Believe the HiPe : hierarchical Perturbation for fast, robust, and model-agnostic saliency mapping

This work is supported by the Industrial Centre for AI Research in Digital Diagnostics (iCAIRD) which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) [project number: 104690].Understanding the predictions made by Artificial Intelligence (AI) systems is becoming more and more important as deep learning models are used for increasingly complex and high-stakes tasks. Saliency mapping – a popular visual attribution method – is one important tool for this, but existing formulations are limited by either computational cost or architectural constraints. We therefore propose Hierarchical Perturbation, a very fast and completely model-agnostic method for interpreting model predictions with robust saliency maps. Using standard benchmarks and datasets, we show that our saliency maps are of competitive or superior quality to those generated by existing model-agnostic methods – and are over 20× faster to compute.Publisher PDFPeer reviewe

Modulation of stem cell adhesion and morphology via facile control over surface presentation of cell adhesion molecules

To encourage cell adhesion on biomaterial surfaces in a more facile, safe, and low-cost fashion, we have demonstrated a noncovalent approach to spatially conjugate β-cyclodextrin (β-CD) modified peptide sequences onto self-assembled adamantane-terminated polystyrene-b-poly(ethylene oxide) (PS-PEO-Ada) films through inclusion complexing interactions between β-CDs and adamantane. By simply blending various ratios of unmodified PS-PEO with a newly synthesized PS-PEO-Ada, we produced PS polymer films that displayed well-organized adamantine-decorated cylindrical PEO domains with varying average interdomain spacings ranging from 29 to 47 nm. The presence of the adamantane moiety at the terminal end of the PEO chain permitted rapid, and importantly, oriented attachment of β-CD functionalized peptides onto these surfaces. This one-step process not only converted these proven nonadherent PS-PEO surfaces into adherent surfaces, but also permitted precisely controlled presentation and surface distribution of the conjugated peptides. The utility of these surfaces as cell culture substrates was confirmed with human mesenchymal stem cells (hMSCs). We observed that with increasing PS-PEO-Ada content in the PEO cylindrical domains, these novel polymer films displayed improved cell attachment and spreading, with notable differences in hMSC morphology. We further confirmed that this novel PS-PEO-Ada surface provides a flexible platform for facile conjugation of mixtures of β-CDs functionalized with different peptides, specifically RGD and IKVAV peptides. The cell adhesion and spreading assays on these surfaces indicated that the morphologies of hMSCs can be easily manipulated, while no significant changes in cell attachment were observed. The lock-and-key peptide conjugation technique presented in this work is applicable to any substrate that incorporates a moiety capable of forming inclusion complexes with α-, β-, and γ-CDs, providing a facile and flexible method by which to construct peptide-conjugated biomaterial substrates for a multitude of applications in fields ranging from cell bioprocessing and regenerative medicine to cell-based assays

Multispectral fingerprinting for improved in vivo cell dynamics analysis

Background: Tracing cell dynamics in the embryo becomes tremendously difficult when cell trajectories cross in space and time and tissue density obscure individual cell borders. Here, we used the chick neural crest (NC) as a model to test multicolor cell labeling and multispectral confocal imaging strategies to overcome these roadblocks. Results: We found that multicolor nuclear cell labeling and multispectral imaging led to improved resolution of in vivo NC cell identification by providing a unique spectral identity for each cell. NC cell spectral identity allowed for more accurate cell tracking and was consistent during short term time-lapse imaging sessions. Computer model simulations predicted significantly better object counting for increasing cell densities in 3-color compared to 1-color nuclear cell labeling. To better resolve cell contacts, we show that a combination of 2-color membrane and 1-color nuclear cell labeling dramatically improved the semi-automated analysis of NC cell interactions, yet preserved the ability to track cell movements. We also found channel versus lambda scanning of multicolor labeled embryos significantly reduced the time and effort of image acquisition and analysis of large 3D volume data sets. Conclusions: Our results reveal that multicolor cell labeling and multispectral imaging provide a cellular fingerprint that may uniquely determine a cell's position within the embryo. Together, these methods offer a spectral toolbox to resolve in vivo cell dynamics in unprecedented detail

Modeling the Effects of Avian Flu (H5N1) Vaccination Strategies on Poultry

The work in this article addresses a problem posed by Dr. Maria Salvato to the CODEE community. The task was to model costs associated with varying vaccination strategies for the Avian Flu virus (H5N1) on chicken populations. The vaccination strategies proposed included vaccination varying proportions of the flock with live virus vaccine, dead virus vaccine, and no vaccination. This article encompasses the construction of a model for the problem using a modification to the SIER model and the subsequent analysis of that model. The analysis of the model revealed the most cost effective vaccination strategy to be vaccination of half the flock with dead virus vaccine

Measuring atomic NOON-states and using them to make precision measurements

A scheme for creating NOON-states of the quasi-momentum of ultra-cold atoms has recently been proposed [New J. Phys. 8, 180 (2006)]. This was achieved by trapping the atoms in an optical lattice in a ring configuration and rotating the potential at a rate equal to half a quantum of angular momentum . In this paper we present a scheme for confirming that a NOON-state has indeed been created. This is achieved by spectroscopically mapping out the anti-crossing between the ground and first excited levels by modulating the rate at which the potential is rotated. Finally we show how the NOON-state can be used to make precision measurements of rotation.Comment: 14 preprint pages, 7 figure

The welfare consequences and efficacy of training pet dogs with remote electronic training collars in comparison to reward based training

This study investigated the welfare consequences of training dogs in the field with manually operated electronic devices (e-collars). Following a preliminary study on 9 dogs, 63 pet dogs referred for recall related problems were assigned to one of three Groups: Treatment Group A were trained by industry approved trainers using e-collars; Control Group B trained by the same trainers but without use of e-collars; and Group C trained by members of the Association of Pet Dog Trainers, UK again without e-collar stimulation (n = 21 for each Group). Dogs received two 15 minute training sessions per day for 4-5 days. Training sessions were recorded on video for behavioural analysis. Saliva and urine were collected to assay for cortisol over the training period. During preliminary studies there were negative changes in dogs' behaviour on application of electric stimuli, and elevated cortisol post-stimulation. These dogs had generally experienced high intensity stim uli without pre-warning cues during training. In contrast, in the subsequent larger, controlled study, trainers used lower settings with a pre-warning function and behavioural responses were less marked. Nevertheless, Group A dogs spent significantly more time tense, yawned more often and engaged in less environmental interaction than Group C dogs. There was no difference in urinary corticosteroids between Groups. Salivary cortisol in Group A dogs was not significantly different from that in Group B or Group C, though Group C dogs showed higher measures than Group B throughout sampling. Following training 92% of owners reported improvements in their dog's referred behaviour, and there was no significant difference in reported efficacy across Groups. Owners of dogs trained using e-collars were less confident of applying the training approach demonstrated. These findings suggest that there is no consistent benefit to be gained from e-collar training but greater welfare concer! ns compared with positive reward based training

Finding help for OCD in Australia : development and evaluation of a clinician directory

Objective: People tend to live with obsessive-compulsive disorder (OCD) for many years before receiving evidence-based treatment. This delay is partly due to a lack of access to information about which healthcare providers offer evidence-based treatment for OCD. This information was not easily accessible online for people in Australia. Methods: In this study, we describe how an online directory of clinicians was developed and evaluated. We report on a needs analysis and survey of treatment-seeking histories among consumers and carers impacted by OCD. We describe the key features of the directory developed, and present survey feedback on its usability and utility. Results: The results validated the need for a directory specific to clinicians who offer evidence-based treatment for OCD, and that it meets essential usability standards. Areas for improvement and further developments were identified. Conclusion: This directory contributes to broader efforts invested to improve the treatment-seeking process for people living with OCD in Australia

Systematic in-vitro evaluation of the NCI/NIH Developmental Therapeutics Program Approved Oncology Drug Set for the identification of a candidate drug repertoire for MLL-rearranged leukemia

Despite significant progress made in the overall cure rate, the prognosis for relapsed and refractory malignancies in children remains extremely poor. Hence, there is an urgent need for studies that enable the timely selection of appropriate agents for Phase I clinical studies. The Pediatric Oncology Experimental Therapeutics Investigators’ Consortium (POETIC) is systematically evaluating libraries of known and novel compounds for activity against subsets of high-risk pediatric malignancies with defined molecular aberrations for future clinical development. In this report, we describe the in-vitro activity of a diverse panel of approved oncology drugs against MLL-rearranged pediatric leukemia cell lines. Agents in the Approved Oncology Drug Set II (National Cancer Institute/National Institutes of Health Developmental Therapeutics Program) were evaluated by in-vitro cytotoxicity assays in pediatric acute lymphoblastic leukemia and acute myeloid leukemia cell lines with MLL gene rearrangements. Validation studies were carried out with patient leukemia cells in culture. Comparative analysis for toxicity against nonmalignant cells was evaluated in normal bone marrow stromal cells and normal human lymphocytes. Results from this study show that 42 of the 89 agents tested have measurable cytotoxicity against leukemia cells, and among these, 12 were effective against all five MLL-rearranged cell lines (IC50 [half maximal inhibitory concentration] < 1 μM). These 12 agents include cladribine, dactinomycin, daunorubicin, docetaxel, etoposide, gemcitabine, mitomycin C, mitoxantrone, teniposide, topotecan, triethylenemelamine, and vinblastine. We show that the Approved Oncology Drug Set II contains a number of agents with potent antileukemic activity in the tested cell lines. As approved drugs, these agents have been used in clinical settings for many years for other malignancies, thus their toxicity profile, pharmacokinetics, and other properties are readily available. Further evaluation of their use in future clinical trials for pediatric leukemia with MLL abnormalities should be considered

Antimicrobial octapeptin C4 analogues active against Cryptococcus species

Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogen Cryptococcus neoformans is a significant contributor to mortality, and its growing resistance to current antifungals an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal. Octapeptin C4 was a potent, selective inhibitor of this fungal pathogen with minimum inhibitory concentration of 1.56 μg/mL. Further testing of octapeptin C4 against 40 clinical isolates of C. neoformans var. grubii or neoformans showed MIC 1.56-3.13 μg/mL while 20 clinical isolates of C. neoformans var. gattii had MIC 0.78-12.5 μg/mL. In each case MIC values for octapeptin C4 were equivalent to, or better than, current antifungal drugs fluconazole and amphotericin B. The negatively charged polysaccharide capsule of C. neoformans influences the pathogens sensitivity to octapeptin C4 while degree of melanisation had little effect. Testing synthetic octapeptin C4 derivatives provided insight into the structure activity relationships, revealing that the lipophilic amino acid moieties are more important to the activity than the cationic diaminobutyric acid groups. Octapeptins have promising potential for development as anticryptococcal therapeutic agents