Immune-related adverse events (irAEs) are unpredictable autoimmune-like toxicities induced by immune checkpoint inhibitors (ICI). irAEs are a consequence of a breakdown in self-tolerance. ICIs can ...induce autoantibody formation, and the presence of antinuclear autoantibodies (ANAs) has been reported in patients who developed irAEs. Our goal was to compare ANA patterns by indirect immunofluorescence at different timepoints before (baseline) and after the initiation of ICI treatment and to analyze the role of ANA pattern changes as predictors of irAEs. This is a 2-year-follow-up prospective study of 152 consecutive patients with solid tumors treated with anti-PD-(L)1 blockade agents. They were included from September 2018 until March 2020 in the Hospital de la Santa Creu I Sant Pau (Barcelona, Spain). We grouped patients into three groups: ANA de novo (patients who showed new ANA patterns at any time after ICI initiation), ANA (ANA positive at baseline without changes in the ANA patterns after initiation of treatment) and non-ANA (ANA negative at baseline and after ICI initiation). We did not find any association between the appearance of ANAs and irAE rates or the number and types of irAEs. However, patients in the ANA de novo group showed higher severe irAE rates (grade ≥ 3) than the other groups. Additionally, in most of the patients with severe irAEs (83.3%), changes in ANA patterns preceded irAE onset. In conclusion, we found ANA induction during ICI therapies in 22 patients and our results suggest that the appearance of ANAs may predict the severity of the irAE.
We experimentally demonstrate optoacoustic cooling via stimulated Brillouin-Mandelstam scattering in a 50 cm long tapered photonic crystal fiber. For a 7.38 GHz acoustic mode, a cooling rate of 219 K ...from room temperature has been achieved. As anti-Stokes and Stokes Brillouin processes naturally break the symmetry of phonon cooling and heating, resolved sideband schemes are not necessary. The experiments pave the way to explore the classical to quantum transition for macroscopic objects and could enable new quantum technologies in terms of storage and repeater schemes.
We report the synthesis of various binary and ternary inorganic and hybrid organic–inorganic iodide nanocrystals (NCs) starting from molecular iodine (I2). The synthesis described herein utilizes a ...reaction between I2 and oleylamine, which results in oleylammonium iodide, an iodide precursor that can be directly used in the preparation of iodide-based NCs. The generality of the synthesis was demonstrated by synthesizing KI, RbI, CsI, AgI, CsPbI3, FAPbI3, Cs4PbI6, Cs3Bi2I9, FA3Bi2I9, and RbAg4I5 NCs. Furthermore, the syntheses are facile and are carried out in vials heated on a hot plate in air. They exhibit not only narrow size distributions, but also, in the case of lead-based perovskites NCs, 70–80% photoluminescence quantum yields. To further prove the high quality of the CsPbI3 and FAPbI3 perovskite NCs, red and infrared bright light-emitting diodes were fabricated, with external quantum efficiencies (EQEs) exceeding 3%, without following any extensive washing procedures.
The antimitotic anti‐cancer drugs, including taxol, perturb spindle dynamics, and induce prolonged, spindle checkpoint‐dependent mitotic arrest in cancer cells. These cells then either undergo ...apoptosis triggered by the intrinsic mitochondrial pathway or exit mitosis without proper cell division in an adaptation pathway. Using a genome‐wide small interfering RNA (siRNA) screen in taxol‐treated HeLa cells, we systematically identify components of the mitotic apoptosis and adaptation pathways. We show that the Mad2 inhibitor p31comet actively promotes mitotic adaptation through cyclin B1 degradation and has a minor separate function in suppressing apoptosis. Conversely, the pro‐apoptotic Bcl2 family member, Noxa, is a critical initiator of mitotic cell death. Unexpectedly, the upstream components of the mitochondrial apoptosis pathway and the mitochondrial fission protein Drp1 contribute to mitotic adaption. Our results reveal crosstalk between the apoptosis and adaptation pathways during mitotic arrest.
Synopsis
Prolonged mitotic arrest induced by anti‐proliferative drugs eventually results in apoptotic cell death or in mitotic exit due to checkpoint adaptation. An RNAi screen in human cancer cells lines offers new insights into the regulatory networks underlying these processes.
Genome‐wide siRNA screen identifies regulators of mitotic cell death and checkpoint adaptation.
The BH3‐only protein Noxa promotes apoptosis during mitotic arrest.
The spindle checkpoint regulator p31comet suppresses mitotic adaptation and facilitates apoptosis.
A Bax/Bak mitochondrial module couples mitotic apoptosis and adaptation.
The mitochondrial fission factor Drp1 promotes mitotic checkpoint adaptation.
An RNAi screen offers new insights into the regulatory networks governing the fate of cancer cells undergoing prolonged drug‐induced mitotic checkpoint arrest.
The processes whereby ecological networks emerge, persist and decay throughout ecosystem development are largely unknown. Here we study networks of plant and arbuscular mycorrhizal fungal (AMF) ...communities along a 120 000 year soil chronosequence, as they undergo assembly (progression) and then disassembly (retrogression). We found that network assembly and disassembly were symmetrical, self‐reinforcing processes that together were capable of generating key attributes of network architecture. Plant and AMF species that had short indirect paths to others in the community (i.e. high centrality), rather than many direct interaction partners (i.e. high degree), were best able to attract new interaction partners and, in the case of AMF species, also to retain existing interactions with plants during retrogression. We then show using simulations that these non‐random patterns of attachment and detachment promote nestedness of the network. These results have implications for predicting extinction sequences, identifying focal points for invasions and suggesting trajectories for restoration.
This study proposes a simple route to obtain starch grafted copolymers from cassava and banana starches chemically modified with amphiphilic maleic anhydride-poly (ethylene glycol) methyl ether ...(Ma-mPEG). The starches were extracted from cassava (StC) and banana (StB) pulp and characterized by FTIR spectroscopy, amylose content, scanning electron microscope (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and average molecular weight. Starches were chemically modified with amphiphilic Ma-mPEG in three mass ratios 1:1, 1:2 and 1:3. Thermal behavior and interactions of Ma-mPEG/starch in the St-g-(Ma-mPEG) copolymers were studied by DSC and TGA. The Tg values showed a higher plasticizer effect in the copolymers obtained from StC. Films were formed from StC-g-(Ma-mPEG) and StB-g-(Ma-mPEG) copolymers, thermal and morphological properties were studied. An increase in the mass ratios of Ma-mPEG and the absence of the glycerol in the formulations formed homogeneous films. StC-g-(Ma-mPEG) 1:3 with 2% concentration showed a potential use as coating in strawberries, presenting a lower weight loss (15.5 ± 5.7%) than the control sample (18.6 ± 3.3%).
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•Starches from banana and cassava pulp were extracted and characterized. Cassava starch showed higher yield.•Starch-mPEG copolymers were synthesized, their thermal and morphological characterization was evaluated.•Cassava starch copolymers showed a higher plasticizer effect when mPEG increased.•Starch copolymers films were formed and characterized•The formulations prepared with cassava starch copolymers and free of glycerol showed potential application as coating.
Electrospun one dimensional (1D) and two dimensional (2D) carbon based polymer nanocomposites are studied in order to determine the effect provided by the two differently structured nanofillers on ...crystallinity and thermo-mechanical properties of the nanofibres. The nanomaterials studied are pristine carbon nanotubes, oxidised carbon nanotubes, reduced graphene oxide and graphene oxide. Functional groups associated with the order structure of the polymers are analysed by infrared and Raman spectroscopies; the morphology is studied by scanning electron microscopy and the crystallinity properties are investigated by differential scanning calorimetry and X-ray diffraction. Differences in crystallisation behaviour between 1D and 2D carbon based nanofibres are shown by their crystallinity degree and their crystal sizes. The nanocomposite crystal sizes perpendicular to the plane (100) decrease with nanofiller content in all cases. The crystallinity trend and crystal sizes are in accordance with storage modulus response. The results also suggest that functionalisation favours interfacial bonding and dispersion of the nanomaterials within the polymer matrix. As a consequence the number of nucleating sites increases which in turn decreases the crystal size in the nanocomposites. These features explain the improved thermo-mechanical properties in the nanocomposites.
An experimental investigation on the gasification of corncobs was conducted in an 18 kW pilot-scale fixed bed system for power generation. The main objective was to determine the effect of gasifying ...corncob mixtures with fines content (particle size below 10 mm) on the performance of the system. To achieve the objective, a 2× 3 factorial arrangement was developed. The analysis considered three resistive loads connected to the generator (4, 8, and 12 kW) and two different size ranges of biomass (one with 100% of chips within the actual recommended size (10–40 mm)) and the other with a content of 15% of fine particles (particle size below 10 mm).
An increase of 15% in fine material content in the feedstock and a stable electricity demand close to the rated capacity, significantly increased the temperature of the process and decreased the mean specific fuel consumption – SFC (2.06 kg/kWh at 67% of rated capacity). H2 and CO production increased by increasing reactor temperature, reaching concentrations of 16.7% and 17% respectively at the higher resistive load (12 kW). Cold gas efficiency varied in the range of 33.7%–37.0%, increasing slightly with the blend of fines content and higher applied load.
•Corncobs were tested in an 18-kW downdraft gasifier for power generation using different resistive loads (4, 8, and 12 kW).•Gasification performance was analyzed using biomass with a fraction of fine particles (particle size below 10 mm).•Gasification temperature, specific fuel consumption, cold gas efficiency, and gas composition were investigated.•Corncob mixtures with 15% of fine materials led to good syngas compositions without affecting the performance of the process.
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