Three-dimensional simulation for fast forward flight of a calliope hummingbird

We present a computational study of flapping-wing aerodynamics of a calliope hummingbird (Selasphorus calliope) during fast forward flight. Three-dimensional wing kinematics were incorporated into the model by extracting time-dependent wing position from high-speed videos of the bird flying in a wind tunnel at 8.3 m s−1. The advance ratio, i.e. the ratio between flight speed and average wingtip speed, is around one. An immersed-boundary method was used to simulate flow around the wings and bird body. The result shows that both downstroke and upstroke in a wingbeat cycle produce significant thrust for the bird to overcome drag on the body, and such thrust production comes at price of negative lift induced during upstroke. This feature might be shared with bats, while being distinct from insects and other birds, including closely related swifts

Performance Deficits of NK1 Receptor Knockout Mice in the 5-Choice Serial Reaction-Time Task: Effects of d-Amphetamine, Stress and Time of Day

Background: The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon.Methods and Results: The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning.Conclusion: In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

The influence of test experience and NK1 receptor antagonists on the performance of NK1R-/- and wildtype mice in the 5 Choice Serial Reaction Time Task

Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater %omissions and premature responses in the 5 Choice Serial Reaction Time Task: ‘5 CSRTT’) and locomotor hyperactivity. Here, we investigated how behaviour in the 5 CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/- mice are mimicked by treating wildtypes with an NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced %omissions. Premature responses also declined, but only in NK1R /- mice in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the %omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the profile of the response suggests that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) have opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5 CSRTT is confounded by animals’ test experience and non-specific drug effects at sites other than NK1R, possibly L type Ca2+v channels

Improving Fetal Head Contour Detection by Object Localisation with Deep Learning

Ultrasound-based fetal head biometrics measurement is a key indicator in monitoring the conditions of fetuses. Since manual measurement of relevant anatomical structures of fetal head is time-consuming and subject to inter-observer variability, there has been strong interest in finding automated, robust, accurate and reliable method. In this paper, we propose a deep learning-based method to segment fetal head from ultrasound images. The proposed method formulates the detection of fetal head boundary as a combined object localisation and segmentation problem based on deep learning model. Incorporating an object localisation in a framework developed for segmentation purpose aims to improve the segmentation accuracy achieved by fully convolutional network. Finally, ellipse is fitted on the contour of the segmented fetal head using least-squares ellipse fitting method. The proposed model is trained on 999 2-dimensional ultrasound images and tested on 335 images achieving Dice coefficient of$$97.73 \pm 1.32$$. The experimental results demonstrate that the proposed deep learning method is promising in automatic fetal head detection and segmentation

Modeling recursive RNA interference.

An important application of the RNA interference (RNAi) pathway is its use as a small RNA-based regulatory system commonly exploited to suppress expression of target genes to test their function in vivo. In several published experiments, RNAi has been used to inactivate components of the RNAi pathway itself, a procedure termed recursive RNAi in this report. The theoretical basis of recursive RNAi is unclear since the procedure could potentially be self-defeating, and in practice the effectiveness of recursive RNAi in published experiments is highly variable. A mathematical model for recursive RNAi was developed and used to investigate the range of conditions under which the procedure should be effective. The model predicts that the effectiveness of recursive RNAi is strongly dependent on the efficacy of RNAi at knocking down target gene expression. This efficacy is known to vary highly between different cell types, and comparison of the model predictions to published experimental data suggests that variation in RNAi efficacy may be the main cause of discrepancies between published recursive RNAi experiments in different organisms. The model suggests potential ways to optimize the effectiveness of recursive RNAi both for screening of RNAi components as well as for improved temporal control of gene expression in switch off-switch on experiments

Aerodynamics of the Hovering Hummingbird

Despite profound musculoskeletal differences, hummingbirds (Trochilidae) are widely thought to employ aerodynamic mechanisms similar to those used by insects. The kinematic symmetry of the hummingbird upstroke and downstroke has led to the assumption that these halves of the wingbeat cycle contribute equally to weight support during hovering, as exhibited by insects of similar size. This assumption has been applied, either explicitly or implicitly, in widely used aerodynamic models, and in a variety of empirical tests. Here we provide measurements of the wake of hovering rufous hummingbirds (Selasphorus rufus) obtained with digital particle image velocimetry that show force asymmetry: hummingbirds produce 75% of their weight support during the downstroke and only 25% during the upstroke. Some of this asymmetry is probably due to inversion of their cambered wings during upstroke. The wake of hummingbird wings also reveals evidence of leading-edge vortices created during the downstroke, indicating that they may operate at Reynolds numbers sufficiently low to exploit a key mechanism typical of insect hovering. Hummingbird hovering approaches that of insects, yet remains distinct because of effects resulting from an inherently dissimilar—avian—body plan

Progress and challenges in the vaccine-based treatment of head and neck cancers

Head and neck (HN) cancer represents one of the most challenging diseases because the mortality remains high despite advances in early diagnosis and treatment. Although vaccine-based approaches for the treatment of advanced squamous cell carcinoma of the head and neck have achieved limited clinical success, advances in cancer immunology provide a strong foundation and powerful new tools to guide current attempts to develop effective cancer vaccines. This article reviews what has to be rather what has been done in the field for the development of future vaccines in HN tumours

Kinematic Plasticity during Flight in Fruit Bats: Individual Variability in Response to Loading

All bats experience daily and seasonal fluctuation in body mass. An increase in mass requires changes in flight kinematics to produce the extra lift necessary to compensate for increased weight. How bats modify their kinematics to increase lift, however, is not well understood. In this study, we investigated the effect of a 20% increase in mass on flight kinematics for Cynopterus brachyotis, the lesser dog-faced fruit bat. We reconstructed the 3D wing kinematics and how they changed with the additional mass. Bats showed a marked change in wing kinematics in response to loading, but changes varied among individuals. Each bat adjusted a different combination of kinematic parameters to increase lift, indicating that aerodynamic force generation can be modulated in multiple ways. Two main kinematic strategies were distinguished: bats either changed the motion of the wings by primarily increasing wingbeat frequency, or changed the configuration of the wings by increasing wing area and camber. The complex, individual-dependent response to increased loading in our bats points to an underappreciated aspect of locomotor control, in which the inherent complexity of the biomechanical system allows for kinematic plasticity. The kinematic plasticity and functional redundancy observed in bat flight can have evolutionary consequences, such as an increase potential for morphological and kinematic diversification due to weakened locomotor trade-offs

Generation of tumour-specific cytotoxic T-cell clones from histocompatibility leucocyte antigen-identical siblings of patients with melanoma

Lymphodepletion and infusion of autologous expanded tumour-infiltrating lymphocytes is effective therapy for patients with malignant melanoma. Antitumour responses are likely to be mediated by HLA class I- and II-restricted immune responses directed at tumour antigens. We assessed whether the peripheral blood of normal HLA-matched siblings of patients with melanoma could be used to generate lymphocytes with antimelanoma activity for adoptive immunotherapy after allogeneic blood or marrow transplantation. Melanoma cell lines were derived from two donors and were used to stimulate the mononuclear cells of three HLA-identical siblings. CD4+ clones dominated cultures. Of these, approximately half were directly cytotoxic towards recipient melanoma cells and secreted interferon-γ in response to tumour stimulation. More than half of the noncytotoxic clones also secreted interferon-γ after melanoma stimulation. No CD4+ clones responded to stimulation with recipient haemopoietic cells. The majority of CD8+ clones directly lysed recipient melanoma, but did not persist in long-term culture in vitro. No crossreactivity with recipient haemopoietic cells was observed. The antigenic target of one CD4+ clone was determined to be an HLA-DR11-restricted MAGE-3 epitope. Antigenic targets of the remaining clones were not elucidated, but appeared to be restricted through a non-HLA-DR class II molecule. We conclude that the blood of allogeneic HLA-matched sibling donors contains melanoma-reactive lymphocyte precursors directed at tumour-associated antigens. Adoptive immunotherapy with unselected or ex vivo-stimulated donor lymphocytes after allogeneic stem cell transplantation has a rational basis for the treatment of malignant melanoma

Learning a Prior on Regulatory Potential from eQTL Data

Genome-wide RNA expression data provide a detailed view of an organism's biological state; hence, a dataset measuring expression variation between genetically diverse individuals (eQTL data) may provide important insights into the genetics of complex traits. However, with data from a relatively small number of individuals, it is difficult to distinguish true causal polymorphisms from the large number of possibilities. The problem is particularly challenging in populations with significant linkage disequilibrium, where traits are often linked to large chromosomal regions containing many genes. Here, we present a novel method, Lirnet, that automatically learns a regulatory potential for each sequence polymorphism, estimating how likely it is to have a significant effect on gene expression. This regulatory potential is defined in terms of “regulatory features”—including the function of the gene and the conservation, type, and position of genetic polymorphisms—that are available for any organism. The extent to which the different features influence the regulatory potential is learned automatically, making Lirnet readily applicable to different datasets, organisms, and feature sets. We apply Lirnet both to the human HapMap eQTL dataset and to a yeast eQTL dataset and provide statistical and biological results demonstrating that Lirnet produces significantly better regulatory programs than other recent approaches. We demonstrate in the yeast data that Lirnet can correctly suggest a specific causal sequence variation within a large, linked chromosomal region. In one example, Lirnet uncovered a novel, experimentally validated connection between Puf3—a sequence-specific RNA binding protein—and P-bodies—cytoplasmic structures that regulate translation and RNA stability—as well as the particular causative polymorphism, a SNP in Mkt1, that induces the variation in the pathway