Performance of a second-generation PFB pilot plant combustor

Second-generation on pressurized fluidized bed combustion (PFBC) plants promise higher efficiency with lower costs of electricity and lower stack emissions. With a conventional reheat cycle and a 3-percent sulfur Pittsburgh No. 8 coal, a 45-percent efficiency (HHV of coal basis) and a cost of electricity {approximately}20 percent lower than that of a pulverized-coal-fired plant with stack gas scrubbing are being projected. This advanced plant concept incorporates three major steps: carbonization, circulating fluidized bed combustion and topping combustion. Foster Wheeler Development Corporation has constructed and operated a second-generation PFB pilot plant at the Foster Wheeler research facility (the John Blizard Research Center) in Livingston, New Jersey. Results of the pilot plant combustor portion of the test program supporting the development of this new type of plant are presented. The fuels evaluated in this test program included several char-sorbent residues produced in a pressurized carbonizer pilot plant and their parent coals. The data confirmed the viability of the PFB combustor concept in terms of both combustion and emissions performance

Endocrine disruptor compounds-a cause of impaired immune tolerance driving inflammatory disorders of pregnancy?

Endocrine disrupting compounds (EDCs) are prevalent and ubiquitous in our environment and have substantial potential to compromise human and animal health. Amongst the chronic health conditions associated with EDC exposure, dysregulation of reproductive function in both females and males is prominent. Human epidemiological studies demonstrate links between EDC exposure and infertility, as well as gestational disorders including miscarriage, fetal growth restriction, preeclampsia, and preterm birth. Animal experiments show EDCs administered during gestation, or to either parent prior to conception, can interfere with gamete quality, embryo implantation, and placental and fetal development, with consequences for offspring viability and health. It has been presumed that EDCs operate principally through disrupting hormone-regulated events in reproduction and fetal development, but EDC effects on maternal immune receptivity to pregnancy are also implicated. EDCs can modulate both the innate and adaptive arms of the immune system, to alter inflammatory responses, and interfere with generation of regulatory T (Treg) cells that are critical for pregnancy tolerance. Effects of EDCs on immune cells are complex and likely exerted by both steroid hormone-dependent and hormone-independent pathways. Thus, to better understand how EDCs impact reproduction and pregnancy, it is imperative to consider how immune-mediated mechanisms are affected by EDCs. This review will describe evidence that several EDCs modify elements of the immune response relevant to pregnancy, and will discuss the potential for EDCs to disrupt immune tolerance required for robust placentation and optimal fetal development.John E. Schjenken, Ella S. Green, Tenuis S. Overduin, Chui Yan Mah, Darryl L. Russell and Sarah A. Robertso

Least Squares and Shrinkage Estimation under Bimonotonicity Constraints

In this paper we describe active set type algorithms for minimization of a smooth function under general order constraints, an important case being functions on the set of bimonotone r-by-s matrices. These algorithms can be used, for instance, to estimate a bimonotone regression function via least squares or (a smooth approximation of) least absolute deviations. Another application is shrinkage estimation in image denoising or, more generally, regression problems with two ordinal factors after representing the data in a suitable basis which is indexed by pairs (i,j) in {1,...,r}x{1,...,s}. Various numerical examples illustrate our methods

Northern European trees show a progressively diminishing response to increasing atmospheric carbon dioxide concentrations

In order to predict accurately how elevated atmospheric CO2 concentrations will affect the global carbon cycle, it is necessary to know how trees respond to increasing CO2 concentrations. In this paper we examine the response over the period AD 1895 – 1994 of three tree species growing across northern Europe to increases in atmospheric CO2 concentrations using parameters derived from stable carbon isotope ratios of trunk cellulose. Using the isotope data we calculate values of intrinsic water-use efficiency (IWUE) and intercellular CO2 concentrations in the leaf (ci). Our results show that trees have responded to higher levels of atmospheric CO2 by increasing IWUE whilst generally maintaining constant ci values. However, the IWUE of most of the trees in this study has not continued to rise in line with increasing atmospheric CO2. This behaviour has implications for estimations of future terrestrial carbon storage

Characterizing the Diverse Mutational Pathways Associated with R5-Tropic Maraviroc Resistance: HIV-1 That Uses the Drug-Bound CCR5 Coreceptor

YesABSTRACT Entry inhibitors represent a potent class of antiretroviral drugs that target a host cell protein, CCR5, an HIV-1 entry coreceptor, and not viral protein. Lack of sensitivity can occur due to preexisting virus that uses the CXCR4 coreceptor, while true resistance occurs through viral adaptation to use a drug-bound CCR5 coreceptor. To understand this R5 resistance pathway, we analyzed >500 envelope protein sequences and phenotypes from viruses of 20 patients from the clinical trials MOTIVATE 1 and 2, in which treatment-experienced patients received maraviroc plus optimized background therapy. The resistant viral population was phylogenetically distinct and associated with a genetic bottleneck in each patient, consistent with de novo emergence of resistance. Recombination analysis showed that the C2-V3-C3 region tends to genotypically correspond to the recombinant’s phenotype, indicating its primary importance in conferring resistance. Between patients, there was a notable lack of commonality in the specific sites conferring resistance, confirming the unusual nature of R5-tropic resistance. We used coevolutionary and positive-selection analyses to characterize the genotypic determinants of resistance and found that (i) there are complicated covariation networks, indicating frequent coevolutionary/compensatory changes in the context of protein structure; (ii) covarying sites under positive selection are enriched in resistant viruses; (iii) CD4 binding sites form part of a unique covariation network independent of the V3 loop; and (iv) the covariation network formed between the V3 loop and other regions of gp120 and gp41 intersects sites involved in glycosylation and protein secretion. These results demonstrate that while envelope sequence mutations are the key to conferring maraviroc resistance, the specific changes involved are context dependent and thus inherently unpredictable. IMPORTANCE The entry inhibitor drug maraviroc makes the cell coreceptor CCR5 unavailable for use by HIV-1 and is now used in combination antiretroviral therapy. Treatment failure with drug-resistant virus is particularly interesting because it tends to be rare, with lack of sensitivity usually associated with the presence of CXCR4-using virus (CXCR4 is the main alternative coreceptor HIV-1 uses, in addition to CD4). We analyzed envelope sequences from HIV-1, obtained from 20 patients who enrolled in maraviroc clinical trials and experienced treatment failure, without detection of CXCR4-using virus. Evolutionary analysis was employed to identify molecular changes that confer maraviroc resistance. We found that in these individuals, resistant viruses form a distinct population that evolved once and was successful as a result of drug pressure. Further evolutionary analysis placed the complex network of interdependent mutational changes into functional groups that help explain the impediments to the emergence of maraviroc-associated R5 drug resistance.X.J. was supported by Medical Research Council (G1001806/1) and Wellcome Trust (097820/Z/11/A) funding and F.F. by a Biotechnology and Biological Sciences Research Council studentship to D.L.R

Overview of the SME: Implications and Phenomenology of Lorentz Violation

The Standard Model Extension (SME) provides the most general observer-independent field theoretical framework for investigations of Lorentz violation. The SME lagrangian by definition contains all Lorentz-violating interaction terms that can be written as observer scalars and that involve particle fields in the Standard Model and gravitational fields in a generalized theory of gravity. This includes all possible terms that could arise from a process of spontaneous Lorentz violation in the context of a more fundamental theory, as well as terms that explicitly break Lorentz symmetry. An overview of the SME is presented, including its motivations and construction. Some of the theoretical issues arising in the case of spontaneous Lorentz violation are discussed, including the question of what happens to the Nambu-Goldstone modes when Lorentz symmetry is spontaneously violated and whether a Higgs mechanism can occur. A minimal version of the SME in flat Minkowski spacetime that maintains gauge invariance and power-counting renormalizability is used to search for leading-order signals of Lorentz violation. Recent Lorentz tests in QED systems are examined, including experiments with photons, particle and atomic experiments, proposed experiments in space and experiments with a spin-polarized torsion pendulum.Comment: 40 pages, Talk presented at Special Relativity: Will it Survive the Next 100 Years? Potsdam, Germany, February, 200

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

Advancement in the pressureless sintering of CP titanium using high-frequency induction heating

High-frequency induction heating is applied as an alternative heating source for pressureless sintering of commercially pure Ti powders, aiming to intensify the sintering process. The effects of the process parameters on the properties of the sintered material are systematically studied. The initial powder compact density is the most influential parameter permitting sintered structures with highly porous to almost fully dense appearance. Short heating time combined with sintering to temperatures just above the β-transus resulted in a strong diffusion bonding between the Ti powder particles, and grain growth is observed at the former boundaries of the neighboring powder particles. The dimpled appearance of the fracture surface at those regions confirmed the strong metallic interparticle bonding. Tensile properties comparable to those of Ti-Grade 3 and Ti-Grade 4 are achieved, which also demonstrates the efficiency of the induction sintering process. A mechanism explaining the fast and efficient sintering is proposed. The process has the added advantage of minimizing the oxygen pickup

Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR