Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies.

Human cells express thousands of different surface proteins that can be used for cell classification, or to distinguish healthy and disease conditions. A method capable of profiling a substantial fraction of the surface proteome simultaneously and inexpensively would enable more accurate and complete classification of cell states. We present a highly multiplexed and quantitative surface proteomic method using genetically barcoded antibodies called phage-antibody next-generation sequencing (PhaNGS). Using 144 preselected antibodies displayed on filamentous phage (Fab-phage) against 44 receptor targets, we assess changes in B cell surface proteins after the development of drug resistance in a patient with acute lymphoblastic leukemia (ALL) and in adaptation to oncogene expression in a Myc-inducible Burkitt lymphoma model. We further show PhaNGS can be applied at the single-cell level. Our results reveal that a common set of proteins including FLT3, NCR3LG1, and ROR1 dominate the response to similar oncogenic perturbations in B cells. Linking high-affinity, selective, genetically encoded binders to NGS enables direct and highly multiplexed protein detection, comparable to RNA-sequencing for mRNA. PhaNGS has the potential to profile a substantial fraction of the surface proteome simultaneously and inexpensively to enable more accurate and complete classification of cell states

an overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT

© Copyright owned by the author(s). MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with H I masses from ∼ 106 to ∼ 1011 M, and luminosities from MR ∼ 12 to MR ∼ −22. The sample is selected to uniformly cover the available range in log(MHI). Our extremely deep observations, down to H I column density limits of well below 1018 cm−2 — or a few hundred times fainter than the typical H I disks in galaxies — will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modeling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT’s capabilities

Housing options for older people in a reimagined housing system: a case study from England

The housing options of older people now extend far beyond the traditional choice between staying put and making do, or moving to specialist housing or residential care. A flexible suite of options has emerged, centred on promoting independence and wellbeing. Valuable insights have been provided into the development, delivery, costs and benefits of these options. Light has also been cast on the experiences and preferences of older people. However, little is know about who gets what housing, where and why. This reflects a tendency within analysis to consider these different housing options in isolation. This study responds by situating the housing options of older people within wider debates about the reimagining of the housing system driven by the neoliberal transformation in housing politics. Taking a case study approach, it explores the gap between the ambitions of policy and realities of provision at the local level, relates this to the particular intersection of state practices and market mechanisms manifest in the case study and, in doing so, rises to the challenge of extending analysis of the impacts of the neoliberal approach on the right to housing to new groups and different settings

MIGHTEE-\HI: Possible interactions with the galaxy NGC~895

The transformation and evolution of a galaxy is strongly influenced by interactions with its environment. Neutral hydrogen (\HI) is an excellent way to trace these interactions. Here, we present \HI\ observations of the spiral galaxy NGC~895, which was previously thought to be isolated. High-sensitivity \HI\ observations from the MeerKAT large survey project MIGHTEE reveal possible interaction features, such as extended spiral arms, and the two newly discovered \HI\ companions, that drive us to change the narrative that it is an isolated galaxy. We combine these observations with deep optical images from the Hyper Suprime Camera to show an absence of tidal debris between NGC 895 and its companions. We do find an excess of light in the outer parts of the companion galaxy MGTH$\_$J022138.1-052631 which could be an indication of external perturbation and thus possible sign of interactions. Our analysis shows that NGC~895 is an actively star-forming galaxy with a SFR of $\mathrm{1.75 \pm 0.09 [M_{\odot}/yr]}$, a value typical for high stellar mass galaxies on the star forming main sequence. It is reasonable to state that different mechanisms may have contributed to the observed features in NGC~895 and this emphasizes the need to revisit the target with more detailed observations. Our work shows the high potential and synergy of using state-of-the-art data in both \HI\ and optical to reveal a more complete picture of galaxy environments.Comment: 14 pages, 10 figures. Accepted for publication in MNRA

Investigation into pedestrian exposure to near-vehicle exhaust emissions

<p>Abstract</p> <p>Background</p> <p>Inhalation of diesel particulate matter (DPM) is known to have a negative impact on human health. Consequently, there are regulations and standards that limit the maximum concentrations to which persons may be exposed and the maximum concentrations allowed in the ambient air. However, these standards consider steady exposure over large spatial and time scales. Due to the nature of many vehicle exhaust systems, pedestrians in close proximity to a vehicle's tailpipe may experience events where diesel particulate matter concentrations are high enough to cause acute health effects for brief periods of time.</p> <p>Methods</p> <p>In order to quantify these exposure events, instruments which measure specific exhaust constituent concentrations were placed near a roadway and connected to the mouth of a mannequin used as a pedestrian surrogate. By measuring concentrations at the mannequin's mouth during drive-by events with a late model diesel truck, a representative estimate of the exhaust constituent concentrations to which a pedestrian may be exposed was obtained. Typical breathing rates were then multiplied by the measured concentrations to determine the mass of pollutant inhaled.</p> <p>Results</p> <p>The average concentration of diesel particulate matter measured over the duration of a single drive-by test often exceeded the low concentrations used in human clinical studies which are known to cause acute health effects. It was also observed that higher concentrations of diesel particulate matter were measured at the height of a stroller than were measured at the mouth of a mannequin.</p> <p>Conclusion</p> <p>Diesel particulate matter concentrations during drive-by incidents easily reach or exceed the low concentrations that can cause acute health effects for brief periods of time. For the case of a particularly well-tuned late-model year vehicle, the mass of particulate matter inhaled during a drive-by incident is small compared to the mass inhaled daily at ambient conditions. On a per breath basis, however, the mass of particulate matter inhaled is large compared to the mass inhaled at ambient conditions. Finally, it was determined that children, infants, or people breathing at heights similar to that of a passing vehicle's tailpipe may be exposed to higher concentrations of particulate matter than those breathing at higher locations, such as adults standing up.</p

An overview of the MHONGOOSE survey: Observing nearby galaxies with MeerKAT

MHONGOOSE is a deep survey of the neutral hydrogen distribution in a representative sample of 30 nearby disk and dwarf galaxies with HI masses from 10^6 to ~10^{11} M_sun, and luminosities from M_R ~ -12 to M_R ~ -22. The sample is selected to uniformly cover the available range in log(M_HI). Our extremely deep observations, down to HI column density limits of well below 10^{18} cm^{-2} - or a few hundred times fainter than the typical HI disks in galaxies - will directly detect the effects of cold accretion from the intergalactic medium and the links with the cosmic web. These observations will be the first ever to probe the very low-column density neutral gas in galaxies at these high resolutions. Combination with data at other wavelengths, most of it already available, will enable accurate modelling of the properties and evolution of the mass components in these galaxies and link these with the effects of environment, dark matter distribution, and other fundamental properties such as halo mass and angular momentum. MHONGOOSE can already start addressing some of the SKA-1 science goals and will provide a comprehensive inventory of the processes driving the transformation and evolution of galaxies in the nearby universe at high resolution and over 5 orders of magnitude in column density. It will be a Nearby Galaxies Legacy Survey that will be unsurpassed until the advent of the SKA, and can serve as a highly visible, lasting statement of MeerKAT's capabilities

Trypanosoma brucei Modifies the Tsetse Salivary Composition, Altering the Fly Feeding Behavior That Favors Parasite Transmission

Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by the Trypanosoma parasite that affects humans and livestock on the African continent. Metacyclic infection rates in natural tsetse populations with Trypanosoma brucei, including the two human-pathogenic subspecies, are very low, even in epidemic situations. Therefore, the infected fly/host contact frequency is a key determinant of the transmission dynamics. As an obligate blood feeder, tsetse flies rely on their complex salivary potion to inhibit host haemostatic reactions ensuring an efficient feeding. The results of this experimental study suggest that the parasite might promote its transmission through manipulation of the tsetse feeding behavior by modifying the saliva composition. Indeed, salivary gland Trypanosoma brucei-infected flies display a significantly prolonged feeding time, thereby enhancing the likelihood of infecting multiple hosts during the process of a single blood meal cycle. Comparison of the two major anti-haemostatic activities i.e. anti-platelet aggregation and anti-coagulation activity in these flies versus non-infected tsetse flies demonstrates a significant suppression of these activities as a result of the trypanosome-infection status. This effect was mainly related to the parasite-induced reduction in salivary gland gene transcription, resulting in a strong decrease in protein content and related biological activities. Additionally, the anti-thrombin activity and inhibition of thrombin-induced coagulation was even more severely hampered as a result of the trypanosome infection. Indeed, while naive tsetse saliva strongly inhibited human thrombin activity and thrombin-induced blood coagulation, saliva from T. brucei-infected flies showed a significantly enhanced thrombinase activity resulting in a far less potent anti-coagulation activity. These data clearly provide evidence for a trypanosome-mediated modification of the tsetse salivary composition that results in a drastically reduced anti-haemostatic potential and a hampered feeding performance which could lead to an increase of the vector/host contact and parasite transmission in field conditions

A dyadic approach to understanding the impact of breast cancer on relationships between partners during early survivorship

© 2016 The Author(s). Background: The shared impact of breast cancer for women and their male partners is emerging as an important consideration during the experience of a breast cancer diagnosis, particularly during survivorship. This study aimed to explore the experiences of women and their partners during early survivorship and contributes a range of insights into the lives of those intimately affected by breast cancer. Methods: In-depth interviews were completed with Australian women survivors of breast cancer (n = 8) and their partners (n = 8), between six months and five years following cessation of treatment. Questions included a focus on the women and their partners' daily experiences during early survivorship, including the management of ongoing symptoms, engagement in leisure and social interests, returning to work, communicating with each other, maintenance of the current relationship and other important roles and responsibilities. Thematic analysis was employed to determine key themes arising from the dyadic accounts of women and their partners' experiences during early breast cancer survivorship. Results: Women and their partners experienced many changes to their previous roles, responsibilities and relationships during early breast cancer survivorship. Couples also reported a range of communication, intimacy and sexuality concerns which greatly impacted their interactions with each other, adding further demands on the relationship. Three significant themes were determined: (1) a disconnection within the relationship - this was expressed as the woman survivor of breast cancer needing to prioritise her own needs, sometimes at the expense of her partner and the relationship; (2) reformulating the relationship - this reflects the strategies used by couples to negotiate changes within the relationship; and (3) support is needed to negotiate the future of the relationship - couples emphasised the need for additional support and resources to assist them in maintaining their relationship during early survivorship. Conclusion: It can be concluded that the early survivorship period represents a crucial time for both women and their partners and there are currently limited options available to meet their shared needs and preferences for support. Findings indicate that a suitable model of care underpinned by a biopsychosocial framework, access to comprehensive assessment, timely support and the provision of targeted resources are urgently needed to assist women and their partners during this critical time

Noise Characterization and Filtering in the MicroBooNE Liquid Argon TPC

The low-noise operation of readout electronics in a liquid argon time projection chamber (LArTPC) is critical to properly extract the distribution of ionization charge deposited on the wire planes of the TPC, especially for the induction planes. This paper describes the characteristics and mitigation of the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase LArTPC comprises two induction planes and one collection sense wire plane with a total of 8256 wires. Current induced on each TPC wire is amplified and shaped by custom low-power, low-noise ASICs immersed in the liquid argon. The digitization of the signal waveform occurs outside the cryostat. Using data from the first year of MicroBooNE operations, several excess noise sources in the TPC were identified and mitigated. The residual equivalent noise charge (ENC) after noise filtering varies with wire length and is found to be below 400 electrons for the longest wires (4.7 m). The response is consistent with the cold electronics design expectations and is found to be stable with time and uniform over the functioning channels. This noise level is significantly lower than previous experiments utilizing warm front-end electronics. Keywords: Cold Electronics; Noise; MicroBooNE; Time projection chambers; Noble liquid detectors; Neutrino detector

Emerging Viruses in the Felidae: Shifting Paradigms

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids