Chandra Observations of A Galactic Supernova Remnant Vela Jr.: A New Sample of Thin Filaments Emitting Synchrotron X-Rays

A galactic supernova remnant (SNR) Vela Jr. (RX J0852.0$-$4622, G266.6$-$1.2) shows sharp filamentary structure on the north-western edge of the remnant in the hard X-ray band. The filaments are so smooth and located on the most outer side of the remnant. We measured the averaged scale width of the filaments ($w_u$ and $w_d$) with excellent spatial resolution of {\it Chandra}, which are in the order of the size of the point spread function of {\it Chandra} on the upstream side and 49.5 (36.0--88.8) arcsec on the downstream side, respectively. The spectra of the filaments are very hard and have no line-like structure, and were well reproduced with an absorbed power-law model with $\Gamma =$2.67 (2.55--2.77), or a {\tt SRCUT} model with $\nu_{rolloff}$ = 4.3 (3.4--5.3)$\times 10^{16}$ Hz under the assumption of $p=0.3$. These results imply that the hard X-rays are synchrotron radiation emitted by accelerated electrons, as mentioned previously. Using a correlation between a function ${\cal B} \equiv \nu_{rolloff}/w_d^2$ and the SNR age, we estimated the distance and the age of Vela Jr.: the estimated distance and age are 0.33 (0.26--0.50) kpc and 660 (420--1400) years, respectively. These results are consistent with previous reports, implying that ${\cal B}$--age relation may be a useful tool to estimate the distance and the age of synchrotron X-ray emitting SNRs.Comment: 19 pages, 8 figures, ApJ, in pres

Computationally designed libraries of fluorescent proteins evaluated by preservation and diversity of function

To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements made in vivo. Additional comparisons were made with a library constructed by error-prone PCR. Among the designed libraries, fluorescent function was preserved for the greatest fraction of samples in a library designed by using a structure-based computational method developed and described here. A trend was observed toward greater diversity of color in designed libraries that better preserved fluorescence. Contrary to trends observed among libraries constructed by error-prone PCR, preservation of function was observed to increase with a library's average mutation level among the four libraries designed with structure-based computational methods

High-Energy Neutrino Astronomy

Kilometer-scale neutrino detectors such as IceCube are discovery instruments covering nuclear and particle physics, cosmology and astronomy. Examples of their multidisciplinary missions include the search for the particle nature of dark matter and for additional small dimensions of space. In the end, their conceptual design is very much anchored to the observational fact that Nature accelerates protons and photons to energies in excess of $10^{20}$ and $10^{13}$ eV, respectively. The cosmic ray connection sets the scale of cosmic neutrino fluxes. In this context, we discuss the first results of the completed AMANDA detector and the reach of its extension, IceCube. Similar experiments are under construction in the Mediterranean. Neutrino astronomy is also expanding in new directions with efforts to detect air showers, acoustic and radio signals initiated by super-EeV neutrinos.Comment: 9 pages, Latex2e, uses ws-procs975x65standard.sty (included), 4 postscript figures. To appear in Proceedings of Thinking, Observing, and Mining the Universe, Sorrento, Italy, September 200

Regulatory modules controlling maize inflorescence architecture

Genetic control of branching is a primary determinant of yield, regulating seed number and harvesting ability, yet little is known about the molecular networks that shape grain-bearing inflorescences of cereal crops. Here, we used the maize (Zea mays) inflorescence to investigate gene networks that modulate determinacy, specifically the decision to allow branch growth. We characterized developmental transitions by associating spatiotemporal expression profiles with morphological changes resulting from genetic perturbations that disrupt steps in a pathway controlling branching. Developmental dynamics of genes targeted in vivo by the transcription factor RAMOSA1, a key regulator of determinacy, revealed potential mechanisms for repressing branches in distinct stem cell populations, including interactions with KNOTTED1, a master regulator of stem cell maintenance. Our results uncover discrete developmental modules that function in determining grass-specific morphology and provide a basis for targeted crop improvement and translation to other cereal crops with comparable inflorescence architectures

Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in a bone metastasis model of human breast cancer

Bone is one of the most frequent sites for metastasis in breast cancer patients often resulting in significant clinical morbidity and mortality. Bisphosphonates are currently the standard of care for breast cancer patients with bone metastasis. We have shown previously that doxycycline, a member of the tetracycline family of antibiotics, reduces total tumour burden in an experimental bone metastasis mouse model of human breast cancer. In this study, we combined doxycycline treatment together with zoledronic acid, the most potent bisphosphonate. Drug administration started 3 days before the injection of the MDA-MB-231 cells. When mice were administered zoledronic acid alone, the total tumour burden decreased by 43% compared to placebo treatment. Administration of a combination of zoledronic acid and doxycycline resulted in a 74% decrease in total tumour burden compared to untreated mice. In doxycycline- and zoledronate-treated mice bone formation was significantly enhanced as determined by increased numbers of osteoblasts, osteoid surface and volume, whereas a decrease in bone resorption was also observed. Doxycycline greatly reduced tumour burden and could also compensate for the increased bone resorption. The addition of zoledronate to the regimen further decreased tumour burden, caused an extensive decrease in bone-associated soft tissue tumour burden (93%), and sustained the bone volume, which could result in a smaller fracture risk. Treatment with zoledronic acid in combination with doxycycline may be very beneficial for breast cancer patients at risk for osteolytic bone metastasis

Anti-tumour activity of bisphosphonates in preclinical models of breast cancer

There is increasing evidence of anti-tumour effects of bisphosphonates from pre-clinical studies, supporting a role for these drugs beyond their traditional use in treatment of cancer-induced bone disease. A range of model systems have been used to investigate the effects of different bisphosphonates on tumour growth, both in bone and at peripheral sites. Most of these studies conclude that bisphosphonates cause a reduction in tumour burden, but that early intervention and the use of high and/or repeated dosing is required. Successful eradication of cancer may only be achievable by targeting the tumour cells directly whilst also modifying the tumour microenvironment. In line with this, bisphosphonates are demonstrated to be particularly effective at reducing breast tumour growth when used in combination with agents that directly target cancer cells. Recent studies have shown that the effects of bisphosphonates on breast tumours are not limited to bone, and that prolonged anti-tumour effects may be achieved following their inclusion in combination therapy. This has opened the field to a new strand of bisphosphonate research, focussed on elucidating their effects on cells and components of the local, regional and distal tumour microenvironment. This review highlights the recent developments in relation to proposed anti-tumour effects of bisphosphonates reported from in vitro and in vivo models, and summarises the data from key breast cancer studies. Evidence for effects on different processes and cell types involved in cancer development and progression is discussed, and the main outstanding issues identified

STAR: predicting recombination sites from amino acid sequence

BACKGROUND: Designing novel proteins with site-directed recombination has enormous prospects. By locating effective recombination sites for swapping sequence parts, the probability that hybrid sequences have the desired properties is increased dramatically. The prohibitive requirements for applying current tools led us to investigate machine learning to assist in finding useful recombination sites from amino acid sequence alone. RESULTS: We present STAR, Site Targeted Amino acid Recombination predictor, which produces a score indicating the structural disruption caused by recombination, for each position in an amino acid sequence. Example predictions contrasted with those of alternative tools, illustrate STAR'S utility to assist in determining useful recombination sites. Overall, the correlation coefficient between the output of the experimentally validated protein design algorithm SCHEMA and the prediction of STAR is very high (0.89). CONCLUSION: STAR allows the user to explore useful recombination sites in amino acid sequences with unknown structure and unknown evolutionary origin. The predictor service is available from