Single-Stage Grid-Connected Forward Microinverter with Boundary Mode Control

This paper presents a microinverter to be integrated into a solar module. The proposed solution combines a forward converter and a constant off-time boundary mode control, providing MPPT capability and unity power factor in a single-stage converter. The transformer structure of the power stage remains as in the classical DC-DC forward converter. Transformer primary windings are utilized for power transfer or demagnetization depending on the grid semi-cycle. Furthermore, bidirectional switches are used on the secondary side allowing direct connection of the inverter to the grid. Design considerations for the proposed solution are provided, regarding the inductance value, transformer turns ratio and frequency variation during a line semi-cycle. The decoupling of the twice the line frequency power pulsation is also discussed, as well as the maximum power point tracking (MPPT) capability. Simulation and experimental results for a 100W prototype are enclosed

Physical and mathematical modeling of wave propagation in the Ariane 5 VEB structure

The separation of the lower stage of the ARIANE 5 Vehicle Equipment Bay (VEB) Structure is to be done using a pyrotechnic device. The wave propagation effects produced by the explosion can affect the electronic equipment, so it was decided to analyze, using both physical and numerical modeling, a small piece of the structure to determine the distribution of the accelerations and the relative importance of damping, stiffness, connections, etc. on the response of the equipment.

Application of backend database contents and structure to the design of spoken dialog services

Current development platforms for designing spoken dialog services feature different kinds of strategies to help designers build, test, and deploy their applications. In general, these platforms are made up of several assistants that handle the different design stages (e.g. definition of the dialog flow, prompt and grammar definition, database connection, or to debug and test the running of the application). In spite of all the advances in this area, in general the process of designing spoken-based dialog services is a time consuming task that needs to be accelerated. In this paper we describe a complete development platform that reduces the design time by using different types of acceleration strategies based on using information from the data model structure and database contents, as well as cumulative information obtained throughout the successive steps in the design. Thanks to these accelerations, the interaction with the platform is simplified and the design is reduced, in most cases, to simple confirmations to the “proposals” that the platform automatically provides at each stage. Different kinds of proposals are available to complete the application flow such as the possibility of selecting which information slots should be requested to the user together, predefined templates for common dialogs, the most probable actions that make up each state defined in the flow, different solutions to solve specific speech-modality problems such as the presentation of the lists of retrieved results after querying the backend database. The platform also includes accelerations for creating speech grammars and prompts, and the SQL queries for accessing the database at runtime. Finally, we will describe the setup and results obtained in a simultaneous summative, subjective and objective evaluations with different designers used to test the usability of the proposed accelerations as well as their contribution to reducing the design time and interaction.

Theoretical Simulation of the A5 VEB Structure Pyrotechnique Shock Propagation

This paper presents some of the modelling criteria that have been used for the study of pyrotechnic shock propagation in the A5 VEB Structure, as well as the main conclusions from a mathematical model of the axymmetric effects in it. The separation of the lower stage of the ARIANE 5 Vehicle Equipment Bay (VEB)Structure is to be done using a pyrotechnic device. The wave propagation effects produced by the explosion have been analyzed with a computer program using as shape functions the analytical solution to the frequency response of a Timoshenko-Rayleigh beams and shells in that way the discretization can have elements as large as possible, depending on the material properties and boundary conditions. Moreover an enormous amount of possibilities in the treatment of concentrated masses, springs and dashpots, either with respect to a fixed reference or between nodes, is open for translational as well as rotational degrees of freedom.

Induced shock loads during the separation of the Ariane 5 VEB structure

Tests used to simulate the separation of the lower stage of the Ariane Vehicle Equipment Bay (VEB) were carried out on a flat full scale model. Theoretical studies carried out prior to testing are described. Three different mathematical methods, finite element, component element, and wave propagation, were used. Comparison of the predicted theoretical results with the actual test results is planned.

Mathematical modelling of pyrotechnic shock in the Ariane 5 VEB structure

The theoretical improvements performed since the last spacecraft and mechanical testing conference on the study of the pyrotechnic shock phenomena produced during the separation of the lower stage of the Ariane 5 Vehicle Equipment Bay (VEB) structure are described. The first theoretical approach used was based on the wave propagation method, including axial and shear waves. The method was changed, in order to capture the bending effects, as well as the influence of the frequency dependent damping values. In addition to the development of the theoretical method, efforts were made to improve the criteria used to model the structure. Comparison of the theoretical predictions with the test results of a flat test sample 1 m width, as well as a preliminary test performed on a small sample, are presented.

The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1

The bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they are not first-stage tumor promoters. The design, computer modeling, NMR solution structure, PKC binding, and functional assays of a unique class of synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C4-C14 spacer domain. Computer modeling of an analog prototype (7a) indicates that it exists preferentially in two distinct conformational classes, one in close agreement with the crystal structure of bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9, lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant levels of in vitro growth inhibitory activity (1.8–170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins.

Plasmodium falciparum antigenic diversity: Evidence of clonal population structure

Plasmodium falciparum, the agent of malignant malaria, is one of mankind’s most severe scourges. Efforts to develop preventive vaccines or remedial drugs are handicapped by the parasite’s rapid evolution of drug resistance and protective antigens. We examine 25 DNA sequences of the gene coding for the highly polymorphic antigenic circumsporozoite protein. We observe total absence of silent nucleotide variation in the two nonrepeated regions of the gene. We propose that this absence reflects a recent origin (within several thousand years) of the world populations of P. falciparum from a single individual; the amino acid polymorphisms observed in these nonrepeat regions would result from strong natural selection. Analysis of these polymorphisms indicates that: (i) the incidence of recombination events does not increase with nucleotide distance; (ii) the strength of linkage disequilibrium between nucleotides is also independent of distance; and (iii) haplotypes in the two nonrepeat regions are correlated with one another, but not with the central repeat region they span. We propose two hypotheses: (i) variation in the highly polymorphic central repeat region arises by mitotic intragenic recombination, and (ii) the population structure of P. falciparum is clonal—a state of affairs that persists in spite of the necessary stage of physiological sexuality that the parasite must sustain in the mosquito vector to complete its life cycle.

Initiation of Assembly of the Cell Envelope Barrier Structure of Stratified Squamous Epithelia

The cell envelope (CE) is a specialized structure that is important for barrier function in terminally differentiated stratified squamous epithelia. The CE is formed inside the plasma membrane and becomes insoluble as a result of cross-linking of constituent proteins by isopeptide bonds formed by transglutaminases. To investigate the earliest stages of assembly of the CE, we have studied human epidermal keratinocytes induced to terminally differentiate in submerged liquid culture as a model system for epithelia in general. CEs were harvested from 2-, 3-, 5-, or 7-d cultured cells and examined by 1) immunogold electron microscopy using antibodies to known CE or other junctional proteins and 2) amino acid sequencing of cross-linked peptides derived by proteolysis of CEs. Our data document that CE assembly is initiated along the plasma membrane between desmosomes by head-to-tail and head-to-head cross-linking of involucrin to itself and to envoplakin and perhaps periplakin. Essentially only one lysine and two glutamine residues of involucrin and two glutamines of envoplakin were used initially. In CEs of 3-d cultured cells, involucrin, envoplakin, and small proline-rich proteins were physically located at desmosomes and had become cross-linked to desmoplakin, and in 5-d CEs, these three proteins had formed a continuous layer extending uniformly along the cell periphery. By this time >15 residues of involucrin were used for cross-linking. The CEs of 7-d cells contain significant amounts of the protein loricrin, typically expressed at a later stage of CE assembly. Together, these data stress the importance of juxtaposition of membranes, transglutaminases, and involucrin and envoplakin in the initiation of CE assembly of stratified squamous epithelia.

Inactive conformation of the serpin α1-antichymotrypsin indicates two-stage insertion of the reactive loop: Implications for inhibitory function and conformational disease

The serpins are a family of proteinase inhibitors that play a central role in the control of proteolytic cascades. Their inhibitory mechanism depends on the intramolecular insertion of the reactive loop into β-sheet A after cleavage by the target proteinase. Point mutations within the protein can allow aberrant conformational transitions characterized by β-strand exchange between the reactive loop of one molecule and β-sheet A of another. These loop-sheet polymers result in diseases as varied as cirrhosis, emphysema, angio-oedema, and thrombosis, and we recently have shown that they underlie an early-onset dementia. We report here the biochemical characteristics and crystal structure of a naturally occurring variant (Leu-55–Pro) of the plasma serpin α1-antichymotrypsin trapped as an inactive intermediate. The structure demonstrates a serpin configuration with partial insertion of the reactive loop into β-sheet A. The lower part of the sheet is filled by the last turn of F-helix and the loop that links it to s3A. This conformation matches that of proposed intermediates on the pathway to complex and polymer formation in the serpins. In particular, this intermediate, along with the latent and polymerized conformations, explains the loss of activity of plasma α1-antichymotrypsin associated with chronic obstructive pulmonary disease in patients with the Leu-55–Pro mutation.

Molecular phylogenetic analysis of evolutionary trends in stonefly wing structure and locomotor behavior

Insects in the order Plecoptera (stoneflies) use a form of two-dimensional aerodynamic locomotion called surface skimming to move across water surfaces. Because their weight is supported by water, skimmers can achieve effective aerodynamic locomotion even with small wings and weak flight muscles. These mechanical features stimulated the hypothesis that surface skimming may have been an intermediate stage in the evolution of insect flight, which has perhaps been retained in certain modern stoneflies. Here we present a phylogeny of Plecoptera based on nucleotide sequence data from the small subunit rRNA (18S) gene. By mapping locomotor behavior and wing structural data onto the phylogeny, we distinguish between the competing hypotheses that skimming is a retained ancestral trait or, alternatively, a relatively recent loss of flight. Our results show that basal stoneflies are surface skimmers, and that various forms of surface skimming are distributed widely across the plecopteran phylogeny. Stonefly wings show evolutionary trends in the number of cross veins and the thickness of the cuticle of the longitudinal veins that are consistent with elaboration and diversification of flight-related traits. These data support the hypothesis that the first stoneflies were surface skimmers, and that wing structures important for aerial flight have become elaborated and more diverse during the radiation of modern stoneflies.

Recent improvements in prediction of protein structure by global optimization of a potential energy function

Recent improvements of a hierarchical ab initio or de novo approach for predicting both α and β structures of proteins are described. The united-residue energy function used in this procedure includes multibody interactions from a cumulant expansion of the free energy of polypeptide chains, with their relative weights determined by Z-score optimization. The critical initial stage of the hierarchical procedure involves a search of conformational space by the conformational space annealing (CSA) method, followed by optimization of an all-atom model. The procedure was assessed in a recent blind test of protein structure prediction (CASP4). The resulting lowest-energy structures of the target proteins (ranging in size from 70 to 244 residues) agreed with the experimental structures in many respects. The entire experimental structure of a cyclic α-helical protein of 70 residues was predicted to within 4.3 Å α-carbon (Cα) rms deviation (rmsd) whereas, for other α-helical proteins, fragments of roughly 60 residues were predicted to within 6.0 Å Cα rmsd. Whereas β structures can now be predicted with the new procedure, the success rate for α/β- and β-proteins is lower than that for α-proteins at present. For the β portions of α/β structures, the Cα rmsd's are less than 6.0 Å for contiguous fragments of 30–40 residues; for one target, three fragments (of length 10, 23, and 28 residues, respectively) formed a compact part of the tertiary structure with a Cα rmsd less than 6.0 Å. Overall, these results constitute an important step toward the ab initio prediction of protein structure solely from the amino acid sequence.

The folding mechanism of larger model proteins: role of native structure.

The folding mechanism of a 125-bead heteropolymer model for proteins is investigated with Monte Carlo simulations on a cubic lattice. Sequences that do and do not fold in a reasonable time are compared. The overall folding behavior is found to be more complex than that of models for smaller proteins. Folding begins with a rapid collapse followed by a slow search through the semi-compact globule for a sequence-dependent stable core with about 30 out of 176 native contacts which serves as the transition state for folding to a near-native structure. Efficient search for the core is dependent on structural features of the native state. Sequences that fold have large amounts of stable, cooperative structure that is accessible through short-range initiation sites, such as those in anti-parallel sheets connected by turns. Before folding is completed, the system can encounter a second bottleneck, involving the condensation and rearrangement of surface residues. Overly stable local structure of the surface residues slows this stage of the folding process. The relation of the results from the 125-mer model studies to the folding of real proteins is discussed.

X-ray absorption fine structure as a monitor of zinc coordination sites during oogenesis of Xenopus laevis.

The x-ray absorption fine structure (XAFS) zinc K-edge steps for intact stages I,II and V,VI Xenopus laevis oocytes demonstrate that the zinc concentration is about 3 and 1 mM, respectively. However, the chi(k) function for the early stage oocytes differs markedly from that for the late one. Analysis of the XAFS data for stage I,II oocytes indicates that zinc is bound to 2.0 +/- 0.5 sulfur atoms at an average coordination distance of 2.29 +/- 0.02 angstroms and 2.0 +/- 0.5 nitrogen or oxygen (N/O) atoms at 2.02 +/- 0.02 angstroms. In marked contrast, in stage V,VI oocytes, zinc is bound to 4.1 +/- 0.4 N/O atoms at an average distance of 1.98 +/- 0.01 angstroms. Our previous studies demonstrated that 90% of the zinc in stage VI oocytes is sequestered within yolk platelets, associated with a single molecule, lipovitellin, the proteolytically processed product of vitellogenin. XAFS analysis of yolk platelets, lipovitellin, and vitellogenin demonstrates that zinc is bound to 4.0 +/- 0.5 N/O ligands at an average distance of 1.98 +/- 0.01 angstroms in each case, identical to that of stage V,VI oocytes. The higher shell contributions in the Fourier transforms indicate that two of the N/O zinc ligands are His in both stage V,VI and I,II oocytes. The results show that in stage I,II oocytes, there is a high concentration of a zinc protein whose zinc coordination site likely is composed of (His)2(Cys)2, such as, e.g., TFIIIA. As the oocytes develop, the predominant zinc species becomes one that exhibits the (His)2(N/0)2 zinc site found in lipovitellin. Hence, the ligands to the zinc atoms in intact oocytes and the changes that take place as a function of oogenesis and after their fertilization, during embryogenesis, now can be examined and explored.

Primary structure of hepatocyte nuclear factor/forkhead homologue 4 and characterization of gene expression in the developing respiratory and reproductive epithelium.

Members of the winged helix/forkhead family of transcription factors are believed to play a role in cell-specific gene expression. A cDNA encoding a member of this family of proteins, termed hepatocyte nuclear factor/forkhead homologue 4 (HFH-4), has been isolated from rat lung and rat testis cDNA libraries. This cDNA contains an open reading frame of 421 amino acids with a conserved DNA binding domain and several potential transactivating regions. During murine lung development, a single species of HFH-4-specific transcript (2.4 kb long) is first detected precisely at the start of the late pseudoglandular stage (embryonic day 14.5) and, by in situ hybridization, is specifically localized to the proximal pulmonary epithelium. The unique temporal and spatial pattern of HFH-4 gene expression in the developing lung defines this protein as a marker for the initiation of bronchial epithelial cell differentiation and suggests that it may play an important role in cell fate determination during lung development. In addition to expression in the pulmonary epithelium, RNA blot analysis reveals 2.4-kb HFH-4 transcripts in the testis and oviduct. By using mice with genetic defects in spermatogenesis, HFH-4 expression in the testis is found to be associated with the appearance of haploid germ cells and in situ hybridization studies indicate that HFH-4 expression is confined to stages I-VII of spermatogenesis. This pattern of HFH-4 gene expression during the early stages of differentiation of haploid germ cells suggests that HFH-4 may play a role in regulating stage-specific gene expression and cell-fate determination during lung development and in spermatogenesis.