Electrophysiological and morphological heterogeneity of slow firing neurons in medial septal/diagonal band complex as revealed by cluster analysis

Slow firing septal neurons modulate hippocampal and neocortical functions. Electrophysiologically, it is unclear whether slow firing neurons belong to a homogeneous neuronal population. To address this issue, whole-cell patch recordings and neuronal reconstructions were performed on rat brain slices containing the medial septum/diagonal band complex (MS/DB). Slow firing neurons were identified by their low firing rate at threshold (\u3c 5Hz) and lack of time-dependent inward rectification (Ih). Unsupervised cluster analysis was used to investigate whether slow firing neurons could be further classified into different subtypes. The parameters used for the cluster analysis included latency for first spike, slow afterhyperpolarizing potential, maximal frequency and action potential (AP) decay slope. Neurons were grouped into three major subtypes. The majority of neurons (55%) were grouped as cluster I. Cluster II (17% of neurons) exhibited longer latency for generation of the first action potential (246.5±20.1 ms). Cluster III (28% of neurons) exhibited higher maximal firing frequency (25.3±1.7 Hz) when compared to cluster I (12.3±0.9 Hz) and cluster II (11.8±1.1 Hz) neurons. Additionally, cluster III neurons exhibited faster action potentials at suprathreshold. Interestingly, cluster II neurons were frequently located in the medial septum whereas neurons in cluster I and III appeared scattered throughout all MS/DB regions. Sholl’s analysis revealed a more complex dendritic arborization in cluster III neurons. Cluster I and II neurons exhibited characteristics of “true” slow firing neurons whereas cluster III neurons exhibited higher frequency firing patterns. Several neurons were labeled with a cholinergic marker, Cy3-conjugated 192 IgG (p75NTR), and cholinergic neurons were found to be distributed among the three clusters. Our findings indicate that slow firing medial septal neurons are heterogeneous and that soma location is an important determinant of their electrophysiological properties. Thus, slow firing neurons from different septal regions have distinct functional properties, most likely related to their diverse connectivity

Temperature Effects in the Composition of Metal Halide Perovskite thin Films

Metal halide perovskites have shown to be a structure with great promise as an efficient photovoltaic, but at the same time it is affected by instability problems that degrade their performance. Degradation mechanisms vary with temperature, moisture, oxidation, and energy conversion during light exposure. We study performance loss due to temperature by probing diffusion of elemental composition across the thickness of films produced by spin coating and for temperatures ranging from 20 to 200°C. X-ray reflectivity was used to identify the electron density, composition, and quality of the films, aided with X-ray fluorescence and X-ray photoelectron spectroscopy studies to obtain information about degradation of the organic phase of the films

Medial septal beta-amyloid 1-40 injections alter septo-hippocampal anatomy and function

Degeneration of septal neurons in Alzheimer’s disease (AD) results in abnormal information processing at cortical circuits and consequent brain dysfunction. The septum modulates the activity of hippocampal and cortical circuits and is crucial to the initiation and occurrence of oscillatory activities such as the hippocampal theta rhythm. Previous studies suggest that amyloid β peptide (Aβ) accumulation may trigger degeneration in AD. This study evaluates the effects of single injections of Aβ 1–40 into the medial septum. Immunohistochemistry revealed a decrease in septal cholinergic (57%) and glutamatergic (53%) neurons in Aβ 1–40 treated tissue. Additionally, glutamatergic terminals were significantly less in Aβ treated tissue. In contrast, septal GABAergic neurons were spared. Unitary recordings from septal neurons and hippocampal field potentials revealed an approximately 50% increase in firing rates of slow firing septal neurons during theta rhythm and large irregular amplitude (LIA) hippocampal activities and a significantly reduced hippocampal theta rhythm power (49%) in Aβ 1–40 treated tissue. Aβ also markedly reduced the proportion of slow firing septal neurons correlated to the hippocampal theta rhythm by 96%. These results confirm that Aβ alters the anatomy and physiology of the medial septum contributing to septohippocampal dysfunction. The Aβ induced injury of septal cholinergic and glutamatergic networks may contribute to an altered hippocampal theta rhythm which may underlie the memory loss typically observed in AD patients

Quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes

Background: Novel therapies in metastatic cancers have contributed to improvements in survival outcomes, yet real-world data suggest that improvements may be mainly driven by those patient groups who already had the highest survival outcomes. This study aimed to develop and apply a framework for quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes based on published aggregate data.Methods: Nine (N = 9) novel therapies for metastatic breast cancer (mBC), metastatic colorectal cancer (mCRC), and metastatic non–small cell lung cancer (mNSCLC) were identified, 3 for each cancer type. Individual patient data (IPD) for overall survival (OS) and progression-free survival (PFS) were replicated from published Kaplan-Meier (KM) curves. For each cancer type, data were pooled for the novel therapies and comparators separately and weighted based on sample size to ensure equal contribution of each therapy in the analyses. Parametric (mixture) distributions were fitted to the weighted data to model and extrapolate survival. The inequality in survival was defined by the absolute difference between groups with the highest and lowest survival for 2 stratifications: one for which survival was stratified into 2 groups and one using 5 groups. Additionally, a linear regression model was fitted to survival estimates for the 5 groups, with the regression coefficient or slope considered as the inequality gradient (IG). The impact of the pooled novel therapies was subsequently defined as the change in survival inequality relative to the pooled comparator therapies. A probabilistic analysis was performed to quantify parameter uncertainty.Results: The analyses found that novel therapies were associated with significant increases in inequalities in survival outcomes relative to their comparators, except in terms of OS for mNSCLC. For mBC, the inequalities in OS increased by 13.9 (95% CI: 1.4; 26.6) months, or 25.0%, if OS was stratified in 5 groups. The IG for mBC increased by 3.2 (0.3; 6.1) months, or 24.7%. For mCRC, inequalities increased by 6.7 (3.0; 10.5) months, or 40.4%, for stratification based on 5 groups; the IG increased by 1.6 (0.7; 2.4) months, or 40.2%. For mNSCLC, inequalities decreased by 14.9 (−84.5; 19.0) months, or 12.2%, for the 5-group stratification; the IG decreased by 2.0 (−16.1; 5.1) months, or 5.5%. Results for the stratification based on 2 groups demonstrated significant increases in OS inequality for all cancer types. In terms of PFS, the increases in survival inequalities were larger in a relative sense compared with OS. For mBC, PFS inequalities increased by 8.7 (5.9; 11.6) months, or 71.7%, for stratification based on 5 groups; the IG increased by 2.0 (1.3; 2.6) months, or 67.6%. For mCRC, PFS inequalities increased by 5.4 (4.2; 6.6) months, or 147.6%, for the same stratification. The IG increased by 1.3 (1.1; 1.6) months, or 172.7%. For mNSCLC, inequalities increased by 18.2 (12.5; 24.4) months, or 93.8%, for the 5-group stratification; the IG increased by 4.0 (2.8; 5.4) months, or 88.1%. Results from the stratification based on 2 groups were similar.Conclusion: Novel therapies for mBC, mCRC, and mNSCLC are generally associated with significant increases in survival inequalities relative to their comparators in randomized controlled trials, though inequalities in OS for mNSCLC decreased nonsignificantly when stratified based on 5 groups. Although further research using real-world IPD is warranted to assess how, for example, social determinants of health affect the impact of therapies on health inequalities among patient groups, the proposed framework can provide important insights in the absence of such data

Fatigue Endurance Investigation of Post-processed Surfaces of LPBF Ti-6Al-4V under Flexural Stress

Numerous research works can be found focusing on fatigue properties of AM components, however most of this literature is focused on uniaxial testing. Because the very few actual components under uniaxial loading conditions found in any application, it is also important to investigate fatigue performance under loads that produce combined stresses, such as bending. This project investigates the fatigue endurance of LPBF Ti-6Al-4V specimens subjected to four different surface finishing prost-processes (milled, ground, polished and abrasive media). The test consisted of a force-controlled cyclic load applied on the specimen in a 4-point bending setup until fracture. The study incorporated mechanical and optical techniques to measure and quantify the characteristic surface roughness of the post-processes. Additionally, failure mechanisms are discussed on fractographs. The data analyses suggested that internal defects commonly present in additively manufactured parts had a more significant impact on the fatigue life than surface roughness of post-processed parts.Mechanical Engineerin

EXPLORING IN718 ALLOY PRODUCTION WITH BI-DIRECTIONAL RASTER AND STOCHASTIC SPOT MELTING TECHNIQUES USING AN OPEN-SOURCE ELECTRON MELTING SYSTEM

This study compares the fabrication of IN718 alloy using bi-directional raster and stochastic spot melting techniques with the open-source FreemeltOne Electron Beam Melting (EBM) system. The research aimed to produce dense parts using both scanning strategies, employing custom Python code for raster melt beam path generation and PixelMelt software for stochastic spot melting path generation. After optimizing process parameters, 10mm height builds for each scanning strategy were fabricated, and their microstructure, hardness, and density were analyzed using optical microscopy and SEM, Vickers microhardness scale, and a pycnometer. The findings reveal valuable insights into the effects of scanning strategies on the microstructure, hardness, and density of IN718 alloy components, advancing additive manufacturing knowledge.Mechanical Engineerin

Effect of molecular and electronic structure on the light harvesting properties of dye sensitizers

The systematic trends in structural and electronic properties of perylene diimide (PDI) derived dye molecules have been investigated by DFT calculations based on projector augmented wave (PAW) method including gradient corrected exchange-correlation effects. TDDFT calculations have been performed to study the visible absorbance activity of these complexes. The effect of different ligands and halogen atoms attached to PDI were studied to characterize the light harvesting properties. The atomic size and electronegativity of the halogen were observed to alter the relaxed molecular geometries which in turn influenced the electronic behavior of the dye molecules. Ground state molecular structure of isolated dye molecules studied in this work depends on both the halogen atom and the carboxylic acid groups. DFT calculations revealed that the carboxylic acid ligands did not play an important role in changing the HOMO-LUMO gap of the sensitizer. However, they serve as anchor between the PDI and substrate titania surface of the solar cell or photocatalyst. A commercially available dye-sensitizer, ruthenium bipyridine (RuBpy), was also studied for electronic and structural properties in order to make a comparison with PDI derivatives for light harvesting properties. Results of this work suggest that fluorinated, chlorinated, brominated, and iyodinated PDI compounds can be useful as sensitizers in solar cells and in artificial photosynthesis.Comment: Single pdf file, 14 pages with 7 figures and 4 table

Vessel Shrinkage as a Sign of Atherosclerosis Progression in Type 2 Diabetes : A Serial Intravascular Ultrasound Analysis

OBJECTIVE—The aim of this study was to determine the natural history of vascular remodeling of atherosclerotic plaques in patients with type 2 diabetes and the predictors of vessel shrinkage