Nucleation and growth evolution of InP dots on InGaP/GaAs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Macroeconomic stability and investment allocation of domestic pension funds in emerging economies: the case of Chile

Includes bibliography

Real macroeconomic stability and the capital account in Chile and Colombia

Includes bibliography

Managing in the public sector for investment and growth

Includes bibliography

Productivity, stability and adaptability in open pollination progenies of Eucalyptus urophylla ST Blake

Prediction of genetic gains within breeding programs is not always compatible with those observed in practice. One reason for this inconsistency is the lack of knowledge of genotype-environment interaction (GxE). The aim of this study was to estimate genetic variation, evaluate the GxE, investigate the genetic correlation between pairs of environments and for the set, and to study the productivity, stability and adaptability at 2 years of age for diameter at breast height (DBH) in five progenies trials of Eucalyptus urophylla, used in a randomized complete block design, with the number of progenies ranging from 138 to 167, four to eight blocks and five to six plants per plot. Estimates of variance components and genetic parameters were obtained using the REML/BLUP method. For analysis of productivity, stability and adaptability, the HMRPGV method was used. The highest DBH growth was observed in Anhembi (10.52 cm) and Uberaba (10.20 cm). Estimates considered high were obtained for the coefficient of individual additive genetic variation (>13.3%) and average heritability among progenies (>0.40), indicating the possibility of obtaining genetic gains by selection among progenies. The coefficient of determination of the GxE was 1.7%, a fact that led to a high value of genotypic correlation between the performance of the progenies and environments (78.1%), indicating that the interaction is simple. The first six progenies showed a coincidence of 100% in the order of stability (HMGV), adaptability (RPGV) and productivity (HMRPGV), being 13% higher than the overall mean of five experiments (9.21 cm). When ordering the progenies, the selection of the 20 best in growth led to an increase in gain ranging of from 10.4 to 70%. Anhembi is the ideal place to have a breeding population which will be good in the other places as well.

Interfacial interactions, charge transport and growth phenomena in Organic Field Effect Transistors

Organic electronics is an emerging field with a vast number of applications having high potential for commercial success. Although an enormous progress has been made in this research area, many organic electronic applications such as organic opto-electronic devices, organic field effect transistors and organic bioelectronic devices still require further optimization to fulfill the requirements for successful commercialization. The main bottle neck that hinders large scale production of these devices is their performances and stability. The performance of the organic devices largely depends on the charge transport processes occurring at the interfaces of various material that it is composed of. As a result, the key ingredient needed for a successful improvement in the performance and stability of organic electronic devices is an in-depth knowledge of the interfacial interactions and the charge transport phenomena taking place at different interfaces. The aim of this thesis is to address the role of the various interfaces between different material in determining the charge transport properties of organic devices. In this framework, I chose an Organic Field Effect Transistor (OFET) as a model system to carry out this study as it An OFET offers various interfaces that can be investigated as it is made up of stacked layers of various material. In order to probe the intrinsic properties that governs the charge transport, we have to be able to carry out thorough investigation of the interactions taking place down at the accumulation layer thickness. However, since organic materials are highly instable in ambient conditions, it becomes quite impossible to investigate the intrinsic properties of the material without the influence of extrinsic factors like air, moisture and light. For this reason, I have employed a technique called the in situ real-time electrical characterization technique which enables electrical characterization of the OFET during the growth of the semiconductor.

Pabp binds to the osk 3'UTR and specifically contributes to osk mRNA stability and oocyte accumulation

RNA localization is tightly coordinated with RNA stability and translation control. Bicaudal-D (Bic-D), Egalitarian (Egl), microtubules and their motors are part of a Drosophila transport machinery that localizes mRNAs to specific cellular regions during oogenesis and embryogenesis. We identified the Poly(A)-binding protein (Pabp) as a protein that forms an RNA-dependent complex with Bic-D in embryos and ovaries. pabp also interacts genetically with Bic-D and, similar to Bic-D, pabp is essential in the germline for oocyte growth and accumulation of osk mRNA in the oocyte. In the absence of pabp, reduced stability of osk mRNA and possibly also defects in osk mRNA transport prevent normal oocyte localization of osk mRNA. pabp also interacts genetically with osk and lack of one copy of pabp(+) causes osk to become haploinsufficient. Moreover, pointing to a poly(A)-independent role, Pabp binds to A-rich sequences (ARS) in the osk 3'UTR and these turned out to be required in vivo for osk function during early oogenesis. This effect of pabp on osk mRNA is specific for this RNA and other tested mRNAs localizing to the oocyte are less and more indirectly affected by the lack of pabp

Phosphatase and tensin homolog regulates stability and activity of EphB1 receptor

Deregulation of receptor tyrosine kinases (RTKs) is linked to a broad range of cancers, stressing the necessity of studying their regulatory pathways. We and others demonstrated previously that c-Cbl is necessary for the lysosomal degradation of erythropoietin-producing hepatocellular B1 (EphB1) carcinoma and epidermal growth factor receptor (EGFR) RTKs. Moreover, the tumor suppressor phosphatase and tensin homolog (PTEN) was shown to modulate c-Cbl-dependent EGFR degradation. We therefore investigated the involvement of PTEN in EphB1 signaling and degradation. We used PTEN mutants, PTEN, and NHERF1 small interfering RNA in CHO-EphB1 and SW480 cells endogenously expressing EphB1 to delineate EphB1-PTEN interactions. PTEN was constitutively associated with c-Cbl, protecting it from degradation. EphB1 stimulation triggered ∼50% serine-threonine PTEN dephosphorylation and PTEN-Cbl complex disruption, a process requiring PTEN protein phosphatase activity. Both proteins independently translocated to EphB1, with PTEN in association with the scaffold protein NHERF1. Biologically, PTEN lipid phosphatase activity impairs EphB1-dependent cell adhesion and chemotaxis. This study demonstrates for the first time in mammalian cells that the Eph receptor and PTEN associate and influence their signaling. Moreover, it contributes to the emerging concept that PTEN regulates expression of RTKs through modulation of their degradation. Finally, it reveals a new role for PTEN protein phosphatase activity involved in this process.

Predictive oncology: a review of multidisciplinary, multiscale in silico modeling linking phenotype, morphology and growth.

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically assess advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we review a multiscale, i.e., from the molecular to the gross tumor scale, mathematical and computational "first-principle" approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We review the feasibility of this methodology that, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as a phenotype-diagnostic tool to predict collective and individual tumor cell invasion of surrounding tissue. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior.

14-3-3SIGMA NEGATIVELY REGULATES THE STABILITY AND SUBCELLULAR LOCALIZATION OF COP1

Mammalian constitutive photomorphogenic 1 (COP1), a p53 E3 ubiquitin ligase, is a key negative regulator for p53. DNA damage leads to the translocation of COP1 to the cytoplasm, but the underlying mechanism remains unknown. We discovered that 14-3-3σ controlled COP1 subcellular localization and protein stability. Investigation of the underlying mechanism suggested that, upon DNA damage, 14-3-3σ bound to phosphorylated COP1 at S387, resulting in COP1 translocation to the cytoplasm and cytoplasmic COP1 ubiquitination and proteasomal degradation. 14-3-3σ targeted COP1 for degradation to prevent COP1-mediated p53 degradation, p53 ubiquitination, and p53 transcription repression. COP1 expression promoted cell proliferation, cell transformation, and tumor progression, attesting to its role in cancer promotion. 14-3-3σ negatively regulated COP1 function and prevented tumor growth in cancer xenografts. COP1 protein levels were inversely correlated with 14-3-3σ protein levels in human breast and pancreatic cancer specimens. Together, these results define a novel, detailed mechanism for the posttranslational regulation of COP1 upon DNA damage and provide a mechanistic explanation of the correlation of COP1 overexpression with 14-3-3σ downregulation during tumorigenesis.

Analysis of mutations in $\beta$-tubulin genes affecting tubulin stability and assembly

Cmd4 is a colcemid-sensitive CHO cell line that is temperature sensitive for growth and expresses an altered $\beta$-tubulin, $\beta\sb1$. One revertant of this cell line, D2, exhibits a further alteration in $\beta\sb1$ resulting in an acidic shift in its isoelectric point and a decrease in its molecular weight to 40 kD, as measured by two dimensional gel electrophoresis. This $\beta$-tubulin variant has been shown to be assembly-defective and unstable. Characterization of the mutant $\beta\sb1$ in D2 by high pressure liquid chromatography (HPLC) revealed the loss of methionine containing tryptic peptides 7,8,9, and 10. Southern analysis of the genomic DNA digested with several different restriction enzymes resulted in the appearance of new restriction fragments 250 base pairs shorter than the corresponding fragments from the wild-type $\beta\sb1$-tubulin gene. Northern analysis on mRNA from D2 revealed two new message products that also differed by 250 bases from the corresponding wild type $\beta$-tubulin transcripts. To precisely define the region of the alteration, cloning and sequencing of the mutant and wild type genomic $\beta$-tubulin genes were conducted. A size-selected EcoRI genomic library was prepared using the Stratagene lambda Zap II phage cloning system. Using subclones of CHO $\beta$-tubulin cDNA as probes, a 2.5 kb wild type clone and a 2.3 kb mutant clone were identified from this library. Each of these was shown to contain a portion of the gene extending from intron 3 through the end of the coding sequence in exon 4 and into the 3$\sp\prime$ untranslated region on the basis of alignment with the published human $\beta$-tubulin sequence. Sequencing of the mutant 2.3 kb clone revealed that the mutation is due to a 246 base pair internal deletion in exon 4 (base pair 756-1001) that encodes amino acids 253-334. This deletion results in the loss of a putative binding site for GTP which could potentially explain the phenotype of this mutant $\beta$-tubulin. Also sequence comparison of the 3$\sp\prime$ untranslated region between different species revealed the conservation of 200 base pairs with 78% homology. It is proposed that this region could play an important role in the regulation of $\beta$-tubulin gene expression. ^

Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development

DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in nonhomologous end joining (NHEJ). However, although Lig4 deficiency causes late embryonic lethality, deficiency in DNA-PK subunits (Ku70, Ku80, and DNA-PKcs) does not. Here we demonstrate that, similar to p53 deficiency, ataxia-telangiectasia-mutated (ATM) gene deficiency rescues the embryonic lethality and neuronal apoptosis, but not impaired lymphocyte development, associated with Lig4 deficiency. However, in contrast to p53 deficiency, ATM deficiency enhances deleterious effects of Lig4 deficiency on growth potential of embryonic fibroblasts (MEFs) and genomic instability in both MEFs and cultured progenitor lymphocytes, demonstrating significant differences in the interplay of p53 vs. ATM with respect to NHEJ. Finally, in dramatic contrast to effects on Lig4 deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK holoenzyme.

The financial stability and access to financing of SMEs in Hungary

The present study was prepared within the framework of cooperation between the Competitiveness Research Centre, operating within the Institute of Business Economics of Corvinus University of Budapest, and the National Association of Entrepreneurs, based on a commission from the latter. Th e goal of the study was to survey the self-financing capabilities and borrowing opportunities of majority Hungarian-owned small and medium-sized enterprises (SMEs), and to identify potential problems. The results of the research revealed that the high proportion of owner’s equity in the financing structure is not due to difficulties with borrowing, but because enterprises that cover their fi nancing primarily from their own resources have other financing opportunities at their disposal. Although general satisfaction with banks shows a diminishing tendency, it can still be interpreted favourably. The majority of companies have not encountered serious borrowing difficulties. With regard to the system of competitive tenders, company managers have sensed some improvement, but general satisfaction is still lacking. Although the research results suggest that the primary obstacle to growth in 2013 was not the lack of credit or external funding, it is important to emphasize that start-ups, young enterprises and micro-enterprises, which struggle the most with financing worries, were not represented in the analysed database.

Specificity, stability and comparative physiology of coral-Symbiodinium mutualisms: Evaluating the potential for acclimation and/or adaptation in reef corals

The relationship between reef corals and endosymbiotic dinoflagellates is fundamental to the existence of coral reefs. To evaluate the fidelity of coral-Symbiodinium mutualisms, corals maintained in aquaria for years were analyzed by denaturant gradient gel electrophoresis (DGGE). Comparing Symbiodinium populations of captive aquarium colonies with known associations in nature is a practical way of examining partner flexibility. The finding of "normal" symbiont populations in corals existing under highly variable conditions supports the premise that most coral colonies possess stable associations. High sensitivity real-time PCR (rtPCR) was used to evaluate background populations of the putatively stress-tolerant Symbiodinium D in reef corals of the Caribbean. Analyses of samples collected during periods of environmental stability indicate the ability of Symbiodinium D to associate with a wider diversity of host taxa than previously recognized. To gain a broader perspective with regard to the ecology of Symbiodinium D1a, rtPCR and DGGE were used to evaluate the symbiont populations of reef corals from Barbados before and after the 2005 mass coral bleaching. Background populations were observed in 56% of the host genera prior to observations of bleaching. These findings indicate that 'stress', not 'bleaching', caused the displacement of 'natural' symbiont population and the opportunistic proliferation of D1a in many host taxa. Of the 12 host taxa monitored before and after the bleaching event, there was a 40% increase in colonies hosting Symbiodinium D1a. Together, these studies elucidate the mechanism responsible for recent observations reporting the emergence of Symbiodinium D following thermal disturbances. These observations are now most easily explained as the disproportionate growth of existing in hospite symbiont populations, rather than novel symbiont acquisition subsequent to bleaching. To evaluate the comparative "fitness" of corals able to host multiple symbiont types, rates of calcification were measured in P. verrucosa hosting either Symbiodinium C1b-c or D1 at elevated temperature. Rates of calcification decreased significantly for both host-symbiont combinations, but differences attributable to symbiont composition were not detected. This research improves our knowledge of the symbiosis biology and ecology of reef corals and contributes information necessary to most accurately predict the response of these ecosystems to global climate changes.

Seawater carbonate chemistry and growth, calcification of Thoracosphaera heimii in a laboratory experiment

Ocean acidification is considered a major threat to marine ecosystems and may particularly affect calcifying organisms such as corals, foraminifera and coccolithophores. Here we investigate the impact of elevated pCO2 and lowered pH on growth and calcification in the common calcareous dinoflagellate Thoracosphaera heimii. We observe a substantial reduction in growth rate, calcification and cyst stability of T. heimii under elevated pCO2. Furthermore, transcriptomic analyses reveal CO2 sensitive regulation of many genes, particularly those being associated to inorganic carbon acquisition and calcification. Stable carbon isotope fractionation for organic carbon production increased with increasing pCO2 whereas it decreased for calcification, which suggests interdependence between both processes. We also found a strong effect of pCO2 on the stable oxygen isotopic composition of calcite, in line with earlier observations concerning another T. heimii strain. The observed changes in stable oxygen and carbon isotope composition of T. heimii cysts may provide an ideal tool for reconstructing past seawater carbonate chemistry, and ultimately past pCO2. Although the function of calcification in T. heimii remains unresolved, this trait likely plays an important role in the ecological and evolutionary success of this species. Acting on calcification as well as growth, ocean acidification may therefore impose a great threat for T. heimii.