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Associação entre polimorfismos nos genes SLC2A1, SLC2A2, HNF1A, TGFB1 e DCP1A e nefropatia em portadores de diabetes mellitus tipo 1 / Association between polymorphisms in the genes SLC2A1, SLC2A2, HNF1A, TGFB1 e DCPA1 and nephropathy in type 1 diabetes patientsTatiana Marques Ferreira da Rocha 11 March 2013 (has links)
A nefropatia diabética (ND) decorre da hiperglicemia crônica, de fatores de risco como a hipertensão arterial e a dislipidemia e de uma susceptibilidade genética já evidenciada em inúmeros estudos clínicos. Uma das características histológicas da ND é o acúmulo de proteínas de matriz extracelular no mesângio, para o qual contribuem várias vias bioquímicas. O GLUT-1, codificado pelo gene SLC2A1, é o principal transportador de glucose da célula mesangial e sua expressão está aumentada no glomérulo de animais diabéticos, o que constitui uma alça de feedback positivo pela qual a glicose extracelular aumentada estimula ainda mais sua própria captação, piorando a lesão mesangial. O GLUT-2, codificado pelo gene SLC2A2, é expresso nas células tubulares e nos podócitos e sua expressão também está aumentada na ND. A expressão deste transportador de glicose é regulada pelo fator de transcrição HNF-1. Participa, ainda, da lesão renal induzida pela hiperglicemia o fator de crescimento transformante - (TGF-), que exerce vários efeitos deletérios, tais como diminuir a atividade de metaloproteinases de matriz e promover fibrose renal. Esse fator de crescimento determina a ativação transcricional de genes-alvo, mas necessita de outros ativadores e co-ativadores da transcrição, tais como a proteína SMIF, codificada pelo gene DCP1A. Tendo em vista a participação das proteínas mencionadas acima na patogênese da ND, o presente estudo teve o objetivo de avaliar a associação de polimorfismos de um único nucleotídeo (SNPs) nos genes SLC2A1, SLC2A2, HNF1A, TGFB1 e DCP1A com a doença renal em portadores de diabetes mellitus tipo 1 (DM1). Um total de 449 pacientes (56,4% do sexo feminino, idade média de 36,0±11,0 anos) com mais de 10 anos de doença foram incluídos e classificados de acordo com o estágio de ND: (1) Ausência de ND: excreção urinária de albumina (EUA) normal (< 30 mg/24h ou < 20 g/min) e creatinina plasmática < 1,7 mg/dL sem tratamento anti-hipertensivo; (2) ND incipiente: microalbuminúria (EUA de 30 299 mg/24h ou 20 199 g/min) e creatinina plasmática < 1,7 mg/dL sem tratamento anti-hipertensivo e (3) ND Franca: macroalbuminúria (EUA > 300 mg/24h ou > 200 g/min) ou proteinúria ou tratamento para reposição renal. Também foram avaliadas as associações dos SNPs com o ritmo de filtração glomerular estimado (RFGe). Os SNPs foram genotipados pela metodologia de reação em cadeia da polimerase em tempo real, com o uso de sondas fluorescentes. As associações dos SNPs com a ND foram avaliadas por análise de regressão logística e os odds ratios (OR) e respectivos intervalos de confiança (IC) de 95% foram calculados após ajuste para possíveis confundidores, que foram incluídos como co-variáveis no modelo de regressão. Valores de P < 0.05 (bicaudal) foram considerados estatisticamente significantes. As seguintes associações foram observadas: (1) gene SLC2A1: genótipos CT+TT do SNP rs841848 conferiram risco para a ND incipiente na população global (OR 1,88; CI95% 1,06-3,34; P= 0,03) e nos pacientes do sexo masculino (OR 2,67; CI95% 1,13-6,35; P=0,0247) e para a ND franca (OR 2,70; CI95% 1,18-6,31; e P= 0,0197) apenas nos pacientes do sexo masculino; genótipos GA+AA do SNP rs1385129 conferiram risco para a ND franca na população do sexo masculino (OR 3,09; CI95% 1,34-7,25; P=0,0085); genótipos AT + TT do SNP rs3820589, conferiram proteção contra a ND incipiente na população global (OR 0,36; CI95% 0,16-0,78; P=0,0132) e na população do sexo feminino (OR 0,14; CI95% 0,02-0,52; P=0,0122). (2) gene SLC2A2: genótipos GA+GG do SNP rs5396 conferiram proteção contra ND franca nos pacientes do sexo masculino (OR 0,29; CI95% 0,12-0,69; P=0,0052); os genótipos AG+GG do SNP rs6800180 conferiram proteção contra a ND franca nos pacientes do sexo masculino (OR 0,16; CI95% 0,14-0,90; P=0,0324). (3) gene HNF1A: genótipos AC + CC do SNP rs1169288 conferiram risco para ND franca na população global (OR 2,23; CI95% 1,16-4,38; P=0,0175); genótipos CG+GG do SNP rs1169289 conferiram risco para ND franca na população global (OR 3,43; CI95% 1,61-7,73; P=0,002); (4) Gene TGFB1: genótipos CT + TT do SNP 1800468 conferiram risco para ND incipiente na população total (OR 2,99; CI95% 1,26-7,02; P 0,0116) e o alelo polimórfico T do SNP rs1800469 conferiu risco para um menor RFGe (p=0,0271). (5) gene DCP1A: o alelo polimórfico A do SNP rs11925433 também se associou com um menor RFGe (p=0,0075). Em conclusão, SNPs em genes que codificam as proteínas envolvidas na patogênese da ND GLUT-1, GLUT-2, HNF-1, TGF- e SMIF conferem susceptibilidade para essa complicação crônica nos portadores de DM1 avaliados no presente estudo / Diabetic nephropathy (DN) results from chronic hyperglycemia, risk factors such as hypertension and dyslipidemia as well as from genetic susceptibility, already demonstrated in numerous clinical studies. A histological feature of DN is the accumulation of extracellular matrix proteins in the mesangium after activation of multiple biochemical pathways. GLUT-1, encoded by gene SLC2A1, is the major glucose transporter in mesangial cell and its expression is increased in the glomeruli of diabetic animals, comprising a positive feedback loop whereby high extracellular glucose stimulates its own uptake and worsening mesangial injury. GLUT-2, encoded by SLC2A2 gene, is expressed in podocytes and tubular cells and its expression is also increased in DN. The expression of this glucose transporter is regulated by the transcription factor HNF-1. Transforming growth factor - (TGF-) also participates in renal injury induced by hyperglycemia, exerting several deleterious effects, such as to decrease the activity of matrix metalloproteinases and to promote renal fibrosis. This growth factor determines the transcriptional activation of target genes, but needs other activators and co-activators, such as the protein named SMIF, encoded by the gene DCP1A. Given the involvement of the aforementioned proteins in the pathogenesis of DN, the present study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) in the genes SLC2A1, SLC2A2, HNF1A, TGFB1 e DCP1A with renal disease in patients with type 1 diabetes mellitus (T1DM). A total of 449 patients (56.4% female, mean age 36.0±11.0 years) with disease duration > 10 years were included and grouped according to DN stages: (1) absence of DN: normal urinary albumin excretion (UAE) (< 30 mg/24h or < 20 g/min) and plasmatic creatinine < 1.7 mg/dL without antihypertensive treatment; (2) incipient DN: microalbuminuria (UAE 30 299 mg/24h or 20 199 g/min) and plasmatic creatinine < 1.7 mg/dL without antihypertensive treatment and (3) overt DN: macroalbuminúria (UAE > 300 mg/24h or > 200 g/min) or proteinuria or renal replacement therapy. Associations of SNPs with estimated glomerular filtration rate (eGFR) were also evaluated. All SNPs were genotyped by real time polymerase chain reaction using fluorescent-labelled probes. Associations of the SNPs with DN were assessed by logistic regression analyses and odds ratios (OR) were calculated after adjustments for possible confounders included as covariables in the regressive model. P values <0.05 (two-tails) were considered significant. The following associations were observed: (1) SLC2A1: genotypes CT+TT from rs841848 conferred risk to incipient DN in the overall population (OR 1.88; 95%IC 1.06-3.34; P= 0.03) and in the male patients (OR 2.67; CI95% 1.13-6.35; P=0.0247) and to overt DN (OR 2.70; CI95% 1.18-6.31; e P= 0.0197) only in the male patients; genotypes GA+AA from rs1385129 conferred risk to overt DN in the male population (OR 3.09; CI95% 1.34-7.25; P=0.0085); genotypes AT + TT from rs3820589 conferred protection against incipient DN in the overall population (OR 0.36; CI95% 0.16-0.78; P=0.0132) and in the female population (OR 0.14; CI95% 0.02-0.52; P=0.0122). (2) SLC2A2: genotypes GA+GG from rs5396 conferred protection against overt DN in the male patients (OR 0.29; CI95% 0.12-0.69; P=0.0052); genotypes AG+GG from rs6800180 conferred protection against overt DN in the male patients (OR 0.16; CI95% 0.14-0.90; P=0.0324). (3) HNF1A: genotypes AC + CC from rs1169288 conferred risk to overt DN in the overall population (OR 2.23; CI95% 1.16-4.38; P=0.0175); genotypes CG+GG from rs1169289 conferred risk to overt DN in the overall population (OR 3.43; CI95% 1.61-7.73; P=0.002); (4) TGFB1: genotypes CT + TT from 1800468 conferred risk to incipient DN in the overall population (OR 2.99; CI95% 1.26-7.02; P=0.0116) and the polymorphic allele T from SNP rs1800469 conferred risk to a lower eGFR (p=0.0271). (5) DCP1A: the polymorphic allele A from SNP rs11925433 was also associated with a lower eGFR (p=0.0075). In conclusion, SNPs in the genes encoding proteins GLUT-1, GLUT-2, HNF-1, TGF- e SMIF, all involved in the pathogenesis of DN, conferred susceptibility to this chronic complication in the T1DM patients evaluated in the present study
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O efeito do laser de baixa intensidade na fibrose intersticial renalOliveira, Fabiana Aparecida Mayrink de 24 February 2011 (has links)
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Previous issue date: 2011-02-24 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Justificativa e Objetivo: Independente da etiologia, a doença renal crônica (DRC)
envolve fibrose generalizada e progressiva do tecido, atrofia tubular e a perda da função
renal. Atualmente, as terapias eficazes para esta condição são escassas. Neste estudo,
foram investigados os efeitos da terapia laser de baixa intensidade (LLLT) sobre a
fibrose intersticial, que ocorre após obstrução ureteral unilateral (OUU) em ratos, um
modelo experimental de doença renal crônica.
Materiais e Métodos: Foram utilizados 32 ratos Wistar, 8 em cada grupo, machos, com
250 a 300g de peso aproximadamente e 8 semanas de idade. O rim obstruído de metade
dos ratos, submetidos à OUU receberam dose única intra-operatória do LLLT (AlGaAs
laser, 780 nm, 22,5 J / cm ², 30 mW, 30 segundos em cada um dos nove pontos). Após
14 dias, a fibrose renal foi avaliada pela coloração por picrosírius e medição da área
transversal sob luz polarizada. Análise imunohistoquímica quantificou células do tecido
renal que expressam marcadores de fibroblastos (FSP-1) e miofibroblastos (α-SMA).
RT-PCR foi realizado para determinar a expressão de mRNA de genes chaves
relacionados com a fibrose: TGF-β1, Smad3 e colágeno I (Col I).
Resultados: No grupo OUU e tratado pelo LLLT os animais apresentaram menos
fibrose renal do que os animais obstruídos (OUU). α-SMA, TGF-β1 e Smad3 foram
aumentados no interstício renal de ratos OUU. LLLT reduziu a expressão de todas essas
moléculas. LLLT não parece ter um efeito significativo no Col I ou FSP-1, que também
foram induzidos por OUU.
Conclusão: Pela primeira vez, nós mostramos que LLLT tem um efeito protetor em
relação à fibrose intersticial renal. Entende-se que, atenuando a inflamação, a
laserterapia pode impedir a ativação tubular e transdiferenciação, que são os dois
processos principais que formam a fibrose renal no modelo OUU. / Background and Objective: Regardless of the etiology, chronic kidney disease (CKD)
involves progressive widespread tissue fibrosis, tubular atrophy and loss of kidney
function. At present, effective therapies to this condition are lacking. We investigated
the effects of low level laser therapy (LLLT) on the interstitial fibrosis that occurs after
unilateral ureteral obstruction (UUO) in rats, an experimental model of CKD.
Study Design/Materials and Methods: We used 32 Wistar rats, 8 in each group,
males, 250 to 300g weight and 8 weeks old. The occluded kidney of half of the Wistar
rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser,
780 nm, 22.5 J/cm², 30 mW, 30 seconds on each of nine points). After 14 days, renal
fibrosis was assessed by Sirius red staining and measurement of the cross-sectional area
under polarized light. Immunohistochemical analyses quantitated the renal tissue cells
that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. RT-PCR was
performed to determine the mRNA expression of key fibrosis-related genes, namely
TGF-β1, Smad3 and collagen I (Col I).
Results: The UUO-LLLT animals had less severe renal fibrosis than OUU animals. α-
SMA, TGF-β1 and Smad3 were increased in the renal interstitium of UUO rats. LLLT
reduced the expression of all of these molecules. LLLT did not appear to have a
significant effect on Col I or FSP-1, which were also induced by UUO.
Conclusion: For the first time, we showed LLLT had a protective effect regarding renal
interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can
prevent tubular activation and transdifferentiation, which are the two processes that
mainly drive the renal fibrosis of the UUO model.
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How did East Germany's Media represent Iran between 1949 and 1989?Klusener, Edgar January 2015 (has links)
This thesis examines how the press of the erstwhile German Democratic Republic represented Iran in the years from 1949 – the year of the GDR’s formation – until 1989, the last complete year before its demise on 3 October 1990. The study focuses on key events in Iranian history such as the overthrow of the Mossadegh government in 1953, the White Revolution, the Islamic Revolution of 1979, and the Iran-Iraq war. It will be shown that although news and articles were based on selected facts, they still presented a picture of Iran that was at best distorted, the distortions and misrepresentations amounting to what could be described as 'factual fiction'. Furthermore, clear evidence will be provided that economical and political relations with Iran were a primary concern of the GDR’s leadership, and thus also of the GDR’s press and have therefore dominated the reporting on Iran. Whatever ideological concerns there may have been, they were hardly ever allowed to get in the way of amicable relations with the Shah or later with the Islamic Republic. Only in periods where the two countries enjoyed less amicable or poor relations, was the press free to critically report events in Iran and to openly support the cause of the SED’s communist Iranian sister party, the Tudeh. Despite East Germany’s diametric ideological environment and despite the fundamentally different role that the GDR’s political system had assigned to the press and to journalism, East Germany’s press was as reliant on the input of the global news agencies as any Western media. The at times almost complete reliance on Western news agencies as sources for news on Iran challenged more than just the hermeneutic hegemony the SED and the GDR’s press wanted to establish. After all, which news and information were made available by the news agencies to the media in both East and West was primarily determined by the business interests of said agencies. The study makes a contribution to three fields: Modern Iranian history, (East-) German history and media studies. The most valid findings were certainly made in the latter.
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Nuclear Import of Smad: A DissertationChen, Xiaochu 18 August 2011 (has links)
Signal transduction by transforming growth factor β (TGF-β) cytokines is mediated by an evolutionarily conserved mechanism that depends on the Smad proteins to transduce an extracellular stimulus into the nucleus. In the unstimulated state, Smads spontaneously shuttle across the nuclear envelope and distribute throughout the cell. Upon TGF-β or bone morphogenetic protein (BMP) stimulation, the receptor-activated Smads are phosphorylated, assemble into complexes with Smad4, and become mostly localized in the nucleus. Such signal-induced nuclear translocation of activated Smads is essential for TGF-β–dependent gene regulation that is critical for embryonic development and homeostasis. The molecular machinery responsible for this process, especially how the activated Smads are imported as complexes, is not entirely clear. Thus, I became interested in investigating the molecular requirements for nuclear targeting of Smads upon stimulation.
Recently, whole-genome RNAi screening offers a complementary cell-based approach to functionally identify molecules that mediate nuclear accumulation of Smads in response to TGF-β. In the first part of this dissertation, I performed a genome-wide RNAi screen that uncovered the importin moleskin (Msk) required in nuclear import of Dpp-activated MAD. Both genetic and biochemical studies further confirmed this finding. I also investigated Smad interactions with the Msk mammalian orthologues, Importin7 and 8 and validated that Smads are bona fide cargos of Imp7/8.
Besides the importin Msk, the screen also uncovered a subset of nucleoporins as required factors in signal-induced nuclear accumulation of MAD. Thus in the second part of this thesis, I focused on how the NPC mediates this Msk-dependent nuclear import of activated MAD. Most of these nucleoporins, including Sec13, Nup75, Nup93 and Nup205, were thought to be structural nucleoporins without known cargo-specific functions. We, however, demonstrated that this subset of nucleoporins was specifically used in the Msk-dependent nuclear import of activated MAD but not the constitutive import of cargos containing a classic nuclear localization signal (cNLS). I also uncovered novel pathway-specific functions of Sec13 and Nup93.
Regulation of TGF-β signaling can be achieved not only by modulating Smad nuclear translocation but also by modifying Smad phosphorylation status. Previously we identified a kinase, Misshapen (Msn), that caused the linker phosphorylation of MAD, resulting in negative regulation of Dpp signaling (Drosophila BMP). In the third part of this thesis, I investigated the biological relevance of Msn kinase to Dpp signaling in Drosophila wings. Both over-expression and RNAi studies suggest that Msn is a negative regulator of the Dpp/MAD pathway in vivo.
As a whole, my findings delineated two critical requirements for MAD nuclear import: the importin Msk and a unique subset of nucleoporins. For the first time, structural Nups are implicated in the direct involvement of cargo import, providing a unique trans-NPC mechanism.
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Crosstalk between the Jak-Stat and Wingless pathways is mediated by Mad in Drosophila melanogaster larval hematopoiesis.Rush, Craig Michael January 2013 (has links)
No description available.
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Synthesis, Characterization, and Reactivity Studies of Au, Ag, and Pd Colloids Prepared by the Solvated Metal Atom Dispersion (SMAD) MethodJose, Deepa January 2009 (has links) (PDF)
Surfactant bound stable colloids of Au, Ag, and Pd were prepared by the solvated Metal Atom Dispersion (SMAD) method, a method involving co-condensation of metal and solvent vapors on the walls of a reactor at 77 k. The as=prepared dodecanethiol-capped Au and Ag colloids consisting of polydisperse nanoparticles were transformed into colloids consisting of highly monodisperse nanoparticles by the digestive ripening process. In the case of Pd colloids, digestive ripening led to the formation of thiolate complexes. The [Pd(SC12H25)2]6 complex formed from the dodecanethiol-capped Pd nanoparticles was found to be a versatile precursor for the synthesis of a variety of Pd nanophases such as Pd(0), PdS, and Pd@PdO by soventless thermolysis. Co-digestive ripening of as-prepared dodecanethiol-capped Au or Ag colloids with Pd colloid resulted in Au@Pd and Ag@Pd core-shell nanoparticles, respectively; attempts to transform the core-shell structures into alloy phases even at high temperatures were unsuccessful.
Phosphine-capped Au nanoparticles were also prepared by the SMAD method and refluxing of this colloid resulted in an Ostwald ripening process rather than the expected digestive ripening due to the labile nature of bound PPh3. The labile nature of the bound phosphine was studied using 31P NMR spectroscopy and utilized in the adsorption of CO.
Palladium nanoparticles obtained from the SMAD Pd-butanone colloids and Pd@PdO nanoparticles prepared by the solventless thermolysis of Pd-dodecanethiolate complex were found to be good catalysts for the generation of H2 from AB via either hydrolysis and methanolysis. The active hydrogen atoms produced during the hydrolysis and methanolysis diffuse into the Pd lattice. It was also noticed that hydrogen atoms that were buried deep inside the Pd lattice cannot be removed completely by heating the sample even at 600°C. Wet chemical reduction method was employed for the synthesis of PVP capped, nearly monodisperse, spherical Ir nanoparticles which undergo a polymer driven self-assembly at 80°C to afford rectangular structures and interlinked particles.
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A Study on Digestive Ripening Mediated Size and Structure Control in Nanoparticles Prepared by Solvated Metal Atom Dispersion MethodBhaskar, Srilakshmi P January 2016 (has links) (PDF)
Recent advancements in nanotechnology and emerging applications of nanomaterials in various fields have stimulated interest in fundamental scientific research dealing with the size and structure controlled synthesis of nanoparticles. The unique properties of nanoparticles are largely size dependent which could be tuned further by varying shape, structure, and surface properties, etc. The preparation of monodisperse nanoparticles is desirable for many applications due to better control over properties and higher performance compared to polydispersity nanoparticles. There are several methods for the synthesis of nanoparticles based on top-down and bottom-up approaches. The main disadvantage of top-down approach is the difficulty in achieving size control. Whereas, uniform nanoparticles with controllable size could be obtained by chemical methods but most of them are difficult to scale up. Moreover, a separate step of size separation is necessary in order to achieve monodispersed which may lead to material loss. In this context, a post-synthetic size modification process known as digestive ripening is highly significant. In this process, addition of a capping agent to poly disperse colloid renders it highly monodisperse either under ambient or thermal conditions. In addition to size control, digestive ripening is also effective in controlling the structure of nanoparticles in colloidal solution comprising two different elements. Use of co-digestive ripening strategy in conjunction with solvated metal atom dispersion (SMAD) method of synthesis resulted in hetero structures such as core–shell,
alloy, and composite nanoparticles. Despite the versatility of digestive ripening process, the underlying mechanism in controlling size and structure of nanoparticles are not understood to date. The aim of this thesis is to gain mechanistic insight into size control of digestive ripening as well as to investigate structure control in various binary systems.
Objectives
Study digestive ripening of Au nanoparticles using various alkyl amines to probe the mechanism
Study co-digestive ripening of binary colloids consisting of two metals, Pd and Cu prepared separately by SMAD method
Study co-digestive ripening of binary colloids consisting of a metal (Au) and a semiconductor (CdS) prepared separately by SMAD method
Study vaporization of bulk brass in SMAD reactor and analyse phase, structure, and morphology of various Cu/Zn bimetallic nanoparticles obtained from bulk brass under various experimental conditions
Significant results
In chapter 1, fundamental processes of nanoparticle formation and common synthetic techniques for the preparation of monodisperse nanoparticles are briefly discussed. Chapter 2 presents a mechanistic study of digestive ripening process with regard to size control using Au nanoparticles as a model system. Three long chain alkyl amine molecules having different chain length were used as digestive ripening agents. The course of digestive ripening process was analysed by UV-visible spectroscopy and transmission electron microscopy. The experimental conditions such as concentration of digestive ripening agent, time, and temperature were found to influence the size distribution of nanoparticles. The average particle size was found to be characteristic of metal-digestive ripening agent combination which is considered as the optimum size preferred during digestive ripening under a given set of experimental conditions. This study discusses stabilization of optimum sized particles, surface etching, and reversibility in digestive ripening.
Chapter 3 describes the synthesis and characterization of PdCu alloy nanoparticles by co-digestive ripening method. Syntheses of individual Pd and Cu colloids were carried out by SMAD method. Pd nanoparticles obtained using THF as solvent and in the absence of any capping agent resulted in an extended small Pd nanowire network assembly. Morphological evolution of spherical Pd nanoparticles from Pd nanowire network structure was observed with the use of capping agent, hexadecyl amine (HDA) in SMAD method. Co-digestive ripening of Pd and Cu colloids was studied at various temperatures. This study revealed temperature dependent diffusion of Cu atoms into Pd lattice forming PdCu alloy nanoparticles.
Next, co-digestive ripening of a colloidal system comprising a metal and a semiconductor was explored. Au-CdS combination was chosen for this study owing to its interesting photocatalytic properties. Chapter 4 deals with the synthesis of Au and CdS nanoparticles by SMAD method and Au/CdS nanocomposite by co-digestive ripening. CdS nanoparticles of size 4.0 + 1.2 nm and Au nanoparticles of size 5.6 + 1.1 nm were obtained as a result of digestive ripening process. Au/CdS nanocomposite obtained by co-digestive ripening was characterized by a matrix-like structure made up of CdS nanoparticles in which Au nanoparticles were embedded. CdS nanoparticles were found to establish an intimate surface contact with Au nanoparticles and the matrix of CdS surrounding Au was developed via aggregation during digestive ripening.
Chapter 5 describes a comprehensive study on various Cu/Zn bimetallic nanoparticles obtained from bulk brass. Vaporization of bulk brass in SMAD reactor led to a deploying
process and further growth of nanoparticles from phase separated Cu and Zn atoms formed a composite structure. The characterization of Cu/Zn nanocomposite revealed covering of composite surface with Cu resulting in a core-shell structure, Cu/Zn@Cu. Post-synthetic digestive ripening of these core-shell composite particles showed diffusion of Zn atoms to the composite surface in addition to size and shape modification. Annealing of Cu/Zn nanocomposites prepared in THF resulted in α-CuZn alloy nanoparticles via sequential transformation through η-CuZn5, γ-Cu5Zn8, and β-CuZn (observed as marten site) phases.
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Intelligence and the Uprising in East Germany 1953: An Example of Political IntelligenceCollins, Steven Morris 08 1900 (has links)
In 1950, the leader of the German Democratic Republic (East Germany), Walter Ulbricht, began a policy of connecting foreign threats with domestic policy failures as if the two were the same, and as if he was not responsible for either. This absolved him of blame for those failures and allowed Ulbricht to define his internal enemies as agents of the western powers. He used the state's secret police force, known as the Stasi, to provide the information that supported his claims of western obstructionism and to intimidate his adversaries. This resulted in a politicization of intelligence whereby Stasi officers slanted information so that it conformed to Ulbricht's doctrine of western interference. Comparisons made of eyewitness' statements to the morale reports filed by Stasi agents show that there was a difference between how the East German worker felt and the way the Stasi portrayed their attitudes to the politburo. Consequently, prior to June 17, 1953, when labor strikes inspired a million East German citizens to rise up against Ulbricht's oppressive government, the politicization of Stasi intelligence caused information over labor unrest to be unreliable at a time of increasing risk to the regime. This study shows the extent of Ulbricht's politicization of Stasi intelligence and its effect on the June 1953 uprising in the German Democratic Republic.
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Das kulturelle Leben in Radeberg 1945 - 1989 als Spiegel der ZeitSchönfuß, Klaus 21 June 2021 (has links)
In der Nachwendezeit nach 1990 wurde viel über die Kultur-Vergangenheit der DDR diskutiert. Was war DDR-Kultur und welche Rolle spielte sie in den fast 45 Jahren SBZ- und DDR-Geschichte? War sie nur ein ideologisches Machtinstrument des herrschenden Systems? Oder war sie Selbstzweck, weil sich vielleicht einzelne Elemente zeitweise „verselbständigt“ hatten? Oder war es nicht einfach das Bedürfnis der meisten Menschen, einfach Freude am Erleben und Genießen von Kunst und Kultur oder sogar beim eigenen aktiven kulturellen Schaffen zu haben, egal ob mit Gleichgesinnten oder allein, und dabei eine tiefe Freude zu empfinden? Viele Fragen, die Antworten möge jeder für sich selbst finden. Unstrittig ist aber, dass unser Leben in dieser Zeit ohne diese Vielfalt an kulturellen Möglichkeiten und Erlebnissen, die auch zu künstlerischen Berufsentwicklungen führte und gefördert wurde, um vieles ärmer gewesen wäre und dass diese Möglichkeiten in der DDR für jeden Interessierten vom Staat kostenlos und mit sehr guter fachlicher Anleitung geboten worden sind.
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Bone morphogenetic proteins differentially regulate pigmentation in human skin cellsSingh, Suman K., Abbas, Waqas A., Tobin, Desmond J. January 2012 (has links)
No / Bone morphogenetic proteins (BMPs) are a large family of multi-functional secreted signalling molecules. Previously BMP2/4 were shown to inhibit skin pigmentation by downregulating tyrosinase expression and activity in epidermal melanocytes. However, a possible role for other BMP family members and their antagonists in melanogenesis has not yet been explored. In this study we show that BMP4 and BMP6, from two different BMP subclasses, and their antagonists noggin and sclerostin were variably expressed in melanocytes and keratinocytes in human skin. We further examined their involvement in melanogenesis and melanin transfer using fully matched primary cultures of adult human melanocytes and keratinocytes. BMP6 markedly stimulated melanogenesis by upregulating tyrosinase expression and activity, and also stimulated the formation of filopodia and Myosin-X expression in melanocytes, which was associated with increased melanosome transfer from melanocytes to keratinocytes. BMP4, by contrast, inhibited melanin synthesis and transfer to below baseline levels. These findings were confirmed using siRNA knockdown of BMP receptors BMPR1A/1B or of Myosin-X, as well as by incubating cells with the antagonists noggin and sclerostin. While BMP6 was found to use the p38MAPK pathway to regulate melanogenesis in human melanocytes independently of the Smad pathway, p38MAPK, PI3-K and Smad pathways were all involved in BMP6-mediated melanin transfer. This suggests that pigment formation may be regulated independently of pigment transfer. These data reveal a complex involvement of regulation of different members of the BMP family, their antagonists and inhibitory Smads, in melanocytes behaviour.
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