Validating costly protected area restoration after (increasing) disasters.

Protected areas such as national parks constitute an increasing land mass globally, but these areas are under increasing threat from climate change events such as drought, flooding, and bushfires. The recent Yosemite National Park fires in California provide an example of this issue. After any such disaster, authorities will need to restore those protected areas to their former state at significant costs within any public funding cycle.

Chasing Red Herrings: Palladium Metal Salt Impurities Feigning KRAS Activity in Biochemical Assays.

Identifying promising chemical starting points for small molecule inhibitors of active, GTP-loaded KRAS "on" remains of great importance to clinical oncology and represents a significant challenge in medicinal chemistry. Here, we describe broadly applicable learnings from a KRAS hit finding campaign: While we initially identified KRAS inhibitors in a biochemical high-throughput screen, we later discovered that compound potencies were all but assay artifacts linked to metal salts interfering with KRAS AlphaScreen assay technology. The source of the apparent biochemical KRAS inhibition was ultimately traced to unavoidable palladium impurities from chemical synthesis.

Do GC/MS methods available for furan and alkylfurans in food provide comparable results? - An interlaboratory study and safety assessment of 2-pentylfuran in food.

A call for data on the occurrence of alkylfurans in food and feed from EFSA triggered the development of new methods to cover next to furan also 2- and 3-methylfuran, 2,5-dimethyl- and 2-ethylfuran as well as 2-pentylfuran. A significant variability was noticed when comparing analysis of 2-pentylfuran and furans in the same matrix performed by different laboratories. To assess the variability an interlaboratory study including eight laboratories was organised.

RNA interaction format: a general data format for RNA interactions.

Summary: RNA molecules play crucial roles in various biological processes. They mediate their function mainly by interacting with other RNAs or proteins. At present, information about these interactions is distributed over different resources, often providing the data in simple tab-delimited formats that differ between the databases.

Biologic disease-modifying anti-rheumatic drugs are equally effective in psoriatic arthritis patients with low and high joint counts.

Objective: A lack of representation in pivotal trials currently limits guidance for the use of biologic DMARDs (bDMARDs) in PsA patients with a low number of actively inflamed joints. The aim of this study was to compare the effectiveness of a first bDMARD in PsA patients with a low vs high number of affected joints.

Methods: PsA patients with available 66/68 joint count assessments were divided into low joint count (LJC) patients when presenting with <3 tender or <3 swollen joints or high joint count (HJC) patients with ≥3 joints in both categories.

Coupling the H295R with ERα and AR U2OS CALUX assays enables simultaneous testing for estrogenic, anti-androgenic and steroidogenic modalities.

Endocrine active substances, including steroidogenesis modulators, have received increased attention. The in vitro H295R steroidogenesis assay (OECD TG 456) is commonly used to test for this modality. However, current detection methods often fail to capture alterations to estrogen biosynthesis.

Valuing Protected Area Tourism Ecosystem Services Using Big Data.

Economic value from protected areas informs decisions for biodiversity conservation and visitor benefits. Calculating these benefits assists governments to allocate limited budget resources. This study estimated tourism ecosystem service expenditure values for a regional protected area network in South Australia (57 parks) using direct transactional data, travel costs and economic multipliers.

Incorporation of Metabolic Activation in the HPTLC-SOS-Umu-C Bioassay to Detect Low Levels of Genotoxic Chemicals in Food Contact Materials.

The safety evaluation of food contact materials requires excluding mutagenicity and genotoxicity in migrates. Testing the migrates using in vitro bioassays has been proposed to address this challenge. To be fit for that purpose, bioassays must be capable of detecting very low, safety relevant concentrations of DNA-damaging substances.

Forest-Based Networks.

In evolutionary studies, it is common to use phylogenetic trees to represent the evolutionary history of a set of species. However, in case the transfer of genes or other genetic information between the species or their ancestors has occurred in the past, a tree may not provide a complete picture of their history. In such cases, tree-based phylogenetic networks can provide a useful, more refined representation of the species' evolution.

Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling.

Oncogenic alterations in human epidermal growth factor receptor 2 (HER2) occur in approximately 2% of patients with non-small cell lung cancer and predominantly affect the tyrosine kinase domain and cluster in exon 20 of the ERBB2 gene. Most clinical-grade tyrosine kinase inhibitors are limited by either insufficient selectivity against wild-type (WT) epidermal growth factor receptor (EGFR), which is a major cause of dose-limiting toxicity or by potency against HER2 exon 20 mutant variants. Here we report the discovery of covalent tyrosine kinase inhibitors that potently inhibit HER2 exon 20 mutants while sparing WT EGFR, which reduce tumor cell survival and proliferation in vitro and result in regressions in preclinical xenograft models of HER2 exon 20 mutant non-small cell lung cancer, concomitant with inhibition of downstream HER2 signaling.

IL-36G promotes cancer-cell intrinsic hallmarks in human gastric cancer cells.

Interleukin-36 gamma (IL-36G) is a member of the IL-36 subfamily of cytokines and acts as a potent driver of inflammation. IL-36G has been extensively characterized in the pathogenesis of psoriasis and has been recently described to play roles in wound healing particularly in the gastrointestinal tract. However, the effects of IL-36G during cancer development including gastric cancer remain unexplored.

Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a single-arm, open-label, proof-of-concept study.

Background: Two randomised controlled trials showed a glucocorticoid-sparing effect of tocilizumab in patients with giant cell arteritis. In the GUSTO trial we aimed to evaluate the efficacy and safety of tocilizumab monotherapy after ultra-short-term glucocorticoid treatment in patients with new-onset giant cell arteritis.

Methods: This investigator-initiated, single-arm, single-centre, open-label, proof-of-concept trial with a Simon's two stage design was done at University Hospital Bern, Bern, Switzerland.

Limitations of currently available oestrogenicity bioassays for effect-based testing of whole foods as the basis for decision making.

The idea that previously unknown hazards can be readily revealed in complex mixtures such as foods is a seductive one, giving rise to the hope that data from effect-based assays of food products collected in market surveys is of suitable quality to be the basis for data-driven decision-making. To study this, we undertook a comparative study of the oestrogenicity of blinded cereal samples, both in a number of external testing laboratories and in our own facility. The results clearly showed little variance in the activities of 9 samples when using a single method, but great differences between the activities from each method.

Quantitative ultrasound to monitor the vascular response to tocilizumab in giant cell arteritis.

Objectives: To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA.

Methods: Eighteen GCA patients received 500 mg for 3 consecutive days (total of 1500mg) i.v.

Vision loss in patients with giant cell arteritis treated with tocilizumab.

Objectives: Giant cell arteritis (GCA) may lead to vision loss. To what extent tocilizumab (TCZ) is able to prevent vision loss is unknown. The aim was to analyze the occurrence of vision loss in a large GCA cohort treated with TCZ.

Nonmechanical parfocal and autofocus features based on wave propagation distribution in lensfree holographic microscopy.

Performing long-term cell observations is a non-trivial task for conventional optical microscopy, since it is usually not compatible with environments of an incubator and its temperature and humidity requirements. Lensless holographic microscopy, being entirely based on semiconductor chips without lenses and without any moving parts, has proven to be a very interesting alternative to conventional microscopy. Here, we report on the integration of a computational parfocal feature, which operates based on wave propagation distribution analysis, to perform a fast autofocusing process.

Rapid screening and detection of inter-type viral recombinants using phylo-k-mers.

Motivation: Novel recombinant viruses may have important medical and evolutionary significance, as they sometimes display new traits not present in the parental strains. This is particularly concerning when the new viruses combine fragments coming from phylogenetically distinct viral types. Here, we consider the task of screening large collections of sequences for such novel recombinants.

A HF Loaded Lewis-Acidic Aluminium Chlorofluoride for Hydrofluorination Reactions.

The very strong Lewis acid aluminium chlorofluoride (ACF) was loaded with anhydrous HF. The interaction between the surface of the catalyst and HF was investigated using a variety of characterization methods, which revealed the formation of polyfluorides. Moreover, the reactivity of the HF-loaded ACF towards the hydrofluorination of alkynes was studied.

F-doping of nanostructured ZnO: a way to modify structural, electronic, and surface properties.

Polycrystalline ZnO is a material often used in heterogeneous catalysis. Its properties can be altered by the addition of dopants. We used gaseous fluorine (F) as direct way to incorporate fluoride in ZnO as anionic dopants.

Value and limitation of structure-based profilers to characterize developmental and reproductive toxicity potential.

The uncertainty regarding the safety of chemicals leaching from food packaging triggers attention. In silico models provide solutions for screening of these chemicals, since many are toxicologically uncharacterized. For hazard assessment, information on developmental and reproductive toxicity (DART) is needed.

Insight into the Structure and Properties of Novel Imidazole-Based Salts of Salicylic Acid.

The preparation of new active pharmaceutical ingredient (API) multicomponent crystal forms, especially co-crystals and salts, is being considered as a reliable strategy to improve API solubility and bioavailability. In this study, three novel imidazole-based salts of the poorly water-soluble salicylic acid (SA) are reported exhibiting a remarkable improvement in solubility and dissolution rate properties. All structures were solved by powder X-ray diffraction.

Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor Disrupts Serine Biosynthesis.

Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of , a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD)-competitive PHGDH inhibitor , which has shown high selectivity against the majority of other dehydrogenase targets.

Electroluminescence and current-voltage measurements of single-(In,Ga)N/GaN-nanowire light-emitting diodes in a nanowire ensemble.

We present the combined analysis of electroluminescence (EL) and current-voltage (-) behavior of single, freestanding (In,Ga)N/GaN nanowire (NW) light-emitting diodes (LEDs) in an unprocessed, self-assembled ensemble grown by molecular beam epitaxy. The data were acquired in a scanning electron microscope equipped with a micromanipulator and a luminescence detection system. Single NW spectra consist of emission lines originating from different quantum wells, and the width of the spectra increases with decreasing peak emission energy.