Detecting a stochastic gravitational wave background with the Laser Interferometer Space Antenna

The random superposition of many weak sources will produce a stochastic background of gravitational waves that may dominate the response of the LISA (Laser Interferometer Space Antenna) gravitational wave observatory. Unless something can be done to distinguish between a stochastic background and detector noise, the two will combine to form an effective noise floor for the detector. Two methods have been proposed to solve this problem. The first is to cross-correlate the output of two independent interferometers. The second is an ingenious scheme for monitoring the instrument noise by operating LISA as a Sagnac interferometer. Here we derive the optimal orbital alignment for cross-correlating a pair of LISA detectors, and provide the first analytic derivation of the Sagnac sensitivity curve.Comment: 9 pages, 11 figures. Significant changes to the noise estimate

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Genetic Relationships of Crown Rust Resistance, Grain Yield, Test Weight, and Seed Weight in Oat

Integrating selection for agronomic performance and quantitative resistance to crown rust, caused by Puccinia coronata Corda var. avenae W.P. Fraser & Ledingham, in oat (Avena sativa L.) requires an understanding of their genetic relationships. This study was conducted to investigate the genetic relationships of crown rust resistance, grain yield, test weight, and seed weight under both inoculated and fungicide-treated conditions. A Design II mating was performed between 10 oat lines with putative partial resistance to crown rust and nine lines with superior grain yield and grain quality potential. Progenies from this mating were evaluated in both crown rust-inoculated and fungicide-treated plots in four Iowa environments to estimate genetic effects and phenotypic correlations between crown rust resistance and grain yield, seed weight, and test weight under either infection or fungicide-treated conditions. Lines from a random-mated population derived from the same parents were evaluated in three Iowa environments to estimate heritabilities of, and genetic correlations between, these traits. Resistance to crown rust, as measured by area under the disease progress curve (AUDPC), was highly heritable (H = 0.89 on an entry-mean basis), and was favorably correlated with grain yield, seed weight, and test weight measured in crown rust-inoculated plots. AUDPC was unfavorably correlated or uncorrelated with grain yield, test weight, and seed weight measured in fungicide-treated plots. To improve simultaneously crown rust resistance, grain yield, and seed weight under both lower and higher levels of crown rust infection, an optimum selection index can be developed with the genetic parameters estimated in this stud

Low-power multi-chip module and board-level links for data transfer

Advanced device technologies such as Vertical Cavity Surface-Emitting Lasers (VCSELs) and diffractive micro lenses can be obtained with novel packaging techniques to allow low-power interconnection of parallel optical signals. These interconnections can be realized directly on circuit boards, in a multi-chip module format, or in packages that emulate electrical connectors. For applications such as stacking of Multi-Chip Module (MCM) layers, the links may be realized in bi-directional form using integrated diffractive microlenses. In the stacked MCM design, consumed electrical power is minimized by use of a relatively high laser output from high efficiency VCSELs, and a receiver design that is optimized for low power, at the expense of dynamic range. Within certain constraints, the design may be extended to other forms such as board-level interconnects

Why does fertilization reduce plant species diversity? Testing three competition-based hypotheses

1 Plant species diversity drops when fertilizer is added or productivity increases. To explain this, the total competition hypothesis predicts that competition above ground and below ground both become more important, leading to more competitive exclusion, whereas the light competition hypothesis predicts that a shift from below-ground to above-ground competition has a similar effect. The density hypothesis predicts that more above-ground competition leads to mortality of small individuals of all species, and thus a random loss of species from plots. 2 Fertilizer was added to old field plots to manipulate both below-ground and above-ground resources, while shadecloth was used to manipulate above-ground resources alone in tests of these hypotheses. 3 Fertilizer decreased both ramet density and species diversity, and the effect remained significant when density was added as a covariate. Density effects explained only a small part of the drop in diversity with fertilizer. 4 Shadecloth and fertilizer reduced light by the same amount, but only fertilizer reduced diversity. Light alone did not control diversity, as the light competition hypothesis would have predicted, but the combination of above-ground and below-ground competition caused competitive exclusion, consistent with the total competition hypothesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75695/1/j.1365-2745.2001.00662.x.pd

Nuclear receptors of the honey bee: annotation and expression in the adult brain

The Drosophila genome encodes 18 canonical nuclear receptors. All of the Drosophila nuclear receptors are here shown to be present in the genome of the honey bee (Apis mellifera). Given that the time since divergence of the Drosophila and Apis lineages is measured in hundreds of millions of years, the identification of matched orthologous nuclear receptors in the two genomes reveals the fundamental set of nuclear receptors required to ‘make’ an endopterygote insect. The single novelty is the presence in the A. mellifera genome of a third insect gene similar to vertebrate photoreceptor-specific nuclear receptor (PNR). Phylogenetic analysis indicates that this novel gene, which we have named AmPNR-like, is a new member of the NR2 subfamily not found in the Drosophila or human genomes. This gene is expressed in the developing compound eye of the honey bee. Like their vertebrate counterparts, arthropod nuclear receptors play key roles in embryonic and postembryonic development. Studies in Drosophila have focused primarily on the role of these transcription factors in embryogenesis and metamorphosis. Examination of an expressed sequence tag library developed from the adult bee brain and analysis of transcript expression in brain using in situ hybridization and quantitative RT-PCR revealed that several members of the nuclear receptor family (AmSVP, AmUSP, AmERR, AmHr46, AmFtz-F1, and AmHnf-4) are expressed in the brain of the adult bee. Further analysis of the expression of AmUSP and AmSVP in the mushroom bodies, the major insect brain centre for learning and memory, revealed changes in transcript abundance and, in the case of AmUSP, changes in transcript localization, during the development of foraging behaviour in the adult. Study of the honey bee therefore provides a model for understanding nuclear receptor function in the adult brain

Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype

Rationale: The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. Objectives: To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. Methods: A total of 118 participants younger than 19 years old with PCD were evaluated prospectively at six centers in North America using standardized procedures for diagnostic testing, spirometry, chest computed tomography, respiratory cultures, and clinical phenotyping. Measurements and Main Results: Clinical features included neonatal respiratory distress (82%), chronic cough (99%), and chronic nasal congestion (97%). There were no differences in clinical features or respiratory pathogens in subjects with outer dynein arm (ODA) defects (ODA alone; n = 54) and ODA plus inner dynein arm (IDA) defects (ODA 1 IDA; n = 18) versus subjects with IDA and central apparatus defects with microtubular disorganization (IDA/ CA/MTD; n = 40). Median FEV 1 was worse in the IDA/CA/MTD group (72% predicted) versus the combined ODA groups (92% predicted; P = 0.003). Median body mass index was lower in the IDA/ CA/MTD group (46th percentile) versus the ODA groups (70th percentile; P = 0.003). For all 118 subjects, median number of lobes with bronchiectasis was three and alveolar consolidation was two. However, the 5- to 11-year-old IDA/CA/MTD group had more lobes of bronchiectasis (median, 5; P = 0.0008) and consolidation (median, 3; P = 0.0001) compared with the ODA groups (median, 3 and 2, respectively). Similar findings were observed when limited to participants with biallelic mutations. Conclusions: Lung disease was heterogeneous across all ultrastructural and genotype groups, but worse in those with IDA/ CA/MTD ultrastructural defects, most of whom had biallelic mutations in CCDC39 or CCDC40