Design and Optimization of Physical Waveform-Diverse and Spatially-Diverse Radar Emissions

With the advancement of arbitrary waveform generation techniques, new radar transmission modes can be designed via precise control of the waveform's time-domain signal structure. The finer degree of emission control for a waveform (or multiple waveforms via a digital array) presents an opportunity to reduce ambiguities in the estimation of parameters within the radar backscatter. While this freedom opens the door to new emission capabilities, one must still consider the practical attributes for radar waveform design. Constraints such as constant amplitude (to maintain sufficient power efficiency) and continuous phase (for spectral containment) are still considered prerequisites for high-powered radar waveforms. These criteria are also applicable to the design of multiple waveforms emitted from an antenna array in a multiple-input multiple-output (MIMO) mode. In this work, three spatially-diverse radar emission design methods are introduced that provide constant amplitude, spectrally-contained waveforms implemented via a digital array radar (DAR). The first design method, denoted as spatial modulation, designs the radar waveforms via a polyphase-coded frequency-modulated (PCFM) framework to steer the coherent mainbeam of the emission within a pulse. The second design method is an iterative scheme to generate waveforms that achieve a desired wideband and/or widebeam radar emission. However, a wideband and widebeam emission can place a portion of the emitted energy into what is known as the `invisible' space of the array, which is related to the storage of reactive power that can damage a radar transmitter. The proposed design method purposefully avoids this space and a quantity denoted as the Fractional Reactive Power (FRP) is defined to assess the quality of the result. The third design method produces simultaneous radar and communications beams in separate spatial directions while maintaining constant modulus by leveraging the orthogonal complement of the emitted directions. This orthogonal energy defines a trade-space between power efficiency gained from constraining waveforms to be constant amplitude and power efficiency lost by emitting energy in undesired directions. The design of FM waveforms via traditional gradient-based optimization methods is also considered. A waveform model is proposed that is a generalization of the PCFM implementation, denoted as coded-FM (CFM), which defines the phase of the waveform via a summation of weighted, predefined basis functions. Therefore, gradient-based methods can be used to minimize a given cost function with respect to a finite set of optimizable parameters. A generalized integrated sidelobe level (GISL) metric is used as the optimization cost function to minimize the correlation range sidelobes of the radar waveform. System specific waveform optimization is explored by incorporating the linear models of three different loopback configurations into the GISL metric to match the optimized waveforms to the particular systems

Characterization and expression analysis of Staphylococcus aureus pathogenicity island 3 - Implications for the evolution of staphylococcal pathogenicity islands

We describe the complete sequence of the 15.9-kb staphylococcal pathogenicity island 3 encoding staphylococcal enterotoxin serotypes B, K, and Q. The island, which meets the generally accepted definition of pathogenicity islands, contains 24 open reading frames potentially encoding proteins of more than 50 amino acids, including an apparently functional integrase. The element is bordered by two 17-bp direct repeats identical to those found flanking staphylococcal pathogenicity island 1. The island has extensive regions of homology to previously described pathogenicity islands, particularly staphylococcal pathogenicity islands 1 and bov. The expression of 22 of the 24 open reading frames contained on staphylococcal pathogenicity island 3 was detected either in vitro during growth in a laboratory medium or serum or in vivo in a rabbit model of toxic shock syndrome using DNA microarrays. The effect of oxygen tension on staphylococcal pathogenicity island 3 gene expression was also examined. By comparison with the known staphylococcal pathogenicity islands in the context of gene expression described here, we propose a model of pathogenicity island origin and evolution involving specialized transduction events and addition, deletion, or recombination of pathogenicity island "modules.

Intraoperative Radiation Therapy for Breast Cancer: Technical Notes

Abstract: Interest in intraoperative radiation therapy (IORT) for breast cancer is increasing as the possible benefits of this technique for the patient become apparent. The rationale for the use of this segmental radiation therapy in place of whole-breast irradiation is based on the finding that approximately 85% of breast relapses are confined to the same quadrant of the breast as the primary tumor. Phase I and II trials have demonstrated no increase in postsurgical complication rates following the use of single-dose IORT in localized breast cancers. Longer follow-up is needed to assess the cosmetic outcome. Clinical trials to evaluate the effectiveness of IORT in the treatment of breast cancer are currently under way at the European Institute of Oncology (EIO) at the University of Milan, Italy, and at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York. Here we report the two different techniques in use in these trials

Food and temperature stressors have opposing effects in determining flexible migration decisions in brown trout (Salmo trutta)

With rapid global change, organisms in natural systems are exposed to a multitude of stressors that likely co‐occur, with uncertain impacts. We explored individual and cumulative effects of co‐occurring environmental stressors on the striking, yet poorly understood, phenomenon of facultative migration. We reared offspring of a brown trout population that naturally demonstrates facultative anadromy (sea migration), under different environmental stressor treatments and measured life history responses in terms of migratory tactics and freshwater maturation rates. Juvenile fish were exposed to reduced food availability, temperatures elevated to 1.8°C above natural conditions or both treatments in combination over 18 months of experimental tank rearing. When considered in isolation, reduced food had negative effects on the size, mass and condition of fish across the experiment. We detected variable effects of warm temperatures (negative effects on size and mass, but positive effect on lipids). When combined with food restriction, temperature effects on these traits were less pronounced, implying antagonistic stressor effects on morphological traits. Stressors combined additively, but had opposing effects on life history tactics: migration increased and maturation rates decreased under low food conditions, whereas the opposite occurred in the warm temperature treatment. Not all fish had expressed maturation or migration tactics by the end of the study, and the frequency of these ‘unassigned’ fish was higher in food deprivation treatments, but lower in warm treatments. Fish showing migration tactics were smaller and in poorer condition than fish showing maturation tactics, but were similar in size to unassigned fish. We further detected effects of food restriction on hypo‐osmoregulatory function of migrants that may influence the fitness benefits of the migratory tactic at sea. We also highlight that responses to multiple stressors may vary depending on the response considered. Collectively, our results indicate contrasting effects of environmental stressors on life history trajectories in a facultatively migratory species

mTOR-dependent translation amplifies microglia priming in aging mice.

peer reviewedMicroglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR complex 1 signaling controlling translation, as well as protein levels of inflammatory mediators. Genetic ablation of mTOR signaling showed a dual yet contrasting effect on microglia priming: it caused an NF-κB-dependent upregulation of priming genes at the mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation, and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1, resulting in decreased binding of eIF4E to eIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating that upregulation of mTOR-dependent translation is an essential aspect of microglia priming in aging and neurodegeneration

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

BACKGROUND: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. METHODOLOGY/PRINCIPAL FINDINGS: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing the NR3C1 gene in the hippocampus of adult rats. Natural variations in maternal care are associated with coordinate epigenetic changes spanning over a hundred kilobase pairs. The adult offspring of high compared to low maternal care mothers show epigenetic changes in promoters, exons, and gene ends associated with higher transcriptional activity across many genes within the locus examined. Other genes in this region remain unchanged, indicating a clustered yet specific and patterned response. Interestingly, the chromosomal region containing the protocadherin-α, -β, and -γ (Pcdh) gene families implicated in synaptogenesis show the highest differential response to maternal care. CONCLUSIONS/SIGNIFICANCE: The results suggest for the first time that the epigenetic response to maternal care is coordinated in clusters across broad genomic areas. The data indicate that the epigenetic response to maternal care involves not only single candidate gene promoters but includes transcriptional and intragenic sequences, as well as those residing distantly from transcription start sites. These epigenetic and transcriptional profiles constitute the first tiling microarray data set exploring the relationship between epigenetic modifications and RNA expression in both protein coding and non-coding regions across a chromosomal locus in the mammalian brain

Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead