Polymeric cGAMP microparticles affect the immunogenicity of a broadly active influenza mRNA lipid nanoparticle vaccine.

Influenza outbreaks are a major burden worldwide annually. While seasonal vaccines do provide protection against infection, they are limited in that they need to be updated every year to account for the constantly mutating virus. Recently, lipid nanoparticles (LNPs) encapsulating mRNA have seen major success as a vaccine platform for SARS-CoV-2. Herein, we applied LNPs to deliver an mRNA encoding a computationally optimized broadly active (COBRA) influenza immunogen. These COBRA mRNA LNPs induced a broadly active neutralizing antibody response and protection after lethal influenza challenge. To further increase the immunogenicity of the COBRA mRNA LNPs, we combined them with acetalated dextran microparticles encapsulating a STING agonist. Contrary to recent findings, the STING agonist decreased the immunogenicity of the COBRA mRNA LNPs which was likely due to a decrease in mRNA translation as shown in vitro. Overall, this work aids in future selection of adjuvants to use with mRNA LNP vaccines.

Enhancement of subunit vaccine delivery with zinc-carnosine coordination polymer through the addition of mannan.

Vaccines represent a pivotal health advancement for preventing infection. However, because carrier systems with repeated administration can invoke carrier-targeted immune responses that diminish subsequent immune responses (e.g., PEG antibodies), there is a continual need to develop novel vaccine platforms. Zinc carnosine microparticles (ZnCar MPs), which are composed of a one-dimensional coordination polymer formed between carnosine and the metal ion zinc, have exhibited efficacy in inducing an immune response against influenza. However, ZnCar MPs' limited suspendability hinders clinical application. In this study, we address this issue by mixing mannan, a polysaccharide derived from yeast, with ZnCar MPs. We show that the addition of mannan increases the suspendability of this promising vaccine formulation. Additionally, since mannan is an adjuvant, we illustrate that the addition of mannan increases the antibody response and T cell response when mixed with ZnCar MPs. Mice vaccinated with mannan + OVA/ZnCar MPs had elevated serum IgG and IgG1 levels in comparison to vaccination without mannan. Moreover, in the mannan + OVA/ZnCar MPs vaccinated group, mucosal washes demonstrated increased IgG, IgG1, and IgG2c titers, and antigen recall assays showed enhanced IFN-γ production in response to MHC-I and MHC-II immunodominant peptide restimulation, compared to the vaccination without mannan. These findings suggest that the use of mannan mixed with ZnCar MPs holds potential for subunit vaccination and its improved suspendability further promotes clinical translation.

Immunogenicity of an adjuvanted broadly active influenza vaccine in immunocompromised and diverse populations.

Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies are inadequate due to antigenic drift/shift of the virus and the elicitation of low immune responses. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert the constantly mutating viruses; however, they are poorly immunogenic on their own. To increase the immunogenicity of subunit vaccines such as this, adjuvants can be delivered with the vaccine. For example, agonists of the stimulator of interferon genes (STING) have proven efficacy as vaccine adjuvants. However, their use in high-risk populations most vulnerable to influenza virus infection has not been closely examined. Here, we utilize a vaccine platform consisting of acetalated dextran microparticles loaded with COBRA HA and the STING agonist cyclic GMP-AMP. We examine the immunogenicity of this platform in mouse models of obesity, aging, and chemotherapy-induced immunosuppression. Further, we examine vaccine efficacy in collaborative cross mice, a genetically diverse population that mimics human genetic heterogeneity. Overall, this vaccine platform had variable efficacy in these populations supporting work to better tailor adjuvants to specific populations.

Giant Left Ventricular Thrombus Formation in the Setting of Severe Aortic Stenosis and Heavy Cigarette Smoking.

The harmful effects of cigarette smoking on the human body have been well documented. However, whether tobacco use is an independent risk factor of valvular heart disease remains debatable. Cigarette smoking has been associated with an inflammatory state and increased levels of tumor necrosis factor alpha, which in turn activates protein kinases involved in ventricular remodeling. Subsequent ventricular dysfunction predisposes to the formation of mural thrombi which may lead to further worsening of hemodynamics. We present a case of severe aortic stenosis and giant left ventricular thrombus formation associated with chronic cigarette smoking.

Rapid iceberg calving following removal of tightly packed pro-glacial mélange.

Iceberg calving is a major contributor to Greenland's ice mass loss. Pro-glacial mélange (a mixture of sea ice, icebergs, and snow) may be tightly packed in the long, narrow fjords that front many marine-terminating glaciers and can reduce calving by buttressing. However, data limitations have hampered a quantitative understanding. We develop a new radar-based approach to estimate time-varying elevations near the mélange-glacier interface, generating a factor of three or more improvement in elevation precision. We apply the technique to Jakobshavn Isbræ, Greenland's major outlet glacier. Over a one-month period in early summer 2016, the glacier experienced essentially no calving, and was buttressed by an unusually thick mélange wedge that increased in thickness towards the glacier front. The extent and thickness of the wedge gradually decreased, with large-scale calving starting once the mélange mass within 7 km of the glacier front had decreased by >40%.

Nuisance Flooding and Relative Sea-Level Rise: the Importance of Present-Day Land Motion.

Sea-level rise is beginning to cause increased inundation of many low-lying coastal areas. While most of Earth's coastal areas are at risk, areas that will be affected first are characterized by several additional factors. These include regional oceanographic and meteorological effects and/or land subsidence that cause relative sea level to rise faster than the global average. For catastrophic coastal flooding, when wind-driven storm surge inundates large areas, the relative contribution of sea-level rise to the frequency of these events is difficult to evaluate. For small scale "nuisance flooding," often associated with high tides, recent increases in frequency are more clearly linked to sea-level rise and global warming. While both types of flooding are likely to increase in the future, only nuisance flooding is an early indicator of areas that will eventually experience increased catastrophic flooding and land loss. Here we assess the frequency and location of nuisance flooding along the eastern seaboard of North America. We show that vertical land motion induced by recent anthropogenic activity and glacial isostatic adjustment are contributing factors for increased nuisance flooding. Our results have implications for flood susceptibility, forecasting and mitigation, including management of groundwater extraction from coastal aquifers.

Recent increases in Arctic freshwater flux affects Labrador Sea convection and Atlantic overturning circulation.

The Atlantic Meridional Overturning Circulation (AMOC) is an important component of ocean thermohaline circulation. Melting of Greenland's ice sheet is freshening the North Atlantic; however, whether the augmented freshwater flux is disrupting the AMOC is unclear. Dense Labrador Sea Water (LSW), formed by winter cooling of saline North Atlantic water and subsequent convection, is a key component of the deep southward return flow of the AMOC. Although LSW formation recently decreased, it also reached historically high values in the mid-1990s, making the connection to the freshwater flux unclear. Here we derive a new estimate of the recent freshwater flux from Greenland using updated GRACE satellite data, present new flux estimates for heat and salt from the North Atlantic into the Labrador Sea and explain recent variations in LSW formation. We suggest that changes in LSW can be directly linked to recent freshening, and suggest a possible link to AMOC weakening.

An Intensive Observation of Calving at Helheim Glacier, East Greenland.

Calving of glacial ice into the ocean from the Greenland Ice Sheet is an important component of global sea level rise. The calving process itself is relatively poorly observed, understood, and modeled; as such, it represents a bottleneck in improving future global sea level estimates in climate models. We organized a pilot project to observe the calving process at Helheim Glacier in East Greenland in an effort to better understand it. During an intensive one-week survey, we deployed a suite of instrumentation including a terrestrial radar interferometer, GPS receivers, seismometers, tsunameters, and an automated weather station. This effort captured a calving process and measured various glaciological, oceanographic, and atmospheric parameters before, during, and after the event. One outcome of our observations is evidence that the calving process actually consists of a number of discrete events, spread out over time, in this instance over at least two days. This time span has implications for models of the process. Realistic projections of future global sea level will depend on accurate parametrization of calving, which will require more sustained observations.

Earthquake and tsunami forecasts: relation of slow slip events to subsequent earthquake rupture.

The 5 September 2012 M(w) 7.6 earthquake on the Costa Rica subduction plate boundary followed a 62-y interseismic period. High-precision GPS recorded numerous slow slip events (SSEs) in the decade leading up to the earthquake, both up-dip and down-dip of seismic rupture. Deeper SSEs were larger than shallower ones and, if characteristic of the interseismic period, release most locking down-dip of the earthquake, limiting down-dip rupture and earthquake magnitude. Shallower SSEs were smaller, accounting for some but not all interseismic locking. One SSE occurred several months before the earthquake, but changes in Mohr-Coulomb failure stress were probably too small to trigger the earthquake. Because many SSEs have occurred without subsequent rupture, their individual predictive value is limited, but taken together they released a significant amount of accumulated interseismic strain before the earthquake, effectively defining the area of subsequent seismic rupture (rupture did not occur where slow slip was common). Because earthquake magnitude depends on rupture area, this has important implications for earthquake hazard assessment. Specifically, if this behavior is representative of future earthquake cycles and other subduction zones, it implies that monitoring SSEs, including shallow up-dip events that lie offshore, could lead to accurate forecasts of earthquake magnitude and tsunami potential.

On the importance of path for phase unwrapping in synthetic aperture radar interferometry.

Phase unwrapping is a key procedure in interferometric synthetic aperture radar studies, translating ambiguous phase observations to topography, and surface deformation estimates. Some unwrapping algorithms are conducted along specific paths based on different selection criteria. In this study, we analyze six unwrapping paths: line scan, maximum coherence, phase derivative variance, phase derivative variance with branch-cut, second-derivative reliability, and the Fisher distance. The latter is a new path algorithm based on Fisher information theory, which combines the phase derivative with the expected variance to get a more robust path, potentially performing better than others in the case of low image quality. In order to compare only the performance of the paths, the same unwrapping function (phase derivative integral) is used. Results indicate that the Fisher distance algorithm gives better results in most cases.

Selection of image fusion quality measures: objective, subjective, and metric assessment.

Accurate quality assessment of fused images, such as combined visible and infrared radiation images, has become increasingly important with the rise in the use of image fusion systems. We bring together three approaches, applying two objective tasks (local target analysis and global target location) to two scenarios, together with subjective quality ratings and three computational metrics. Contrast pyramid, shift-invariant discrete wavelet transform, and dual-tree complex wavelet transform fusion are applied, as well as levels of JPEG2000 compression. The differing tasks are shown to be more or less appropriate for differentiating among fusion methods, and future directions pertaining to the creation of task-specific metrics are explored.

Assessment of fused videos using scanpaths: a comparison of data analysis methods.

The increased interest in image fusion (combining images of two or more modalities such as infrared and visible light radiation) has led to a need for accurate and reliable image assessment methods. Previous work has often relied upon subjective quality ratings combined with some form of computational metric analysis. However, we have shown in previous work that such methods do not correlate well with how people perform in actual tasks utilising fused images. The current study presents the novel use of an eye-tracking paradigm to record how accurately participants could track an individual in various fused video displays. Participants were asked to track a man in camouflage outfit in various input videos (visible and infrared originals, a fused average of the inputs; and two different wavelet-based fused videos) whilst also carrying out a secondary button-press task. The results were analysed in two ways, once calculating accuracy across the whole video, and by dividing the video into three time sections based on video content. Although the pattern of results depends on the analysis, the accuracy for the inputs was generally found to be significantly worse than that for the fused displays. In conclusion, both approaches have good potential as new fused video assessment methods, depending on what task is carried out.

Space geodesy: subsidence and flooding in New Orleans.

It has long been recognized that New Orleans is subsiding and is therefore susceptible to catastrophic flooding. Here we present a new subsidence map for the city, generated from space-based synthetic-aperture radar measurements, which reveals that parts of New Orleans underwent rapid subsidence in the three years before Hurricane Katrina struck in August 2005. One such area is next to the Mississippi River-Gulf Outlet (MRGO) canal, where levees failed during the peak storm surge: the map indicates that this weakness could be explained by subsidence of a metre or more since their construction.