Gravitationally Collapsing Shells in (2+1) Dimensions

We study gravitationally collapsing models of pressureless dust, fluids with pressure, and the generalized Chaplygin gas (GCG) shell in (2+1)-dimensional spacetimes. Various collapse scenarios are investigated under a variety of the background configurations such as anti-de Sitter(AdS) black hole, de Sitter (dS) space, flat and AdS space with a conical deficit. As with the case of a disk of dust, we find that the collapse of a dust shell coincides with the Oppenheimer-Snyder type collapse to a black hole provided the initial density is sufficiently large. We also find -- for all types of shell -- that collapse to a naked singularity is possible under a broad variety of initial conditions. For shells with pressure this singularity can occur for a finite radius of the shell. We also find that GCG shells exhibit diverse collapse scenarios, which can be easily demonstrated by an effective potential analysis.Comment: 27 pages, Latex, 11 figures, typos corrected, references added, minor amendments in introduction and conclusion introd

An evaporation-based model of thermal neutron induced ternary fission of plutonium

Ternary fission probabilities for thermal neutron induced fission of plutonium are analyzed within the framework of an evaporation-based model where the complexity of time-varying potentials, associated with the neck collapse, are included in a simplistic fashion. If the nuclear temperature at scission and the fission-neck-collapse time are assumed to be ~1.2 MeV and ~10^-22 s, respectively, then calculated relative probabilities of ternary-fission light-charged-particle emission follow the trends seen in the experimental data. The ability of this model to reproduce ternary fission probabilities spanning seven orders of magnitude for a wide range of light-particle charges and masses implies that ternary fission is caused by the coupling of an evaporation-like process with the rapid re-arrangement of the nuclear fluid following scission.Comment: 25 pages, 12 figures, accepted for publication in IJMP

Enhancing single-molecule photostability by optical feedback from quantum-jump detection

We report an optical technique that yields an enhancement of single-molecule photostability, by greatly suppressing photobleaching pathways which involve photoexcitation from the triplet state. This is accomplished by dynamically switching off the excitation laser when a quantum-jump of the molecule to the triplet state is optically detected. This procedure leads to a lengthened single-molecule observation time and an increased total number of detected photons. The resulting improvement in photostability unambiguously confirms the importance of photoexcitation from the triplet state in photobleaching dynamics, and may allow the investigation of new phenomena at the single-molecule level

Isotropic reconstruction of 3D fluorescence microscopy images using convolutional neural networks

Fluorescence microscopy images usually show severe anisotropy in axial versus lateral resolution. This hampers downstream processing, i.e. the automatic extraction of quantitative biological data. While deconvolution methods and other techniques to address this problem exist, they are either time consuming to apply or limited in their ability to remove anisotropy. We propose a method to recover isotropic resolution from readily acquired anisotropic data. We achieve this using a convolutional neural network that is trained end-to-end from the same anisotropic body of data we later apply the network to. The network effectively learns to restore the full isotropic resolution by restoring the image under a trained, sample specific image prior. We apply our method to $3$ synthetic and $3$ real datasets and show that our results improve on results from deconvolution and state-of-the-art super-resolution techniques. Finally, we demonstrate that a standard 3D segmentation pipeline performs on the output of our network with comparable accuracy as on the full isotropic data

Nerve-targeted probes for fluorescence-guided intraoperative imaging.

A fundamental goal of many surgeries is nerve preservation, as inadvertent injury can lead to patient morbidity including numbness, pain, localized paralysis and incontinence. Nerve identification during surgery relies on multiple parameters including anatomy, texture, color and relationship to surrounding structures using white light illumination. We propose that fluorescent labeling of nerves can enhance the contrast between nerves and adjacent tissue during surgery which may lead to improved outcomes. Methods: Nerve binding peptide sequences including HNP401 were identified by phage display using selective binding to dissected nerve tissue. Peptide dye conjugates including FAM-HNP401 and structural variants were synthesized and screened for nerve binding after topical application on fresh rodent and human tissue and in-vivo after systemic IV administration into both mice and rats. Nerve to muscle contrast was quantified by measuring fluorescent intensity after topical or systemic administration of peptide dye conjugate. Results: Peptide dye conjugate FAM-HNP401 showed selective binding to human sural nerve with 10.9x fluorescence signal intensity (1374.44 ± 425.96) compared to a previously identified peptide FAM-NP41 (126.17 ± 61.03). FAM-HNP401 showed nerve-to-muscle contrast of 3.03 ± 0.57. FAM-HNP401 binds and highlight multiple human peripheral nerves including lower leg sural, upper arm medial antebrachial as well as autonomic nerves isolated from human prostate. Conclusion: Phage display has identified a novel peptide that selectively binds to ex-vivo human nerves and in-vivo using rodent models. FAM-HNP401 or an optimized variant could be translated for use in a clinical setting for intraoperative identification of human nerves to improve visualization and potentially decrease the incidence of intra-surgical nerve injury

Self-organized transition to coherent activity in disordered media

Synchronized oscillations are of critical functional importance in many biological systems. We show that such oscillations can arise without centralized coordination in a disordered system of electrically coupled excitable and passive cells. Increasing the coupling strength results in waves that lead to coherent periodic activity, exhibiting cluster, local and global synchronization under different conditions. Our results may explain the self-organized transition in a pregnant uterus from transient, localized activity initially to system-wide coherent excitations just before delivery.Comment: 5 pages, 4 figure

Evolution of a fluorinated green fluorescent protein

The fluorescence of bacterial cells expressing a variant (GFPm) of the green fluorescent protein (GFP) was reduced to background levels by global replacement of the leucine residues of GFPm by 5,5,5-trifluoroleucine. Eleven rounds of random mutagenesis and screening via fluorescence-activated cell sorting yielded a GFP mutant containing 20 amino acid substitutions. The mutant protein in fluorinated form showed improved folding efficiency both in vivo and in vitro, and the median fluorescence of cells expressing the fluorinated protein was improved {approx}650-fold in comparison to that of cells expressing fluorinated GFPm. The success of this approach demonstrates the feasibility of engineering functional proteins containing many copies of abiological amino acid constituents

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

GABAergic Projection Neurons Route Selective Olfactory Inputs to Specific Higher-Order Neurons

SummaryWe characterize an inhibitory circuit motif in the Drosophila olfactory system, parallel inhibition, which differs from feedforward or feedback inhibition. Excitatory and GABAergic inhibitory projection neurons (ePNs and iPNs) each receive input from antennal lobe glomeruli and send parallel output to the lateral horn, a higher center implicated in regulating innate olfactory behavior. Ca2+ imaging of specific lateral horn neurons as an olfactory readout revealed that iPNs selectively suppressed food-related odor responses, but spared signal transmission from pheromone channels. Coapplying food odorant did not affect pheromone signal transmission, suggesting that the differential effects likely result from connection specificity of iPNs, rather than a generalized inhibitory tone. Ca2+ responses in the ePN axon terminals show no detectable suppression by iPNs, arguing against presynaptic inhibition as a primary mechanism. The parallel inhibition motif may provide specificity in inhibition to funnel specific olfactory information, such as food and pheromone, into distinct downstream circuits