Bottromycin A2 is a structurally unique ribosomally synthesized and post‐translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug‐resistant bacteria. The ...structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare β‐methylated amino acid residues. The N‐terminus of a precursor peptide (BtmD) is converted into bottromycin A2 by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations in this pathway, including the unprecedented macrocyclization. To understand the pathway in detail, an untargeted metabolomic approach that harnesses mass spectral networking was used to assess the metabolomes of a series of pathway mutants. This analysis has yielded key information on the function of a variety of previously uncharacterized biosynthetic enzymes, including a YcaO domain protein and a partner protein that together catalyze the macrocyclization.
A detailed understanding of bottromycin biosynthesis was obtained by harnessing a mass‐spectral network (represented by colored nodes in the picture) to analyze a series of pathway mutants. This method provides fresh insights into how this potent antibiotic is assembled, and shows that a YcaO domain protein works with a hydrolase‐like protein to catalyze the formation of the macrocyclic amidine.
Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % ...and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones.
Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs).
40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively.
DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.
To develop mitigation measures for the protection of bats in close proximity to onshore wind turbines, new detection techniques covering large-scale environments and techniques, which are able to ...track individuals are required. Radar based observations, successfully applied in ornithological studies, offer a promising potential, but come with challenges regarding the comparability of measurements and noise interference (ground clutter) from objects within detection range. This paper presents improvements of a commercially available inexpensive pulse radar for 3D spatial detection of bat-sized objects in onshore wind parks. A new analytical spatial detection volume model is presented incorporating calibrated radar data and landscape parameters such as clutter. Computer simulation programs to process the analytical spatial detection volume model were developed. For model calibration, the minimum signal power of the radar was experimentally determined with the radar cross section (RCS) of an artificial bat (similar to Nyctalus noctula), resulting in a maximum detection range of 800 m and a corresponding RCS of 12.7 cm². Additionally, the spatial volume for radar detection was optimized with a clutter shielding fence (CSF). Adjusting the volume model by incorporating a theoretical model of the CSF, an extension of the detection volume by a factor of 2.5 was achieved, while the total volume of a 105° horizontal angular radar image section yields 0.0105 km³. Extrapolation and comparison with state-of-the-art acoustic bat detection result in a 270 times larger volume, confirming the large-scale detection capabilities of the pulse radar.
Bottromycin A2 is a structurally unique ribosomally synthesized and post‐translationally modified peptide (RiPP) that possesses potent antibacterial activity towards multidrug‐resistant bacteria. The ...structural novelty of bottromycin stems from its unprecedented macrocyclic amidine and rare β‐methylated amino acid residues. The N‐terminus of a precursor peptide (BtmD) is converted into bottromycin A2 by tailoring enzymes encoded in the btm gene cluster. However, little was known about key transformations in this pathway, including the unprecedented macrocyclization. To understand the pathway in detail, an untargeted metabolomic approach that harnesses mass spectral networking was used to assess the metabolomes of a series of pathway mutants. This analysis has yielded key information on the function of a variety of previously uncharacterized biosynthetic enzymes, including a YcaO domain protein and a partner protein that together catalyze the macrocyclization.
Eine massenspektrometrische Analyse (repräsentiert durch das Netzwerk im Bildhintergrund) gibt Aufschluss über die Biosynthese von Bottromycin. Neben neuen Einblicken in den Aufbau dieses starken Antibiotikums wird gezeigt, dass ein YcaO‐Domänenprotein mit einem Hydrolase‐artigen Protein bei der katalytischen Bildung des Amidin‐Makrocyclus zusammenarbeitet.
Risk stratification in upper gastrointestinal bleeding (UGIB) currently relies on clinical parameters and risk scores. HemoPill
®
acute (Ovesco Endoscopy, Tuebingen, Germany) is a pill-shaped, orally ...administered sensor capsule for real-time blood detection. The aim of this study was to evaluate the system in clinical routine.
Sixty-one consecutive patients in whom the HemoPill
®
had been used at 12 international hospitals between July 2019 and March 2020 were retrospectively analysed. Indications for application were the clinical suspicion of UGIB, small bowel bleeding, of rebleeding after hemostasis. Primary endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse events and change of clinical course.
The capsule was used in 45 (73%) patients with UGIB, in 12 (20%) patients with small bowel bleeding and in four (7%) patients for exclusion of rebleeding. Technical success was 98%. 35/60 (58%) cases were capsule-positive and among these, endoscopy showed bleeding in 20/35 (57%) cases. None of the 25 capsule-negative patients rebled. Emergency endoscopy could be avoided in 18/25 (72%) cases. Serious adverse events did not occur.
HemoPill
®
-based blood detection is feasible and safe. Negative capsule results might 'downgrade' the need for urgent endoscopy.
To develop mitigation measures for the protection of bats in close proximity to onshore wind turbines, new detection techniques covering large-scale environments and techniques, which are able to ...track individuals are required. Radar based observations, successfully applied in ornithological studies, offer a promising potential, but come with challenges regarding the comparability of measurements and noise interference (ground clutter) from objects within detection range. This paper presents improvements of a commercially available inexpensive pulse radar for 3D spatial detection of bat-sized objects in onshore wind parks. A new analytical spatial detection volume model is presented incorporating calibrated radar data and landscape parameters such as clutter. Computer simulation programs to process the analytical spatial detection volume model were developed. For model calibration, the minimum signal power of the radar was experimentally determined with the radar cross section (RCS) of an artificial bat (similar to Nyctalus noctula), resulting in a maximum detection range of 800 m and a corresponding RCS of 12.7 cm². Additionally, the spatial volume for radar detection was optimized with a clutter shielding fence (CSF). Adjusting the volume model by incorporating a theoretical model of the CSF, an extension of the detection volume by a factor of 2.5 was achieved, while the total volume of a 105° horizontal angular radar image section yields 0.0105 km³. Extrapolation and comparison with state-of-the-art acoustic bat detection result in a 270 times larger volume, confirming the large-scale detection capabilities of the pulse radar.
The maximum likelihood estimation of the left-truncated log-logistic distribution with a given truncation point is analyzed in detail from both mathematical and numerical perspectives. These maximum ...likelihood equations often do not possess a solution, even for small truncations. A simple criterion is provided for the existence of a regular maximum likelihood solution. In this case a profile likelihood function can be constructed and the optimisation problem is reduced to one dimension. When the maximum likelihood equations do not admit a solution for certain data samples, it is shown that the Pareto distribution is the \(L^1\)-limit of the degenerated left-truncated log-logistic distribution. Using this mathematical information, a highly efficient Monte Carlo simulation is performed to obtain critical values for some goodness-of-fit tests. The confidence tables and an interpolation formula are provided and several applications to real world data are presented.
In highly automated driving (HAD), it is still an open question how machines can safely hand over control to humans, and if an advance notice with additional explanations can be beneficial in ...critical situations. Conceptually, use of formal methods from AI – description logic (DL) and automated planning – in order to more reliably predict when a handover is necessary, and to increase the advance notice for handovers by planning ahead at runtime, can provide a technological support for explanations using natural language generation. However, in this work we address only the user’s perspective with two contributions: First, we evaluate our concept in a driving simulator study (N=23) and find that an advance notice and spoken explanations were preferred over classical handover methods. Second, we propose a framework and an example test scenario specific to handovers that is based on the results of our study.
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