A pitfall of piecewise-polytropic equation of state inference

The only messenger radiation in the Universe which one can use to statistically probe the Equation of State (EOS) of cold dense matter is that originating from the near-field vicinities of compact stars. Constraining gravitational masses and equatorial radii of rotating compact stars is a major goal for current and future telescope missions, with a primary purpose of constraining the EOS. From a Bayesian perspective it is necessary to carefully discuss prior definition; in this context a complicating issue is that in practice there exist pathologies in the general relativistic mapping between spaces of local (interior source matter) and global (exterior spacetime) parameters. In a companion paper, these issues were raised on a theoretical basis. In this study we reproduce a probability transformation procedure from the literature in order to map a joint posterior distribution of Schwarzschild gravitational masses and radii into a joint posterior distribution of EOS parameters. We demonstrate computationally that EOS parameter inferences are sensitive to the choice to define a prior on a joint space of these masses and radii, instead of on a joint space interior source matter parameters. We focus on the piecewise-polytropic EOS model, which is currently standard in the field of astrophysical dense matter study. We discuss the implications of this issue for the field.Comment: 16 pages, 9 figures. Accepted for publication in MNRA

Unraveling the senses of Phytophthora; leads to novel control strategies?

Oomycetes cause devastating diseases on plants and animals. They cause major yield losses in many crop plants and their control heavily depends on agrochemicals. This is certainly true for the potato late blight pathogen Phytophthora infestans. Strong concerns about adverse effects of agrochemicals on food safety and environment are incentives for the development of novel, environmental friendly control strategies preferably based on natural products. Cyclic lipopeptides (CLPs) were recently discovered as a new class of natural compounds with strong activities against oomycetes including Phytophthora. CLPs lyse zoospores, inhibit mycelial growth and effectively reduce late blight disease. In order to unravel how Phytophthora senses CLPs and other environmental signals we follow two approaches. On the one hand, we monitor genome wide changes in gene expression induced by CLPs with the aim to identify the cellular pathways targeted by CLPs. On the other hand, we analyse components of ubiquitous signal transduction pathways with the aim to identify features that are unique for Phytophthora or oomycetes and, hence, could be suitable targets for novel anti-oomycete agents. Mining and comparing whole genome sequences have revealed that Phytophthora harbours many novel phospholipid modifying enzymes, unique for oomycetes. They have aberrant combinations of catalytic and regulatory domains occasionally combined with transmembrane domains. The latter resemble receptors that might be activated by extracellular ligands. Phospholipids, the substrates of these enzymes, are structural membrane components that also function in signalling. Together these findings open new avenues of research aimed at target-discovery in oomycetes

Activation of the STAT3/Acute Phase Response Factor Transcription Factor by Interleukin-5

The receptor for interleukin-5 (IL-5R) is composed of a unique a chain (IL-5Ra) expressed on eosinophils and basophils, associated with a bc subunit, which is shared by the receptors for IL-3 and granulocyte macrophagecolony stimulating factor. One of the molecular events activated via the IL-5R is the JAK/STAT signaling pathway. Recent reports have shown that IL-5 induces tyrosine phosphorylation of JAK2 followed by the subsequent cell type-specific activation of either STAT1a or STAT5. To identify additional STAT proteins activated by IL-5, we co-transfected the IL-5R with STAT cDNAs in COS cells. We found that IL-5 induces binding of STAT3 to the intercellular adhesion molecule-1 pIRE, and activates STAT3-dependent transcription. Moreover, endogenous STAT3 was tyrosine phosphorylated and activated in human IL-5-stimulated BaF3 cells ectopically expressing the human IL-5R (BaF3/IL5R). These data imply that multiple STAT proteins are involved in gene regulation by IL-5 in a cell type-specific manner. We further demonstrate using C-terminal truncations of the aand bc subunits of the IL-5R that the membrane-proximal regions of both subunits are required for STAT activation. Interestingly, a bc receptor mutant lacking intracellular tyrosine residues is able to mediate STAT3 activation, suggesting that tyrosine phosphorylation of the bc receptor is not essential for STAT3 activation

Differential Activation of Functionally Distinct STAT5 Proteins by IL-5 and GM-CSF During Eosinophil and Neutrophil Differentiation from Human CD34^+ Hematopoietic Stem Cells

Interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF) are important cytokines for the proliferation, differentiation, and acti-vation of myeloid lineages. The JAK/STAT pathway is one of the signaling pathways implicated in mediating biological responses induced by these cytokines. Previous studies have demonstrated that these cytokines predomi-nantly activate an 80 kDa STAT5 isoform in mature granulocytes. To better understand the role of STAT pro-teins during growth and differentiation of granulocytes, we evaluated differentiation of human CD34^+ hematopoi-etic stem cells ex vivo toward eosinophils and neutrophils. Bandshift experiments showed that in an early stage of both differentiation pathways (14 days), the 94 kDa STAT5B protein was activated by both IL-5 (eosino-phil lineage) and GM-CSF (neutrophil lineage). How-ever, during maturation of both lineages (days 21 and 28), increased expression of a functionally distinct 80 kDa STAT5 isoform was observed, resulting in het-erodimer DNA-binding complexes containing both the 94 and 80 kDa STAT5 proteins. The finding that functionally distinct isoforms of STAT5 are activated during the early and late differentiation stages of granulocytes suggests that they might be involved in regulating different biological functions in these cells

STAT3ß, a Splice Variant of Transcription Factor STAT3, Is a Dominant Negative Regulator of Transcription

The 89-kDa STAT3 protein is a latent transcription factor which is activated in response to cytokines (interleukin (IL)-5 and -6) and growth factors (epidermal growth factor). Binding of IL-5 to its specific receptor activates JAK2 which leads to the tyrosine phosphorylation of STAT3 proteins. Here we report the cloning of a cDNA encoding a variant of the transcription factor STAT3 (named STAT3b) which was isolated by screening an eosinophil cDNA library. Compared to wild-type STAT3, STAT3b lacks an internal domain of 50 base pairs located near the C terminus. This splice product is a naturally occurring isoform of STAT3 and encodes a 80-kDa protein. We found by reconstitution of the human IL-5R in COS cells that like STAT3, STAT3bis phosphorylated on tyrosine and binds to the pIRE from the ICAM-1 promoter after IL-5 stimulation. However, STAT3b fails to activate a pIRE containing promoter in transient transfection assays. Instead, co-expression of STAT3binhibits the transactivation potential of STAT3. These results suggests that STAT3b functions as a negative regulator of transcription

Training self-regulated learning skills with video modeling examples: Do task-selection skills transfer?

Self-assessment and task-selection skills are crucial in self-regulated learning situations in which students can choose their own tasks. Prior research suggested that training with video modeling examples, in which another person (the model) demonstrates and explains the cyclical process of problem-solving task performance, self-assessment, and task-selection, is effective for improving adolescents’ problem-solving posttest performance after self-regulated learning. In these examples, the models used a specific task-selection algorithm in which perceived mental effort and self-assessed performance scores were combined to determine the complexity and support level of the next task, selected from a task database. In the present study we aimed to replicate prior findings and to investigate whether transfer of task-selection skills would be facilitated even more by a more general, heuristic task-selection training than the task-specific algorithm. Transfer of task-selection skills was assessed by having students select a new task in another domain for a fictitious peer student. Results showed that both heuristic and algorithmic training of self-assessment and task-selection skills improved problem-solving posttest performance after a self-regulated learning phase, as well as transfer of task-selection skills. Heurist

Comparison of the roles of mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase signal transduction in neutrophil effector function

Although it is known that many stimuli can activate mitogen- activated protein kinases (MAPKs) and phosphatidylinositol 3- kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPKkinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony- stimulating factor, platelet-activating factor (PAF) and N-for- mylmethionyl-leucyl-phenylalanine are capable of activating both p44^(ERK1) and p42^(ERK2) MAPKs and phosphotyrosine-asso- ciated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21^(ras) by both tyrosine kinase and G-protein- coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, super- oxide generation, neutrophil migration and PAF release. In- cubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the acti- vation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2 . PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning

A Composite C/EBP Binding Site Is Essential for the Activity of the Promoter of the IL-3/IL-5/Granulocyte-Macrophage Colony-Stimulating Factor Receptor ßc Gene

The common ß-chain (ßc) is the main signaling component of the heterodimeric receptors for IL-3, IL-5, and GM-CSF and is primarily expressed on myeloid cells. The proximal ßc promoter is regulated by GGAA binding proteins, including PU.1, a hemopoietic specific member of the Ets family. However, it is not likely that PU.1 alone accounts for the myeloid-restricted expression of the ßc subunit. Here we describe the identification of a C/EBP binding enhancer that is located 2 kb upstream of the transcription start site. The enhancer contains two elements that bind C/EBPa and -ß in U937 cells, while C/EBPe is also bound in extracts of HL-60 cells. Importantly, deletion of the enhancer or mutation of either of one of the C/EBP sites results in a complete loss of promoter activity in cell lines as well as in primary cells, showing the importance of C/EBP members inßc gene activation. We further show that PU.1 has to cooperate with C/EBP proteins to induce bc transcription. Since the ßc is already expressed on CD341 cells, these results demonstrate that both C/EBP and PU.1 are not only important for the myeloid-specific gene regulation at later stages of myeloid differentiation