Miracle-dz/UniFAR-FTUs huggingface dataset:
Monte Carlo Simulations of Heat Deposition during Photothermal Skin Cancer Therapy Using Nanoparticles

Photothermal therapy using nanoparticles is a promising new approach for the treatment of cancer. The principle is to utilise plasmonic nanoparticle light interaction for efficient heat conversion. However, there are many hurdles to overcome before it can be accepted in clinical practice. One issue is a current poor characterization of the thermal dose that is distributed over the tumour region and the surrounding normal tissue. Here, we use Monte Carlo simulations of photon radiative transfer through tissue and subsequent heat diffusion calculations, to model the spatial thermal dose in a skin cancer model. We validate our heat rise simulations against experimental data from the literature and estimate the concentration of nanorods in the tumor that are associated with the heat rise. We use the cumulative equivalent minutes at 43 °C (CEM43) metric to analyse the percentage cell kill across the tumour and the surrounding normal tissue. Overall, we show that computer simulations of photothermal therapy are an invaluable tool to fully characterize thermal dose within tumour and normal tissue.
Molecular characterization of hepatic epithelioid hemangioendothelioma reveals alterations in various genes involved in DNA repair, epigenetic regulation, signaling pathways, and cell cycle control

Epithelioid hemangioendotheliomas (EHE) of the liver are rare, low‐malignant vascular tumors whose molecular pathogenesis is incompletely understood. The diagnosis of EHE is challenging, and the course of the disease can be highly variable. Therapeutic options for EHE are limited, including resection of primary and metastatic tumors, organ transplantation and rather ineffective systemic approaches. Driver mutations have been reported (fusion transcripts of either YAP‐TFE3 or WWTR1‐CAMTA1) but comprehensive molecular profiling has not been performed. Our aim was to molecularly characterize hepatic EHE to identify new molecular targets. Eight primary hepatic EHE were analyzed by next‐generation sequencing using a 409‐gene panel. The majority of primary hepatic EHE revealed a low number of mutations. Genes that were mutated primarily are involved in DNA repair, epigenetic regulation, signaling pathways and cell cycle control, indicating that EHE present with mutations in various functions. Although only detecting a low mutation rate, a comparison with comprehensive databases (target db V3) revealed mutations in five genes with putative therapeutical options. Therefore, our findings help to shed light on the molecular background of EHE and might pave the way to new therapeutic approaches.
2,3,7,8-Tetrachlorodibenzo-p-dioxin modifies alternative splicing in mouse liver

Alternative splicing is a co-transcriptional mechanism that generates protein diversity by including or excluding exons in different combinations, thereby expanding the diversity of protein isoforms of a single gene. Abnormalities in this process can result in deleterious effects to human health, and several xenobiotics are known to interfere with splicing regulation through multiple mechanisms. These changes could lead to human diseases such as cancer, neurological disorders, autoimmune diseases, and developmental disorders. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant generated as a byproduct of various industrial activities. Exposure to this dioxin has been linked to a wide range of pathologies through the alteration of multiple cellular processes. However, the effects of TCDD exposure on alternative splicing have not yet been studied. Here, we investigated whether a single po. dose of 5 μg/kg or 500 μg/kg TCDD influence hepatic alternative splicing in adult male C57BL/6Kou mouse. We identified several genes whose alternative splicing of precursor messenger RNAs was modified following TCDD exposure. In particular, we demonstrated that alternative splicing of Cyp1a1, Ahrr, and Actn1 was significantly altered after TCDD treatment. These findings show that the exposure to TCDD has an impact on alternative-splicing, and suggest a new avenue for understanding TCDD-mediated toxicity and pathogenesis.
Reply to Sun et al., “Identifying Composition Novelty in Microbiome Studies: Improvement of Prediction Accuracy”

To quantitatively measure the beta diversities between microbiomes, Microbiome Search Engine (MSE) (1) calculates phylogeny similarity using operational taxonomy unit (OTU) profiles; for both query and database samples, all 16S rRNA gene sequences are mapped to the Greengenes database (version 13-8) (2) for reference-based OTU picking with a 97% cutoff. Thus, in MSE, the comparison between query and database samples is approximately at the species level (3), although the actual taxonomic resolution varies according to taxon, due to differences in the evolutionary rates of the 16S rRNAs. Moreover, in MSE, both the relative abundance (with 16S rRNA gene copy number normalization [4]) and the phylogenetic structures of OTUs are utilized for similarity calculation (as in UniFrac [5, 6]), yet the speed is optimized by nonrecursive computing to enable real-time responses (7). By comparing the query sample (i.e., dust from university dormitories) provided by Sun …
Second order structure functions for higher powers of turbulent velocity

We experimentally study the temporal second-order structure functions for integer powers of turbulent fluid velocity fluctuations , in three dimensional (3D) and two dimensional (2D) turbulence. Here is a composite time-series constructed by averaging the concurrent time-series () sampled at N spatially distributed Eulerian points. The N = 1 case has been extensively studied for velocity fluctuations (m = 1) and to a lesser extent for m > 1. The averaging method in case of N > 1 diverges from the Kolmogorov framework and has not been studied because fluctuations in are expected to smooth with increasing N leaving behind uninteresting large-scale mean flow information, but we find this is not so. We report the evolution of scaling exponents for in going from a single (N = 1) to a spatial average over several Eulerian points (). Our 3D experiments in a tank with rotating jets at the floor show for all m-values in agreement with prior results and evolves to an asymptotic value of . The evolution of follows the functional form , where points is the only fit parameter representing the convergence rate constant. Results for the 2D experiments conducted in a gravity assisted soap film in the enstrophy cascade regime are in sharp contrast with their 3D counterparts. Firstly varies polynomially with m and asymptotes to a constant value at m = 5. Secondly, the evolution of is logarithmic , where A and B are fit parameters and eventually deviates at large N and asymptotes to for all m. The starkly different convergence forms (exponential in 3D versus logarithmic in 2D) may be interpreted as a signature of inter-scale couplings in the respective turbulent flows by decomposing the two-point correlator for into a self-correlation and cross-correlation term. In addition to aiding in the theoretical development, the results may also have implications for determination of resolution in 2D turbulence experiments and simulations, wind energy and atmospheric boundary layer turbulence.
Evaluation of Lower Limb Neuromuscular System Observability and Estimability of Muscle Activity

Abstract In this work, we describe a method for estimating the muscle activity without drawing any assumptions regarding optimality principles in human motor control strategies; further, the method does not require any neural circuitry modeling which limits the neurophysiological terms and estimability of the method. We introduce the concept of system observability, which can reconstruct states from outputs and their derivatives based on system dynamics. Based on neuromuscular system observability, we estimate the muscle activity from joint torques and kinematics of multiple locomotive gaits, while considering the unknown neural inputs as system disturbances. Moreover, to quantify the robustness of the method, the degree of observability and parameter sensitivity are evaluated. Finally, the neurophysiological implications and generality of the method are addressed.
CrossTalk proposal: The glymphatic system supports convective exchange of cerebrospinal fluid and brain interstitial fluid that is mediated by perivascular aquaporin‐4

Jeffrey Iliff and Matthew Simon VISN 20 Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA Neuroscience Graduate Program, Oregon Health & Science University, Portland, OR, USA
Analysis of Byzantine Attacks for Target Tracking in Wireless Sensor Networks

Herein, the problem of target tracking in wireless sensor networks (WSNs) is investigated in the presence of Byzantine attacks. More specifically, we analyze the impact of Byzantine attacks on the performance of a tracking system. First, under the condition of jointly estimating the target state and the attack parameters, the posterior Cramer–Rao lower bound (PCRLB) is calculated. Then, from the perspective of attackers, we define the optimal Byzantine attack and theoretically find a way to achieve such an attack with minimal cost. When the attacked nodes are correctly identified by the fusion center (FC), we further define the suboptimal Byzantine attack and also find a way to realize such an attack. Finally, in order to alleviate the negative impact of attackers on the system performance, a modified sampling importance resampling (SIR) filter is proposed. Simulation results show that the tracking results of the modified SIR filter can be close to the true trajectory of the moving target. In addition, when the quantization level increases, both the security performance and the estimation performance of the tracking system are improved.
Formononetin ameliorates cognitive disorder via PGC-1α pathway in neuroinflammation conditions in high-fat diet-induced mice.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in many modern societies. Previous studies have shown that neuroinflammation is one of the pathogenesis of AD. Formononetin (FN), an isoflavone compound extracted from Trifolium pratense L. , has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. The present study focused on the protective activities of FN on a high-fat diet (HFD)-induced cognitive decline and explored the underlying mechanisms. We found that FN (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol (TC) and triglyceride (TG) in HFD-induced mice. Meanwhile, we observed HFD significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas FN reversed this effect. Additionally, FN markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in HFD-induced mice. The mechanism study showed that FN suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of HFD-induced mice. Taken together, our results showed that FN could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.
Hyperoxidation of mitochondrial peroxiredoxin limits H2O2‐induced cell death in yeast

Hydrogen peroxide (H2O2) plays important roles in cellular signaling, yet nonetheless is toxic at higher concentrations. Surprisingly, the mechanism(s) of cellular H2O2 toxicity remain poorly understood. Here, we reveal an important role for mitochondrial 1‐Cys peroxiredoxin from budding yeast, Prx1, in regulating H2O2‐induced cell death. We show that Prx1 efficiently transfers oxidative equivalents from H2O2 to the mitochondrial glutathione pool. Deletion of PRX1 abrogates glutathione oxidation and leads to a cytosolic adaptive response involving upregulation of the catalase, Ctt1. Both of these effects contribute to improved cell viability following an acute H2O2 challenge. By replacing PRX1 with natural and engineered peroxiredoxin variants, we could predictably induce widely differing matrix glutathione responses to H2O2. Therefore, we demonstrated a key role for matrix glutathione oxidation in driving H2O2‐induced cell death. Finally, we reveal that hyperoxidation of Prx1 serves as a switch‐off mechanism to limit oxidation of matrix glutathione at high H2O2 concentrations. This enables yeast cells to strike a fine balance between H2O2 removal and limitation of matrix glutathione oxidation.
A Novel Application of Dynamic Navigation System in Socket Shield Technique.

The socket shield technique has been demonstrated to have great potential in preserving hard and soft tissue dimensions after tooth extraction to achieve optimal esthetic results. The preparation of the socket shield, however, is technique-sensitive due to limited access to the extraction sockets and variations in root anatomies. The dynamic navigation system allows clinicians to visualize the movement of the cutting instrument and its position relative to anatomical structures in real-time. This greatly enhances clinicians' abilities to perform surgeries accurately. This report describes a novel method of using such system to prepare the socket shield in a precise and efficient manner.
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Augments Thrombolysis of tPA (Tissue-Type Plasminogen Activator) in Aged Rats After Stroke.

Background and Purpose- Stroke is a leading cause of disability worldwide, mainly affecting the elderly. However, preclinical studies in aged ischemic animals are limited. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a naturally occurring tetrapeptide with vascular-protective properties. The present study investigated the effect of AcSDKP on tPA (tissue-type plasminogen activator)-induced thrombolysis in aged rats after ischemic stroke. Methods- Aged male rats (18 months) were subjected to embolic middle cerebral artery occlusion. Rats subjected to 4 hours of middle cerebral artery occlusion were randomized into the following groups: (1) AcSDKP; (2) tPA; (3) AcSDKP in combination with tPA; and (4) saline. Neurological deficits, cerebral microvascular patency and integrity, and infarction were examined at 1 day and 7 days after middle cerebral artery occlusion. In vitro experiments were performed to examine the effect of AcSDKP on aged cerebral endothelial cell permeability. Results- Compared with saline, AcSDKP, or tPA as monotherapy did not have any therapeutic effects, whereas AcSDKP in combination with tPA significantly reduced cerebral tissue infarction and improved neurological outcome without increasing cerebral hemorrhage. Concurrently, the combination treatment significantly augmented microvascular perfusion and reduced thrombosis and blood-brain barrier leakage. In vitro, compared with cerebral endothelial cells from ischemic adult rats, the endothelial cells from ischemic aged rats exhibited significantly increased leakage. AcSDKP suppressed tPA-induced aged endothelial cell leakage and reduced expression of ICAM-1 (intercellular adhesion molecule 1) and NF (nuclear factor)-κB. Conclusions- The present study provides evidence for the therapeutic efficacy of AcSDKP in combination tPA for the treatment of embolic stroke in aged rats at 4 hours after stroke onset. AcSDKP likely acts on cerebral endothelial cells to enhance the benefits of tPA by increasing tissue perfusion and augmenting the integrity of the blood-brain barrier.
Anti‐CRISPR AcrIIC3 discriminates between Cas9 orthologs via targeting the variable surface of the HNH nuclease domain

Clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas systems constitute the adaptive immunity of bacteria and archaea, degrading nucleic acids of invading phages and plasmids. In response, phages employ anti‐CRISPR (Acr) proteins as a counterdefense mechanism to neutralize the host immunity. AcrIIC3 directly inhibits target DNA cleavage of type II‐C Cas9 of Neisseria meningitidis. Here, we show that AcrIIC3 interacts with the HNH nuclease domain of N. meningitidis Cas9 to inhibit its nuclease activity in an allosteric manner. The crystal structure of the AcrIIC3–HNH complex reveals that AcrIIC3 binds opposite the active site on the HNH nuclease domain. AcrIIC3 employs a unique interface for HNH, allowing it to discriminate between Cas9 orthologs, which contrasts with the broad spectrum of Cas9 inhibition by AcrIIC1. Interface residues of HNH provide key electrostatic and hydrophobic interactions that determine the host specificity of AcrIIC3. Mutations that replace HNH interfaces of N. meningitidis Cas9 with those of Geobacillus stearothermophilus Cas9 or Campylobacter jejuni Cas9 significantly attenuate AcrIIC3 binding, illustrating that the divergent interaction surface confers the host specificity of AcrIIC3. Our study demonstrates that the variable sequences of binding interface can define the target specificity of Acr proteins, suggesting potential applications in Cas9 control for gene editing.
Generation of hematopoietic cells from mouse pluripotent stem cells in a 3D culture system of self‐assembling peptide hydrogel

In vitro generation of hematopoietic stem cells from pluripotent stem cells (PSCs) can be regarded as novel therapeutic approaches for replacing bone marrow transplantation without immune rejection or graft versus host disease. To date, many different approaches have been evaluated in terms of directing PSCs toward different hematopoietic cell types, yet, low efficiency and no function restrict the further hematopoietic differentiation study, our research aims to develop a three dimension (3D) hematopoietic differentiation approach that serves as recapitulation of embryonic development in vitro to a degree of complexity not achievable in a two dimension culture system. We first found that mouse PSCs could be efficiently induced to hematopoietic differentiation with an expression of hematopoietic makers, such as c‐kit, CD41, and CD45 within self‐assembling peptide hydrogel. Colony‐forming cells assay results suggested mouse PSCs (mPSCs) could be differentiated into multipotential progenitor cells and 3D induction system derived hematopoietic colonies owned potential of differentiating into lymphocyte cells. In addition, in vivo animal transplantation experiment showed that mPSCs (CD45.2) could be embedded into nonobese diabetic/severe combined immunodeficiency mice (CD45.1) with about 3% engraftment efficiency after 3 weeks transplantation. This study demonstrated that we developed the 3D induction approach that could efficiently promote the hematopoietic differentiation of mPSCs in vitro and obtained the multipotential progenitors that possessed the short‐term engraftment potential.
An integrated access control and lighting configuration system for smart buildings

This article presents an integrated access control and lighting configuration system for smart buildings. The system uses two-factor authentication, one based on face recognition and other on RFID TAG, and identifies the user inside a room and performs an automatic lighting configuration based on user’s behavior. The communication among the devices is performed by Radio Frequency using the low to medium frequency spectrum (LMRF), without providing direct Internet access, and, hence, avoiding known Internet security issues. This system can be easily deployed on meeting rooms or offices in business or government buildings. Through the evaluations we observe an acceptable processing execution time, an acceptable communication time and the robustness of the system.
Enhancement of the geomagnetic field reduces the phototaxis of rice brown planthopper Nilaparvata lugens associated with frataxin down‐regulation

The geomagnetic field (GMF) is an environmental cue that provides directional information for animals. The intensity of GMF is varied over space and time. Variations in the GMF intensity affect the navigation of animals and their physiology. In this study, the phototaxis of the migratory insect rice planthopper Nilaparvata lugens (N. lugens) and frataxin in N. lugens (Nl‐fh), which is a mitochondrial protein required for cellular iron homeostasis and iron‐sulfur cluster assembly, were investigated by using different intensities of magnetic field. From the results, individuals of N. lugens showed decreased phototaxis when reared and tested in a behavioral arena under a strong magnetic field. Besides the reduction in performance, an accompanying effect of the strong magnetic field condition was a reduced level of Nl‐fh‐messenger RNA, and a Nl‐fh knockdown indeed impaired the phototactic behavior in a tested sample of insects. This leads to the conclusion that the expression of frataxin is dependent on the strength of the surrounding magnetic field and that functional frataxin facilitates phototactic behavior in N. lugens.
Glutamatergic Input Varies with Phrenic Motor Neuron Size.

Like all skeletal muscles, the diaphragm muscle accomplishes a range of motor behaviors by recruiting different motor unit types in an orderly fashion. Recruitment of phrenic motor neurons (PhMNs) is generally assumed to be based primarily on the intrinsic properties of PhMNs with an equal distribution of descending excitatory inputs to all PhMNs. However, differences in pre-synaptic excitatory input across PhMNs of varying sizes could also contribute to the orderly recruitment pattern. In the spinal cord of Sprague-Dawley rats, we retrogradely labeled PhMNs using cholera toxin B (CTB) and validated a robust confocal imaging-based technique that utilizes semi-automated processing to identify pre-synaptic glutamatergic (Glu) terminals within a defined distance around the somal membrane of PhMNs of varying size. Our results revealed an ~10% higher density of Glu terminals at PhMNs in the lower tertile of somal surface area. These smaller PhMNs are likely recruited first to accomplish lower force ventilatory behaviors of the diaphragm as compared to larger PhMNs in the upper tertile that are recruited to accomplish higher force expulsive behaviors. These results suggest that differences in excitatory synaptic input to PhMNs may also contribute to the orderly recruitment of diaphragm motor units.