Synthetic Nanoparticles for Vaccines and Immunotherapy

The immune system plays a critical role in our health. No other component of human physiology plays a decisive role in as diverse an array of maladies, from deadly diseases with which we are all familiar to equally terrible esoteric conditions: HIV, malaria, pneumococcal and influenza infections; cancer; atherosclerosis; autoimmune diseases such as lupus, diabetes, and multiple sclerosis. The importance of understanding the function of the immune system and learning how to modulate immunity to protect against or treat disease thus cannot be overstated. Fortunately, we are entering an exciting era where the science of immunology is defining pathways for the rational manipulation of the immune system at the cellular and molecular level, and this understanding is leading to dramatic advances in the clinic that are transforming the future of medicine.1,2 These initial advances are being made primarily through biologic drugs– recombinant proteins (especially antibodies) or patient-derived cell therapies– but exciting data from preclinical studies suggest that a marriage of approaches based in biotechnology with the materials science and chemistry of nanomaterials, especially nanoparticles, could enable more effective and safer immune engineering strategies. This review will examine these nanoparticle-based strategies to immune modulation in detail, and discuss the promise and outstanding challenges facing the field of immune engineering from a chemical biology/materials engineering perspectiveNational Institutes of Health (U.S.) (Grants AI111860, CA174795, CA172164, AI091693, and AI095109)United States. Department of Defense (W911NF-13-D-0001 and Awards W911NF-07-D-0004

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Thermal Analysis of the Formation of Chunky Graphite during Solidification of Heavy-section Spheroidal Graphite Iron Parts

Analysis of cooling curves recorded at the centre of large blocks cast with near-eutectic spheroidal graphite cast irons prone to give chunky graphite has been checked against microstructure observations. It has been observed that solidification proceeds totally at temperatures lower than the stable eutectic temperature and the following solidification sequence could be proposed: 1) nucleation of primary graphite in the liquid; 2) initial eutectic reaction processing by growth of austenite-like dendrites encapsulating the primary nodules; 3) bulk eutectic reaction related to nucleation and then growth of CHG cells and of secondary nodules, these latter giving spheroidal graphite eutectic cells. It was found that the maximum recalescence during the eutectic reaction first increases with the volume of the block affected by chunky graphite, and then decreases when most of the material is affected. Interestingly enough, a relationship between the volume of the blocks affected by CHG and the recalescence measured on TA cups has been observed

Silurian sedimentation in the South Qilian Belt: arc‐continent collision‐related deposition in the NE Tibet Plateau?

The South Qilian belt mainly comprises an early Paleozoic arc‐ophiolite complex, accretionary prism, micro‐continental block, and foreland basin. These elements represent accretion‐collision during Cambrian to Silurian time in response to closure of the Proto‐Tethyan Ocean in the NE of the present‐day Tibet Plateau. Closure of the Proto‐Tethyan Ocean between the Central Qilian block and the Oulongbuluke block and the associated collision took place from NE to SW in a zipper‐like style. Sediment would have been dispersed longitudinally SW‐ward with a progressive facies migration from marginal alluvial sediments toward slope deep‐water and deep‐sea turbidites. This migration path indicates an ocean basin that shrank toward the SW. The Balonggongga’er Formation in the western South Qilian belt represents the fill of a latest Ordovician‐Silurian remnant ocean basin that separated the Oulongbuluke block from the Central Qilian block, and records Silurian closure of the Proto‐Tethyan Ocean and subduction beneath the Central Qilian block. However, alluvial deposits in the Lajishan area were accumulated in a retro‐foreland basin, indicating that continent‐continent collision in the eastern South Qilian belt occurred at c. 450‐440 Ma. These results demonstrate that the Proto‐Tethyan Ocean closed diachronously during early Paleozoic time