Publications by authors named "Markus Wenzel"

18 Publications

  • Page 1 of 1

Wheat Anaphylaxis in Adults Differs from Reactions to Other Types of Food.

J Allergy Clin Immunol Pract 2021 Apr 5. Epub 2021 Apr 5.

Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

Background: Wheat is one of the most commonly consumed foods and a known elicitor of anaphylaxis in children and adults. Reactions in adults are often cofactor dependent and characterized by a prolonged time between food intake and the onset of symptoms making the diagnosis of wheat anaphylaxis challenging.

Objective: To characterize a cohort of patients with the history of wheat anaphylaxis to better understand this atypical phenotype of anaphylaxis.

Methods: Data from the European Anaphylaxis Registry from 2007 to 2019 (n = 10,636) including 250 patients (213 adults and 37 children) with a history of anaphylaxis caused by wheat were analyzed.

Results: Wheat was the most common food elicitor of anaphylaxis in adults in the registry in Central Europe. Reactions to wheat in adults were frequently associated with exercise as a cofactor (82.8%) and partially delayed (57.5%). Only 36.9% of patients had atopic comorbidities, which was uncommonly low for adult patients allergic to other kinds of foods (63.2%). Anaphylaxis to wheat presented frequently with cardiovascular symptoms (86.7%) including severe symptoms such as loss of consciousness (41%) and less often with respiratory symptoms (53.6%). The reactions to wheat were more severe than reactions to other foods (odds ratio [OR] = 4.33), venom (OR = 1.58), or drugs (OR = 2.11).

Conclusions: Wheat is a relevant elicitor of anaphylaxis in adults in Central Europe. Wheat anaphylaxis is highly dependent on the presence of cofactors and less frequently associated with atopic diseases compared with other food allergies. More data on mechanisms of wheat-induced anaphylaxis are required to develop preventive measures for this potentially life-threatening disease.
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http://dx.doi.org/10.1016/j.jaip.2021.03.037DOI Listing
April 2021

Risk estimation of SARS-CoV-2 transmission from bluetooth low energy measurements.

NPJ Digit Med 2020 6;3:129. Epub 2020 Oct 6.

Fraunhofer Heinrich Hertz Institute, 10587 Berlin, Germany.

Digital contact tracing approaches based on Bluetooth low energy (BLE) have the potential to efficiently contain and delay outbreaks of infectious diseases such as the ongoing SARS-CoV-2 pandemic. In this work we propose a machine learning based approach to reliably detect subjects that have spent enough time in close proximity to be at risk of being infected. Our study is an important proof of concept that will aid the battery of epidemiological policies aiming to slow down the rapid spread of COVID-19.
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http://dx.doi.org/10.1038/s41746-020-00340-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538938PMC
October 2020

USMPep: universal sequence models for major histocompatibility complex binding affinity prediction.

BMC Bioinformatics 2020 Jul 2;21(1):279. Epub 2020 Jul 2.

Fraunhofer Heinrich Hertz Institute, Einsteinufer 37, Berlin, 10587, Germany.

Background: Immunotherapy is a promising route towards personalized cancer treatment. A key algorithmic challenge in this process is to decide if a given peptide (neoepitope) binds with the major histocompatibility complex (MHC). This is an active area of research and there are many MHC binding prediction algorithms that can predict the MHC binding affinity for a given peptide to a high degree of accuracy. However, most of the state-of-the-art approaches make use of complicated training and model selection procedures, are restricted to peptides of a certain length and/or rely on heuristics.

Results: We put forward USMPep, a simple recurrent neural network that reaches state-of-the-art approaches on MHC class I binding prediction with a single, generic architecture and even a single set of hyperparameters both on IEDB benchmark datasets and on the very recent HPV dataset. Moreover, the algorithm is competitive for a single model trained from scratch, while ensembling multiple regressors and language model pretraining can still slightly improve the performance. The direct application of the approach to MHC class II binding prediction shows a solid performance despite of limited training data.

Conclusions: We demonstrate that competitive performance in MHC binding affinity prediction can be reached with a standard architecture and training procedure without relying on any heuristics.
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http://dx.doi.org/10.1186/s12859-020-03631-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330990PMC
July 2020

UDSMProt: universal deep sequence models for protein classification.

Bioinformatics 2020 04;36(8):2401-2409

Department of Video Coding & Analytics, Fraunhofer Heinrich Hertz Institute, Berlin 10587, Germany.

Motivation: Inferring the properties of a protein from its amino acid sequence is one of the key problems in bioinformatics. Most state-of-the-art approaches for protein classification are tailored to single classification tasks and rely on handcrafted features, such as position-specific-scoring matrices from expensive database searches. We argue that this level of performance can be reached or even be surpassed by learning a task-agnostic representation once, using self-supervised language modeling, and transferring it to specific tasks by a simple fine-tuning step.

Results: We put forward a universal deep sequence model that is pre-trained on unlabeled protein sequences from Swiss-Prot and fine-tuned on protein classification tasks. We apply it to three prototypical tasks, namely enzyme class prediction, gene ontology prediction and remote homology and fold detection. The proposed method performs on par with state-of-the-art algorithms that were tailored to these specific tasks or, for two out of three tasks, even outperforms them. These results stress the possibility of inferring protein properties from the sequence alone and, on more general grounds, the prospects of modern natural language processing methods in omics. Moreover, we illustrate the prospects for explainable machine learning methods in this field by selected case studies.

Availability And Implementation: Source code is available under https://github.com/nstrodt/UDSMProt.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178389PMC
April 2020

Integrating neurophysiologic relevance feedback in intent modeling for information retrieval.

J Assoc Inf Sci Technol 2019 Sep 12;70(9):917-930. Epub 2019 Mar 12.

Neurotechnology Group Technische Universität Berlin Berlin 10587 Germany.

The use of implicit relevance feedback from neurophysiology could deliver effortless information retrieval. However, both computing neurophysiologic responses and retrieving documents are characterized by uncertainty because of noisy signals and incomplete or inconsistent representations of the data. We present the first-of-its-kind, fully integrated information retrieval system that makes use of online implicit relevance feedback generated from brain activity as measured through electroencephalography (EEG), and eye movements. The findings of the evaluation experiment (N = 16) show that we are able to compute online neurophysiology-based relevance feedback with performance significantly better than chance in complex data domains and realistic search tasks. We contribute by demonstrating how to integrate in interactive intent modeling this inherently noisy implicit relevance feedback combined with scarce explicit feedback. Although experimental measures of task performance did not allow us to demonstrate how the classification outcomes translated into search task performance, the experiment proved that our approach is able to generate relevance feedback from brain signals and eye movements in a realistic scenario, thus providing promising implications for future work in neuroadaptive information retrieval (IR).
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http://dx.doi.org/10.1002/asi.24161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853416PMC
September 2019

Automatic classification of dopamine transporter SPECT: deep convolutional neural networks can be trained to be robust with respect to variable image characteristics.

Eur J Nucl Med Mol Imaging 2019 Dec 31;46(13):2800-2811. Epub 2019 Aug 31.

Department for Diagnostic and Interventional Radiology and Nuclear Medicine, University Hospital Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

Purpose: This study investigated the potential of deep convolutional neural networks (CNN) for automatic classification of FP-CIT SPECT in multi-site or multi-camera settings with variable image characteristics.

Methods: The study included FP-CIT SPECT of 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls, and 438 Parkinson's disease patients. SPECT images were smoothed with an isotropic 18-mm Gaussian kernel resulting in 3 different PPMI settings: (i) original (unsmoothed), (ii) smoothed, and (iii) mixed setting comprising all original and all smoothed images. A deep CNN with 2,872,642 parameters was trained, validated, and tested separately for each setting using 10 random splits with 60/20/20% allocation to training/validation/test sample. The putaminal specific binding ratio (SBR) was computed using a standard anatomical ROI predefined in MNI space (AAL atlas) or using the hottest voxels (HV) analysis. Both SBR measures were trained (ROC analysis, Youden criterion) using the same random splits as for the CNN. CNN and SBR trained in the mixed PPMI setting were also tested in an independent sample from clinical routine patient care (149 with non-neurodegenerative and 149 with neurodegenerative parkinsonian syndrome).

Results: Both SBR measures performed worse in the mixed PPMI setting compared to the pure PPMI settings (e.g., AAL-SBR accuracy = 0.900 ± 0.029 in the mixed setting versus 0.957 ± 0.017 and 0.952 ± 0.015 in original and smoothed setting, both p < 0.01). In contrast, the CNN showed similar accuracy in all PPMI settings (0.967 ± 0.018, 0.972 ± 0.014, and 0.955 ± 0.009 in mixed, original, and smoothed setting). Similar results were obtained in the clinical sample. After training in the mixed PPMI setting, only the CNN provided acceptable performance in the clinical sample.

Conclusions: These findings provide proof of concept that a deep CNN can be trained to be robust with respect to variable site-, camera-, or scan-specific image characteristics without a large loss of diagnostic accuracy compared with mono-site/mono-camera settings. We hypothesize that a single CNN can be used to support the interpretation of FP-CIT SPECT at many different sites using different acquisition hardware and/or reconstruction software with only minor harmonization of acquisition and reconstruction protocols.
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http://dx.doi.org/10.1007/s00259-019-04502-5DOI Listing
December 2019

WHO and ITU establish benchmarking process for artificial intelligence in health.

Lancet 2019 Jul 29;394(10192):9-11. Epub 2019 Mar 29.

China Academy of Information and Communications Technology, Beijing, China.

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http://dx.doi.org/10.1016/S0140-6736(19)30762-7DOI Listing
July 2019

Implicit relevance feedback from electroencephalography and eye tracking in image search.

J Neural Eng 2018 04;15(2):026002

Fachgebiet Neurotechnologie, Technische Universität Berlin, Marchstr. 23, 10587 Berlin, Germany. Equal contributions.

Objective: Methods from brain-computer interfacing (BCI) open a direct access to the mental processes of computer users, which offers particular benefits in comparison to standard methods for inferring user-related information. The signals can be recorded unobtrusively in the background, which circumvents the time-consuming and distracting need for the users to give explicit feedback to questions concerning the individual interest. The obtained implicit information makes it possible to create dynamic user interest profiles in real-time, that can be taken into account by novel types of adaptive, personalised software. In the present study, the potential of implicit relevance feedback from electroencephalography (EEG) and eye tracking was explored with a demonstrator application that simulated an image search engine.

Approach: The participants of the study queried for ambiguous search terms, having in mind one of the two possible interpretations of the respective term. Subsequently, they viewed different images arranged in a grid that were related to the query. The ambiguity of the underspecified search term was resolved with implicit information present in the recorded signals. For this purpose, feature vectors were extracted from the signals and used by multivariate classifiers that estimated the intended interpretation of the ambiguous query.

Main Result: The intended interpretation was inferred correctly from a combination of EEG and eye tracking signals in 86% of the cases on average. Information provided by the two measurement modalities turned out to be complementary.

Significance: It was demonstrated that BCI methods can extract implicit user-related information in a setting of human-computer interaction. Novelties of the study are the implicit online feedback from EEG and eye tracking, the approximation to a realistic use case in a simulation, and the presentation of a large set of photographies that had to be interpreted with respect to the content.
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http://dx.doi.org/10.1088/1741-2552/aa9999DOI Listing
April 2018

The Berlin Brain-Computer Interface: Progress Beyond Communication and Control.

Front Neurosci 2016 21;10:530. Epub 2016 Nov 21.

Bernstein Focus: NeurotechnologyBerlin, Germany; Machine Learning Group, Technische Universität BerlinBerlin, Germany; Department of Brain and Cognitive Engineering, Korea UniversitySeoul, South Korea.

The combined effect of fundamental results about neurocognitive processes and advancements in decoding mental states from ongoing brain signals has brought forth a whole range of potential neurotechnological applications. In this article, we review our developments in this area and put them into perspective. These examples cover a wide range of maturity levels with respect to their applicability. While we assume we are still a long way away from integrating Brain-Computer Interface (BCI) technology in general interaction with computers, or from implementing neurotechnological measures in safety-critical workplaces, results have already now been obtained involving a BCI as research tool. In this article, we discuss the reasons why, in some of the prospective application domains, considerable effort is still required to make the systems ready to deal with the full complexity of the real world.
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http://dx.doi.org/10.3389/fnins.2016.00530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116473PMC
November 2016

Is Neural Activity Detected by ERP-Based Brain-Computer Interfaces Task Specific?

PLoS One 2016 28;11(10):e0165556. Epub 2016 Oct 28.

Neurotechnology Group, Technische Universität Berlin, Berlin, Germany.

Objective: Brain-computer interfaces (BCIs) that are based on event-related potentials (ERPs) can estimate to which stimulus a user pays particular attention. In typical BCIs, the user silently counts the selected stimulus (which is repeatedly presented among other stimuli) in order to focus the attention. The stimulus of interest is then inferred from the electroencephalogram (EEG). Detecting attention allocation implicitly could be also beneficial for human-computer interaction (HCI), because it would allow software to adapt to the user's interest. However, a counting task would be inappropriate for the envisaged implicit application in HCI. Therefore, the question was addressed if the detectable neural activity is specific for silent counting, or if it can be evoked also by other tasks that direct the attention to certain stimuli.

Approach: Thirteen people performed a silent counting, an arithmetic and a memory task. The tasks required the subjects to pay particular attention to target stimuli of a random color. The stimulus presentation was the same in all three tasks, which allowed a direct comparison of the experimental conditions.

Results: Classifiers that were trained to detect the targets in one task, according to patterns present in the EEG signal, could detect targets in all other tasks (irrespective of some task-related differences in the EEG).

Significance: The neural activity detected by the classifiers is not strictly task specific but can be generalized over tasks and is presumably a result of the attention allocation or of the augmented workload. The results may hold promise for the transfer of classification algorithms from BCI research to implicit relevance detection in HCI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0165556PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085039PMC
June 2017

Classification of Eye Fixation Related Potentials for Variable Stimulus Saliency.

Front Neurosci 2016 15;10:23. Epub 2016 Feb 15.

Neurotechnology Group, Technische Universität Berlin Berlin, Germany.

Objective: Electroencephalography (EEG) and eye tracking can possibly provide information about which items displayed on the screen are relevant for a person. Exploiting this implicit information promises to enhance various software applications. The specific problem addressed by the present study is that items shown in real applications are typically diverse. Accordingly, the saliency of information, which allows to discriminate between relevant and irrelevant items, varies. As a consequence, recognition can happen in foveal or in peripheral vision, i.e., either before or after the saccade to the item. Accordingly, neural processes related to recognition are expected to occur with a variable latency with respect to the eye movements. The aim was to investigate if relevance estimation based on EEG and eye tracking data is possible despite of the aforementioned variability.

Approach: Sixteen subjects performed a search task where the target saliency was varied while the EEG was recorded and the unrestrained eye movements were tracked. Based on the acquired data, it was estimated which of the items displayed were targets and which were distractors in the search task.

Results: Target prediction was possible also when the stimulus saliencies were mixed. Information contained in EEG and eye tracking data was found to be complementary and neural signals were captured despite of the unrestricted eye movements. The classification algorithm was able to cope with the experimentally induced variable timing of neural activity related to target recognition.

Significance: It was demonstrated how EEG and eye tracking data can provide implicit information about the relevance of items on the screen for potential use in online applications.
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http://dx.doi.org/10.3389/fnins.2016.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753317PMC
February 2016

EEG-based usability assessment of 3D shutter glasses.

J Neural Eng 2016 Feb 8;13(1):016003. Epub 2015 Dec 8.

Neurotechnology Group, Technische Universität Berlin, Berlin, Germany.

Objective: Neurotechnology can contribute to the usability assessment of products by providing objective measures of neural workload and can uncover usability impediments that are not consciously perceived by test persons. In this study, the neural processing effort imposed on the viewer of 3D television by shutter glasses was quantified as a function of shutter frequency. In particular, we sought to determine the critical shutter frequency at which the 'neural flicker' vanishes, such that visual fatigue due to this additional neural effort can be prevented by increasing the frequency of the system.

Approach: Twenty-three participants viewed an image through 3D shutter glasses, while multichannel electroencephalogram (EEG) was recorded. In total ten shutter frequencies were employed, selected individually for each participant to cover the range below, at and above the threshold of flicker perception. The source of the neural flicker correlate was extracted using independent component analysis and the flicker impact on the visual cortex was quantified by decoding the state of the shutter from the EEG.

Main Result: Effects of the shutter glasses were traced in the EEG up to around 67 Hz-about 20 Hz over the flicker perception threshold-and vanished at the subsequent frequency level of 77 Hz.

Significance: The impact of the shutter glasses on the visual cortex can be detected by neurotechnology even when a flicker is not reported by the participants. Potential impact. Increasing the shutter frequency from the usual 50 Hz or 60 Hz to 77 Hz reduces the risk of visual fatigue and thus improves shutter-glass-based 3D usability.
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http://dx.doi.org/10.1088/1741-2560/13/1/016003DOI Listing
February 2016

Randomized controlled trial of noninvasive positive pressure ventilation (NPPV) versus servoventilation in patients with CPAP-induced central sleep apnea (complex sleep apnea).

Sleep 2013 Aug 1;36(8):1163-71. Epub 2013 Aug 1.

Kloster Grafschaft, Pulmonary Medicine I, Home Mechanical Ventilation Unit and Sleep Laboratory, Schmallenberg, Germany.

Study Objectives: To compare the treatment effect of noninvasive positive pressure ventilation (NPPV) and anticyclic servoventilation in patients with continuous positive airway pressure (CPAP)-induced central sleep apnea (complex sleep apnea).

Design: Randomized controlled trial.

Setting: Sleep center.

Patients: Thirty patients who developed complex sleep apnea syndrome (CompSAS) during CPAP treatment.

Interventions: NPPV or servoventilation.

Measurements And Results: Patients were randomized to NPPV or servo-ventilation. Full polysomnography (PSG) was performed after 6 weeks. On CPAP prior to randomization, patients in the NPPV and servoventilator arm had comparable apnea-hypopnea indices (AHI, 28.6 ± 6.5 versus 27.7 ± 9.7 events/h (mean ± standard deviation [SD])), apnea indices (AI,19 ± 5.6 versus 21.1 ± 8.6 events/h), central apnea indices (CAI, 16.7 ± 5.4 versus 18.2 ± 7.1 events/h), oxygen desaturation indices (ODI,17.5 ± 13.1 versus 24.3 ± 11.9 events/h). During initial titration NPPV and servoventilation significantly improved the AHI (9.1 ± 4.3 versus 9 ± 6.4 events/h), AI (2 ± 3.1 versus 3.5 ± 4.5 events/h) CAI (2 ± 3.1 versus 2.5 ± 3.9 events/h) and ODI (10.1 ± 4.5 versus 8.9 ± 8.4 events/h) when compared to CPAP treatment (all P < 0.05). After 6 weeks we observed the following differences: AHI (16.5 ± 8 versus 7.4 ± 4.2 events/h, P = 0.027), AI (10.4 ± 5.9 versus 1.7 ± 1.9 events/h, P = 0.001), CAI (10.2 ± 5.1 versus 1.5 ± 1.7 events/h, P < 0.0001)) and ODI (21.1 ± 9.2 versus 4.8 ± 3.4 events/h, P < 0.0001) for NPPV and servoventilation, respectively. Other sleep parameters were unaffected by any form of treatment.

Conclusions: After 6 weeks, servoventilation treated respiratory events more effectively than NPPV in patients with complex sleep apnea syndrome.
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http://dx.doi.org/10.5665/sleep.2878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700713PMC
August 2013

Visuomotor functional network topology predicts upcoming tasks.

J Neurosci 2012 Jul;32(29):9960-8

Bernstein Center for Computational Neuroscience, Charité-Universitätsmedizin, D-10115 Berlin, Germany.

It is a vital ability of humans to flexibly adapt their behavior to different environmental situations. Constantly, the rules for our sensory-to-motor mappings need to be adapted to the current task demands. For example, the same sensory input might require two different motor responses depending on the actual situation. How does the brain prepare for such different responses? It has been suggested that the functional connections within cortex are biased according to the present rule to guide the flow of information in accordance with the required sensory-to-motor mapping. Here, we investigated with fMRI whether task settings might indeed change the functional connectivity structure in a large-scale brain network. Subjects performed a visuomotor response task that required an interaction between visual and motor cortex: either within each hemisphere or across the two hemispheres of the brain depending on the task condition. A multivariate analysis on the functional connectivity graph of a cortical visuomotor network revealed that the functional integration, i.e., the connectivity structure, is altered according to the task condition already during a preparatory period before the visual cue and the actual movement. Our results show that the topology of connection weights within a single network changes according to and thus predicts the upcoming task. This suggests that the human brain prepares to respond in different conditions by altering its large scale functional connectivity structure even before an action is required.
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http://dx.doi.org/10.1523/JNEUROSCI.1604-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6621299PMC
July 2012

Proteome dynamics and early salt stress response of the photosynthetic organism Chlamydomonas reinhardtii.

BMC Genomics 2012 May 31;13:215. Epub 2012 May 31.

Max Delbrück Center for Molecular Medicine Berlin, Berlin Institute for Medical Systems Biology (BIMSB), Berlin, Germany.

Background: The cellular proteome and metabolome are underlying dynamic regulation allowing rapid adaptation to changes in the environment. System-wide analysis of these dynamics will provide novel insights into mechanisms of stress adaptation for higher photosynthetic organisms. We applied pulsed-SILAC labeling to a photosynthetic organism for the first time and we established a method to study proteome dynamics in the green alga Chlamydomonas reinhardtii, an emerging model system for plant biology. In addition, we combined the analysis of protein synthesis with metabolic profiling to study the dynamic changes of metabolism and proteome turnover under salt stress conditions.

Results: To study de novo protein synthesis an arginine auxotroph Chlamydomonas strain was cultivated in presence of stable isotope-labeled arginine for 24 hours. From the time course experiment in 3 salt concentrations we could identify more than 2500 proteins and their H/L ratio in at least one experimental condition; for 998 protiens at least 3 ratio counts were detected in the 24 h time point (0 mM NaCl). After fractionation we could identify 3115 proteins and for 1765 of them we determined their de novo synthesis rate. Consistently with previous findings we showed that RuBisCO is among the most prominent proteins in the cell; and similar abundance and turnover for the small and large RuBisCO subunit could be calculated. The D1 protein was identified among proteins with a high synthesis rates. A global median half-life of 45 h was calculated for Chlamydomonas proteins under the chosen conditions.

Conclusion: To investigate the temporal co-regulation of the proteome and metabolome, we applied salt stress to Chlamydomonas and studied the time dependent regulation of protein expression and changes in the metabolome. The main metabolic response to salt stress was observed within the amino acid metabolism. In particular, proline was up-regulated manifold and according to that an increased carbon flow within the proline biosynthetic pathway could be measured. In parallel the analysis of abundance and de novo synthesis of the corresponding enzymes revealed that metabolic rearrangements precede adjustments of protein abundance.
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http://dx.doi.org/10.1186/1471-2164-13-215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444938PMC
May 2012

Short-term effect of controlled instead of assisted noninvasive ventilation in chronic respiratory failure due to chronic obstructive pulmonary disease.

Respir Care 2007 Dec;52(12):1734-40

Zentrum für Pneumologie, Beatmung, und Schlafmedizin Allergologie, Fachkrankenhaus Kloster Grafschaft, Annostrasse 1, 57392 Schmallenberg, Germany.

Background: Noninvasive positive-pressure ventilation (NPPV) unloads respiratory muscles. Spontaneous-breathing ventilation modes require patient effort to trigger the ventilator, whereas controlled modes potentially economize on patient triggering effort and thus achieve more complete respiratory muscle rest. Data on controlled NPPV have not been published to date. We hypothesize that controlled ventilation is feasible in patients with hypercapnic chronic obstructive pulmonary disease.

Methods: We measured blood gas values, respiratory muscle strength, spontaneous breathing pattern, and lung function before and after a 3-month period of NPPV in 305 patients (213 male, mean +/- SD age 61.3 +/- 8.6 y). The subjects used a controlled NPPV mode when they could tolerate it.

Results: Ninety-one percent of the patients were able to adapt to a controlled NPPV mode. In those patients, daytime P(CO(2)) decreased from 56.7 +/- 7.5 mm Hg to 47.5 +/- 6.6 mm Hg (p < 0.001) and P(O(2)) increased from 49.2 +/- 8.8 mm Hg to 56.2 +/- 8.5 mm Hg (p < 0.001). Their mean maximum inspiratory pressure increased from 42.3 +/- 16.9 cm H(2)O to 48.4 +/- 18.0 cm H(2)O (p < 0.001). Their mean vital capacity increased from 1.89 +/- 0.62 L to 1.99 +/- 0.67 L (p = 0.004). And their spontaneous breathing pattern became less rapid and shallow.

Conclusions: Controlled NPPV is feasible in patients with hypercapnic chronic obstructive pulmonary disease. We observed improved blood gas values, lung function, and inspiratory muscle strength.
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December 2007

The cytoplasmic tail of the alpha3 integrin subunit promotes neurite outgrowth in PC12 cells.

J Neurosci Res 2005 Dec;82(6):753-61

Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Institut für Biochemie und Molekularbiologie, Berlin-Dahlem, Germany.

Binding of integrins to proteins of the extracellular matrix (ECM) provides structural and signaling information for biological processes such as cell proliferation, migration, neurite outgrowth, and differentiation. Integrins represent a family of heterodimeric transmembrane cell surface receptors. Besides connecting the ECM with the cytoskeleton, integrins also induce various signaling pathways in response to ligand binding. Integrin ligation leads to cytoplasmic protein-protein interactions requiring both integrin cytoplasmic tails. These sequences are initiation points for focal adhesion formation and subsequent signal transduction cascades. In this study, we addressed the question of whether the short cytoplasmic tail of the alpha(3) integrin subunit of alpha(3)beta(1) integrin is required for alpha(3)beta(1) integrin-dependent processes. For this purpose, cDNA representing the extracellular and transmembrane domain of the interleukin 2 receptor (IL2R) alpha subunit and the cytoplasmic sequence of the alpha(3) integrin subunit was transfected into PC12 cells. Autonomous expression of the cytoplasmic alpha(3) tail does not affect attachment but leads to inhibition of neuronal differentiation on laminin 5. This indicates that the cytoplasmic alpha(3) sequence is not required for cell attachment but is necessary for long-term adhesion and for the reorganization of the cytoskeleton that precedes neuronal differentiation. Inhibition of neurite outgrowth by chimeric IL2R-alpha(3) can be rescued by treatment of transfected cells with the pharmacological inhibitor Y27632, which inhibits the RhoA downstream effector Rho kinase alpha.
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http://dx.doi.org/10.1002/jnr.20693DOI Listing
December 2005

Sterile water is unnecessary in a continuous positive airway pressure convection-type humidifier in the treatment of obstructive sleep apnea syndrome.

Chest 2005 Oct;128(4):2138-40

Annostr. 1, Krankenhaus Kloster Grafschaft, Zentrum für Pneumologie, Beatmungs- und Schlafmedizin, D-57392 Schmallenberg, Germany.

Objective: We investigated the necessity of using sterile water in humidifiers for avoiding respiratory tract infections during nasal continuous positive airway pressure (nCPAP) therapy.

Methods: Water in a convection-type humidifier (Sirius; Heinen and Löwenstein GmbH; Bad Ems, Germany) was labeled with (99m)Tc-diethylenetriamine penta-acetic acid. Low-flow (2 L/min, 4 L/min, or 6 L/min) and high-flow (31 to 46 L/min) rates were applied, rates typical for nCPAP. Heat and moisture exchange filters were placed behind the start of the tube to measure any radioactive aerosol.

Results: We demonstrated that no radioactive aerosols were produced, either with low or high flows.

Conclusions: The convection-type humidifier produces water vapor but does not aerosolize the water. We conclude that bacteria, other microorganisms, or even solutes that may be contained in the water cannot be transported into the air and thus will not be deposited in the lung. In order to avoid respiratory tract infections, sterile water is not required, at least in this particular humidifier. We suggest that nonsterile tap water is probably a safe alternative.
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http://dx.doi.org/10.1378/chest.128.4.2138DOI Listing
October 2005