898 research outputs found

    Region of the anomalous compression under Bondi-Hoyle accretion

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    We investigate the properties of an axisymmetric non-magnetized gas flow without angular momentum on a small compact object, in particular, on a Schwarzschild black hole in the supersonic region near the object; the velocity of the object itself is assumed to be low compared to the speed of sound at infinity. First of all, we see that the streamlines intersect (i.e., a caustic forms) on the symmetry axis at a certain distance rxr_x from the center on the front side if the pressure gradient is neglected. The characteristic radial size of the region, in which the streamlines emerging from the sonic surface at an angle no larger than θ0\theta_0 to the axis intersect, is Δr=rxθ02/3.\Delta r= r_x\theta^2_0/3. To refine the flow structure in this region, we numerically compute the system in the adiabatic approximation without ignoring the pressure. We estimate the parameters of the inferred region with anomalously high matter temperature and density accompanied by anomalously high energy release.Comment: 10 pages, 2 figure

    Deep learning for novel antimicrobial peptide design

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    Antimicrobial resistance is an increasing issue in healthcare as the overuse of antibacterial agents rises during the COVID-19 pandemic. The need for new antibiotics is high, while the arsenal of available agents is decreasing, especially for the treatment of infections by Gram-negative bacteria like Escherichia coli. Antimicrobial peptides (AMPs) are offering a promising route for novel antibiotic development and deep learning techniques can be utilised for successful AMP design. In this study, a long short-term memory (LSTM) generative model and a bidirectional LSTM classification model were constructed to design short novel AMP sequences with potential antibacterial activity against E. coli. Two versions of the generative model and six versions of the classification model were trained and optimised using Bayesian hyperparameter optimisation. These models were used to generate sets of short novel sequences that were classified as antimicrobial or non-antimicrobial. The validation accuracies of the classification models were 81.6–88.9% and the novel AMPs were classified as antimicrobial with accuracies of 70.6–91.7%. Predicted three-dimensional conformations of selected short AMPs exhibited the alpha-helical structure with amphipathic surfaces. This demonstrates that LSTMs are effective tools for generating novel AMPs against targeted bacteria and could be utilised in the search for new antibiotics leads

    Retrovirus-Mediated Transduction of Cultured Epidermal Keratinocytes

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    Retrovirus-mediated gene transfer is an efficient means of introducing and expressing exogenous gene(s) in many cell types including keratinocytes. However, parameters of transduction and gene expression have not been systematically analyzed for keratinocytes. To carry out such a study we have transduced cultures of newborn foreskin cells with retroviral vectors that encode the genes for neomycin resistance (neor) and for beta-galactosidase (B-gal). The neor gene is a dominant selectable marker and the B-gal gene encodes a histochemically detectable product. Our key findings are the following: 1) all keratinocytes that form colonies can be successfully transduced at a viral titer greater than 5 × 106 colony-forming units/ml; 2) transduction is effected by integration of a single copy of retroviral DNA; 3) transduced cells are not at a growth disadvantage and, in fact, single clones of transduced keratinocytes can be expanded to yield over 109 cells, suggesting that stem cells are transduced; 4) whereas most transduced colonies exhibit B-gal staining in a high percentage of constituent cells, some colonies had a mosaic or sectored staining pattern; 5) expression of the non-selectable B-gal gene was somewhat greater in differentiated cells of the culture as compared to nondifferentiated precursors. The ability to transduce stem cells at a high efficiency and to follow expression of transduced genes in clonal progeny will allow lineage mapping in stratified epithelial tissues

    Perturbations on steady spherical accretion in Schwarzschild geometry

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    The stationary background flow in the spherically symmetric infall of a compressible fluid, coupled to the space-time defined by the static Schwarzschild metric, has been subjected to linearized perturbations. The perturbative procedure is based on the continuity condition and it shows that the coupling of the flow with the geometry of space-time brings about greater stability for the flow, to the extent that the amplitude of the perturbation, treated as a standing wave, decays in time, as opposed to the amplitude remaining constant in the Newtonian limit. In qualitative terms this situation simulates the effect of a dissipative mechanism in the classical Bondi accretion flow, defined in the Newtonian construct of space and time. As a result of this approach it becomes impossible to define an acoustic metric for a conserved spherically symmetric flow, described within the framework of Schwarzschild geometry. In keeping with this view, the perturbation, considered separately as a high-frequency travelling wave, also has its amplitude reduced.Comment: 8 pages, no figur

    The cJUN NH2-terminal kinase (JNK) signaling pathway promotes genome stability and prevents tumor initiation

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    Breast cancer is the most commonly diagnosed malignancy in women. Analysis of breast cancer genomic DNA indicates frequent loss-of-function mutations in components of the cJUN NH2-terminal kinase (JNK) signaling pathway. Since JNK signaling can promote cell proliferation by activating the AP1 transcription factor, this apparent association of reduced JNK signaling with tumor development was unexpected. We examined the effect of JNK deficiency in the murine breast epithelium. Loss of JNK signaling caused genomic instability and the development of breast cancer. Moreover, JNK deficiency caused widespread early neoplasia and rapid tumor formation in a murine model of breast cancer. This tumor suppressive function was not mediated by a role of JNK in the growth of established tumors, but by a requirement of JNK to prevent tumor initiation. Together, these data identify JNK pathway defects as \u27driver\u27 mutations that promote genome instability and tumor initiation

    Implications of nonlinearity for spherically symmetric accretion

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    We subject the steady solutions of a spherically symmetric accretion flow to a time-dependent radial perturbation. The equation of the perturbation includes nonlinearity up to any arbitrary order, and bears a form that is very similar to the metric equation of an analogue acoustic black hole. Casting the perturbation as a standing wave on subsonic solutions, and maintaining nonlinearity in it up to the second order, we get the time-dependence of the perturbation in the form of a Li\'enard system. A dynamical systems analysis of the Li\'enard system reveals a saddle point in real time, with the implication that instabilities will develop in the accreting system when the perturbation is extended into the nonlinear regime. The instability of initial subsonic states also adversely affects the temporal evolution of the flow towards a final and stable transonic state.Comment: 14 pages, ReVTeX. Substantially revised with respect to the previous version. Three figures and a new section (Sec. VI) adde

    Self-Assembling Peptide Nanofiber Scaffolds Accelerate Wound Healing

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    Cutaneous wound repair regenerates skin integrity, but a chronic failure to heal results in compromised tissue function and increased morbidity. To address this, we have used an integrated approach, using nanobiotechnology to augment the rate of wound reepithelialization by combining self-assembling peptide (SAP) nanofiber scaffold and Epidermal Growth Factor (EGF). This SAP bioscaffold was tested in a bioengineered Human Skin Equivalent (HSE) tissue model that enabled wound reepithelialization to be monitored in a tissue that recapitulates molecular and cellular mechanisms of repair known to occur in human skin. We found that SAP underwent molecular self-assembly to form unique 3D structures that stably covered the surface of the wound, suggesting that this scaffold may serve as a viable wound dressing. We measured the rates of release of EGF from the SAP scaffold and determined that EGF was only released when the scaffold was in direct contact with the HSE. By measuring the length of the epithelial tongue during wound reepithelialization, we found that SAP scaffolds containing EGF accelerated the rate of wound coverage by 5 fold when compared to controls without scaffolds and by 3.5 fold when compared to the scaffold without EGF. In conclusion, our experiments demonstrated that biomaterials composed of a biofunctionalized peptidic scaffold have many properties that are well-suited for the treatment of cutaneous wounds including wound coverage, functionalization with bioactive molecules, localized growth factor release and activation of wound repair

    Secular instability in quasi-viscous disc accretion

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    A first-order correction in the α\alpha-viscosity parameter of Shakura and Sunyaev has been introduced in the standard inviscid and thin accretion disc. A linearised time-dependent perturbative study of the stationary solutions of this "quasi-viscous" disc leads to the development of a secular instability on large spatial scales. This qualitative feature is equally manifest for two different types of perturbative treatment -- a standing wave on subsonic scales, as well as a radially propagating wave. Stability of the flow is restored when viscosity disappears.Comment: 15 pages, 2 figures, AASTeX. Added some new material and upgraded the reference lis
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