Improved Average Complexity for Comparison-Based Sorting

This paper studies the average complexity on the number of comparisons for sorting algorithms. Its information-theoretic lower bound is $n \lg n - 1.4427n + O(\log n)$. For many efficient algorithms, the first $n\lg n$ term is easy to achieve and our focus is on the (negative) constant factor of the linear term. The current best value is $-1.3999$ for the MergeInsertion sort. Our new value is $-1.4106$, narrowing the gap by some $25\%$. An important building block of our algorithm is "two-element insertion," which inserts two numbers $A$ and $B$, $A<B$, into a sorted sequence $T$. This insertion algorithm is still sufficiently simple for rigorous mathematical analysis and works well for a certain range of the length of $T$ for which the simple binary insertion does not, thus allowing us to take a complementary approach with the binary insertion.Comment: 21 pages, 2 figure

Zebrafish prox1b Mutants Develop a Lymphatic Vasculature, and prox1b Does Not Specifically Mark Lymphatic Endothelial Cells

Background: The expression of the Prospero homeodomain transcription factor (Prox1) in a subset of cardinal venous cells specifies the lymphatic lineage in mice. Prox1 is also indispensible for the maintenance of lymphatic cell fate, and is therefore considered a master control gene for lymphangiogenesis in mammals. In zebrafish, there are two prox1 paralogues, the previously described prox1 (also known as prox1a) and the newly identified prox1b. Principal Findings: To investigate the role of the prox1b gene in zebrafish lymphangiogenesis, we knocked-down prox1b and found that depletion of prox1b mRNA did not cause lymphatic defects. We also generated two different prox1b mutant alleles, and maternal-zygotic homozygous mutant embryos were viable and did not show any lymphatic defects. Furthermore, the expression of prox1b was not restricted to lymphatic vessels during zebrafish development. Conclusion: We conclude that Prox1b activity is not essential for embryonic lymphatic development in zebrafish

Use of radiolabelled choline as a pharmacodynamic marker for the signal transduction inhibitor geldanamycin

There is an urgent need to develop non-invasive pharmacodynamic endpoints for the evaluation of new molecular therapeutics that inhibit signal transduction. We hypothesised that, when labelled appropriately, changes in choline kinetics could be used to assess geldanamycin pharmacodynamics, which involves inhibition of the HSP90 molecular chaperone→Raf1→Mitogenic Extracellular Kinase→Extracellular Signal-Regulated Kinase 1 and 2 signal transduction pathway. Towards identifying a potential pharmacodynamic marker response, we have studied radiolabelled choline metabolism in HT29 human colon carcinoma cells following treatment with geldanamycin. We studied the effects of geldanamycin, on net cellular accumulation of (methyl-14C)choline and (methyl-14C)phosphocholine production. In parallel experiments, the effects of geldanamycin on extracellular signal-regulated kinase 1 and 2 phosphorylation and cell viability were also assessed. Additional validation studies were carried out with the mitogenic extracellular kinase inhibitor U0126 as a positive control; a cyclin-dependent kinase-2 inhibitor roscovitine and the phosphatidylinositol 3-kinase inhibitor LY294002 as negative controls. Hemicholinium-3, an inhibitor of choline transport and choline kinase activity was included as an additional control. In exponentially growing HT29 cells, geldanamycin inhibited extracellular signal-regulated kinase 1 and 2 phosphorylation in a concentration- and time-dependent manner. These changes were associated with a reduction in (methyl-14C)choline uptake, (methyl-14C) phosphocholine production and cell viability. Brief exposure to U0126, suppressed phosphocholine production to the same extent as Hemicholinium-3. In contrast to geldanamycin and U0126, which act upstream of extracellular signal-regulated kinase 1 and 2, roscovitine and LY294002 failed to suppress phosphocholine production. Our results suggest that when labelled with carbon-11 isotope, (methyl-11C)choline may be a useful pharmacodynamic marker for the non-invasive evaluation of geldanamycin analogues

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Depurated fish as an alternative reference for field-based biomarker monitoring

The whole of the Swan-Canning Estuary, in the south-west of Australia, is impacted by human activity, and the selection of a local reference site to assess the impact of environmental contamination on the health of biota is not possible. To determine whether fish depurated under laboratory conditions could be used as an alternative to a reference site; adult black bream (Acanthopagrus butcheri) were collected from the estuary and maintained in clean water (S24) for 3 months. A suite of biomarkers of fish health were assessed, and the results were compared with field-captured black bream from three sites within the estuary (Ascot, Claisebrook, and Riverton). Comparisons of a subset of biomarkers were also made between hatchery-bred juvenile fish and the depurated fish. Biomarker levels were up to 3.8 times higher in field captured fish compared with depurated fish, while DNA integrity was lower. EROD activity was comparable in the hatchery-bred black bream to the depurated fish while s-SDH levels were two times higher in the hatchery fish. From the results obtained, field-captured black bream depurated for 3 months are suitable to determine reference/baseline levels for biomarker of health studies in estuarine environments

Lifted graphical models: a survey

Lifted graphical models provide a language for expressing dependencies between different types of entities, their attributes, and their diverse relations, as well as techniques for probabilistic reasoning in such multi-relational domains. In this survey, we review a general form for a lifted graphical model, a par-factor graph, and show how a number of existing statistical relational representations map to this formalism. We discuss inference algorithms, including lifted inference algorithms, that efficiently compute the answers to probabilistic queries over such models. We also review work in learning lifted graphical models from data. There is a growing need for statistical relational models (whether they go by that name or another), as we are inundated with data which is a mix of structured and unstructured, with entities and relations extracted in a noisy manner from text, and with the need to reason effectively with this data. We hope that this synthesis of ideas from many different research groups will provide an accessible starting point for new researchers in this expanding field

Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing

$\textbf{Objective}$ Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. $\textbf{Methods}$ Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. $\textbf{Results}$ Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (A$^{+}$P$_{+}$). Unbiased clustering analysis of P$^{+}$ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P$^{+}$ neurons expressed the leptin receptor ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively). $\textbf{Conclusion}$ These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.This work was supported by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1 & MRC_MC_UU_12012/5), a Wellcome Trust Strategic Award (100574/Z/12/Z), and the Helmholtz Alliance ICEMED

Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing

$\textbf{Objective}$ Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. $\textbf{Methods}$ Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. $\textbf{Results}$ Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (A$^{+}$P$_{+}$). Unbiased clustering analysis of P$^{+}$ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P$^{+}$ neurons expressed the leptin receptor ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively). $\textbf{Conclusion}$ These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.This work was supported by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1 & MRC_MC_UU_12012/5), a Wellcome Trust Strategic Award (100574/Z/12/Z), and the Helmholtz Alliance ICEMED

Reliability of Therapist Effects in Practice-Based Psychotherapy Research : A Guide for the Planning of Future Studies

This paper aims to provide researchers with practical information on sample sizes for accurate estimations of therapist effects (TEs). The investigations are based on an integrated sample of 48,648 patients treated by 1800 therapists. Multilevel modeling and resampling were used to realize varying sample size conditions to generate empirical estimates of TEs. Sample size tables, including varying sample size conditions, were constructed and study examples given. This study gives an insight into the potential size of the TE and provides researchers with a practical guide to aid the planning of future studies in this field