Isotopic liftings of Clifford algebras and applications in elementary particle mass matrices

Isotopic liftings of algebraic structures are investigated in the context of Clifford algebras, where it is defined a new product involving an arbitrary, but fixed, element of the Clifford algebra. This element acts as the unit with respect to the introduced product, and is called isounit. We construct isotopies in both associative and non-associative arbitrary algebras, and examples of these constructions are exhibited using Clifford algebras, which although associative, can generate the octonionic, non-associative, algebra. The whole formalism is developed in a Clifford algebraic arena, giving also the necessary pre-requisites to introduce isotopies of the exterior algebra. The flavor hadronic symmetry of the six u,d,s,c,b,t quarks is shown to be exact, when the generators of the isotopic Lie algebra su(6) are constructed, and the unit of the isotopic Clifford algebra is shown to be a function of the six quark masses. The limits constraining the parameters, that are entries of the representation of the isounit in the isotopic group SU(6), are based on the most recent limits imposed on quark masses.Comment: 19 page

Invariant variational principle for Hamiltonian mechanics

It is shown that the action for Hamiltonian equations of motion can be brought into invariant symplectic form. In other words, it can be formulated directly in terms of the symplectic structure $\omega$ without any need to choose some 1-form $\gamma$, such that $\omega= d \gamma$, which is not unique and does not even generally exist in a global sense.Comment: final version; to appear in J.Phys.A; 17 pages, 2 figure

Appropriateness and efficacy of Spa therapy for musculoskeletal disorders. A Delphi method consensus initiative among experts in Italy.

OBJECTIVE: The aim of the study was to identify the main aspects concerning appropriateness and efficacy of Spa therapy for musculoskeletal pathologies. METHODS: A committee of 8 experts from Italian universities, public hospitals, territorial services, research institutes and patient associations was set up. Clinicians from Italian medical centers specialized in rheumatology, rehabilitation and thermal medicine took part in a Delphi process aimed at obtaining consensus statements among the participants. RESULTS: Large consensus was obtained for statements grouped under the following main themes: treatment indications; choice of treatment modality and treatment efficacy. CONCLUSIONS: The experts developed a number of consensus statements which may be used as a practical reference to guide the choice of physicians to treat musculoskeletal diseases with Spa therapy

Nonlocal, noncommutative picture in quantum mechanics and distinguished canonical maps

Classical nonlinear canonical (Poisson) maps have a distinguished role in quantum mechanics. They act unitarily on the quantum phase space and generate $\hbar$-independent quantum canonical maps. It is shown that such maps act in the noncommutative phase space as dictated by the classical covariance. A crucial observation made is that under the classical covariance the local quantum mechanical picture can become nonlocal in the Hilbert space. This nonlocal picture is made equivalent by the Weyl map to a noncommutative picture in the phase space formulation of the theory. The connection between the entanglement and nonlocality of the representation is explored and specific examples of the generation of entanglement are provided by using such concepts as the generalized Bell states. That the results have direct application in generating vacuum soliton configurations in the recently popular scalar field theories of noncommutative coordinates is also demonstrated.Comment: 14 pages, one figur

Lentiviral Vector-Mediated Correction of a Mouse Model of Leukocyte Adhesion Deficiency Type I

Leukocyte adhesion deficiency type I (LAD-I) is a primary immunodeficiency caused by mutations in the ITGB2 gene and is characterized by recurrent and life-threatening bacterial infections. These mutations lead to defective or absent expression of β2 integrins on the leukocyte surface, compromising adhesion and extravasation at sites of infection. Three different lentiviral vectors (LVs) conferring ubiquitous or preferential expression of CD18 in myeloid cells were constructed and tested in human and mouse LAD-I cells. All three hCD18-LVs restored CD18 and CD11a membrane expression in LAD-I patient-derived lymphoblastoid cells. Corrected cells recovered the ability to aggregate and bind to sICAM-1 after stimulation. All vectors induced stable hCD18 expression in hematopoietic cells from mice with a hypomorphic Itgb2 mutation (CD18(HYP)), both in vitro and in vivo after transplantation of corrected cells into primary and secondary CD18(HYP) recipients. hCD18(+) hematopoietic cells from transplanted CD18(HYP) mice also showed restoration of mCD11a surface co-expression. The analysis of in vivo neutrophil migration in CD18(HYP) mice subjected to two different inflammation models demonstrated that the LV-mediated gene therapy completely restored neutrophil extravasation in response to inflammatory stimuli. Finally, these vectors were able to correct the phenotype of human myeloid cells derived from CD34(+) progenitors defective in ITGB2 expression. These results support for the first time the use of hCD18-LVs for the treatment of LAD-I patients in clinical trials

Canonical quantization of so-called non-Lagrangian systems

We present an approach to the canonical quantization of systems with equations of motion that are historically called non-Lagrangian equations. Our viewpoint of this problem is the following: despite the fact that a set of differential equations cannot be directly identified with a set of Euler-Lagrange equations, one can reformulate such a set in an equivalent first-order form which can always be treated as the Euler-Lagrange equations of a certain action. We construct such an action explicitly. It turns out that in the general case the hamiltonization and canonical quantization of such an action are non-trivial problems, since the theory involves time-dependent constraints. We adopt the general approach of hamiltonization and canonical quantization for such theories (Gitman, Tyutin, 1990) to the case under consideration. There exists an ambiguity (not reduced to a total time derivative) in associating a Lagrange function with a given set of equations. We present a complete description of this ambiguity. The proposed scheme is applied to the quantization of a general quadratic theory. In addition, we consider the quantization of a damped oscillator and of a radiating point-like charge.Comment: 13 page

The Moyal-Lie Theory of Phase Space Quantum Mechanics

A Lie algebraic approach to the unitary transformations in Weyl quantization is discussed. This approach, being formally equivalent to the $\star$-quantization, is an extension of the classical Poisson-Lie formalism which can be used as an efficient tool in the quantum phase space transformation theory.Comment: 15 pages, no figures, to appear in J. Phys. A (2001

Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas

This article is available open access through the publisher’s website. Copyright @ 2009 The Authors.Background - Clusterin expression in various types of human cancers may be higher or lower than in normal tissue, and clusterin may promote or inhibit apoptosis, cell motility, and inflammation. We investigated the role of clusterin in tumor development in mouse models of neuroblastoma. Methods - We assessed expression of microRNAs in the miR-17-92 cluster by real-time reverse transcription–polymerase chain reaction in MYCN-transfected SH-SY5Y and SH-EP cells and inhibited expression by transfection with microRNA antisense oligonucleotides. Tumor development was studied in mice (n = 66) that were heterozygous or homozygous for the MYCN transgene and/or for the clusterin gene; these mice were from a cross between MYCN-transgenic mice, which develop neuroblastoma, and clusterin-knockout mice. Tumor growth and metastasis were studied in immunodeficient mice that were injected with human neuroblastoma cells that had enhanced (by clusterin transfection, four mice per group) or reduced (by clusterin short hairpin RNA [shRNA] transfection, eight mice per group) clusterin expression. All statistical tests were two-sided. Results - Clusterin expression increased when expression of MYCN-induced miR-17-92 microRNA cluster in SH-SY5Y neuroblastoma cells was inhibited by transfection with antisense oligonucleotides compared with scrambled oligonucleotides. Statistically significantly more neuroblastoma-bearing MYCN-transgenic mice were found in groups with zero or one clusterin allele than in those with two clusterin alleles (eg, 12 tumor-bearing mice in the zero-allele group vs three in the two-allele group, n = 22 mice per group; relative risk for neuroblastoma development = 4.85, 95% confidence interval [CI] = 1.69 to 14.00; P = .005). Five weeks after injection, fewer clusterin-overexpressing LA-N-5 human neuroblastoma cells than control cells were found in mouse liver or bone marrow, but statistically significantly more clusterin shRNA-transfected HTLA230 cells (3.27%, with decreased clusterin expression) than control-transfected cells (1.53%) were found in the bone marrow (difference = 1.74%, 95% CI = 0.24% to 3.24%, P = .026). Conclusions - We report, to our knowledge, the first genetic evidence that clusterin is a tumor and metastasis suppressor gene.Sport Aiding Medical Research for Kids (SPARKS), Great Ormond Street Hospital/National Health Service, the National Cancer Institute and University of Parma

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study

Background: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. Objectives: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. Animals: Three hundred and fifty-four dogs with MMVD and cardiomegaly. Materials and Methods: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. Results: At day 35, heart size had reduced in the pimobendan group:median change in (Delta) LVIDDN -0.06 (IQR:-0.15 to + 0.02), P < 0.0001, and LA:Ao -0.08 (IQR:-0.23 to + 0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in Delta LVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in Delta LA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. Conclusions and Clinical Importance: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo

The Inverse Variational Problem for Autoparallels

We study the problem of the existence of a local quantum scalar field theory in a general affine metric space that in the semiclassical approximation would lead to the autoparallel motion of wave packets, thus providing a deviation of the spinless particle trajectory from the geodesics in the presence of torsion. The problem is shown to be equivalent to the inverse problem of the calculus of variations for the autoparallel motion with additional conditions that the action (if it exists) has to be invariant under time reparametrizations and general coordinate transformations, while depending analytically on the torsion tensor. The problem is proved to have no solution for a generic torsion in four-dimensional spacetime. A solution exists only if the contracted torsion tensor is a gradient of a scalar field. The corresponding field theory describes coupling of matter to the dilaton field.Comment: 13 pages, plain Latex, no figure