Sorin V. Sabau

The Geometry of hamilton and lagrange spaces

Preface. 1. The geometry of tangent bundle. 2. Finsler spaces. 3. Lagrange spaces. 4. The geometry of cotangent bundle. 5. Hamilton spaces. 6. Cartan spaces. 7. The duality between Lagrange and Hamilton spaces. 8. Symplectic transformations of the differential geometry of T* M. 9. The dual bundle of a k-osculator bundle. 10. Linear connections on the manifold T*2M. 11. Generalized Hamilton spaces of order 2. 12. Hamilton spaces of order 2. 13. Cartan spaces of order 2. Bibliography. Index.

A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

BackgroundGastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells.MethodsDGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively.ResultsDGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild-type KRAS resulted in the inhibition of cell growth and suppression of p44/42 MAP kinase and AKT activity.ConclusionOur study highlights the utility of DGS for identification of copy-number alterations. Using DGS, we identified KRAS as a gene that is amplified in human gastric cancer. We demonstrated that gene amplification likely forms the molecular basis of overactivation of KRAS in gastric cancer. Additional studies using a larger cohort of gastric cancer specimens are required to determine the diagnostic and therapeutic implications of KRAS amplification and overexpression.

cDNA Microarray Analyses Reveal Candidate Marker Genes for the Detection of Ascidian Disease in Korea

Abstract A serious disease of the ascidian Halocynthia roretzi has been spread extensively among Korean aquaculture sites. To reveal the cause of the disease and establish a monitoring system for it, we constructed a cDNA microarray spotted with 2,688 cDNAs derived from H. roretzi hemocyte cDNA libraries to detect genes differentially expressed in hemocytes between diseased and non-diseased ascidians. We detected 21 genes showing increased expression and 16 genes showing decreased expression in hemocytes from diseased ascidians compared with those from non-diseased ascidians. RT-PCR analyses confirmed that the expression levels of genes encoding astacin, lysozyme, ribosomal protein PO, and ubiquitin-ribosomal protein L40e fusion protein were increased in hemocytes from diseased ascidians, while those of genes encoding HSP40, HSP70, fibronectin, carboxypeptidase and lactate dehydrogenase were decreased. These genes were expressed not only in hemocytes but also in various other tissues in ascidians. Furthermore, the expression of glutathione-S transferase omega, which is known to be up-regulated in H. roretzi hemocytes during inflammatory responses, was strongly increased in hemocytes from diseased ascidians. These gene expression profiles suggest that immune and inflammatory reactions occur in the hemocytes of diseased ascidians. These genes will be good markers for detecting and monitoring this disease of ascidians in Korean aquaculture sites.

Localization and characterization of γ-glutamyl cyclotransferase in cancer cells

Using differential display analysis, we have identified a novel rat gene whose expression is increased during tumor progression in rat mammary carcinoma cell lines. This gene is an ortholog of the human chromosome 7 open reading frame 24 gene (C7orf24) and encodes a protein of 188 amino acids with no recognized protein domains. C7orf24 has been identified as γ-glutamyl cyclotransferase (GGCT), an important enzyme functioning in glutathione homeostasis. Our Northern and Western blot analyses revealed that the GGCT gene is expressed in various normal human and tumor tissues, as well as in cancer cell lines. Among the tumor tissues tested, lung tumor tissue expressed GGCT mRNA more strongly than normal lung tissue. The GGCT protein was found to be localized in the cytoplasmic region of cultured cells, where it forms a homodimer. Analysis of various deletion mutants of the GGCT protein revealed that the region containing amino acid residues 61-120 of the protein is required for its cytoplasmic localization. The comparison of the soft agar colony formation of HBL-100 cells stably expressing GGCT with that of control HBL-100 cells revealed that GGCT does not promote colony formation, suggesting that the role it plays in lung cancer cells is not related to tumorigenesis.

A pathophysiological approach to metabolic syndrome using factor analysis in an adult Romanian population

Abstract The aim of the study was to examine the role of insulin resistance in etiopathogenesis of metabolic syndrome in an adult Romanian population using exploratory factor analysis. We analyzed 228 non-diabetic subjects randomized in respect to the age and sex distribution of the general population. For each patient, age, sex, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), HDL-cholesterol (HDL), plasma triglycerides (TG), fasting plasma glucose (FPG) and fasting insulin were obtained. Factor analysis was performed using principal component analysis, with Varimax rotation of the major determinants of metabolic syndrome. Mean age was 48.9 ± 12.7 years; 107 (46.9%) were men and 121 (53.1%) women. We found three major factors, which are correlated with metabolic syndrome and may explain its variance. Factor 1 comprises SBP and DBP in men and SBP, DBP and BMI in women. Factor 2 comprises BMI, HDL, TG and FPG in men and BMI, TG and FPG in women. Factor 3 comprises fasting insulin in men and fasting insulin, TG and HDL in women. The finding of more than one factor suggests that insulin resistance is not the only pathophysiological mechanism involved. These factors appear to work independently of each other in men, but they intersect in women, suggesting that the pathophysiology of metabolic syndrome may be different in women compared with men.

Kosambi-Cartan-Chern (KCC) theory for higher order dynamical systems

The Kosambi-Cartan-Chern (KCC) theory represents a powerful mathematical method for the investigation of the properties of dynamical systems. The KCC theory introduces a geometric description of the time evolution of a dynamical system, with the solution curves of the dynamical system described by methods inspired by the theory of geodesics in a Finsler spaces. The evolution of a dynamical system is geometrized by introducing a non-linear connection, which allows the construction of the KCC covariant derivative, and of the deviation curvature tensor. In the KCC theory the properties of any dynamical system are described in terms of five geometrical invariants, with the second one giving the Jacobi stability of the system. Usually, the KCC theory is formulated by reducing the dynamical evolution equations to a set of second order differential equations. In the present paper we introduce and develop the KCC approach for dynamical systems described by systems of arbitrary

A Gauss-Bonnet-type formula on Riemann-Finsler surfaces with nonconstant indicatrix volume

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Identification of Genes Downstream of Nodal in the Ciona intestinalis Embryo

-dimensional first order differential equations. We investigate in detail the properties of the

Jacobi stability analysis of scalar field models with minimal coupling to gravity in a cosmological background

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Metric structures associated to Finsler metrics

-dimensional autonomous dynamical systems, as well as the relationship between the linear stability and the Jacobi stability. As a main result we find that only even-dimensional dynamical systems can exhibit both Jacobi stability and instability behaviors, while odd-dimensional dynamical systems are always Jacobi unstable, no matter their Lyapunov stability. As applications of the developed formalism we consider the geometrization and the study of the Jacobi stability of the complex dynamical networks, and of the