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A new method for size-resolved chemical analysis of nucleation mode aerosol particles (size range from ∼10 to ∼30 nm) is presented. The Thermal Desorption Differential Mobility Analyzer (TD-DMA) uses an online, discontinuous principle. The particles are charged, a specific size is selected by differential mobility analysis and they are collected on a filament by electrostatic precipitation. Subsequently, the sampled mass is evaporated in a clean carrier gas and analyzed by a chemical ionization mass spectrometer. Gas-phase measurements are performed with the same mass spectrometer during the sampling of particles. The characterization shows reproducible results, with a particle size resolution of 1.19 and the transmission efficiency for 15 nm particles being slightly above 50 %. The signal from the evaporation of a test substance can be detected starting from 0.01 ng and shows a linear response in the mass spectrometer. Instrument operation in the range of pg m−3 is demonstrated by an example measurement of 15 nm particles produced by nucleation from dimethylamine, sulfuric acid and water.
A new method for size resolved chemical analysis of nucleation mode aerosol particles (size range from ~10 to ~30 nm) is presented. The Thermal Desorption Differential Mobility Analyzer (TD-DMA) uses an online, discontinuous principle. The particles are charged, a specific size is selected by differential mobility analysis and they are collected on a filament by electrostatic precipitation. Subsequently, the sampled mass is evaporated in a clean carrier gas and analyzed by a chemical ionization mass spectrometer. Gas phase measurements are performed with the same mass spectrometer during the sampling of particles. The characterization shows reproducible results, with a particle size resolution of 1.19 and the transmission efficiency for 15 nm particles being slightly above 50 %. The signal from the evaporation of a test substance can be detected starting from 0.01 ng and shows a linear response in the mass spectrometer. Instrument operation in the range of pg/m3 is demonstrated by an example measurement of 15 nm particles produced by nucleation from dimethylamine, sulfuric acid and water.
Amines are potentially important for atmospheric new particle formation, but their concentrations are usually low with typical mixing ratios in the pptv range or even smaller. Therefore, the demand for highly sensitive gas-phase amine measurements has emerged in the last several years. Nitrate chemical ionization mass spectrometry (CIMS) is routinely used for the measurement of gasphase sulfuric acid in the sub-pptv range. Furthermore, extremely low volatile organic compounds (ELVOCs) can be detected with a nitrate CIMS. In this study we demonstrate that a nitrate CIMS can also be used for the sensitive measurement of dimethylamine (DMA, (CH3/2NH) using the NO3−•(HNO3)1 − 2• (DMA) cluster ion signal. Calibration measurements were made at the CLOUD chamber during two different measurement campaigns. Good linearity between 0 and ~120 pptv of DMA as well as a sub-pptv detection limit of 0.7 pptv for a 10 min integration time are demonstrated at 278K and 38% RH.
We present a compact and versatile cryofocusing– thermodesorption unit, which we developed for quantitative analysis of halogenated trace gases in ambient air. Possible applications include aircraft-based in situ measurements, in situ monitoring and laboratory operation for the analysis of flask samples. Analytes are trapped on adsorptive material cooled by a Stirling cooler to low temperatures (e.g. -80°C) and subsequently desorbed by rapid heating of the adsorptive material (e.g. 200°C). The set-up involves neither the exchange of adsorption tubes nor any further condensation or refocusing steps. No moving parts are used that would require vacuum insulation. This allows for a simple and robust design. Reliable operation is ensured by the Stirling cooler, which neither contains a liquid refrigerant nor requires refilling a cryogen. At the same time, it allows for significantly lower adsorption temperatures compared to commonly used Peltier elements. We use gas chromatography – mass spectrometry (GC–MS) for separation and detection of the preconcentrated analytes after splitless injection. A substance boiling point range of approximately -80 to +150°C and a substance mixing ratio range of less than 1 ppt (pmol mol−1)to more than 500 ppt in preconcentrated sample volumes of 0.1 to 10 L of ambient air is covered, depending on the application and its analytical demands. We present the instrumental design of the preconcentration unit and demonstrate capabilities and performance through the examination of analyte breakthrough during adsorption, repeatability of desorption and analyte residues in blank tests. Examples of application are taken from the analysis of flask samples collected at Mace Head Atmospheric Research Station in Ireland using our laboratory GC–MS instruments and by data obtained during a research flight with our in situ aircraft instrument GhOSTMS (Gas chromatograph for the Observation of Tracers – coupled with a Mass Spectrometer).
We present a compact and versatile cryofocusing–thermodesorption unit, which we developed for quantitative analysis of halogenated trace gases in ambient air. Possible applications include aircraft-based in situ measurements, in situ monitoring and laboratory operation for the analysis of flask samples. Analytes are trapped on adsorptive material cooled by a Stirling cooler to low temperatures (e.g. −80 °C) and subsequently desorbed by rapid heating of the adsorptive material (e.g. +200 °C). The set-up involves neither the exchange of adsorption tubes nor any further condensation or refocusing steps. No moving parts are used that would require vacuum insulation. This allows for a simple and robust design. Reliable operation is ensured by the Stirling cooler, which neither contains a liquid refrigerant nor requires refilling a cryogen. At the same time, it allows for significantly lower adsorption temperatures compared to commonly used Peltier elements. We use gas chromatography – mass spectrometry (GC–MS) for separation and detection of the preconcentrated analytes after splitless injection. A substance boiling point range of approximately −80 to +150 °C and a substance mixing ratio range of less than 1 ppt (pmol mol−1) to more than 500 ppt in preconcentrated sample volumes of 0.1 to 10 L of ambient air is covered, depending on the application and its analytical demands. We present the instrumental design of the preconcentration unit and demonstrate capabilities and performance through the examination of analyte breakthrough during adsorption, repeatability of desorption and analyte residues in blank tests. Examples of application are taken from the analysis of flask samples collected at Mace Head Atmospheric Research Station in Ireland using our laboratory GC–MS instruments and by data obtained during a research flight with our in situ aircraft instrument GhOST-MS (Gas chromatograph for the Observation of Tracers – coupled with a Mass Spectrometer).
This commentary is an introduction for students to the Society of Environmental Toxicology and Chemistry (SETAC) and its Student Advisory Council (SAC). As young academics face challenges while trying to develop their careers, SETAC and the SAC help facilitate student involvement in the various communities within the society that can help to develop the students’ careers within the environmental sciences [e.g. the German Language Branch (GLB)]. This piece would also like to emphasize and pay homage to the continual cooperation between the SAC and the ESEU, which provides a scientific platform to communicate internationally and beyond the borders of SETAC, as well as offer heartfelt congratulations from the SAC to the GLB for their "20 Years SETAC GLB" and deep gratitude for their strong advocacy and support of the SAC.
The human amygdala is thought to play a pivotal role in the processing of emotionally significant sensory information. The major subdivisions of the human amygdala—the laterobasal group (LB), the superficial group (SF), and the centromedial group (CM)—have been anatomically delineated, but the functional response properties of these amygdala subregions in humans are still unclear. We combined functional MRI with cyto-architectonically defined probabilistic maps to analyze the response characteristics of amygdala subregions in subjects presented with auditory stimuli. We found positive auditory stimulation-related signal changes predominantly in probabilistically defined LB, and negative responses predominantly in SF and CM. In the left amygdala, mean response magnitude in the core area of LB with 90–100% assignment probability was significantly larger than in the core areas of SF and CM. These differences were observed for pleasant and unpleasant stimuli. Our findings reveal that the probabilistically defined anatomical subregions of the human amygdala show distinctive fMRI response patterns. The stronger auditory responses in LB as compared with SF and CM may reflect a predominance of auditory inputs to human LB, similar to many animal species in which the majority of sensory, including auditory, afferents project to this subdivision of the amygdala. Our study indicates that the intrinsic functional differentiation of the human amygdala may be probed using fMRI combined with probabilistic anatomical maps.
Comprehensive landscape of active deubiquitinating enzymes profiled by advanced chemoproteomics
(2019)
Enzymes that bind and process ubiquitin, a small 76-amino-acid protein, have been recognized as pharmacological targets in oncology, immunological disorders, and neurodegeneration. Mass spectrometry technology has now reached the capacity to cover the proteome with enough depth to interrogate entire biochemical pathways including those that contain DUBs and E3 ligase substrates. We have recently characterized the breast cancer cell (MCF7) deep proteome by detecting and quantifying ~10,000 proteins, and within this data set, we can detect endogenous expression of 65 deubiquitylating enzymes (DUBs), whereas matching transcriptomics detected 78 DUB mRNAs. Since enzyme activity provides another meaningful layer of information in addition to the expression levels, we have combined advanced mass spectrometry technology, pre-fractionation, and more potent/selective ubiquitin active-site probes with propargylic-based electrophiles to profile 74 DUBs including distinguishable isoforms for 5 DUBs in MCF7 crude extract material. Competition experiments with cysteine alkylating agents and pan-DUB inhibitors combined with probe labeling revealed the proportion of active cellular DUBs directly engaged with probes by label-free quantitative (LFQ) mass spectrometry. This demonstrated that USP13, 39, and 40 are non-reactive to probe, indicating restricted enzymatic activity under these cellular conditions. Our extended chemoproteomics workflow increases depth of covering the active DUBome, including isoform-specific resolution, and provides the framework for more comprehensive cell-based small-molecule DUB selectivity profiling.
Salt bridges in lipid bilayers play a decisive role in the dynamic assembly and downstream signaling of the natural killer and T-cell receptors. Here, we describe the identification of an inter-subunit salt bridge in the membrane within yet another key component of the immune system, the peptide-loading complex (PLC). The PLC regulates cell surface presentation of self-antigens and antigenic peptides via molecules of the major histocompatibility complex class I. We demonstrate that a single salt bridge in the membrane between the transporter associated with antigen processing TAP and the MHC I-specific chaperone tapasin is essential for the assembly of the PLC and for efficient MHC I antigen presentation. Molecular modeling and all-atom molecular dynamics simulations suggest an ionic lock-switch mechanism for the binding of TAP to tapasin, in which an unfavorable uncompensated charge in the ER-membrane is prevented through complex formation. Our findings not only deepen the understanding of the interaction network within the PLC, but also provide evidence for a general interaction principle of dynamic multiprotein membrane complexes in immunity.
Simple Summary: The study compares the effects on complete remission rate (CR) of a single dose of durvalumab/tremelimumab immediately after a single-cycle platinum and docetaxel as part of induction therapy for a controlled trial in head and neck cancer with chemotherapy alone from a historical collective. The CR rate was 60.3% after induction chemoimmunotherapy (ICIT; induction chemotherapy plus double immune checkpoint blockade) compared with 40.3% after induction chemotherapy (IC) alone. Patients with HPV-positive oropharyngeal cancer may benefit the most from additive double checkpoint inhibition, which is presumably due to the higher amount of infiltrating immune cells. Patients older than 60 years without HPV-positive oropharyngeal cancer are unlikely to benefit.
Abstract: To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m2 d1-3 and docetaxel 75 mg/m2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.
Aims: SARS-CoV-2 infection is associated with adverse outcomes in patients with cardiovascular disease. Here, we analyzed whether specific biomarkers predict the clinical course of COVID-19 in patients with cardiovascular comorbidities. Methods and results: We enrolled 2147 patients with SARS-CoV-2 infection which were included in the Lean European Open Survey on SARS-CoV‑2 (LEOSS)-registry from March to June 2020. Clinical data and laboratory values were collected and compared between patients with and without cardiovascular comorbidities in different clinical stages of the disease. Predictors for mortality were calculated using multivariate regression analysis. We show that patients with cardiovascular comorbidities display significantly higher markers of myocardial injury and thrombo-inflammatory activation already in the uncomplicated phase of COVID-19. In multivariate analysis, elevated levels of troponin [OR 1.54; (95% CI 1.22–1.96), p < 0.001)], IL-6 [OR 1.69 (95% CI 1.26–2.27), p < 0.013)], and CRP [OR 1.32; (95% CI 1.1–1.58), p < 0.003)] were predictors of mortality in patients with COVID-19. Conclusion: Patients with cardiovascular comorbidities show elevated markers of thrombo-inflammatory activation and myocardial injury, which predict mortality, already in the uncomplicated phase of COVID-19. Starting targeted anti-inflammatory therapy and aggressive anticoagulation already in the uncomplicated phase of the disease might improve outcomes after SARS-CoV-2 infection in patients with cardiovascular comorbidities.
Purpose: To test the effect of anatomic variants of the prostatic apex overlapping the membranous urethra (Lee type classification), as well as median urethral sphincter length (USL) in preoperative multiparametric magnetic resonance imaging (mpMRI) on the very early continence in open (ORP) and robotic-assisted radical prostatectomy (RARP) patients. Methods: In 128 consecutive patients (01/2018–12/2019), USL and the prostatic apex classified according to Lee types A–D in mpMRI prior to ORP or RARP were retrospectively analyzed. Uni- and multivariable logistic regression models were used to identify anatomic characteristics for very early continence rates, defined as urine loss of ≤ 1 g in the PAD-test. Results: Of 128 patients with mpMRI prior to surgery, 76 (59.4%) underwent RARP vs. 52 (40.6%) ORP. In total, median USL was 15, 15 and 10 mm in the sagittal, coronal and axial dimensions. After stratification according to very early continence in the PAD-test (≤ 1 g vs. > 1 g), continent patients had significantly more frequently Lee type D (71.4 vs. 54.4%) and C (14.3 vs. 7.6%, p = 0.03). In multivariable logistic regression models, the sagittal median USL (odds ratio [OR] 1.03) and Lee type C (OR: 7.0) and D (OR: 4.9) were independent predictors for achieving very early continence in the PAD-test. Conclusion: Patients’ individual anatomical characteristics in mpMRI prior to radical prostatectomy can be used to predict very early continence. Lee type C and D suggest being the most favorable anatomical characteristics. Moreover, longer sagittal median USL in mpMRI seems to improve very early continence rates.
Background: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. Results: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
Nucleation of jet engine oil vapours is a large source of aviation-related ultrafine particles
(2022)
Large airports are a major source of ultrafine particles, which spread across densely populated residential areas, affecting air quality and human health. Jet engine lubrication oils are detectable in aviation-related ultrafine particles, however, their role in particle formation and growth remains unclear. Here we show the volatility and new-particle-formation ability of a common synthetic jet oil, and the quantified oil fraction in ambient ultrafine particles downwind of Frankfurt International Airport, Germany. We find that the oil mass fraction is largest in the smallest particles (10-18 nm) with 21% on average. Combining ambient particle-phase concentration and volatility of the jet oil compounds, we determine a lower-limit saturation ratio larger than 1 × 105 for ultra-low volatility organic compounds. This indicates that the oil is an efficient nucleation agent. Our results demonstrate that jet oil nucleation is an important mechanism that can explain the abundant observations of high number concentrations of non-refractory ultrafine particles near airports.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets
(2018)
NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.
Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.
Highlights
• Artificial intelligence systems for mechanically ventilated patients are increasing.
• The clinical and financial impact of these models are often unexamined.
• We developed a generic health-economic model for artificial intelligence systems.
• This model assesses the cost-effectiveness for many different scenarios.
• The developed framework is easily adjustable to other (clinical) situations.
Abstract
Purpose: The health and economic consequences of artificial intelligence (AI) systems for mechanically ventilated intensive care unit patients often remain unstudied. Early health technology assessments (HTA) can examine the potential impact of AI systems by using available data and simulations. Therefore, we developed a generic health-economic model suitable for early HTA of AI systems for mechanically ventilated patients.
Materials and methods: Our generic health-economic model simulates mechanically ventilated patients from their hospitalisation until their death. The model simulates two scenarios, care as usual and care with the AI system, and compares these scenarios to estimate their cost-effectiveness.
Results: The generic health-economic model we developed is suitable for estimating the cost-effectiveness of various AI systems. By varying input parameters and assumptions, the model can examine the cost-effectiveness of AI systems across a wide range of different clinical settings.
Conclusions: Using the proposed generic health-economic model, investors and innovators can easily assess whether implementing a certain AI system is likely to be cost-effective before an exact clinical impact is determined. The results of the early HTA can aid investors and innovators in deployment of AI systems by supporting development decisions, informing value-based pricing, clinical trial design, and selection of target patient groups.
Buchbesprechungen
(2016)
Es werden folgende Publikation rezensiert: Ackermann & Sachteleben: Identifizierung der Hotspots der Biologischen Vielfalt in Deutschland; Bellin-Harder: In der Schwebe. Vegetationsdynamik und Pflegeprognostik. Ein vegetationskundlicher Beitrag zur Gartendenkmalpflege am Beispiel der Löwenburg im Bergpark Wilhelmshöhe, Kassel; Düll & Kutzelnigg: Taschenlexikon der Pflanzen Deutschlands und angrenzender Länder. Die wichtigsten mitteleuropäischen Arten im Porträt; Nassauischer Verein für Naturkunde: Zwischen Mittelrhein und Taunus. Naturschätze in Lorch am Rhein; Parolly & Rohwer: Schmeil-Fitschen. Die Flora Deutschlands und der angrenzenden Länder; Pusch et al: Die Botaniker Thüringens.