A cosmopolitan temptation

For some, the transnationalization of political action and communicative space in the European Union heralds an emergent cosmopolitan order. Need that be so? There are supranational institutions in the EU as well as transnational political and cultural spaces and cross-border communicative flows. However, the Union's member states remain key controllers of citizenship rights and purveyors of collective identities. And for many purposes they still maintain strongly bounded national public spheres. Because the EU's overall character as a polity remains unresolved, this has consequences for the organization of communicative spaces. The EU is a field of tensions and contradictions that is inescapably rooted in institutional realities. Wishful thinking about cosmopolitanism can get in the way of clear analysis

The rms-flux relations in different branches in Cyg X-2

In this paper, the rms-flux (root mean square-flux) relation along the Z-track of the bright Z-Source Cyg X-2 is analyzed using the observational data of Rossi X-ray Timing Explorer (RXTE). Three types of rms-flux relations, i.e. positive, negative, and 'arch'-like correlations are found in different branches. The rms is positively correlated with flux in normal branch (NB), but anti-correlated in the vertical horizontal branch (VHB). The rms-flux relation shows an 'arch'-like shape in the horizontal branch (HB). We also try to explain this phenomenon using existing models.Comment: Accepted for publication in Astrophysics & Space Scienc

On the Radio/X-ray Correlation in Microquasars

[Context] The broadband spectral energy distribution of microquasars has proven to be a valuable tool for assessing the roles of jets and accretion flows in microquasars, as well as the coupling between the two. The coupling might manifest itself observationally in the correlated radio and X-ray variabilities of a source. Such a radio/X-ray correlation has indeed been seen in several microquasars during the low-hard state and subsequently been claimed to be universal for all. If proven, the universal correlation would have profound implications on theoretical models. However, there is already observational evidence that suggests otherwise. [Aims] In this paper, we critically examine the radio/X-ray correlation in a sample of microquasars, in the low-hard state as well as during state transitions, with a goal of testing the claimed universality of the correlation on observational grounds. [Methods] We have assembled a comprehensive data set from the simultaneous/contemporaneous radio and X-ray observations of representative microquasars. The data have allowed us to quantify the radio/X-ray correlation on a source by source basis. [Results] We find that the radio/X-ray correlation of microquasars exhibits diverse behaviors, both in the low-hard and transitional states, ranging from being very week (or none at all) to very strong. There is even a hint of spectral dependence of the correlation in some cases. [Conclusions] Our results rule out the claimed universality of the radio/X-ray correlation of microquasars, even for the low-hard state. On the other hand, we do find that the radio and X-ray variabilities are, to varying degrees, correlated in most cases.Comment: 6 pages, 4 figures, accepted by A&

States and transitions in black-hole binaries

With the availability of the large database of black-hole transients from the Rossi X-Ray Timing Explorer, the observed phenomenology has become very complex. The original classification of the properties of these systems in a series of static states sorted by mass accretion rate proved not to be able to encompass the new picture. I outline here a summary of the current situation and show that a coherent picture emerges when simple properties such as X-ray spectral hardness and fractional variability are considered. In particular, fast transition in the properties of the fast time variability appear to be crucial to describe the evolution of black-hole transients. Based on this picture, I present a state-classification which takes into account the observed transitions. I show that, in addition to transients systems, other black-hole binaries and Active Galactic Nuclei can be interpreted within this framework. The association between these states and the physics of the accretion flow around black holes will be possible only through modeling of the full time evolution of galactic transient systems.Comment: 30 pages, 11 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Targeted Drug Delivery by Gemtuzumab Ozogamicin: Mechanism-Based Mathematical Model for Treatment Strategy Improvement and Therapy Individualization

Gemtuzumab ozogamicin (GO) is a chemotherapy-conjugated anti-CD33 monoclonal antibody effective in some patients with acute myeloid leukemia (AML). The optimal treatment schedule and optimal timing of GO administration relative to other agents remains unknown. Conventional pharmacokinetic analysis has been of limited insight for the schedule optimization. We developed a mechanism-based mathematical model and employed it to analyze the time-course of free and GO-bound CD33 molecules on the lekemic blasts in individual AML patients treated with GO. We calculated expected intravascular drug exposure (I-AUC) as a surrogate marker for the response to the drug. A high CD33 production rate and low drug efflux were the most important determinants of high I-AUC, characterizing patients with favorable pharmacokinetic profile and, hence, improved response. I-AUC was insensitive to other studied parameters within biologically relevant ranges, including internalization rate and dissociation constant. Our computations suggested that even moderate blast burden reduction prior to drug administration enables lowering of GO doses without significantly compromising intracellular drug exposure. These findings indicate that GO may optimally be used after cyto-reductive chemotherapy, rather than before, or concomitantly with it, and that GO efficacy can be maintained by dose reduction to 6 mg/m2 and a dosing interval of 7 days. Model predictions are validated by comparison with the results of EORTC-GIMEMA AML19 clinical trial, where two different GO schedules were administered. We suggest that incorporation of our results in clinical practice can serve identification of the subpopulation of elderly patients who can benefit most of the GO treatment and enable return of the currently suspended drug to clinic

Reduced Susceptibility to Interference in the Consolidation of Motor Memory before Adolescence

Are children superior to adults in consolidating procedural memory? This notion has been tied to “critical,” early life periods of increased brain plasticity. Here, using a motor sequence learning task, we show, in experiment 1, that a) the rate of learning during a training session, b) the gains accrued, without additional practice, within a 24 hours post-training interval (delayed consolidation gains), and c) the long-term retention of these gains, were as effective in 9, 12 and 17-year-olds and comparable to those reported for adults. However, a follow-up experiment showed that the establishment of a memory trace for the trained sequence of movements was significantly more susceptible to interference by a subsequent motor learning experience (practicing a reversed movement sequence) in the 17-year-olds compared to the 9 and 12-year-olds. Unlike the 17-year-olds, the younger age-groups showed significant delayed gains even after interference training. Altogether, our results indicate the existence of an effective consolidation phase in motor learning both before and after adolescence, with no childhood advantage in the learning or retention of a motor skill. However, the ability to co-consolidate different, successive motor experiences, demonstrated in both the 9 and 12-year-olds, diminishes after puberty, suggesting that a more selective memory consolidation process takes over from the childhood one. Only the adult consolidation process is gated by a recency effect, and in situations of multiple, clashing, experiences occurring within a short time-interval, adults may less effectively establish in memory experiences superseded by newer ones

Long Term Variability of Cyg X-1 I. X-ray spectral-temporal correlations in the hard state

We present the long term evolution of the timing properties of the black hole candidate Cygnus X-1 in the 0.002-128 Hz frequency range as monitored from 1998 to 2001 with the RXTE. The hard state power spectral density (PSD) is well modeled as the sum of four Lorentzians, which describe distinct broad noise components. Before 1998 July, Cyg X-1 was in a "quiet" hard state characterized primarily by the first three of these broad Lorentzians. Around 1998 May, this behavior changed: the total fractional rms amplitude decreased, the peak frequencies of the Lorentzians increased, the average time lag slightly increased, and the X-ray spectrum softened. The change in the timing parameters is mainly due to a strong decrease in the amplitude of the third Lorentzian. Since then, an unusually large number of X-ray flares have been observed. During these "failed state transitions", the X-ray power spectrum changes to that of the intermediate state. Modeling this PSD with the four Lorentzians, we find that the first Lorentzian component is suppressed relative to the second and third Lorentzian. Also the frequency-dependent time lags increase significantly. We confirm the interpretation as failed state transitions with observations from the 2001 Jan. and 2001 Oct. soft states. Such behavior suggests that some or all of the Lorentzian components are associated with the accretion disk corona. We discuss the physical interpretation of our results.Comment: 21 pages, 16 figures, the sections on failed state transitions have been restructured for clarity, a section on thin Lorentzians has been added, and the definition of Q has been adapted to general us

Differential Expression of CD163 on Monocyte Subsets in Healthy and HIV-1 Infected Individuals

CD163, a haptoglobin-hemoglobin (Hp-Hb) scavenger receptor, expressed by monocytes and macrophages, is important in resolution of inflammation. Age-related non-AIDS co-morbidities in HIV-infected individuals, particularly dementia and cardiovascular disease, result in part from effects of HIV-1 infection on monocyte and macrophage biology. CD163 co-expression on CD14+CD16++ monocytes has been proposed as a useful biomarker for HIV-1 disease progression and the presence of HIV associated dementia. Here we investigated CD163 expression on monocyte subsets ex vivo, on cultured macrophages, and soluble in plasma, in the setting of HIV-1 infection. Whole blood immunophenotyping revealed CD163 expression on CD14++CD16- monocytes but not on CD14+CD16++ monocytes (P = 0.004), supported by CD163 mRNA levels. Incubation with M-CSF induced CD163 protein expression on CD14+CD16++ monocytes to the same extent as CD14++CD16− monocytes. CD163 expression on CD14++CD16+ monocytes from HIV-infected subjects was significantly higher than from uninfected individuals, with a trend towards increased expression on CD14++CD16− monocytes (P = 0.019 and 0.069 respectively), which is accounted for by HIV-1 therapy including protease inhibitors. Shedding of CD163 was shown to predominantly occur from the CD14++CD16− subset after Ficoll isolation and LPS stimulation. Soluble CD163 concentration in plasma from HIV-1 infected donors was similar to HIV-1 uninfected donors. Monocyte CD163 expression in HIV-1 infected patients showed a complicated relationship with classical measures of disease progression. Our findings clarify technical issues regarding CD163 expression on monocyte subsets and further elucidates its role in HIV-associated inflammation by demonstrating that CD163 is readily lost from CD14++CD16− monocytes and induced in pro-inflammatory CD14+CD16++ monocytes by M-CSF. Our data show that all monocyte subsets are potentially capable of differentiating into CD163-expressing anti-inflammatory macrophages given appropriate stimuli. Levels of CD163 expression on monocytes may be a potential biomarker reflecting efforts by the immune system to resolve immune activation and inflammation in HIV-infected individuals