Programing stimuli-responsiveness of gelatin with electron beams: Basic effects and development of a hydration-controlled biocompatible demonstrator

Biomimetic materials with programmable stimuli responsiveness constitute a highly attractive material class for building bioactuators, sensors and active control elements in future biomedical applications. With this background, we demonstrate how energetic electron beams can be utilized to construct tailored stimuli responsive actuators for biomedical applications. Composed of collagen-derived gelatin, they reveal a mechanical response to hydration and changes in pH-value and ion concentration, while maintaining their excellent biocompatibility and biodegradability. While this is explicitly demonstrated by systematic characterizing an electron-beam synthesized gelatin-based actuator of cantilever geometry, the underlying materials processes are also discussed, based on the fundamental physical and chemical principles. When applied within classical electron beam lithography systems, these findings pave the way for a novel class of highly versatile integrated bioactuators from micro-to macroscales

Quellmonitoring zur optimierten Quellwassernutzung

Im Rahmen eines Forschungsprojekts wurde bei einzelnen Quellfassungen eine kontinuierliche Überwachung zur Erfassung von Veränderungen der Trinkwassereigenschaften aufgrund hydrologischer Ereignisse durchgeführt. Die Quellfassungen wurden dabei mit einer kontinuierlichen Erfassung von Schüttung (in l/s mittels Messwehr und Wasserstand bzw. Wasserzähler), Wassertemperatur (in C), elektrischer Leitfähigkeit (S/cm), Trübung (FTU), spektralem Absorptionskoeffizient (SAK254) (Abs/m), gelöstem organischem Kohlenstoff (DOC mg/l) und Transmission (%) jeweils mittels 10-Minuten- bzw. Stundenwerten überwacht. Zusätzlich wurde zur Erfassung von unmittelbaren Niederschlagsereignissen im Fassungsgebiet eine Niederschlagsmessung (Zeit und Menge) eingesetzt und es wurden vergleichende Laboranalysen durchgeführt. Im Rahmen dieser Überwachung wurde zusätzlich die Anwendung der eingesetzten Messinstrumente an Extremstandorten (z. B. kein Stromanschluss) evaluiert. Für den Wasserversorger können durch die Anwendung einer über eine gewisse Zeit durchgeführten kontinuierlichen Quellüberwachung Vorteile für die Einschätzung besonderer Betriebssituationen durch Kenntnis der Beeinflussung und des Ausmaßes entstehen, um eine optimierte Quellnutzung aufzubauen. Sind die quellspezifischen Wirkungen auf Basis eines Quellmonitorings bekannt (Prozessverständnis), kann die Quellnutzung oft mit sehr einfachen Maßnahmen, wie kurzfristiges Ausleiten des nativen Wassers oder Einsatz einer zeitlich begrenzten Desinfektionsmaßnahme, optimiert werden. Durch die Anwendung von Messinstrumenten mit geringer Stromaufnahme und Akkusystemen konnte auch an Extremstandorten eine Überwachung über mehrere Monate durchgeführt werden. Aufbauend auf dem durchgeführten Quellmonitoring konnten Anforderungen an eine Messstation definiert werden.In the context of a research project, individual wells were continuously monitored to identify and measure changes in drinking-water quality in response to hydrological events. Specifically, the criteria flow rate (in l/s using a measuring weir and water level, or water flow meter), water temperature (in C), electrical conductivity (S/cm), turbidity (FTU), spectral absorption coefficient (SAC 254), dissolved organic carbon (DOC mg/l) and transmission (%) were continuously monitored at 10-minute or hourly intervals. In addition, the times and volumes of precipitation events were recorded, and comparative laboratory analyses were conducted. Lastly, the monitoring equipments suitability for use at extreme locations (e.g. those with no electrical power outlets) was evaluated. For water providers, continuous monitoring could help to assess special operating situations, providing insights into their scope of influence and helping promote optimized well use. Once well monitoring has been used to determine the well-specific effects, the usage of the well can often be optimized with the help of simple measures, e.g. temporarily diverting the native water or employing a short-term disinfectant. By using measuring equipment with low power requirements and rechargeable battery systems, it was also possible to conduct monitoring over several months at extreme locations. Further, the results of the well-monitoring efforts were used to define a set of criteria for monitoring stations.(VLID)214289

Clavicle Elevation or Shoulder Girdle Depression in Acromioclavicular Joint Dislocation: A Radiological Investigation

Background: The side-comparative coracoclavicular (CC) distance is used to describe the vertical instability component of acute acromioclavicular (AC) joint dislocations. Elevation of the clavicle or a depression of the shoulder girdle can lead to an increased CC distance. The dislocation direction has not yet been investigated and is not included in common classification systems. Hypothesis: Clavicle elevation is primarily responsible for vertical dislocation in AC joint separation. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Weighted and nonweighted bilateral plain anteroposterior views of the shoulder girdles of patients with AC joint dislocations (Rockwood [RW] types III and V), diagnosed in our trauma department between 2001 and 2018, were included in this study. After determining the CC distance, a side-comparative determination of the positions of both the clavicle and shoulder girdle, with reference to the spinal column, was conducted. Results: In total, 245 bilateral plain anteroposterior views were evaluated (RW III, n = 116; RW V, n = 129). All patients showed a side-comparative clavicle elevation (mean +/- SD: RW III, 5 +/- 14 mm; RW V, 11 +/- 17 mm) in weighted and nonweighted views. While no depression of the shoulder girdle was measured in RW III injuries (weighted and nonweighted views, 0 +/- 11 mm), dropping of the shoulder girdle in RW V lesions on nonweighted views was observed (-5 +/- 11 mm). Conclusion: Vertical dislocation is mostly associated with clavicle elevation in RW III injures, while in high-grade AC joint dislocations (RW V), a combination of clavicle elevation and shoulder girdle depression is present. A significantly greater superior displacement of the clavicle in RW V injuries was seen in weighted views, while a depression of the shoulder girdle could be detected in nonweighted views. For the first time, these results include the dislocation direction in the classification of an AC joint injury. Further studies are needed to investigate the extent to which dislocation types differ in optimal therapy and outcome

NGS-guided precision oncology in metastatic breast and gynecological cancer: first experiences at the CCC Munich LMU

PURPOSE Comprehensive genomic profiling identifying actionable molecular alterations aims to enable personalized treatment for cancer patients. The purpose of this analysis was to retrospectively assess the impact of personalized recommendations made by a multidisciplinary tumor board (MTB) on the outcome of patients with breast or gynecological cancers, who had progressed under standard treatment. Here, first experiences of our Comprehensive Cancer Center Molecular Tumor Board are reported. METHODS All patients were part of a prospective local registry. 95 patients diagnosed with metastatic breast cancer or gynecological malignancies underwent extended molecular profiling. From May 2017 through March 2019, the MTB reviewed all clinical cases considering tumor profile and evaluated molecular alterations regarding further diagnostic and therapeutic recommendations. RESULTS 95 patients with metastatic breast or gynecological cancers were discussed in the MTB (68% breast cancer, 20% ovarian cancer, 5% cervical cancer, 3% endometrial cancer and 4% others). Genes with highest mutation rate were PIK3CA and ERBB2. Overall, 34 patients (36%) received a biomarker-based targeted therapy recommendation. Therapeutic recommendations were implemented in nine cases; four patients experienced clinical benefit with a partial response or disease stabilization lasting over 4~months. CONCLUSION In the setting of a multidisciplinary molecular tumor board, a small but clinically meaningful group of breast and gynecological cancer patients benefits from comprehensive genomic profiling. Broad and successful implementation of precision medicine is complicated by patient referral at late stage disease and limited access to targeted agents and early clinical trials. TRIAL REGISTRATION NUMBER 284-10 (03.05.2018)

A database accelerator for energy-efficient query processing and optimization

Data processing on a continuously growing amount of information and the increasing power restrictions have become an ubiquitous challenge in our world today. Besides parallel computing, a promising approach to improve the energy efficiency of current systems is to integrate specialized hardware. This paper presents a Tensilica RISC processor extended with an instruction set to accelerate basic database operators frequently used in modern database systems. The core was taped out in a 28 nm SLP CMOS technology and allows energy-efficient query processing as well as query optimization by applying selectivity estimation techniques. Our chip measurements show an 1000x energy improvement on selected database operators compared to state-of-the-art systems

Dose-compatible grating-based phase-contrast mammography on mastectomy specimens using a compact synchrotron source

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phasecontrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischemic heart?

Despite advances in myocardial reperfusion therapies, acute myocardial ischemia/reperfusion injury and consequent ischemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signaling networks activated in the ischemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischemia, putting it in the context of the human "diseasome".Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischemia/reperfusion injury and ischemic heart failure in the post-genomic era

Programing stimuli-responsiveness of gelatin with electron beams: basic effects and development of a hydration-controlled biocompatible demonstrator

Abstract Biomimetic materials with programmable stimuli responsiveness constitute a highly attractive material class for building bioactuators, sensors and active control elements in future biomedical applications. With this background, we demonstrate how energetic electron beams can be utilized to construct tailored stimuli responsive actuators for biomedical applications. Composed of collagen-derived gelatin, they reveal a mechanical response to hydration and changes in pH-value and ion concentration, while maintaining their excellent biocompatibility and biodegradability. While this is explicitly demonstrated by systematic characterizing an electron-beam synthesized gelatin-based actuator of cantilever geometry, the underlying materials processes are also discussed, based on the fundamental physical and chemical principles. When applied within classical electron beam lithography systems, these findings pave the way for a novel class of highly versatile integrated bioactuators from micro- to macroscales