An approximate renormalization-group transformation for Hamiltonian systems with three degrees of freedom

We construct an approximate renormalization transformation that combines Kolmogorov-Arnold-Moser (KAM)and renormalization-group techniques, to analyze instabilities in Hamiltonian systems with three degrees of freedom. This scheme is implemented both for isoenergetically nondegenerate and for degenerate Hamiltonians. For the spiral mean frequency vector, we find numerically that the iterations of the transformation on nondegenerate Hamiltonians tend to degenerate ones on the critical surface. As a consequence, isoenergetically degenerate and nondegenerate Hamiltonians belong to the same universality class, and thus the corresponding critical invariant tori have the same type of scaling properties. We numerically investigate the structure of the attracting set on the critical surface and find that it is a strange nonchaotic attractor. We compute exponents that characterize its universality class.Comment: 10 pages typeset using REVTeX, 7 PS figure

The WEBT Campaign on the Blazar 3C279 in 2006

The quasar 3C279 was the target of an extensive multiwavelength monitoring campaign from January through April 2006, including an optical-IR-radio monitoring campaign by the Whole Earth Blazar Telescope (WEBT) collaboration. In this paper we focus on the results of the WEBT campaign. The source exhibited substantial variability of optical flux and spectral shape, with a characteristic time scale of a few days. The variability patterns throughout the optical BVRI bands were very closely correlated with each other. In intriguing contrast to other (in particular, BL Lac type) blazars, we find a lag of shorter- behind longer-wavelength variability throughout the RVB ranges, with a time delay increasing with increasing frequency. Spectral hardening during flares appears delayed with respect to a rising optical flux. This, in combination with the very steep IR-optical continuum spectral index of ~ 1.5 - 2.0, may indicate a highly oblique magnetic field configuration near the base of the jet. An alternative explanation through a slow (time scale of several days) acceleration mechanism would require an unusually low magnetic field of < 0.2 G, about an order of magnitude lower than inferred from previous analyses of simultaneous SEDs of 3C279 and other FSRQs with similar properties.Comment: Accepted for publication in Ap

The unprecedented optical outburst of the quasar 3C 454.3. The WEBT campaign of 2004-2005

The radio quasar 3C 454.3 underwent an exceptional optical outburst lasting more than 1 year and culminating in spring 2005. The maximum brightness detected was R = 12.0, which represents the most luminous quasar state thus far observed (M_B ~ -31.4). In order to follow the emission behaviour of the source in detail, a large multiwavelength campaign was organized by the Whole Earth Blazar Telescope (WEBT). Continuous optical, near-IR and radio monitoring was performed in several bands. ToO pointings by the Chandra and INTEGRAL satellites provided additional information at high energies in May 2005. The historical radio and optical light curves show different behaviours. Until about 2001.0 only moderate variability was present in the optical regime, while prominent and long-lasting radio outbursts were visible at the various radio frequencies, with higher-frequency variations preceding the lower-frequency ones. After that date, the optical activity increased and the radio flux is less variable. This suggests that the optical and radio emissions come from two separate and misaligned jet regions, with the inner optical one acquiring a smaller viewing angle during the 2004-2005 outburst. Moreover, the colour-index behaviour (generally redder-when-brighter) during the outburst suggests the presence of a luminous accretion disc. A huge mm outburst followed the optical one, peaking in June-July 2005. The high-frequency (37-43 GHz) radio flux started to increase in early 2005 and reached a maximum at the end of our observing period (end of September 2005). VLBA observations at 43 GHz during the summer confirm theComment: 7 pages, 4 figures, to be published in A&

The radio delay of the exceptional 3C 454.3 outburst. Follow-up WEBT observations in 2005-2006

In spring 2005 the blazar 3C 454.3 was observed in an unprecedented bright state from the near-IR to the hard X-ray frequencies. A mm outburst peaked in June-July 2005, and it was followed by a flux increase at high radio frequencies. In this paper we report on multifrequency monitoring by the WEBT aimed at following the further evolution of the outburst in detail. In particular, we investigate the expected correlation and time delays between the optical and radio emissions in order to derive information on the variability mechanisms and jet structure. A comparison among the light curves at different frequencies is performed by means of visual inspection and discrete correlation function, and the results are interpreted with a simple model taking into account Doppler factor variations of geometric origin. The high-frequency radio light curves show a huge outburst starting during the dimming phase of the optical one and lasting more than 1 year. The first phase is characterized by a slow flux increase, while in early 2006 a major flare is observed. The lower-frequency radio light curves show a progressively delayed and fainter event, which disappears below 8 GHz. We suggest that the radio major peak is not physically connected with the spring 2005 optical one, but it is actually correlated with a minor optical flare observed in October-November 2005. This interpretation involves both an intrinsic and a geometric mechanism. The former is represented by disturbances travelling down the emitting jet, the latter being due to the curved-jet motion, with the consequent differential changes of viewing angles of the different emitting regions.Comment: 5 pages, 3 figures, to be published in A&A (Letters

Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background HTLV-I is associated with the development of an aggressive form of lymphocytic leukemia known as adult T-cell leukemia/lymphoma (ATLL). A major obstacle for effective treatment of ATLL resides in the genetic diversity of tumor cells and their ability to acquire resistance to chemotherapy regimens. As a result, most patients relapse and current therapeutic approaches still have limited long-term survival benefits. Hence, the development of novel approaches is greatly needed. Methods In this study, we found that a small molecule inhibitor of poly (ADP-ribose) polymerase (PARP), PJ-34, is very effective in activating S/G2M cell cycle checkpoints, resulting in permanent cell cycle arrest and reactivation of p53 transcription functions and caspase-3-dependent apoptosis of HTLV-I-transformed and patient-derived ATLL tumor cells. We also found that HTLV-I-transformed MT-2 cells are resistant to PJ-34 therapy associated with reduced cleaved caspase-3 activation and increased expression of RelA/p65. Conclusion Since PJ-34 has been tested in clinical trials for the treatment of solid tumors, our results suggest that some ATLL patients may be good candidates to benefit from PJ-34 therapy

Targeting N-myristoylation for therapy of B-cell lymphomas

N-myristoyltransferases (NMTs) target many signaling proteins to membranes. Here the authors show an NMT inhibitor named PCLX-001 selectively kills lymphoma cells by shutting down their main survival signaling pathway and offers an additional treatment strategy for lymphoma patients

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways