Evaluation of HPFH and δβ-thalassemia mutations in a Brazilian group with high Hb F levels.

Fetal hemoglobin (Hb F) is characteristic of the fetal development period. However, in some genetic conditions, such as hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia (δβ-thalassemia), Hb F continues to be produced in adulthood. We evaluated the frequency of two mutations of HPFH, HPFH-1 and HPFH-2 African, and two mutations in δβ-thalassemia, Sicilian and Spanish, in a Brazilian population. Peripheral blood samples were collected from adults from hospitals and blood centers in southeast and northeast Brazil. These individuals were healthy and without complaints of anemia, but had increased Hb F. Samples were submitted to electrophoretic and chromatographic analyses to quantify Hb F values and, subsequently, to molecular analyses to verify the mutations. In the molecular analysis, 16 of the 60 samples showed a heterozygous profile for the HPFH mutations, two for HPFH-1 and 14 for HPFH-2. In the same sample set, three were heterozygous for Spanish δβ-thalassemia and none were heterozygous for Sicilian δβ- thalassemia. The Hb F values in the HPFH-2 heterozygotes differed from those previously reported for this mutation. In this group, the HPFH mutations were more frequent than the δβ-thalassemia mutations. The finding of these mutations in this Brazilian population reflects the mixing process that occurred during its formation.

Informe de la Reunión del Grupo Regional de Expertos sobre Pesca en Alta Mar = Report of the Meeting of the Regional Group of Experts on High Seas Fisheries

Incluye Bibliografía

Geochemistry and Pb-207/Pb-206 zircon ages of granitoids from the southern portion of the Tamboril-Santa Quiteria granitic-migmatitic complex, Ceara Central Domain, Borborema Province (NE Brazil)

The Tamboril-Santa Quiteria Complex is an important Neoproterozoic granitic-migmatitic unit from the Ceara Central Domain that developed from ca. 650 to 610 Ma. In general the granitoids range in composition from diorite to granite with predominance (up to 85%) of granitic to monzogranitic composition with biotite as the main mafic AFM phase. Geochemical and Pb-207/Pb-206 evaporation zircon geochronology studies were applied in a group of these abundant monzogranitic rocks from the region of Novo Oriente in the southern portion of the Ceara Central Domain. In this area the granitoids are weakly peraluminous biotite granitoids and deformed biotite granitoids of high-K calc-alkaline and ferroan composition, which we interpreted as primary magmas (segregated diatexites) derived from the partial melting of crustal material. The close temporal relation of this magmatism with local eclogitic and regional high temperature metamorphism in Ceara Central Domain point out to an orogenic setting, arguably emplaced during the collisional stage. Subordinate coeval juvenile mantle incursions are also present. This crustally derived magmatism is the primary product of the continental thickening that resulted from the collision between the rocks represented by the Amazonian-West African craton (Sao Luiz cratonic fragment) to the northwest and the Paleoproterozoic-Archean basement of the Borborema Province to the southeast along the Transbrasiliano tectonic corridor. (C) 2011 Elsevier Ltd. All rights reserved.

SPATIO-TEMPORAL AND FUNCTIONAL STRUCTURE OF THE AMPHIPOD COMMUNITIES OFF SANTOS, SOUTHWESTERN ATLANTIC

The amphipod fauna was employed to investigate a bottom environmental gradient in the continental shelf adjacent to Santos Bay. The constant flow of less saline water from the estuarine complex of the Santos and Sao Vicente rivers besides the seasonal intrusion of the cold saline South Atlantic Central Water (SACW) bring a highly dynamic water regime to the area. Density, distribution, diversity and functional structure of the communities were studied on a depth gradient from 10 to 100 m on two cruises in contrasting seasons, winter 2005 and summer 2006. Twenty-one sediment samples were taken with a 0.09m(2) box corer. Temperature and salinity were measured at each station and an additional surface sediment sample was obtained with the box corer for granulometric and chemical analyses. Sixty species were collected on each survey and higher density values were found in summer. A priori one-way Analysis of Similarities (ANOSIM) indicated the existence of three different groups of amphipods related to the depth gradient: the Coastal group, the Mixed Zone group and the Deep Zone group. The Coastal Zone in both cruises was inhabited by a community presenting low diversity and density, besides high dominance of the infaunal tube-dweller Ampelisca paria; the area around 30 m presented the highest values of all the ecological indicators and the species showed several life styles; the outer area, situated between 50 and 100 m depth in the SACW domain, presented a community characterized by lower diversity and high biomass and density values. A season-depth ANOSIM showed the influence of depth and season for the Coastal and Mixed Zone groups whereas no seasonal difference was obtained for the Deep Zone group. The synergistic effect of the SACW and depth in the first place, followed by physical changes in substrate, seem to be the main factors controlling the fauna's distribution. In addition, the estuarine waters from Santos Bay apparently had no effect on the establishment of the environmental gradient observed on the adjacent shelf. Diversity, distribution, functional groups and trophic conditions of superficial sediments are discussed in the light of the main oceanographic processes present on the southern Brazilian shelf.

Lyotropic mixture made of potassium laurate/1-undecanol/K2SO4/water presenting high birefringences and large biaxial nematic phase domain: a laser conoscopy study

The lyotropic liquid crystalline quaternary mixture made of potassium laurate (KL), potassium sulphate, 1-undecanol and water was investigated by experimental optical methods (optical microscopy and laser conoscopy). In a particular temperature and relative concentrations range, the three nematic phases (two uniaxial and one biaxial) were identified. The biaxial domain in the temperature/KL concentration surface is larger when compared to other lyotropic mixtures. Moreover, this new mixture gives nematic phases with higher birefringence than similar systems. The behavior of the symmetric tensor order parameter invariants sigma(3) and sigma(2) calculated from the measured optical birefringences supports that the uniaxial-to-biaxial transitions are of second order, described by a mean-field theory.

Dynamic symmetry loss of high-frequency hysteresis loops in single-domain particles with uniaxial anisotropy

Understanding how magnetic materials respond to rapidly varying magnetic fields, as in dynamic hysteresis loops, constitutes a complex and physically interesting problem. But in order to accomplish a thorough investigation, one must necessarily consider the effects of thermal fluctuations. Albeit being present in all real systems, these are seldom included in numerical studies. The notable exceptions are the Ising systems, which have been extensively studied in the past, but describe only one of the many mechanisms of magnetization reversal known to occur. In this paper we employ the Stochastic Landau-Lifshitz formalism to study high-frequency hysteresis loops of single-domain particles with uniaxial anisotropy at an arbitrary temperature. We show that in certain conditions the magnetic response may become predominantly out-of-phase and the loops may undergo a dynamic symmetry loss. This is found to be a direct consequence of the competing responses due to the thermal fluctuations and the gyroscopic motion of the magnetization. We have also found the magnetic behavior to be exceedingly sensitive to temperature variations, not only within the superparamagnetic-ferromagnetic transition range usually considered, but specially at even lower temperatures, where the bulk of interesting phenomena is seen to take place. (C) 2011 Elsevier B.V. All rights reserved.

SLCO1B1 rs4149056 polymorphism associated with statin-induced myopathy is differently distributed according to ethnicity in the Brazilian general population: Amerindians as a high risk ethnic group

Background Recent studies reported the association between SLCO1B1 polymorphisms and the development of statin-induced myopathy. In the scenario of the Brazilian population, being one of the most heterogeneous in the world, the main aim here was to evaluate SLCO1B1 polymorphisms according to ethnic groups as an initial step for future pharmacogenetic studies. Methods One hundred and eighty-two Amerindians plus 1,032 subjects from the general urban population were included. Genotypes for the SLCO1B1 rs4149056 (c.T521C, p.V174A, exon 5) and SLCO1B1 rs4363657 (g.T89595C, intron 11) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis with the Rotor Gene 6000® instrument. Results The frequencies of the SLCO1B1 rs4149056 and rs4363657 C variant allele were higher in Amerindians (28.3% and 26.1%) and were lower in African descent subjects (5.7% and 10.8%) compared with Mulatto (14.9% and 18.2%) and Caucasian descent (14.8% and 15.4%) ethnic groups (p < 0.001 and p < 0.001, respectively). Linkage disequilibrium analysis show that these variant alleles are in different linkage disequilibrium patterns depending on the ethnic origin. Conclusion Our findings indicate interethnic differences for the SLCO1B1 rs4149056 C risk allele frequency among Brazilians. These data will be useful in the development of effective programs for stratifying individuals regarding adherence, efficacy and choice of statin-type.

Spatio-temporal and functional structure of the amphipod communities off Santos, Southwestern Atlantic

The amphipod fauna was employed to investigate a bottom environmental gradient in the continental shelf adjacent to Santos Bay. The constant flow of less saline water from the estuarine complex of the Santos and São Vicente rivers besides the seasonal intrusion of the cold saline South Atlantic Central Water (SACW) bring a highly dynamic water regime to the area. Density, distribution, diversity and functional structure of the communities were studied on a depth gradient from 10 to 100 m on two cruises in contrasting seasons, winter 2005 and summer 2006. Twenty-one sediment samples were taken with a 0.09m² box corer. Temperature and salinity were measured at each station and an additional surface sediment sample was obtained with the box corer for granulometric and chemical analyses. Sixty species were collected on each survey and higher density values were found in summer. A priori one-way Analysis of Similarities (ANOSIM) indicated the existence of three different groups of amphipods related to the depth gradient: the Coastal group, the Mixed Zone group and the Deep Zone group. The Coastal Zone in both cruises was inhabited by a community presenting low diversity and density, besides high dominance of the infaunal tube-dweller Ampelisca paria; the area around 30 m presented the highest values of all the ecological indicators and the species showed several life styles; the outer area, situated between 50 and 100 m depth in the SACW domain, presented a community characterized by lower diversity and high biomass and density values. A season-depth ANOSIM showed the influence of depth and season for the Coastal and Mixed Zone groups whereas no seasonal difference was obtained for the Deep Zone group. The synergistic effect of the SACW and depth in the first place, followed by physical changes in substrate, seem to be the main factors controlling the fauna's distribution. In addition, the estuarine waters from Santos Bay apparently had no effect on the establishment of the environmental gradient observed on the adjacent shelf. Diversity, distribution, functional groups and trophic conditions of superficial sediments are discussed in the light of the main oceanographic processes present on the southern Brazilian shelf.

High-performance switching architectures for optical networks

The need for high bandwidth, due to the explosion of new multi\-media-oriented IP-based services, as well as increasing broadband access requirements is leading to the need of flexible and highly reconfigurable optical networks. While transmission bandwidth does not represent a limit due to the huge bandwidth provided by optical fibers and Dense Wavelength Division Multiplexing (DWDM) technology, the electronic switching nodes in the core of the network represent the bottleneck in terms of speed and capacity for the overall network. For this reason DWDM technology must be exploited not only for data transport but also for switching operations. In this Ph.D. thesis solutions for photonic packet switches, a flexible alternative with respect to circuit-switched optical networks are proposed. In particular solutions based on devices and components that are expected to mature in the near future are proposed, with the aim to limit the employment of complex components. The work presented here is the result of part of the research activities performed by the Networks Research Group at the Department of Electronics, Computer Science and Systems (DEIS) of the University of Bologna, Italy. In particular, the work on optical packet switching has been carried on within three relevant research projects: the e-Photon/ONe and e-Photon/ONe+ projects, funded by the European Union in the Sixth Framework Programme, and the national project OSATE funded by the Italian Ministry of Education, University and Scientific Research. The rest of the work is organized as follows. Chapter 1 gives a brief introduction to network context and contention resolution in photonic packet switches. Chapter 2 presents different strategies for contention resolution in wavelength domain. Chapter 3 illustrates a possible implementation of one of the schemes proposed in chapter 2. Then, chapter 4 presents multi-fiber switches, which employ jointly wavelength and space domains to solve contention. Chapter 5 shows buffered switches, to solve contention in time domain besides wavelength domain. Finally chapter 6 presents a cost model to compare different switch architectures in terms of cost.

B-type cytochromes of the DOMON domain superfamily (Novel redox elements of plant plasma membrane)

The aim of the present study is understanding the properties of a new group of redox proteins having in common a DOMON-type domain with characteristics of cytochromes b. The superfamily of proteins containing a DOMON of this type includes a few protein families. With the aim of better characterizing this new protein family, the present work addresses both a CyDOM protein (a cytochrome b561) and a protein only comprised of DOMON(AIR12), both of plant origin. Apoplastic ascorbate can be regenerated from monodehydroascorbate by a trans-plasma membrane redox system which uses cytosolic ascorbate as a reductant and comprises a high potential cytochrome b. We identified the major plasma membrane (PM) ascorbate-reducible b-type cytochrome of bean (Phaseolus vulgaris) and soybean (Glycine max) hypocotyls as orthologs of Arabidopsis auxin-responsive gene air12. The protein, which is glycosylated and glycosylphosphatidylinositol-anchored to the external side of the PM in vivo, was expressed in Pichia pastoris in a recombinant form, lacking the glycosylphosphatidylinositol-modification signal, and purified from the culture medium. Recombinant AIR12 is a soluble protein predicted to fold into a β-sandwich domain and belonging to the DOMON superfamily. It is shown to be a b-type cytochrome with a symmetrical α-band at 561 nm, to be fully reduced by ascorbate and fully oxidized by monodehydroascorbate. Redox potentiometry suggests that AIR12 binds two high-potential hemes (Em,7 +135 and +236 mV). Phylogenetic analyses reveal that the auxin-responsive genes AIR12 constitute a new family of plasma membrane b-type cytochromes specific to flowering plants. Although AIR12 is one of the few redox proteins of the PM characterized to date, the role of AIR12 in trans-PM electron transfer would imply interaction with other partners which are still to be identified. Another part of the present project was aimed at understanding of a soybean protein comprised of a DOMON fused with a well-defined b561 cytochrome domain (CyDOM). Various bioinformatic approaches show this protein to be composed of an N-terminal DOMON followed by b561 domain. The latter contains five transmembrane helices featuring highly conserved histidines, which might bind haem groups. The CyDOM has been cloned and expressed in the yeast Pichia pastoris, and spectroscopic analyses have been accomplished on solubilized yeast membranes. CyDOM clearly reveal the properties of b-type cytochrome. The results highlight the fact that CyDOM is clearly able to lead an electron flux through the plasmamembrane. Voltage clamp experiments demonstrate that Xenopus laevis oocytes transformed with CyDOM of soybean exhibit negative electrical currents in presence of an external electron acceptor. Analogous investigations were carried out with SDR2, a CyDOM of Drosophila melanogaster which shows an electron transport capacity even higher than plant CyDOM. As quoted above, these data reinforce those obtained in plant CyDOM on the one hand, and on the other hand allow to attribute to SDR2-like proteins the properties assigned to CyDOM. Was expressed in Regenerated tobacco roots, transiently transformed with infected a with chimeral construct GFP: CyDOM (by A. rhizogenes infection) reveals a plasmamembrane localization of CyDOM both in epidermal cells of the elongation zone of roots and in root hairs. In conclusion. Although the data presented here await to be expanded and in part clarified, it is safe to say they open a new perspective about the role of this group of proteins. The biological relevance of the functional and physiological implications of DOMON redox domains seems noteworthy, and it can but increase with future advances in research. Beyond the very finding, however interesting in itself, of DOMON domains as extracellular cytochromes, the present study testifies to the fact that cytochrome proteins containing DOMON domains of the type of “CyDOM” can transfer electrons through membranes and may represent the most important redox component of the plasmamembrane as yet discovered.

Paleoenvironment and Paleoecology of a Late Paleocene High-Latitude Terrestrial Succession, Arkose Ridge Formation at Box Canyon, Southern Talkeetna Mountains, Alaska

Paleogene sedimentary rocks of the Arkose Ridge Formation (Talkeetna Mountains, Alaska) preserve a record of a fluvial-lacustrine depositional environment and its forested ecosystem in an active basin among the convergent margin tectonic processes that shaped southern Alaska. An -800 m measured succession at Box Canyon indicates braid-plain deposition with predominantly gravelly deposits low in the exposure to sandy and muddy facies associations below an overlying lava flow sequence. U-Pb geochronology on zircons from a tuff and a sandstone within the measured section, as well as an Ar/Ar date from the overlying lava constrain the age of the sedimentary succession to between similar to 59 Ma and 48 Ma Fossil plant remains occur throughout the Arkose Ridge Formation as poorly-preserved coalified woody debris and fragmentary leaf impressions. At Box Canyon, however, a thin la-custrine depositional lens of rhythmically laminated mudrocks yielded fish fossils and a well-preserved floral assemblage including foliage and reproductive organs representing conifers, sphenopsids, monocots, and dicots. Leaf physiognomic methods to estimate paleoclimate were applied to the dicot leaf collection and indicate warm temperate paleotemperatures (-11-15 +/- -4 degrees C MAT) and elevated paleoprecipitation (-120 cm/yr MAP) estimates as compared to modem conditions; results that are parallel with previously published estimates from the partly coeval Chickaloon Formation deposited in more distal depositional environments in the same basin. The low abundance of leaf herbivory in the Box Canyon dicot assemblage (-9% of leaves damaged) is also similar to the results from assemblages in the meander-plain depositional systems of the Chickaloon. This new suite of data informs models of the tectonostratigraphic evolution of southern Alaska and the developing understanding of terrestrial paleoecology and paleoclimate at high latitudes during the Late Paleocene-Early Eocene greenhouse climate phase. (c) 2014 Elsevier B.V. All rights reserved.

Multicycle dose-intensive chemotherapy for women with high-risk primary breast cancer: results of International Breast Cancer Study Group Trial 15-95

PURPOSE: To compare adjuvant dose-intensive epirubicin and cyclophosphamide chemotherapy administered with filgrastim and progenitor cell support (DI-EC) with standard-dose anthracycline-based chemotherapy (SD-CT) for patients with early-stage breast cancer and a high risk of relapse, defined as stage II disease with 10 or more positive axillary nodes; or an estrogen receptor-negative or stage III tumor with five or more positive axillary nodes. PATIENTS AND METHODS: Three hundred forty-four patients were randomized after surgery to receive seven cycles of SD-CT over 22 weeks, or three cycles of DI-EC (epirubicin 200 mg/m2 plus cyclophosphamide 4 gm/m2 with filgrastim and progenitor cell support) over 6 weeks. All patients were assigned tamoxifen at the completion of chemotherapy. The primary end point was disease-free survival (DFS). RESULTS: After a median follow-up of 5.8 years (range, 3 to 8.4 years), 188 DFS events had occurred (DI-EC, 86 events; SD-CT, 102 events). The 5-year DFS was 52% for DI-EC and 43% for SD-CT, with hazard ratio of DI-EC compared with SD-CT of 0.77 (95% CI, 0.58 to 1.02; P = .07). The 5-year overall survival was 70% for DI-EC and 61% for SD-CT, with a hazard ratio of 0.79 (95% CI, 0.56 to 1.11; P = .17). There were eight cases (5%) of anthracycline-induced cardiomyopathy (two fatal) among those who received DI-EC. Women with hormone receptor-positive tumors benefited significantly from DI-EC. CONCLUSION: There was a trend in favor of DI-EC with respect to disease-free survival. A larger trial or meta-analysis will be required to reveal the true effect of dose-intensive therapy.

Time-domain modeling of high-frequency electromagnetic wave propagation, overhead wires, and earth

Prediction of radiated fields from transmission lines has not previously been studied from a panoptical power system perspective. The application of BPL technologies to overhead transmission lines would benefit greatly from an ability to simulate real power system environments, not limited to the transmission lines themselves. Presently circuitbased transmission line models used by EMTP-type programs utilize Carson’s formula for a waveguide parallel to an interface. This formula is not valid for calculations at high frequencies, considering effects of earth return currents. This thesis explains the challenges of developing such improved models, explores an approach to combining circuit-based and electromagnetics modeling to predict radiated fields from transmission lines, exposes inadequacies of simulation tools, and suggests methods of extending the validity of transmission line models into very high frequency ranges. Electromagnetics programs are commonly used to study radiated fields from transmission lines. However, an approach is proposed here which is also able to incorporate the components of a power system through the combined use of EMTP-type models. Carson’s formulas address the series impedance of electrical conductors above and parallel to the earth. These equations have been analyzed to show their inherent assumptions and what the implications are. Additionally, the lack of validity into higher frequencies has been demonstrated, showing the need to replace Carson’s formulas for these types of studies. This body of work leads to several conclusions about the relatively new study of BPL. Foremost, there is a gap in modeling capabilities which has been bridged through integration of circuit-based and electromagnetics modeling, allowing more realistic prediction of BPL performance and radiated fields. The proposed approach is limited in its scope of validity due to the formulas used by EMTP-type software. To extend the range of validity, a new set of equations must be identified and implemented in the approach. Several potential methods of implementation have been explored. Though an appropriate set of equations has not yet been identified, further research in this area will benefit from a clear depiction of the next important steps and how they can be accomplished. Prediction of radiated fields from transmission lines has not previously been studied from a panoptical power system perspective. The application of BPL technologies to overhead transmission lines would benefit greatly from an ability to simulate real power system environments, not limited to the transmission lines themselves. Presently circuitbased transmission line models used by EMTP-type programs utilize Carson’s formula for a waveguide parallel to an interface. This formula is not valid for calculations at high frequencies, considering effects of earth return currents. This thesis explains the challenges of developing such improved models, explores an approach to combining circuit-based and electromagnetics modeling to predict radiated fields from transmission lines, exposes inadequacies of simulation tools, and suggests methods of extending the validity of transmission line models into very high frequency ranges. Electromagnetics programs are commonly used to study radiated fields from transmission lines. However, an approach is proposed here which is also able to incorporate the components of a power system through the combined use of EMTP-type models. Carson’s formulas address the series impedance of electrical conductors above and parallel to the earth. These equations have been analyzed to show their inherent assumptions and what the implications are. Additionally, the lack of validity into higher frequencies has been demonstrated, showing the need to replace Carson’s formulas for these types of studies. This body of work leads to several conclusions about the relatively new study of BPL. Foremost, there is a gap in modeling capabilities which has been bridged through integration of circuit-based and electromagnetics modeling, allowing more realistic prediction of BPL performance and radiated fields. The proposed approach is limited in its scope of validity due to the formulas used by EMTP-type software. To extend the range of validity, a new set of equations must be identified and implemented in the approach. Several potential methods of implementation have been explored. Though an appropriate set of equations has not yet been identified, further research in this area will benefit from a clear depiction of the next important steps and how they can be accomplished.