Ultra-Sensitive Hot-Electron Nanobolometers for Terahertz Astrophysics

The background-limited spectral imaging of the early Universe requires spaceborne terahertz (THz) detectors with the sensitivity 2-3 orders of magnitude better than that of the state-of-the-art bolometers. To realize this sensitivity without sacrificing operating speed, novel detector designs should combine an ultrasmall heat capacity of a sensor with its unique thermal isolation. Quantum effects in thermal transport at nanoscale put strong limitations on the further improvement of traditional membrane-supported bolometers. Here we demonstrate an innovative approach by developing superconducting hot-electron nanobolometers in which the electrons are cooled only due to a weak electron-phonon interaction. At T<0.1K, the electron-phonon thermal conductance in these nanodevices becomes less than one percent of the quantum of thermal conductance. The hot-electron nanobolometers, sufficiently sensitive for registering single THz photons, are very promising for submillimeter astronomy and other applications based on quantum calorimetry and photon counting.Comment: 19 pages, 3 color figure

Population genomics of sub-Saharan Drosophila melanogaster: African diversity and non-African admixture

(ABRIDGED) We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations

On the accuracy of language trees

Historical linguistics aims at inferring the most likely language phylogenetic tree starting from information concerning the evolutionary relatedness of languages. The available information are typically lists of homologous (lexical, phonological, syntactic) features or characters for many different languages. From this perspective the reconstruction of language trees is an example of inverse problems: starting from present, incomplete and often noisy, information, one aims at inferring the most likely past evolutionary history. A fundamental issue in inverse problems is the evaluation of the inference made. A standard way of dealing with this question is to generate data with artificial models in order to have full access to the evolutionary process one is going to infer. This procedure presents an intrinsic limitation: when dealing with real data sets, one typically does not know which model of evolution is the most suitable for them. A possible way out is to compare algorithmic inference with expert classifications. This is the point of view we take here by conducting a thorough survey of the accuracy of reconstruction methods as compared with the Ethnologue expert classifications. We focus in particular on state-of-the-art distance-based methods for phylogeny reconstruction using worldwide linguistic databases. In order to assess the accuracy of the inferred trees we introduce and characterize two generalizations of standard definitions of distances between trees. Based on these scores we quantify the relative performances of the distance-based algorithms considered. Further we quantify how the completeness and the coverage of the available databases affect the accuracy of the reconstruction. Finally we draw some conclusions about where the accuracy of the reconstructions in historical linguistics stands and about the leading directions to improve it.Comment: 36 pages, 14 figure

On misunderstanding Heraclitus: The justice of organisation structure

Writers on organisational change often refer to the cosmology of Heraclitus in their work. Some use these references to support arguments for the constancy and universality of organisational change and the consignment to history of organisational continuity and stability. These writers misunderstand the scope of what Heraclitus said. Other writers focus exclusively on the idea that originated with Heraclitus that the universe is composed of processes and not of things. This idea, which has been particularly associated with Heraclitus’s thought from the time of Plato, does indeed provide a rich source of insights into organisational analysis, not least the current trends towards giving proper attention to processual studies of organisational change. Yet there is some uncertainty as to whether Heraclitus actually said that the universe was composed exclusively of processes rather than things, and even if that was what he thought, he intended his ideas on flux to be understood not in isolation but in the context of other aspects of his cosmology. Writers on organisational change seldom make reference to this wider context. Heraclitus was a rational but also a religious thinker. A central element in his thought was the notion of divine Justice, which to a Greek of his era meant the order of the universe. Remote as his Olympian theology may seem today, it sets a crucial and entirely rational context for understanding his ideas about flux. It means that ideas about continuity and stability were quite as important in Heraclitus’s cosmology as his more commonly quoted ideas about change. This paper sets out an overview of Heraclitus’s philosophy, insofar as it appears to have potential relevance to organisational analysis, and discusses how far it supports or contradicts the ideas that organisational change scholars have drawn from it

Genome-wide fine-scale recombination rate variation in Drosophila melanogaster

Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and diversity

Osvaldo and Isis retrotransposons as markers of the Drosophila buzzatii colonization in Australia

Background: Transposable elements (TEs) constitute an important source of genetic variability owing to their jumping and regulatory properties, and are considered to drive species evolution. Several factors that are able to induce TE transposition in genomes have been documented (for example environmental stress and inter- and intra-specific crosses) but in many instances the reasons for TE mobilisation have yet to be elucidated. Colonising populations constitute an ideal model for studying TE behaviour and distribution as they are exposed to different environmental and new demographic conditions. In this study, the distribution of two TEs, Osvaldo and Isis, was examined in two colonising populations of D. buzzatii from Australia. Comparing Osvaldo copy numbers between Australian and Old World (reported in previous studies) colonisations provides a valuable tool for elucidating the colonisation process and the effect of new conditions encountered by colonisers on TEs. Results: The chromosomal distributions of Osvaldo and Isis retrotransposons in two colonising populations of D. buzzatii from Australia revealed sites of high insertion frequency (>10%) and low frequency sites. Comparisons between Osvaldo insertion profiles in colonising populations from the Old World and Australia demonstrate a tendency towards a higher number of highly occupied sites with higher insertion frequency in the Old World than in Australian populations. Tests concerning selection against deleterious TE insertions indicate that Isis is more controlled by purifying selection than Osvaldo. The distribution of both elements on chromosomal arms follows a Poisson distribution and there are non-significant positive correlations between highly occupied sites and chromosomal inversions. Conclusions: The occupancy profile of Osvaldo and Isis retrotransposons is characterised by the existence of high and low insertion frequency sites in the populations. These results demonstrate that Australian D. buzzatii populations were subjected to a founder effect during the colonisation process. Moreover, there are more sites with high insertion frequency in the Old World colonisation than in the Australian colonisation, indicating a probable stronger bottleneck effect in Australia. The results suggest that selection does not seem to play a major role, compared to demography, in the distribution of transposable elements in the Australian populations

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth

Glucocorticoid Effects on the Programming of AT1b Angiotensin Receptor Gene Methylation and Expression in the Rat

Adverse events in pregnancy may ‘programme’ offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11β-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence

Laparoscopic cholecystectomy for melanoma metastatic to the gallbladder: is it an adequate surgical procedure? Report of a case and review of the literature

<p>Abstract</p> <p>Background</p> <p>Only 2% to 4% of patients with melanoma will be diagnosed with gastrointestinal metastasis during the course of their disease. The most common sites of gastrointestinal metastases from melanoma include the small bowel (35%–67%), colon (9%–15%) and stomach (5%–7%), with a median survival of 6–10 months after surgery, and 18% survival at five years. Metastatic melanoma to the gallbladder is extremely rare and it is associated with a very poor prognosis.</p> <p>Case presentation</p> <p>We report a case of a 54-year old man presented to observation with diagnosis of 6.1 mm thick, Clark's level IV, ulcerated melanoma of the trunk, developing in the course of the disease metastatic involvement of the gallbladder as first site of recurrence, treated by laparoscopic cholecystectomy. To date only few cases of patients with metastatic melanoma of the gallbladder treated by this surgical procedure have been reported in literature.</p> <p>Conclusion</p> <p>Gallbladder metastasis represents a rare event as a first site of recurrence. It must be considered a possible expression of systemic disease also despite radiological absence of other metastatic lesions. Laparoscopic approach has a possible therapeutic role, but open surgery has also a concomitant diagnostic purpose because gives the possibility of manual exploration of abdominal cavity, useful particularly to reveal bowel metastatic lesions, not easily identifiable by preoperative imaging examinations.</p