Calcium-independent exo-endocytosis coupling at small central synapses

At presynaptic terminals, neurotransmitters are released by synaptic vesicle exocytosis at the active zone. In order to maintain efficient neurotransmission and proper synaptic structure, sites of vesicle fusion must be cleared rapidly by endocytosis. Therefore, the coupling of exo- and endocytosis is crucial. Despite many years of research, the exact molecular and biophysical requirements for the coupling of exo- and endocytosis remain unclear. We investigate whether endocytosis can be triggered in a calcium-independent fashion by evoking calcium-independent exocytosis using a hypertonic sucrose solution. We demonstrate that endocytosis can be triggered, in the absence of calcium influx, in a clathrin-independent manner that relies on actin polymerization. Our findings point to a central role of membrane tension dependent on actin for efficient coupling of exo- and endocytosis

A Radiation Imaging Detector Made by Postprocessing a Standard CMOS Chip

An unpackaged microchip is used as the sensing element in a miniaturized gaseous proportional chamber. Thisletter reports on the fabrication and performance of a complete radiation imaging detector based on this principle. Our fabrication schemes are based on wafer-scale and chip-scale postprocessing.\ud Compared to hybrid-assembled gaseous detectors, our microsystem shows superior alignment precision and energy resolution, and offers the capability to unambiguously reconstruct 3-D radiation tracks on the spot.\u

A neural network approach for chatter prediction in turning

[EN] Machining processes, including turning, are a critical capability for discrete part production. One limitation to high material removal rates and reduced cost in these processes is chatter, or unstable spindle speed-chip width combinations that exhibit self-excited vibration. In this paper, an artificial neural network (ANN) is applied to model turning stability. The analytical stability limit is used to generate a data set that trains the ANN. It is observed that the number and distribution of training points influences the ability of the ANN model to capture the smaller, more closely spaced lobes that occur at lower spindle speeds. Overall, the ANN is successful (>90% accuracy) at predicting the stability behavior after appropriate training.The authors gratefully acknowledge financial support from the UNC ROI program. Elena Perez-Bernabeu and Miguel Selles also acknowledge support from Universitat Politenica de Valencia (PAID-00-17). Additionally, some of the neural net figures and the 10-fold cross validation figures are based on the TikZ codes provided on StackExchange-TeX by various users. Harish Cherukuri would like to thank them for their valuable advice.Cherukuri, H.; Pérez Bernabeu, E.; Sellés, M.; Schmitz, TL. (2019). A neural network approach for chatter prediction in turning. Procedia Manufacturing. 34:885-892. https://doi.org/10.1016/j.promfg.2019.06.1598858923

Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis

We hypothesized in 1998 that gap junctions might be located between the axons of principal hippocampal neurons, based on the shape of spikelets (fast prepotentials), occurring during gap junction-mediated very fast (to approximately 200 Hz) network oscillations in vitro. More recent electrophysiological, pharmacological and dye-coupling data indicate that axonal gap junctions exist; so far, they appear to be located about 100 microm from the soma, in CA1 pyramidal neurons. Computer modeling and theory predict that axonal gap junctions can lead to very fast network oscillations under three conditions: a) there are spontaneous axonal action potentials; b) the number of gap junctions in the network is neither too low (not less than to approximately 1.5 per cell on average), nor too high (not more than to approximately 3 per cell on average); c) action potentials can cross from axon to axon via gap junctions. Simulated oscillations resemble biological ones, but condition (c) remains to be demonstrated directly. Axonal network oscillations can, in turn, induce oscillatory activity in larger neuronal networks, by a variety of mechanisms. Axonal networks appear to underlie in vivo ripples (to approximately 200 Hz field potential oscillations superimposed on physiological sharp waves), to drive gamma (30-70 Hz) oscillations that appear in the presence of carbachol, and to initiate certain types of ictal discharge. If axonal gap junctions are important for seizure initiation in humans, there could be practical consequences for antiepileptic therapy: at least one gap junction-blocking compound, carbenoxolone, is already in clinical use (for treatment of ulcer disease), and it crosses the blood-brain barrier

Technological aspects of gaseous pixel detectors fabrication

Integrated gaseous pixel detectors consisting of a metal punctured foil suspended in the order of 50μm over a pixel readout chip by means by SU-8 insulating pillars have been fabricated. SU-8 is used as sacrificial layer but metallization over uncrosslinked SU-8 presents adhesion and stress problems. In this paper we describe the several methods we have investigated to fabricate a metal layer on top of a partially crosslinked SU-8 film and the challenges we have encountered. The fabrication process using wafer post processing has been proven, but in cases where single chip processing is desirable, edge bead is a major problem to overcome as it can cover a considerable chip area, reducing the detector performance; we show different techniques to reduce this edge bead and improve detection efficiency

Usage Pattern Recognition in Student Activities

Proceedings of: 6th European Conference of Technology Enhanced Learning, EC-TEL 2011, Palermo, Italy, September 20-23, 2011.This paper presents an approach of collecting contextualized attention metadata combined from inside as well as outside a LMS and analyzing them to create feedback about the student activities for the teaching staff. Two types of analyses were run on the collected data: first, key actions were extracted to identify usage patterns and tendencies throughout the whole course and then usage statistics and patterns were identified for some key actions in more detail. Results of both analyses were visualized and presented to the teaching staff for evaluation.The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007- 2013) under grant agreement no 231396 (ROLE project). Work was also partially funded by the Learn3 project (TIN2008-05163/TSI), the eMadrid project (S2009/TIC-1650), and the Acción Integrada DE2009-0051

Quantum walk on distinguishable non-interacting many-particles and indistinguishable two-particle

We present an investigation of many-particle quantum walks in systems of non-interacting distinguishable particles. Along with a redistribution of the many-particle density profile we show that the collective evolution of the many-particle system resembles the single-particle quantum walk evolution when the number of steps is greater than the number of particles in the system. For non-uniform initial states we show that the quantum walks can be effectively used to separate the basis states of the particle in position space and grouping like state together. We also discuss a two-particle quantum walk on a two- dimensional lattice and demonstrate an evolution leading to the localization of both particles at the center of the lattice. Finally we discuss the outcome of a quantum walk of two indistinguishable particles interacting at some point during the evolution.Comment: 8 pages, 7 figures, To appear in special issue: "quantum walks" to be published in Quantum Information Processin

Infection of ferrets with wild type-based recombinant canine distemper virus overwhelms the immune system and causes fatal systemic disease

Canine distemper virus (CDV) causes systemic infection resulting in severe and often fatal disease in a large spectrum of animal host species. The virus is closely related to measles virus and targets myeloid, lymphoid, and epithelial cells, but CDV is more virulent and the infection spreads more rapidly within the infected host. Here, we aimed to study the pathogenesis of wild-type CDV infection by experimentally inoculating ferrets with recombinant CDV (rCDV) based on an isolate directly obtained from a naturally infected raccoon. The recombinant virus was engineered to express a fluorescent reporter protein, facilitating assessment of viral tropism and virulence. In ferrets, this wild type-based rCDV infected myeloid, lymphoid, and epithelial cells, and the infection resulted in systemic dissemination to multiple tissues and organs, especially those of the lymphatic system. High infection percentages in immune cells resulted in depletion of these cells both from circulation and from lymphoid tissues. The majority of CDV-infected ferrets reached their humane endpoints within 20 d and had to be euthanized. In that period, the virus also reached the central nervous system in several ferrets, but we did not observe the development of neurological complications during the study period of 23 d. Two out of 14 ferrets survived CDV infection and developed neutralizing antibodies. We show for the first time the pathogenesis of a non-adapted wild type-based rCDV in ferrets. IMPORTANCE Infection of ferrets with recombinant canine distemper virus (rCDV) expressing a fluorescent reporter protein has been used as proxy to understand measles pathogenesis and immune suppression in humans. CDV and measles virus use the same cellular receptors, but CDV is more virulent, and infection is often associated with neurological complications. rCDV strains in current use have complicated passage histories, which may have affected their pathogenesis. Here, we studied the pathogenesis of the first wild type-based rCDV in ferrets. We used macroscopic fluorescence to identify infected cells and tissues; multicolor flow cytometry to determine viral tropism in immune cells; and histopathology and immunohistochemistry to characterize infected cells and lesions in tissues. We conclude that CDV often overwhelmed the immune system, resulting in viral dissemination to multiple tissues in the absence of a detectable neutralizing antibody response. This virus is a promising tool to study the pathogenesis of morbillivirus infections.</p

Inoculation of raccoons with a wild-type-based recombinant canine distemper virus results in viremia, lymphopenia, fever, and widespread histological lesions

Raccoons are naturally susceptible to canine distemper virus (CDV) infection and can be a potential source of spill-over events. CDV is a highly contagious morbillivirus that infects multiple species of carnivores and omnivores, resulting in severe and often fatal disease. Here, we used a recombinant CDV (rCDV) based on a full-genome sequence detected in a naturally infected raccoon to perform pathogenesis studies in raccoons. Five raccoons were inoculated intratracheally with a recombinant virus engineered to express a fluorescentreporter protein, and extensive virological, serological, histological, and immunohistochemical assessments were performed at differenttime points post inoculation. rCDV-infected white blood cells were detected as early as 4 days post inoculation (dpi). Raccoon necropsies at 6 and 8 dpi revealed replication in the lymphoid tissues, preceding spread into peripheral tissues observed during necropsies at 21 dpi. Whereas lymphocytes, and to a lesser extent myeloid cells, were the main target cells of CDV at early time points, CDV additionally targeted epithelia at 21 dpi. At this later time point, CDV-infected cells were observed throughout the host. We observed lymphopenia and lymphocyte depletion from lymphoid tissues after CDV infection, in the absence of detectable CDV neutralizing antibodies and an impaired ability to clear CDV, indicating that the animals were severely immunosuppressed. The use of a wild-type-based recombinant virus in a natural host species infection study allowed systematic and sensitive assessment of antigen detection by immunohistochemistry, enabling further comparative pathology studies of CDV infection in differentspecies.</p