Spectro-timing analysis of Cygnus X-1 during a fast state transition

We present the analysis of two long, quasi-uninterrupted RXTE observations of Cygnus X-1 that span several days within a 10 d interval. The spectral characteristics during this observation cover the region where previous observations have shown the source to be most dynamic. Despite that the source behavior on time scales of hours and days is remarkably similar to that on year time scales. This includes a variety of spectral/temporal correlations that previously had only been observed over Cyg X-1's long-term evolution. Furthermore, we observe a full transition from a hard to a soft spectral state that occurs within less than 2.5 hours - shorter than previously reported for any other similar Cyg X-1 transition. We describe the spectra with a phenomenological model dominated by a broken power law, and we fit the X-ray variability power spectra with a combination of a cutoff power law and Lorentzian components. The spectral and timing properties are correlated: the power spectrum Lorentzian components have an energy-dependent amplitude, and their peak frequencies increase with photon spectral index. Averaged over 3.2-10 Hz, the time lag between the variability in the 4.5-5.7 keV and 9.5-15 keV bands increases with decreasing hardness when the variability is dominated by the Lorentzian components during the hard state. The lag is small when there is a large power law noise contribution, shortly after the transition to the soft state. Interestingly, the soft state not only shows the shortest lags, but also the longest lags when the spectrum is at its softest and faintest. We discuss our results in terms of emission models for black hole binaries.Comment: 13 pages, 15 figures, accepted for publication in Astronomy and Astrophysic

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

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

PF-4var/CXCL4L1 Predicts Outcome in Stable Coronary Artery Disease Patients with Preserved Left Ventricular Function

Background: Platelet-derived chemokines are implicated in several aspects of vascular biology. However, for the chemokine platelet factor 4 variant (PF-4var/CXCL4L1), released by platelets during thrombosis and with different properties as compared to PF-4/CXCL4, its role in heart disease is not yet studied. We evaluated the determinants and prognostic value of the platelet-derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary artery disease (CAD). Methodology/Principal Findings: From 205 consecutive patients with stable CAD and preserved left ventricular (LV) function, blood samples were taken at inclusion and were analyzed for PF-4var, RANTES, platelet factor-4 and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Patients were followed (median follow-up 2.5 years) for the combined endpoint of cardiac death, non-fatal acute myocardial infarction, stroke or hospitalization for heart failure. Independent determinants of PF-4var levels (median 10 ng/ml; interquartile range 8-16 ng/ml) were age, gender and circulating platelet number. Patients who experienced cardiac events (n = 20) during follow-up showed lower levels of PF-4var (8.5 [5.3-10] ng/ml versus 12 [8-16] ng/ml, p = 0.033). ROC analysis for events showed an area under the curve (AUC) of 0.82 (95% CI 0.73-0.90, p<0.001) for higher NT-proBNP levels and an AUC of 0.32 (95% CI 0.19-0.45, p = 0.009) for lower PF-4var levels. Cox proportional hazard analysis showed that PF-4var has an independent prognostic value on top of NT-proBNP. Conclusions: We conclude that low PF-4var/CXCL4L1 levels are associated with a poor outcome in patients with stable CAD and preserved LV function. This prognostic value is independent of NT-proBNP levels, suggesting that both neurohormonal and platelet-related factors determine outcome in these patients

Periodontal status of rheumatoid arthritis patients in khartoum state

<p>Abstract</p> <p>Background</p> <p>Few studies have investigated the periodontal condition among Rheumatoid arthritis in Sudan. The present study described the periodontal condition among Sudanese patients suffering from rheumatoid arthritis and to compare them with those of non-rheumatic subjects.</p> <p>Methods</p> <p>A group of eighty rheumatoid arthritis patients was selected from Patient's Rheumatoid Clinics in Khartoum State during the period of January to May 2010. A control group of eighty patients with the same age and gender was selected for the study. Both Rheumatoid arthritis patients and the control group were examined for their plaque index, gingival index, and clinical attachment loss.</p> <p>Results</p> <p>The results revealed that there were no significant differences in plaque and gingival index among study and control groups, with mean plaque index of (1.25 ± 0.4) for patients and (1.17 ± 0.28) for the control group (p-value is 0.3597). The mean gingival index was (1.2 ± 0.24) for the patients and (1.2 ± 0.33) for the control (p = is 0.3049). The results showed statistically significant differences in clinical attachment loss between study and control groups, with mean clinical attachment loss of (1.03 ± 0.95) for the study group and (0.56 ± 0.63) for the control group (p = 0.0002). The study revealed that no association exists between the type of drug used to treat rheumatoid arthritis (NSAIDs & DMARDs) and the periodontal parameters (plaque index, gingival index, and clinical attachment loss).</p> <p>Conclusion</p> <p>A significant relationship between periodontal disease and Rheumatoid Arthritis does exist, but no difference between plaque and gingival index has been detected among study and control groups.</p

Increased Migration of Monocytes in Essential Hypertension Is Associated with Increased Transient Receptor Potential Channel Canonical Type 3 Channels

Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels