A single nucleotide deletion at the C1 inhibitor gene as the cause of hereditary angioedema: insights from a Brazilian family

Background: Hereditary angioedema is an autosomal dominant disease characterized by episodes of subcutaneous and submucosal edema. It is caused by deficiency of the C1 inhibitor protein, leading to elevated levels of bradykinin. More than 200 mutations in C1 inhibitor gene have been reported. The aim of this study was to analyze clinical features of a large family with an index case of hereditary angioedema and to determine the disease-causing mutation in this family. Methods: Family pedigree was constructed with 275 individuals distributed in five generations. One hundred and sixty-five subjects were interviewed and investigated for mutation at the C1 inhibitor gene. Subjects reporting a history of recurrent episodes of angioedema and/or abdominal pain attacks underwent evaluation for hereditary angioedema. Results: We have identified a novel mutation at the C1 inhibitor gene, c.351delC, which is a single-nucleotide deletion of a cytosine on exon 3, resulting in frameshift with premature stop codon. Sequencing analysis of the hypothetical truncated C1 inhibitor protein allowed us to conclude that, if transcription occurs, this protein has no biological activity. Twenty-eight members of the family fulfilled diagnostic criteria for hereditary angioedema and all of them presented the c.351delC mutation. Variation in clinical presentation and severity of disease was observed among these patients. One hundred and thirty-seven subjects without hereditary angioedema did not have the c.351delC mutation. Conclusion: The present study provides definitive evidence to link a novel genetic mutation to the development of hereditary angioedema in patients from a Brazilian family.

Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha-238 and-308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study

Background The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)-alpha promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Methods Polymorphisms were identified using PCR/SSP. Alleles, genotypes, and haplotypes frequencies were compared using Fisher`s test. Results More severe disease was found in male patients. It may be suggested that alleles B*37, Cw*06, Cw*12, and DRB1*07 were associated with severe disease course, while B*57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF-238 G/G genotype frequency (OR: 3.21; CI: 1.06-9.71; P = 0.04) in the group with severe disease. Conclusions Polymorphisms in the TNF-alpha SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.

Improvement of the electrolytic properties of Y2O3-based materials using a crystallographic index

Y2O3 is a c-type rare earth oxide with a fluorite-related structure. This material has been used to refractory because of its high thermal stability and excellent resistance to hydration. In this study, the effective index was suggested in order to improve the electrolytic properties of Y2O3-based oxide. (CexY1-x)(2)O3+delta (x = 0.25 and 0.3) and [LaaSrbCe0.25Y(1-a-b)](2)O3+delta (a = 0.05, 0.1 and 0.15, b = 0, 0.006 and 0.0125) were prepared as the examples with intermediate and high index, respectively. The specimens with high index value such as (La0.15Ce0.25Y0.60)(2)O-3.25 and (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.24 consisted of two phases such as c-type and fluorite, although (Ce0.25Y0.75)(2)O-3.25 with intermediate index value had a single phase of c-type rare earth oxide. Microanalysis indicates that a grain in the (La0.1Sr0.0125Ce0.25Y0.6375)(2)O-3.23(7) sintered body consists of c-type and fluorite phases. An interface between c-type and fluorite phases is coherent in a grain. This suggests that this effective index guides the crystal structure in the specimen to fluorite and the examined composition introduces the interface between c-type and fluorite in the microstructure. The electrochemical properties of specimens including Y2O3 were characterized on the basis of the suggested index. The electrical conductivity of Y2O3-based materials increased with an increase of the index. The apparent activation energy of Y2O3-based materials decreased with increasing index. The ionic transport number of oxygen of the specimens was improved by enhancement of the index, confirming validity of the index. The oxide ionic conductive region of (La0.1Sr0.0125Ce0.25Y0.(6375))(2)O-3.23(7) with high effective index extended up to P-O2 = 10(-18) atm at 800 degreesC, although the specimens with low or intermediate index showed p- or n-type semi-conduction in the same P-O2 region at 800 and 1000 degreesC. These results suggest that the interface between c-type and fluorite phases also contributes to improve the electrolytic properties in the grain. It is concluded that the improvement of electrolytic properties in Y2O3-based materials is attributable to the microstructure with interface between two phases in a grain and the fluorite structure guided by the suggested index. (C) 2001 Published by Elsevier Science B.V.

The strain-driven pyrochlore to "defect fluorite" phase transition in rare earth sesquioxide stabilized cubic zirconias

The relationship between the ordering characteristic of the pyrochlore structure type and that characteristic of the defect fluorite structure type (immediately on either side of two phase regions separating the two structure types) in a range of rare eath sesquioxide stabilized cubic zirconias is investigated via electron diffraction and imaging. Systematic structural change as a function of composition and relative size of the constituent metal ions is highlighted and a multi-q to single-q = 1/2 [111]* model proposed for the observed pyrochlore to defect fluorite phase transition. Strain introduced into the close-packed {111} metal ion planes of the defect fluorite average structure by the local cation and oxygen vacancy distribution is pointed to as the likely origin of the observed behavior. (C) 2001 Academic Press

Single-electron measurements with a micromechanical resonator

A mechanical electroscope based on a change in the resonant frequency of a cantilever one micron in size in the presence of charge has recently been fabricated. We derive the decoherence rate of a charge superposition during measurement with such a device using a master equation theory adapted from quantum optics. We also investigate the information produced by such a measurement, using a quantum trajectory approach. Such instruments could be used in mesoscopic electronic systems, and future solid-state quantum computers, so it is useful to know how they behave when used to measure quantum superpositions of charge.

A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alpha beta heteromeric glycine receptor chloride channels

This study investigated the residues responsible for the reduced picrotoxin sensitivity of the alpha beta heteromeric glycine receptor relative to the alpha homomeric receptor. By analogy with structurally related receptors, the beta subunit M2 domain residues P278 and F282 were considered the most likely candidates for mediating this effect. These residues align with G254 and T258 of the alpha subunit. The T258A, T258C and T258F mutations dramatically reduced the picrotoxin sensitivity of the alpha homomeric receptor. Furthermore, the converse F282T mutation in the beta subunit increased the picrotoxin sensitivity of the alpha beta heteromeric receptor. The P278G mutation in the beta subunit did not affect the picrotoxin sensitivity of the alpha beta heteromer. Thus, a ring of five threonines at the M2 domain depth corresponding to alpha subunit T258 is specifically required for picrotoxin sensitivity. Mutations to alpha subunit T258 also profoundly influenced the apparent glycine affinity. A substituted cysteine accessibility analysis revealed that the T258C sidechain increases its pore exposure in the channel open state. This provides further evidence for an allosteric mechanism of picrotoxin inhibition, but renders it unlikely that picrotoxin las an allosterically acting 'competitive' antagonist) binds to this residue.

An in situ study of photosynthetic oxygen exchange and electron transport rate in the marine macroalga Ulva lactuca (Chlorophyta)

Direct comparisons between photosynthetic O-2 evolution rate and electron transport rate (ETR) were made in situ over 24 h using the benthic macroalga Ulva lactuca (Chlorophyta), growing and measured at a depth of 1.8 m, where the midday irradiance rose to 400-600 mumol photons m(-2) s(-1). O-2 exchange was measured with a 5-chamber data-logging apparatus and ETR with a submersible pulse amplitude modulated (PAM) fluorometer (Diving-PAM). Steady-state quantum yield ((Fm'-Ft)/Fm') decreased from 0.7 during the morning to 0.45 at midday, followed by some recovery in the late afternoon. At low to medium irradiances (0-300 mumol photons m(-2) s(-1)), there was a significant correlation between O-2 evolution and ETR, but at higher irradiances, ETR continued to increase steadily, while O-2 evolution tended towards an asymptote. However at high irradiance levels (600-1200 mumol photons m-(2) s(-1)) ETR was significantly lowered. Two methods of measuring ETR, based on either diel ambient light levels and fluorescence yields or rapid light curves, gave similar results at low to moderate irradiance levels. Nutrient enrichment (increases in [NO3-], [NH4+] and [HPO42-] of 5- to 15-fold over ambient concentrations) resulted in an increase, within hours, in photosynthetic rates measured by both ETR and O-2 evolution techniques. At low irradiances, approximately 6.5 to 8.2 electrons passed through PS II during the evolution of one molecule of O-2, i.e., up to twice the theoretical minimum number of four. However, in nutrient-enriched treatments this ratio dropped to 5.1. The results indicate that PAM fluorescence can be used as a good indication of the photosynthetic rate only at low to medium irradiances.

Efficient time-independent wave packet scattering calculations within a Lanczos subspace: H+O-2 (J=0) state-to-state reaction probabilities

An efficient Lanczos subspace method has been devised for calculating state-to-state reaction probabilities. The method recasts the time-independent wave packet Lippmann-Schwinger equation [Kouri , Chem. Phys. Lett. 203, 166 (1993)] inside a tridiagonal (Lanczos) representation in which action of the causal Green's operator is affected easily with a QR algorithm. The method is designed to yield all state-to-state reaction probabilities from a given reactant-channel wave packet using a single Lanczos subspace; the spectral properties of the tridiagonal Hamiltonian allow calculations to be undertaken at arbitrary energies within the spectral range of the initial wave packet. The method is applied to a H+O-2 system (J=0), and the results indicate the approach is accurate and stable. (C) 2002 American Institute of Physics.

Use of confocal microscopy to follow the development of penetrative hyphae during growth of Rhizopus oligosporus in an artificial solid-state fermentation system

Two methods were compared for determining the concentration of penetrative biomass during growth of Rhizopus oligosporus on an artificial solid substrate consisting of an inert gel and starch as the sole source of carbon and energy. The first method was based on the use of a hand microtome to make sections of approximately 0.2- to 0.4-mm thickness parallel to the substrate surface and the determination of the glucosamine content in each slice. Use of glucosamine measurements to estimate biomass concentrations was shown to be problematic due to the large variations in glucosamine content with mycelial age. The second method was a novel method based on the use of confocal scanning laser microscopy to estimate the fractional volume occupied by the biomass. Although it is not simple to translate fractional volumes into dry weights of hyphae due to the lack of experimentally determined conversion factors, measurement of the fractional volumes in themselves is useful for characterizing fungal penetration into the substrate. Growth of penetrative biomass in the artificial model substrate showed two forms of growth with an indistinct mass in the region close to the substrate surface and a few hyphae penetrating perpendicularly to the surface in regions further away from the substrate surface. The biomass profiles against depth obtained from the confocal microscopy showed two linear regions on log-linear plots, which are possibly related to different oxygen availability at different depths within the substrate. Confocal microscopy has the potential to be a powerful tool in the investigation of fungal growth mechanisms in solid-state fermentation. (C) 2003 Wiley Periodicals, Inc.

Environmental performance of aquaculture in Rondônia state, Brazil

The objective of this study was to analyze the environmental performance of aquaculture in the city of Colorado do Oeste, Rondônia State, Brazil. Fifteen fish farmers were interviewed. For data collection, structured interviews were carried out, using a questionnaire based on information supplied by the United Nations Food and Agriculture Organization (FAO). The questionnaire considered 12 items, organized into three main topics: a) social and legal standards b) environmental standards c) standards of food safety and hygiene. The questionnaire considered 12 items, organized into three main topics: a) social and legal standards b) environmental standards c) standards of food safety and hygiene. Aquaculture in the city of Colorado do Oeste, Rondônia presents two fish production systems: extensive and semi-intensive. In the semi-intensive system, stocking rate was one fish per m3, on average; tambaqui (Colossoma macropomum), tilapias (Oreochromis spp.), pirarucu (Arapaima gigas) and pintado (Pseudoplatystoma spp.) were the species farmed at the largest number. The rate of water renewal was due to the greater availability of natural food in this system. Water renewal was constant in the ponds (1,500 liters per minute). In the semi-intensive system using dug ponds, alevins were stocked and fed during the entire rearing time with natural and exogenous food. The extensive system relied on the natural production of the pond, with stocking density limited by the production of natural food. The little renewal of water made the cultivation tank itself acted as a decantation lake, with the occurrence of oxidation and sedimentation of residual organic matter, consisting of feces, debris and organic fertilizer. Production of reduced effluent volume took place in the extensive system, compared to the cultivation area. In addition, there was high water turbidity, caused by high concentration of planktonic organisms, and low concentrations of dissolved oxygen in the water. Data showed that nine estates of the interviewed fish farmers had critical environmental performance (less than 30.0%). Six estates of fish farmers had bad environmental performance (between 30.0 and 50.0%) (Coefficient of sustentainability = green square x 100 ÷ Total Questions less the yellow squares)

Electrical transport properties of CuS single crystals

Electrical resistivity, transverse magnetoresistance and thermoelectric power measurements were performed on CuS high quality single crystals in the range 1.2-300 K and under fields of up to 16 T. The zero field resistivity data are well described below 55 K by a quasi-2D model, consistent with a carrier confinement at lower temperatures, before the transition to the superconducting state. The transverse magnetoresistance develops mainly below 30 K and attains values as large as 470% for a 16 T field at 5 K, this behaviour being ascribed to a band effect mechanism, with a possible magnetic field induced DOS change at the Fermi level. The transverse magnetoresistance shows no signs of saturation, following a power law with field Delta rho/rho(0) proportional to H(1.4), suggesting the existence of open orbits for carriers at the Fermi surface. The thermoelectric power shows an unusual temperature dependence, probably as a result of the complex band structure of CuS.

IOPT Petri Net State Space Generation Algorithm with Maximal-Step Execution Semantics

This paper presents an algorithm to efficiently generate the state-space of systems specified using the IOPT Petri-net modeling formalism. IOPT nets are a non-autonomous Petri-net class, based on Place-Transition nets with an extended set of features designed to allow the rapid prototyping and synthesis of system controllers through an existing hardware-software co-design framework. To obtain coherent and deterministic operation, IOPT nets use a maximal-step execution semantics where, in a single execution step, all enabled transitions will fire simultaneously. This fact increases the resulting state-space complexity and can cause an arc "explosion" effect. Real-world applications, with several million states, will reach a higher order of magnitude number of arcs, leading to the need for high performance state-space generator algorithms. The proposed algorithm applies a compilation approach to read a PNML file containing one IOPT model and automatically generate an optimized C program to calculate the corresponding state-space.

Efficient Implementation Of A Single-Precision Floating-Point Arithmetic Unit on FPGA

This paper presents a single precision floating point arithmetic unit with support for multiplication, addition, fused multiply-add, reciprocal, square-root and inverse squareroot with high-performance and low resource usage. The design uses a piecewise 2nd order polynomial approximation to implement reciprocal, square-root and inverse square-root. The unit can be configured with any number of operations and is capable to calculate any function with a throughput of one operation per cycle. The floatingpoint multiplier of the unit is also used to implement the polynomial approximation and the fused multiply-add operation. We have compared our implementation with other state-of-the-art proposals, including the Xilinx Core-Gen operators, and conclude that the approach has a high relative performance/area efficiency. © 2014 Technical University of Munich (TUM).

Multifunctional controller architecture for sold-state marx modulator based on FPGA

This paper proposes a multifunctional architecture to implement field-programmable gate array (FPGA) controllers for power converters and presents a prototype for a pulsed power generator based on a solid-state Marx topology. The massively parallel nature of reconfigurable hardware platforms provides very high processing power and fast response times allowing the implementation of many subsystems in the same device. The prototype includes the controller, a failure detection system, an interface with a safety/emergency subsystem, a graphical user interface, and a virtual oscilloscope to visualize the generated pulse waveforms, using a single FPGA. The proposed architecture employs a modular design that can be easily adapted to other power converter topologies.

Single side damage simulations and detection in beam-like structures

Beam-like structures are the most common components in real engineering, while single side damage is often encountered. In this study, a numerical analysis of single side damage in a free-free beam is analysed with three different finite element models; namely solid, shell and beam models for demonstrating their performance in simulating real structures. Similar to experiment, damage is introduced into one side of the beam, and natural frequencies are extracted from the simulations and compared with experimental and analytical results. Mode shapes are also analysed with modal assurance criterion. The results from simulations reveal a good performance of the three models in extracting natural frequencies, and solid model performs better than shell while shell model performs better than beam model under intact state. For damaged states, the natural frequencies captured from solid model show more sensitivity to damage severity than shell model and shell model performs similar to the beam model in distinguishing damage. The main contribution of this paper is to perform a comparison between three finite element models and experimental data as well as analytical solutions. The finite element results show a relatively well performance.