An ASCA Study of the W51 Complex

We present the analysis of ASCA archival data from the Galactic source W51. The ASCA spectra show that the soft (kT<= 2.5 keV) X-rays are of thermal origin and are compatible with W51C being a single, isothermal (kT~0.3 keV) supernova remnant at the far-side of the Sagittarius arm. The ASCA images reveal hard (kT>=2.5 keV) X-ray sources which were not seen in previous X-ray observations. Some of these sources are coincident with massive star-forming regions and the spectra are used to derive X-ray parameters. By comparing the X-ray absorbing column density with atomic hydrogen column density, we infer the location of star-forming regions relative to molecular clouds. There are unidentified hard X-ray sources superposed on the supernova remnant and we discuss the possibility of their association.Comment: 13 pages, 11 figures, to be published in Astronomical Journa

Observation of First-Order Metal-Insulator Transition without Structural Phase Transition in VO_2

An abrupt first-order metal-insulator transition (MIT) without structural phase transition is first observed by current-voltage measurements and micro-Raman scattering experiments, when a DC electric field is applied to a Mott insulator VO_2 based two-terminal device. An abrupt current jump is measured at a critical electric field. The Raman-shift frequency and the bandwidth of the most predominant Raman-active A_g mode, excited by the electric field, do not change through the abrupt MIT, while, they, excited by temperature, pronouncedly soften and damp (structural MIT), respectively. This structural MIT is found to occur secondarily.Comment: 4 pages, 4 figure

Observation of Scarred Modes in Asymmetrically Deformed Microcylinder Lasers

We report observation of lasing in the scarred modes in an asymmetrically deformed microcavity made of liquid jet. The observed scarred modes correspond to morphology-dependent resonance of radial mode order 3 with their Q values in the range of 10^6. Emission directionality is also observed, corresponding to a hexagonal unstable periodic orbit.Comment: 4 pages, 6 figure

Dynamic Temporal Change of Cerebral Microbleeds: Long-Term Follow-Up MRI Study

Background: Cerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI. Methods/Principal Findings: From October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval.12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs$5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count. Conclusion: During the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomati

Intensity modulated radiation therapy dose painting for localized prostate cancer using(11)C-choline positron emission tomography scans

PURPOSE: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using¹¹C-choline positron emission tomography PET scans in patients with localized prostate cancer. METHODS AND MATERIALS: This was an RT planning study of 8 patients with prostate cancer who had ¹¹C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. RESULTS: All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS: IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.Joe H. Chang, Daryl Lim Joon, Sze Ting Lee, Sylvia J. Gong, Nigel J. Anderson, Andrew M. Scott, Ian D. Davis, David Clouston, Damien Bolton, Christopher S. Hamilton, Vincent Kho

eIF2A, an initiator tRNA carrier refractory to eIF2 kinases, functions synergistically with eIF5B

The initiator tRNA (Met-tRNA(i)(Met)) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNAiMet on the small ribosomal subunit. Eukarya contain the Met-tRNAiMet carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its -subunit by stress-activated eIF2 kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNAiMet on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNAiMet, eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B-eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.112Ysciescopu

A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer

BACKGROUND: In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). METHODS: This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. RESULTS: Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. CONCLUSIONS: The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01011075

The rostroventral part of the thalamic reticular nucleus modulates fear extinction

The thalamus has been implicated in fear extinction, yet the role of the thalamic reticular nucleus (TRN) in this process remains unclear. Here, in mice, we show that the rostroventral part of the TRN (TRNrv) is critically involved in the extinction of tone-dependent fear memory. Optogenetic excitation of TRNrv neurons during extinction learning dramatically facilitated, whereas the inhibition disrupted, the fear extinction. Single unit recordings demonstrated that TRNrv neurons selectively respond to conditioned stimuli but not to neutral stimuli. TRNrv neurons suppressed the spiking activity of the medial part of the dorsal midline thalamus (dMTm), and a blockade of this inhibitory pathway disrupted fear extinction. Finally, we found that the suppression of dMTm projections to the central amygdala promotes fear extinction, and TRNrv neurons have direct connections to this pathway. Our results uncover a previously unknown function of the TRN and delineate the neural circuit for thalamic control of fear memory. © The Author(s) 201911Nsci

Comparison of [(11)C]choline positron emission tomography with T2- and diffusion-weighted magnetic resonance imaging for delineating malignant intraprostatic lesions

Purpose: To compare the accuracy of ¹¹C-choline (CHOL) positron emission tomography (PET) with the combination of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. Methods and Materials: This study included 21 patients who underwent CHOL-PET and T2W-/DW-MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined the reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), sensitivity and specificity. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. Results: The best automatic contouring method, SUV60, had similar correlations (DSC 0.59) with the manual PET contours (DSC 0.52, P=0.127) and significantly better correlations than the manual MRI contours (DSC 0.37, P<0.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. Conclusions: CHOL-PET is superior to the combination of T2W- and DW-MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies, 3 however may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict for how well CHOL-PET delineates IPLs.Joe H. Chang, Daryl Lim Joon, Ian D. Davis, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O'Sullivan, Yin P. Goh, Damien Bolton, Andrew M. Scott, Vincent Kho