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Vergleichende standortbezogene Analyse der Radialzuwachs-Trockenstresstoleranz von Waldkiefern und Douglasien im Forstgut Sattelmühle
No full textVergleichende Analyse des Radialzuwachses von lebenden und abgestorbenen Pinus sylvestris in Bezug auf das Verhältnis von Frühholz- zu Spätholz - eine dendroökologische Analyse im Wald von Hartheim am Rhein
No full textPlant proteases: guardians of proteome integrity and regulators of protein function
No full textProteases degrade proteins that are damaged, misfolded, or no longer needed. This enables plants to repurpose their proteomes in response to environmental cues and adapt to adverse conditions. Proteases also play key roles in plant growth and development by the selective degradation of regulatory proteins. However, there is much more to proteases than just protein degradation. They can also act in a highly site-specific manner, ensuring protein maturation after subcellular targeting, regulating protein activity and function, and releasing or modulating peptide signals. Since their activity is irreversible and potentially deleterious, proteases are tightly controlled by endogenous inhibitors and other regulatory mechanisms. The reviews and research articles in this Special Issue put a timely spotlight on the fascinating diversity, function, and regulation of proteases in plants, discuss current challenges and technical developments, and provide a perspective on their use for crop protection
Intratumoral heterogeneity of cancer driver genomic alterations in myxoid liposarcomas
No full textBackgroundMyxoid liposarcomas (MLS) are rare malignant mesenchymal tumors characterized by specific translocations t(12;16) and t(12;22) with limited additional driver mutations, most notably in PIK3CA and the TERT promoter. PIK3CA is considered a promising therapeutic target. However, effective treatments require the uniform presence of mutation throughout the tumor. Therefore, this study evaluated intratumoral heterogeneity of driver mutations in MLS.MethodsIn total, 170 samples from 20 tumors (12 patients) were analyzed using an MLS-specific next-generation sequencing (NGS) panel. This included detecting the t(12;16) and t(12;22) translocations and known driver mutations.ResultsPatient-specific t(12;16) or t(12;22) translocations were detected in all 20 tumors (159 of 170 samples; 94%) and remained identical in primary tumors, recurrences, and metastases. TERT promoter mutations were identified in 17 of 20 tumors (85%) and were distributed similarly across samples. In contrast, PIK3CA mutations were present in only 66 of 170 samples (39%), with these and the remaining driver mutations localized only in subclones within individual tumors.ConclusionsTherapies that target PIK3CA are unlikely to succeed because of its limited subclonal distribution. In contrast, the ubiquitous presence of t(12;16), t(12;22), and TERT promoter mutations across MLS tumors suggests that these are more effective therapeutic targets for future treatment strategies
A phase IIb single‐center study to assess the efficacy of apremilast for the treatment of nummular eczema
No full textBackgroundThe pathogenesis of nummular eczema (NE) remains unclear, and no targeted therapy has been approved. Apremilast is a small molecule inhibitor targeting phosphodiesterase-4.Patients and MethodsA phase IIb randomized, double-blind, placebo-controlled study evaluating the effects of apremilast or placebo in patients with NE. Patients received apremilast (30 mg BID) or placebo until week 16 followed by an open label phase in which all patients were treated with apremilast until week 32. The primary endpoint was the number of patients achieving an improvement in Physician's Global Assessment (PGA) by two or more points or an absolute PGA of 0 or 1 at week 16. Secondary endpoints included changes in skin physiology, life quality, or dermato-pathology.Results33 patients were enrolled, of whom 31 were randomized to apremilast (n = 15) or placebo (n = 16). 1/15 (6.7%) patients in the apremilast group and 4/16 (25.0%) in the placebo group reached the primary endpoint (p = 0.369). There was no difference between placebo and apremilast with regard to all secondary endpoints at week 16 and week 32. The safety profile was in accordance with the known safety profile of apremilast.ConclusionPhosphodiesterase-4 inhibition by apremilast showed no beneficial effects for the treatment of NE
Disease characteristics and treatments associated with outcome in primary angiitis of the central nervous system - a multicenter cohort study in 163 patients
No full textObjectiveThe aim was to determine patient, disease, and treatment characteristics associated with outcome in patients with primary angiitis of the central nervous system (PACNS) in a large multicenter German cohort.MethodsIn a retrospective, observational cohort study, we analyzed 163 adult patients who met the diagnostic criteria for PACNS. Data were collected from January 2004 to December 2018 in 13 tertiary care centers in Germany. Survival, recurrence-free survival and long-term global disability were assessed.ResultsOf 163 patients with PACNS (median [interquartile range (IQR)] age 48 [39–59.5] years; 73 [45%] women), 29 (18%) died, 84 (52%) had a poor outcome (modified Rankin scale [mRS] 3–6 at last follow-up), and 82 (50%) patients relapsed. Poorer survival was associated with patient age (hazard ratio [HR], 1.96 [95% confidence interval (CI), 1.41–2.74] per 10 years), longer time between initial manifestation and diagnosis (HR, 1.01 [95% CI, 1.00–1.01] per month), and necrotizing subtype (HR, 10.2 [95% CI, 2.18–48.2]). Long-term disability was associated with older age (odds ratio [OR], 1.40 [95% CI, 1.07–1.86] per 10 years), and worse mRS score at diagnosis (OR, 4.43 [95% CI, 1.97–10.4]). Patients treated with cyclophosphamide alone or in combination with steroids had a lower incidence of relapse than untreated patients (HR, 0.44 [95% CI, 0.22–0.86]; HR, 0.47 [95% CI, 0.24–0.92]).InterpretationIn patients with PACNS, the long-term outcome depends on several patient and disease characteristics. Our results favor treatment with cyclophosphamide alone or in combination with steroids, because this was associated with a reduction in the relapse rate. ANN NEUROL 2025;98:883–89
Hearing restoration by a low-weight power-efficient multichannel optogenetic cochlear implant system
No full textObjective. In case of deafness, electrical cochlear implants (eCIs) bypass dysfunctional or lost hair cells by direct stimulation of the auditory nerve. However, spectral selectivity of eCI sound coding is low as the wide current spread from each electrode activates large sets of neurons along the tonotopic axis of the cochlea. As light can be better confined in space, optical cochlear implants (oCIs) combined with cochlear optogenetics promise to overcome this shortcoming of eCIs. This requires appropriate sound processing and control of multiple microscale emitters. Approach. Here, we describe the development, characterisation, and application of a preclinical miniaturised low-weight and wireless LED-based multichannel oCI system for hearing restoration, and its comparison to its sister eCI system. We present exemplary implementation of these systems in behavioural studies on freely moving rats. Main results. The system, which weights 15 g, is 20 mm in diameter and 20 mm in height, performed for up to 8 h in behavioural experiments on freely moving rats proving its utility for cueing auditory tasks in deaf animals. Significance. The head-worn oCI system enabled deafened rats to perform a locomotion task in response to acoustic stimulation proving the concept of multichannel optogenetic hearing restoration in rodents. This paves the way for implementation in other species and development of future clinical oCI systems for improved hearing restoration
Calibration of large-area perovskite on silicon tandem solar cell modules
No full textThis work focuses on the development and verification of new measurement methods for the precise characterization and calibration of large-area perovskite on silicon (PSC/Si) tandem modules in indoor and outdoor measurements. For this task a particular challenge arises from the series connection of the individual subcells in monolithic tandem devices, which leads to current limitations and thus requires precise consideration of the measurement spectrum. For conducting indoor measurements, a spectral adjustment procedure for light-emitting diode (LED) based solar simulators was developed, analyzed, and verified. This includes a methodology for determining suitable simulator settings which is tailored to the high number of spectrally different individual light sources, as well as a new method for the precise spectral characterization of multi-light-source solar simulators. The developed procedure was first applied to an LED-based cell solar simulator and verified through a measurement comparison conducted on a stable III-V-based tandem solar cell with the calibration laboratory for solar cells (CalLab PV Cells) at the Fraunhofer Institute for Solar Energy Systems (ISE). With a deviation of only 0.3% for the maximum output power ( mpp) measured under standard test conditions, the applicability of the procedure was successfully demonstrated. Following this approach, the spectral characterization of a large-area LED-based solar simulator was conducted, based on which a new method for measuring the external quantum efficiency (EQE) of large-area tandem modules was developed. The procedure was verified by a measurement comparison carried out on a PSC/Si single-cell module with CalLab PV Cells, resulting in average deviations of 1.2% (rel.) for the EQE datapoints of the top- and 2% (rel.) for EQE datapoints of the bottom-cell. Additionally, this fast procedure was successfully applied to a large-area PSC/Si module. Based on this result it was demonstrated that the module EQE determined with this new approach can be used for the spectral adjustment of the LED-based solar simulator introducing only minor additional measurement uncertainty. Finally, the full calibration of a large-area PSC/Si module was conducted using the procedures developed in this work. In addition to the maximum power output measured traceably to metrological standards and under steady-state conditions, the calibration also included the determination of the module EQE, the evaluation of temperature coefficients as well as a spectrometric characterization (SMC). This measurement represents the first traceable calibration of a large-area PSC/Si tandem module worldwide. The device achieved an efficiency of 25.00% with an uncertainty of 0.83% (abs.). In addition, outdoor measurements enabled the investigation of bifacial modules. Based on measurements of a large-area bifacial PSC/Si tandem module, general effects arising from the combination of bifaciality, and tandem architecture were qualitatively investigated and described. Particular attention was paid to the complex interplay between device temperature, front side spectral conditions as well as rear side irradiance which significantly influences the performance characteristics of bifacial tandem devices and constantly changes during outdoor measurements. Based on these findings, an outdoor measurement procedure to quantitatively determine the bifaciality characteristics of tandem modules was developed and exemplarily applied to a PSC/Si single-cell module. This method allowed for the analysis and quantification of the module’s performance under varying spectral and irradiance conditions. In combination with newly introduced parameters for the precise characterization of bifacial tandems, it was possible to scale measurement results to different rear-side intensities. This, in turn, represents an important step towards standardized measurement methods for bifacial tandem devices. Additionally, it was shown how, based on these results, possible optimization approaches for bifacial tandem devices can be identified, and their performance potential quantitatively determined.Diese Arbeit beschäftigt sich mit der Entwicklung und Verifizierung neuer Messmethoden für die präzise Charakterisierung und Kalibrierung großflächiger Perowskit auf Silizium (PSC/Si) Tandem-Module in Indoor und Outdoor-Messungen. Dabei ergibt sich eine besondere Herausforderung aus der Serien-Verschaltung der einzelnen Teilzellen in monolithischen TandemSolarzellen, welche zu Stromlimitierungen führt und daher eine präzise Berücksichtig des Messspektrums erforderlich macht. Für die Durchführung von Indoor-Messungen wurde zunächst eine Methode für die spektrale Anpassung „light-emitting diode“ (LED) basierter Sonnensimulatoren entwickelt, analysiert und verifiziert. Diese umfasst neben einer Methodik zur Ermittlung geeigneter Spektral-Einstellungen, die auf die hohe Anzahl spektral unterschiedlicher Einzellichtquellen angepasst ist, auch eine neue Prozedur zur präzisen spektralen Charakterisierung von Multi-Lichtquellen-Simulatoren. Dieentwickelte Vorgehensweise wurde zunächst auf einen LED-basierten Zell-Sonnensimulator angewendet und durch einen an einer stabilen III-V-basierten Tandem-Solarzelle durchgeführten Messvergleich mit dem Kalibrierlabor für Solarzellen (CalLab PV Cells) des Fraunhofer-Instituts für Solare Energiesysteme (ISE) verifiziert. Mit einer Abweichung von nur 0.3% für die unter Standard-Testbedingungen gemessenen maximalen Leistung ( MPP) konnte die Anwendbarkeit der neu entwickelten Prozedur erfolgreich nachgewiesen werden. Basierend auf dieser Vorgehensweise wurde die spektrale Charakterisierung eines großflächigen LED basierten Sonnensimulators durchgeführt und darauf aufbauend eine neue Methode zur Messung der externen Quanteneffizienz (EQE) großflächiger Tandem-Module entwickelt. Diese wurde durch einen an einem PSC/Si Einzeller-Modul durchgeführten Messvergleich mit dem CalLab PV Cells verifiziert, wobei sichmittlere Abweichungen von 1.2% (rel.) für die EQE-Datenpunkte der Oberzelle und 2% (rel.) für die EQE-Datenpunkte der Unterzelle ergaben. Zudem wurde dieses schnelle Verfahren erfolgreich auf ein großflächiges PSC/Si Modul angewendet, wobei gezeigt werden konnte, dass die Verwendung der so ermittelten EQE für die Spektralanpassung des LED-basierten Sonnensimulators lediglich zu einer geringfügig höheren Messunsicherheit führt. Basierend auf diesen Methoden konnte eine vollständige Kalibrierung eines großflächigen PSC/Si Moduls durchgeführt werden. Neben der auf metrologische Standards rückführbaren und unter stabilen Bedingungen gemessenen Modulleistung umfasste diese auch die Bestimmung der Modul-EQE, die Ermittlung von Temperaturkoeffizienten sowie die Durchführung einer spektrometrischen Charakterisierung (SMC). Diese Messung stellt die weltweit erste rückführbare Kalibrierung eines großflächigen PSC/Si Moduls dar, dessen Wirkungsgrad von 25.00% mit einer Unsicherheit von 0.83% (abs.) angegeben werden konnte. Die Durchführung von Außenmessungen ermöglichte zudem die Untersuchung bifazialer TandemModule. Basierend auf Messungen eines großflächigen bifazialen PSC/Si Tandem-Moduls konnten zunächst generelle Effekte, die sich aus der Kombination von Bifazialität und Tandem-Architektur ergeben, qualitativ untersucht und beschrieben werden. Ein besonderes Augenmerk wurde dabei auf das komplexe Zusammenspiel von Modultemperatur, dem vorderseitig eingestrahlten Spektrum sowie der rückseitigen Bestrahlungsstärke gelegt, welches die Leistungsmerkmale bifazialer Tandem-Module maßgeblich beeinflusst und sich während Außenmessungen ständig ändert. Basierend auf den in diesen Untersuchungen gewonnenen Erkenntnissen wurde eine Außen-Messmethode zur quantitativen Bestimmung der bifazialen Eigenschaften von TandemModulen entwickelt und exemplarisch an einem PSC/Si Einzeller-Modul durchgeführt. Diese Methode ermöglicht in Kombination mit den ebenfalls neu eingeführten Parametern zur akkuraten Beschreibung bifazialer Tandems erstmals eine Skalierung von Messergebnissen auf verschiedene Rückseiten-Einstrahlungs-Intensitäten, was einen wichtigen Schritt hin zu standardisierten Messmethoden darstellt. Basierend auf diesen Untersuchungen konnten zudem mögliche Optimierungsansätze für bifaziale Tandems identifiziert und deren Leistungspotenzial quantitativ bestimmt werden
Prediction of obesity levels based on physical activity and eating habits with a machine learning model integrated with explainable artificial intelligence
No full textObjectives: This study aims to build a machine learning (ML) prediction model integrated with explainable artificial intelligence (XAI) to categorize obesity levels from physical activity and dietary patterns. The inclusion of XAI methodologies facilitates a comprehensive understanding of the risk factors influencing the model predictions and thus increases transparency in the identification of obesity risk factors.Methods: Six ML models were used: Bernoulli Naive Bayes, CatBoost, Decision Tree, Extra Trees Classifier, Histogram-based Gradient Boosting and Support Vector Machine. For each model, hyperparameters were tuned by random search methodology and model effectiveness was evaluated by repeated holdout testing. SHAP (SHapley Additive Annotations) and LIME (Local Interpretable Model Independent Annotations) interpretability methods were used to generate local and global feature importance measures.Results: The CatBoost model exhibited the highest overall performance and achieved superior results in accuracy, precision, F1 score and AUC metrics. Nonetheless, other models such as Decision Tree and Histogram-based Gradient Boosting also yielded strong and competitive results. The results also highlighted age, weight, height and specific food patterns as key predictors of obesity. In terms of interpretability, LIME showed superior in fidelity, whereas SHAP showed improved sparsity and consistency across models, facilitating a comprehensive understanding of trait importance.Conclusion: This research demonstrates that ML algorithms, when integrated with XAI technologies, can accurately predict obesity levels and explain important contributing risk factors. The use of SHAP and LIME increases model transparency, facilitating the identification of specific lifestyle patterns linked to obesity risk. These findings help to formulate more precise intervention techniques guided by a reliable and understandable predictive framework
Positive mental health predicts amelioration of suicidal ideation in patients undergoing cognitive behavioral therapy
No full textBackground: Positive mental health has been shown to confer resilience against suicidal ideation and behavior. Yet, studies on treatment seeking populations are rare.The aim of the present study was to investigate, whether PMH predicts the amelioration of suicidal ideation in patients undergoing psychotherapy.Method: Data from N = 959 outpatients (61.2% female; age: M(SD) = 36.58 (13.29), range: 18–82 years), who took part in a pretreatment and a posttreatment assessment after 12 sessions of cognitive behavioral therapy, were included. Self-report measures of positive mental health, depression, and suicidal ideation/behavior were used.Results: Pretreatment PMH was shown to predict posttreatment suicidal ideation – after controlling for age, gender, pretreatment depression, suicidal ideation and lifetime suicide attempts.Discussion: Positive mental health might be understood as a protective factor in dealing with suicidal ideation. Findings underscore the need to focus on positive mental health in the risk-assessment and treatment of suicidal patients