Reducing control noise in gravitational wave detectors with interferometric local damping of suspended optics.

Control noise is a limiting factor in the low-frequency performance of the Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we model the effects of using new sensors called Homodyne Quadrature Interferometers (HoQIs) to control the suspension resonances. We show that if we were to use HoQIs, instead of the standard shadow sensors, we could suppress resonance peaks up to tenfold more while simultaneously reducing the noise injected by the damping system. Through a cascade of effects, this will reduce the resonant cross-coupling of the suspensions, allow for improved stability for feed-forward control, and result in improved sensitivity of the detectors in the 10-20 Hz band. This analysis shows that improved local sensors, such as HoQIs, should be used in current and future detectors to improve low-frequency performance.

Sensors and actuators for the advanced LIGO A+ upgrade.

Advanced Laser Interferometer Gravitational-wave Observatory (LIGO A+) is a major upgrade to LIGO-the Laser Interferometer Gravitational-wave Observatory. For the A+ project, we have developed, produced, and characterized sensors and electronics to interrogate new optical suspensions designed to isolate optics from vibrations. The central element is a displacement sensor with an integrated electromagnetic actuator known as a BOSEM (Birmingham Optical Sensor and ElectroMagnetic actuator) and its readout and drive electronics required to integrate them into LIGO's control and data system. In this paper, we report on the improvements to the sensors and the testing procedures undertaken to meet the enhanced performance requirements set out by the A+ upgrade to the detectors. The best devices reach a noise level of 4.5 ×10-11m/Hz at a measurement frequency of 1 Hz, an improvement of 6.7 times over standard devices.

Structured ternary fluids as nanocrystal incubators for enhanced crystallization control.

In crystallization from solution, a ubiquitous process in both industry and the natural world, nucleation is usually the rate-determining step, followed by faster crystal growth. Consequently, crystals typically exist in the nm-size range for such limited times that their investigation and manipulation is hindered. Here, we show that, owing to a degree of restricted diffusion, crystallization in structured ternary fluids (STFs) can proceed via higher nucleation rate and slower crystal growth pathways. This enables STFs to act as nanocrystal incubators, with the nanocrystals existing for extended times. We demonstrate that this generates enhanced crystallization control, with the three ambient pressure polymorphs of glycine, the α-, γ- and ß-forms, all crystallizing from the octanol/ethanol/water STF, despite the well-known difficulty in crystallizing the slow growing γ-form and the instability of the ß-form. The ability of STFs to produce notoriously hard to crystallize polymorphs should make them a versatile tool, ideal for polymorph discovery. This may enable a step change in the current, scatter-gun approach to polymorph screening. Furthermore, we show that aliquots of the nanocrystal-containing fluids can successfully seed metastable solutions. Hence, STFs may ultimately help provide a generic methodology for producing crystals and seed suspensions of any desired polymorph to supersede current targeted crystallization and seeding strategies.

Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

A new genus, Perplexacara, and new generic placements of species of Australian marsh beetles (Coleoptera: Scirtidae) based on morphology and molecular genetic data.

The Australian Scirtidae species previously identified as misplaced in the widespread genus Prionocyphon Redtenbacher are revisited as well as their possible relationship with the Australian genus Macrodascillus (Lea) using sequence data from the mitochondrial gene, cytochrome oxidase subunit 1 and two nuclear genes, elongation factor 1-alpha and Topoisomerase. The study confirmed the conclusion of Cooper et al. (2014) that the species did not belong in Prionocyphon. The study also included a species from each of three possibly related genera, Chameloscyphon Watts, Daploeuros Watts and Dasyscyphon Watts. Chameloscyphon huonensis Watts, Dasyscyphon victoriaensis Watts and Daploeuros lamingtonensis Watts were recovered as separate lineages with C. huonensis linking with Das. victoriaensis and Dap. lamingtonensis isolated. The species previously included in Prionocyphon were shown to belong in two genera, Macrodascillus and a new genus Perplexacara: Perplexacara caementum (Watts) new combination, P. latusmandibulara (Watts) new combination, P. macroflavida (Watts) new combination, Macrodascillus scalaris (Lea), M. insolitus (Watts) new combination and M. lamingtonensis (Watts) new combination.

Experiences and attitudes of hereditary cancer screening patients in a consumer directed testing model.

BACKGROUND: Since 2015, the Information is Power initiative has offered free and reduced cost hereditary cancer screening to the North Alabama population with a consumer-initiated model. Patients received pre-test and post-test education through a genetic counseling video. Positive results also received a call from a genetic counselor. OBJECTIVE: We surveyed past Information is Power patients to assess if video education and electronic result delivery addressed the needs of a hereditary cancer screening population. METHODS: An electronic survey was sent out to Information is Power patients who opted into research contact. The survey assessed participant knowledge, satisfaction with result delivery, and perceived uncertainty after receiving test results. RESULTS: 213 participants completed the survey. Eighteen percent of participants would have preferred individual communication with a genetics specialist about their results. Over 99 % of survey participants correctly interpreted a positive result, while 73 % correctly interpreted a negative result. Overall, participants were certain about the impact of their genetic test results. PRACTICE IMPLICATIONS: These findings support a model of population genetic testing and genetic counseling that is sustainable while meeting the educational needs of most participants. Observed misconceptions surrounding a negative result should be highlighted in future population screening patient resources to meet patient needs.

New genera, species and combinations in the Pseudomicrocara Armstrong group (Coleoptera: Scirtidae) based on morphology supported by mitochondrial and nuclear gene sequence data.

The Australian Scirtidae genus Pseudomicrocara Armstrong, previously shown to be polyphyletic, is revised using both morphology and sequence data from the mitochondrial gene cytochrome oxidase subunit 1 and two nuclear genes, elongation factor 1-alpha and topoisomerase. Twenty-three genera, 16 of which are new, are recognised based on morphology, primarily of the mandibles and maxillary palpi, and male and female genitalia. Maximum likelihood and Bayesian phylogenetic analyses were used to examine relationships among species from 21 of the 23 recognised genera. Fifteen of the genera were recovered as distinct lineages. A further six, Accolabass Watts, Anocyphon gen. nov., Copiacyphon gen. nov., Nasutuscyphon gen. nov., Pseudomicrocara and Saprocyphon gen. nov. were considered to be genera based on both morphology and phylogenetic analysis but their species composition is uncertain and will require more work to confirm. The 17 new genera are fully described, keys are provided to all the genera in the Pseudomicrocara group, and to all the species in the genera Copiacyphon gen. nov., Spilotocyphon gen. nov., Accolabass Watts, Saltuscyphon gen. nov. and Vadumcyphon gen. nov. The male aedeagi of all new genera and species are illustrated, as are the female prehensors of some species.                The following genera are described as new: Alpestriscyphon gen. nov., Anthocara gen. nov., Anocyphon gen. nov., Copiacyphon gen. nov., Furcacyphon gen. nov., Latuscara gen. nov., Pictacara gen. nov., Nasutuscyphon gen. nov., Nektriscyphon gen. nov., Pumiliocara gen. nov., Ruborcara gen. nov., Saltuscyphon gen. nov., Saprocyphon gen. nov., Sisyracyphon gen. nov., Spilotocyphon gen. nov., Tenebriocyphon gen. nov. and Vadumcyphon gen. nov. A total of 45 new combinations are proposed. The following species are described as new: Accolabass monteithi sp. nov.; Alpestriscyphon bartlefrere sp. nov., Al. spurgeon sp. nov.; Anocyphon lepus sp. nov.; Copiacyphon brindaleensis sp. nov., C. cardinalis sp. nov., C. dytikos sp. nov.; Pumiliocara peneparva sp. nov.; Ruborcara saintae sp. nov.; Saltuscyphon montanus sp. nov., Sal. teraniaensis sp. nov.; Saprocyphon bithongensis sp. nov.; Sisyracyphon brisbanensis sp. nov., S. bulburinensis sp. nov.; Spilotocyphon occidentalis sp. nov., Sp. orientalis sp. nov., Sp. zwicki sp. nov.; Vadumcyphon centralis sp. nov., V. rugosus sp. nov. A checklist of all Australian taxa in the redefined Pseudomicrocara group is included.                Sequence data of the Argentinian species Pseudomicrocara antarctica (Fairmaire) is included. Phylogenetic analyses place this species as a distinct lineage within the Pseudomicrocara group.

Intragenomic internal transcribed spacer 2 variation in a genus of parasitoid wasps (Hymenoptera: Braconidae): implications for accurate species delimitation and phylogenetic analysis.

A recent DNA barcoding study of Australian microgastrines (Hymenoptera: Braconidae) sought to use next-generation sequencing of the cytochrome c oxidase subunit 1 (COI) barcoding gene region, the wingless (WG) gene and the internal transcribed spacer 2 (ITS2) to delimit molecular species in a highly diverse group of parasitic wasps. Large intragenomic distances between ITS2 variants, often larger than the average interspecific variation, caused difficulties in using ITS2 for species delimitation in both threshold and tree-based approaches, and the gene was not included in the reported results of the previous DNA barcoding study. We here report on the intragenomic, and the intra- and interspecies, variation in ITS2in the microgastrine genus Diolcogasterto further investigate the value of ITS2as a marker for species delimitation and phylogenetics of the Microgastrinae. Distinctive intragenomic variant patterns were found in different species of Diolcogaster, with some species possessing a single major variant, and others possessing many divergent variants. Characterizing intragenomic variation of ITS2is critical as it is a widely used marker in hymenopteran phylogenetics and species delimitation, and large intragenomic distances such as those found in this study may obscure phylogenetic signal.

Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data.

Metabolomics is perhaps the most challenging of the -omics fields, given the complexity of an organism's metabolome and the rapid rate at which it changes. When one sets out to study metabolism there are numerous dynamic variables that can influence metabolism that must be considered. Recognizing the experimental challenges confronting researchers who undertake metabolism studies, workshops like the one at University of Alabama at Birmingham have been established to offer instructional guidance. A summary of the UAB course training materials is being published as a two-part Special Feature Tutorial. In this month's Part I the authors discuss details of good experimental design and sample collection and handling. In an upcoming Part II, the authors discuss in detail the various aspects of data analysis.

Patterns of population genetic variation in sympatric chiltoniid amphipods within a calcrete aquifer reveal a dynamic subterranean environment.

Calcrete aquifers from the Yilgarn region of arid central Western Australia contain an assemblage of obligate groundwater invertebrate species that are each endemic to single aquifers. Fine-scale phylogeographic and population genetic analyses of three sympatric and independently derived species of amphipod (Chiltoniidae) were carried out to determine whether there were common patterns of population genetic structure or evidence for past geographic isolation of populations within a single calcrete aquifer. Genetic diversity in amphipod mitochondrial DNA (cytochrome c oxidase subunit I gene) and allozymes were examined across a 3.5 km(2) region of the Sturt Meadows calcrete, which contains a grid of 115 bore holes (=wells). Stygobiont amphipods were found to have high levels of mitochondrial haplotype diversity coupled with low nucleotide diversity. Mitochondrial phylogeographic structuring was found between haplogroups for one of the chiltoniid species, which also showed population structuring for nuclear markers. Signatures of population expansion in two of the three species, match previous findings for diving beetles at the same site, indicating that the system is dynamic. We propose isolation of populations in refugia within the calcrete, followed by expansion events, as the most likely source of intraspecific genetic diversity, due to changes in water level influencing gene flow across the calcrete.

A multicentre study comparing two methods for serum free light chain analysis.

BACKGROUND: Serum free light chain analysis is now well established in the investigation of monoclonal gammopathies. In the UK there has, until recently, been a single supplier of kits for such analysis. Recently, a second method using monoclonal antisera was introduced. We have compared the performance of these two kits in four routine laboratories. METHOD: Samples submitted for routine analysis (327 samples, 258 [79%] from patients with B-cell lymphoproliferative disease) for serum free light chains were tested by both technologies (Freelite, Binding Site and N Latex FLC, Siemens), according to the manufacturers' instructions. RESULTS: Qualitative data were available by both methods on 313 samples for serum free kappa chains and 324 samples for lambda free light chains. We found poor correspondence of 81% for kappa and 74% for lambda. Five percent of samples were significantly discordant in these assays. CONCLUSIONS: These assays perform very differently in clinical practice. They cannot be used interchangeably, especially if monitoring patient responses to therapy.

What lies beneath: molecular phylogenetics and ancestral state reconstruction of the ancient subterranean Australian Parabathynellidae (Syncarida, Crustacea).

The crustacean family Parabathynellidae is an ancient and significant faunal component of subterranean ecosystems. Molecular data were generated in order to examine phylogenetic relationships amongst Australian genera and assess the species diversity of this group within Australia. We also used the resultant phylogenetic framework, in combination with an ancestral state reconstruction (ASR) analysis, to explore the evolution of two key morphological characters (number of segments of the first and second antennae), previously used to define genera, and assess the oligomerization principle (i.e. serial appendage reduction over time), which is commonly invoked in crustacean systematics. The ASR approach also allowed an assessment of whether there has been convergent evolution of appendage numbers during the evolution of Australian parabathynellids. Sequence data from the mtDNA COI and nDNA 18S rRNA genes were obtained from 32 parabathynellid species (100% of described genera and ~25% of described species) from key groundwater regions across Australia. Phylogenetic analyses revealed that species of each known genus, defined by traditional morphological methods, were monophyletic, suggesting that the commonly used generic characters are robust for defining distinct evolutionary lineages. Additionally, ancestral state reconstruction analysis provided evidence for multiple cases of convergent evolution for the two morphological characters evaluated, suggesting that caution needs to be shown when using these characters for elucidating phylogenetic relationships, particularly when there are few morphological characters available for reconstructing relationships. The ancestral state analysis contradicted the conventional view of parabathynellid evolution, which assumes that more simplified taxa (i.e. those with fewer-segmented appendages and setae) are derived and more complex taxa are primitive.

Evidence for population fragmentation within a subterranean aquatic habitat in the Western Australian desert.

The evolution of subterranean animals following multiple colonisation events from the surface has been well documented, but few studies have investigated the potential for species diversification within cavernicolous habitats. Isolated calcrete (carbonate) aquifers in central Western Australia have been shown to contain diverse assemblages of aquatic subterranean invertebrate species (stygofauna) and to offer a unique model system for exploring the mechanisms of speciation in subterranean ecosystems. In this paper, we investigated the hypothesis that microallopatric speciation processes (fragmentation and isolation by distance (IBD)) occur within calcretes using a comparative phylogeographic study of three stygobiontic diving beetle species, one amphipod species and a lineage of isopods. Specimens were sequenced for the mitochondrial cytochrome c oxidase 1 gene from three main sites: Quandong Well, Shady Well (SW) and Mt. Windarra (MW), spanning a 15 km region of the Laverton Downs Calcrete. Phylogenetic and haplotype network analyses revealed that each species possessed a single divergent clade of haplotypes that were present only at the southern MW site, despite the existence of other haplotypes at MW that were shared with SW. IBD between MW and SW was evident, but the common phylogeographic pattern most likely resulted from fragmentation, possibly by a salt lake adjacent to MW. These findings suggest that microallopatric speciation within calcretes may be a significant diversifying force, although the proportion of stygofauna species that may have resulted from in situ speciation in this system remains to be determined.

Loss of type III transforming growth factor-beta receptor expression is due to methylation silencing of the transcription factor GATA3 in renal cell carcinoma.

Loss of transforming growth factor-beta receptor III (TbetaRIII) correlates with loss of transforming growth factor-beta (TGF-beta) responsiveness and suggests a role for dysregulated TGF-beta signaling in clear cell renal cell carcinoma (ccRCC) progression and metastasis. Here we identify that for all stages of ccRCC TbetaRIII expression is downregulated in patient-matched tissue samples and cell lines. We find that this loss of expression is not due to methylation of the gene and we define GATA3 as the first transcriptional factor to positively regulate TbetaRIII expression in human cells. We localize GATA3's binding to a 10-bp region of the TbetaRIII proximal promoter. We demonstrate that GATA3 mRNA is downregulated in all stages, of ccRCC, mechanistically show that GATA3 is methylated in ccRCC patient tumor tissues as well as cell lines, and that inhibiting GATA3 expression in normal renal epithelial cells downregulates TbetaRIII mRNA and protein expression. These data support a sequential model whereby loss of GATA3 expression through epigenetic silencing decreases TbetaRIII expression during ccRCC progression.

DNA barcoding of stygofauna uncovers cryptic amphipod diversity in a calcrete aquifer in Western Australia's arid zone.

The arid Yilgarn region of Western Australia contains numerous subterranean calcrete aquifers with unique assemblages of obligate groundwater invertebrates (stygofauna). We aimed to establish a DNA barcoding framework for the macro-invertebrates present in a single calcrete, as a basis for future assessment of biodiversity of the Yilgarn calcretes and for investigating food webs. Intense sampling of a bore field grid in the Sturt Meadows calcrete was undertaken to obtain representatives of the entire macro-invertebrate ecosystem. A 623-bp fragment of the mitochondrial cytochrome c oxidase 1 (COI) gene was used to provide DNA barcodes for stygobiont macro-invertebrates plus terrestrial organisms that are found in the calcrete. Phylogenetic analyses revealed the existence of 12 divergent monophyletic groups of haplotypes. Subterranean amphipods (Chiltoniidae) showed three groups of COI haplotypes with sequence divergences between them of >11%. Allozyme analyses found a large number of fixed allelic differences between these three amphipod groups, indicating that there are three morphologically cryptic species within the Sturt Meadows calcrete. Unlike the sister triplet of dytiscid beetles present, the amphipods are not sister clades and are more closely related to other Yilgarn and non-Yilgarn amphipods than to each other. Our results show that the aquifer contains at least 12 macro-invertebrate species and DNA barcoding provides a useful means for discriminating species in this system.

The effects of sibutramine on the microstructure of eating behaviour and energy expenditure in obese women.

Given the suggestion that many potential anti-obesity drugs may enhance within-meal satiation, few studies have directly measured the effects of any drug on the microstructure of human eating behaviour. The effects of 7 days dosing with sibutramine 10 mg and 15 mg a day on appetite and energy balance were determined in 30 obese women (BMI 34.6 +/- 3.3 kg/m2, age 46.0 +/- 12.9 years) using a Universal Eating Monitor (UEM) and indirect calorimetry, in a double-blind, placebo-controlled crossover study. At day 7, sibutramine 10 mg and 15 mg reduced food intake by 16.6% and 22.3%, respectively (p < 0.001), compared with placebo. Sibutramine reduced eating rate compared with placebo rather than meal length (10 mg p < 0.05; 15 mg p < 0.001). In addition, sibutramine 10 mg significantly reduced hunger later in the meal (p < 0.05) and sibutramine 15 mg increased fullness early in the meal (p < 0.01), both of which are consistent with enhanced within-meal satiation. Sibutramine had little effect on resting metabolic rate, although 15 mg did significantly reduce respiratory quotient at several time points during the test day. These results provide novel evidence that decreased consumption of a test meal induced by sibutramine is primarily because of reduced eating rate, enhancing the deceleration in cumulative food intake within a meal associated with the development of satiety. Changes in within-meal appetite ratings appear particularly sensitive to drug-induced enhancement of satiation, and may provide key indices for assessing the therapeutic potential of novel anti-obesity drugs.

Fine-scale comparative phylogeography of a sympatric sister species triplet of subterranean diving beetles from a single calcrete aquifer in Western Australia.

Calcrete aquifers in the arid Yilgarn region of central Western Australia are a biodiversity hotspot for stygofauna. A distinct pattern of interspecific size class variation among subterranean dytiscid beetle species has been observed in 29 of these aquifers where either two or three small, medium and/or large sympatric species are found that are in some cases sister species. We used a 3.5 km(2) grid of bores to sample dytiscids on a fine-scale and employed a comparative phylogeographical and population genetic approach to investigate the origins of a sympatric sister species triplet of diving beetles from a single aquifer. Mitochondrial DNA sequence data from the Cytochrome oxidase c subunit I gene revealed that all three species have high levels of haplotype diversity with ancient (approximately 1 million years ago) intra-specific coalescence of haplotypes, but low levels of nucleotide diversity. Population analyses provide evidence for multiple expansion events within each species. There was spatial heterogeneity in the distribution of genetic variation and abundance both within and among the three taxa. Population analyses revealed significant fine-scale differentiation with isolation by distance for Paroster macrosturtensis and P. mesosturtensis, but not the smallest species P. microsturtensis. Haplotype network analyses provided limited or no evidence for past population fragmentation within the large and small species, but substantial historical divergence was observed in P. mesosturtensis that was not spatially structured. A patchy population structure with contemporaneous and historical isolation by distance in the three species is likely to have been a significant isolating and diversifying force, preventing us from ruling out a potential role for allopatric divergence during speciation of this beetle sister triplet.

Highs and lows of coeliac screening.

Coeliac screening is one of the most frequently requested investigations in immunology laboratories. This study evaluates seven commercial anti-tissue transglutaminase (tTG) enzyme-linked immunosorbent assay (ELISA) kits across a varied population of 80 routine samples received for coeliac screening. This investigation assesses whether or not absorbance levels can be used to detect low serum IgA and whether or not raised IgA concentrations can interfere with IgA-tTG results. Sensitivity and specificity varied hugely and four out of the seven methods required cut-off value modification to attain 100% sensitivity with endomysial testing. Four of the seven kits identified low IgA samples with greater than 90% accuracy, but sensitivity dropped to 75% in others. All the kits were affected by raised serum IgA concentrations, leading to false-positive results. There was notable variation between the seven kits in respect of high IgA concentrations and positive IgA-tTG results, with concordance analysis indicating a weak linear relationship between IgA concentration and tTG value. This study concludes that there is significant variability between the commercial tTG assays in the diagnostic market. Laboratories should be aware of their kit's limitations and may need to adjust cut-off values to maximise sensitivity. It is possible to identify IgA deficiency from the tTG values, but the ability to do this varies between manufacturers. Raised IgA levels continue to affect the specificity of IgA-tTG assays and interference by polyclonal and monoclonal IgA should be considered in samples with positive tTG and negative endomysial results.