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Funding agencies and field experts promote reuse of scientific data and biomaterial beyond the scope of the original project. The availability of research data, however, is limited by the interest of original authors as well as the privacy rights of the study participants, especially in the biomedical sciences. On the other hand, for an available data set to be a useful contribution to the scientific community, it has to be findable and accessible with reasonable effort. Therefore, using the R Shiny library, we designed and implemented a software for data discovery and feasibility analyses with compliance to regulatory and contractual regulations. Due to its genericity, it was successfully tested with heterogeneous data sets and ultimately applied to the data and biomaterial of the German Center for Cardiovascular Research (DZHK). The resulting tool - named the Feasibility Explorer - is publicly available and can be used by researchers to get an overview of data and biomaterial available in the DZHK and to select collectives in the process of submitting a usage application. To implement the rights of participants and original authors, data is integrated by querying the informed consent and not persistently stored. All calculations on the data are performed server-sided and only aggregated information is send to a client, whereas the extent of information was strictly limited to a necessary minimum that allows an applicant to assess whether an application is worthwhile.

Aims: Health data captured by commercially available smart devices may represent meaningful patient-reported outcome measures (PROMs) in heart failure (HF) patients. The purpose of this study was to test this hypothesis by evaluating the feasibility of a new telemonitoring concept for patients following initial HF hospitalization., Methods and Results: We designed a cardio patient monitoring platform (CPMP) that comprised mobile iOS-based applications for patients' smartphone/smartwatch and the equivalent application on a physicians' tablet. It allowed for safe and continuous data transmission of self-measured physiological parameters, activity data, and patient-reported symptoms. In a prospective feasibility trial with 692 patient days from 10 patients hospitalized for newly diagnosed HF with reduced ejection fraction (mean left ventricular ejection fraction (LVEF) 26.5 ± 9.8%), we examined the CPMP during the first 2 months following discharge (69 ± 15 observation days per patient). The mean daily step count recorded by the mobile devices emerged as a promising new PROM. Its 14 day average increased over the study period (3612 ± 3311 steps/day at study inclusion and 7069 ± 5006 steps/day at end of study; P < 0.0001). It is unique for continuously reflecting real-life activity and correlated significantly with traditional surrogate parameters of cardiac performance including LVEF (r = 0.44; 95% CI 0.07-0.71; P = 0.0232), 6 min walk test (r = 0.67; 95% CI 0.38-0.84; P = 0.0002), and scores in health-related quality of life questionnaires., Conclusions: We provide the first patient monitoring platform for HF patients that relies on commercially available iOS/watchOS-based devices. Our study suggests it is ready for implementation as a tool for recording meaningful PROMs in future HF trials and telemonitoring., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Sucrose transport across membranes requires the activity of transport proteins. Sucrose-specific SWEET proteins mediate sugar efflux out of the cytosol and SUC proteins catalyze the uptake of sucrose from the apoplast. Both transport processes are involved in phloem loading in source leaves as well as in the post-phloem pathway in sink tissues. An important step during the characterization of new sucrose transporters is to analyze their transport activity. This is usually achieved by heterologous expression of the respective gene in yeast cells or Xenopus oocytes and subsequent uptake measurements. However, in some cases, mistargeting to internal membranes or the lack of protein modifications and/or interaction partners in the heterologous system can interfere with uptake analyses. Therefore, a new in planta method was developed that is based on mesophyll protoplasts as expression system and the fluorescent sucrose analog esculin to monitor uptake activities by confocal microscopy. In this chapter we describe the design of constructs required to analyze sucrose transporters in protoplasts, the experimental setup of the protoplast-esculin assay, and the quantitative evaluation of the obtained data. The quantification of esculin uptake allows the application of the new assay to a variety of questions, e.g., by comparison of point mutants, splice variants, or transporters with and without interaction partners.

Pollen tube growth requires a high amount of metabolic energy and precise targeting toward the ovules. Sugars, especially glucose, can serve as nutrients and as signaling molecules. Unexpectedly, in vitro assays revealed an inhibitory effect of glucose on pollen tube elongation, contradicting the hypothesis that monosaccharide uptake is a source of nutrition for growing pollen tubes. Measurements with Förster resonance energy transfer-based nanosensors revealed that glucose is taken up into pollen tubes and that the intracellular concentration is in the low micromolar range. Pollen tubes of stp4-6-8-9-10-11 sextuple knockout plants generated by crossings and CRISPR/Cas9 showed only a weak response to glucose, indicating that glucose uptake into pollen tubes is mediated mainly by these six monosaccharide transporters of the SUGAR TRANSPORT PROTEIN (STP) family. Analyses of HEXOKINASE1 ( HXK1 ) showed a strong expression of this gene in pollen. Together with the glucose insensitivity and altered semi-in vivo growth rate of pollen tubes from hxk1 knockout lines, this strongly suggests that glucose is an important signaling molecule for pollen tubes, is taken up by STPs, and detected by HXK1. Equimolar amounts of fructose abolish the inhibitory effect of glucose indicating that only an excess of glucose is interpreted as a signal. This provides a possible model for the discrimination of signaling and nutritional sugars., (© 2018 American Society of Plant Biologists. All rights reserved.)

The controlled distribution of sugars between assimilate-exporting source tissues and sugar-consuming sink tissues is a key element for plant growth and development. Monosaccharide transporters of the SUGAR TRANSPORT PROTEIN (STP) family contribute to the uptake of sugars into sink cells. Here, we report on the characterization of STP7, STP8, and STP12, three previously uncharacterized members of this family in Arabidopsis ( Arabidopsis thaliana ). Heterologous expression in yeast ( Saccharomyces cerevisiae ) revealed that STP8 and STP12 catalyze the high-affinity proton-dependent uptake of glucose and also accept galactose and mannose. STP12 additionally transports xylose. STP8 and STP12 are highly expressed in reproductive organs, where their protein products might contribute to sugar uptake into the pollen tube and the embryo sac. stp8.1 and stp12.1 T-DNA insertion lines developed normally, which may point toward functional redundancy with other STPs. In contrast to all other STPs, STP7 does not transport hexoses but is specific for the pentoses l-arabinose and d-xylose. STP7- promoter-reporter gene plants showed an expression of STP7 especially in tissues with high cell wall turnover, indicating that STP7 might contribute to the uptake and recycling of cell wall sugars. Uptake analyses with radioactive l-arabinose revealed that 11 other STPs are able to transport l-arabinose with high affinity. Hence, functional redundancy might explain the missing-mutant phenotype of two stp7 T-DNA insertion lines. Together, these data complete the characterization of the STP family and present the STPs as new l-arabinose transporters for potential biotechnological applications., (© 2018 American Society of Plant Biologists. All Rights Reserved.)

Pollen tubes are fast growing, photosynthetically inactive cells. Their energy demand is covered by specific transport proteins in the plasma membrane that mediate the uptake of sugars. Here we report on the functional characterization of AtSTP10, a previously uncharacterized member of the SUGAR TRANSPORT PROTEIN family. Heterologous expression of STP10 cDNA in yeast revealed that the encoded protein catalyses the high-affinity uptake of glucose, galactose and mannose. The transporter is sensitive to uncouplers of transmembrane proton gradients, indicating that the protein acts as a hexose-H(+)symporter. Analyses of STP10 mRNA and STP10 promoter-reporter gene studies revealed a sink-specific expression pattern of STP10 in primordia of lateral roots and in pollen tubes. This restriction to sink organs is mediated by intragenic regions of STP10 qPCR analyses with cDNA of in vitro grown pollen tubes showed that STP10 expression was down-regulated in the presence of 50mM glucose. However, in pollen tubes of glucose-insensitive plants, which lack the glucose sensor hexokinase1 (HXK1), no glucose-induced down-regulation of STP10 expression was detected. A stp10T-DNA insertion line developed normally, which may point towards functional redundancy. The data presented in this paper indicate that a high-affinity glucose uptake system is induced in growing pollen tubes under low glucose conditions and that this regulation may occur through the hexokinase pathway., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

In University Medical Centers, heterogeneous data are generated that cannot always be clearly attributed to patient care or biomedical research. Each data set has to adhere to distinct intrinsic and operational quality standards. However, only if high-quality data, tools to work with the data, and most importantly guidelines and rules of how to work with the data are addressed adequately, an infrastructure can be sustainable. Here, we present the IT Research Architecture of the University Medical Center Göttingen and describe our ten years' experience and lessons learned with infrastructures in networked medical research.

Although national eHealth strategies have existed now for more than a decade in many countries, they have been implemented with varying success. In Germany, the eHealth strategy so far has resulted in a roll out of electronic health cards for all citizens in the statutory health insurance, but in no clinically meaningful IT-applications. The aim of this study was to test the technical and organisation feasibility, usability, and utility of an eDischarge application embedded into a laboratory Health Telematics Infrastructure (TI). The tests embraced the exchange of eDischarge summaries based on the multiprofessional HL7 eNursing Summary standard between a municipal hospital and a nursing home. All in all, 36 transmissions of electronic discharge documents took place. They demonstrated the technical-organisation feasibility and resulted in moderate usability ratings. A comparison between eDischarge and paper-based summaries hinted at higher ratings of utility and information completeness for eDischarges. Despite problems with handling the electronic health card, the proof-of-concept for the first clinically meaningful IT-application in the German Health TI could be regarded as successful.

Objectives: When new cochlear implant (CI) sound processors are being introduced by the manufacturers, usually the newest generation implants benefit first from the new technology in order to release the full potential of the new hardware. Subsequently, for the Advanced Bionics system the Harmony behind-the-ear processor was only compatible to the newer generation implants, i.e. the CII and HiRes90K, at the time of market release. After further development of a new Digital Signal Processing code the Harmony could also support the first implant generation, the 'C1' (Clarion 1.0 and 1.2). This study reports on a field trial with a new sound processor designed to be used with older generation CIs from Advanced Bionics, focussing on ergonomic and performance benefits., Methods: Speech perception tests (Freiburger monosyllables, HSM sentence tests) were performed at a baseline appointment with the subject's clinical processor, followed by the fitting of the Harmony. After a 1 month take-home period the tests were repeated with the Harmony. Additionally, subjective evaluation through questionnaires and a structured interview were administered after upgrading to the sound processor 'C1 Harmony'. Adult users of Advanced Bionics C1 series CIs (n = 29) participated in this study., Results: The new processor provided superior performance in many, though not all, of the speech recognition measurements. Subjective reports indicated certain practical benefits from the new processor, particularly for previous users of body-worn processors. Overall, 80% of the subjects preferred the new processor., Conclusion: The positive outcomes from this trial have resulted in the decision to make the new C1 Harmony processor available to all existing users of the early C1 devices.

The eyespot of Chlamydomonas reinhardtii is a light-sensitive organelle important for phototactic orientation of the alga. Here, we found that eyespot size is strain specific and downregulated in light. In a strain in which the blue light photoreceptor phototropin was deleted by homologous recombination, the light regulation of the eyespot size was affected. We restored this dysfunction in different phototropin complementation experiments. Complementation with the phototropin kinase fragment reduced the eyespot size, independent of light. Interestingly, overexpression of the N-terminal light, oxygen or voltage sensing domains (LOV1+LOV2) alone also affected eyespot size and phototaxis, suggesting that aside from activation of the kinase domain, they fulfill an independent signaling function in the cell. Moreover, phototropin is involved in adjusting the level of channelrhodopsin-1, the dominant primary receptor for phototaxis within the eyespot. Both the level of channelrhodopsin-1 at the onset of illumination and its steady state level during the light period are downregulated by phototropin, whereas the level of channelrhodopsin-2 is not significantly altered. Furthermore, a light intensity-dependent formation of a C-terminal truncated phototropin form was observed. We propose that phototropin is a light regulator of phototaxis that desensitizes the eyespot when blue light intensities increase.