Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Application of Two Multiplex Real-Time PCR Assays for the Detection of Mycobacterium ulcerans in Clinical and Environmental Samples

ABSTRACT Mycobacterium ulcerans is a slow-growing environmental bacterium that causes a severe skin disease known as Buruli ulcer. PCR has become a reliable and rapid method for the diagnosis of M. ulcerans infection in humans and has been used for the detection of M. ulcerans in the environment. This paper describes the development of a TaqMan assay targeting IS2404 multiplexed with an internal positive control to monitor inhibition with a detection limit of less than 1 genome equivalent of DNA. The assay improves the turnaround time for diagnosis and replaces conventional gel-based PCR as the routine method for laboratory confirmation of M. ulcerans infection in Victoria, Australia. Following analysis of 415 clinical specimens, the new test demonstrated 100% sensitivity and specificity compared with culture. Another multiplex TaqMan assay targeting IS2606 and the ketoreductase-B domain of the M. ulcerans mycolactone polyketide synthase genes was designed to augment the specificity of the IS2404 PCR for the analysis of a variety of environmental samples. Assaying for these three targets enabled the detection of M. ulcerans DNA in soil, sediment, and mosquito extracts collected from an area of endemicity for Buruli ulcer in Victoria with a high degree of confidence. Final confirmation was obtained by the detection and sequencing of variable-number tandem repeat (VNTR) locus 9, which matched the VNTR locus 9 sequence obtained from the clinical isolates in this region. This suite of new methods is enabling rapid progress in the understanding of the ecology of this important human pathogen.
Deconstructing Planning as Satisfiability

The idea of encoding planning as satisfiability was proposed in 1992 as a method for generating interesting SAT problems, but did not appear to be a practical approach to planning (Kautz & Selman 1992). This changed in 1996, when Satplan was shown to be competitive with current planning technology, leading to a mini-explosion of interest in the approach (Kautz & Selman 1996). Within a few years, however, heuristic search planning appeared to be vastly superior to planning as satisfiability, and many researchers wrote off the earlier success of the approach as a fluke. It was therefore rather surprising when Satplan won first place for optimal STRIPS planning in the 2004 ICAPS planning competition (Edelkamp et al. 2004). This talk will attempt to deconstruct the reasons for Satplan’s successes and failures, and discuss ways the approach might be extended to handle “open” domains, metric constraints, and domain symmetries.
An investigation of chromospheric activity spanning the Vaughan-Preston gap: impact on stellar ages

Context. Chromospheric activity is widely used as an age indicator for solar-type stars based on the early evidence that there is a smooth evolution from young and active to old and inactive stars. However, this transition may require modification as chromospheric activity is not a viable age indicator for stars older than 1 Gyr. Aims. We analysed chromospheric activity in five solar-type stars in two open clusters, in order to study how chromospheric activity evolves with time. Methods. We took UVES high-resolution, high S/N ratio spectra of 3 stars in IC 4756 and 2 in NGC 5822, which were combined with a previously studied data-set and reanalysed here. The emission core of the deep, photospheric Ca II K line was used as a probe of the chromospheric activity. Results. All of the 5 stars in the new sample, including those in the 1.2 Gyr-old NGC 5822, have activity levels comparable to those of Hyades and Praesepe. Conclusions. A likely interpretation of our data is that solar-type-star chromospheric activity, from the age of the Hyades until that of the Sun, does not evolve smoothly. Stars change from active to inactive, crossing the activity range corresponding to the Vaughan-Preston gap, on a time-scale that might be as short as 200 Myr. Evolution before and after such a transition is much less significant than cyclical and long-term variations. We show that data presented in the literature to support a correlation between age and activity could be also interpreted differently in the light of our results. Suggestions have been published that relevant stellar structures and/or dynamos are different for active and inactive stars. These provide a natural explanation for the observations presented here. More observations are required in order to strengthen our results, especially a long-term follow up of our two targets in the 1.2-Gyr old cluster NGC 5822.
Ocean circulation response to anthropogenic-aerosol and greenhouse gas forcing in the CSIRO-Mk3.6 coupled climate model

We use the CSIRO-Mk3.6 coupled climate model to examine the impact of anthropogenic aerosols (AAs) and long-lived greenhouse gases (GHGs) on aspects of the global ocean circulation. Focusing on the second half of the twentieth century, we compare multiple ten member ensembles of historical climate change, which are forced by different combinations of forcing agents; these different simulations enable us to separately diagnose the effects of changes in AAs and GHGs. We also compare ten member 21st century ensembles driven by Representative Concentration Pathways 4.5 (RCP4.5) and 8.5 (RCP8.5). To a large degree the pattern of change in the oceans due to the impact of AAs is similar to the effect of increasing GHGs, but of opposite sign. The Atlantic Meridional Overturning Circulation (and associated North Atlantic Deep Water formation) strengthens in response to historical changes in AAs but weakens in response to increasing GHGs. Similarly, the Indonesian Throughflow strengthens in response to AAs, and weakens in response to increasing GHGs. The Drake Passage Transport, however, shows a small weakening (strengthening) due to historical changes in AAs (GHGs) in the ensemble mean. The change in the Drake Passage Transport is much clearer in the 21st century, in which it increases strongly in response to increasing GHGs and decreasing AAs in both RCP4.5 and RCP8.5. The results suggests that without the influence of AAs, changes in ocean circulation would have already followed a path much more like one dominated by increasing GHGs. Considering that the AA levels are expected to decrease during the next few decades, the effects of increasing GHGs on ocean circulation will be amplified accordingly.
Relative log convergent cohomology and relative rigid cohomology III

In this paper, we develop the theory of relative log convergent cohomology of radius $\lambda$ ($0 < \lambda \leq 1$), which is a generalization of the notion of relative log convergent cohomology in the previous paper. By comparing this cohomology with relative log crystalline cohomology, relative rigid cohomology and its variants and by using some technique of hypercovering, we prove a version of Berthelot's conjecture on the overconvergence of relative rigid cohomology for proper smooth families.
Human and organisational aspects of remote patient monitoring in residential care homes

Demographic changes in the population, with a growing proportion of elderly people, make the efficient and effective provision of healthcare for this age group an increasingly important issue. We examine the organisational and human aspects of introducing a Remote Patient Monitoring (RPM) system that uses wireless and broadband networks into three residential care homes in the UK. Stakeholders were identified, and semi-structured one-to-one interviews were carried out in order to identify issues deemed most important to each group. The work is novel, as it requires examination of the issues of communication between healthcare workers in several primary and secondary care organisations. The key finding was the need to identify the changes in working practice and interpersonal communication. A key factor in particular was the change in relationships: staff in the remote centre needing to learn to seek support when reporting and requesting assistance for a problem; and for the staff at the health centres to respond appropriately.
Testing for Polygenic Effects in Genome‐Wide Association Studies

To confirm associations with a large number of single nucleotide polymorphisms (SNPs), each with only a small effect size, as hypothesized in the polygenic theory for schizophrenia, the International Schizophrenia Consortium (2009, Nature 460:748–752) proposed a polygenic risk score (PRS) test and demonstrated its effectiveness when applied to psychiatric disorders. The basic idea of the PRS test is to use a half of the sample to select and up‐weight those more likely to be associated SNPs, and then use the other half of the sample to test for aggregated effects of the selected SNPs. Intrigued by the novelty and increasing use of the PRS test, we aimed to evaluate and improve its performance for GWAS data. First, by an analysis of the PRS test, we point out its connection with the Sum test [Chapman and Whittaker, , Genet Epidemiol 32:560–566; Pan, , Genet Epidemiol 33:497–507]; given the known advantages and disadvantages of the Sum test, this connection motivated the development of several other polygenic tests, some of which may be more powerful than the PRS test under certain situations. Second, more importantly, to overcome the low statistical efficiency of the data‐splitting strategy as adopted in the PRS test, we reformulate and thus modify the PRS test, obtaining several adaptive tests, which are closely related to the adaptive sum of powered score (SPU) test studied in the context of rare variant analysis [Pan et al., 2014, Genetics 197:1081–1095]. We use both simulated data and a real GWAS dataset of alcohol dependence to show dramatically improved power of the new tests over the PRS test; due to its superior performance and simplicity, we recommend the whole sample‐based adaptive SPU test for polygenic testing. We hope to raise the awareness of the limitations of the PRS test and potential power gain of the adaptive SPU test.
Text classification based on partial least square analysis

Latent Semantic Indexing (LSI) is a favorite feature extraction method used in text classification. Since when important global features for all the classes can be determined by LSI, important local features for small classes may be ignored, this leads to poor performance on these small classes. To solve this problem, a novel method based on Partial Least Square (PLS) analysis is proposed by integrating class information into the latent classification structure. Important features are extracted according to both their descriptive power of document contents as in LSI, and their capacity of discriminating classes. The extracted features are applied to several classification algorithms: SVM, kNN, C4.5 and SMO. Experiments on Reuters prove that the features extracted by our method outperform those extracted by LSI in all the cases. In particular, the gain obtained by our method is the most apparent on small classes.
GNB3, eNOS, and Mitochondrial DNA Polymorphisms Correlate to Natural Longevity in a Xinjiang Uygur Population

Background In centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 (GNB3) and nitrate (NO2) production associated with endothelial nitric oxide synthase (eNOS), commonly appearing in age-related diseases, remains undetermined. Objective The association between the mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated. Methods A total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS. Associations between polymorphic loci, genotypes, and longevity were analyzed. Results 165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19; n = 65) and nonagenarian groups (M∶F = 61/39; n = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%. Conclusions Applying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G, GNB3 C825T, and eNOS polymorphisms are useful as a genetic basis for longevity.
Mediation of tubuloglomerular feedback by adenosine: Evidence from mice lacking adenosine 1 receptors

Adenosine is a determinant of metabolic control of organ function increasing oxygen supply through the A2 class of adenosine receptors and reducing oxygen demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence was deleted by homologous recombination. Homozygous A1AR mutants that do not express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and without gross anatomical abnormalities. Plasma and urinary electrolytes were not different between genotypes. Likewise, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR+/+, A1AR+/−, and A1AR−/− mice. TGF responses to an increase in loop of Henle flow rate from 0 to 30 nl/min, whether determined as change of stop flow pressure or early proximal flow rate, were completely abolished in A1AR−/− mice (stop flow pressure response, −6.8 ± 0.55 mmHg and −0.4 ± 0.2 in A1AR+/+ and A1AR−/− mice; early proximal flow rate response, −3.4 ± 0.4 nl/min and +0.02 ± 0.3 nl/min in A1AR+/+ and A1AR−/− mice). Absence of TGF responses in A1AR-deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues.
Cis- and trans-acting functions required for endocytosis of the yeast pheromone receptors

The Saccharomyces cerevisiae a-factor receptor (STE3) is subject to two modes of endocytosis: a constitutive process that occurs in the absence of ligand and a regulated process that is triggered by binding of ligand. Both processes result in delivery of the receptor to the vacuole for degradation. Receptor mutants deleted for part of the COOH- terminal cytoplasmic domain are disabled for constitutive, but not ligand-dependent internalization. Trans-acting mutants that impair constitutive endocytosis have been isolated. One of these, ren1-1, is blocked at a late step in the endocytic pathway, as receptor accumulates in a prevacuolar endosome-like compartment. REN1 is identical to VPS2, a gene required for delivery of newly synthesized vacuolar enzymes to the vacuole. Based on this identity, we suggest a model in which the transport pathways to the vacuole--the endocytic pathway and the vacuolar biogenesis pathway--merge at an intermediate endocytic compartment. As receptor also accumulates at the surface of ren1 cells, receptor may recycle from the putative endosome to the surface, or REN1 may also be required to carry out an early step in endocytosis.
Reduction of chemical networks. II. Analysis of the fractional ionisation in protoplanetary discs

We analyse the evolution of the fractional ionisation in a steady-state protoplanetary disc over 10 6 yr. We consider a disc model with a vertical temperature gradient and with gas-grain chemistry including surface reactions. The ionisation due to stellar X-rays, stellar and interstellar UV radiation, cosmic rays and radionuclide decay is taken into account. Using our reduction schemes as a tool for the analysis, we isolate small sets of chemical reactions that reproduce the evolution of the ionisation degree at representative disc locations with an accuracy of 50%–100%. On the basis of fractional ionisation, the disc can be divided into three distinct layers. In the dark dense midplane the ionisation degree is sustained by cosmic rays and radionuclides only and is very low, $\la$10 -12 . This region corresponds to the so-called “dead zone” in terms of the angular momentum transport driven by MHD turbulence. The ionisation degree can be accurately reproduced by chemical networks with about 10 species and a similar number of reactions. In the intermediate layer the chemistry of the fractional ionisation is driven mainly by the attenuated stellar X-rays and is far more complicated. For the first time, we argue that surface hydrogenation of long carbon chains can be of crucial importance for the evolution of the ionisation degree in protoplanetary discs. In the intermediate layer reduced networks contain more than a 100 species and hundreds of reactions. Finally, in the unshielded low-density surface layer of the disc the chemical life cycle of the ionisation degree comprises a restricted set of photoionisation-recombination processes. It is sufficient to keep about 20 species and reactions in reduced networks. Furthermore, column densities of key molecules are calculated and compared to the results of other recent studies and observational data. The relevance of our results to the MHD modelling of protoplanetary discs is discussed.
HaLoop

The growing demand for large-scale data mining and data analysis applications has led both industry and academia to design new types of highly scalable data-intensive computing platforms. MapReduce and Dryad are two popular platforms in which the dataflow takes the form of a directed acyclic graph of operators. These platforms lack built-in support for iterative programs, which arise naturally in many applications including data mining, web ranking, graph analysis, model fitting, and so on. This paper presents HaLoop, a modified version of the Hadoop MapReduce framework that is designed to serve these applications. HaLoop not only extends MapReduce with programming support for iterative applications, it also dramatically improves their efficiency by making the task scheduler loop-aware and by adding various caching mechanisms. We evaluated HaLoop on real queries and real datasets. Compared with Hadoop, on average, HaLoop reduces query runtimes by 1.85, and shuffles only 4% of the data between mappers and reducers.
Removal of GABAA Receptor γ2 Subunits from Parvalbumin Neurons Causes Wide-Ranging Behavioral Alterations

We investigated the behavioral significance of fast synaptic inhibition by αβγ2-type GABAA receptors on parvalbumin (Pv) cells. The GABAA receptor γ2 subunit gene was selectively inactivated in Pv-positive neurons by Cre/loxP recombination. The resulting Pv-Δγ2 mice were relatively healthy in the first postnatal weeks; but then as Cre started to be expressed, the mice progressively developed wide-ranging phenotypic alterations including low body weight, motor deficits and tremor, decreased anxiety levels, decreased pain sensitivity and deficient prepulse inhibition of the acoustic startle reflex and impaired spatial learning. Nevertheless, the deletion was not lethal, and mice did not show increased mortality even after one year. Autoradiography with t-butylbicyclophosphoro[35S]thionate suggested an increased amount of GABAA receptors with only α and β subunits in central nervous system regions that contained high levels of parvalbumin neurons. Using BAC-transgenesis, we reduced some of the Pv-Δγ2 phenotype by selectively re-expressing the wild-type γ2 subunit back into some Pv cells (reticular thalamic neurons and cerebellar Pv-positive neurons). This produced less severe impairments of motor skills and spatial learning compared with Pv-Δγ2 mice, but all other deficits remained. Our results reveal the widespread significance of fast GABAergic inhibition onto Pv-positive neurons for diverse behavioral modalities, such as motor coordination, sensorimotor integration, emotional behavior and nociception.
Self-rated health, life-style, and psychoendocrine measures of stress in healthy adult women

Abstract Background. Self-rated health (SRH) is a robust predictor of subsequent health outcome, independent of objective health measures and life-style-related health risk factors. However, the determinants of SRH are as yet largely unknown. In accordance with the prevailing stress theory, we hypothesized that SRH is associated with personal coping resources, psychological strain, life-style variables, and endocrine variables. Methods. A total of 106 healthy women, 22–59 years of age, were followed for up to 3 years with annual blood sampling (cortisol, prolactin, testosterone) and written questionnaires in which information on SRH, psychological strain, coping resources, socio-economic and life-style variables was sought. Results. In bivariate, screening logistic regression analyses, intended to find candidate variables for a final analysis model, all coping resource variables (sense of coherence, mastery, and self-esteem) were significantly related to SRH, and so were two psychological strain variables (vital exhaustion, and sleep disturbances), one life-style variable (fitness), but none of the endocrine variables. In the final multivariate analysis model, including all candidate variables, only vital exhaustion (P < 0.0001), fitness (P = 0.0002), and sense of coherence (P = 0.0006) were independently associated with SRH, together explaining 74% of the SRH variance. Conclusion. Some elements of the hypothesis, i.e. the effects of coping resources, psychological strain, and life-style variables on SRH, were supported by the results, while others, i.e. effects of endocrine measures on SRH, were not, indicating a possible gender difference.