Spectral properties of random graphs with fixed equitable partition

We define a graph to be $S$-regular if it contains an equitable partition given by a matrix $S$. These graphs are generalizations of both regular and bipartite, biregular graphs. An $S$-regular matrix is defined then as a matrix on an $S$-regular graph consistent with the graph's equitable partition. In this paper we derive the limiting spectral density for large, random $S$-regular matrices as well as limiting functions of certain statistics for their eigenvector coordinates as a function of eigenvalue. These limiting functions are defined in terms of spectral measures on $S$-regular trees. In general, these spectral measures do not have a closed-form expression; however, we provide a defining system of polynomials for them. Finally, we explore eigenvalue bounds of $S$-regular graph, proving an expander mixing lemma, Alon-Bopana bound, and other eigenvalue inequalities in terms of the eigenvalues of the matrix $S$.Comment: 24 pages, 3 figure

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease.

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation

ICOSeg: real-time ICOS protein expression segmentation from immunohistochemistry slides using a lightweight conv-transformer network.

In this article, we propose ICOSeg, a lightweight deep learning model that accurately segments the immune-checkpoint biomarker, Inducible T-cell COStimulator (ICOS) protein in colon cancer from immunohistochemistry (IHC) slide patches. The proposed model relies on the MobileViT network that includes two main components: convolutional neural network (CNN) layers for extracting spatial features; and a transformer block for capturing a global feature representation from IHC patch images. The ICOSeg uses an encoder and decoder sub-network. The encoder extracts the positive cell's salient features (i.e., shape, texture, intensity, and margin), and the decoder reconstructs important features into segmentation maps. To improve the model generalization capabilities, we adopted a channel attention mechanism that added to the bottleneck of the encoder layer. This approach highlighted the most relevant cell structures by discriminating between the targeted cell and background tissues. We performed extensive experiments on our in-house dataset. The experimental results confirm that the proposed model achieves more significant results against state-of-the-art methods, together with an 8× reduction in parameters

Arthroscopic rotator cuff repair with a fibrin scaffold containing growth factors and autologous progenitor cells derived from humeral cBMA improves clinical outcomes in high risk patients

PURPOSE: To report the clinical outcomes after biologically augmented rotator cuff repair (RCR) with a fibrin scaffold derived from autologous whole blood and supplemented with concentrated bone marrow aspirate (cBMA) harvested at the proximal humerus. METHODS: Patients who underwent arthroscopic RCR with biologic augmentation using a fibrin clot scaffold (“Mega- Clot”) containing progenitor cells and growth factors from proximal humerus BMA and autologous whole blood between April 2015 and January 2018 were prospectively followed. Only high-risk patients in primary and revision cases that possessed relevant comorbidities or physically demanding occupation were included. Minimum follow-up for inclusion was 1 year. The visual analog score for pain (VAS), American Shoulder and Elbow Surgeons (ASES), Simple Shoulder Test (SST), Single Assessment Numerical Evaluation (SANE), and Constant-Murley scores were collected preoperatively and at final follow-up. In vitro analyses of the cBMA and fibrin clot using nucleated cell count, colony forming units, and live/dead assays were used to quantify the substrates. RESULTS: Thirteen patients (56.9 ± 7.7 years) were included. The mean follow-up was 26.9 ± 17.7 months (n = 13). There were significant improvements in all outcome scores from the preoperative to the postoperative state: VAS (5.6 ± 2.5 to 3.1 ± 3.2; P < .001), ASES (42.0 ± 17.1 to 65.5 ± 30.6; P < .001), SST (3.2 ± 2.8 to 6.5 ± 4.7; P = .002), SANE (11.5 ± 15.6 to 50.3 ± 36.5; P < .001), and Constant-Murley (38.9 ± 17.5 to 58.1 ± 26.3; P < .001). Six patients (46%) had retears on postoperative MRI, despite all having improvements in pain and function except one. All failures were chronic rotator cuff tears, and all were revision cases except one (1.6 ± 0.5 previous RCRs). The representative sample of harvested cBMA showed an average of 28.5 ± 9.1 × 10(6) nucleated cells per mL. CONCLUSIONS: Arthroscopic rotator cuff repairs that are biologically augmented with a fibrin scaffold containing growth factors and autologous progenitor cells derived from autologous whole blood and humeral cBMA can improve clinical outcomes in primary, as well as revision cases in high-risk patients. However, the incidence of retears remains a concern in this population, demanding further improvements in biologic augmentation. LEVEL OF EVIDENCE: IV, therapeutic case series

Frequent malaria illness episodes in two Malawian patients on antiretroviral therapy soon after stopping cotrimoxazole preventive therapy

We describe two Malawian adults on successful antiretroviral therapy who experienced frequent malaria episodes after stopping cotrimoxazole prophylaxis. We argue that, in addition to stopping cotrimoxazole, diminished malaria immunity and drug interactions between efavirenz and artemether–lumefantrine may have played a causative role in the recurrent malaria our patients experienced

Parallelized computational 3D video microscopy of freely moving organisms at multiple gigapixels per second

To study the behavior of freely moving model organisms such as zebrafish (Danio rerio) and fruit flies (Drosophila) across multiple spatial scales, it would be ideal to use a light microscope that can resolve 3D information over a wide field of view (FOV) at high speed and high spatial resolution. However, it is challenging to design an optical instrument to achieve all of these properties simultaneously. Existing techniques for large-FOV microscopic imaging and for 3D image measurement typically require many sequential image snapshots, thus compromising speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over a 135-cm^2 area, achieving up to 230 frames per second at throughputs exceeding 5 gigapixels (GPs) per second. 3D-RAPID features a 3D reconstruction algorithm that, for each synchronized temporal snapshot, simultaneously fuses all 54 images seamlessly into a globally-consistent composite that includes a coregistered 3D height map. The self-supervised 3D reconstruction algorithm itself trains a spatiotemporally-compressed convolutional neural network (CNN) that maps raw photometric images to 3D topography, using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. As a result, our end-to-end 3D reconstruction algorithm is robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. The scalable hardware and software design of 3D-RAPID addresses a longstanding problem in the field of behavioral imaging, enabling parallelized 3D observation of large collections of freely moving organisms at high spatiotemporal throughputs, which we demonstrate in ants (Pogonomyrmex barbatus), fruit flies, and zebrafish larvae