Molecular Understanding of the Enhancement in Organic Aerosol Mass at High Relative Humidity.

The mechanistic pathway by which high relative humidity (RH) affects gas-particle partitioning remains poorly understood, although many studies report increased secondary organic aerosol (SOA) yields at high RH. Here, we use real-time, molecular measurements of both the gas and particle phase to provide a mechanistic understanding of the effect of RH on the partitioning of biogenic oxidized organic molecules (from α-pinene and isoprene) at low temperatures (243 and 263 K) at the CLOUD chamber at CERN. We observe increases in SOA mass of 45 and 85% with increasing RH from 10-20 to 60-80% at 243 and 263 K, respectively, and attribute it to the increased partitioning of semi-volatile compounds. At 263 K, we measure an increase of a factor 2-4 in the concentration of C10H16O2-3, while the particle-phase concentrations of low-volatility species, such as C10H16O6-8, remain almost constant. This results in a substantial shift in the chemical composition and volatility distribution toward less oxygenated and more volatile species at higher RH (e.g., at 263 K, O/C ratio = 0.55 and 0.40, at RH = 10 and 80%, respectively). By modeling particle growth using an aerosol growth model, which accounts for kinetic limitations, we can explain the enhancement in the semi-volatile fraction through the complementary effect of decreased compound activity and increased bulk-phase diffusivity. Our results highlight the importance of particle water content as a diluting agent and a plasticizer for organic aerosol growth.

Empathy-based counterspeech can reduce racist hate speech in a social media field experiment.

Despite heightened awareness of the detrimental impact of hate speech on social media platforms on affected communities and public discourse, there is little consensus on approaches to mitigate it. While content moderation-either by governments or social media companies-can curb online hostility, such policies may suppress valuable as well as illicit speech and might disperse rather than reduce hate speech. As an alternative strategy, an increasing number of international and nongovernmental organizations (I/NGOs) are employing counterspeech to confront and reduce online hate speech. Despite their growing popularity, there is scant experimental evidence on the effectiveness and design of counterspeech strategies (in the public domain). Modeling our interventions on current I/NGO practice, we randomly assign English-speaking Twitter users who have sent messages containing xenophobic (or racist) hate speech to one of three counterspeech strategies-empathy, warning of consequences, and humor-or a control group. Our intention-to-treat analysis of 1,350 Twitter users shows that empathy-based counterspeech messages can increase the retrospective deletion of xenophobic hate speech by 0.2 SD and reduce the prospective creation of xenophobic hate speech over a 4-wk follow-up period by 0.1 SD. We find, however, no consistent effects for strategies using humor or warning of consequences. Together, these results advance our understanding of the central role of empathy in reducing exclusionary behavior and inform the design of future counterspeech interventions.

Preclinical Assessment of a MUC12-Targeted BiTE (Bispecific T-cell Engager) Molecule.

MUC12 is a transmembrane mucin that is highly expressed in >50% of primary and metastatic colorectal tumors. MUC12 is also expressed by normal epithelial cells of the colon and small intestine. Although MUC12 localization in normal epithelial cells is restricted to the apical membrane, expression in tumors is depolarized and shows broad membrane localization. The differential localization of MUC12 in tumor cells as compared with normal cells makes it a potential therapeutic target. Here, we evaluated targeting of MUC12 with a BiTE (bispecific T-cell engager) molecule. We generated a panel of proof-of-concept half-life extended (HLE) BiTE molecules that bind MUC12 on tumor cells and CD3 on T cells. We prioritized one molecule based on in vitro activity for further characterization in vivo In vitro, the MUC12 HLE BiTE molecule mediated T-cell-redirected lysis of MUC12-expressing cells with half-maximal lysis of 4.4 ± 0.9 to 117 ± 78 pmol/L. In an exploratory cynomolgus monkey toxicology study, the MUC12 HLE BiTE molecule administered at 200 µg/kg with a step dose to 1,000 µg/kg was tolerated with minimal clinical observations. However, higher doses were not tolerated, and there was evidence of damage in the gastrointestinal tract, suggesting dose levels projected to be required for antitumor activity may be associated with on-target toxicity. Together, these data demonstrate that the apically restricted expression of MUC12 in normal tissues is accessible to BiTE molecule target engagement and highlight the difficult challenge of identifying tumor-selective antigens for solid tumor T-cell engagers.

Bedside hand vein inspection for noninvasive central venous pressure assessment.

Rapid estimates of the central venous pressure (CVP) can be helpful to administer early fluid therapy or to manage cardiac preload in intensive care units, operating rooms or emergency rooms in order to start and monitor an adequate medical therapy. Invasive CVP measurements have inherent and non-negligible complication rates as well as great expenditures. Several noninvasive methods of CVP measurements, like ultrasound-guided techniques, are available, but require trained skills and special equipment which might not be at hand in all situations. Our purpose was to evaluate the feasibility and accuracy of CVP estimates assessed upon the height of hand veins collapse (HVC) using invasively measured CVP as the gold standard. The HVC was determined by slowly lifting the patient's hand while watching the dorsal hand veins to collapse. The vertical distance from the dorsal hand to a transducer air zero port was noted and converted to mmHg. The observer was blinded to the simultaneously measured CVP values, which were categorized as low (<7 mmHg), normal (7-12 mmHg) and high (>12 mmHg). Measurements were performed in 82 patients who had a median [IQR] age of 67 [60;74]. Median CVP was 12 [8;15] mmHg and the median absolute difference between the measured HVC and CVP was 4 [2;7] mmHg. The Spearman correlation coefficient between CVP and HVC was 0.55, 95%-CI [0.35;0.69]. Overall CVP categorization was correct in 45% of the cases. HVC had a sensitivity of 92% for a low CVP with a negative predictive value of 98%. A high HVC had a sensitivity of 29% but a high specificity of 94% for a high CVP. The overall performance of observing the hand vein collapse to estimate CVP was only moderate in the intensive care setting. However, the median difference to the CVP was low and HVC identifies a low CVP with a high sensitivity and excellent negative predictive value.

Pain sensation in human osteoarthritic knee joints is strongly enhanced by diabetes mellitus.

The major burden of knee joint osteoarthritis (OA) is pain. Since in elder patients diabetes mellitus is an important comorbidity of OA, we explored whether the presence of diabetes mellitus has a significant influence on pain intensity at the end stage of knee OA, and we aimed to identify factors possibly related to changes of pain intensity in diabetic patients. In 23 diabetic and 47 nondiabetic patients with OA undergoing total knee arthroplasty, we assessed the pain intensity before the operation using the "Knee Injury and Osteoarthritis Outcome Score". Furthermore, synovial tissue, synovial fluid (SF), cartilage, and blood were obtained. We determined the synovitis score, the concentrations of prostaglandin E2 and interleukin-6 (IL-6) in the SF and serum, and of C-reactive protein and HbA1c and other metabolic parameters in the serum. We performed multivariate regression analyses to study the association of pain with several parameters. Diabetic patients had on average a higher Knee Injury and Osteoarthritis Outcome Score pain score than nondiabetic patients (P < 0.001). Knee joints from diabetic patients exhibited on average higher synovitis scores (P = 0.024) and higher concentrations of IL-6 in the SF (P = 0.003) than knee joints from nondiabetic patients. Multivariate regression analysis showed that patients with higher synovitis scores had more intense pain independent of all investigated confounders, and that the positive association between pain intensities and IL-6 levels was dependent on diabetes mellitus and/or synovitis. These data suggest that diabetes mellitus significantly increases pain intensity of knee OA, and that in diabetic patients higher pain intensities were determined by stronger synovitis.

Modeling and Simulation of Viscous Electro-Active Polymers.

Electro-active materials are capable of undergoing large deformation when stimulated by an electric field. They can be divided into electronic and ionic electro-active polymers (EAPs) depending on their actuation mechanism based on their composition. We consider electronic EAPs, for which attractive Coulomb forces or local re-orientation of polar groups cause a bulk deformation. Many of these materials exhibit pronounced visco-elastic behavior. Here we show the development and implementation of a constitutive model, which captures the influence of the electric field on the visco-elastic response within a geometrically non-linear finite element framework. The electric field affects not only the equilibrium part of the strain energy function, but also the viscous part. To adopt the familiar additive split of the strain from the small strain setting, we formulate the governing equations in the logarithmic strain space and additively decompose the logarithmic strain into elastic and viscous parts. We show that the incorporation of the electric field in the viscous response significantly alters the relaxation and hysteresis behavior of the model. Our parametric study demonstrates that the model is sensitive to the choice of the electro-viscous coupling parameters. We simulate several actuator structures to illustrate the performance of the method in typical relaxation and creep scenarios. Our model could serve as a design tool for micro-electro-mechanical systems, microfluidic devices, and stimuli-responsive gels such as artificial skin, tactile displays, or artificial muscle.