92 research outputs found
Relativistic ejecta from XRF 060218 and the rate of cosmic explosions
Over the last decade, long-duration gamma-ray bursts (GRBs) including the
subclass of X-ray flashes (XRFs) have been revealed to be a rare variety of
Type Ibc supernova (SN). While all these events result from the death of
massive stars, the electromagnetic luminosities of GRBs and XRFs exceed those
of ordinary Type Ibc SNe by many orders of magnitude. The essential physical
process that causes a dying star to produce a GRB or XRF, and not just an SN,
remains the crucial open question. Here we present radio and X-ray observations
of XRF 060218 (associated with SN 2006aj), the second nearest GRB identified
to-date, which allow us to measure its total energy and place it in the larger
context of cosmic explosions. We show that this event is 100 times less
energetic but ten times more common than cosmological GRBs. Moreover, it is
distinguished from ordinary Type Ibc SNe by the presence of 10^48 erg coupled
to mildly-relativistic ejecta, along with a central engine (an accretion-fed,
rapidly rotating compact source) which produces X-rays for weeks after the
explosion. This suggests that the production of relativistic ejecta is the key
physical distinction between GRBs/XRFs and ordinary SNe, while the nature of
the central engine (black hole or magnetar) may distinguish typical bursts from
low-luminosity, spherical events like XRF 060218.Comment: To appear in Nature on August 31 2006 (15 pages, 3 figures, 1 table,
including Supplementary Information
Cardiac injuries in blunt chest trauma
Blunt chest traumas are a clinical challenge, both for diagnosis and treatment. The use of cardiovascular magnetic resonance can play a major role in this setting. We present two cases: a 12-year-old boy and 45-year-old man. Late gadolinium enhancement imaging enabled visualization of myocardial damage resulting from the trauma
A phase II study of the bispecific antibody MDX-H210 (anti-HER2 × CD64) with GM-CSF in HER2+ advanced prostate cancer
The proto-oncogene HER2 presents a novel therapeutic target. We report results in 25 patients with HER2+ advanced prostate cancer treated with the bispecific antibody MDX-H210 15 μg m−2by intravenous infusion plus GM-CSF 5 μg kg−1day−1by subcutaneous injection for 4 days repeated weekly for 6 weeks. Patients with stable disease or better received further cycles of treatment until disease progression or study withdrawal. 1 patient received no treatment and 4 received less than 1 cycle and are included in the toxicity analysis only. Median duration of follow up was 105+ (range 21–188) days. Toxicity was generally NCI-CTG 0–2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1 grade 3 event (allergic reaction) resulting in discontinuation of the study medication. There were 9 further grade 3 events not resulting in trial withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients had a >50% PSA response of median duration 128 (range 71–184+) days. 7/12 (58%) patients with evaluable pain had improvements in pain scores. The PSA relative velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre-study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma with acceptable toxicity; further studies are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.co
Somatic sex-specific transcriptome differences in Drosophila revealed by whole transcriptome sequencing
<p>Abstract</p> <p>Background</p> <p>Understanding animal development and physiology at a molecular-biological level has been advanced by the ability to determine at high resolution the repertoire of mRNA molecules by whole transcriptome resequencing. This includes the ability to detect and quantify rare abundance transcripts and isoform-specific mRNA variants produced from a gene.</p> <p>The sex hierarchy consists of a pre-mRNA splicing cascade that directs the production of sex-specific transcription factors that specify nearly all sexual dimorphism. We have used deep RNA sequencing to gain insight into how the Drosophila sex hierarchy generates somatic sex differences, by examining gene and transcript isoform expression differences between the sexes in adult head tissues.</p> <p>Results</p> <p>Here we find 1,381 genes that differ in overall expression levels and 1,370 isoform-specific transcripts that differ between males and females. Additionally, we find 512 genes not regulated downstream of <it>transformer </it>that are significantly more highly expressed in males than females. These 512 genes are enriched on the × chromosome and reside adjacent to dosage compensation complex entry sites, which taken together suggests that their residence on the × chromosome might be sufficient to confer male-biased expression. There are no transcription unit structural features, from a set of features, that are robustly significantly different in the genes with significant sex differences in the ratio of isoform-specific transcripts, as compared to random isoform-specific transcripts, suggesting that there is no single molecular mechanism that generates isoform-specific transcript differences between the sexes, even though the sex hierarchy is known to include three pre-mRNA splicing factors.</p> <p>Conclusions</p> <p>We identify thousands of genes that show sex-specific differences in overall gene expression levels, and identify hundreds of additional genes that have differences in the abundance of isoform-specific transcripts. No transcription unit structural feature was robustly enriched in the sex-differentially expressed transcript isoforms. Additionally, we found that many genes with male-biased expression were enriched on the × chromosome and reside adjacent to dosage compensation entry sites, suggesting that differences in sex chromosome composition contributes to dimorphism in gene expression. Taken together, this study provides new insight into the molecular underpinnings of sexual differentiation.</p
Physics of Neutron Star Crusts
The physics of neutron star crusts is vast, involving many different research
fields, from nuclear and condensed matter physics to general relativity. This
review summarizes the progress, which has been achieved over the last few
years, in modeling neutron star crusts, both at the microscopic and macroscopic
levels. The confrontation of these theoretical models with observations is also
briefly discussed.Comment: 182 pages, published version available at
<http://www.livingreviews.org/lrr-2008-10
Neuregulin Promotes Incomplete Autophagy of Prostate Cancer Cells That Is Independent of mTOR Pathway Inhibition
Growth factors activating the ErbB receptors have been described in prostate tumors. The androgen dependent prostate cancer cell line, LNCaP, expresses the ErbB-1, ErbB-2 and ErbB-3 receptor tyrosine kinases. Previously, it was demonstrated that NRG activates ErbB-2/ErbB-3 heterodimers to induce LNCaP cell death, whereas, EGF activates ErbB-1/ErbB-1 or ErbB-1/ErbB-2 dimers to induce cell growth and survival. It was also demonstrated that PI3K inhibitors repressed this cell death suggesting that in androgen deprived LNCaP cells, NRG activates a PI3K-dependent pathway associated with cell death.In the present study we demonstrate that NRG induces autophagy in LNCaP cells, using LC3 as a marker. However, the autophagy induced by NRG may be incomplete since p62 levels elevate. We also demonstrated that NRG- induced autophagy is independent of mammalian target of rapamycin (mTOR) inhibition since NRG induces Akt and S6K activation. Interestingly, inhibition of reactive oxygen species (ROS) by N-acetylcysteine (NAC), inhibited NRG-induced autophagy and cell death. Our study also identified JNK and Beclin 1 as important components in NRG-induced autophagy and cell death. NRG induced elevation in JNK phosphorylation that was inhibited by NAC. Moreover, inhibitor of JNK inhibited NRG-induced autophagy and cell death. Also, in cells overexpressing Bcl-2 or cells expressing sh-RNA against Beclin 1, the effects of NRG, namely induction of autophagy and cell death, were inhibited.Thus, in LNCaP cells, NRG-induces incomplete autophagy and cell death that depend on ROS levels. These effects of NRG are mediated by signaling pathway that activates JNK and Beclin 1, but is independent of mTOR inhibition
The Evolution of Compact Binary Star Systems
We review the formation and evolution of compact binary stars consisting of
white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and
BHs are thought to be the primary astrophysical sources of gravitational waves
(GWs) within the frequency band of ground-based detectors, while compact
binaries of WDs are important sources of GWs at lower frequencies to be covered
by space interferometers (LISA). Major uncertainties in the current
understanding of properties of NSs and BHs most relevant to the GW studies are
discussed, including the treatment of the natal kicks which compact stellar
remnants acquire during the core collapse of massive stars and the common
envelope phase of binary evolution. We discuss the coalescence rates of binary
NSs and BHs and prospects for their detections, the formation and evolution of
binary WDs and their observational manifestations. Special attention is given
to AM CVn-stars -- compact binaries in which the Roche lobe is filled by
another WD or a low-mass partially degenerate helium-star, as these stars are
thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure
Current cardiac imaging techniques for detection of left ventricular mass
Estimation of left ventricular (LV) mass has both prognostic and therapeutic value independent of traditional risk factors. Unfortunately, LV mass evaluation has been underestimated in clinical practice. Assessment of LV mass can be performed by a number of imaging modalities. Despite inherent limitations, conventional echocardiography has fundamentally been established as most widely used diagnostic tool. 3-dimensional echocardiography (3DE) is now feasible, fast and accurate for LV mass evaluation. 3DE is also superior to conventional echocardiography in terms of LV mass assessment, especially in patients with abnormal LV geometry. Cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) are currently performed for LV mass assessment and also do not depend on cardiac geometry and display 3-dimensional data, as well. Therefore, CMR is being increasingly employed and is at the present standard of reference in the clinical setting. Although each method demonstrates advantages over another, there are also disadvantages to receive attention. Diagnostic accuracy of methods will also be increased with the introduction of more advanced systems. It is also likely that in the coming years new and more accurate diagnostic tests will become available. In particular, CMR and CCT have been intersecting hot topic between cardiology and radiology clinics. Thus, good communication and collaboration between two specialties is required for selection of an appropriate test
Variations in Stress Sensitivity and Genomic Expression in Diverse S. cerevisiae Isolates
Interactions between an organism and its environment can significantly influence
phenotypic evolution. A first step toward understanding this process is to
characterize phenotypic diversity within and between populations. We explored
the phenotypic variation in stress sensitivity and genomic expression in a large
panel of Saccharomyces strains collected from diverse
environments. We measured the sensitivity of 52 strains to 14 environmental
conditions, compared genomic expression in 18 strains, and identified gene
copy-number variations in six of these isolates. Our results demonstrate a large
degree of phenotypic variation in stress sensitivity and gene expression.
Analysis of these datasets reveals relationships between strains from similar
niches, suggests common and unique features of yeast habitats, and implicates
genes whose variable expression is linked to stress resistance. Using a simple
metric to suggest cases of selection, we found that strains collected from oak
exudates are phenotypically more similar than expected based on their genetic
diversity, while sake and vineyard isolates display more diverse phenotypes than
expected under a neutral model. We also show that the laboratory strain S288c is
phenotypically distinct from all of the other strains studied here, in terms of
stress sensitivity, gene expression, Ty copy number, mitochondrial content, and
gene-dosage control. These results highlight the value of understanding the
genetic basis of phenotypic variation and raise caution about using laboratory
strains for comparative genomics
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