ALMA Survey of Lupus Class III Stars: Early Planetesimal Belt Formation and Rapid Disk Dispersal

Class III stars are those in star forming regions without large non-photospheric infrared emission, suggesting recent dispersal of their protoplanetary disks. We observed 30 class III stars in the 1-3 Myr Lupus region with ALMA at ∼856μm, resulting in 4 detections that we attribute to circumstellar dust. Inferred dust masses are 0.036 − 0.093M⊕, ∼1 order of magnitude lower than any previous measurements; one disk is resolved with radius ∼80 au. Two class II sources in the field of view were also detected, and 11 other sources, consistent with sub-mm galaxy number counts. Stacking non-detections yields a marginal detection with mean dust mass ∼0.0048M⊕. We searched for gas emission from the CO J=3-2 line, and present its detection to NO Lup inferring a gas mass (4.9 ± 1.1) × 10−5 M⊕ and gas-to-dust ratio 1.0 ± 0.4. Combining our survey with class II sources shows a gap in the disk mass distribution from 0.09 − 2M⊕ for >0.7M⊙ Lupus stars, evidence of rapid dispersal of mm-sized dust from protoplanetary disks. The class III disk mass distribution is consistent with a population model of planetesimal belts that go on to replenish the debris disks seen around main sequence stars. This suggests that planetesimal belt formation does not require long-lived protoplanetary disks, i.e., planetesimals form within ∼2 Myr. While all 4 class III disks are consistent with collisional replenishment, for two the gas and/or mid-IR emission could indicate primordial circumstellar material in the final stages of protoplanetary disk dispersal. Two class III stars without sub-mm detections exhibit hot emission that could arise from ongoing planet formation processes inside ∼1 au

Neurotrophin gene augmentation by electrotransfer to improve cochlear implant hearing outcomes

This Review outlines the development of DNA-based therapeutics for treatment of hearing loss, and in particular, considers the potential to utilize the properties of recombinant neurotrophins to improve cochlear auditory (spiral ganglion) neuron survival and repair. This potential to reduce spiral ganglion neuron death and indeed re-grow the auditory nerve fibres has been the subject of considerable pre-clinical evaluation over decades with the view of improving the neural interface with cochlear implants. This provides the context for discussion about the development of a novel means of using cochlear implant electrode arrays for gene electrotransfer. Mesenchymal cells which line the cochlear perilymphatic compartment can be selectively transfected with (naked) plasmid DNA using array - based gene electrotransfer, termed ‘close-field electroporation’. This technology is able to drive expression of brain derived neurotrophic factor (BDNF) in the deafened guinea pig model, causing re-growth of the spiral ganglion peripheral neurites towards the mesenchymla cells, and hence into close proximity with cochlear implant electrodes within scala tympani. This was associated with functional enhancement of the cochlear implant neural interface (lower neural recruitment thresholds and expanded dynamic range, measured using electrically - evoked auditory brainstem responses). The basis for the efficiency of close-field electroporation arises from the compression of the electric field in proximity to the ganged cochlear implant electrodes. The regions close to the array with highest field strength corresponded closely to the distribution of bioreporter cells (adherent human embryonic kidney (HEK293)) expressing green fluorescent reporter protein (GFP) following gene electrotransfer. The optimization of the gene electrotransfer parameters using this cell-based model correlated closely with in vitro and in vivo cochlear gene delivery outcomes. The migration of the cochlear implant electrode array-based gene electrotransfer platform towards a clinical trial for neurotrophin-based enhancement of cochlear implants is supported by availability of a novel regulatory compliant mini-plasmid DNA backbone (pFAR4; plasmid Free of Antibiotic Resistance v.4) which could be used to package a ‘humanized’ neurotrophin expression cassette. A reporter cassette packaged into pFAR4 produced prominent GFP expression in the guinea pig basal turn perilymphatic scalae. More broadly, close-field gene electrotransfer may lend itself to a spectrum of potential DNA therapeutics applications benefitting from titratable, localised, delivery of naked DNA, for gene augmentation, targeted gene regulation, or gene substitution strategies

High-resolution ALMA and HST images of q¹ Eri: an asymmetric debris disc with an eccentric Jupiter

We present Atacama Large Millimetre/sub-Millimetre Array (ALMA) 1.3 and 0.86 mm observations of the nearby (17.34 pc) F9V star q1 Eri (HD 10647, HR 506). This system, with age ∼1.4 Gyr, hosts a ∼2 au radial velocity planet and a debris disc with the highest fractional luminosity of the closest 300 FGK type stars. The ALMA images, with resolution ∼0′′.5, reveal a broad (34–134 au) belt of millimetre emission inclined by 76.7 ± 1.0 degrees with maximum brightness at 81.6 ± 0.5 au. The images reveal an asymmetry, with higher flux near the south-west ansa, which is also closer to the star. Scattered light observed with the Hubble Space Telescope is also asymmetric, being more radially extended to the north-east. We fit the millimetre emission with parametric models and place constraints on the disc morphology, radius, width, dust mass, and scale height. We find that the south-west ansa asymmetry is best fitted by an extended clump on the inner edge of the disc, consistent with perturbations from a planet with mass 8M⊕−11MJup at ∼60 au that may have migrated outwards, similar to Neptune in our Solar system. If the measured vertical aspect ratio of h = 0.04 ± 0.01 is due to dynamical interactions in the disc, then this requires perturbers with sizes >1200 km. We find tentative evidence for a 0.86 mm excess within 10 au, 70±22 μJy, that may be due to an inner planetesimal belt. We find no evidence for CO gas, but set an upper bound on the CO gas mass of 4 × 10−6 M⊕ (⁠3σ⁠), consistent with cometary abundances in the Solar system

Chlorfenapyr: a new insecticide with novel mode of action can control pyrethroid resistant malaria vectors

<p>Abstract</p> <p>Background</p> <p>Malaria vectors have acquired widespread resistance to many of the currently used insecticides, including synthetic pyrethroids. Hence, there is an urgent need to develop alternative insecticides for effective management of insecticide resistance in malaria vectors. In the present study, chlorfenapyr was evaluated against <it>Anopheles culicifacies </it>and <it>Anopheles stephensi </it>for its possible use in vector control.</p> <p>Methods</p> <p>Efficacy of chlorfenapyr against <it>An. culicifacies </it>and <it>An. stephensi </it>was assessed using adult bioassay tests. In the laboratory, determination of diagnostic dose, assessment of residual activity on different substrates, cross-resistance pattern with different insecticides and potentiation studies using piperonyl butoxide were undertaken by following standard procedures. Potential cross-resistance patterns were assessed on field populations of <it>An. culicifacies</it>.</p> <p>Results</p> <p>A dose of 5.0% chlorfenapyr was determined as the diagnostic concentration for assessing susceptibility applying the WHO tube test method in anopheline mosquitoes with 2 h exposure and 48 h holding period. The DDT-resistant/malathion-deltamethrin-susceptible strain of <it>An. culicifacies </it>species C showed higher LD50 and LD99 (0.67 and 2.39% respectively) values than the DDT-malathion-deltamethrin susceptible <it>An. culicifacies </it>species A (0.41 and 2.0% respectively) and <it>An. stephensi </it>strains (0.43 and 2.13% respectively) and there was no statistically significant difference in mortalities among the three mosquito species tested (p > 0.05). Residual activity of chlorfenapyr a.i. of 400 mg/m²on five fabricated substrates, namely wood, mud, mud+lime, cement and cement + distemper was found to be effective up to 24 weeks against <it>An. culicifacies </it>and up to 34 weeks against <it>An. stephensi</it>. No cross-resistance to DDT, malathion, bendiocarb and deltamethrin was observed with chlorfenapyr in laboratory-reared strains of <it>An. stephensi </it>and field-caught <it>An. culicifacies. </it>Potentiation studies demonstrated the antagonistic effect of PBO.</p> <p>Conclusion</p> <p>Laboratory studies with susceptible and resistant strains of <it>An. culicifacies </it>and <it>An. stephensi</it>, coupled with limited field studies with multiple insecticide-resistant <it>An. culicifacies </it>have shown that chlorfenapyr can be a suitable insecticide for malaria vector control, in multiple-insecticide-resistant mosquitoes especially in areas with pyrethroid resistant mosquitoes.</p

A perspective on the measurement of time in plant disease epidemiology

The growth and development of plant pathogens and their hosts generally respond strongly to the temperature of their environment. However, most studies of plant pathology record pathogen/host measurements against physical time (e.g. hours or days) rather than thermal time (e.g. degree-days or degree-hours). This confounds the comparison of epidemiological measurements across experiments and limits the value of the scientific literature

Nurses' experiences of communicating respect to patients: Influences and challenges

A qualitative study utilizing Interpretive Phenomenological Analysis of a sample of nursing interviews to explore the ways in which respect is conceptualized and communicated to patients.Background: Respectful care is central to ethical codes of practice and optimal patient care, but little is known about the influences on and challenges in communicating respect. Research question: What are the intra- and inter-personal influences on nurses’ communication of respect? Research design and participants: Semi-structured interviews with 12 hospital-based UK registered nurses were analysed using interpretative phenomenological analysis to explore their experiences of communicating respect to patients and associated influences. Ethical considerations: The study was approved by the Institutional ethics board and National Health Service Trust. Findings: Three interconnected superordinate themes were identified: ‘private self: personal attitudes’, ‘outward self: showing respect’ and ‘reputational self: being perceived as respectful’. Respectful communication involved a complex set of influences, including attitudes of respect towards patients, needs and goals, beliefs around the nature of respectful communication, skills and influencing sociocultural factors. A tension between the outward self as intended and perceived presented challenges for nurses’ reputational self as respectful, with negative implications for patient care. Discussion: The study offers an in-depth understanding of intra- and inter-personal influences on communicating respect, and sheds light on challenges involved, helping provide practical insights to support respectful care. Conclusion: Findings stress the need for improved conceptualisations of respect in healthcare settings to formally recognise the complex attitudinal and socially constructed nature of respect and for appropriate professional training to improve its communicatio

Anopheles gambiae PGRPLC-Mediated Defense against Bacteria Modulates Infections with Malaria Parasites

Recognition of peptidoglycan (PGN) is paramount for insect antibacterial defenses. In the fruit fly Drosophila melanogaster, the transmembrane PGN Recognition Protein LC (PGRP-LC) is a receptor of the Imd signaling pathway that is activated after infection with bacteria, mainly Gram-negative (Gram−). Here we demonstrate that bacterial infections of the malaria mosquito Anopheles gambiae are sensed by the orthologous PGRPLC protein which then activates a signaling pathway that involves the Rel/NF-κB transcription factor REL2. PGRPLC signaling leads to transcriptional induction of antimicrobial peptides at early stages of hemolymph infections with the Gram-positive (Gram+) bacterium Staphylococcus aureus, but a different signaling pathway might be used in infections with the Gram− bacterium Escherichia coli. The size of mosquito symbiotic bacteria populations and their dramatic proliferation after a bloodmeal, as well as intestinal bacterial infections, are also controlled by PGRPLC signaling. We show that this defense response modulates mosquito infection intensities with malaria parasites, both the rodent model parasite, Plasmodium berghei, and field isolates of the human parasite, Plasmodium falciparum. We propose that the tripartite interaction between mosquito microbial communities, PGRPLC-mediated antibacterial defense and infections with Plasmodium can be exploited in future interventions aiming to control malaria transmission. Molecular analysis and structural modeling provided mechanistic insights for the function of PGRPLC. Alternative splicing of PGRPLC transcripts produces three main isoforms, of which PGRPLC3 appears to have a key role in the resistance to bacteria and modulation of Plasmodium infections. Structural modeling indicates that PGRPLC3 is capable of binding monomeric PGN muropeptides but unable to initiate dimerization with other isoforms. A dual role of this isoform is hypothesized: it sequesters monomeric PGN dampening weak signals and locks other PGRPLC isoforms in binary immunostimulatory complexes further enhancing strong signals

‘Sub-Prime’ Water, Low-Security Entitlements and Policy Challenges in Over-Allocated River Basins: the Case of the Murray–Darling Basin

Environmental policy is often implemented using market instruments. In some cases, including carbon taxing, the links between financial products and the environmental objectives, are transparent. In other cases, including water markets, the links are less transparent. In Australia’s Murray–Darling Basin (MDB), financial water products are known as ‘entitlements’, and are similar to traditional financial products, such as shares. The Australian water market includes ‘Low Security’ entitlements, which are similar to ‘sub-prime’ mortgage bonds because they are unlikely to yield an amount equal to their financial worth. Nearly half the water purchased under the Murray–Darling Basin Plan for environmental purposes is ‘Low Security’. We suggest that the current portfolio of water held by the Australian Government for environmental purposes reflects the mortgage market in the lead-up to the global financial crisis. Banks assumed that the future value of the mortgage market would reflect past trends. Similarly, it is assumed that the future value of water products will reflect past trends, without considering climate change. Historic records of allocations to ‘Low Security’ entitlements in the MDB suggest that, in the context of climate change, the Basin Plan water portfolio may fall short of the target annual average yield of 2075 GL by 511 GL. We recommend adopting finance sector methods including ‘hedging’ ‘Low Security’ entitlements by purchasing an additional 322–2755 GL of ‘Low Security’, or 160–511 GL of ‘High Security’ entitlements. Securing reliable environmental water is a global problem. Finance economics present opportunities for increasing the reliability of environmental flows

Optimality of Human Contour Integration

For processing and segmenting visual scenes, the brain is required to combine a multitude of features and sensory channels. It is neither known if these complex tasks involve optimal integration of information, nor according to which objectives computations might be performed. Here, we investigate if optimal inference can explain contour integration in human subjects. We performed experiments where observers detected contours of curvilinearly aligned edge configurations embedded into randomly oriented distractors. The key feature of our framework is to use a generative process for creating the contours, for which it is possible to derive a class of ideal detection models. This allowed us to compare human detection for contours with different statistical properties to the corresponding ideal detection models for the same stimuli. We then subjected the detection models to realistic constraints and required them to reproduce human decisions for every stimulus as well as possible. By independently varying the four model parameters, we identify a single detection model which quantitatively captures all correlations of human decision behaviour for more than 2000 stimuli from 42 contour ensembles with greatly varying statistical properties. This model reveals specific interactions between edges closely matching independent findings from physiology and psychophysics. These interactions imply a statistics of contours for which edge stimuli are indeed optimally integrated by the visual system, with the objective of inferring the presence of contours in cluttered scenes. The recurrent algorithm of our model makes testable predictions about the temporal dynamics of neuronal populations engaged in contour integration, and it suggests a strong directionality of the underlying functional anatomy

The integration of occlusion and disparity information for judging depth in autism spectrum disorder

In autism spectrum disorder (ASD), atypical integration of visual depth cues may be due to flattened perceptual priors or selective fusion. The current study attempts to disentangle these explanations by psychophysically assessing within-modality integration of ordinal (occlusion) and metric (disparity) depth cues while accounting for sensitivity to stereoscopic information. Participants included 22 individuals with ASD and 23 typically developing matched controls. Although adults with ASD were found to have significantly poorer stereoacuity, they were still able to automatically integrate conflicting depth cues, lending support to the idea that priors are intact in ASD. However, dissimilarities in response speed variability between the ASD and TD groups suggests that there may be differences in the perceptual decision-making aspect of the task