Search

Seit Längerem vermutet, nun ausdrücklich vom Gerichtshof bestätigt: Zwar kann unverbindliches Unionshandeln nicht Gegenstand einer Rechtmäßigkeitsprüfung im Rahmen der Nichtigkeitsklage sein, sehr wohl jedoch im Gültigkeitsverfahren. Der Ausspruch ist aus einer Rechtsschutzperspektive nicht nur interessant, weil er unterstreicht, dass das Gültigkeitsverfahren hinsichtlich des Kontrollgegenstands grundsätzlich keinen Vorbehalt kennt. In den beiden Rechtssachen wird das Rechtsschutzbedürfnis, das dem Einzelnen gegenüber nicht verbindlichen Unionshandlungen erwachsen kann, deutlich.

BackgroundOxidative stress from excess reactive oxygen species (ROS) is a hypothesized contributor to preterm birth. Per- and polyfluoroalkyl substances (PFAS) exposure is reported to generate ROS in laboratory settings, and is linked to adverse birth outcomes globally. However, to our knowledge, the relationship between PFAS and oxidative stress has not been examined in the context of human pregnancy.ObjectiveTo investigate the associations between prenatal PFAS exposure and oxidative stress biomarkers among pregnant people.MethodsOur analytic sample included 428 participants enrolled in the Illinois Kids Development Study and Chemicals In Our Bodies prospective birth cohorts between 2014 and 2019. Twelve PFAS were measured in second trimester serum. We focused on seven PFAS that were detected in>65% of participants. Urinary levels of 8-isoprostane-prostaglandin-F2α, prostaglandin-F2α, 2,3-dinor-8-iso-PGF2α, and 2,3-dinor-5,6-dihydro-8-iso-PGF2α were measured in the second and third trimesters as biomarkers of oxidative stress. We fit linear mixed-effects models to estimate individual associations between PFAS and oxidative stress biomarkers. We used quantile g-computation and Bayesian kernel machine regression (BKMR) to assess associations between the PFAS mixture and averaged oxidative stress biomarkers.ResultsLinear mixed-effects models showed that an interquartile range increase in perfluorooctane sulfonic acid (PFOS) was associated with an increase in 8-isoprostane-prostaglandin-F2α (β=0.10, 95% confidence interval=0, 0.20). In both quantile g-computation and BKMR, and across all oxidative stress biomarkers, PFOS contributed the most to the overall mixture effect. The six remaining PFAS were not significantly associated with changes in oxidative stress biomarkers.ConclusionsOur study is the first to investigate the relationship between PFAS exposure and biomarkers of oxidative stress during human pregnancy. We found that PFOS was associated with elevated levels of oxidative stress, which is consistent with prior work in animal models and cell lines. Future research is needed to understand how prenatal PFAS exposure and maternal oxidative stress may affect fetal development.

Photonic integrated circuits (PICs) can drastically expand the capabilities of quantum and classical optical information science and engineering. PICs are commonly fabricated using selective material etching, a subtractive process. Thus, the chip’s functionality cannot be substantially altered once fabricated. Here, we propose to exploit wide-bandgap non-volatile phase-change materials (PCMs) to create rewritable PICs. A PCM-based PIC can be written using a nanosecond pulsed laser without removing any material, akin to rewritable compact disks. The whole circuit can then be erased by heating, and a new circuit can be rewritten. We designed a dielectric-assisted PCM waveguide consisting of a thick dielectric layer on top of a thin layer of wide-bandgap PCMs Sb2S3 and Sb2Se3. The low-loss PCMs and our designed waveguides lead to negligible optical loss. Furthermore, we analyzed the spatiotemporal laser pulse shape to write the PICs. Our proposed platform will enable low-cost manufacturing and have a far-reaching impact on the rapid prototyping of PICs, validation of new designs, and photonic education.

Conventional electronic and photonic devices are inherently 2D and rigid because of the substrates on which they are fabricated. However, the world is not flat and stiff: There are many application...

A modified version of the Student Success Skills (SSS) curriculum, designed to help address the need for intervention in executive functioning skills, metacognition skills, and social skills, was offered to a small group of students in eighth grade who were identified with learning disabilities to positively impact their learning strategies and knowledge. The purpose of this pilot study was to measure the effects of this modified version of SSS on students’ (a) skills and behaviors associated with improved school performance; (b) generalization of those skills to scenarios; and (c) school-related outcomes, including a teacher report. The study design applied a single subject multiple probe across students. The primary dependent variable measured in this study was the number of school-success-related skills and strategies students identified. Findings suggest a functional relation between the modified version of SSS and participants’ ability to name skills and behaviors associated with school success. The findings of the current study, as a collaboration with school counselors and special educators, provide a first step towards illustrating the impact of a modified SSS intervention with students with IEPs. Students reported enjoying and learning from the lessons.

We present and erratum to our review article [Opt. Mater. Express 12, 2145 (2022)10.1364/OME.456428]. This erratum corrects the references in Table 3, a typo, and a misleading sentence. These corrections do not affect conclusions of the original review article.

In order to analyse and understand ecosystem responses with respect to different environmental challenges a wide range of data is needed. Based on the results of a scientific gap analysis, LTER CWN focuses on a prioritisation of observation parameters completing the existing observation programmes at five LTER sites in Austria. The resulting data needs to be made available in an open and standardised manner following the information management principles of existing European scale initiatives like eLTER, LTER Europe or ILTER. One of the challenges for the LTER CWN Data Management is to integrate a number of heterogeneous systems at the level of the participating partners, who run the monitoring activities and facilitate the data flow from the observation sites to the central data provision. The resulting data files are automatically ingested into a central database that ultimately provides time series data of each parameter and for each site through an OGC-SOS service to the public under an open access data policy. This article provides an overview of the information architecture and tools used in order to ensure for the data to be Findable Accessible Interoperable and Reusable (FAIR).

Chalcogenide phase change materials (PCMs) are truly remarkable compounds whose unique switchable optical and electronic properties have fueled an explosion of emerging applications in electronics and photonics. Key to any application is the ability of PCMs to reliably switch between crystalline and amorphous states over a large number of cycles. While this issue has been extensively studied in the case of electronic memories, current PCM-based photonic devices show limited endurance. This review discusses the various parameters that impact crystallization and re-amorphization of several PCMs, their failure mechanisms, and formulate design rules for enhancing cycling durability of these compounds.

Excess nitrogen (N) deposition and gaseous N emissions from industrial, domestic, and agricultural sources have led to increased nitrate leaching, the loss of biological diversity, and has affected carbon (C) sequestration in forest ecosystems. Nitrate leaching affects the purity of karst water resources, which contribute around 50% to Austria&rsquo, s drinking water supply. Here we present an evaluation of the drivers of dissolved inorganic N (DIN) concentrations and fluxes from a karst catchment in the Austrian Alps (LTER Z&ouml, belboden) from 27 years of records. In addition, a hydrological model was used together with climatic scenario data to predict expected future runoff dynamics. The study area was exposed to increasing N deposition during the 20th century (up to 30 to 35 kg N ha&minus, 1 y&minus, 1), which are still at levels of 25.5 &plusmn, 3.6 and 19.9 &plusmn, 4.2 kg N ha&minus, 1 in the spruce and the mixed deciduous forests, respectively. Albeit N deposition was close to or exceeded critical loads for several decades, 70&ndash, 83% of the inorganic N retained in the catchment from 2000 to 2018, and NO3- concentrations in the runoff stayed &lt, 10 mg L&minus, 1 unless high-flow events occurred or forest stand-replacing disturbances. We identified tree growth as the main sink for inorganic N, which might together with lower runoff, increase retention of only weakly decreasing N deposition in the future. However, since recurring forest stand-replacement is predicted in the future as a result of a combination of climatically driven disturbance agents, pulses of elevated nitrate concentrations in the catchment runoff will likely add to groundwater pollution.

We report a fully-packaged 3-D integrated photonics platform with devices placed at arbitrary pre-defined locations in 3-D. We further demonstrated the application of the platform to mechanical strain sensing.

Many young people with complex needs choose further education (FE) to support their hopes for independence, employment and friendships. However, provision often falls short of what is needed to make a successful transition to adult life. This FE Project was initiated by educational psychologists to support a systemic approach to develop the quality of the educational offer for young people with complex needs at age 16+. An action research model was used to support a cyclical process of planning, action and reflection. This brought key stakeholders together to develop joint understanding of good practice, increase communication and cross provision working, and to improve provision. Issues with the current system were identified with the key stakeholders and were addressed using the action planning approach.The project delivered a number of key outcomes:Data were analysed to predict the needs of the future 16+ population in the geographical area.A literature review was conducted to highlight national good practice in the further education of pupils with complex needs and this was used to develop practical guidance for local implementation.School and college curriculum and assessments used to track student progress were compared and mapped across provisions to demonstrate how skill levels in schools translate to the adult curriculum.Transition processes and timings were evaluated to identify changes that would facilitate successful transition from schools to local further education.Written guidance was developed to support local colleges in assessing and planning provision for individual pupils using evidence based strategies and interventions.The outcomes of the project were evaluated and discussed.

Among the many known health benefits of tea catechins count anti-inflammatory and neuroprotective activities, as well as effects on the regulation of food intake. Here we address cannabimimetic bioactivity of catechin derivatives occurring in tea leaves as a possible cellular effector of these functionalities. Competitive radioligand binding assays using recombinant human cannabinoid receptors expressed in Chem-1 and CHO cells identified (-)-epigallocatechin-3-O-gallate, EGCG (K(i)=33.6 microM), (-)-epigallocatechin, EGC (K(i)=35.7 microM), and (-)-epicatechin-3-O-gallate, ECG (K(i)=47.3 microM) as ligands with moderate affinity for type 1 cannabinoid receptors, CB1. Binding to CB2 was weaker with inhibition constants exceeding 50 microM for EGC and ECG. The epimers (+)-catechin and (-)-epicatechin exhibited negligible affinities for both CB1 and CB2. It can be concluded that central nervous cannabinoid receptors may be targeted by selected tea catechins but signaling via peripheral type receptors is less likely to play a major role in vivo.

Despite its popularity and widespread use, the efficacy of Echinacea products remains unclear and controversial. Among the various compounds isolated from Echinacea, ketoalkenes and ketoalkenynes exclusively found in the pale purple coneflower (E. pallida) are major components of the extracts. In contrast to E. purpurea alkamides, these compounds have not been synthesized and studied for immunostimulatory effects. We present a practical and useful synthetic approach to the ketoalkenes using palladium-catalyzed cross-coupling reactions and the pharmaceutical results at the human cannabinoid receptors. The synthetic route developed provides overall good yields for the ketoalkenes and is applicable to other natural products with similar 1,4-diene motifs. No significant activity was observed at either receptor, indicating that the ketoalkenes from E. pallida are not responsible for immunomodulatory effects mediated via the cannabinergic system. However, newly synthesized non-natural analogues showed micro-molar potency at both cannabinoid receptors.

Human cannabinoid receptors 1 (hCB 1 R) and 2 (hCB 2 R) are expressed in the CNS and couple to G i /G o -proteins. The aim of this study was to compare coupling of hCB 1 R and hCB 2 R to Gα i2 β 1 γ 2 in Sf9 insect cells. High-affinity agonist binding at hCB 1 R, but not at hCB 2 R, was resistant to guanine nucleotides. hCB 1 R activated Gα i2 β 1 γ 2 much more rapidly than hCB 2 R in the [ 35 S]guanosine 5′-[γ-thio]triphosphate ([ 35 S]GTPγS) binding assay. Moreover, hCB 1 R exhibited a higher constitutive activity than hCB 2 R as assessed by the relative inhibitory effects of inverse agonists on [ 35 S]GTPγS binding and steady-state high-affinity GTPase activity compared to the stimulatory effects of the hCB 1/2 R agonist CP 55,940 [(-)- cis -3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]- trans -4-(3-hydroxypropyl)cyclohexanol]. Gα i2 β 1 γ 2 coupled to hCB 2 R exhibited higher GDP- and GTPγS-affinities than Gα i2 β 1 γ 2 coupled to hCB 1 R. NaCl effectively reduced constitutive activity of hCB 1 R but not of hCB 2 R. Collectively, hCB 1 R and hCB 2 R couple differentially to Gα i2 β 1 γ 2 . Moreover, hCB 1 R exhibits higher constitutive activity than hCB 2 R. These differences point to distinct functions of hCB 1 R and hCB 2 R in the CNS.

Conventional integrated photonic devices are fabricated on rigid semiconductor or dielectric substrates and are therefore inherently incompatible with soft biological tissues. Over the past few years, we have developed a suite of active and passive photonic devices and systems integrated on plastic substrates which can be bent, twisted, and stretched without compromising their optical performance. In this talk, we will review the latest progress in multi-material photonic integration on unconventional flexible substrates, and discuss emerging applications of flexible photonics in biological sensing and high-bandwidth data communications.

Cannabinoid receptors (CBR) are important drug targets for the treatment of various inflammatory, metabolic and neurological diseases. Therefore, sensitive test systems for the assessment of ligands are needed. In this study, a steady-state GTPase assay for human CBR subtypes 1 and 2 was developed to characterize the pharmacological property of ligands at a very proximal point of the signal transduction cascade. Establishing these in vitro test sytems, we studied cell or tissue membranes heterogenously or endogenously expressing CBR, such as CBR-infected Human Embryonic Kidney (HEK) 293 cells, rat cerebellum and spleen cells. The lack of effects in the GTPase assay and in [(35)S]GTPgammaS binding experiments in these expression system, directed us to use Spodoptera frugiperda (Sf9) cells. Co-expressing CBR, different Galpha-subunits, Gbetagamma heterodimer, and RGS (Regulator of G-protein signaling)-proteins in Sf9 cell membranes greatly improved the sensitivity of the assay, with highest GTPase activation in the CBR + Galpha(i2) + Gbeta(1)gamma(2) + RGS4 system. We examined exogenous and endogenous standard ligands as well as secondary metabolites as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), dodeca-2E,4E-dienoic acid isobutylamide, an alkylamide from Echinacea purpurea, and an E. purpurea hexane extract according their agonistic and antagonistic properties. The suitability of the assay for screening procedures was also proven by detecting the activity of Delta(9)-THC in a matrix of other less active compounds (Delta(9)-THC-free Cannabis sativa extract). In conclusion, we have developed highly sensitive test systems for the analysis of CBR ligands.

Human cannabinoid receptors 1 (hCB(1)R) and 2 (hCB(2)R) are expressed in the CNS and couple to G(i)/G(o)-proteins. The aim of this study was to compare coupling of hCB(1)R and hCB(2)R to G(alpha)(i2)beta(1)gamma(2) in Sf9 insect cells. High-affinity agonist binding at hCB(1)R, but not at hCB(2)R, was resistant to guanine nucleotides. hCB(1)R activated G(alpha)(i2)beta(1)gamma(2) much more rapidly than hCB(2)R in the [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTPgammaS) binding assay. Moreover, hCB(1)R exhibited a higher constitutive activity than hCB(2)R as assessed by the relative inhibitory effects of inverse agonists on [(35)S]GTPgammaS binding and steady-state high-affinity GTPase activity compared to the stimulatory effects of the hCB(1/2)R agonist CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol]. G(alpha)(i2)beta(1)gamma(2) coupled to hCB(2)R exhibited higher GDP- and GTPgammaS-affinities than G(alpha)(i2)beta(1)gamma(2) coupled to hCB(1)R. NaCl effectively reduced constitutive activity of hCB(1)R but not of hCB(2)R. Collectively, hCB(1)R and hCB(2)R couple differentially to G(alpha)(i2)beta(1)gamma(2). Moreover, hCB(1)R exhibits higher constitutive activity than hCB(2)R. These differences point to distinct functions of hCB(1)R and hCB(2)R in the CNS.