In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

/pdf/engineering-precision-nanoparticles-for-drug-delivery-2rxrncxb99.pdf

Engineering precision nanoparticles for drug delivery

Place and grid cells in the hippocampal formation provide foundational representations of environmental location, and potentially of locations within conceptual spaces. Some accounts predict that environmental sensory information and self-motion are encoded in complementary representations, while other models suggest that both features combine to produce a single coherent representation. Here, we use virtual reality to dissociate visual environmental from physical motion inputs, while recording place and grid cells in mice navigating virtual open arenas. Place cell firing patterns predominantly reflect visual inputs, while grid cell activity reflects a greater influence of physical motion. Thus, even when recorded simultaneously, place and grid cell firing patterns differentially reflect environmental information (or ‘states’) and physical self-motion (or ‘transitions’), and need not be mutually coherent. Place cells and grid cells are known to encode spatial information about an animal’s location relative to the surrounding environment. Here, the authors show that place cells predominantly encode environmental sensory inputs, while grid cell activity reflects a greater influence of physical motion.

/pdf/differential-influences-of-environment-and-self-motion-on-2q46moy92h.pdf

Differential influences of environment and self-motion on place and grid cell firing.

Let X(t) be the number of tumor cells at time t, and Pr{X(t) = n} = pn(t) is the density of X. A “birth”, i.e., an increase of one of the total population of cancer cells, can occur either by mutation of a normal cell caused by the action of the carcinogen, consisting of randomly (Poisson) distributed hits, or by reproduction of existing cancer cells. A death of a tumor cell occurs as an additive combination of non-immunological and immunological elements. Once a tumor is initiated by carcinogenic action, it undergoes a birth and death process with infinitesimal birth rate linear and infinitesimal death rate composed of a linear and a nonlinear term, the former due to non-immunological deaths, the latter to immunological feedback. The death rate per tumor cell due to immunological response is proportional to the total number of antigen-producing (tumor) cells; thus, the total death rate is quadratic. Although this assumes a very simple mechanism for the action of immunological feedback, it is nevertheless a first step.

The Mathematical Model

All-solid-state lithium ion batteries (ASSLBs) are considered next-generation devices for energy storage due to their advantages in safety and potentially high energy density. As the key component in ASSLBs, solid-state electrolytes (SSEs) with non-flammability and good adaptability to lithium metal anodes have attracted extensive attention in recent years. Among the current SSEs, composite solid-state electrolytes (CSSEs) with multiple phases have greater flexibility to customize and combine the advantages of single-phase electrolytes, which have been widely investigated recently and regarded as promising candidates for commercial ASSLBs. Based on existing investigations, herein, we present a comprehensive overview of the recent developments in CSSEs. Initially, we introduce the historical development from solid-state ionic conductors to CSSEs, and then summarize the fundamentals including mechanisms of lithium ion transport, key evaluation parameters, design principles, and key materials. Four main types of advanced structures for CSSEs are classified and highlighted according to the recent progress. Moreover, advanced characterization and computational simulation techniques including machine learning are reviewed for the first time, and the main challenges and perspectives of CSSEs are also provided for their future development.

A review of composite solid-state electrolytes for lithium batteries: fundamentals, key materials and advanced structures.

The Tolman-Eichenbaum Machine: Unifying Space and Relational Memory through Generalization in the Hippocampal Formation.

We present a mouse virtual reality (VR) system which restrains head-movements to horizontal rotations, compatible with multi-photon imaging. This system allows expression of the spatial navigation and neuronal firing patterns characteristic of real open arenas (R). Comparing VR to R: place and grid, but not head-direction, cell firing had broader spatial tuning; place, but not grid, cell firing was more directional; theta frequency increased less with running speed, whereas increases in firing rates with running speed and place and grid cells' theta phase precession were similar. These results suggest that the omni-directional place cell firing in R may require local-cues unavailable in VR, and that the scale of grid and place cell firing patterns, and theta frequency, reflect translational motion inferred from both virtual (visual and proprioceptive) and real (vestibular translation and extra-maze) cues. By contrast, firing rates and theta phase precession appear to reflect visual and proprioceptive cues alone.

Spatial cell firing during virtual navigation of open arenas by head-restrained mice.

We present a mouse virtual reality (VR) system which restrains head-movements to horizontal rotations, potentially compatible with multi-photon imaging. We show that this system allows expression of the spatial navigational behaviour and neuronal firing patterns characteristic of real open arenas (R). Place and grid, but not head-direction, cell firing had broader spatial tuning in VR than R. Theta frequency increased less with running speed in VR than in R, while firing rates increased similarly in both. Place, but not grid, cell firing was more directional in VR than R. These results suggest that the scale of grid and place cell firing patterns, and the frequency of theta, reflect translational motion inferred from both virtual (visual and proprioceptive) cues and uncontrolled static (vestibular translation and extra-maze) cues, while firing rates predominantly reflect visual and proprioceptive motion. They also suggest that omni-directional place cell firing in R reflects local cues unavailable in VR.

https://www.biorxiv.org/content/biorxiv/early/2018/01/11/246744.full.pdf

Yi Lu

Papers

Differential influences of environment and self-motion on place and grid cell firing.

Spatial cell firing during virtual navigation of open arenas by head-restrained mice.

Spatial cell firing during virtual navigation of open arenas by head-restrained mice