During the first Cloud and Aerosol Characterization Experiment (CLACE-1) in February and March 2000 various methods were used to characterize the aerosol at the high-alpine site Jungfraujoch, ...Switzerland (3580
m asl). One aim of the campaign was to perform the size-resolved chemical analysis of single particles under conditions of the free troposphere in real-time. Evaluation of single particle spectra measured predominantly in the size range between 0.5 and
5
μ
m
and determination of spectra patterns of the most frequent particle classes showed a great variability ranging from pure carbon particles over carbon particles internally mixed with salts and/or secondary components to mineral dust particles. Such mineral particles sometimes showed internal mixtures with carbon indicating scavenging effects of carbonaceous material by minerals. This can be due to coagulation or condensation of organic molecules on the mineral particles. Observation of internally mixed carbon particles is an indication for atmospheric transformation processes of pure carbon particles. Such internally mixed particles can strongly influence cloud formation due to an increase in particle size and hygroscopicity.
High abundance of mineral and carbon-containing particles could be correlated to enhanced light absorption and light scattering coefficients, respectively. Semi-quantitative evaluation of mass spectra using relative sensitivity factors showed comparable ratios of selected ion pairs compared to bulk concentrations determined by ion chromatography.
Scientific Data 4:170003 doi: 10.1038/sdata.2017.3 (2018); Published 14 March 2017; Updated 8 May 2018 The affiliation of Cathrine Lund Myhre was incorrectly stated in the original publication. It ...is: 19 NILU -Norwegian Institute for Air Research, Instituttveien 18, Kjeller 2007, Norway.
In this study we investigate the occurrence of primary biological aerosol particles (PBAP) over all sectors of the Southern Ocean (SO) based on a 90-day dataset collected during the Antarctic ...Circumnavigation Expedition (ACE) in austral summer 2016-2017. Super-micrometer PBAP (1 to 16 µm diameter) were measured by a wide band integrated bioaerosol sensor (WIBS-4). Low (3σ) and high (9σ) fluorescence thresholds are used to obtain statistics on fluorescent and hyper-fluorescent PBAP, respectively. Our focus is on data obtained over the pristine ocean, i.e. more than 200 km away from land. The results indicate that (hyper-)fluorescent PBAP are correlated to atmospheric variables associated with sea spray aerosol (SSA) particles (wind speed, total super-micrometer aerosol number concentration, chloride and sodium concentrations). This suggests that a main source of PBAP over the SO is SSA. The median fraction of fluorescent and hyper-fluorescent PBAP to super-micrometer SSA is 1.6% and 0.13%, respectively. We demonstrate that the fraction of (hyper-)fluorescent PBAP to total super-micrometer particles positively correlates with concentrations of bacteria and several taxa of phytoplankton measured in seawater, indicating that marine biota concentrations modulate the PBAP source flux. We investigate the fluorescent properties of (hyper-)fluorescent PBAP for several events that occurred near land masses. We find that the fluorescence signal characteristics of particles near land is much more variable than over the pristine ocean. We conclude that the source and concentration of fluorescent PBAP over the open ocean is similar across all sectors of the SO.
Environmental monitoring involves the quantification of microscopic cells and particles
such as algae, plant cells, pollen, or fungal spores. Traditional methods using conventional
microscopy require ...expert knowledge, are time-intensive and not wellsuited
for automated high throughput. Multispectral imaging flow cytometry (MIFC)
allows measurement of up to 5000 particles per second from a fluid suspension and
can simultaneously capture up to 12 images of every single particle for brightfield
and different spectral ranges, with up to 60x magnification. The high throughput of
MIFC has high potential for increasing the amount and accuracy of environmental
monitoring, such as for plant-pollinator interactions, fossil samples, air, water or food
quality that currently rely on manual microscopic methods. Automated recognition of
particles and cells is also possible, when MIFC is combined with deep-learning computational
techniques. Furthermore, various fluorescence dyes can be used to stain
specific parts of the cell to highlight physiological and chemical features including:
vitality of pollen or algae, allergen content of individual pollen, surface chemical composition
(carbohydrate coating) of cells, DNA- or enzyme-activity staining. Here, we
outline the great potential for MIFC in environmental research for a variety of
research fields and focal organisms. In addition, we provide best practice
recommendations.
The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of ...pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL-TRAIL-R system to their own advantage. However, novel insight on two fronts - how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered - gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL-TRAIL-R system - as well as the gaps therein - and discuss the opportunities and challenges in effectively targeting this pathway.
Osteochondral defects are difficult to treat because the articular cartilage and the subchondral bone have dissimilar characteristics and abilities to regenerate. Bioinspired scaffolds are designed ...to mimic structural and biological cues of the native osteochondral unit, supporting both cartilaginous and subchondral bone repair and the integration of the newly formed osteochondral matrix with the surrounding tissues. The aim of this review is to outline fundamental requirements and strategies for the development of biomimetic scaffolds reproducing the unique and multifaceted anatomical structure of the osteochondral unit. Recent progress in preclinical animal studies using bilayer and multilayer scaffolds, together with continuous gradient scaffolds will be discussed and placed in a translational perspective with data emerging from their clinical application to treat osteochondral defects in patients.
Accurate, reproducible, and fast quantification of N-glycans is crucial not only for the development and quality control of modern glycosylated biopharmaceuticals, but also in clinical biomarker ...discovery. Several methods exist for fluorescent labeling of N-glycans and subsequent chromatographic separation and quantification. However, the methods can be complex, lengthy, and expensive. Here we report an automated ultrafiltration-based N-glycoanalytical workflow combined with a glycan labeling strategy that is based on the reaction of glycosylamines with fluorescent carbamate. The entire protocol is quick, simple, and cost-effective and requires less than 1 μg of protein per sample. As many as 768 affinity purified IgG glycoprotein samples can be prepared in a single run with a liquid handling platform.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for specifically killing cancer cells, whereas in resistant cancers, TRAIL/TRAIL-R can promote metastasis via Rac1 and ...PI3K. It remains unknown, however, whether and to what extent TRAIL/TRAIL-R signaling in cancer cells can affect the immune microenvironment. Here we show that TRAIL-triggered cytokine secretion from TRAIL-resistant cancer cells is FADD dependent and identify the TRAIL-induced secretome to drive monocyte polarization to myeloid-derived suppressor cells (MDSCs) and M2-like macrophages. TRAIL-R suppression in tumor cells impaired CCL2 production and diminished both lung MDSC presence and tumor growth. In accordance, the receptor of CCL2, CCR2, is required to facilitate increased MDSC presence and tumor growth. Finally, TRAIL and CCL2 are co-regulated with MDSC/M2 markers in lung adenocarcinoma patients. Collectively, endogenous TRAIL/TRAIL-R-mediated CCL2 secretion promotes accumulation of tumor-supportive immune cells in the cancer microenvironment, thereby revealing a tumor-supportive immune-modulatory role of the TRAIL/TRAIL-R system in cancer biology.
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•TRAIL induces a cytokine cancer secretome in a FADD- and caspase-8-dependent manner•FADD promotes tumor growth along with accumulation of M2-like immune cells in vivo•The TRAIL-induced secretome recruits M2-like immune cells to tumors via CCR2•TRAIL/CCL2 correlate with a tumor-supportive immune profile in lung cancer patients
Hartwig et al. show that endogenous TRAIL signaling in cancer cells induces a FADD-dependent secretome that promotes the accumulation of M2-like immune cells and tumor growth via host CCR2.
An improvement in progression-free survival was shown with trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer in the progression-free survival ...interim analysis of the DESTINY-Breast03 trial. The aim of DESTINY-Breast03 was to compare the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine.
This open-label, randomised, multicentre, phase 3 trial was done in 169 study centres in North America, Asia, Europe, Australia, and South America. Eligible patients were aged 18 or older, had HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab and a taxane, had an Eastern Cooperative Oncology Group performance status 0–1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumours version 1.1. Patients were randomly assigned (1:1) to receive trastuzumab deruxtecan 5·4 mg/kg or trastuzumab emtansine 3·6 mg/kg, both administered by intravenous infusion every 3 weeks. Randomisation was stratified by hormone receptor status, previous treatment with pertuzumab, and history of visceral disease, and was managed through an interactive web-based system. Within each stratum, balanced block randomisation was used with a block size of four. Patients and investigators were not masked to the treatment received. The primary endpoint was progression-free survival by blinded independent central review. The key secondary endpoint was overall survival and this prespecified second overall survival interim analysis reports updated overall survival, efficacy, and safety results. Efficacy analyses were performed using the full analysis set. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03529110.
Between July 20, 2018, and June 23, 2020, 699 patients were screened for eligibility, 524 of whom were enrolled and randomly assigned to receive trastuzumab deruxtecan (n=261) or trastuzumab emtansine (n=263). Median duration of study follow-up was 28·4 months (IQR 22·1–32·9) with trastuzumab deruxtecan and 26·5 months (14·5–31·3) with trastuzumab emtansine. Median progression-free survival by blinded independent central review was 28·8 months (95% CI 22·4–37·9) with trastuzumab deruxtecan and 6·8 months (5·6–8·2) with trastuzumab emtansine (hazard ratio HR 0·33 95% CI 0·26–0·43; nominal p<0·0001). Median overall survival was not reached (95% CI 40·5 months–not estimable), with 72 (28%) overall survival events, in the trastuzumab deruxtecan group and was not reached (34·0 months–not estimable), with 97 (37%) overall survival events, in the trastuzumab emtansine group (HR 0·64 95% CI 0·47–0·87; p=0·0037). The number of grade 3 or worse treatment-emergent adverse events was similar in patients who received trastuzumab deruxtecan versus trastuzumab emtansine (145 56% patients versus 135 52% patients). Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 39 (15%) patients treated with trastuzumab deruxtecan and eight (3%) patients treated with trastuzumab emtansine, with no grade 4 or 5 events in either group.
Trastuzumab deruxtecan showed a significant improvement in overall survival versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer, as well as the longest reported median progression-free survival, reaffirming trastuzumab deruxtecan as the standard of care in the second-line setting. A manageable safety profile of trastuzumab deruxtecan was confirmed with longer treatment duration.
Daiichi Sankyo and AstraZeneca.
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