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Ibuprofen is a non-steroidal, anti-inflammatory drug that is widely prescribed for its analgesic, antipyretic, and anti-inflammatory actions to treat pain, symptoms of rheumatoid arthritis and fever, but it is also known to cause stomach-related side effects. The development of efficient drug delivery systems for this compound to prevent these side effects is hampered by its poor water solubility. In this work, we show that graphite oxide and its derivatives have great potential as effective drug delivery systems not only to overcome side effects but also to increase the short biological half-life of ibuprofen. We studied the adsorption capacity of graphite oxide and carboxylated and sulfonated graphene oxide for this drug and its release in simulated gastric and intestinal fluid. The obtained compounds were characterized by X-ray diffraction, thermogravimetric analysis and Fourier transform infrared spectroscopy. DFT calculations were conducted to elucidate the Ibuprofen/host interactions, to establish which properties of these carbon nanomaterials control the loading and release, as well as to provide a better understanding of the orientation of the drug molecules on the single-layer GO.

This study presents part of the results of the CALISHTO campaign (Cloud-AerosoL InteractionS in the Helmos Background TropOsphere) that took place in autumn 2021 at the free-troposphere high-altitude Helmos station (2314 m a.s.l.). A Time-of-Flight Aerosol Chemical Speciation Monitor (ToF-ACSM, Aerodyne) was deployed among other instruments (AE31, PVM-100, SMPS, EC/OC analyzer) in the framework of the campaign. The chemical characterization of the non-refractory PM1 (NR-PM1), the influence from the Boundary Layer / Free Troposphere, the origin of the incoming masses and the influence of clouds were studied. The sources of PM1 including the non-refractory species of ACSM (organics and inorganics) combined with the equivalent black carbon were also investigated by applying the PMF model to the combined dataset. The results showed that there is a great variability of aerosol characteristics depending on the height of the PBL and the origin of the air masses. During September the station was exposed to PBL emissions, and thus displayed much higher mass concentrations of NR-PM1 than October and November. Concerning the sources of PM1, different types were identified with ammonium sulphate and oxygenated organics being predominant, as expected for aged aerosol with the degree of ageing investigated against air mass origin and microphysical parameters.

It is well established that the Aerosol-Cloud Interaction (ACI) processes play a key-role in global precipitation and are a strong modulator of cloud radiative forcing and climate, and yet remain poorly understood despite decades of research. Aerosol-cloud interactions are one of the most uncertain aspects of anthropogenic climate change (Seinfeld et al., 2016a; IPCC, 2021).Global datasets on cloud microphysical state – especially droplet number concentration and size distribution – provide important constraints that are required for reducing the ACI uncertainty. Recently, Quaas et al. (2020) showed that satellite remote sensing is the only approach that offers the potential of obtaining global datasets with frequent coverage; current retrieval algorithms, however, carry many uncertainties and require constraints that can only be addressed with in situ and/or ground-based remote sensing observations.Our study aims to evaluate retrievals of cloud droplet number (Nd), effective radius (reff) and optical thickness provided by the CLoud property dAtAset using SEVIRI - Edition 3 (CLAAS-3) cloud products of Satellite Application Facility on Climate Monitoring (CM SAF). For this reason, we used co-located in-situ measurements of aerosols and cloud dynamical properties in conjunction with remote sensing observations at the high-altitude regional background station Hellenic Atmospheric Aerosol and Climate Change (HAC2) during the Cloud-AerosoL InteractionS in the Helmos background TropOsphere (CALISHTO) campaign, which took place from Fall 2021 to Spring 2022 at Mount Helmos in Peloponnese, Greece (https://calishto.panacea-ri.gr/).In this study, we adopt an approach first applied to droplet retrievals in an urban environment (Foskinis et al. 2022). Ground-based remote sensing instrumentation involved includes a Doppler depolarization lidar (HALO) at 1550 nm to provide the vertical velocity (w) of the air masses, a Doppler cloud radar at 94 GHz (RPG) to provide the equivalent reflectivity factor (Z), and the mean Doppler velocity (VD), and a radiometer at 89 GHz provides the liquid water path (LWP). Furthermore, the in-situ instrumentations employed a co-located scanning Mobility Particle Size (SMPS) measuring the size distribution of submicron aerosol, and a Time-of-Flight Aerosol Chemical Speciation Monitor (ToF-ACSM) to provide the aerosol chemical composition of the aerosols. The in-situ dataset together with the airmass vertical velocity distributions are used as input to a state-of-the art parameterization to predict the droplet number (Nd) in clouds formed in the vicinity of the HAC2 station. Retrievals with the the CLAAS-3 cloud properties product from CMSAF are then evaluated with in-situ observations carried out with a cloud probe instrument (PVM-100) and the droplet number calculations.Compared to our previous study (Foskinis et al. 2022), this study is implemented in a different physical system, where we examined again the dependence of the Spectral Dispersion of Droplets (SDD) on Nd and we found a new optimized expression between SDD-Nd which can be used on the established droplet number retrieval algorithm (Bennartz et al., 2007) for non-precipitating planetary boundary layer clouds in order to mitigate the bias.

Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of 50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;KrasG12D mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo. In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624–34. ©2016 AACR.

Fig S1. Phospho-aspirin inhibits the growth of human PC cells. Figure S2. Phospho-aspirin induces apoptosis in human PC cells. Figure S3. Phospho-aspirin induces p53 acetylation in human PC cells and xenografts. Figure S4: PA does not inhibit PGE2 levels in PC cells. Figure S5. Expression levels of phospho-EGFR (p-EGFR) in multiple human PC cells. Figure S6. Phospho-aspirin inhibits EGFR phosphorylation in PC cells. Figure S7. Serum amylase and lipase levels. Figure S8. Representative images of acinar cells explants at day 0 and the resulting metaplasia (day 5).

En este trabajo, analizo las funciones más frecuentemente atribuidas a la responsabilidad civil. Sostendré que la única función distintiva es la implementación de la justicia interpersonal. El resto de las funciones pueden ser satisfechas por otras instituciones con igual o mayor éxito que la responsabilidad civil. Finalmente, intento mostrar que algunas funciones, sin ser distintivas, son necesarias, en tanto una vez se pone en marcha un sistema de responsabilidad, estas se cumplen indefectiblemente.

Supplemental material

Remote sensing has been a key resource for developing extensive and detailed datasets for studying and constraining aerosol-cloud-climate interactions. However, aerosol-cloud collocation challenges, algorithm limitations, as well as difficulties in unraveling dynamic from aerosol-related effects on cloud microphysics, have long challenged precise retrievals of cloud droplet number concentrations. By combining a series of remote sensing techniques and in situ measurements at ground level, we developed a semi-automated approach that can address several retrieval issues for a robust estimation of cloud droplet number for non-precipitating Planetary Boundary Layer (PBL) clouds. The approach is based on satellite retrievals of the PBL cloud droplet number (Ndsat) using the geostationary meteorological satellite data of the Optimal Cloud Analysis (OCA) product, which is obtained by the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) of the European Organization for the Exploitation of Meteorological Satellites (EUMETSAT). The parameters of the retrieval are optimized through closure with droplet number obtained from a combination of ground-based remote sensing data and in situ observations at ground level. More specifically, the remote sensing data are used to retrieve cloud-scale vertical velocity, and the in situ aerosol measurements at ground level were used constrain as input to a state-of-the-art droplet activation parameterization to predict the respective Cloud Condensation Nuclei (CCN) spectra, cloud maximum supersaturation and droplet number concentration (Nd), accounting for the effects of vertical velocity distribution and lateral entrainment. Closure studies between collocated Nd and Ndsat are then used to evaluate exising droplet spectral width parameters used for the retrieval of droplet number, and determine the optimal values for retrieval. This methodology, used to study aerosol-cloud interactions for non-precipitating clouds formed over the Athens Metropolitan Area (AMA), Greece from March to May 2020, shows that droplet closure can be achieved to within 30%, comparable to the level of closure obtained in many in situ studies. Given this, the ease of applying this approach with satellite data obtained from SEVIRI with high temporal (15 min) and spatial resolution (3.6 km × 4.6 km), opens the possibility of continuous and reliable Ndsat, giving rise to high value datasets for aerosol-cloud-climate interaction studies.

En este breve escrito presento una concepción de la responsabilidad civil entendida como una forma de responsabilidad interpersonal. En primer lugar, intento brindar una caracterización de la práctica, identificando el problema que aborda la responsabilidad civil, examinando en qué se diferencia de otras formas de responsabilidad y cuál es su modo típico de operar. En segundo lugar, me centro en su estructura, a fin de analizar las normas que son distintivas de la práctica, cómo están relacionadas entre sí y con otras normas que, sin ser distintivas, son necesarias para su funcionamiento.

Purpose: To identify a new cortical vitreous segmentation protocol for non invasive standardised investigation of Neovascularisation (NV) with detection of regression of NV activity in Proliferative Diabetic Retinopathy (PDR). Design: Retrospective study. Participants: One hundred and eighty-six eyes of 93 consecutive diabetic patients (mean age: 52.6 ± 11.0 years) imaged using Topcon Triton® Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) from June 2015 to January 2017. Methods: Scans were performed through the macula, optic disc and areas of possible NV in mid-peripheral retina using 6 × 6 mm and/or 9 × 9 mm raster-patterns in three segmentation protocols: Vitreo-Retinal (VRS), Outer-Vitreous (OVS) and Core-Vitreous Segmentation (CVS). Any suspicion of PDR was confirmed in all patients by Heidelberg® Widefield-Fundus-Fluorescein-Angiography (WF-FFA) and/or Optos® Ultra-WF-FFA (UWF-FFA). Inter-observer reproducibility of NV diagnosis and agreement between SS-OCTA and UWF-FFA were assessed. Primary outcome was the identification of an effective and reproducible segmentation protocol. Secondary outcome was the identification of NV regression after treatment. Results: Sensitivity-specificity reached, respectively, the value of 100 to 100 in detecting NVD, and 96.6 to 100 in detecting NVE in compared areas. SS-OCTA was able to confirm absence of blood flow within the residual NV plexus when using VRS protocol in 30 eyes in which regression of NV with absence of leakage was documented on FFA. Conclusion: Three segmentation protocols (VRS, OVS and CVS) with different but complementary characteristics, allowed a reproducible and standardised investigation of NVD and NVE. The proposed new SS-OCTA cortical vitreous segmentation protocols may be of value when identifying and assessing NV-activity (VRS, OVS and CVS) or NV-regression (VRS) in PDR and therefore, response to therapy.