAT6 was shown to act as a central activator of the genes expression upon IL-4 signaling, with both direct and indirect effects on Th2 cell transcriptome. The core transcription factor network induced by IL-4 was identified from a kinetic analysis of the transcriptome. Type 1 diabetes is an autoimmune disease influenced by both the genetic susceptibility of an individual and the disease-triggering environmental factors. To improve understanding of the autoimmune processes driving pathogenesis in the prediabetic phase in humans, a unique series of prospective whole-blood RNA samples collected from HLA-susceptible children in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study was studied. Changes in different timewindows of the pathogenesis process were identified, and especially the type 1 interferon response was activated early and throughout the preclinical T1D. The hygiene hypothesis states that allergic diseases, and lately also autoimmune diseases, could be prevented by infections and other microbial contacts acquired in early childhood, or even prenatally. To study the effects of the standard of hygiene on the development of neonatal immune system, cord blood samples from children born in Finland (high standard of living), Estonia (rapid economic growth) and Russian Karelia (low standard of living) were compared. Children born in Russian Karelia deviated from Finnish and Estonian children in many aspects of the neonatal immune system, which was developmentally more mature in Karelia, resembling that of older infants. The results of this thesis offer significant new information on the regulatory networks associated with immune-mediated diseases in human. The results will facilitate understanding and further research on the role of the identified target genes and mechanisms driving the allergic inflammation and type 1 diabetes, hopefully leading to a new era of drug development.

TRP channels, omega-3 fatty acids, and oxidative stress in neurodegeneration: from the cell membrane to intracellular cross-links

The transient receptor potential channels family (TRP channels) is a relatively new group of cation channels that modulate a large range of physiological mechanisms. In the nervous system, the functions of TRP channels have been associated with thermosensation, pain transduction, neurotransmitter release, and redox signaling, among others. However, they have also been extensively correlated with the pathogenesis of several innate and acquired diseases. On the other hand, the omega-3 polyunsaturated fatty acids (n-3 fatty acids) have also been associated with several processes that seem to counterbalance or to contribute to the function of several TRPs. In this short review, we discuss some of the remarkable new findings in this field. We also review the possible roles played by n-3 fatty acids in cell signaling that can both control or be controlled by TRP channels in neurodegenerative processes, as well as both the direct and indirect actions of n-3 fatty acids on TRP channels.

Macroeconomic trouble and policy challenges in the wake of the financial bust

Contrasting with the 1929 great crisis, authorities intervened forcefully in 2008 to stop the disintegration of the financial system. Governments and central banks then sought to revise the prudential regulation in depth. It would be optimistic, however, to believe that prudential measures, alone, could deliver full economic recovery, at least in the countries that had been involved in the financial turmoil. Indeed, the collapse of the "state of confidence" and the negative effects of private debts on consumption and investment decisions have fed depressive forces and policy challenges which could hold for a while, even once the financial sector is made safe. On the one hand, the economic slowdown and the direct and indirect assistance provided by the governments to the private sectors are having a heavy impact on public finances, meanwhile, on the other hand, the massive amounts of money which artificially inflated the prices of housing and financial products could produce inflationary pressures in the post-crisis period, unless a new assets bubble is allowed for. Authorities could therefore be facing high unemployment in a damaged context of public deficits and inflationary pressures. The paper aims at discussing these new challenges. The inadequacy of inflation targets and fiscal orthodoxy in a depressed economy is emphasized, and the outlines of a Post Keynesian alternative policy are examined.

Spectral retinal image processing and analysis for ophthalmology

Diabetic retinopathy, age-related macular degeneration and glaucoma are the leading causes of blindness worldwide. Automatic methods for diagnosis exist, but their performance is limited by the quality of the data. Spectral retinal images provide a significantly better representation of the colour information than common grayscale or red-green-blue retinal imaging, having the potential to improve the performance of automatic diagnosis methods. This work studies the image processing techniques required for composing spectral retinal images with accurate reflection spectra, including wavelength channel image registration, spectral and spatial calibration, illumination correction, and the estimation of depth information from image disparities. The composition of a spectral retinal image database of patients with diabetic retinopathy is described. The database includes gold standards for a number of pathologies and retinal structures, marked by two expert ophthalmologists. The diagnostic applications of the reflectance spectra are studied using supervised classifiers for lesion detection. In addition, inversion of a model of light transport is used to estimate histological parameters from the reflectance spectra. Experimental results suggest that the methods for composing, calibrating and postprocessing spectral images presented in this work can be used to improve the quality of the spectral data. The experiments on the direct and indirect use of the data show the diagnostic potential of spectral retinal data over standard retinal images. The use of spectral data could improve automatic and semi-automated diagnostics for the screening of retinal diseases, for the quantitative detection of retinal changes for follow-up, clinically relevant end-points for clinical studies and development of new therapeutic modalities.

Production Linkages Between Informal and Formal Activities Considering Domestic and Imported Inputs: an Application of the Minimal-Flow-Analysis Method to Senegal.

We apply to the Senegalese input-output matrix of 1990, disagregated into formal and informal activities, a recently designed structural analytical method (Minimal-Flow-Analysis) which permits to depict the direct and indirect production likanges existing between activities.

Global Internet governance and the public interest in communication

Élaborée à partir d’une étude de cas extensive focalisant sur les perspectives multiples et concurrentes ayant émergé lors des négociations sur la gouvernance de l’Internet, thématique ayant dominé l’agenda politique du Sommet mondial sur la société de l’information (SMSI), cette thèse examine les manières avec lesquelles les débats mondiaux sur la gouvernance de l’Internet influencent la notion d’intérêt public en communication. Établie sur la base d’une observation participante extensive, d’entrevues semi-structurées et de l’analyse d’une documentation formelle et informelle associée au SMSI, cette thèse fait état de l’émergence des enjeux associés à la gouvernance de l’Internet au SMSI et présente une analyse approfondie des négociations ayant porté sur cet enjeu. Le cadre théorique développé par Lawrence Lessig au travers duquel « le code est la loi » est appliqué afin d’expliquer comment les différents acteurs ont débattu et ultimement atteint un consensus sur les frontières venant séparer les enjeux normatifs de politique publique et les questions techniques de régulation et de gestion du réseau. Cette thèse discute également de l’évolution des débats autour de la gouvernance mondiale de l’Internet ayant pris place à la suite de la conclusion du SMSI. Sur la base de cette étude de cas, un ensemble de conclusions sont formulées sur les acteurs et les caractéristiques institutionnelles ayant influencé les négociations sur la gouvernance de l’internet. Il est également suggéré que le SMSI a redéfini une discussion étroite sur la gestion d’un ensemble de fonctions techniques de l’Internet en un domaine de politique publique plus large de gouvernance mondiale de l’Internet. Il est également défendu que la notion d’intérêt public dans la gouvernance mondiale de l’Internet est conceptualisée autour des processus de participation et d’intégration des différentes parties prenantes au processus politique. Les implications directes et indirectes qui découlent de ce constat pour comprendre plus largement la notion d’intérêt public dans le domaine de la communication sont également présentées et discutées. En conclusion, cette thèse s’interroge sur les implications programmatiques des éléments ayant été précédemment soulevées pour la recherche médiatique et communicationnelle.

Work, personality and psychological distress : direct and moderating effects of the Big Five personality traits

L’objectif de ce mémoire est d’examiner les nombreuses associations qui existent entre les conditions de l’organisation du travail, les traits de personnalité et la détresse psychologique au travail. La question de recherche principale était : est-ce que les cinq grands traits de personnalité (Big Five personality traits) ont un effet modérateur sur la relation entre les conditions de l’organisation du travail et la détresse psychologique. De nombreuses autres questions ont aussi été considérées. Pour répondre aux vingt-et-une hypothèses proposées dans cette recherche, nous avons utilisé des données secondaires d’une étude transversale de 395 employés d’un service de police municipal. À la suite d’analyses multivariées, nous avons pu observer quatre associations significatives. Concernant les conditions de l’organisation du travail, nous avons trouvé que les demandes psychologiques en milieu de travail augment la détresse psychologique, tandis que le support d’un superviseur la diminue. En ce qui concerne, les traits de personnalité, nous avons trouvé qu’être névrotique (neuroticism) augmente la détresse psychologique. Finalement, nous avons trouvé un effet modérateur du trait de personnalité, être consciencieux (conscientiousness), sur la relation entre les demandes psychologiques et la détresse psychologique. Bref, nos résultats nous indiquent que les cinq grands traits de personnalité (Big Five personality traits) ont une influence mitigée sur la santé mentale en milieu de travail.

Photothermal and photoacoustic investigations on certain polymers and semi conducting materials

Material synthesizing and characterization has been one of the major areas of scientific research for the past few decades. Various techniques have been suggested for the preparation and characterization of thin films and bulk samples according to the industrial and scientific applications. Material characterization implies the determination of the electrical, magnetic, optical or thermal properties of the material under study. Though it is possible to study all these properties of a material, we concentrate on the thermal and optical properties of certain polymers. The thermal properties are detennined using photothermal beam deflection technique and the optical properties are obtained from various spectroscopic analyses. In addition, thermal properties of a class of semiconducting compounds, copper delafossites, arc determined by photoacoustic technique.Photothermal technique is one of the most powerful tools for non-destructive characterization of materials. This forms a broad class of technique, which includes laser calorimetry, pyroelectric technique, photoacollstics, photothermal radiometric technique, photothermal beam deflection technique etc. However, the choice of a suitable technique depends upon the nature of sample and its environment, purpose of measurement, nature of light source used etc. The polynler samples under the present investigation are thermally thin and optically transparent at the excitation (pump beam) wavelength. Photothermal beam deflection technique is advantageous in that it can be used for the detennination of thermal diffusivity of samples irrespective of them being thermally thick or thennally thin and optically opaque or optically transparent. Hence of all the abovementioned techniques, photothemlal beam deflection technique is employed for the successful determination of thermal diffusivity of these polymer samples. However, the semi conducting samples studied are themlally thick and optically opaque and therefore, a much simpler photoacoustic technique is used for the thermal characterization.The production of polymer thin film samples has gained considerable attention for the past few years. Different techniques like plasma polymerization, electron bombardment, ultra violet irradiation and thermal evaporation can be used for the preparation of polymer thin films from their respective monomers. Among these, plasma polymerization or glow discharge polymerization has been widely lIsed for polymer thin fi Im preparation. At the earlier stages of the discovery, the plasma polymerization technique was not treated as a standard method for preparation of polymers. This method gained importance only when they were used to make special coatings on metals and began to be recognized as a technique for synthesizing polymers. Thc well-recognized concept of conventional polymerization is based on molecular processcs by which thc size of the molecule increases and rearrangemcnt of atoms within a molecule seldom occurs. However, polymer formation in plasma is recognized as an atomic process in contrast to the above molecular process. These films are pinhole free, highly branched and cross linked, heat resistant, exceptionally dielectric etc. The optical properties like the direct and indirect bandgaps, refractive indices etc of certain plasma polymerized thin films prepared are determined from the UV -VIS-NIR absorption and transmission spectra. The possible linkage in the formation of the polymers is suggested by comparing the FTIR spectra of the monomer and the polymer. The thermal diffusivity has been measured using the photothermal beam deflection technique as stated earlier. This technique measures the refractive index gradient established in the sample surface and in the adjacent coupling medium, by passing another optical beam (probe beam) through this region and hence the name probe beam deflection. The deflection is detected using a position sensitive detector and its output is fed to a lock-in-amplifIer from which the amplitude and phase of the deflection can be directly obtained. The amplitude and phase of the deflection signal is suitably analyzed for determining the thermal diffusivity.Another class of compounds under the present investigation is copper delafossites. These samples in the form of pellets are thermally thick and optically opaque. Thermal diffusivity of such semiconductors is investigated using the photoacoustic technique, which measures the pressure change using an elcctret microphone. The output of the microphone is fed to a lock-in-amplificr to obtain the amplitude and phase from which the thermal properties are obtained. The variation in thermal diffusivity with composition is studied.

Studies On The Effect Of Laser Radiation And Other Mutagens On Plants

The effect of lasers of three wavelengths in the visible region - 476, 488 and 514 nm on mitotic and meiotic cell divisions, growth, yield and activity of specific enzymes were studied in two taxonomically diverse plant species — A/lium cepa L. and Vicia faba. The effect of laser exposures was compared with the effect of two physical mutagens (Gamma and Ultraviolet radiations) and two chemical mutagens (Ethyl Methane Sulphonate and Hydroxyl amine). The study indicated that lasers could be mutagenic causing aberration in the mitotic and meiotic cell divisions while also producing changes in the growth and yield of the plants. Lasers of higher wavelengths 488 and 514 nm caused aberrations in the early stages of mitotic cell division whereas lasers of lower wavelengths (476 nm) caused more aberrations in the later stages of mitotic cell division. Laser exposure of 488 nm wavelength at power density 400 mW induced higher mitotic and meiotic aberrations and also induced higher pollen sterility than lasers of 476 and 514 nm. The frequency of mitotic aberrations induced by lasers was lesser than that caused by y-irradiation but comparable to that induced by EMS and HA. Lasers cause mutations in higher frequencies than UV. Lasers had a stimulatory effect on growth and yield in both plant species. This stimulatory effect of lasers on germination could not however be correlated to the activity of amylase and protease, the key enzymes in seed gennination. Enzymes such as peroxidase and catalase, involved in scavenging of free oxygen radicals often produced by irradiation, did not show increased activity in laser irradiated samples. Further studies are required for elucidating the exact mechanisms by which lasers cause mutations

Recession-induced societal changes- Challanges and Opportunities

The greatest damage inflicted by the recent recession has not necessarily been financial but emotional and psychological. There are a lot of direct and indirect societal challenges ,changes and oppurtunuties that were brought by recession everywhere including in India. In this paper an attempt is made to analyse such societal changes challenges and oppurtunities.

Preparation and Study of Optical Properties of CdS, CdS-TiO2 and CdS-Au Nanocomposites for Photonic Applications

Nanophotonics can be regarded as a fusion of nanotechnology and photonics and it is an emerging field providing researchers opportunities in fundamental science and new technologies. In recent times many new methodsand techniques have been developed to prepare materials at nanoscale dimensions. Most of these materials exhibit unique and interesting optical properties and behavior. Many of these have been found to be very useful to develop new devices and systems such as tracers in biological systems, optical limiters, light emitters and energy harvesters. This thesis presents a summary of the work done by the author in the field by choosing a few semiconductor systems to prepare nanomaterials and nanocomposites. Results of the study of linear and nonlinear optical properties of materials thus synthesized are also presented in the various chapters of this thesis. CdS is the material chosen here and the methods and the studies of the detailed investigation are presented in this thesis related to the optical properties of CdS nanoparticles and its composites. Preparation and characterization methods and experimental techniques adopted for the investigations were illustrated in chapter 2 of this thesis. Chapter 3 discusses the preparation of CdS, TiO2 and Au nanoparticles. We observed that the fluorescence behaviour of the CdS nanoparticles, prepared by precipitation technique, depends on excitation wavelength. It was found that the peak emission wavelength can be shifted by as much as 147nm by varyingthe excitation wavelengths and the reason for this phenomenon is the selective excitation of the surface states in the nanoparticles. This provided certain amount of tunability for the emission which results from surface states.TiO2 nanoparticle colloids were prepared by hydrothermal method. The optical absorption study showed a blue shift of absorption edge, indicating quantum confinement effect. The large spectral range investigated allows observing simultaneously direct and indirect band gap optical recombination. The emission studies carried out show four peaks, which are found to be generated from excitonic as well as surface state transitions. It was found that the emission wavelengths of these colloidal nanoparticles and annealed nanoparticles showed two category of surface state emission in addition to the excitonic emission. Au nanoparticles prepared by Turkevich method showed nanoparticles of size below 5nm using plasmonic absorption calculation. It was also found that there was almost no variation in size as the concentration of precursor was changed from 0.2mM to 0.4mM.We have observed SHG from CdS nanostructured thin film prepared onglass substrate by chemical bath deposition technique. The results point out that studied sample has in-plane isotropy. The relative values of tensor components of the second-order susceptibility were determined to be 1, zzz 0.14, xxz and 0.07. zxx These values suggest that the nanocrystals are oriented along the normal direction. However, the origin of such orientation remains unknown at present. Thus CdS is a promising nonlinear optical material for photonic applications, particularly for integrated photonic devices. CdS Au nanocomposite particles were prepared by mixing CdS nanoparticles with Au colloidal nanoparticles. Optical absorption study of these nanoparticles in PVA solution suggests that absorption tail was red shifted compared to CdS nanoparticles. TEM and EDS analysis suggested that the amount of Au nanoparticles present on CdS nanoparticles is very small. Fluorescence emission is unaffected indicating the presence of low level of Au nanoparticles. CdS:Au PVA and CdS PVA nanocomposite films were fabricated and optically characterized. The results showed a red-shift for CdS:Au PVA film for absorption tail compared to CdS PVA film. Nonlinear optical analysis showed a huge nonlinear optical absorption for CdS:Au PVA nanocomposite and CdS:PVA films. Also an enhancement in nonlinear optical absorption is found for CdS:Au PVA thin film compared to the CdS PVA thin film. This enhancement is due to the combined effect of plasmonic as well as excitonic contribution at high input intensity. Samples of CdS doped with TiO2 were also prepared and the linear optical absorption spectra of these nanocompositeparticles clearly indicated the influence of TiO2 nanoparticles. TEM and EDS studies have confirmed the presence of TiO2 on CdS nanoparticles. Fluorescence studies showed that there is an increase in emission peak around 532nm for CdS nanoparticles. Nonlinear optical analysis of CdS:TiO2 PVA nanocomposite films indicated a large nonlinear optical absorption compared to that of CdS:PVA nanocomposite film. The values of nonlinear optical absorption suggests that these nanocomposite particles can be employed for optical limiting applications. CdSe-CdS and CdSe-ZnS core-shell QDs with varying shell size were characterized using UV–VIS spectroscopy. Optical absorption and TEM analysis of these QDs suggested a particle size around 5 nm. It is clearly shown that the surface coating influences the optical properties of QDs in terms of their size. Fluorescence studies reveal the presence of trap states in CdSe-CdS and CdSe- ZnS QDs. Trap states showed an increase as a shell for CdS is introduced and increasing the shell size of CdS beyond a certain value leads to a decrease in the trap state emission. There is no sizeable nonlinear optical absorption observed. In the case of CdSe- ZnS QDs, the trap state emission gets enhanced with the increase in ZnS shell thickness. The enhancement of emission from trap states transition due to the increase in thickness of ZnS shell gives a clear indication of distortion occurring in the spherical symmetry of CdSe quantum dots. Consequently the nonlinear optical absorption of CdSe-ZnS QDs gets increased and the optical limiting threshold is decreased as the shell thickness is increased in respect of CdSe QDs. In comparison with CdSe-CdS QDs, CdSe-ZnS QDs possess much better optical properties and thereby CdSe-ZnS is a strong candidate for nonlinear as well as linear optical applications.