Time-of-arrival distributions from position-momentum and energy-time joint measurements

The position-momentum quasi-distribution obtained from an Arthurs and Kelly joint measurement model is used to obtain indirectly an ``operational'' time-of-arrival (TOA) distribution following a quantization procedure proposed by Kocha\'nski and W\'odkiewicz [Phys. Rev. A 60, 2689 (1999)]. This TOA distribution is not time covariant. The procedure is generalized by using other phase-space quasi-distributions, and sufficient conditions are provided for time covariance that limit the possible phase-space quasi-distributions essentially to the Wigner function, which, however, provides a non-positive TOA quasi-distribution. These problems are remedied with a different quantization procedure which, on the other hand, does not guarantee normalization. Finally an Arthurs and Kelly measurement model for TOA and energy (valid also for arbitrary conjugate variables when one of the variables is bounded from below) is worked out. The marginal TOA distribution so obtained, a distorted version of Kijowski's distribution, is time covariant, positive, and normalized

The Chiral Potts Models Revisited

In honor of Onsager's ninetieth birthday, we like to review some exact results obtained so far in the chiral Potts models and to translate these results into language more transparent to physicists, so that experts in Monte Carlo calculations, high and low temperature expansions, and various other methods, can use them. We shall pay special attention to the interfacial tension $\epsilon_r$ between the $k$ state and the $k-r$ state. By examining the ground states, it is seen that the integrable line ends at a superwetting point, on which the relation $\epsilon_r=r\epsilon_1$ is satisfied, so that it is energetically neutral to have one interface or more. We present also some partial results on the meaning of the integrable line for low temperatures where it lives in the non-wet regime. We make Baxter's exact results more explicit for the symmetric case. By performing a Bethe Ansatz calculation with open boundary conditions we confirm a dilogarithm identity for the low-temperature expansion which may be new. We propose a new model for numerical studies. This model has only two variables and exhibits commensurate and incommensurate phase transitions and wetting transitions near zero temperature. It appears to be not integrable, except at one point, and at each temperature there is a point, where it is almost identical with the integrable chiral Potts model.Comment: J. Stat. Phys., LaTeX using psbox.tex and AMS fonts, 69 pages, 30 figure

Modeling Initiation of Ewing Sarcoma in Human Neural Crest Cells

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC). Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC) progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis

Influence of gestational age at initiation of antihypertensive therapy: secondary analysis of CHIPS trial data (control of hypertension in pregnancy study)

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight 48 hours (Pinteraction=0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks (Pinteraction=0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes

Ubiquitin E3 Ligase Ring1b/Rnf2 of Polycomb Repressive Complex 1 Contributes to Stable Maintenance of Mouse Embryonic Stem Cells

Polycomb repressive complex 1 (PRC1) core member Ring1b/Rnf2, with ubiquitin E3 ligase activity towards histone H2A at lysine 119, is essential for early embryogenesis. To obtain more insight into the role of Ring1b in early development, we studied its function in mouse embryonic stem (ES) cells.We investigated the effects of Ring1b ablation on transcriptional regulation using Ring1b conditional knockout ES cells and large-scale gene expression analysis. The absence of Ring1b results in aberrant expression of key developmental genes and deregulation of specific differentiation-related pathways, including TGFbeta signaling, cell cycle regulation and cellular communication. Moreover, ES cell markers, including Zfp42/Rex-1 and Sox2, are downregulated. Importantly, retained expression of ES cell regulators Oct4, Nanog and alkaline phosphatase indicates that Ring1b-deficient ES cells retain important ES cell specific characteristics. Comparative analysis of our expression profiling data with previously published global binding studies shows that the genes that are bound by Ring1b in ES cells have bivalent histone marks, i.e. both active H3K4me3 and repressive H3K27me3, or the active H3K4me3 histone mark alone and are associated with CpG-'rich' promoters. However, deletion of Ring1b results in deregulation, mainly derepression, of only a subset of these genes, suggesting that additional silencing mechanisms are involved in repression of the other Ring1b bound genes in ES cells.Ring1b is essential to stably maintain an undifferentiated state of mouse ES cells by repressing genes with important roles during differentiation and development. These genes are characterized by high CpG content promoters and bivalent histone marks or the active H3K4me3 histone mark alone

Light-Ion-Induced Multifragmentation: The ISiS Project

An extensive study of GeV light-ion-induced multifragmentation and its possible interpretation in terms of a nuclear liquid-gas phase transition has been performed with the Indiana Silicon Sphere (ISiS)4 pi detector array. Measurements were performed with 5-15 GeV/c p, pbar, and pion beams incident on $^{197}$Au and 2-5 GeV $^3$He incident on $^{nat}$Ag and $^{197}$Au targets. Both the reaction dynamics and the subsequent decay of the heavy residues have been explored. The data provide evidence for a dramatic change in the reaction observables near an excitation energy of E*/A = 4-5 MeV per residue nucleon. In this region, fragment multiplicities and energy spectra indicate emission from an expanded/dilute source on a very short time scale (20-50 fm/c). These properties, along with caloric curve and scaling-law behavior, yield a pattern that is consistent with a nuclear liquid-gas phase transition.Comment: 67 pages, 44 figures, all included in tar fil

Caffeine Reduces 11β-Hydroxysteroid Dehydrogenase Type 2 Expression in Human Trophoblast Cells through the Adenosine A2B Receptor

Maternal caffeine consumption is associated with reduced fetal growth, but the underlying molecular mechanisms are unknown. Since there is evidence that decreased placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is linked to fetal growth restriction, we hypothesized that caffeine may inhibit fetal growth partly through down regulating placental 11β-HSD2. As a first step in examining this hypothesis, we studied the effects of caffeine on placental 11β-HSD2 activity and expression using our established primary human trophoblast cells as an in vitro model system. Given that maternal serum concentrations of paraxanthine (the primary metabolite of caffeine) were greater in women who gave birth to small-for-gestational age infants than to appropriately grown infants, we also studied the effects of paraxanthine. Our main findings were: (1) both caffeine and paraxanthine decreased placental 11β-HSD2 activity, protein and mRNA in a concentration-dependent manner; (2) this inhibitory effect was mediated by the adenosine A2B receptor, since siRNA-mediated knockdown of this receptor prevented caffeine- and paraxanthine-induced inhibition of placental 11β-HSD2; and (3) forskolin (an activator of adenyl cyclase and a known stimulator of 11β-HSD2) abrogated the inhibitory effects of both caffeine and paraxanthine, which provides evidence for a functional link between exposure to caffeine and paraxanthine, decreased intracellular levels of cAMP and reduced placental 11β-HSD2. Taken together, these findings reveal that placental 11β-HSD2 is a novel molecular target through which caffeine may adversely affect fetal growth. They also uncover a previously unappreciated role for the adenosine A2B receptor signaling in regulating placental 11β-HSD2, and consequently fetal development

Comparative Developmental Expression Profiling of Two C. elegans Isolates

Gene expression is known to change during development and to vary among genetically diverse strains. Previous studies of temporal patterns of gene expression during C. elegans development were incomplete, and little is known about how these patterns change as a function of genetic background. We used microarrays that comprehensively cover known and predicted worm genes to compare the landscape of genetic variation over developmental time between two isolates of C. elegans. We show that most genes vary in expression during development from egg to young adult, many genes vary in expression between the two isolates, and a subset of these genes exhibit isolate-specific changes during some developmental stages. This subset is strongly enriched for genes with roles in innate immunity. We identify several novel motifs that appear to play a role in regulating gene expression during development, and we propose functional annotations for many previously unannotated genes. These results improve our understanding of gene expression and function during worm development and lay the foundation for linkage studies of the genetic basis of developmental variation in gene expression in this important model organism

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention