Development of air quality boxes based on low-cost sensor technology for ambient air quality monitoring

Analyses of the relationships between climate, air substances and health usually concentrate on urban environments because of increased urban temperatures, high levels of air pollution and the exposure of a large number of people compared to rural environments. Ongoing urbanization, demographic ageing and climate change lead to an increased vulnerability with respect to climate-related extremes and air pollution. However, systematic analyses of the specific local-scale characteristics of health-relevant atmospheric conditions and compositions in urban environments are still scarce because of the lack of high-resolution monitoring networks. In recent years, low-cost sensors (LCS) became available, which potentially provide the opportunity to monitor atmospheric conditions with a high spatial resolution and which allow monitoring directly at vulnerable people. In this study, we present the atmospheric exposure low-cost monitoring (AELCM) system for several air substances like ozone, nitrogen dioxide, carbon monoxide and particulate matter, as well as meteorological variables developed by our research group. The measurement equipment is calibrated using multiple linear regression and extensively tested based on a field evaluation approach at an urban background site using the high-quality measurement unit, the atmospheric exposure monitoring station (AEMS) for meteorology and air substances, of our research group. The field evaluation took place over a time span of 4 to 8 months. The electrochemical ozone sensors (SPEC DGS-O3: R(2): 0.71–0.95, RMSE: 3.31–7.79 ppb) and particulate matter sensors (SPS30 PM1/PM2.5: R(2): 0.96–0.97/0.90–0.94, RMSE: 0.77–1.07 µg/m(3)/1.27–1.96 µg/m(3)) showed the best performances at the urban background site, while the other sensors underperformed tremendously (SPEC DGS-NO2, SPEC DGS-CO, MQ131, MiCS-2714 and MiCS-4514). The results of our study show that meaningful local-scale measurements are possible with the former sensors deployed in an AELCM unit

Beeinflussung des Ertragspotentials von Gerste und Weizen durch Modifikation ährenarchitektonischer Eigenschaften mittels Cas-Endonuklease-vermittelter Mutagenese

Die vorliegende Arbeit beschreibt die Anwendung des Genome Engineerings mittels RNA-vermittelter Cas9-Endonuklease in den Getreidearten Weizen und Gerste. Dieses neue Werkzeug der Pflanzenzüchtung ermöglicht, innerhalb eines kurzen Zeitraumes spezifische Veränderungen im Genom von Getreide zu induzieren und dadurch gezielt Merkmale der Pflanzen zu verändern. Hierfür wurden zu verändernde Zielmotive im Weizen-Gen Branched head (Bh)/ Wheat frizzy panicle (Wfzp) bzw. in den Gersten-Genen Squamosa-promotor binding protein-like 14 und 17 (Spl14/Spl17) ausgewählt und passende guide RNA(gRNA)/cas9-Konstrukte kloniert. Die Aktivität der gRNAs wurde in Epidermiszellen von Weizen bzw. Gerste und in Weizenprotoplasten untersucht. Die stabile Transformation erfolgte anhand unreifer Embryonen über ballistischen Gentransfer (Weizen) bzw. durch Agrobakterien-vermittelte Übertragung von T-DNA (Gerste). Die anschließend regenerierten Pflanzen wurden auf die Anwesenheit der T-DNA und induzierter Mutationen untersucht. Im Weizen wurden mutierte Regenerate durch Selbstungen, Kreuzungen und die Anwendung von Haploidentechnologie in nachfolgende Generationen überführt und eine Kollektion von Pflanzen mit verschieden mutierten Allelen einschließlich Kombinationen mutierter homoeologer Allele zusammengestellt. Resultierende Pflanzen mit ein oder zwei mutierten Bh/Wfzp-Homoeoallelen waren T-DNA-frei und zeigten phänotypische Veränderungen der Ährenarchitektur, der Korngröße, der Kornanzahl und zum Teil auch bezüglich der Wurzeln. Das Vorhandensein von drei mutierten Bh/Wfzp-Homoeoallelen führte zum Teil zu sehr drastischen Veränderungen der Ähren, welche überzählige Ährchen und auch Verzweigungen ausbildeten. Jedoch führten diese Mutationen zu einem hohen Verlust an Fertilität. Insgesamt konnte die Bedeutung des Transkriptionsfaktors BH/WFZP für die Entwicklung der Ähre und der Körner sowie für die Wurzeln weiter erschlossen werden. Die in Gerste induzierten Mutationen in Spl14 führten grundsätzlich zu einer verzögerten generativen Entwicklung und teilweise zur Reaktivierung der Ausbildung der lateralen Ährchen. Die Ähren waren zudem verkürzt und bildeten weniger Körner. Die erzeugten Mutationen in Spl17 beeinflussten nicht die generative Entwicklung, jedoch die Ährenlänge und Kornbildung. Pflanzen mit Doppelmutationen in Spl14 und Spl17 zeigten eine drastische Verschärfung des spl14-Phänotyps, wobei die generative Entwicklung so sehr gestört war, dass keine Ähren ausgebildet werden konnten. Dies legt den Schluss nahe, dass SPL14 eine zentrale Rolle für die frühe generative Entwicklung spielt und SPL17 dabei als Co-Faktor wirkt.This thesis describes the application of genome engineering using RNA-mediated Cas9 endonuclease in the cereal species wheat and barley. This new breeding tool makes it possible to induce specific changes in the genome of cereals within a short period of time, thereby specifically modifying plant characteristics. For this purpose, target motifs were selected in the wheat gene Branched head (Bh)/ Wheat frizzy panicle (Wfzp) and in the barley genes Squamosa-promoter binding protein-like 14 and 17 (Spl14/Spl17) and suitable guide RNA (gRNA)/cas9 constructs were cloned. The activity of the gRNAs was investigated in wheat and barley epidermal cells and in wheat protoplasts. Stable genetic transformation was carried out via ballistic gene transfer (wheat) or Agrobacterium-mediated introduction of T-DNA (barley) to immature embryos. The subsequently regenerated plants were examined for the presence of T-DNA and induced mutations. In wheat, regenerated mutant plants were generatively propagated by selfing, crossing and the application of haploid technology, and a collection of individuals carrying various mutated alleles including combinations of mutated homoeologous alleles was deployed. Resulting plants with one or two mutant Bh/Wfzp homoeoalleles were T-DNA-free and showed phenotypic modifications in ear phenotype, grain size, grain number and partially in roots. The presence of three mutant Bh/Wfzp homoeoalleles typically led to very drastic changes in the ears, which formed supernumerary spikelets and were also branching, which was associated with a great loss in fertility. Overall, the importance of the transcription factor BH/WFZP for the development of the spike and the grains as well as for the roots was further elucidated in the present investigation. The mutations in Spl14 induced in barley led to delayed generative development and in some cases to the reactivation of lateral spikelet formation. In addition, the ears were shortened and formed fewer grains. The mutations produced in Spl17 did not affect generative development, but did affect ear length and grain formation. Plants carrying double mutations in Spl14 and Spl17 showed a drastic aggravation of the spl14 phenotype, with generative development severely disrupted so that no ears could be formed. This suggests that SPL14 exerts a major function in early generative development and SPL17 acts as a co-factor

Blessing and curse of bioclimatic variables: a comparison of different calculation schemes and datasets for species distribution modeling within the extended Mediterranean area

Bioclimatic variables (BCVs) are the most widely used predictors within the field of species distribution modeling, but recent studies imply that BCVs alone are not sufficient to describe these limits. Unfortunately, the most popular database, WorldClim, offers only a limited selection of bioclimatological predictors; thus, other climatological datasets should be considered, and, for data consistency, the BCVs should also be derived from the respective datasets. Here, we investigate how well the BCVs are represented by different datasets for the extended Mediterranean area within the period 1970–2020, how different calculation schemes affect the representation of BCVs, and how deviations among the datasets differ regionally. We consider different calculation schemes for quarters/months, the annual mean temperature (BCV-1), and the maximum temperature of the warmest month (BCV-5). Additionally, we analyzed the effect of different temporal resolutions for BCV-1 and BCV-5. Differences resulting from different calculation schemes are presented for ERA5-Land. Selected BCVs are analyzed to show differences between WorldClim, ERA5-Land, E-OBS, and CRU. Our results show that (a) differences between the two calculation schemes for BCV-1 diminish as the temporal resolution decreases, while the differences for BCV-5 increase; (b) with respect to the definition of the respective month/quarter, intra-annual shifts induced by the calculation schemes can have substantially different effects on the BCVs; (c) all datasets represent the different BCVs similarly, but with partly large differences in some subregions; and (d) the largest differences occur when specific month/quarters are defined by precipitation. In summary, (a) since the definition of BCVs matches different calculation schemes, transparent communication of the BCVs calculation schemes is required; (b) the calculation, integration, or elimination of BCVs has to be examined carefully for each dataset, region, period, or species; and (c) the evaluated datasets provide, except in some areas, a consistent representation of BCVs within the extended Mediterranean region

Determination of Intra- and Extracellular Metabolic Adaptations of 3D Cell Cultures upon Challenges in Real-Time by NMR.

NMR flow devices provide longitudinal real-time quantitative metabolome characterisation of living cells. However, discrimination of intra- and extracellular contributions to the spectra represents a major challenge in metabolomic NMR studies. The present NMR study demonstrates the possibility to quantitatively measure both metabolic intracellular fingerprints and extracellular footprints on human control fibroblasts by using a commercially available flow tube system with a standard 5 mm NMR probe. We performed a comprehensive 3D cell culture system characterisation. Diffusion NMR was employed for intra- and extracellular metabolites separation. In addition, complementary extracellular footprints were determined. The implemented perfused NMR bioreactor system allowed the determination of 35 metabolites and intra- and extracellular separation of 19 metabolites based on diffusion rate differences. We show the reliability and sensitivity of NMR diffusion measurements to detect metabolite concentration changes in both intra- and extracellular compartments during perfusion with different selective culture media, and upon complex I inhibition with rotenone. We also demonstrate the sensitivity of extracellular footprints to determine metabolic variations at different flow rates. The current method is of potential use for the metabolomic characterisation of defect fibroblasts and for improving physiological comprehension

Validation of spatial variability in downscaling results from the VALUE perfect predictor experiment

The spatial dependence of meteorological variables is crucial for many impacts, for example, droughts, floods, river flows, energy demand, and crop yield. There is thus a need to understand how well it is represented in downscaling (DS) products. Within the COST Action VALUE, we have conducted a comprehensive analysis of spatial variability in the output of over 40 different DS methods in a perfect predictor setup. The DS output is evaluated against daily precipitation and temperature observations for the period 1979?2008 at 86 sites across Europe and 53 sites across Germany. We have analysed the dependency of correlations of daily temperature and precipitation series at station pairs on the distance between the stations. For the European data set, we have also investigated the complexity of the downscaled data by calculating the number of independent spatial degrees of freedom. For daily precipitation at the German network, we have additionally evaluated the dependency of the joint exceedance of the wet day threshold and of the local 90th percentile on the distance between the stations. Finally, we have investigated regional patterns of European monthly precipitation obtained from rotated principal component analysis. We analysed Perfect Prog (PP) methods, which are based on statistical relationships derived from observations, as well as Model Output Statistics (MOS) approaches, which attempt to correct simulated variables. In summary, we found that most PP DS methods, with the exception of multisite analog methods and a method that explicitly models spatial dependence yield unrealistic spatial characteristics. Regional climate model?based MOS methods showed good performance with respect to correlation lengths and the joint occurrence of wet days, but a substantial overestimation of the joint occurrence of heavy precipitation events. These findings apply to the spatial scales that are resolved by our observation network, and similar studies with higher resolutions, which are relevant for small hydrological catchment, are desirable.Funding Information: EU. Grant Number: EU COST Action ES110

Targeting lactate dehydrogenase B-dependent mitochondrial metabolism affects tumor initiating cells and inhibits tumorigenesis of non-small cell lung cancer by inducing mtDNA damage.

Once considered a waste product of anaerobic cellular metabolism, lactate has been identified as a critical regulator of tumorigenesis, maintenance, and progression. The putative primary function of lactate dehydrogenase B (LDHB) is to catalyze the conversion of lactate to pyruvate; however, its role in regulating metabolism during tumorigenesis is largely unknown. To determine whether LDHB plays a pivotal role in tumorigenesis, we performed 2D and 3D in vitro experiments, utilized a conventional xenograft tumor model, and developed a novel genetically engineered mouse model (GEMM) of non-small cell lung cancer (NSCLC), in which we combined an LDHB deletion allele with an inducible model of lung adenocarcinoma driven by the concomitant loss of p53 (also known as Trp53) and expression of oncogenic KRAS (G12D) (KP). Here, we show that epithelial-like, tumor-initiating NSCLC cells feature oxidative phosphorylation (OXPHOS) phenotype that is regulated by LDHB-mediated lactate metabolism. We show that silencing of LDHB induces persistent mitochondrial DNA damage, decreases mitochondrial respiratory complex activity and OXPHOS, resulting in reduced levels of mitochondria-dependent metabolites, e.g., TCA intermediates, amino acids, and nucleotides. Inhibition of LDHB dramatically reduced the survival of tumor-initiating cells and sphere formation in vitro, which can be partially restored by nucleotide supplementation. In addition, LDHB silencing reduced tumor initiation and growth of xenograft tumors. Furthermore, we report for the first time that homozygous deletion of LDHB significantly reduced lung tumorigenesis upon the concomitant loss of Tp53 and expression of oncogenic KRAS without considerably affecting the animal's health status, thereby identifying LDHB as a potential target for NSCLC therapy. In conclusion, our study shows for the first time that LDHB is essential for the maintenance of mitochondrial metabolism, especially nucleotide metabolism, demonstrating that LDHB is crucial for the survival and proliferation of NSCLC tumor-initiating cells and tumorigenesis

Noble gases and radiocarbon in natural gases

In samples of pure natural gas hydrates from Hydrate Ridge, Cascadia Margin, virtually no helium and neon components are present providing evidence that the light noble gases are not incorporated into the structure of natural methane hydrates. In contrast, the hydrates contain significant amounts of argon, krypton and xenon. These gases show a distinct fractionation pattern, with the heavier ones preferentially incorporated into the gas hydrate structure. The hydrate methane is devoid of 14C indicating that there is no contribution of a recent (14C-active) organic carbon reservoir to the hydrate carbon pool. On the basis of the δ13C and δ2H signature, it appears that microbial CO2-reduction is the dominant CH4 production pathway

How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining μXRF and statistical analysis. Part II: Clinical application

International audienceIn this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique

Evaluation of the Reproductive and Developmental Risks of Caffeine

A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the “pregnancy signal,” which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the “caffeine teratogenic syndrome.” Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152–187, 2011. © 2011 Wiley-Liss, Inc