Modulator Property of the Intrinsic Cortical Projection from Layer 6 to Layer 4

Layer 4 of the sensory neocortex receives widespread convergent inputs from thalamic, intracortical, and corticocortical sources. Yet, the relative information bearing roles for most of these pathways remain largely undefined. Here we show that the intracortical projections from layer 6 to layer 4 exhibit a physiological property that is consistent with a modulator role. Using in vitro slice preparations of the auditory and somatosensory cortices, we found that electrical stimulation or photostimulation of layer 6 elicits a prolonged depolarizing response that is attributable to the activation of group 1 metabotropic glutamate receptors. These results complement the known physiological properties of the layer 6 to layer 4 pathway, and further suggest that this pathway is not a principle conduit for information flow, but rather acts as a modulator of cortical activity

Drivers and Modulators in the Central Auditory Pathways

The classic view of auditory information flow depicts a simple serial route from the periphery through tonotopically-organized nuclei in the brainstem, midbrain and thalamus, ascending eventually to the neocortex. Yet, complicating this picture are numerous parallel ascending and descending pathways, whose roles in auditory processing are poorly defined. To address this ambiguity, we have identified several anatomical and physiological properties that distinguish the auditory glutamatergic pathways into two groups that we have termed “drivers” and “modulators”. Driver pathways are associated with information-bearing pathways, while modulator pathways modify these principal information streams. These properties illuminate the potential roles of some previously ill-defined auditory pathways, and may be extended further to categorize either unknown or mischaracterized pathways throughout the auditory system

Lattice Thermal Conductivity of Ultra High Temperature Ceramics ZrB2 and HfB2 from Atomistic Simulations

Atomistic Green-Kubo simulations are performed to evaluate the lattice thermal conductivity for single crystals of the ultra high temperature ceramics ZrB2 and HfB2 for a range of temperatures. Recently developed interatomic potentials are used for these simulations. Heat current correlation functions show rapid oscillations which can be identified with mixed metal-Boron optical phonon modes. Agreement with available experimental data is good

Multiscale Modeling of Ultra High Temperature Ceramics (UHTC) ZrB2 and HfB2: Application to Lattice Thermal Conductivity

We are developing a multiscale framework in computational modeling for the ultra high temperature ceramics (UHTC) ZrB2 and HfB2. These materials are characterized by high melting point, good strength, and reasonable oxidation resistance. They are candidate materials for a number of applications in extreme environments including sharp leading edges of hypersonic aircraft. In particular, we used a combination of ab initio methods, atomistic simulations and continuum computations to obtain insights into fundamental properties of these materials. Ab initio methods were used to compute basic structural, mechanical and thermal properties. From these results, a database was constructed to fit a Tersoff style interatomic potential suitable for atomistic simulations. These potentials were used to evaluate the lattice thermal conductivity of single crystals and the thermal resistance of simple grain boundaries. Finite element method (FEM) computations using atomistic results as inputs were performed with meshes constructed on SEM images thereby modeling the realistic microstructure. These continuum computations showed the reduction in thermal conductivity due to the grain boundary network

Multiscale Modeling of Grain Boundaries in ZrB2: Structure, Energetics, and Thermal Resistance

A combination of ab initio, atomistic and finite element methods (FEM) were used to investigate the structures, energetics and lattice thermal conductance of grain boundaries for the ultra high temperature ceramic ZrB2. Atomic models of idealized boundaries were relaxed using density functional theory. Information about bonding across the interfaces was determined from the electron localization function. The Kapitza conductance of larger scale versions of the boundary models were computed using non-equilibrium molecular dynamics. The interfacial thermal parameters together with single crystal thermal conductivities were used as parameters in microstructural computations. FEM meshes were constructed on top of microstructural images. From these computations, the effective thermal conductivity of the polycrystalline structure was determined

Clinical monitoring of tooth wear progression in patients over a period of one year using CAD/CAM

Purpose: The aim of this study was to clinically monitor the progression of tooth wear over a period of 1 year in a cohort of referred tooth wear patients through the use of a computer-aided design/ computer-assisted manufacture (CAD/CAM) scanner and a standardized scanning/assessment methodology. Materials and Methods: Polyether impressions were made of 11 participants (130 teeth) at baseline and at 1 year. Impressions were poured in type IV dental stone and the anterior teeth were 3D scanned. A surface-matching software was used to compare 1-year and baseline scans and identify any dimensional differences. Results: Parafunctional habits were reported by all patients. All participants exhibited tooth wear ≥ 140 μm in depth and extending to ≥ 280 μm in at least one tooth. Maxillary central incisors were the most commonly and severely affected teeth. Conclusion: The ability of the developed CAD/CAM scanning methodology in clinical monitoring of tooth wear was demonstrated. Further research is needed to assess its practicality in large-scale epidemiologic tooth wear studies

Structure-based inhibitors of amyloid beta core suggest a common interface with tau.

Alzheimer's disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tangles which track with cognitive decline in humans. Here, we report the crystal structure of an Aβ core segment determined by MicroED and in it, note characteristics of both fibrillar and oligomeric structure. Using this structure, we designed peptide-based inhibitors that reduce Aβ aggregation and toxicity of already-aggregated species. Unexpectedly, we also found that these inhibitors reduce the efficiency of Aβ-mediated tau aggregation, and moreover reduce aggregation and self-seeding of tau fibrils. The ability of these inhibitors to interfere with both Aβ and tau seeds suggests these fibrils share a common epitope, and supports the hypothesis that cross-seeding is one mechanism by which amyloid is linked to tau aggregation and could promote cognitive decline

Serologic Evidence of Lyssavirus Infections among Bats, the Philippines

Active surveillance for lyssaviruses was conducted among populations of bats in the Philippines. The presence of past or current Lyssavirus infection was determined by use of direct fluorescent antibody assays on bat brains and virus neutralization assays on bat sera. Although no bats were found to have active infection with a Lyssavirus, 22 had evidence of neutralizing antibody against the Australian bat lyssavirus (ABLV). Seropositivity was statistically associated with one species of bat, Miniopterus schreibersi. Results from the virus neutralization assays are consistent with the presence in the Philippines of a naturally occurring Lyssavirus related to ABLV