Protein expression patterns and metal metabolites in a protogynous hermaphrodite fish, the ricefield eel (Monopterus albus).

BACKGROUND: The ricefield eel Monopterus albus undergoes a natural sex change from female to male during its life cycle, and previous studies have shown the potential mechanisms of this transition at the transcriptional and protein levels. However, the changes in protein levels have not been fully explored, especially in the intersexual stage. RESULTS: In the present study, the protein expression patterns in the gonadal tissues from five different periods, the ovary (OV), early intersexual stage gonad (IE), middle intersexual stage gonad (IM), late intersexual stage gonad (IL), and testis (TE), were determined by untargeted proteomics sequencing. A total of 5125 proteins and 394 differentially expressed proteins (DEPs) were detected in the gonadal tissues. Of the 394 DEPs, there were 136 between the OV and IE groups, 20 between the IM and IE groups, 179 between the IL and IM groups, and 59 between the TE and IL groups. Three candidate proteins, insulin-like growth factor 2 mRNA-binding protein 3 isoform X1 (Igf2bp3), triosephosphate isomerase (Tpi), and Cu-Zn superoxide dismutase isoform X1 [(Cu-Zn) Sod1], were validated by western blotting to verify the reliability of the data. Furthermore, metal metabolite-related proteins were enriched in the IL vs. IM groups and TE vs. IL groups, which had close relationships with sex change, including Cu2+-, Ca2+-, Zn2+- and Fe2+/Fe3+-related proteins. Analysis of the combined transcriptome data revealed consistent protein/mRNA expression trends for two metal metabolite-related proteins/genes [LOC109953912 and calcium Binding Protein 39 Like (cab39l)]. Notably, we detected significantly higher levels of Cu2+ during the sex change process, suggesting that Cu2+ is a male-related metal metabolite that may have an important function in male reproductive development. CONCLUSIONS: In summary, we analyzed the protein profiles of ricefield eel gonadal tissues in five sexual stages (OV, IE, IM, IL, and TE) and verified the plausibility of the data. After preforming the functional enrichment of metal metabolite-related DEPs, we detected the contents of the metal metabolites Zn2+, Cu2+, Ca2+, and Fe2+/Fe3+ at these five stages and screened for (Cu-Zn) Sod1 and Mmp-9 as possible key proteins in the sex reversal process.

Population structure and adaptability analysis of Schizothorax o'connori based on whole-genome resequencing.

BACKGROUND: Schizothorax o'connori is an endemic fish distributed in the upper and lower reaches of the Yarlung Zangbo River in China. It has experienced a fourth round of whole gene replication events and is a good model for exploring the genetic differentiation and environmental adaptability of fish in the Qinghai-Tibet Plateau. The uplift of the Qinghai-Tibet Plateau has led to changes in the river system, thereby affecting gene exchange and population differentiation between fish populations. With the release of fish whole genome data, whole genome resequencing has been widely used in genetic evolutionary analysis and screening of selected genes in fish, which can better elucidate the genetic basis and molecular environmental adaptation mechanisms of fish. Therefore, our purpose of this study was to understand the population structure and adaptive characteristics of S. o'connori using the whole-genome resequencing method. RESULTS: The results showed that 23,602,746 SNPs were identified from seven populations, mostly distributed on chromosomes 2 and 23. There was no significant genetic differentiation between the populations, and the genetic diversity was relatively low. However, the Zangga population could be separated from the Bomi, Linzhi, and Milin populations in the cluster analysis. Based on historical dynamics analysis of the population, the size of the ancestral population of S. o'connori was affected by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Glacial Age. The selected sites were mostly enriched in pathways related to DNA repair and energy metabolism. CONCLUSION: Overall, the whole-genome resequencing analysis provides valuable insights into the population structure and adaptive characteristics of S. o'connori. There was no obvious genetic differentiation at the genome level between the S. o'connori populations upstream and downstream of the Yarlung Zangbo River. The current distribution pattern and genetic diversity are influenced by the late accelerated uplift of the Qinghai Tibet Plateau and the Fourth Ice Age. The selected sites of S. o'connori are enriched in the energy metabolism and DNA repair pathways to adapt to the low temperature and strong ultraviolet radiation environment at high altitude.

FoxH1 Represses the Promoter Activity of cyp19a1a in the Ricefield Eel (Monopterus albus).

Forkhead box H1 (FoxH1) is a sexually dimorphic gene in Oreochromis niloticus, Oplegnathus fasciatus, and Acanthopagrus latus, indicating that it is essential for gonadal development. In the present study, the molecular characteristics and potential function of FoxH1 and the activation of the cyp19a1a promoter in vitro were evaluated in Monopterus albus. The levels of foxh1 in the ovaries were three times higher than those in the testes and were regulated by gonadotropins (Follicle-Stimulating Hormone and Human Chorionic Gonadotropin). FoxH1 colocalized with Cyp19a1a in the oocytes and granulosa cells of middle and late vitellogenic follicles. In addition, three FoxH1 binding sites were identified in the proximal promoter of cyp19a1a, namely, FH1 (-871/-860), FH2 (-535/-524), and FH3 (-218/-207). FoxH1 overexpression significantly attenuated the activity of the cyp19a1a promoter in CHO cells, and FH1/2 mutation increased promoter activity. Taken together, these results suggest that FoxH1 may act as an important regulator in the ovarian development of M. albus by repressing cyp19a1a promoter activity, which provides a foundation for the study of FoxH1 function in bony fish reproductive processes.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder. Mast cells play an important role in AD because they regulate allergic reactions and inflammatory responses. However, whether and how the modulation of mast cell activity affects AD has not been determined. In this study, we aimed to determine the effects and mechanisms of 3-O-cyclohexanecarbonyl-11-keto-ß-boswellic acid (CKBA). This natural compound derivative alleviates skin inflammation by inhibiting mast cell activation and maintaining skin barrier homeostasis in AD. CKBA markedly reduced serum IgE levels and alleviated skin inflammation in calcipotriol (MC903)-induced AD mouse model. CKBA also restrained mast cell degranulation both in vitro and in vivo. RNA-seq analysis revealed that CKBA downregulated the extracellular signal-regulated kinase (ERK) signaling in BM-derived mast cells activated by anti-2,4-dinitrophenol/2,4-dinitrophenol-human serum albumin. We proved that CKBA suppressed mast cell activation via ERK signaling using the ERK activator (t-butyl hydroquinone) and inhibitor (selumetinib; AZD6244) in AD. Thus, CKBA suppressed mast cell activation in AD via the ERK signaling pathway and could be a therapeutic candidate drug for AD.

A Shortened Model for Logan Reference Plot Implemented via the Self-Supervised Neural Network for Parametric PET Imaging.

Dynamic PET imaging provides superior physiological information than conventional static PET imaging. However, the dynamic information is gained at the cost of a long scanning protocol; this limits the clinical application of dynamic PET imaging. We developed a modified Logan reference plot model to shorten the acquisition procedure in dynamic PET imaging by omitting the early-time information necessary for the conventional reference Logan model. The proposed model is accurate theoretically, but the straightforward approach raises the sampling problem in implementation and results in noisy parametric images. We then designed a self-supervised convolutional neural network to increase the noise performance of parametric imaging, with dynamic images of only a single subject for training. The proposed method was validated via simulated and real dynamic [Formula: see text]-fallypride PET data. Results showed that it accurately estimated the distribution volume ratio (DVR) in dynamic PET with a shortened scanning protocol, e.g., 20 minutes, where the estimations were comparable with those obtained from a standard dynamic PET study of 120 minutes of acquisition. Further comparisons illustrated that our method outperformed the shortened Logan model implemented with Gaussian filtering, regularization, BM4D and the 4D deep image prior methods in terms of the trade-off between bias and variance. Since the proposed method uses data acquired in a short period of time upon the equilibrium, it has the potential to add clinical values by providing both DVR and Standard Uptake Value (SUV) simultaneously. It thus promotes clinical applications of dynamic PET studies when neuronal receptor functions are studied.

The early assessment of harmful algal bloom risk in the East China Sea.

The East China Sea (ECS) is seriously impacted by harmful algal blooms (HABs). Therefore, early assessments of HAB risk in this area are extremely important. Using long-term historical HAB observation data and satellite-derived sea surface temperatures (SSTs), we found that the annual number of HAB events was positively correlated with the mean March SST and negatively correlated with the SST change rate from March to July in nearshore waters (< 50 m). A simple method of HAB risk assessment was therefore proposed based on either March SST (threshold: 13 °C) or SST change rate (threshold: 3.6 °C/month). Validation against a k-means classification scheme indicated that the overall accuracy based on the March SST threshold was 85%, with a kappa coefficient of 0.69. The SST-based method facilitates the assessment of HAB risk in the ECS 1-2 months in advance, thus helping to reduce the damage caused by HABs.

A back-projection-and-filtering-like (BPF-like) reconstruction method with the deep learning filtration from listmode data in TOF-PET.

PURPOSE: The time-of-flight (TOF) information improves signal-to-noise ratio (SNR) for positron emission tomography (PET) imaging. Existing analytical algorithms for TOF PET usually follow a filtered back-projection process on reconstructing images from the sinogram data. This work aims to develop a back-projection-and-filtering-like (BPF-like) algorithm that reconstructs the TOF PET image directly from listmode data rapidly. METHODS: We extended the 2D conventional non-TOF PET projection model to a TOF case, where projection data are represented as line integrals weighted by the one-dimensional TOF kernel along the projection direction. After deriving the central slice theorem and the TOF back-projection of listmode data, we designed a deep learning network with a modified U-net architecture to perform the spatial filtration (reconstruction filter). The proposed BP-Net method was validated via Monte Carlo simulations of TOF PET listmode data with three different time resolutions for two types of activity phantoms. The network was only trained on the simulated full-dose XCAT dataset and then evaluated on XCAT and Jaszczak data with different time resolutions and dose levels. RESULTS: Reconstructed images show that when compared with the conventional BPF algorithm and the MLEM algorithm proposed for TOF PET, the proposed BP-Net method obtains better image quality in terms of peak signal-to-noise ratio, relative mean square error, and structure similarity index; besides, the reconstruction speed of the BP-Net is 1.75 times faster than BPF and 29.05 times faster than MLEM using 15 iterations. The results also indicate that the performance of the BP-Net degrades with worse time resolutions and lower tracer doses, but degrades less than BPF or MLEM reconstructions. CONCLUSION: In this work, we developed an analytical-like reconstruction in the form of BPF with the reconstruction filtering operation performed via a deep network. The method runs even faster than the conventional BPF algorithm and provides accurate reconstructions from listmode data in TOF-PET, free of rebinning data to a sinogram.

Machine Learning-Based Noninvasive Quantification of Single-Imaging Session Dual-Tracer 18F-FDG and 68Ga-DOTATATE Dynamic PET-CT in Oncology.

68Ga-DOTATATE PET-CT is routinely used for imaging neuroendocrine tumor (NET) somatostatin receptor subtype 2 (SSTR2) density in patients, and is complementary to FDG PET-CT for improving the accuracy of NET detection, characterization, grading, staging, and predicting/monitoring NET responses to treatment. Performing sequential 18F-FDG and 68Ga-DOTATATE PET scans would require 2 or more days and can delay patient care. To align temporal and spatial measurements of 18F-FDG and 68Ga-DOTATATE PET, and to reduce scan time and CT radiation exposure to patients, we propose a single-imaging session dual-tracer dynamic PET acquisition protocol in the study. A recurrent extreme gradient boosting (rXGBoost) machine learning algorithm was proposed to separate the mixed 18F-FDG and 68Ga-DOTATATE time activity curves (TACs) for the region of interest (ROI) based quantification with tracer kinetic modeling. A conventional parallel multi-tracer compartment modeling method was also implemented for reference. Single-scan dual-tracer dynamic PET was simulated from 12 NET patient studies with 18F-FDG and 68Ga-DOTATATE 45-min dynamic PET scans separately obtained within 2 days. Our experimental results suggested an 18F-FDG injection first followed by 68Ga-DOTATATE with a minimum 5 min delayed injection protocol for the separation of mixed 18F-FDG and 68Ga-DOTATATE TACs using rXGBoost algorithm followed by tracer kinetic modeling is highly feasible.

An Original 2-D Analytical Model for Investigating Coupled Vibrations of Finite Piezoelectric Resonators.

This article deals with 2-D modeling of coupled vibrations of finite piezoelectric resonators. A general solution for all the physical quantities in the Cartesian and cylindrical coordinate systems is deduced from the governing equations by expansion in series summation of trigonometric functions of thickness coordinate and trigonometric or Bessel functions of the lateral one. The essential difference between this model and the earlier ones is that instead of expressing mainly in the thickness coordinate and integration through the thickness, the solutions are expressed in the form of double Fourier series augmented by single Fourier or Fourier-Bessel series, which contributes to better satisfy the mechanical and electrical boundary conditions. The dynamic stiffness matrix of the system is developed. Electrical impedances of a typical piezoelectric parallelepiped under stress-free and symmetrical loading conditions and its frequency spectrum for different width-to-thickness ratios are calculated using our model as well as by the finite element method. A comparison shows an excellent agreement. Finally, theoretical and measured electrical impedances of a piezoelectric parallelepiped and a piezoelectric disk are compared and discussed. The 2-D theoretical model proposed here is shown to be accurate and efficient for coupled vibration analysis of piezoelectric resonators and is applicable for any set of finite dimensions and crystal symmetry.

Accurate coupled vibration analysis of a piezoelectric ceramic cylinder by the superposition method.

The radial and thickness extensional vibration modes in piezoelectric cylinders are always inevitably coupled due to the finite dimension, Poisson's ratio, and piezoelectric effect. In this paper, an analytical model based on the superposition method is developed to obtain the coupled dynamic response of a piezoelectric cylinder under an applied voltage. The problem can be described mathematically by three partial differential equations with mixed boundary conditions in the cylindrical coordinates system. To solve this, the problem is decomposed first into two building block - vibrations in radial and thickness directions. In each building block, the expressions of displacements and electric potential are assumed and then the induced dynamic responses, such as in-plane stress and electric displacements, are calculated. Finally, the vibration responses of the two building blocks are superimposed to satisfy the mixed boundary conditions using Fourier and Fourier-Bessel series expansions. Electrical impedance of a typical piezoelectric disk and frequency spectrum of piezoelectric cylinders of different diameter-to-thickness ratios are calculated by the present analytical method as well as by finite element method. Comparison shows an excellent agreement. This analytical model can be applied to material characterization and the design and the optimization of the active elements of piezoelectric devices.

Modeling and Experimental Characterization of Bonding Delaminations in Single-Element Ultrasonic Transducer.

Ultrasonic transducers performance can be seriously deteriorated by loss of adhesion between some constitutive elements such as the active element, the backing, or the matching layer. In the present work, the influence of bonding delaminations on the performance of a single-element ultrasonic transducer, which is composed of a piezoelectric disk, a backing, and a matching layer, is studied numerically and experimentally. Based on the positions between layers, two cases, i.e., delaminations between ceramic and backing or between ceramic and matching layer, are considered. Each case involves three different types of delaminations, which are marked as delamination type (DT)-I, II, and III. DT-I, a circular shape delamination, starts from the center and expands towards the peripheric zone; DT-II, an annular shape delamination, starts from the peripheric zone and expands towards the center; DT-III is a sector shape delamination with a given angle. The numerical simulations are performed by the finite element method and the influence of delaminations on the electromechanical admittance (EMA) of the transducer is investigated. 3D printed backings and matching layers are mounted on a PZT sample to assemble delaminated single-element transducers. An impedance analyzer is used for experimental measurements. Comparison between numerical and experimental results shows a reasonable agreement making changes in EMA an interesting indicator to inform about the occurrence and severity of delaminations in a single-element ultrasonic transducer.

Retinal image measurements and their association with chronic kidney disease in Chinese patients with type 2 diabetes: the NCD study.

AIMS: Retinal and renal microcirculations are known to share similar physiological changes during early diabetes because of abnormal glucose metabolism and other processes. The retinal vasculature therefore may serve as potential biomarker for the early identification of those at high risk of chronic kidney disease (CKD) in diabetes. METHODS: Data from 1925 patients (aged 49.0 ± 10.3) with type 2 diabetes were analyzed. Various retinal image measurements (RIMs) were collected using a validated fully automated computer program. Multiple logistic regressions were performed to investigate the correlation between RIMs and CKD. RESULTS: In logistic regression adjusting for multiple variables, wider venular calibers in the central and middle zones and narrower arteriolar caliber in the central zone were associated with CKD (p < 0.001, p = 0.020, and p < 0.001, respectively). Increased arteriolar tortuosity was associated with CKD (p = 0.035). Multiple image texture measurements were also significantly associated with CKD. CONCLUSIONS: Renal dysfunction in type 2 diabetes was associated with various retinal image measurements. These non-invasive image measurements may serve as potential biomarkers for the early identification and monitoring of individuals at high risk of CKD in the course of diabetes.

Health Monitoring of Single-Element Piezoelectric Transducer Using Its Electromechanical Admittance.

The transducer is an essential part of all ultrasonic systems used for applications such as medical diagnostics, therapy, nondestructive evaluation, and cleaning because its health condition is vital to their proper operation. Defects within the active element, backing or other constitutive elements, and loss of adhesion between layers can significantly weaken the performance of a transducer. The objective of this work is to determine procedures to monitor the behavior of a single-element probe during its lifetime and detect degradations before they significantly affect the performance of the system. To achieve this, electromechanical admittance (EMA)-based method is envisaged numerically and experimentally. A simplified single-element transducer consisting of a piezoceramic disk, a bonding layer, and a backing is studied and the influence of bonding delamination on EMA is investigated. This study considers three different types of delaminations, which are named, respectively, "center" (circular delamination from the center of the disk toward the peripheric zone), "peripheric" (annular delamination from the peripheric zone toward the center), and "wedge" (wedge-shaped delamination with a given angle). For each case, a numerical model based on the finite-element (FE) method is developed: a 2-D FE analysis is implemented for the first two types of delaminations, taking advantage of their axisymmetric structure, and "wedge" delamination is modeled in 3-D. Then, transducers with different shapes of 3-D printed backings are mounted and experiments are conducted using an impedance analyzer. Finally, experimental results are found to be in good agreement with numerical solutions and it shows that changes in EMA can particularly reveal the occurrence and extent of delamination in an ultrasound probe.

Comprehensive retinal vascular measurements: a novel association with renal function in type 2 diabetic patients in China.

To examine the association between various retinal vascular measurements and microalbuminuria in patients with type 2 diabetes in a northwestern China study. Data from 911 patients with type 2 diabetes were analyzed. Novel retinal vascular measurements from the whole vascular tree were extracted using a validated fully automatic computer program. Retinal vascular measurements were analyzed continuously and categorically for associations with microalbuminuria using multiple logistic regressions, adjusted for related variables. In logistic regression adjusting for multiple variables, microalbuminuria was associated with smaller peripheral arteriolar caliber, larger peripheral venular caliber, larger arteriolar tortuosity, and smaller arteriolar fractal dimension (p = 0.028, p < 0.001, p = 0.038, p = 0.035, respectively). In further categorical analyses, microalbuminuria was related to smaller peripheral arteriolar caliber [T1 vs. T3: odds ratio (OR) 2.029; 95% confidence interval (CI) 1.186-3.473], larger peripheral venular caliber (T1 vs. T3: OR 0.609; 95% CI 0.362-1.024), and smaller arteriolar fractal dimension (T1 vs. T3: OR 1.659; 95% CI 1.028-2.675). Microalbuminuria in type 2 diabetes is associated with both retinal vascular caliber and geometry. These noninvasive vascular measurements serve as potential preclinical markers to identify populations at high risk of early kidney disease in the course of diabetes.

Automated quantification of superficial retinal capillaries and large vessels for diabetic retinopathy on optical coherence tomographic angiography.

Optical coherence tomography angiography (OCTA) is a relatively new technique with capillary-level resolution, which has shown great potential for the diagnosis of diabetic retinopathy (DR). A fully automatic algorithm for the quantitative measurement of microcirculatory changes in sight-threatening DR is presented. The foveal avascular zone (FAZ) segmentation was improved with a graph-theoretic method and the large vessels and capillaries were separately identified and analyzed. The method was evaluated in healthy and diabetic eyes with various stages of retinopathy. Results showed that, compared with the healthy group, the diabetic group showed a significantly larger large vessel density, but a significantly smaller capillary density (P < .001). Circularity of FAZ was significantly smaller while nonperfusion area was significantly larger in the diabetic group. The combined variable of all image metrics reached an area under the ROC of 0.853 (95% CI, 0.784-0.923) for mild to moderate nonproliferative DR and 0.950 (95% CI, 0.922-0.979) for proliferative DR. Microvascular and FAZ changes with various DR stages can be accurately delineated using the developed automatic program. Quantitative metrics on OCTA serve as potential biomarkers for the staging of DR.

Distinctive Analysis of Macular Superficial Capillaries and Large Vessels Using Optical Coherence Tomographic Angiography in Healthy and Diabetic Eyes.

Purpose: To quantify and evaluate macular superficial capillaries and large vessels separately using an optical coherence tomographic angiography (OCTA)-based automatic segmentation algorithm. Methods: In this cross-sectional study, all eyes were scanned using an OCTA device with 3 × 3 mm cube centered on the fovea. Retinal large vessels (arterioles/venules) were automatically segmented from superficial vasculature en-face images. All images were normalized, binarized, and skeletonized for quantification. Metrics of retinal capillaries were calculated by subtracting the measurements of large vessels from total vasculature. Perfusion density (PD), vessel length density (VLD), and vessel diameter index (VDI) within Early Treatment Diabetic Retinopathy Study (ETDRS) 3-mm ring were calculated for total superficial vasculature, large vessels (PDlarge, VLDlarge, and VDIlarge) and capillaries (PDcap, VLDcap, and VDIcap), respectively. Results: Fifty-nine eyes from 59 healthy participants (mean age, 45 ± 14 years, 36 females) and 118 eyes from 67 patients with diabetes mellitus (mean age, 57 ± 10 years, 28 females) were included. The diabetic cohort included four subgroups (35 eyes without diabetic retinopathy, 30 eyes with mild to moderate nonproliferative diabetic retinopathy [NPDR], 27 eyes with severe NPDR, and 26 eyes with PDR). Linear regression showed that all above metrics were correlated with the disease stage (from healthy state to PDR), and the ß value was -0.76, 0.24, -0.78, 0.80, 0.30, 0.77, -0.81, 0.16, and -0.82 for VD, VDlarge, VDcap, VDI, VDIlarge, VDIcap, VLD, VLDlarge, and VLDcap, respectively. Conclusions: Retinal capillaries and large vessels responded differently in the context of diabetes. VLD of capillary is a potentially reliable metric in diabetic retinopathy staging.

An improved arteriovenous classification method for the early diagnostics of various diseases in retinal image.

(BACKGROUND AND OBJECTIVES): Retinal artery and vein classification is an important task for the automatic computer-aided diagnosis of various eye diseases and systemic diseases. This paper presents an improved supervised artery and vein classification method in retinal image. (METHODS): Intra-image regularization and inter-subject normalization is applied to reduce the differences in feature space. Novel features, including first-order and second-order texture features, are utilized to capture the discriminating characteristics of arteries and veins. (RESULTS): The proposed method was tested on the DRIVE dataset and achieved an overall accuracy of 0.923. (CONCLUSION): This retinal artery and vein classification algorithm serves as a potentially important tool for the early diagnosis of various diseases, including diabetic retinopathy and cardiovascular diseases.

Smartphone-Based Accurate Analysis of Retinal Vasculature towards Point-of-Care Diagnostics.

Retinal vasculature analysis is important for the early diagnostics of various eye and systemic diseases, making it a potentially useful biomarker, especially for resource-limited regions and countries. Here we developed a smartphone-based retinal image analysis system for point-of-care diagnostics that is able to load a fundus image, segment retinal vessels, analyze individual vessel width, and store or uplink results. The proposed system was not only evaluated on widely used public databases and compared with the state-of-the-art methods, but also validated on clinical images directly acquired with a smartphone. An Android app is also developed to facilitate on-site application of the proposed methods. Both visual assessment and quantitative assessment showed that the proposed methods achieved comparable results to the state-of-the-art methods that require high-standard workstations. The proposed system holds great potential for the early diagnostics of various diseases, such as diabetic retinopathy, for resource-limited regions and countries.

Direct 3D Analyses Reveal Barrel-Specific Vascular Distribution and Cross-Barrel Branching in the Mouse Barrel Cortex.

Whether vascular distribution is spatially specific among cortical columns is a fundamental yet controversial question. Here, we have obtained 1-µm resolution 3D datasets that cover the whole mouse barrel cortex by combining Nissl staining with micro-optical sectioning tomography to simultaneously visualize individual cells and blood vessels, including capillaries. Pinpointing layer IV of the posteromedial barrel subfield, direct 3D reconstruction and quantitative analysis showed that (1) penetrating vessels preferentially locate in the interbarrel septa/barrel wall (75.1%) rather than the barrel hollows, (2) the branches of 70% penetrating vessels only reach the neighboring but not always all the neighboring barrels and the other 30% extend beyond the neighboring barrels and may provide cross-barrel blood supply or drainage, (3) the branches of 59.6% penetrating vessels reach all the neighboring barrels, while the rest only reach part of them, and (4) the length density of microvessels in the interbarrel septa/barrel wall is lower than that in the barrel hollows with a ratio of 0.92. These results reveal that the penetrating vessels and microvessels exhibit a barrel-specific organization, whereas the branches of penetrating vessels do not, which suggests a much more complex vascular distribution pattern among cortical columns than previously thought.

Pixelated transmission-mode diamond X-ray detector.

Fabrication and testing of a prototype transmission-mode pixelated diamond X-ray detector (pitch size 60-100 µm), designed to simultaneously measure the flux, position and morphology of an X-ray beam in real time, are described. The pixel density is achieved by lithographically patterning vertical stripes on the front and horizontal stripes on the back of an electronic-grade chemical vapor deposition single-crystal diamond. The bias is rotated through the back horizontal stripes and the current is read out on the front vertical stripes at a rate of ∼ 1 kHz, which leads to an image sampling rate of ∼ 30 Hz. This novel signal readout scheme was tested at beamline X28C at the National Synchrotron Light Source (white beam, 5-15 keV) and at beamline G3 at the Cornell High Energy Synchrotron Source (monochromatic beam, 11.3 keV) with incident beam flux ranges from 1.8 × 10(-2) to 90 W mm(-2). Test results show that the novel detector provides precise beam position (positional noise within 1%) and morphology information (error within 2%), with an additional software-controlled single channel mode providing accurate flux measurement (fluctuation within 1%).