European evidence based consensus for endoscopy in inflammatory bowel disease

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Microtubule organization in presynaptic boutons relies on the formin DAAM

Regulation of the cytoskeleton is fundamental to the development and functioning of synaptic terminals, such as neuromuscular junctions. Nevertheless, despite identification of numerous proteins that regulate synaptic actin and microtubule dynamics, the mechanisms of cytoskeletal control during terminal arbor formation has remained largely elusive. Here, we show that DAAM, a member of the formin family of cytoskeleton organizing factors, is an important presynaptic regulator of neuromuscular junction development in Drosophila We demonstrate that the actin filament assembly activity of DAAM plays a negligible role in terminal formation; rather, DAAM is necessary for synaptic microtubule organization. Genetic interaction studies consistently link DAAM with the Wg/Ank2/Futsch module of microtubule regulation and bouton formation. Finally, we provide evidence that DAAM is tightly associated with the synaptic active zone scaffold, and electrophysiological data point to a role in the modulation of synaptic vesicle release. Based on these results, we propose that DAAM is an important cytoskeletal effector element of the Wg/Ank2 pathway involved in the determination of basic synaptic structures, and, additionally, DAAM may couple the active zone scaffold to the presynaptic cytoskeleton

Design Of Broadband Generators Using Chaotic Electronic Circuits

Nonlinear discrete-time dynamic systems with chaotic behaviour are known to generate noise-like signals which have a power density spectrum distributed over a certain frequency range (broadband signals). This paper deals with the systematic design of such systems which generate signals with prescribed probability density function (pdf) and power density spectrum (pds). I. INTRODUCTION The nonlinear discrete-time system is described by the state equations x(k + 1) = f (x(k)); k = 0; 1; 2; : : : (1) where x is the state vector of the system, k the discrete-time variable, and f a map of the state space into itself. For defined properties of f the system will generate a chaotic sequence. In this paper the design algorithms for three special kinds of systems are discussed: ffl one-dimensional continuous-value systems where the map f is realised according to the prescribed signal properties, ffl n-dimensional binary-value systems with a state matrix f adapted to the prescribed signal pro..

Potentials of digital business ecosystems in the healthcare market

The German healthcare market faces numerous future challenges in order to increase or at least maintain the current level of care. Due to an aging society, multi-morbidity, a low degree of digitization, and few innovations, it is becoming increasingly difficult for the German healthcare market to maintain quality of care. Digital healthcare ecosystems are a promising means to establish digitization in the healthcare system. This study presents the results of five expert interviews in the German healthcare market. The analysis of the interviews shows massive potentials in the areas of "Improvement in Quality of Care," "Reduction of Costs," and "Innovativeness" that can be achieved through Digital Health Ecosystems. The study contributes to the future orientation and digitalization of the health care market and shows possible directions of development.</p

Particle filter de-noising of voxel-specific time-activity-curves in personalized 177Lu therapy

Background: Currently, there is a high interest in Lu-177 targeted radionuclide therapies, which could be attributed to favorable results obtained from Lu-177 compounds targeting neuro-endocrine and prostate tumors. SPECT based dosimetry could be used for deriving dose values for individual voxels, as is the standard in external-beam radiation-therapy (EBRT). For this a time-activity-curve (TAC) at voxel resolution and also a voxel-wise modeling of radiation energy deposition are necessary. But a voxel-wise determination of TACs is problematic, since several confounding factors exist, such as e.g. poor count-statistics or registration inaccuracies, which add noise to the observed activity states. A particle filter (PF) is a class of methods which applies regularization based on a model of the temporal evolution of activity states. The aim of this study is to introduce the application of PFs for de-noising of per-voxel time-activity curves. Methods: We applied a PF for de-noising the TACs of 26 patients, who underwent Lu-177-DOTATOC or -PSMA therapy. The TACs were obtained from fiilly-quantitative, serial SPECT (/CT) data, acquired at 4 h, 24 h, 48 h, 72 h p.i. The model used in the PF was a mono-exponential decay and its free parameters were determined based on objective criteria. The time-integrated activities (TIA) resulting from the PF (PFF) were compared to the results of a mono-exponential fit (SF) of individual voxels in several volumes of interest (kidneys, spleen, tumors). Additionally, an organ-averaged TIA was derived from whole-organ VOIs and subsequent curve-fitting. This whole-organ TIA was also compared to the whole-organ TIAs obtained from summation of the voxel-wise TIAs from PFF and SF. Results: The number of particles was set to 1000. Optimal values for noise of observations and noise of the model were 0.25 and 0.5, respectively The deviation of whole-organ TIAs from conventional organ-based dosimetry and the summation of the voxel-wise TIAs was substantial for SF (kidneys -22.3%, spleen -49.6%, tumor -60.0%), as well as for PFF (kidneys -37.1%, spleen -57.9%, tumor -70.9%). The distribution of voxel-wise half-lives resulting from the PFF method was considerably closer to the organ-averaged value, and the number of implausibly long half-lives (>physical HL) was reduced. Conclusion: The PFF leads to voxel-wise half-lives, which are more plausible than those resulting from SF. However, one has to admit that voxel-wise fitting generally leads to considerable deviations from the organ-averaged TIA as obtained by conventional whole-organ evaluation. Unfortunately, we did not have ground-truth TIA of our patient data and proper ground-truth could even be impossible to obtain. Nevertheless, there are strong indicators that particle filtering can be used for reducing voxel-wise TAC noise

Presynaptic spinophilin tunes neurexin signalling to control active zone architecture and function

Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis

Three-dimensional analysis of bone formation after maxillary sinus augmentation by means of microcomputed tomography : a pilot study

Although many studies have analyzed the suitability of different grafting materials for maxillary sinus augmentation by means of histomorphometry in conventional histologic strains, the three-dimensional (3D) structure and remodeling of these grafts after healing beneath the sinus membrane remain unclear. The aim of the present study was to determine whether microcomputed tomography is a suitable method to evaluate the 3D structure and remodeling of grafts after sinus floor augmentation

Separation of presynaptic Cav2 and Cav1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca2+ pump PMCA

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca2+ signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)–triggered presynaptic Ca2+ entry remain unclear. Combining Drosophila genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Drosophila Cav2 homolog, Dmca1A or cacophony, and the Cav1 homolog, Dmca1D) but with spatial and functional separation. Cav2 within active zones is required for AP-triggered neurotransmitter release. By contrast, Cav1 localizes predominantly around active zones and contributes substantially to AP-evoked Ca2+ influx but has a small impact on release. Instead, L-type calcium currents through Cav1 fine-tune short-term plasticity and facilitate SV recycling. Separate control of SV exo- and endocytosis by AP-triggered presynaptic Ca2+ influx through different channels demands efficient measures to protect the neurotransmitter release machinery against Cav1-mediated Ca2+ influx. We show that the plasma membrane Ca2+ ATPase (PMCA) resides in between active zones and isolates Cav2-triggered release from Cav1-mediated dynamic regulation of recycling and short-term plasticity, two processes which Cav2 may also contribute to. As L-type Cav1 channels also localize next to PQ-type Cav2 channels within axon terminals of some central mammalian synapses, we propose that Cav2, Cav1, and PMCA act as a conserved functional triad that enables separate control of SV release and recycling rates in presynaptic terminals

Estimation of [177Lu]PSMA-617 tumor uptake based on voxel-wise 3D Monte Carlo tumor dosimetry in patients with metastasized castration resistant prostate cancer

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