Browse Articles

Feasibility test of 3 dimensional patient specific quality assurance of gamma knife radiosurgery using novel mobile phospor probe system

Preclinical dose assessment of cyberknife with small animal intracranial irradiation using a 3D printed mouse phantom

Uncovering bifurcation behaviors of biochemical reaction systems from network topology

Abstract The regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited knowledge of reaction kinetics, bifurcation behaviors in biological systems remain largely underexplored. To address this, we developed a mathematical method, Structural Bifurcation Analysis (SBA), which decomposes the system into substructures and determines important aspects of bifurcation behaviors—such as substructures responsible for bifurcation conditions, bifurcation-inducing parameters, and bifurcating variables—solely from network topology. We establish a direct relationship between SBA and classical bifurcation analysis, enabling the study of systems even in the presence of conserved quantities. Additionally, we provide a step-by-step bifurcation analysis for general use. We applied our method to the macrophage M1/M2 polarization system. Our analysis reveals that the network structure strongly constrains possible patterns of polarization. We also clarify the dependency of the M1/M2 balance on gene expression levels and predict the emergence of intermediate polarization patterns under gene deletions, including SOCS3, which are experimentally testable.

Raw QPP-RNG randomness via system jitter across platforms: a NIST SP 800-90B evaluation

Abstract High-quality randomness is fundamental to the security of modern cryptographic systems. We present QPP-RNG, a true random number generator (TRNG) that harvests entropy from diverse system-level jitters–including CPU pipeline timing divergences, DRAM refresh cycle perturbations, cache miss-driven memory access latencies, and other subtle hardware and operating system-induced fluctuations. QPP-RNG’s core mechanism measures the elapsed time of randomized array sorting operations–where each Fisher-Yates shuffle is infinitesimally perturbed by these microscopic jitters–and amplifies these timing variations into cryptographically strong randomness through a quantum permutation pad (QPP) architecture, all achievable on commodity hardware. The raw output of QPP-RNG underwent rigorous evaluation for independent and identically distributed (IID) behavior using the NIST SP 800-90B IID test suite, alongside the comprehensive NIST SP 800-22 and ENT statistical test batteries. Across a range of platforms, including Windows, macOS, and Raspberry Pi, QPP-RNG consistently achieved high IID min-entropy between $$7.85$$ and $$7.95$$  bits/byte. It passed all NIST SP 800-90B IID tests with $$p$$ -values significantly above the $$\alpha =0.01$$ threshold, confirming that its generated randomness is statistically indistinguishable from ideal IID sources derived directly from system jitter. Cross-platform analyses spanning x86_64 and ARM64 architectures further demonstrate that the extracted jitter fingerprint–and consequently the generated randomness–exhibits remarkable statistical consistency, irrespective of the underlying hardware or operating system. QPP-RNG’s entropy density compares favorably with leading commercial entropy sources. It matches or slightly exceeds the NIST IID-certified min-entropy of ID Quantique’s Quantis QRNG (7.8744 bits/byte), and significantly outperforms both Red Hat’s CPU Time Jitter RNG (7.4528 bits/byte) and Quside’s PCIe One quantum entropy source (6.5136 bits/byte). Even against specialized hardware RNGs like Microchip’s ECC608 (4.0568 bits/byte), QPP-RNG demonstrates superior performance using only general-purpose processors. By effectively transforming otherwise discarded system noise into a reliable and high-quality entropy stream, QPP-RNG establishes a novel paradigm for embedded security, providing a robust entropy source on general-purpose devices without specialized hardware. This makes it especially well-suited for resource-constrained Internet of Things (IoT) and edge computing applications where strong entropy sources are paramount.

Acceleration towards clean energy with the emergence of promising signs of shallow geothermal resources in Northwestern Iran

Classifying social and physical pain from multimodal physiological signals using machine learning

Elastic constants identification for laminated composites using laser doppler vibrometry and an inversion method based on legendre orthogonal polynomial expansion

Microscopic theory of polariton group velocity renormalization

Isotope-driven hydrogel smart windows for self-adaptive thermoregulation

The structure of the Tad pilus alignment complex reveals a periplasmic conduit for pilus extension

Abstract The Tad ( T ight ad herence) pilus is a bacterial appendage implicated in virulence, cell-cell aggregation, and biofilm formation. Despite its homology to the well-characterised Type IV pilus, the structure and assembly mechanism of the Tad pilus are poorly understood. Here, we investigate the role of the Tad pilus protein RcpC from Pseudomonas aeruginosa . Our analyses reveal that RcpC forms a dodecameric periplasmic complex, anchored to the inner membrane by a transmembrane helix, and interacting with the outer membrane secretin RcpA. We use single-particle Cryo-EM to elucidate the structure of the RcpC dodecamer, and cell-based assays to demonstrate that the RcpC-RcpA complex is essential for Tad-mediated cell-cell aggregation. Collectively, these data demonstrate that RcpC forms the Tad pilus alignment complex, which provides a conduit across the periplasm for the Tad pilus filament to access the extracellular milieu. Our experimental data and structure-based model allow us to propose a mechanism for Tad plus assembly.

Single urinary extracellular vesicle proteomics identifies complement receptor CD35 as a biomarker for sepsis-associated acute kidney injury

Exploring the intersection of natural sciences and information technology via entropy and randomness

Tunable reciprocal and nonreciprocal contributions to 1D Coulomb drag

Vinyl cyclopropanes as a unifying platform for enantioselective remote difunctionalization of alkenes

Abstract Asymmetric remote difunctionalization of alkenes is a longstanding challenge in synthetic chemistry, offering the potential to install two functional groups simultaneously across distal carbon atoms in a stereocontrolled manner. While ingenious strategies have been devised to achieve this transformation, a general catalytic system for remote, enantioselective hetero-carbofunctionalization and dicarbofunctionalization of alkenes has remained elusive. Here, we present a nickel/photoredox dual-catalyzed asymmetric remote 1,5-carbosulfonylation and 1,5-dicarbofunctionalization of vinyl cyclopropanes. This cascade reaction integrates radical addition, C–C bond cleavage, and cross-coupling to functionalize two distal carbon atoms with high enantioselectivity. Our protocol demonstrates broad substrate scope, excellent functional group tolerance, and significant synthetic utility, as evidenced by late-stage functionalization and product derivatization. Our mechanistic investigations support the involvement of a Ni(0)/Ni(I)/Ni(III) catalytic cycle in our system. This work establishes a versatile platform for remote alkene difunctionalization, expanding the toolbox of enantioselective synthetic methods and unlocking new avenues for complex molecule construction.

Time-dependent catalytic activity in aging condensates

Abstract Biomolecular condensates are dynamic cellular compartments that concentrate proteins and enzymes to regulate biochemical reactions in time and space. While these condensates can enhance enzyme activity, how this function changes as condensates age remains poorly understood. Here, we design synthetic catalytic condensates that selectively recruit enzymes to investigate this temporal evolution. We show that catalytic condensates exhibit time-dependent activity: they initially accelerate enzymatic reactions but gradually lose efficiency due to the transition from liquid-like to solid-like states. This aging process, characterized by protein aggregation and loss of selective barriers, impairs enzyme function both in vitro and living cells. We further demonstrate that small molecules which influence aging dynamics can modulate catalytic efficiency of condensates. Our findings show that condensate aging as a key regulator of enzymatic activity and provide crucial insights for designing functional synthetic condensates.

Simulations and active learning enable efficient identification of an experimentally-validated broad coronavirus inhibitor

Abstract Drug screening resembles finding a needle in a haystack: identifying a few effective inhibitors from a large pool of potential drugs. Large experimental screens are expensive and time-consuming, while virtual screening trades off computational efficiency and experimental correlation. Here we develop a framework that combines molecular dynamics (MD) simulations with active learning. Two components drastically reduce the number of candidates needing experimental testing to less than 20: (1) a target-specific score that evaluates target inhibition and (2) extensive MD simulations to generate a receptor ensemble. The active learning approach reduces the number of compounds requiring experimental testing to less than 10 and cuts computational costs by ∼29-fold. Using this framework, we discovered BMS-262084 as a potent inhibitor of TMPRSS2 (IC50 = 1.82 nM). Cell-based experiments confirmed BMS-262084’s efficacy in blocking entry of various SARS-CoV-2 variants and other coronaviruses. The identified inhibitor holds promise for treating viral and other diseases involving TMPRSS2.

Epigenomic diagnosis and prognosis of Acute Myeloid Leukemia

Abstract Despite the critical role of DNA methylation, clinical implementations harnessing its promise have not been described in acute myeloid leukemia. Utilizing DNA methylation from 3314 leukemia patient samples across 11 harmonized cohorts, we describe the Acute Leukemia Methylome Atlas, which includes robust models capable of accurately predicting AML subtypes. A genome-wide prognostic model as well as a targeted panel of 38 CpGs significantly predict five-year survival in our pediatric and adult test cohorts. To accelerate rapid clinical utility, we develop a specimen-to-result protocol that uses long-read nanopore sequencing and machine learning to characterize patients’ whole genomes and epigenomes. Clinical validation on patient samples confirms high concordance between epigenomic signatures and genomic lesions, though uniquely rare karyotypes remained challenging due to limited available training data. These results unveil the potential for increased affordability, speed, and accuracy for patients in need of complex molecular diagnosis and prognosis.

An on-chip phased array for non-classical light

Abstract Quantum science and technology can offer fundamental enhancements in sensing, communications and computing. The expansion from wired to wireless links is an exciting prospect for quantum technologies. For classical technologies, the advent of phased arrays enabled directional and adaptive wireless links by manipulating electromagnetic waves over free space. Here we demonstrate a phased array system on a chip that can receive, image and manipulate non-classical light over free space. We use an integrated photonic-electronic system with more than 1000 functional components on-chip to detect squeezed light. By integrating an array of 32 sub-wavelength engineered metamaterial antennas, we demonstrate a direct free-space-to-chip interface for reconfigurable quantum links. On the same chip, we implement a large-scale array of quantum-limited coherent receivers that can resolve non-classical signals simultaneously across 32 channels. With coherent readout and manipulation of these signals, we demonstrate 32-pixel imaging and spatially configurable reception of squeezed light over free space. Our work advances wireless quantum technologies that could enable practical applications in quantum communications and sensing.

Cas13d-mediated isoform-specific RNA knockdown with a unified computational and experimental toolbox

How different cardioplegic solutions influence genes expression and cytokine response in an immature rat heart model of ischemia/reperfusion?

Introduction The use of cardioplegia not only achieves cardiac arrest but also minimizes ischemic/reperfusion (I/R) injury, potentially improving short- or long-term outcomes. The aim of this study was to evaluate the impact of different cardioplegic solutions – del Nido, Custodiol HTK and St. Thomas on genes expression and cytokines response in an immature rat heart model of I/R using the Langendorff preparation. Expression of genes which are involved in cell cycle, proliferation, apoptosis resistance and response to hypoxia were determined in cardiac tissue, as well as levels pro/anti-inflammatory cytokines were measured. Methods A total of 39 male Wistar albino rats were utilized in this study. Experimental animals were divided into 3 groups, four animals in each following groups: St. Thomas (ST), Custodiol HTK (HTK) and del Nido (DN) group. Moreover, each of these groups was divided into 3 groups according to ischemia’s time: 1h ischemia with 20 min reperfusion time, 2h ischemia with 40 min reperfusion time, 4h ischemia with 80 min reperfusion and control groups (K-PRF) with 30 minutes of perfusion was performed in the K-PRF (n = 3). The heart was removed from the chest and immediately frozen at –81°C. Results All cardioplegic solutions effectively modulate the expression of HIF1A, FOS, and BNIP2 genes. The results indicated that DN actively induces HIF1A within the first hour. Compared to the ST, and HTK groups, the expression of the HIF1A gene was on average 2 times higher (P < 0.01). Similar results were observed in the 2-hour group. After 4 hours, the effect of cardioplegic solutions continued to maintain the dynamics, but the differences were not statistically significant. The expression of the FOS gene after 2 and 4 hours of incubation with the DN solution remained significantly higher compared to ST (P < 0.05) and HTK (P < 0.05). A comparative analysis with the perfusion group showed that BNIP2 gene expression in the ST and HTK solution groups was significantly lower than in perfused tissue (P < 0.05). Pro-inflammatory cytokines: TNF-alpha, IL-6 and anti-inflammatory cytokines: IL-4 and IL-10 were evaluated. The results showed that there was no statistically significant difference between the groups (P > 0.05). Conclusion In our experiment, statistically significant differences were not observed in cytokines. Although statistically significant differences were observed only in gene expression, and only in the rat model, the overall results suggest that del Nido cardioplegic solution may provide better cellular protection. It is also worth mentioning that gene expression and cytokines change are not direct markers of cardioprotection. Further research is needed to confirm these results in human tissues and broader clinical settings.