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Protamines are unique sperm-specific proteins that package and protect paternal chromatin until fertilization. A subset of mammalian species expresses two protamines (PRM1 and PRM2), while in others PRM1 is sufficient for sperm chromatin packaging. Alterations of the species-specific ratio between PRM1 and PRM2 are associated with infertility. Unlike PRM1, PRM2 is generated as a precursor protein consisting of a highly conserved N-terminal domain, termed cleaved PRM2 (cP2), which is consecutively trimmed off during chromatin condensation. The carboxyterminal part, called mature PRM2 (mP2), interacts with DNA and together with PRM1, mediates chromatin-hypercondensation. The removal of the cP2 domain is believed to be imperative for proper chromatin condensation, yet, the role of cP2 is not yet understood. We generated mice lacking the cP2 domain while the mP2 is still expressed. We show that the cP2 domain is indispensable for complete sperm chromatin protamination and male mouse fertility. cP2 deficient sperm show incomplete PRM2 incorporation, resulting in a severely altered protamine ratio, retention of transition proteins and aberrant retention of the testis specific histone variant H2A.L.2. During epididymal transit, cP2 deficient sperm seem to undergo ROS mediated degradation leading to complete DNA fragmentation. The cP2 domain therefore seems to be a key aspect in the complex crosstalk between histones, transition proteins and protamines during sperm chromatin condensation. Overall, we present the first step towards understanding the role of the cP2 domain in paternal chromatin packaging and open up avenues for further research.

In this study, the feasibility of Micro-Electro-Mechanical System (MEMS) accelerometers and an image-assisted total station (IATS) for short- and long-term deformation monitoring of bridge structures is investigated. The MEMS sensors of type BNO055 from Bosch as part of a geo-sensor network are mounted at different positions of the bridge structure. In order to degrade the impact of systematic errors on the acceleration measurements, the deterministic calibration parameters are determined for fixed positions using a KUKA youBot in a climate chamber over certain temperature ranges. The measured acceleration data, with a sampling frequency of 100 Hz, yields accurate estimates of the modal parameters over short time intervals but suffer from accuracy degradation for absolute position estimates with time. To overcome this problem, video frames of a passive target, attached in the vicinity of one of the MEMS sensors, are captured from an embedded on-axis telescope camera of the IATS of type Leica Nova MS50 MultiStation with a practical sampling frequency of 10 Hz. To identify the modal parameters such as eigenfrequencies and modal damping for both acceleration and displacement time series, a damped harmonic oscillation model is employed together with an autoregressive (AR) model of coloured measurement noise. The AR model is solved by means of a generalized expectation maximization (GEM) algorithm. Subsequently, the estimated model parameters from the IATS are used for coordinate updates of the MEMS sensor within a Kalman filter approach. The experiment was performed for a synthetic bridge and the analysis shows an accuracy level of sub-millimetre for amplitudes and much better than 0.1 Hz for the frequencies.

Objective: Stakeholders involved in developing recommendations need to have a common understanding of health outcomes and the perspective of affected individuals. In this paper we report on the development and application of health outcome descriptors (HODs) to inform decision-making by panels developing guideline recommendations. Study Design and Setting: Ten American Society of Hematology guideline panels addressing the management of venous thromboembolism developed HODs, rated their importance and health utility, applied them to prioritize outcomes, and to balance potential benefits and harms to formulate recommendations. Results: It was feasible to involve 18 panelists in developing 127 HODs. There was high agreement (82%) across the ten panels about outcomes perceived as critical or important for decision-making. Panelists' utility ratings of the outcomes were strongly correlated with panelists' outcome importance ratings (Pearson's r =-0.88). HODs were incorporated into Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence-to-decision (EtD) frameworks to support a shared understanding of health outcomes in panel deliberations. Conclusion: HODs serve as a valuable tool to promote an explicit, common understanding of health outcomes during clinical guideline development and across different stakeholders. They are helpful across multiple steps of guideline development to facilitate panels' judgements, aiming to avoid variable implicit interpretations of health outcomes. (C) 2021 Elsevier Inc. All rights reserved.

This paper describes how a 3D object capturing is performed by kinematic terrestrial laser scanning (k-TLS) using a novel multi-sensor system (MSS). Due to the high accuracy requirements of s3D = 1 mm, special requirements arise. Here, a profile laser scanner on a mobile platform is moved along the object and highly accurate georeferenced by a laser tracker. This enables an efficient acquisition of large objects, resulting in a time reduction of up to 70 % compared to static terrestrial laser scanning (s-TLS). The main developments presented in the paper concern the topics: mobile platforms (types and damping), system calibration, high-accurate pointwise georeferencing and the final quality assessment of the data.