Effects of new nonlinear couplings in relativistic effective field theory

We extend the relativistic mean field theory model of Sugahara and Toki by adding new couplings suggested by modern effective field theories. An improved set of parameters is developed with the goal to test the ability of the models based on effective field theory to describe the properties of finite nuclei and, at the same time, to be consistent with the trends of Dirac-Brueckner-Hartree-Fock calculations at densities away from the saturation region. We compare our calculations with other relativistic nuclear force parameters for various nuclear phenomena.

From Galilean-invariant to relativistic wave equations

Through an imaginary change of coordinates in the Galilei algebra in 4 space dimensions and making use of an original idea of Dirac and Lvy-Leblond, we are able to obtain the relativistic equations of Dirac and of Bargmann and Wigner starting with the (Galilean-invariant) Schrdinger equation.

[Doublon: 10.1007/s00428-009-0853-4] Soft tissue sarcomas with complex genomic profiles.

Soft tissue sarcomas (STS) with complex genomic profiles (50% of all STS) are predominantly composed of spindle cell/pleomorphic sarcomas, including leiomyosarcoma, myxofibrosarcoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, malignant peripheral nerve sheath tumor, angiosarcoma, extraskeletal osteosarcoma, and spindle cell/pleomorphic unclassified sarcoma (previously called spindle cell/pleomorphic malignant fibrous histiocytoma). These neoplasms show, characteristically, gains and losses of numerous chromosomes or chromosome regions, as well as amplifications. Many of them share recurrent aberrations (e.g., gain of 5p13-p15) that seem to play a significant role in tumor progression and/or metastatic dissemination. In this paper, we review the cytogenetic, molecular genetic, and clinicopathologic characteristics of the most common STS displaying complex genomic profiles. Features of diagnostic or prognostic relevance will be discussed when needed.

Molecular genetics of ocular diseases

The eye is a complex organ, which provides one of our most important senses, sight. The retina is the neuronal component of the eye and represents the connection with the central nervous system for the transmission of the information that leads to image processing. Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration, in which the primary death of rods, resulting in night blindness, is always followed by the loss of cones, which leads to legal blindness. Clinical and genetic heterogeneity in retinitis pigmentosa is not only due to different mutations in different genes, but also to different effects of the same mutation in different individuals, sometimes even within the same family. My thesis work has been mainly focused on an autosomal dominant form of RP linked to mutations in the PRPF31 gene, which often shows reduced penetrance. Our study has led to the identification of the major regulator of the penetrance of PRPF31 mutations, the CNOT3 protein, and to the characterization of its mechanism of action. Following the same rationale of investigating molecular mechanisms that are responsible for clinical and genetic heterogeneity of retinitis pigmentosa, we studied a recessive form of the disease associated with mutations in the recently-identified gene FAMI61 A, where mutations in the same gene give rise to variable clinical manifestations. Our data have increased the knowledge of the relationship between genotype and phenotype in this form of the disease. Whole genome sequencing technique was also tested as a strategy for disease gene identification in unrelated patients with recessive retinitis pigmentosa and proved to be effective in identifying disease-causing variants that might have otherwise failed to be detected with other screening methods. Finally, for the first time we reported a choroidal tumor among the clinical manifestations of PTEN hamartoma tumor syndrome, a genetic disorder caused by germline mutations of the tumor suppressor gene PTEN. Our study has highlighted the heterogeneity of this choroidal tumor, showing that genetic and/or epigenetic alterations in different genes may contribute to the tumor development and growth. - L'oeil est un organe complexe, à l'origine d'un de nos sens les plus importants, la vue. La rétine est la composante neuronale de l'oeil qui constitue la connexion avec le système nerveux central pour la transmission de l'information et qui conduit à la formation des images. La rétinite pigmentaire (RP) est une des formes les plus courantes de dégénérescence rétinienne héréditaire, dans laquelle la mort primaire de bâtonnets, entraînant la cécité nocturne, est toujours suivie par la perte de cônes qui conduit à la cécité complète. L'hétérogénéité clinique et génétique dans la rétinite pigmentaire n'est pas seulement due aux différentes mutations dans des gènes différents, mais aussi à des effets différents de la même mutation chez des individus différents, parfois même dans la même famille. Mon travail de thèse s'est principalement axé sur une forme autosomique dominante de RP liée à des mutations dans le gène PRPF31, associées souvent à une pénétrance réduite, me conduisant à l'identification et à la caractérisation du mécanisme d'action du régulateur principal de la pénétrance des mutations: la protéine CNOT3. Dans la même logique d'étude des mécanismes moléculaires responsables de l'hétérogénéité clinique et génétique de la RP, nous avons étudié une forme récessive de la maladie associée à des mutations dans le gène récemment identifié FAMI61 A, dont les mutations dans le même gène donnent lieu à des manifestations cliniques différentes. Nos données ont ainsi accru la connaissance de la relation entre le génotype et le phénotype dans cette forme de maladie. La technique de séquençage du génome entier a été ensuite testée en tant que stratégie pour l'identification du gène de la maladie chez les patients atteints de RP récessive. Cette approche a montré son efficacité dans l'identification de variantes pathologiques qui n'auraient pu être détectées avec d'autres méthodes de dépistage. Enfin, pour la première fois, nous avons identifié une tumeur choroïdienne parmi les manifestations cliniques du PTEN hamartoma tumor syndrome, une maladie génétique causée par des mutations germinales du gène suppresseur de tumeur PTEN. Notre étude a mis en évidence l'hétérogénéité de cette tumeur choroïdienne, montrant que les altérations génétiques et/ou épigénétiques dans les différents gènes peuvent contribuer au développement et à la croissance tumorale.

Anomalous specific-heat jump in a two-component ultracold Fermi gas

The thermodynamic functions of a Fermi gas with spin population imbalance are studied in the temperature-asymmetry plane in the BCS limit. The low-temperature domain is characterized by an anomalous enhancement of the entropy and the specific heat above their values in the unpaired state, decrease of the gap and eventual unpairing phase transition as the temperature is lowered. The unpairing phase transition induces a second jump in the specific heat, which can be measured in calorimetric experiments. While the superfluid is unstable against a supercurrent carrying state, it may sustain a metastable state if cooled adiabatically down from the stable high-temperature domain. In the latter domain the temperature dependence of the gap and related functions is analogous to the predictions of the BCS theory.

Scaling calculation of isoscalar giant resonances in relativistic Thomas-Fermi theory

We derive analytical expressions for the excitation energy of the isoscalar giant monopole and quadrupole resonances in finite nuclei, by using the scaling method and the extended ThomasFermi approach to relativistic mean-field theory. We study the ability of several nonlinear σω parameter sets of common use in reproducing the experimental data. For monopole oscillations the calculations agree better with experiment when the nuclear matter incompressibility of the relativistic interaction lies in the range 220260 MeV. The breathing-mode energies of the scaling method compare satisfactorily with those obtained in relativistic RPA and time-dependent mean-field calculations. For quadrupole oscillations, all the analyzed nonlinear parameter sets reproduce the empirical trends reasonably well.

RNA interference against aquaporin-4 decreases the apparent diffusion coefficient in the normal brain

Aim: Diffusion weighted magnetic resonance imaging (MRI) is now widely used in human brain diagnosis.1 To date molecular mechanisms underlying changes in Apparent Diffusion Coefficient (ADC) signals remain poorly understood. AQP4, localized to astrocytes, is one of the most highly expressed cerebral AQPs.2 AQP4 is involved in water movement within the cell membrane of cultured astrocytes.3 We hypothesize that AQP4 contributes to water diffusion and underlying ADC values in normal brain. Methods: We used an RNA interference (RNAi) protocol in vivo, to acutely knockdown expression of AQP4 in rat brain and to determine whether this was associated with changes in brain ADC values using MRI protocols as previously described.4 RNAi was performed using specific small interference RNA (siRNA) against AQP4 (siAQP4) and a non-targeted-siRNA (siGLO) as a control. The specificity and efficiency of the siAQP4 were first tested in vitro in astrocyte and hippocampal slice cultures. In vivo, siRNAs were injected into the rat cortex 3d prior to MRI acquisition and AQP4 was assessed by western blot (n=4) and immunohistochemistry (n=6). Histology was performed on adjacent slices. Results: siAQP4 application on primary astrocyte cultures induced a 76% decrease in AQP4 expression after 4 days. In hippocampal slice cultures; we also found a significant decrease in AQP4 expression in astrocytes after siAQP4. In vivo, injection of non-targeted siRNA (siGLO) tagged with CY3 allowed us to show that GFAP positive cells (astrocytes) were positively stained with CY3-siGLO, showing efficient transfection. Western blot and immunohistochemical analysis showed that siAQP4 induced a ~30% decrease in AQP4 expression without modification of tissue properties or cell death. After siAQP4 treatment, a significant decrease in ADC values (~50%) were observed without altered of T2 values. Conclusions: Together these results suggest that AQP4 reduces water diffusion through the astrocytic plasma membrane and decreases ADC values. Our findings demonstrate for the first time that astrocytic AQP4 contributes significantly to brain water diffusion and ADC values in normal brain. These results open new avenues to interpretation of ADC values under normal physiological conditions and in acute and chronic brain injuries.

Bacterial-induced protection against allergy through a novel multi-component immunoregulatory mechanism

Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. We have found that pulmonary exposure with the bacterium Escherichia coli leads to a suppression of allergic airway inflammation, characterized by reduced airway-hyperresponsiveness, eosinophilia and cytokine production by T cells in the lung. This immune modulation was neither mediated by the induction of a Th1 response nor regulatory T cells; was dependent on TLR-4 but did not involve TLR-desensitization. Dendritic cell migration to the draining lymph nodes and subsequent activation of T cells was unaffected by prior exposure to E.coli indicating that the immunomodulation was limited to the lung environment. In non-treated control mice ovalbumin was primarily presented by airway CD11b+ CD11c+ DCs expressing high levels of MHC class II molecules whilst the DCs in E.coli-treated mice displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production by ovalbuminspecific effector T cells recruited to the airways was significantly reduced. The suppression of airways hyper responsiveness was mediated through the recruitment of IL-17-producing gd-T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of TNF-alpha. Taken together, these data reveal a novel multi-component immunoregulatory pathway that acts to protect the airways from allergic inflammation.

From Galilean-invariant to relativistic wave equations

Through an imaginary change of coordinates in the Galilei algebra in 4 space dimensions and making use of an original idea of Dirac and Lvy-Leblond, we are able to obtain the relativistic equations of Dirac and of Bargmann and Wigner starting with the (Galilean-invariant) Schrdinger equation.

Classical cross sections for relativistic spinning particles

We propose a definition of classical differential cross sections for particles with essentially nonplanar orbits, such as spinning ones. We give also a method for its computation. The calculations are carried out explicitly for electromagnetic, gravitational, and short-range scalar interactions up to the linear terms in the slow-motion approximation. The contribution of the spin-spin terms is found to be at best 10-6 times the post-Newtonian ones for the gravitational interaction.

Quantitative antibiogram as a typing method for the prospective epidemiological surveillance and control of MRSA: comparison with molecular typing.

OBJECTIVE: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. METHODS: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). SETTING: 1,000-bed tertiary university medical center. RESULTS: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. CONCLUSIONS: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics tested.

Protein level expression of Toll-like receptors 2, 4 and 9 in renal disease.

Background. Toll-like receptors (TLR) recognize a variety of ligands, including pathogen-associated molecular patterns and link innate and adaptive immunity. Individual receptors can be up-regulated during infection and inflammation. We examined the expression of selected TLRs at the protein level in various types of renal disease.Methods. Frozen sections of renal biopsies were stained with monoclonal antibodies to TLR-2, -4 and -9.Results. Up-regulation of the three TLRs studied was seen, although the extent was modest. TLR-2- and -4-positive cells belonged to the population of infiltrating inflammatory cells; only in the case of TLR-9 were intrinsic glomerular cells positive in polyoma virus infection and haemolytic uraemic syndrome (HUS).Conclusions. Evidence for the involvement of the three TLRs tested in a variety of human renal diseases was found. These findings add to our understanding of the role of the innate immune system in kidney disease.

Effect of a transverse magnetic field on resonant magnetization tunneling in high-spin molecules

The recent observation of steps at regular intervals of magnetic field in the hysteresis loops of oriented crystals of the spin-10 molecular magnet Mn12O12(CH3COO)16(H2O)4 has been attributed to resonant tunneling between spin states. Here, we investigate the effect on the relaxation rate of applying the magnetic field at an angle with respect to the easy axis of magnetization. We find that the position of the resonances is independent of the transverse component of the field, and is determined solely by the longitudinal component. On the other hand, a transverse field significantly increases the relaxation rate, both on and off resonance. We discuss classical and quantum mechanical interpretations of this effect

Fine structure of the vaccinia virus gene encoding the precursor of the major core protein 4 a.

A 6008 base pair fragment of the vaccinia virus DNA containing the gene for the precursor of the major core protein 4 a, which has been designated P4 a, was sequenced. A long open reading frame (ORF) encoding a protein of molecular weight 102,157 started close to the position where the P4 a mRNA had been mapped. Analysis of the mRNA by S1 nuclease mapping and primer extension indicated that the 5' end defined by the former method is not the true 5' end. This suggests that the P4 a coding region is preceded by leader sequences that are not derived from the immediate vicinity of the gene, similar to what has been reported for another late vaccinia virus mRNA. The sequenced DNA contained several further ORFs on the same, or opposite DNA strand, providing further evidence for the close spacing of protein-coding sequences in the viral genome.