Frequency invariant beamforming for two-dimensional and three-dimensional arrays

A novel method for the design of two-dimensional (2-D) and three-dimensional (3-D)arrays with frequency invariant beam patterns is proposed. By suitable substitu- tions, the beam pattern of a 2-D or 3-D arrays can be regarded as the 3-D or 4-D Fourier transform of its spatial and temporal parameters. Since frequency invariance can be easily imposed in the Fourier domain, a simple design method is derived. Design examples for the 2-D case are provided

Single-Phase Rare-Earth Oxide/Aluminum Oxide Glasses

Glasses that comprise rare-earth oxides and aluminum oxide plus, optionally, lesser amounts of other oxides, have been invented. The other oxide(s) can include SiO2, B2O3, GeO2, and/or any of a variety of glass-forming oxides that have been used heretofore in making a variety of common and specialty glasses. The glasses of the invention can be manufactured in bulk single-phase forms to ensure near uniformity in optical and mechanical characteristics, as needed for such devices as optical amplifiers, lasers, and optical waveguides (including optical fibers). These glasses can also be formulated to have high indices of refraction, as needed in some of such devices

Exploring pulse shaping for Z using graded-density impactors on gas guns (final report for LDRD project 79879).

While isentropic compression experiment (ICE) techniques have proved useful in deducing the high-pressure compressibility of a wide range of materials, they have encountered difficulties where large-volume phase transitions exist. The present study sought to apply graded-density impactor methods for producing isentropic loading to planar impact experiments to selected such problems. Cerium was chosen due to its 20% compression between 0.7 and 1.0 GPa. A model was constructed based on limited earlier dynamic data, and applied to the design of a suite of experiments. A capability for handling this material was installed. Two experiments were executed using shock/reload techniques with available samples, loading initially to near the gamma-alpha transition, then reloading. As well, two graded-density impactor experiments were conducted with alumina. A method for interpreting ICE data was developed and validated; this uses a wavelet construction for the ramp wave and includes corrections for the ''diffraction'' of wavelets by releases or reloads reflected from the sample/window interface. Alternate methods for constructing graded-density impactors are discussed

Complex interactions of HIV-1 nucleocapsid protein with oligonucleotides

The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of this activity, it plays a crucial role in virus replication as a cofactor during reverse transcription, and is probably important in other steps of the replication cycle as well. We previously reported that NC binds with high-affinity to the repeating sequence d(TG)(n). We have now analyzed the interaction between NC and d(TG)(4) in considerable detail, using surface plasmon resonance (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA), isothermal titration calorimetry (ITC) and electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). Our results show that the interactions between these two molecules are surprisngly complex: while the K(d) for binding of a single d(TG)(4) molecule to NC is only ∼5 nM in 150 mM NaCl, a single NC molecule is capable of interacting with more than one d(TG)(4) molecule, and conversely, more than one NC molecule can bind to a single d(TG)(4) molecule. The strengths of these additional binding reactions are quantitated. The implications of this multivalency for the functions of NC in virus replication are discussed

Ibuprofen inhibits colitis-induced overexpression of tumor-related Rac1b

The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene which are sufficient for initiation of hyperplastic growth but not for tumor progression. The analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant B-Raf and both events were shown to cooperate in tumor cell survival. Here we provide evidence for increased expression of Rac1b in samples from inflammatory bowel disease patients as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the non-steroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumour cells through a cyclooxygenase inhibition-independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely inflammation can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors and in cancer prophylaxis following colon inflammation disorders

HECTD2, a candidate susceptibility gene for Alzheimer's disease on 10q

Background: Late onset Alzheimer's disease (LOAD) is a neurodegenerative disorder characterised by the deposition of amyloid plaques and neurofibrillary tangles in the brain and is the major cause of dementia. Multiple genetic loci, including 10q, have been implicated in LOAD but to date, with the exception of APOE, the underlying genes have not been identified. HECTD2 maps to 10q and has been implicated in susceptibility to human prion diseases which are also neurodegenerative conditions associated with accumulation of misfolded host proteins. In this study we test whether the HECTD2 susceptibility allele seen in prion disease is also implicated in LOAD.Methods: DNA from 320 individuals with Alzheimer's disease and 601 controls were genotyped for a HECTD2 intronic tagging SNP, rs12249854 (A/T). Groups were further analysed following stratification by APOE genotype.Results: The rs12249854 minor allele (A) frequency was higher (5.8%) in the Alzheimer's disease group as compared to the controls (3.9%), however, this was not statistically significant (P = 0.0668). No significant difference was seen in minor allele frequency in the presence or absence of the APOE epsilon 4 allele.Conclusion: The common haplotypes of HECTD2, tagged by rs12249854, are not associated with susceptibility to LOAD

The Soft Power of Anglia: British Cold War Cultural Diplomacy in the USSR

This article contributes to the growing literature on the cultural Cold War through an exploration of the British national projection magazine Anglia, produced by the Foreign Office for distribution in the USSR from 1962 to 1992. As well as drawing attention to the significance of national magazines in general, the article sheds light on Britain's distinctive approach to propaganda and cultural diplomacy during the Cold War. It considers why the magazine was set up and endured for so long, despite considerable reservations about its value. It examines how Britain was projected in a manner that accorded with British understandings about the need for ‘subtle’ propaganda. Finally, it addresses the question of the magazine's impact in the USSR

Association of Estimated Glomerular Filtration Rate and Urinary Uromodulin Concentrations with Rare Variants Identified by UMOD Gene Region Sequencing

Background: Recent genome-wide association studies (GWAS) have identified common variants in the UMOD region associated with kidney function and disease in the general population. To identify novel rare variants as well as common variants that may account for this GWAS signal, the exons and 4 kb upstream region of UMOD were sequenced. Methodology/Principal Findings Individuals (n = 485) were selected based on presence of the GWAS risk haplotype and chronic kidney disease (CKD) in the ARIC Study and on the extremes of of the UMOD gene product, uromodulin, in urine (Tamm Horsfall protein, THP) in the Framingham Heart Study (FHS). Targeted sequencing was conducted using capillary based Sanger sequencing (3730 DNA Analyzer). Variants were tested for association with THP concentrations and estimated glomerular filtration rate (eGFR), and identified non-synonymous coding variants were genotyped in up to 22,546 follow-up samples. Twenty-four and 63 variants were identified in the 285 ARIC and 200 FHS participants, respectively. In both studies combined, there were 33 common and 54 rare (MAF<0.05) variants. Five non-synonymous rare variants were identified in FHS; borderline enrichment of rare variants was found in the extremes of THP (SKAT p-value = 0.08). Only V458L was associated with THP in the FHS general-population validation sample (p = 9*10$^{−3}$, n = 2,522), but did not show direction-consistent and significant association with eGFR in both the ARIC (n = 14,635) and FHS (n = 7,520) validation samples. Pooling all non-synonymous rare variants except V458L together showed non-significant associations with THP and eGFR in the FHS validation sample. Functional studies of V458L revealed no alternations in protein trafficking. Conclusions/Significance: Multiple novel rare variants in the UMOD region were identified, but none were consistently associated with eGFR in two independent study samples. Only V458L had modest association with THP levels in the general population and thus could not account for the observed GWAS signal