Summary TGF-β blockade significantly slows tumor growth through many mechanisms, including activation of CD8+ T-cells and macrophages. Here, we show that TGF-β blockade also increases neutrophil-attracting chemokines resulting in an influx of CD11b+/Ly6G+ tumor-associated neutrophils (TAN) that are hypersegmented, more cytotoxic to tumor cells, and express higher levels of pro-inflammatory cytokines. Accordingly, following TGF-β blockade, depletion of these neutrophils significantly blunts anti-tumor effects of treatment and reduces CD8+ T-cell activation. In contrast, in control tumors, neutrophil depletion decreases tumor growth and results in more activated CD8+ T-cells intra-tumorally. Together, these data suggest that TGF-β within the tumor microenvironment induces a population of TAN with a pro-tumor phenotype. TGF-β blockade results in the recruitment and activation of TAN with an anti-tumor phenotype.

Since emotions are expressed through a combination of verbal and nonverbal channels, a joint analysis of speech and gestures is required to understand expressive human communication. To facilitate such investigations, this paper describes a new corpus named the ''interactive emotional dyadic motion capture database'' (IEMOCAP), collected by the Speech Analysis and Interpretation Laboratory (SAIL) at the University of Southern California (USC). This database was recorded from ten actors in dyadic sessions with markers on the face, head, and hands, which provide detailed information about their facial expressions and hand movements during scripted and spontaneous spoken communication scenarios. The actors performed selected emotional scripts and also improvised hypothetical scenarios designed to elicit specific types of emotions (happiness, anger, sadness, frustration and neutral state). The corpus contains approximately 12 h of data. The detailed motion capture information, the interactive setting to elicit authentic emotions, and the size of the database make this corpus a valuable addition to the existing databases in the community for the study and modeling of multimodal and expressive human communication.

Management of prosthetic vascular graft infections caused by Pseudomonas aeruginosa can be a significant challenge to clinicians. These infections often do not resolve with antibiotic therapy alone due to antibiotic resistance/tolerance by bacteria, poor ability of antibiotics to permeate/reduce biofilms and/or other factors. Bacteriophage OMKO1 binding to efflux pump proteins in P. aeruginosa was consistent with an evolutionary trade-off: wildtype bacteria were killed by phage whereas evolution of phage-resistance led to increased antibiotic sensitivity. However, phage clinical-use has not been demonstrated. Here, we present a case report detailing therapeutic application of phage OMKO1 to treat a chronic P. aeruginosa infection of an aortic Dacron graft with associated aorto-cutaneous fistula. Following a single application of phage OMKO1 and ceftazidime, the infection appeared to resolve with no signs of recurrence.

We investigated the fusion of high-speed liquid droplets as a way to record the kinetics of liquid-phase chemical reactions on the order of microseconds. Two streams of micrometer-size droplets collide with one another. The droplets that fused (13 μm in diameter) at the intersection of the two streams entered the heated capillary inlet of a mass spectrometer. The mass spectrum was recorded as a function of the distance x between the mass spectrometer inlet and the droplet fusion center. Fused droplet trajectories were imaged with a high-speed camera, revealing that the droplet fusion occurred approximately within a 500-μm radius from the droplet fusion center and both the size and the speed of the fused droplets remained relatively constant as they traveled from the droplet fusion center to the mass spectrometer inlet. Evidence is presented that the reaction effectively stops upon entering the heated inlet of the mass spectrometer. Thus, the reaction time was proportional to x and could be measured and manipulated by controlling the distance x. Kinetic studies were carried out in fused water droplets for acid-induced unfolding of cytochrome c and hydrogen-deuterium exchange in bradykinin. The kinetics of the former revealed the slowing of the unfolding rates at the early stage of the reaction within 50 μs. The hydrogendeuterium exchange revealed the existence of two distinct populations with fast and slow exchange rates. These studies demonstrated the power of this technique to detect reaction intermediates in fused liquid droplets with microsecond temporal resolution.mass spectrometry | liquid microdroplets | reaction kinetics | protein unfolding | hydrogen-deuterium isotope exchange T ime-resolved measurements of reaction intermediates are crucial for understanding the fast kinetics of chemical reactions. Various approaches have been implemented to improve the temporal resolution of kinetic measurements in liquid reactions (1, 2), which are often limited by the mixing time. One approach for improving the mixing time involves the use of turbulent flow to increase the shear stress in fluid channels (3). Another approach is to stimulate the rapid initiation of a reaction by photo-triggered initiation (4), electron transfer (5), or temperature jump/rise (6). A small-size reactor was also used for rapid mixing so that the time required for diffusion-dependent mixing is minimized (7-10).Among various methods for detecting reaction intermediates, mass spectrometry has been a powerful tool for probing reaction products because it can discriminate similar species by their mass-to-charge ratio while simultaneously measuring multiple species. Time-resolved mass spectrometry (11) has been widely used for measuring the kinetics of protein-ligand complexation, organometallic compound formation, and enzyme-catalyzed processes. Despite these efforts for improving temporal resolution, time-resolved mass spectrometry has been limited to the millisecond timescale, with a recent achievement of 300 μs (12).A major obstacle for imp...

Background Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications. Methods We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres—including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes—were collected by Northwestern University (Chicago, IL, USA) and analysed. Findings Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41–51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19. Interpretation The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients. Funding National Institutes of Health. Video Abstract Early outcomes after lung transplantation for severe COVID-19