Activiteit

Global change is leading to warming, acidification, and oxygen loss in the ocean. In the Southern California Bight, an eastern boundary upwelling system, these stressors are exacerbated by the localized discharge of anthropogenically enhanced nutrients from a coastal population of 23 million people. #link# Here, we use simulations with a high-resolution, physical-biogeochemical model to quantify the link between terrestrial and atmospheric nutrients, organic matter, and carbon inputs and biogeochemical change in the coastal waters of the Southern California Bight. The model is forced by large-scale climatic drivers and a reconstruction of local inputs via rivers, wastewater outfalls, and atmospheric deposition; it captures the fine scales of ocean circulation along the shelf; and it is validated against a large collection of physical and biogeochemical observations. Local land-based and atmospheric inputs, enhanced by anthropogenic sources, drive a 79% increase in phytoplankton biomass, a 23% increase in primary production, and a nearly 44% increase in subsurface respiration rates along the coast in summer, reshaping the biogeochemistry of the Southern California Bight. Seasonal reductions in subsurface oxygen, pH, and aragonite saturation state, by up to 50 mmol m-3, 0.09, and 0.47, respectively, rival or exceed the global open-ocean oxygen loss and acidification since the preindustrial period. The biological effects of these changes on local fisheries, proliferation of harmful algal blooms, water clarity, and submerged aquatic vegetation have yet to be fully explored.Mechanical metamaterials are artificial composites that exhibit a wide range of advanced functionalities such as negative Poisson’s ratio, shape shifting, topological protection, multistability, extreme strength-to-density ratio, and enhanced energy dissipation. In particular, flexible metamaterials often harness zero-energy deformation modes. To date, such flexible metamaterials have a single property, for example, a single shape change, or are pluripotent, that is, they can have many different responses, but typically require complex actuation protocols. Here, we introduce a class of oligomodal metamaterials that encode a few distinct properties that can be selectively controlled under uniaxial compression. To demonstrate this concept, we introduce a combinatorial design space containing various families of metamaterials. These families include monomodal (i.e., with a single zero-energy deformation mode); oligomodal (i.e., with a constant number of zero-energy deformation modes); and plurimodal (i.e., with many zero-energy deformation modes), whose number increases with system size. We then confirm the multifunctional nature of oligomodal metamaterials using both boundary textures and viscoelasticity. In particular, we realize a metamaterial that has a negative (positive) Poisson’s ratio for low (high) compression rate over a finite range of strains. The ability of our oligomodal metamaterials to host multiple mechanical responses within a single structure paves the way toward multifunctional materials and devices.The goal of cancer-drug delivery is to achieve high levels of therapeutics within tumors with minimal systemic exposure that could cause toxicity. Producing biologics directly in situ where they diffuse and act locally is an attractive alternative to direct administration of recombinant therapeutics, as secretion by the tumor itself provides high local concentrations that act in a paracrine fashion continuously over an extended duration (paracrine delivery). We have engineered a SHielded, REtargeted ADenovirus (SHREAD) gene therapy platform that targets specific cells based on chosen surface markers and converts them into biofactories secreting therapeutics. In GW441756 supplier of concept, a clinically approved antibody is delivered to orthotopic tumors in a model system in which precise biodistribution can be determined using tissue clearing with passive CLARITY technique (PACT) with high-resolution three-dimensional imaging and feature quantification within the tumors made transparent. We demonstrate high levels of tumor cell-specific transduction and significant and durable antibody production. PACT gives a localized quantification of the secreted therapeutic and allows us to directly observe enhanced pore formation in the tumor and destruction of the intact vasculature. In situ production of the antibody led to an 1,800-fold enhanced tumor-to-serum antibody concentration ratio compared to direct administration. Our detailed biochemical and microscopic analyses thus show that paracrine delivery with SHREAD could enable the use of highly potent therapeutic combinations, including those with systemic toxicity, to reach adequate therapeutic windows.Understanding how the young infant brain starts to categorize the flurry of ambiguous sensory inputs coming in from its complex environment is of primary scientific interest. Here, we test the hypothesis that senses other than vision play a key role in initiating complex visual categorizations in 20 4-mo-old infants exposed either to a baseline odor or to their mother’s odor while their electroencephalogram (EEG) is recorded. Various natural images of objects are presented at a 6-Hz rate (six images/second), with face-like object configurations of the same object categories (i.e., eliciting face pareidolia in adults) interleaved every sixth stimulus (i.e., 1 Hz). In the baseline odor context, a weak neural categorization response to face-like stimuli appears at 1 Hz in the EEG frequency spectrum over bilateral occipitotemporal regions. Critically, this face-like-selective response is magnified and becomes right lateralized in the presence of maternal body odor. This reveals that nonvisual cues systematically associated with human faces in the infant’s experience shape the interpretation of face-like configurations as faces in the right hemisphere, dominant for face categorization. At the individual level, this intersensory influence is particularly effective when there is no trace of face-like categorization in the baseline odor context. These observations provide evidence for the early tuning of face-(like)-selective activity from multisensory inputs in the developing brain, suggesting that perceptual development integrates information across the senses for efficient category acquisition, with early maturing systems such as olfaction driving the acquisition of categories in later-developing systems such as vision.