Crystal Structure of Thermotoga maritima α-Glucosidase AglA Defines a New Clan of NAD+-dependent Glycosidases

Glycoside hydrolase family 4 represents an unusual group of glucosidases with a requirement for NAD(+), divalent metal cations, and reducing conditions. The family is also unique in its inclusion of both alpha- and beta-specific enzymes. The alpha-glucosidase A, AglA, from Thermotoga maritima is a typical glycoside hydrolase family 4 enzyme, requiring NAD(+) and Mn2+ as well as strongly reducing conditions for activity. Here we present the crystal structure of the protein complexed with NAD(+) and maltose, refined at a resolution of 1.9 Angstrom. The NAD(+) is bound to a typical Rossman fold NAD(+)-binding site, and the nicotinamide moiety is localized close to the maltose substrate. Within the active site the conserved Cys-174 and surrounding histidines are positioned to play a role in the hydrolysis reaction. The electron density maps indicate that Cys-174 is oxidized to a sulfinic acid. Most likely, the strongly reducing conditions are necessary to reduce the oxidized cysteine side chain. Notably, the canonical set of catalytic acidic residues common to other glucosidases is not present in the active site. This, combined with a high structural homology to NAD-dependent dehydrogenases, suggests an unusual and possibly unique mechanism of action for a glycoside-hydrolyzing enzyme

A new proof for the approximation of the Log-function by Kantorovich polynomials in the LpL_p-norm

Not available

Redetermination of EuScO3

Single crystals of europium(III) scandate(III), with ideal formula EuScO3, were grown from the melt using the micro-pulling-down method. The title compound crystallizes in an ortho­rhom­bic distorted perovskite-type structure, where Eu occupies the eightfold coordinated A sites (site symmetry m) and Sc resides on the centres of corner-sharing [ScO6] octa­hedra (B sites with site symmetry ). The structure of EuScO3 has been reported previously based on powder diffraction data [Liferovich & Mitchell (2004). J. Solid State Chem. 177, 2188–2197]. The results of the current redetermination based on single-crystal diffraction data shows an improvement in the precision of the structral and geometric parameters and reveals a defect-type structure. Site-occupancy refinements indicate an Eu deficiency on the A site coupled with O defects on one of the two O-atom positions. The crystallochemical formula of the investigated sample may thus be written as A(□0.032Eu0.968)BScO2.952

ORCA-SPOT: An Automatic Killer Whale Sound Detection Toolkit Using Deep Learning

Large bioacoustic archives of wild animals are an important source to identify reappearing communication patterns, which can then be related to recurring behavioral patterns to advance the current understanding of intra-specific communication of non-human animals. A main challenge remains that most large-scale bioacoustic archives contain only a small percentage of animal vocalizations and a large amount of environmental noise, which makes it extremely difficult to manually retrieve sufficient vocalizations for further analysis – particularly important for species with advanced social systems and complex vocalizations. In this study deep neural networks were trained on 11,509 killer whale (Orcinus orca) signals and 34,848 noise segments. The resulting toolkit ORCA-SPOT was tested on a large-scale bioacoustic repository – the Orchive – comprising roughly 19,000 hours of killer whale underwater recordings. An automated segmentation of the entire Orchive recordings (about 2.2 years) took approximately 8 days. It achieved a time-based precision or positive-predictive-value (PPV) of 93.2% and an area-under-the-curve (AUC) of 0.9523. This approach enables an automated annotation procedure of large bioacoustics databases to extract killer whale sounds, which are essential for subsequent identification of significant communication patterns. The code will be publicly available in October 2019 to support the application of deep learning to bioaoucstic research. ORCA-SPOT can be adapted to other animal species

Beurteilung von Oberflächen durch Prozeßsimulation

Die Oberflächenqualität wird durch das dynamische Verhalten der Maschine beim Umfangsplanfräsen wesentlich beeinflußt. Beim Fräsvorgang entstehen durch den Zahneingriff auf der Werkstückoberfläche Zykloidenbewegungen in Form von spitzen Wellenbergen und runden Wellentälern. Zur Beurteilung von Oberflächen wurde ein Softwarepaket entwickelt, mit dem sowohl der kinematisch reine Prozeß als auch der durch das dynamische Verhalten der Maschine gestörte Prozeß, dargestellt werden kann. Durch Definition einer Kennzahl für die Ungleichmäßigkeit der Rillenabfolge können mit diesem Instrumentarium verschiedene Prozesse bzw. deren Störungen in ihrer Auswirkung auf die Oberflächenqualität verglichen werden. Am Institut für Werkzeugmaschinen der Universität Stuttgart werden mit Betriebsschwingungs- und Modalanalysen, Konstruktionsänderungen auch im Hinblick auf Oberflächenqualität in der Holzbearbeitung durchgeführt. In einer dreiteiligen Serie zur Oberflächenqualität beim Umfangsplanfräsen werden die Möglichkeiten beschrieben, die aus der Auswertung von Oberflächenprofilen zur Maschinenoptimierung entstehen

Advanced high pressure turbine blade repair technologies

Components in aircraft engines and gas turbines are exposed to extreme conditions in order to increase performance and efficiency of the overall engine, hence there is an increasing need for cost-effective and time-efficient repair strategies. Presented here are two novel approaches to the repair of Nickel-based components. The hybrid brazing process involves the application of a repair coating, a nickel-based filler material, a NiCoCrAlY and an aluminium layer, by thermal spraying followed by a heat treatment and combined brazing-aluminizing process. This significantly shortens the conventional repair brazing process and yields superior results. Single-crystal additive repair by laser cladding is applied for the repair of small or large defects in single-crystal turbine blades by enabling monocrystalline solidification of the cladded material by use of a temperature gradient, thereby allowing for the regeneration of these expensive components. The novel approach that combines layer-wise addition of material and laser melting enables the formation of highly monocrystalline structures

Cortical hypertrophy with a short, curved uncemented hip stem does not have any clinical impact during early follow-up

Background: Short stems have become more and more popular for cementless total hip arthroplasty in the past few years. While conventional, uncemented straight stems for primary total hip arthroplasty (THA) have shown high survival rates in the long term, it is not known whether uncemented short stems represent a reasonable alternative. As cortical hypertrophy has been reported for short stems, the aim of this study was to determine the radiographic prevalence of cortical hypertrophy and to assess the clinical outcome of a frequently used short, curved hip stem. Methods: We retrospectively studied the clinical and radiographic results of our first 100 consecutive THAs (97 patients) using the Fitmore® hip stem. Mean age at the time of index arthroplasty was 59 years (range, 19 – 79 years). Clinical outcome and radiographic results were assessed with a minimum follow-up of 2 years, and Kaplan-Meier survivorship analysis was used to estimate survival for different endpoints. Results: After a mean follow-up of 3.3 years (range, 2.0 – 4.4 years), two patients (two hips) had died, and three patients (four hips) were lost to follow-up. Kaplan-Meier analysis estimated a survival rate of 100 % at 3.8 years, with revision for any reason as the endpoint. No femoral component showed radiographic signs of loosening. No osteolysis was detected. Cortical hypertrophy was found in 50 hips (63 %), predominantly in Gruen zone 3 and 5. In the cortical hypertrophy group, two patients (two hips; 4 %) reported some thigh pain in combination with pain over the greater trochanter region during physical exercise (UCLA Score 6 and 7). There was no significant difference concerning the clinical outcome between the cortical hypertrophy and no cortical hypertrophy group. Conclusions: The survival rate and both clinical and the radiographic outcome confirm the encouraging results for short, curved uncemented stems. Postoperative radiographs frequently displayed cortical hypertrophy but it had no significant effect on the clinical outcome in the early follow-up. Further clinical and radiographic follow-up is necessary to detect possible adverse, long-term, clinical effects of cortical hypertrophy

ORCA-SPY enables killer whale sound source simulation, detection, classification and localization using an integrated deep learning-based segmentation

Acoustic identification of vocalizing individuals opens up new and deeper insights into animal communications, such as individual-/group-specific dialects, turn-taking events, and dialogs. However, establishing an association between an individual animal and its emitted signal is usually non-trivial, especially for animals underwater. Consequently, a collection of marine species-, array-, and position-specific ground truth localization data is extremely challenging, which strongly limits possibilities to evaluate localization methods beforehand or at all. This study presents ORCA-SPY, a fully-automated sound source simulation, classification and localization framework for passive killer whale (Orcinus orca) acoustic monitoring that is embedded into PAMGuard, a widely used bioacoustic software toolkit. ORCA-SPY enables array- and position-specific multichannel audio stream generation to simulate real-world ground truth killer whale localization data and provides a hybrid sound source identification approach integrating ANIMAL-SPOT, a state-of-the-art deep learning-based orca detection network, followed by downstream Time-Difference-Of-Arrival localization. ORCA-SPY was evaluated on simulated multichannel underwater audio streams including various killer whale vocalization events within a large-scale experimental setup benefiting from previous real-world fieldwork experience. Across all 58,320 embedded vocalizing killer whale events, subject to various hydrophone array geometries, call types, distances, and noise conditions responsible for a signal-to-noise ratio varying from −14.2 dB to 3 dB, a detection rate of 94.0 % was achieved with an average localization error of 7.01∘. ORCA-SPY was field-tested on Lake Stechlin in Brandenburg Germany under laboratory conditions with a focus on localization. During the field test, 3889 localization events were observed with an average error of 29.19∘ and a median error of 17.54∘. ORCA-SPY was deployed successfully during the DeepAL fieldwork 2022 expedition (DLFW22) in Northern British Columbia, with a mean average error of 20.01∘ and a median error of 11.01∘ across 503 localization events. ORCA-SPY is an open-source and publicly available software framework, which can be adapted to various recording conditions as well as animal species

Motion Biomarkers Showing Maximum Contrast Between Healthy Subjects and Parkinson's Disease Patients Treated With Deep Brain Stimulation of the Subthalamic Nucleus. A Pilot Study

Background: Classic motion abnormalities in Parkinson's disease (PD), such as tremor, bradykinesia, or rigidity, are well-covered by standard clinical assessments such as the Unified Parkinson's Disease Rating Scale (UPDRS). However, PD includes motor abnormalities beyond the symptoms and signs as measured by UPDRS, such as the lack of anticipatory adjustments or compromised movement smoothness, which are difficult to assess clinically. Moreover, PD may entail motor abnormalities not yet known. All these abnormalities are quantifiable via motion capture and may serve as biomarkers to diagnose and monitor PD. Objective: In this pilot study, we attempted to identify motion features revealing maximum contrast between healthy subjects and PD patients with deep brain stimulation (DBS) of the nucleus subthalamicus (STN) switched off and on as the first step to develop biomarkers for detecting and monitoring PD patients' motor symptoms. Methods: We performed 3D gait analysis in 7 out of 26 PD patients with DBS switched off and on, and in 25 healthy control subjects. We computed feature values for each stride, related to 22 body segments, four time derivatives, left–right mean vs. difference, and mean vs. variance across stride time. We then ranked the feature values according to their distinguishing power between PD patients and healthy subjects. Results: The foot and lower leg segments proved better in classifying motor anomalies than any other segment. Higher degrees of time derivatives were superior to lower degrees (jerk > acceleration > velocity > displacement). The averaged movements across left and right demonstrated greater distinguishing power than left–right asymmetries. The variability of motion was superior to motion's absolute values. Conclusions: This small pilot study identified the variability of a smoothness measure, i.e., jerk of the foot, as the optimal signal to separate healthy subjects' from PD patients' gait. This biomarker is invisible to clinicians' naked eye and is therefore not included in current motor assessments such as the UPDRS. We therefore recommend that more extensive investigations be conducted to identify the most powerful biomarkers to characterize motor abnormalities in PD. Future studies may challenge the composition of traditional assessments such as the UPDRS

Towards a Coronavirus-Based HIV Multigene Vaccine

Human immunodeficiency virus (HIV) infection represents one of the major health threats in the developing world. The costly treatment of infected individuals with multiple highly efficient anti-HIV drugs is only affordable in industrialized countries. Thus, an efficient vaccination strategy is required to prevent the further spread of the infection. The molecular biology of coronaviruses and particular features of the human coronavirus 229E (HCoV 229E) indicate that HCoV 229E-based vaccine vectors can become a new class of highly efficient vaccines. First, the receptor of HCoV 229E, human aminopeptidase N (hAPN or CD13) is expressed mainly on human dendritic cells (DCs) and macrophages indicating that targeting of HCoV 229E-based vectors to professional antigen presenting cells can be achieved by receptor-mediated transduction. Second, HCoV 229E structural genes can be replaced by multiple transcriptional units encoding various antigens. These virus-like particles (VLPs) containing HCoV 229E-based vector RNA have the ability to transduce human DCs and to mediate heterologous gene expression in these cells. Finally, coronavirus infections are associated with mainly respiratory and enteric diseases, and natural transmission of coronaviruses occurs via mucosal surfaces. In humans, HCoV 229E causes common cold by infecting the upper respiratory tract. HCoV 229E infections are mainly encountered in children and re-infection occurs frequently in adults. It is thus most likely that pre-existing immunity against HCoV 229E will not significantly impact on the vaccination efficiency if HCoV 229E-based vectors are used in humans