88 research outputs found
X-Ray Observations of V4641 SGR (= SAX J1819.3-2525) During the Brief and Violent Outburst of 2003
We present the results of detailed analysis of pointed X-ray observations by
RXTE PCA/HEXTE of the black hole X-ray binary (BHXRB) system V4641 Sgr (= SAX
J1819.3-2525) during its outburst of August 2003. Soft X-ray (3-20 keV) flux
variations by factors of 10 or more on timescales of minutes or shorter were
seen. The rapid and strong variability of this source sets it apart from
typical XRBs. In spite of large luminosity fluctuations, the spectral state of
the source did not change significantly during the dwells which suggests that
the physical emission processes did not change much during the observations.
The energy spectra during the dwells were dominated by a hard Comptonized
powerlaw component, indicative of the canonical low/hard state observed in
other BHXRBs. No soft thermal component was found in three out of the four RXTE
pointings. However spectral deconvolution of the observation with largest
average luminosity suggests an obscured, hot accretion disk. During one of the
observations we detected a short term (about 100s) soft X-ray dropout which is
apparently due to variability in the observed column density. Strong Fe
K fluorescent emisssion line near 6.5 keV was detected with large
equivalent widths in the range of 700 - 1000eV. In the temporal domain, the
Fourier power spectra were dominated by red noise below a few Hz. Poisson noise
dominated at higher frequencies and no high frequency features were detected.
The strong Comptonized spectra, broad iron emission line, absence of disk
component in the spectra, absence of any timing variability above few Hz and
occasional large changes in the column density along the line-of-sight, all
support an enshrouded black hole with occasional outflow and a very dynamic
environment.Comment: 27 pages, 10 figures (1 color figure), accepted for publication in
the Astrophysical Journal. It is tentatively scheduled for the ApJ 01
February 2006, v637, 2 issu
Benign afebrile cluster convulsions with gastroenteritis: an observational study
BACKROUND: The occurrence of afebrile seizures in association with viral gastroenteritis, without dehydration or electrolyte imbalance, is virtually unknown outside Asia. They are reported to have a benign prognosis and not to require specific investigations or therapy. METHODS: We report the occurrence of such afebrile convulsions in association with viral gastroenteritis without dehydration or electrolyte imbalance, over a 3-year period, in a cohort of 14 British children. RESULTS: The children (5 males and 9 females, 10 Caucasians and 4 Asians) were aged 9 to 60 months (median 14.5 months). All 14 had a normal neurological examination and normal serum biochemistry. Twelve children had generalised seizures and 2 had, in addition, absence seizures. The number of seizures per child ranged from 1 to 8. Most convulsions were short with 85.7% of children having the longest seizure not longer than 4 minutes. The longest duration for a seizure was 10 minutes and occurred in 2 children. Convulsions did not recur after the first day in 10 children, 3 children had recurrences the second day and one child on the fourth day. No convulsions recurred after 4 days. Cerebrospinal fluid studies, computed tomography and electroencephalogram (EEG) were performed on two children who had prolonged seizures and the results were normal. No pathogenic bacteria were grown in any of the stools. Enzyme immunoassay detection of Rotavirus in the stools was positive in 7 of the 10 children where it was tested. All 14 children recovered spontaneously within a few days. On long-term follow of up to 31 months (median 16 months), none had further convulsions and all had normal development milestones. CONCLUSIONS: Afebrile seizures in association with viral gastroenteritis do also occur outside Asia. Recognition of this entity should lead to reassurance of the parents. As in previously published series, investigations such as lumbar puncture, neuroimaging and EEG are usually normal and may not be necessary in most cases. Likewise, published data indicate that long-term anticonvulsant therapy is not usually warranted and the prognosis seems to be reassuring
Gamma-Secretase-Dependent and -Independent Effects of Presenilin1 on ÎČ-Catenin·Tcf-4 Transcriptional Activity
Presenilin1 (PS1) is a component of the Îł-secretase complex mutated in cases of Familial Alzheimer's disease (FAD). PS1 is synthesized as a 50 kDa peptide subsequently processed to two 29 and 20 kDa subunits that remain associated. Processing of PS1 is inhibited by several mutations detected in FAD patients. PS1 acts as negative modulator of ÎČ-catenin·Tcf-4 transcriptional activity. In this article we show that in murine embryonic fibroblasts (MEFs) the mechanisms of action of the processed and non-processed forms of PS1 on ÎČ-catenin·Tcf-4 transcription are different. Whereas non-processed PS1 inhibits ÎČ-catenin·Tcf-4 activity through a mechanism independent of Îł-secretase and associated with the interaction of this protein with plakoglobin and Tcf-4, the effect of processed PS1 is prevented by Îł-secretase inhibitors, and requires its interaction with E- or N-cadherin and the generation of cytosolic terminal fragments of these two cadherins, which in turn destabilize the ÎČ-catenin transcriptional cofactor CBP. Accordingly, the two forms of PS1 interact differently with E-cadherin or ÎČ-catenin and plakoglobin: whereas processed PS1 binds E-cadherin with high affinity and ÎČ-catenin or plakoglobin weakly, the non-processed form behaves inversely. Moreover, contrarily to processed PS1, that decreases the levels of c-fos RNA, non-processed PS1 inhibits the expression c-myc, a known target of ÎČ-catenin·Tcf-4, and does not block the activity of other transcriptional factors requiring CBP. These results indicate that prevention of PS1 processing in FAD affects the mechanism of repression of the transcriptional activity dependent on ÎČ-catenin
Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial
Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population
Palladium-Catalyzed Oxidative Alkynylation of Alkenes via CâC Bond Cleavage under Oxygen Atmosphere
Synthesis of a Pentasaccharide Repeating Unit of the Extracellular Polysaccharide Produced by Lactobacillus Delbrueckii
Olaparib in patients with mCRPC with homologous recombination repair gene alterations: PROfound Asian subset analysis.
BackgroundThe Phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control; randomized 2:1 to olaparib or control) in men with homologous recombination repair gene alterations and metastatic castration-resistant prostate cancer whose disease progressed on prior next-generation hormonal agent.MethodsWe present efficacy and safety data from an exploratory post hoc analysis of olaparib in the PROfound Asian subset. Analyses were not planned, alpha controlled or powered. Of 101 Asian patients enrolled in Japan (n=57), South Korea (n=29) and Taiwan (n=15), 66 and 35 patients received olaparib and control, respectively.ResultsRadiographic progression-free survival (rPFS) and overall survival (OS) favored olaparib versus control in Cohort A [rPFS 7.2 vs. 4.5 months, HR 0.58, 95% CI 0.29-1.21, P = 0.14 (nominal); OS 23.4 vs. 17.8 months, HR 0.81, 95% CI 0.40-1.74, P = 0.57 (nominal)] and Cohorts A+B [rPFS 5.8 vs. 3.5 months, HR 0.69, 95% CI 0.42-1.16, P = 0.13 (nominal); OS 18.6 vs. 16.2 months, HR 0.96, 95% CI 0.56-1.70, P = 0.9 (nominal)]. Olaparib showed greatest improvement in patients harboring BRCA alterations [rPFS 9.3 vs. 3.5 months, HR 0.17, 95% CI 0.06-0.49, P = 0.0003 (nominal); OS 26.8 vs. 14.3 months, HR 0.62, 95% CI 0.24-1.79, P = 0.34 (nominal)]. Safety data were consistent with the known profile of olaparib, with no new safety signals identified.ConclusionIn PROfound, there was a statistically significant improvement in outcomes reported in the global population of patients with metastatic castration-resistant prostate cancer and alterations in homologous recombination repair genes whose disease progressed on prior next-generation hormonal agent compared with control. For the subset of Asian patients reported here, exploratory analysis suggested that there was also an improvement in outcomes versus control. The safety and tolerability of olaparib in Asian patients were similar to that of the PROfound global population.Clinical trial numberClinicalTrials.gov NCT02987543
Toward the Selective Inhibition of G Proteins: Total Synthesis of a Simplified YM-254890 Analog
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