Cortical circuit principles predict patterns of trauma induced tauopathy in humans.

Connections in the cortex of diverse mammalian species are predicted reliably by the Structural Model for direction of pathways and signal processing (reviewed in ). The model is rooted in the universal principle of cortical systematic variation in laminar structure and has been supported widely for connection patterns in animals but has not yet been tested for humans. Here, in brains of individuals neuropathologically diagnosed with chronic traumatic encephalopathy (CTE) we studied whether the hyperphosphorylated tau (p-tau) pathology parallels connection sequence in time by circuit mechanisms.

Optical coherence tomography holds promise to transform the diagnostic anatomic pathology gross evaluation process.

Significance: Real-time histology can close a variety of gaps in tissue diagnostics. Currently, gross pathology analysis of excised tissue is dependent upon visual inspection and palpation to identify regions of interest for histopathological processing. Such analysis is limited by the variable correlation between macroscopic and microscopic findings.

Shortwave infrared spatial frequency domain imaging for non-invasive measurement of tissue and blood optical properties.

Significance: The shortwave infrared (SWIR) optical window (∼900 to 2000 nm) has attracted interest for deep tissue imaging due to the lower scattering of light. SWIR spatial frequency domain imaging (SWIR SFDI) provides wide-field tissue optical property measurements in this wavelength band. Key design and performance characteristics, such as portability, wavelength selection, measurement resolution, and the effect of skin have not yet been addressed for SWIR SFDI.

High optode-density wearable diffuse optical probe for monitoring paced breathing hemodynamics in breast tissue.

Significance: Diffuse optical imaging (DOI) provides in vivo quantification of tissue chromophores such as oxy- and deoxyhemoglobin (HbO2 and HHb, respectively). These parameters have been shown to be useful for predicting neoadjuvant treatment response in breast cancer patients. However, most DOI devices designed for the breast are nonportable, making frequent longitudinal monitoring during treatment a challenge.

Modulation frequency selection and efficient look-up table inversion for frequency domain diffuse optical spectroscopy.

Significance: Frequency domain diffuse optical spectroscopy (FD-DOS) uses intensity modulated light to measure the absorption and reduced scattering coefficients of turbid media such as biological tissue. Some FD-DOS instruments utilize a single modulation frequency, whereas others use hundreds of frequencies. The effect of modulation frequency choice and measurement bandwidth on optical property (OP) extraction accuracy has not yet been fully characterized.

Evaluation of the prognostic value of GDF-15, ABC-AF-bleeding score and ABC-AF-death score in patients with atrial fibrillation across different geographical areas.

Objectives: Growth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk.

Interferometric diffuse correlation spectroscopy improves measurements at long source-detector separation and low photon count rate.

Significance: The use of diffuse correlation spectroscopy (DCS) has shown efficacy in research studies as a technique capable of noninvasively monitoring blood flow in tissue with applications in neuromonitoring, exercise science, and breast cancer management. The ability of DCS to resolve blood flow in these tissues is related to the optical sensitivity and signal-to-noise ratio (SNR) of the measurements, which in some cases, particularly adult cerebral blood flow measurements, is inadequate in a significant portion of the population. Improvements to DCS sensitivity and SNR could allow for greater clinical translation of this technique.

Diffuse correlation spectroscopy measurements of blood flow using 1064 nm light.

Significance: Diffuse correlation spectroscopy (DCS) is an established optical modality that enables noninvasive measurements of blood flow in deep tissue by quantifying the temporal light intensity fluctuations generated by dynamic scattering of moving red blood cells. Compared with near-infrared spectroscopy, DCS is hampered by a limited signal-to-noise ratio (SNR) due to the need to use small detection apertures to preserve speckle contrast. However, DCS is a dynamic light scattering technique and does not rely on hemoglobin contrast; thus, there are significant SNR advantages to using longer wavelengths (>1000  nm) for the DCS measurement due to a variety of biophysical and regulatory factors.

OpenSFDI: an open-source guide for constructing a spatial frequency domain imaging system.

: Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (μ) and reduced scattering () on a pixel-by-pixel basis. Measurements of μ at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, three-wavelength SFDI system capable of quantifying μ and as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue.

Comparison of Measured and Simulated Urban Soil Hydrologic Properties.

Urban communities use hydrologic models to plan for and assess the effectiveness of stormwater control measures. Although emphasis is placed on soils as permeable surfaces that regulate the rainfall-runoff process, representative soil hydrologic parameters for urban areas are rare. The extent to which measured and commonly simulated hydrologic data may differ is also largely uncharacterized.

Entorhinal volume, aerobic fitness, and recognition memory in healthy young adults: A voxel-based morphometry study.

Converging evidence supports the hypothesis effects of aerobic exercise and environmental enrichment are beneficial for cognition, in particular for hippocampus-supported learning and memory. Recent work in humans suggests that exercise training induces changes in hippocampal volume, but it is not known if aerobic exercise and fitness also impact the entorhinal cortex. In animal models, aerobic exercise increases expression of growth factors, including brain derived neurotrophic factor (BDNF).

THink: Inferring Cognitive Status from Subtle Behaviors.

The Digital Clock Drawing Test is a fielded application that provides a major advance over existing neuropsychological testing technology. It captures and analyzes high precision information about both outcome and process, opening up the possibility of detecting subtle cognitive impairment even when test results appear superficially normal. We describe the design and development of the test, document the role of AI in its capabilities, and report on its use over the past seven years.

THink: Inferring Cognitive Status from Subtle Behaviors.

The Digital Clock Drawing Test is a fielded application that provides a major advance over existing neuropsychological testing technology. It captures and analyzes high precision information about both outcome and process, opening up the possibility of detecting subtle cognitive impairment even when test results appear superficially normal. We describe the design and development of the test, document the role of AI in its capabilities, and report on its use over the past seven years.

Reduction of eotaxin production and eosinophil recruitment by pulmonary autologous macrophage transfer in a cockroach allergen-induced asthma model.

We sought to investigate the effects of cockroach allergen (CRA) exposure on the lung macrophage population to determine how different macrophage phenotypes influence exacerbation of disease. CRA exposure caused significantly reduced expression of CD86 on lung macrophages. These effects were not systemic, as peritoneal macrophage CD86 expression was not altered.

Glucose-dependent insulinotropic polypeptide regulates dipeptide absorption in mouse jejunum.

Glucose-dependent insulinotropic polypeptide (GIP) secreted from jejunal mucosal K cells augments insulin secretion and plays a critical role in the pathogenesis of obesity and Type 2 diabetes mellitus. In recent studies, we have shown GIP directly activates Na-glucose cotransporter-1 (SGLT1) and enhances glucose absorption in mouse jejunum. It is not known whether GIP would also regulate other intestinal nutrient absorptive processes.

A New Distributed Algorithm for Side-Chain Positioning in the Process of Protein Docking.

is an important component of computational protein docking methods. Existing SCP methods and available software have been designed for protein folding applications where side-chain positioning is also important. As a result they do not take into account significant special structure that SCP for docking exhibits.

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema.

The relation between the progression of chronic obstructive pulmonary disease (COPD) and exacerbations is unclear. Currently, no animal model of acute exacerbation of COPD (AECOPD) exists. The objectives of this study were to evaluate the effects of mechanical forces induced by deep inspirations (DIs) on short-term deterioration of lung structure and function to mimic AECOPD.

Spatial variation in membrane excitability modulated by 4-AP-sensitive K+ channels in the axons of the crayfish neuromuscular junction.

Current-clamp recordings were made from the primary (1°) and secondary (2°) branching points (BPs) of axons at the crayfish neuromuscular junction. Action potential (AP) firing initiated by current injected at the 2° BP showed strong adaptation or high-frequency firing at threshold current, whereas AP firing frequency at the 1° BP exhibited a gradual rise with increasing current amplitude. The voltage threshold for AP (V(TH)) was higher at the 2° BP than the 1° BP.

Orai1 and Ca2+-independent phospholipase A2 are required for store-operated Icat-SOC current, Ca2+ entry, and proliferation of primary vascular smooth muscle cells.

Store-operated Ca(2+) entry (SOCE) is important for multiple functions of vascular smooth muscle cells (SMC), which, depending of their phenotype, can resemble excitable and nonexcitable cells. Similar to nonexcitable cells, Orai1 was found to mediate Ca(2+)-selective (CRAC-like) current and SOCE in dedifferentiated cultured SMC and smooth muscle-derived cell lines. However, the role of Orai1 in cation-selective store-operated channels (cat-SOC), which are responsible for SOCE in primary SMC, remains unclear.

Modeling the dynamics of airway constriction: effects of agonist transport and binding.

Recent advances have revealed that during exogenous airway challenge, airway diameters cannot be adequately predicted by their initial diameters. Furthermore, airway diameters can also vary greatly in time on scales shorter than a breath. To better understand these phenomena, we developed a multiscale model that allowed us to simulate aerosol challenge in the airways during ventilation.

Tidal stretches do not modulate responsiveness of intact airways in vitro.

Studies on isolated tracheal airway smooth muscle (ASM) strips have shown that length/force fluctuations, similar to those likely occurring during breathing, will mitigate ASM contractility. These studies conjecture that, solely by reducing length oscillations on a healthy, intact airway, one can create airway hyperresponsiveness, but this has never been explicitly tested. The intact airway has additional complexities of geometry and structure that may impact its relevance to isolated ASM strips.

Actin polymerization in differentiated vascular smooth muscle cells requires vasodilator-stimulated phosphoprotein.

Our group has previously shown that vasoconstrictors increase net actin polymerization in differentiated vascular smooth muscle cells (dVSMC) and that increased actin polymerization is linked to contractility of vascular tissue (Kim et al., Am J Physiol Cell Physiol 295: C768-778, 2008). However, the underlying mechanisms are largely unknown.

Freud's dreams of reason: the Kantian structure of psychoanalysis.

Freud (and later commentators) have failed to explain how the origins of psychoanalytical theory began with a positivist investment without recognizing a dual epistemological commitment: simply, Freud engaged positivism because he believed it generally equated with empiricism, which he valued, and he rejected "philosophy," and, more specifically, Kantianism, because of the associated transcendental qualities of its epistemology. But this simple dismissal belies a deep investment in Kant's formulation of human reason, in which rationality escapes natural cause and thereby bestows humans with cognitive and moral autonomy. Freud also segregated human rationality: he divided the mind between (1) an unconscious grounded in the biological and thus subject to its own laws, and (2) a faculty of autonomous reason, lodged in consciousness and free of natural forces to become the repository of interpretation and free will.

Estimating the diameter of airways susceptible for collapse using crackle sound.

Airways that collapse during deflation generate a crackle sound when they reopen during subsequent reinflation. Since each crackle is associated with the reopening of a collapsed airway, the likelihood of an airway to be a crackle source is identical to its vulnerability to collapse. To investigate this vulnerability of airways to collapse, crackles were recorded during the first inflation of six excised rabbit lungs from the collapsed state, and subsequent reinflations from 5, 2, 1, and 0 cmH(2)O end-expiratory pressure levels.