Steady-State Stability of Current Mode Active-Clamp ZVS DC-DC Converters

Active-clamp dc-dc converters are pulsewidth-modulated converters having two switches featuring zero-voltage switching at frequencies beyond 100 kHz. Generalized equivalent circuits valid for steady-state and dynamic performance have been proposed for the family of active-clamp converters. The active-clamp converter is analyzed for its dynamic behavior under current control in this paper. The steady-state stability analysis is presented. On account of the lossless damping inherent in the active-clamp converters, it appears that the stability region in the current-controlled active-clamp converters get extended for duty ratios, a little greater than 0.5, unlike in conventional hard-switched converters. The conventional graphical approach fails to assess the stability of current-controlled active-clamp converters due to the coupling between the filter inductor current and resonant inductor current. An analysis that takes into account the presence of the resonant elements is presented to establish the condition for stability. This method correctly predicts the stability of the current-controlled active-clamp converters. A simple expression for the maximum duty cycle for subharmonic free operation is obtained. The results are verified experimentally.

Classification of Protein Kinases on the Basis of Both Kinase and Non-Kinase Regions

Background: Protein phosphorylation is a generic way to regulate signal transduction pathways in all kingdoms of life. In many organisms, it is achieved by the large family of Ser/Thr/Tyr protein kinases which are traditionally classified into groups and subfamilies on the basis of the amino acid sequence of their catalytic domains. Many protein kinases are multidomain in nature but the diversity of the accessory domains and their organization are usually not taken into account while classifying kinases into groups or subfamilies. Methodology: Here, we present an approach which considers amino acid sequences of complete gene products, in order to suggest refinements in sets of pre-classified sequences. The strategy is based on alignment-free similarity scores and iterative Area Under the Curve (AUC) computation. Similarity scores are computed by detecting common patterns between two sequences and scoring them using a substitution matrix, with a consistent normalization scheme. This allows us to handle full-length sequences, and implicitly takes into account domain diversity and domain shuffling. We quantitatively validate our approach on a subset of 212 human protein kinases. We then employ it on the complete repertoire of human protein kinases and suggest few qualitative refinements in the subfamily assignment stored in the KinG database, which is based on catalytic domains only. Based on our new measure, we delineate 37 cases of potential hybrid kinases: sequences for which classical classification based entirely on catalytic domains is inconsistent with the full-length similarity scores computed here, which implicitly consider multi-domain nature and regions outside the catalytic kinase domain. We also provide some examples of hybrid kinases of the protozoan parasite Entamoeba histolytica. Conclusions: The implicit consideration of multi-domain architectures is a valuable inclusion to complement other classification schemes. The proposed algorithm may also be employed to classify other families of enzymes with multidomain architecture.

Modelling initial survival and growth of radiata pine in New Zealand.

A sensitive framework has been developed for modelling young radiata pine survival, its growth and its size class distribution, from time of planting to age 5 or 6 years. The data and analysis refer to the Central North Island region of New Zealand. The survival function is derived from a Weibull probability density function, to reflect diminishing mortality with the passage of time in young stands. An anamorphic family of trends was used, as very little between-tree competition can be expected in young stands. An exponential height function was found to fit best the lower portion of its sigmoid form. The most appropriate basal area/ha exponential function included an allometric adjustment which resulted in compatible mean height and basal area/ha models. Each of these equations successfully represented the effects of several establishment practices by making coefficients linear functions of site factors, management activities and their interactions. Height and diameter distribution modelling techniques that ensured compatibility with stand values were employed to represent the effects of management practices on crop variation. Model parameters for this research were estimated using data from site preparation experiments in the region and were tested with some independent data sets.

Euclideanization of Majorana and Weyl Fermions

A continuous procedure is presented for euclideanization of Majorana and Weyl fermions without doubling their degrees of freedom. The Euclidean theory so obtained is SO(4) invariant and Osterwalder-Schrader (OS) positive. This enables us to define a one-complex parameter family of the N=1 supersymmetric Yang-Mills (SSYM) theories which interpolate between the Minkowski and a Euclidean SSYM theory. The interpolating action, and hence the Euclidean action, manifests all the continous symmetries of the original Minkowski space theory.

Regulation and Function of GATA Transcription Factors in Adrenocortical Tumors and Granulosa Cells

Transcription factors play a key role in tumor development, in which dysfunction of genes regulating tissue growth and differentiation is a central phenomenon. The GATA family of transcription factors consists of six members that bind to a consensus DNA sequence (A/T)GATA(A/G) in gene promoters and enhancers. The two GATA factors expressed in the adrenal cortex are GATA-4 and GATA-6. In both mice and humans, GATA-4 can be detected only during the fetal period, whereas GATA-6 expression is abundant both throughout development and in the adult. It is already established that GATA factors are important in both normal development and tumorigenesis of several endocrine organs, and expression of GATA-4 and GATA-6 is detected in adrenocortical tumors. The aim of this study was to elucidate the function of these factors in adrenocortical tumor growth. In embryonal development, the adrenocortical cells arise and differentiate from a common pool with gonadal steroidogenic cells, the urogenital ridge. As the adult adrenal cortex undergoes constant renewal, it is hypothesized that undifferentiated adrenocortical progenitor cells reside adjacent to the adrenal capsule and give rise to daughter cells that differentiate and migrate centripetally. A diverse array of hormones controls the differentiation, growth and survival of steroidogenic cells in the adrenal gland and the gonads. Factors such as luteinizing hormone and inhibins, traditionally associated with gonadal steroidogenic cells, can also influence the function of adrenocortical cells in physiological and pathophysiological states. Certain inbred strains of mice develop subcapsular adrenocortical tumors in response to gonadectomy. In this study, we found that these tumors express GATA-4, normally absent from the adult adrenal cortex, while GATA-6 expression is downregulated. Gonadal markers such as luteinizing hormone receptor, anti-Müllerian hormone and P450c17 are also expressed in the neoplastic cells, and the tumors produce gonadal hormones. The tumor cells have lost the expression of melanocortin-2 receptor and the CYP enzymes necessary for the synthesis of corticosterone and aldosterone. By way of xenograft studies utilizing NU/J nude mice, we confirmed that chronic gonadotropin elevation is sufficient to induce adrenocortical tumorigenesis in susceptible inbred strains. Collectively, these studies suggest that subcapsular adrenocortical progenitor cells can, under certain conditions, adopt a gonadal fate. We studied the molecular mechanisms involved in gene regulation in endocrine cells in order to elucidate the role of GATA factors in endocrine tissues. Ovarian granulosa cells express both GATA-4 and GATA-6, and the TGF-β signaling pathway is active in these cells. Inhibin-α is both a target gene for, and an atypical or antagonistic member of the TGF-β growth factor superfamily. In this study, we show that GATA-4 is required for TGF-β-mediated inhibin-α promoter activation in granulosa cells, and that GATA-4 physically interacts with Smad3, a TGF-β downstream protein. Apart from the regulation of steroidogenesis and other events in normal tissues, TGF-β signaling is implicated in tumors of multiple organs, including the adrenal cortex. Another signaling pathway found often to be aberrantly active in adrenocortical tumors is the Wnt pathway. As both of these pathways regulate the expression of inhibin-α, a transcriptional target for GATA-4 and GATA-6, we wanted to investigate whether GATA factors are associated with the components of these signaling cascades in human adrenocortical tumors. We found that the expression of Wnt co-receptors LRP5 and LRP6, Smad3, GATA-6 and SF-1 was diminished in adrenocortical carcinomas with poor outcome. All of these factors drive inhibin-α expression, and their expression in adrenocortical tumors correlated with that of inhibin-α. The results support a tumor suppressor role previously suggested for inhibin-α in the mouse adrenal cortex, and offer putative pathways associated with adrenocortical tumor aggressiveness. Unraveling the role of GATA factors and associated molecules in human and mouse adrenocortical tumors could ultimately contribute to the development of diagnostic tools and future therapies for these diseases.

An algebraic formulation of static isotropy and design of statically isotropic 6–6 Stewart platform manipulators

In this paper, we present an algebraic method to study and design spatial parallel manipulators that demonstrate isotropy in the force and moment distributions. We use the force and moment transformation matrices separately, and derive conditions for their isotropy individually as well as in combination. The isotropy conditions are derived in closed-form in terms of the invariants of the quadratic forms associated with these matrices. The formulation is applied to a class of Stewart platform manipulator, and a multi-parameter family of isotropic manipulators is identified analytically. We show that it is impossible to obtain a spatially isotropic configuration within this family. We also compute the isotropic configurations of an existing manipulator and demonstrate a procedure for designing the manipulator for isotropy at a given configuration.

Optimum Design of Composite Laminates for Strength by Ranking

In this paper we describe a method for the optimum design of fiber rein forced composite laminates for strength by ranking. The software developed based on this method is capable of designing laminates for strength; which are subjected to inplane and/or bending loads and optionally hygrothermal loads. Symmetric laminates only are considered which are assumed to be made of repeated sublaminate construction. Various layup schemes are evaluated based on the laminated plate theory and quadratic failure cri terion for the given mechanical and hygrothermal loads. The optimum layup sequence in the sublaminate and the number of such sublaminates required are obtained. Further, a ply-drop round-off scheme is adopted to arrive at an optimum laminate thickness. As an example, a family of 0/90/45/ -45 bi-directional lamination schemes are examined for dif ferent types of loads and the gains in optimising the ply orientations in a sublaminate are demonstrated.

Propagation of quasi-simple waves in a compressible rotating atmosphere

A class of self-propagating linear and nonlinear travelling wave solutions for compressible rotating fluid is studied using both numerical and analytical techiques. It is shown that, in general, a three dimensional linear wave is not periodic. However, for some range of wave numbers depending on rotation, horizontally propagating waves are periodic. When the rotation ohgr is equal to $$\sqrt {(\gamma - 1)/(4\gamma )}$$ , all horizontal waves are periodic. Here, gamma is the ratio of specific heats. The analytical study is based on phase space analysis. It reveals that the quasi-simple waves are periodic only in some plane, even when the propagation is horizontal, in contrast to the case of non-rotating flows for which there is a single parameter family of periodic solutions provided the waves propagate horizontally. A classification of the singular points of the governing differential equations for quasi-simple waves is also appended.

Src Homology 3-interacting Domain of Rv1917c of Mycobacterium tuberculosis Induces Selective Maturation of Human Dendritic Cells by Regulating PI3K-MAPK-NF-kappa B Signaling and Drives Th2 Immune Responses

Mycobacterium tuberculosis, an etiological agent of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Pathogenic mycobacteria survive in the host by subverting host innate immunity. Dendritic cells (DCs) are professional antigen-presenting cells that are vital for eliciting immune responses to infectious agents, including pathogenic mycobacteria. DCs orchestrate distinct Th responses based on the signals they receive. In this perspective, deciphering the interactions of the proline-glutamic acid/proline-proline-glutamic acid (PE/PPE) family of proteins of M. tuberculosis with DCs assumes significant pathophysiological attributes. In this study, we demonstrate that Rv1917c (PPE34), a representative member of the proline-proline-glutamic-major polymorphic tandem repeat family, interacts with TLR2 and triggers functional maturation of human DCs. Signaling perturbations implicated a critical role for integrated cross-talk among PI3K-MAPK and NF-kappa B signaling cascades in Rv1917c-induced maturation of DCs. However, this maturation of DCs was associated with a secretion of high amounts of anti-inflammatory cytokine IL-10, whereas Th1-polarizing cytokine IL-12 was not induced. Consistent with these results, Rv1917c-matured DCs favored secretion of IL-4, IL-5, and IL-10 from CD4(+) T cells and contributed to Th2-skewed cytokine balance ex vivo in healthy individuals and in patients with pulmonary tuberculosis. Interestingly, the Rv1917c-skewed Th2 immune response involved induced expression of cyclooxygenase-2 (COX-2) in DCs. Taken together, these results indicate that Rv1917c facilitates a shift in the ensuing immunity toward the Th2 phenotype and could aid in immune evasion by mycobacteria.

Cloning, expression, purification, crystallization and preliminary X-ray studies of a secreted lectin (Rv1419) from Mycobacterium tuberculosis

A secreted lectin, Rv1419, from Mycobacterium tuberculosis has been cloned, expressed, purified and crystallized and the crystals have been characterized. This represents the first X-ray investigation of a lectin or lectin-like molecule from the pathogen. The cubic crystals contain one molecule in the asymmetric unit. Sequence comparisons indicate that the lectin has a beta-trefoil fold and belongs to a well characterized family of carbohydrate-binding modules. Structural analysis of the crystals is in progress.

Nucleotide sequence of the first cosmid from the Mycobacterium leprae genome project: structure and function of the Rif-Str regions

The nucleotide sequence of cosmid B1790, carrying the Rif-Str regions of the Mycobacterium leprae chromosome, has been determined. Twelve open reading frames were identified in the 36716bp sequence, representing 40% of the coding capacity. Five ribosomal proteins, two elongation factors and the β and β'subunits of RNA polymerase have been characterized and two novel genes were found. One of these encodes a member of the so-called ABC family of ATP-binding proteins while the other appears to encode an enzyme involved in repairing genomic lesions caused by free radicals. This finding may well be significant as M. leprae, an intracellular pathogen, lives within macrophages.

Role of GDNF and its Cross-Talk with Other Growth Factors in the Dopaminergic System

Parkinson´s Disease (PD) is a neurodegenerative movement disorder resulting from loss of dopaminergic (DA) neurons in substantia nigra (SN). Possible causative treatment strategies for PD include neurotrophic factors, which protect and in some cases restore the function of dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) family of neurotrophic factors have been to date the most promising candidates for treatment of PD, demonstrating both neuroprotective and neurorestorative properties. We have investigated the role of GDNF in the rodent dopaminergic system and its possible crosstalk with other growth factors. We characterized the GDNF-induced gene expression changes by DNA microarray analysis in different neuronal systems, including in vitro cultured Neuro2A cells treated with GDNF, as well as midbrains from GDNF heterozygous (Hz) knockout mice. These microarray experiments, resulted in the identification of GDNF-induced genes, which were also confirmed by other methods. Further analysis of the dopaminergic system of GDNF Hz mice demonstrated about 40% reduction in GDNF levels, revealed increased intracellular dopamine concentrations and FosB/DeltaFosB expression in striatal areas. These animals did not show any significant changes in behavioural analysis of acute and repeated cocaine administration on locomotor activity, nor did they exhibit any changes in dopamine output following treatment with acute cocaine. We further analysed the significance of GDNF receptor RET signalling in dopaminergic system of MEN2B knock-in animals with constitutively active Ret. The MEN2B animals showed a robust increase in extracellular dopamine and its metabolite levels in striatum, increased tyrosine hydroxylase (TH) and dopamine transporter (DAT) protein levels by immunohistochemical staining and Western blotting, as well as increased Th mRNA levels in SN. MEN2B mice had increased number of DA neurons in SN by about 25% and they also exhibited increased sensitivity to the stimulatory effects of cocaine. We also developed a semi-throughput in vitro micro-island assay for the quantification of neuronal survival and TH levels by computer-assisted methodology from limited amounts of tissue. This assay can be applied for the initial screening for dopaminotrophic molecules, as well as chemical drug library screening. It is applicable to any neuronal system for the screening of neurotrophic molecules. Since our microarray experiments revealed possible GDNF-VEGF-C crosstalk we further concentrated on studying the neurotrophic effects of VEGF-C. We showed that VEGF-C acts as a neurotrophic molecule for the DA neurons both in vitro and in vivo, however without additive effect when used together with GDNF. The neuroprotective effect for VEGF-C in vivo in rat 6-OHDA model of PD was demonstrated. The possible signalling mechanisms of VEGF-C in the nervous system were investigated - infusion of VEGF-C to rat brain induced ERK activation, however no direct activation of RET signalling in vitro was found. VEGF-C treatment of rat striatum lead to up-regulation of VEGFR-1-3, indicating that VEGF-C can regulate the expression level of its own receptor. VEGF-C dopaminotrophic activity in vivo was further supported by increased vascular tissue in the neuroprotection experiments.

Structural refinement using high-resolution powder X-ray diffraction data of Ca0.5Ti2P3O12, a low-thermal-expansion material

The structures of Ca0.5Ti2P3O12 and Sr0.5Ti2P3O12, low-thermal-expansion materials, have been refined by the Rietveld method using high-resolution powder X-ray diffraction (XRD) data. The assignment of space group R[3 with combining macron] to NASICON-type compounds containing divalent cations is confirmed. 31P magic-angle spinning nuclear magnetic resonance (MASNMR) data are presented as supporting data. A comparison of changes in the polyhedral network resulting from the cation distribution, is made with NaTi2P3O12 and Nb2P3O12. Factors that may govern thermal expansion in this family of compounds are discussed.

Reactivity and catalytic activity of layered YBA2CU3O7-delta (123) type defect perovskites

The chemical modifications of structure, reactivity and catalytic properties of layered triple perovskite oxides, related to the YBa2Cu3O7-delta (123) system, have been briefly reviewed. These oxides form a versatile family of materials with wide-ranging chemical and physical properties. The multiple sites available for chemical doping, and the ability to reversibly intercalate oxygen at the defect sites have rendered these oxides important model systems in the area of oxide catalysis. An attempt has been made to comprehend the hitherto known catalytic reactions and correlate them to various factors like structure, oxygen diffusional limitations, different geometries adopted by various substituents, oxidative non-stoichiometry and activation energy for oxygen desorption. In particular, results on the enhanced catalytic activity of cobalt-substituted 123 oxide systems towards the selective catalytic oxidation of ammonia to nitric oxide and carbon monoxide to carbon dioxide are presented.

Two-mode quantum systems: Invariant classification of squeezing transformations and squeezed states

A general analysis of squeezing transformations for two-mode systems is given based on the four-dimensional real symplectic group Sp(4, R). Within the framework of the unitary (metaplectic) representation of this group, a distinction between compact photon-number-conserving and noncompact photon-number-nonconserving squeezing transformations is made. We exploit the U(2) invariant squeezing criterion to divide the set of all squeezing transformations into a two-parameter family of distinct equivalence classes with representative elements chosen for each class. Familiar two-mode squeezing transformations in the literature are recognized in our framework and seen to form a set of measure zero. Examples of squeezed coherent and thermal states are worked out. The need to extend the heterodyne detection scheme to encompass all of U(2) is emphasized, and known experimental situations where all U(2) elements can be reproduced are briefly described.