The 74MHz System on the Very Large Array

The Naval Research Laboratory and the National Radio Astronomy Observatory completed implementation of a low frequency capability on the VLA at 73.8 MHz in 1998. This frequency band offers unprecedented sensitivity (~25 mJy/beam) and resolution (~25 arcsec) for low-frequency observations. We review the hardware, the calibration and imaging strategies, comparing them to those at higher frequencies, including aspects of interference excision and wide-field imaging. Ionospheric phase fluctuations pose the major difficulty in calibrating the array. Over restricted fields of view or at times of extremely quiescent ionospheric ``weather'', an angle-invariant calibration strategy can be used. In this approach a single phase correction is devised for each antenna, typically via self-calibration. Over larger fields of view or at times of more normal ionospheric ``weather'' when the ionospheric isoplanatic patch size is smaller than the field of view, we adopt a field-based strategy in which the phase correction depends upon location within the field of view. This second calibration strategy was implemented by modeling the ionosphere above the array using Zernike polynomials. Images of 3C sources of moderate strength are provided as examples of routine, angle-invariant calibration and imaging. Flux density measurements indicate that the 74 MHz flux scale at the VLA is stable to a few percent, and tied to the Baars et al. value of Cygnus A at the 5 percent level. We also present an example of a wide-field image, devoid of bright objects and containing hundreds of weaker sources, constructed from the field-based calibration. We close with a summary of lessons the 74 MHz system offers as a model for new and developing low-frequency telescopes. (Abridged)Comment: 73 pages, 46 jpeg figures, to appear in ApJ

Probing Cation Antisite Disorder in Gd2Ti2O7 Pyrochlore by Site-specific NEXAFS and XPS

Disorder in Gd2Ti2O7 is investigated by near-edge x-ray-absorption fine structure (NEXAFS) and x-ray photoelectron spectroscopy (XPS). NEXAFS shows Ti4+ ions occupy octahedral sites with a tetragonal distortion induced by vacant oxygen sites. O 1s XPS spectra obtained with a charge neutralization system from Gd2Ti2O7(100) and the Gd2Ti2O7 pyrochlore used by Chen et al. [Phys. Rev. Lett. 88, 105901 (2002)], both yielded a single peak, unlike the previous result on the latter that found two peaks. The current results give no evidence for an anisotropic distribution of Ti and O. The extra features reported in the aforementioned communication resulted from charging effects and incomplete surface cleaning. Thus, a result confirming the direct observation of simultaneous cation-anion antisite disordering and lending credence to the split vacancy model has been clarified

Extracellular Heat Shock Protein (Hsp)70 and Hsp90α Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion

Breast cancer is second only to lung cancer in cancer-related deaths in women, and the majority of these deaths are caused by metastases. Obtaining a better understanding of migration and invasion, two early steps in metastasis, is critical for the development of treatments that inhibit breast cancer metastasis. In a functional proteomic screen for proteins required for invasion, extracellular heat shock protein 90 alpha (Hsp90α) was identified and shown to activate matrix metalloproteinase 2 (MMP-2). The mechanism of MMP-2 activation by Hsp90α is unknown. Intracellular Hsp90α commonly functions with a complex of co-chaperones, leading to our hypothesis that Hsp90α functions similarly outside of the cell. In this study, we show that a complex of co-chaperones outside of breast cancer cells assists Hsp90α mediated activation of MMP-2. We demonstrate that the co-chaperones Hsp70, Hop, Hsp40, and p23 are present outside of breast cancer cells and co-immunoprecipitate with Hsp90α in vitro and in breast cancer conditioned media. These co-chaperones also increase the association of Hsp90α and MMP-2 in vitro. This co-chaperone complex enhances Hsp90α-mediated activation of MMP-2 in vitro, while inhibition of Hsp70 in conditioned media reduces this activation and decreases cancer cell migration and invasion. Together, these findings support a model in which MMP-2 activation by an extracellular co-chaperone complex mediated by Hsp90α increases breast cancer cell migration and invasion. Our studies provide insight into a novel pathway for MMP-2 activation and suggest Hsp70 as an additional extracellular target for anti-metastatic drug development

Molecular Characterization of NRXN1 Deletions from 19,263 Clinical Microarray Cases Identifies Exons Important for Neurodevelopmental Disease Expression

PURPOSE: The purpose of the current study was to assess the penetrance of NRXN1 deletions. METHODS: We compared the prevalence and genomic extent of NRXN1 deletions identified among 19,263 clinically referred cases to that of 15,264 controls. The burden of additional clinically relevant copy-number variations (CNVs) was used as a proxy to estimate the relative penetrance of NRXN1 deletions. RESULTS: We identified 41 (0.21%) previously unreported exonic NRXN1 deletions ascertained for developmental delay/intellectual disability that were significantly greater than in controls (odds ratio (OR) = 8.14; 95% confidence interval (CI): 2.91-22.72; P \u3c 0.0001). Ten (22.7%) of these had a second clinically relevant CNV. Subjects with a deletion near the 3\u27 end of NRXN1 were significantly more likely to have a second rare CNV than subjects with a 5\u27 NRXN1 deletion (OR = 7.47; 95% CI: 2.36-23.61; P = 0.0006). The prevalence of intronic NRXN1 deletions was not statistically different between cases and controls (P = 0.618). The majority (63.2%) of intronic NRXN1 deletion cases had a second rare CNV at a prevalence twice as high as that for exonic NRXN1 deletion cases (P = 0.0035). CONCLUSIONS: The results support the importance of exons near the 5\u27 end of NRXN1 in the expression of neurodevelopmental disorders. Intronic NRXN1 deletions do not appear to substantially increase the risk for clinical phenotypes.Genet Med 19 1, 53-61

Genetic and transcriptomic analysis of transcription factor genes in the model halophilic Archaeon: coordinate action of TbpD and TfbA

<p>Abstract</p> <p>Background</p> <p>Archaea are prokaryotic organisms with simplified versions of eukaryotic transcription systems. Genes coding for the general transcription factors TBP and TFB are present in multiple copies in several Archaea, including <it>Halobacterium </it>sp. NRC-1. Multiple TBP and TFBs have been proposed to participate in transcription of genes via recognition and recruitment of RNA polymerase to different classes of promoters.</p> <p>Results</p> <p>We attempted to knock out all six TBP and seven TFB genes in <it>Halobacterium </it>sp. NRC-1 using the <it>ura</it>3-based gene deletion system. Knockouts were obtained for six out of thirteen genes, <it>tbp</it>CDF and <it>tfb</it>ACG, indicating that they are not essential for cell viability under standard conditions. Screening of a population of 1,000 candidate mutants showed that genes which did not yield mutants contained less that 0.1% knockouts, strongly suggesting that they are essential. The transcriptomes of two mutants, Δ<it>tbp</it>D and Δ<it>tfb</it>A, were compared to the parental strain and showed coordinate down regulation of many genes. Over 500 out of 2,677 total genes were regulated in the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutants with 363 regulated in both, indicating that over 10% of genes in both strains require the action of both TbpD and TfbA for normal transcription. Culturing studies on the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains showed them to grow more slowly than the wild-type at an elevated temperature, 49°C, and they showed reduced viability at 56°C, suggesting TbpD and TfbA are involved in the heat shock response. Alignment of TBP and TFB protein sequences suggested the expansion of the TBP gene family, especially in <it>Halobacterium </it>sp. NRC-1, and TFB gene family in representatives of five different genera of haloarchaea in which genome sequences are available.</p> <p>Conclusion</p> <p>Six of thirteen TBP and TFB genes of <it>Halobacterium </it>sp. NRC-1 are non-essential under standard growth conditions. TbpD and TfbA coordinate the expression of over 10% of the genes in the NRC-1 genome. The Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains are temperature sensitive, possibly as a result of down regulation of heat shock genes. Sequence alignments suggest the existence of several families of TBP and TFB transcription factors in <it>Halobacterium </it>which may function in transcription of different classes of genes.</p

Radio & Optical Interferometry: Basic Observing Techniques and Data Analysis

Astronomers usually need the highest angular resolution possible, but the blurring effect of diffraction imposes a fundamental limit on the image quality from any single telescope. Interferometry allows light collected at widely-separated telescopes to be combined in order to synthesize an aperture much larger than an individual telescope thereby improving angular resolution by orders of magnitude. Radio and millimeter wave astronomers depend on interferometry to achieve image quality on par with conventional visible and infrared telescopes. Interferometers at visible and infrared wavelengths extend angular resolution below the milli-arcsecond level to open up unique research areas in imaging stellar surfaces and circumstellar environments. In this chapter the basic principles of interferometry are reviewed with an emphasis on the common features for radio and optical observing. While many techniques are common to interferometers of all wavelengths, crucial differences are identified that will help new practitioners avoid unnecessary confusion and common pitfalls. Concepts essential for writing observing proposals and for planning observations are described, depending on the science wavelength, angular resolution, and field of view required. Atmospheric and ionospheric turbulence degrades the longest-baseline observations by significantly reducing the stability of interference fringes. Such instabilities represent a persistent challenge, and the basic techniques of phase-referencing and phase closure have been developed to deal with them. Synthesis imaging with large observing datasets has become a routine and straightforward process at radio observatories, but remains challenging for optical facilities. In this context the commonly-used image reconstruction algorithms CLEAN and MEM are presented. Lastly, a concise overview of current facilities is included as an appendix.Comment: 45 pages, 14 Figures; an abridged version of a chapter to appear in Volume 2 of Planets, Stars and Stellar Systems, to be published in 2011 by Springe