A multistep transversal linearization (MTL) method in non-linear dynamics through a Magnus characterization

A new form of a multi-step transversal linearization (MTL) method is developed and numerically explored in this study for a numeric-analytical integration of non-linear dynamical systems under deterministic excitations. As with other transversal linearization methods, the present version also requires that the linearized solution manifold transversally intersects the non-linear solution manifold at a chosen set of points or cross-section in the state space. However, a major point of departure of the present method is that it has the flexibility of treating non-linear damping and stiffness terms of the original system as damping and stiffness terms in the transversally linearized system, even though these linearized terms become explicit functions of time. From this perspective, the present development is closely related to the popular practice of tangent-space linearization adopted in finite element (FE) based solutions of non-linear problems in structural dynamics. The only difference is that the MTL method would require construction of transversal system matrices in lieu of the tangent system matrices needed within an FE framework. The resulting time-varying linearized system matrix is then treated as a Lie element using Magnus’ characterization [W. Magnus, On the exponential solution of differential equations for a linear operator, Commun. Pure Appl. Math., VII (1954) 649–673] and the associated fundamental solution matrix (FSM) is obtained through repeated Lie-bracket operations (or nested commutators). An advantage of this approach is that the underlying exponential transformation could preserve certain intrinsic structural properties of the solution of the non-linear problem. Yet another advantage of the transversal linearization lies in the non-unique representation of the linearized vector field – an aspect that has been specifically exploited in this study to enhance the spectral stability of the proposed family of methods and thus contain the temporal propagation of local errors. A simple analysis of the formal orders of accuracy is provided within a finite dimensional framework. Only a limited numerical exploration of the method is presently provided for a couple of popularly known non-linear oscillators, viz. a hardening Duffing oscillator, which has a non-linear stiffness term, and the van der Pol oscillator, which is self-excited and has a non-linear damping term.

Crystallite size effects in stacking faulted nickel hydroxide and its electrochemical behaviour

P-Nickel hydroxide comprises a long range periodic arrangement of atoms with a stacking sequence of AC AC AC-having an ideal composition Ni(OH)(2). Variation in the preparative conditions can lead to the changes in the stacking sequence (AC AC BA CB AC AC or AC AC AB AC AC) This type of variation in stacking sequence can result in the formation of stacking fault in nickel hydroxide. The stability of the stacking fault depends on the free energy content of the sample. Stacking faults in nickel hydroxide is essential for better electrochemical activity. Also there are reports correlating particle size to the better electrochemical activity. Here we present the effect of crystallite size on the stacking faulted nickel hydroxide samples. The electrochemical performance of stacking faulted nickel hydroxide with small crystallite size exchanges 0.8e/Ni, while the samples with larger crystallite size exchange 0.4e/Ni. Hence a right combination of crystallite size and stacking fault content has to be controlled for good electrochemical activity of nickel hydroxide. (C) 2008 Elsevier B.V. All rights reserved.

Characterization of LRRTM and NGR gene families: Expression and functions

Some leucine-rich repeat (LRR) -containing membrane proteins are known regulators of neuronal growth and synapse formation. In this work I characterize two gene families encoding neuronal LRR membrane proteins, namely the LRRTM (leucine-rich repeat, transmembrane neuronal) and NGR (Nogo-66 receptor) families. I studied LRRTM and NGR family member's mRNA tissue distribution by RT-PCR and by in situ hybridization. Subcellular localization of LRRTM1 protein was studied in neurons and in non-neuronal cells. I discovered that LRRTM and NGR family mRNAs are predominantly expressed in the nervous system, and that each gene possesses a specific expression pattern. I also established that LRRTM and NGR family mRNAs are expressed by neurons, and not by glial cells. Within neurons, LRRTM1 protein is not transported to the plasma membrane; rather it localizes to endoplasmic reticulum. Nogo-A (RTN4), MAG, and OMgp are myelin-associated proteins that bind to NgR1 to limit axonal regeneration after central nervous system injury. To better understand the functions of NgR2 and NgR3, and to explore the possible redundancy in the signaling of myelin inhibitors of neurite growth, I mapped the interactions between NgR family and the known and candidate NgR1 ligands. I identified high-affinity interactions between RTN2-66, RTN3-66 and NgR1. I also demonstrate that Rtn3 mRNA is expressed in the same glial cell population of mouse spinal cord white matter as Nogo-A mRNA, and thus it could have a role in myelin inhibition of axonal growth. To understand how NgR1 interacts with multiple structurally divergent ligands, I aimed first to map in more detail the nature of Nogo-A:NgR1 interactions, and then to systematically map the binding sites of multiple myelin ligands in NgR1 by using a library of NgR1 expression constructs encoding proteins with one or multiple surface residues mutated to alanine. My analysis of the Nogo-A:NgR1 -interactions revealed a novel interaction site between the proteins, suggesting a trivalent Nogo-A:NgR1-interaction. Our analysis also defined a central binding region on the concave side of NgR1's LRR domain that is required for the binding of all known ligands, and a surrounding region critical for binding MAG and OMgp. To better understand the biological role of LRRTMs, I generated Lrrtm1 and Lrrtm3 knock out mice. I show here that reporter genes expressed from the targeted loci can be used for maping the neuronal connections of Lrrtm1 and Lrrtm3 expressing neurons in finer detail. With regard to LRRTM1's role in humans, we found a strong association between a 70 kb-spanning haplotype in the proposed promoter region of LRRTM1 gene and two possibly related phenotypes: left-handedness and schizophrenia. Interestingly, the responsible haplotype was linked to phenotypic variability only when paternally inherited. In summary, I identified two families of neuronal receptor-like proteins, and mapped their expression and certain protein-protein interactions. The identification of a central binding region in NgR1 shared by multiple ligands may facilitate the design and development of small molecule therapeutics blocking binding of all NgR1 ligands. Additionally, the genetic association data suggests that allelic variation upstream of LRRTM1 may play a role in the development of left-right brain asymmetry in humans. Lrrtm1 and Lrrtm3 knock out mice developed as a part of this study will likely be useful for schizophrenia and Alzheimer s disease research.

Transonic Properties of Accretion Disk Around Compact Objects

An accretion flow is necessarily transonic around a black hole. However, around a neutron star it may or may not be transonic, depending on the inner disk boundary conditions influenced by the neutron star. I will discuss various transonic behavior of the disk fluid in general relativistic (or pseudo general relativistic) framework. I will address that there are four types of sonic/critical point. possible to form in an accretion disk. It will be shown that how the fluid properties including location of sonic point's vary with angular momentum of the compact object which controls the overall disk dynamics and outflows.

Structural transformations in Mn2NiGa due to residual stress

Powder x-ray diffraction study of Mn2NiGa ferromagnetic shape memory alloy shows the existence of a 7M monoclinic modulated structure at room temperature (RT). The structure of Mn2NiGa is found to be highly dependent on residual stress. For higher stress, the structure is tetragonal at RT, and for intermediate stress it is 7M monoclinic. However, only when the stress is considerably relaxed, the structure is cubic, as is expected at RT since the martensitic transition temperature is 230 K.

Molecular basis for the development of diagnostic methods and specific treatment modalities for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unknown aetiology and poor prognosis. IPF is characterized by alveolar epithelial damage that leads tissue remodelling and ultimately to the loss of normal lung architecture and function. Treatment has been focused on anti-inflammatory therapies, but due to their poor efficacy new therapeutic modalities are being sought. There is a need for early diagnosis and also for differential diagnostic markers for IPF and other interstitial lung diseases. The study utilized patient material obtained from bronchoalveolar lavage (BAL), diagnostic biopsies or lung transplantation. Human pulmonary fibroblast cell cultures were propagated and asbestos-induced pulmonary fibrosis in mice was used as an experimental animal model of IPF. The possible markers for IPF were scanned by immunohistochemistry, RT-PCR, ELISA and western blot. Matrix metalloproteinases (MMPs) are proteolytic enzymes that participate in tissue remodelling. Microarray studies have introduced potential markers that could serve as additional tools for the assessment of IPF and one of the most promising was MMP 7. MMP-7 protein levels were measured in the BAL fluid of patients with idiopathic interstitial lung diseases or idiopathic cough. MMP-7 was however similarly elevated in the BAL fluid of all these disorders and thus cannot be used as a differential diagnostic marker for IPF. Activation of transforming growth factor (TGF)-ß is considered to be a key element in the progression of IPF. Bone morphogenetic proteins (BMP) are negative regulators of intracellular TGF-ß signalling and BMP-4 signalling is in turn negatively regulated by gremlin. Gremlin was found to be highly upregulated in the IPF lungs and IPF fibroblasts. Gremlin was detected in the thickened IPF parenchyma and endothelium of small capillaries, whereas in non-specific interstitial pneumonia it localized predominantly in the alveolar epithelium. Parenchymal gremlin immunoreactivity might indicate IPF-type interstitial pneumonia. Gremlin mRNA levels were higher in patients with end-stage fibrosis suggesting that gremlin might be a marker for more advanced disease. Characterization of the fibroblastic foci in the IPF lungs showed that immunoreactivity to platelet-derived growth factor (PDGF) receptor-α and PDGF receptor-β was elevated in IPF parenchyma, but the fibroblastic foci showed only minor immunoreactivity to the PDGF receptors or the antioxidant peroxiredoxin II. Ki67 positive cells were also observed predominantly outside the fibroblastic foci, suggesting that the fibroblastic foci may not be composed of actively proliferating cells. When inhibition of profibrotic PDGF-signalling by imatinib mesylate was assessed, imatinib mesylate reduced asbestos-induced pulmonary fibrosis in mice as well as human pulmonary fibroblast migration in vitro but it had no effect on the lung inflammation.

Reactive Pulsed Laser Deposition of titanium nitride thin film: Optimization of process parameters using Secondary Ion Mass Spectrometry

Reactive Pulsed Laser Deposition is a single step process wherein the ablated elemental metal reacts with a low pressure ambient gas to form a compound. We report here a Secondary Ion Mass Spectrometry based analytical methodology to conduct minimum number of experiments to arrive at optimal process parameters to obtain high quality TiN thin film. Quality of these films was confirmed by electron microscopic analysis. This methodology can be extended for optimization of other process parameters and materials. (C) 2009 Elsevier B.V. All rights reserved.

1-[5-Acetyl-4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridin-3-yl]eth anone monohydrate

The 1,4-dihydropyridine ring in the title hydrate, C17H18BrNO2 center dot H2O, has a flattened-boat conformation, and the benzene ring is occupies a position orthogonal to this [dihedral angle: 82.19 (16)degrees]. In the crystal packing, supramolecular arrays mediated by N-H center dot center dot center dot O-water and O-water-H center dot center dot center dot O-carbonyl hydrogen bonding are formed in the bc plane. A highly disordered solvent molecule is present within a molecular cavity defined by the organic and water molecules. Its contribution to the electron density was removed from the observed data in the final cycles of refinement and the formula, molecular weight and density are given without taking into account the contribution of the solvent molecule.

Accuracy of absorbed dose in external photon beam radiotherapy : what level is sufficient and how to approach it?

Radiation therapy (RT) plays currently significant role in curative treatments of several cancers. External beam RT is carried out mostly by using megavoltage beams of linear accelerators. Tumor eradication and normal tissue complications correlate to dose absorbed in tissues. Normally this dependence is steep and it is crucial that actual dose within patient accurately correspond to the planned dose. All factors in a RT procedure contain uncertainties requiring strict quality assurance. From hospital physicist´s point of a view, technical quality control (QC), dose calculations and methods for verification of correct treatment location are the most important subjects. Most important factor in technical QC is the verification that radiation production of an accelerator, called output, is within narrow acceptable limits. The output measurements are carried out according to a locally chosen dosimetric QC program defining measurement time interval and action levels. Dose calculation algorithms need to be configured for the accelerators by using measured beam data. The uncertainty of such data sets limits for best achievable calculation accuracy. All these dosimetric measurements require good experience, are workful, take up resources needed for treatments and are prone to several random and systematic sources of errors. Appropriate verification of treatment location is more important in intensity modulated radiation therapy (IMRT) than in conventional RT. This is due to steep dose gradients produced within or close to healthy tissues locating only a few millimetres from the targeted volume. The thesis was concentrated in investigation of the quality of dosimetric measurements, the efficacy of dosimetric QC programs, the verification of measured beam data and the effect of positional errors on the dose received by the major salivary glands in head and neck IMRT. A method was developed for the estimation of the effect of the use of different dosimetric QC programs on the overall uncertainty of dose. Data were provided to facilitate the choice of a sufficient QC program. The method takes into account local output stability and reproducibility of the dosimetric QC measurements. A method based on the model fitting of the results of the QC measurements was proposed for the estimation of both of these factors. The reduction of random measurement errors and optimization of QC procedure were also investigated. A method and suggestions were presented for these purposes. The accuracy of beam data was evaluated in Finnish RT centres. Sufficient accuracy level was estimated for the beam data. A method based on the use of reference beam data was developed for the QC of beam data. Dosimetric and geometric accuracy requirements were evaluated for head and neck IMRT when function of the major salivary glands is intended to be spared. These criteria are based on the dose response obtained for the glands. Random measurement errors could be reduced enabling lowering of action levels and prolongation of measurement time interval from 1 month to even 6 months simultaneously maintaining dose accuracy. The combined effect of the proposed methods, suggestions and criteria was found to facilitate the avoidance of maximal dose errors of up to even about 8 %. In addition, their use may make the strictest recommended overall dose accuracy level of 3 % (1SD) achievable.

KAT5 (Tip60) is a potential therapeutic target in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura. Asbestos exposure (through inhalation) is the most well established risk factor for mesothelioma. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Lysine acetyltransferases (KATs) including KAT5 have been linked with the development of cisplatin resistance. This gene may therefore be altered in MPM and could represent a novel candidate target for intervention. Using RT-PCR screening the expression of all known KAT5 variants was found to be markedly increased in malignant tumors compared to benign pleura. When separated according to histological subtype, KAT5 was significantly overexpressed in both the sarcomatoid and biphasic subgroups for all transcript variants. A panel of MPM cell lines including the normal pleural cells LP9 and Met5A was screened for expression of KAT5 variants. Treatment of cells with a small molecule inhibitor of KAT5 (MG-149) caused significant inhibition of cellular proliferation (p<0.0001), induction of apoptosis and was accompanied by significant induction of pro-inflammatory cytokines/chemokines.

Formal Verification of Full-Wave Rectifier: A Case Study

We present a case study of formal verification of full-wave rectifier for analog and mixed signal designs. We have used the Checkmate tool from CMU [1], which is a public domain formal verification tool for hybrid systems. Due to the restriction imposed by Checkmate it necessitates to make the changes in the Checkmate implementation to implement the complex and non-linear system. Full-wave rectifier has been implemented by using the Checkmate custom blocks and the Simulink blocks from MATLAB from Math works. After establishing the required changes in the Checkmate implementation we are able to efficiently verify, the safety properties of the full-wave rectifier.

Heat-shock protein 70-2 (HSP70-2) expression in bladder urothelial carcinoma is associated with tumour progression and promotes migration and invasion

Purpose: Testis specific heat-shock protein 70-2 (HSP70-2), a member of HSP70 chaperone family, is essential for the growth of spermatocytes and cancer cells. We investigated the association of HSP70-2 expression with clinical behaviour and progression of urothelial carcinoma of bladder. Experimental design: We assessed the HSP70-2 expression by RT-PCR and HSP70-2 protein expression by immunofluorescence, flow cytometry, immunohistochemistry and Western blotting in urothelial carcinoma patient specimens and HTB-1, UMUC-3, HTB-9, HTB-2 and normal human urothelial cell lines. Further, to investigate the role of HSP70-2 in bladder tumour development, HSP70-2 was silenced in the high-grade invasive HTB-1 and UMUC-3 cells. The malignant properties of urothelial carcinoma cells were examined using colony formation, migration assay, invasion assay in vitro and tumour growth in vivo. Results: Our RT-PCR analysis and immunohistochemistry analysis revealed that HSP70-2 was expressed in both moderate to well-differentiated and high-grade invasive urothelial carcinoma cell lines studied and not in normal human urothelial cells. In consistence with these results, HSP70-2 expression was also observed in superficially invasive (70%) and muscle-invasive (90%) patient's tumours. Furthermore, HSP70-2 knockdown significantly suppressed cellular motility and invasion ability. An in vivo xenograft study showed that inhibition of HSP70-2 significantly suppressed tumour growth. Conclusions: In conclusion, our data suggest that the HSP70-2 expression is associated with early spread and progression of urothelial carcinoma of bladder cancer and that HSP70-2 can be the potential therapeutic target for bladder urothelial carcinoma. (C) 2009 Elsevier Ltd. All rights reserved.

Identification of genes associated with tumorigenesis of meibomian cell carcinoma by microarray analysis

Meibomian cell carcinoma (MCC) is a malignant tumor of the meibomian glands located in the eyelids. No information exists on the cytogenctic and genetic aspects of MCC. There is no report on the gene expression profile of MCC. Thus there is a need, for both scientific and clinical reasons, to identify genes and pathways that are involved in the development and progression of MCC. We analyzed the gene expression profile of MCC by the microarray technique. Forty-four genes were upregulated and 149 genes were downregulated in MCC. Differential expression data were confirmed for 5 genes by semiquantitative RT-PCR in MCC tumors: GTF2H4, RBM12, UBE2D3, DDX17, and LZTS1. We found dysregulation of two major pathways in MCC: MAPK and JAK/STAT. Clusters of genes on chromosomes 1, 12, and 19 were dysregUlated in MCC. The data presented here will facilitate the identification of specific markers and therapeutic targets for the treatment of MCC patients. (c) 2007 Elsevier Inc. All rights reserved.

(2E)-3-(4-Bromophenyl)-1-(2-methyl-4phenyl-3-quinolyl)prop-2-en-1-one

The conformation about the ethene bond [1.316 (3) angstrom] in the title compound, C25H18BrNO, is E. The quinoline ring forms dihedral angles of 67.21 (10) and 71.68 (10)degrees with the benzene and bromo-substituted benzene rings, respectively. High-lighting the non-planar arrangement of aromatic rings, the dihedral angle formed between the benzene rings is 58.57 (12)degrees.