ABSTRACT
We proposed a 2D 1 × 64 silicon optical phased array with a backside silicon-etched structure to achieve high tuning efficiency and a wide longitudinal steering range. At the radiator array, the n-i-n heater was implemented to steer the light in a longitudinal direction through the thermo-optic effect. The deep reactive ion etching process was utilized to generate the 600â µm depth air trench with a 1.8â cm2 area from the backside of the radiator array. We achieved almost 100% increment in terms of tuning efficiency, which is 1.56°/W for the proposed structure and 0.78°/W for the conventional structure.
ABSTRACT
Magnetic resonance imaging (MRI) can extract the tissue conductivity values from in vivo data using the so-called phase-based magnetic resonance electrical properties tomography (MR-EPT). However, this procedure suffers from noise amplification caused by the use of the Laplacian operator. To counter this issue, we propose a novel preprocessing denoiser for magnetic resonance transceive phase images, operating in an unsupervised manner. Inspired by the deep image prior approach, we apply the random initialization of a convolutional neural network, which enforces an implicit regularization. Additionally, we introduce Stein's unbiased risk estimator, which is the unbiased estimator of the mean square error for optimizing the network without the need for label images. This modification not only tackles the overfitting problem inherent in the deep image prior approach but also operates within a purely unsupervised framework. In addition, instead of using phase images, we use real and imaginary images, which aligns with the theoretical model of the risk estimator. Our generative model needs neither the preparation of training datasets nor prior training procedure, and it maintains adaptability across various resolutions and signal-to-noise ratio levels. In testing. our method significantly diminished residual error remaining in phase maps, quantitatively as well as qualitatively, for both phantom and simulated brain data. Furthermore, it outperformed other denoising methods in reducing noise amplification and boundary error. When applied to healthy volunteer and patient data, the proposed method revealed reduced error in the reconstructed conductivity maps, with conductivity values aligning well with established literature values. To the best of our knowledge, this is the first blind approach using a purely unsupervised denoising framework that can implement a 2D phase-based MR-EPT reconstruction algorithm. The source code is available at https://github.com/Yonsei-MILab/Implicit-Regularization-forMREPT-with-SURE.
ABSTRACT
Although supplementation with docosahexaenoic acid (DHA) during porcine oocyte IVM is well-established, the available data are limited due to the lack of consistency. Moreover, to our knowledge, the anti-oxidant effects of DHA on porcine oocytes have not been reported. Hence, this study aimed to examine the effects of DHA supplementation on the regulation of energy metabolism during porcine oocyte maturation to improve oocyte maturation and embryonic development. By supplementing the IVM medium with various DHA concentrations, 25 µM DHA was identified as the optimal concentration which improved intraoocyte glutathione content and enhanced embryonic development after parthenogenesis. Compared to embryos derived from the control group, those derived from SCNT or IVF showed significantly improved blastocyst formation upon DHA supplementation during IVM. In addition, various transcription factors associated with oocyte development and apoptosis in mature oocytes were beneficially regulated in the DHA-treated oocytes. Moreover, DHA improved the AMP-activated protein kinase (AMPK)-regulatory ability of porcine oocytes and ameliorated nuclear maturation and embryonic development, which were decreased by artificially downregulating AMPK. To our knowledge, this is the first study to examine the effects of DHA as an AMPK regulator on oocyte maturation and embryo development in pigs. Furthermore, DHA addition to the IVM medium upregulated the relative expression of genes associated with mitochondrial potential and lipid metabolism. Therefore, the membrane potential of mitochondria (evaluated based on the JC-1 aggregate/JC-1 monomer ratio) and the levels of fatty acids and lipid droplets in matured oocytes increased, resulting in increased ATP synthesis. In conclusion, the DHA treatment of porcine oocytes with 25 µM DHA during IVM enhances the homeostasis of energy metabolism by improving mitochondrial function and lipid metabolism, leading to improved quality of matured oocytes and enhanced embryonic developmental potential of in vitro produced (IVP) embryos. Thus, 25 µM DHA supplementation could serve as a tool for improving the quality of IVP embryos. The study findings provide a basis for further research on improving the production efficiency of cloned animals by securing high-quality matured oocytes and enhancing energy metabolism in mammalian oocytes, including those of pigs.
Subject(s)
Docosahexaenoic Acids , Embryonic Development , Energy Metabolism , In Vitro Oocyte Maturation Techniques , Oocytes , Animals , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/administration & dosage , Oocytes/drug effects , Swine/embryology , In Vitro Oocyte Maturation Techniques/veterinary , In Vitro Oocyte Maturation Techniques/methods , Energy Metabolism/drug effects , Embryonic Development/drug effects , Homeostasis/drug effects , FemaleABSTRACT
Cell-free protein synthesis (CFPS) reactions can be used to detect nucleic acids. However, most CFPS systems rely on a toehold switch and exhibit the following critical limitations: (i) off-target signals due to leaky translation in the absence of target nucleic acids, (ii) a suboptimal detection limit of approximately 30 nM without pre-amplification, and (iii) labor-intensive screening processes due to sequence constraints for the target nucleic acids. To overcome these shortcomings, we developed a new split T7 switch-mediated CFPS system in which the split T7 promoter was applied to a three-way junction structure to selectively initiate transcription-translation only in the presence of target nucleic acids. Both fluorescence and colorimetric detection systems were constructed by employing different reporter proteins. Notably, we introduced the self-complementation of split fluorescent proteins to streamline preparation of the proposed system, enabling versatile applications. Operation of this one-pot approach under isothermal conditions enabled the detection of target nucleic acids at concentrations as low as 10 pM, representing more than a thousand times improvement over previous toehold switch-based approaches. Furthermore, the proposed system demonstrated high specificity in detecting target nucleic acids and compatibility with various reporter proteins encoded in the expression region. By eliminating issues associated with the previous toehold switch system, our split T7 switch-mediated CFPS system could become a core platform for detecting various target nucleic acids.
Subject(s)
Biosensing Techniques , Cell-Free System , Nucleic Acids , Protein Biosynthesis , Biosensing Techniques/methods , Nucleic Acids/chemistry , Bacteriophage T7/genetics , Colorimetry/methods , Promoter Regions, Genetic , Limit of Detection , Viral Proteins , HumansABSTRACT
The reaction of Li[(TAML)CoIII]·3H2O (TAML = tetraamido macrocyclic tetraanionic ligand) with iodosylbenzene at 253 K in acetone in the presence of redox-innocent metal ions (Sc(OTf)3 and Y(OTf)3) or triflic acid affords a blue species 1, which is converted reversibly to a green species 2 upon cooling to 193 K. The electronic structures of 1 and 2 have been determined by combining advanced spectroscopic techniques (X-band electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR), X-ray absorption spectroscopy/extended X-ray absorption fine structure (XAS/EXAFS), and magnetic circular dichroism (MCD)) with ab initio theoretical studies. Complex 1 is best represented as an S = 1/2 [(Sol)(TAMLâ¢+)CoIII---OH(LA)]- species (LA = Lewis/Brønsted acid and Sol = solvent), where an S = 1 Co(III) center is antiferromagnetically coupled to S = 1/2 TAMLâ¢+, which represents a one-electron oxidized TAML ligand. In contrast, complex 2, also with an S = 1/2 ground state, is found to be multiconfigurational with contributions of both the resonance forms [(H-TAML)CoIVâO(LA)]- and [(H-TAMLâ¢+)CoIIIâO(LA)]-; H-TAML and H-TAMLâ¢+ represent the protonated forms of TAML and TAMLâ¢+ ligands, respectively. Thus, the interconversion of 1 and 2 is associated with a LA-associated tautomerization event, whereby H+ shifts from the terminal -OH group to TAMLâ¢+ with the concomitant formation of a terminal cobalt-oxo species possessing both singlet (SCo = 0) Co(III) and doublet (SCo = 1/2) Co(IV) characters. The reactivities of 1 and 2 at different temperatures have been investigated in oxygen atom transfer (OAT) and hydrogen atom transfer (HAT) reactions to compare the activation enthalpies and entropies of 1 and 2.
ABSTRACT
We introduce the heterocumulene ligand [(Ad)NCC(tBu)]- (Ad=1-adamantyl (C10H15), tBu=tert-butyl, (C4H9)), which can adopt two forms, the azaalleneyl and ynamide. This ligand platform can undergo a reversible chelotropic shift using Brønsted acid-base chemistry, which promotes an unprecedented spin-state change of the [VIII] ion. These unique scaffolds are prepared via addition of 1-adamantyl isonitrile (C≡NAd) across the alkylidyne in complexes [(BDI)V≡CtBu(OTf)] (A) (BDI-=ArNC(CH3)CHC(CH3)NAr), Ar=2,6-iPr2C6H3) and [(dBDI)V≡CtBu(OEt2)] (B) (dBDI2-=ArNC(CH3)CHC(CH2)NAr). Complex A reacts with C≡NAd, to generate the high-spin [VIII] complex with a κ1-N-ynamide ligand, [(BDI)V{κ1-N-(Ad)NCC(tBu)}(OTf)] (1). Conversely, B reacts with C≡NAd to generate a low-spin [VIII] diamagnetic complex having a chelated κ2-C,N-azaalleneyl ligand, [(dBDI)V{κ2-N,C-(Ad)NCC(tBu)}] (2). Theoretical studies have been applied to better understand the mechanism of formation of 2 and the electronic reconfiguration upon structural rearrangement by the alteration of ligand denticity between 1 and 2.
ABSTRACT
The purpose of this study was to compare the efficiency of the production of cloned transgenic Yucatan miniature pigs (YMPs) using two recipient breeds, i.e., YMPs and domestic pigs (DPs), under various embryo transfer conditions. We initially assessed the in vitro developmental competence of embryos obtained via somatic cell nuclear transfer (SCNT) from three different transgenic donor cells. No difference was observed among the three groups regarding developmental competence. Furthermore, the cloning efficiency remained consistent among the three groups after the transfer of the SCNT embryos to each surrogate mother. Subsequently, to compare the efficiency of the production of cloned transgenic YMPs between the two recipient breeds using varying parameters, including ovulation status (preovulation and postovulation), duration of in vitro culture (IVC) (incubated within 24 h and 24-48 h), and the number of transferred SCNT embryos (less than and more than 300), we assessed the pregnancy rates, delivery rates, mean offspring counts, and cloning efficiency. Regarding the ovulation status, YMPs exhibited higher pregnancy rates, delivery rates, and cloning efficiency compared with DPs in both statuses. Moreover, the pregnancy rates, delivery rates, and cloning efficiency were affected by the ovulation status in DPs, but not in YMPs. The comparison of IVC duration between groups revealed that YMPs had higher pregnancy rates vs. DPs in both conditions. SCNT embryos cultured for 24-48 h in YMPs yielded higher delivery rates and cloning efficiency compared with those cultured for less than 24 h in DPs. Finally, the analysis based on the number of transferred SCNT embryos showed that both the pregnancy and delivery rates were higher in YMPs vs. DPs. However, the highest average number of offspring was obtained when more than 300 SCNT embryos were transferred into DPs, whereas the cloning efficiency was higher in YMPs vs. DPs. Our results suggest that YMPs are more suitable recipients than are DPs under various conditions for the production of cloned transgenic YMPs.
Subject(s)
Cloning, Organism , Nuclear Transfer Techniques , Pregnancy , Female , Swine/genetics , Animals , Swine, Miniature/genetics , Animals, Genetically Modified , Cloning, Organism/veterinary , Cloning, Organism/methods , Nuclear Transfer Techniques/veterinary , Embryo Transfer/veterinary , Embryo Transfer/methodsABSTRACT
Synthetic oligonucleotides have become a fundamental tool in a wide range of biological fields, including synthetic biology, biosensing, and DNA storage. Reliable access to equipment for synthesizing high-density oligonucleotides in the laboratory ensures research security and the freedom of research expansion. In this study, we introduced the Open-Source Inkjet DNA Synthesizer (OpenIDS), an open-source inkjet-based microarray synthesizer that offers ease of construction, rapid deployment, and flexible scalability. Utilizing 3D printing, Arduino, and Raspberry Pi, this newly designed synthesizer achieved robust stability with an industrial inkjet printhead. OpenIDS maintains low production costs and is therefore suitable for self-fabrication and optimization in academic laboratories. Moreover, even non-experts can create and control the synthesizer with a high degree of freedom for structural modifications. Users can easily add printheads or alter the design of the microarray substrate according to their research needs. To validate its performance, we synthesized oligonucleotides on 144 spots on a 15 × 25-mm silicon wafer filled with controlled pore glass. The synthesized oligonucleotides were analyzed using urea polyacrylamide gel electrophoresis.
Subject(s)
DNA , Oligonucleotides , DNA/chemistry , Microarray AnalysisABSTRACT
BACKGROUND: While breast ultrasound (US) is a useful tool for diagnosing breast masses, it can entail false-positive biopsy results because of some overlapping features between benign and malignant breast masses and subjective interpretation. PURPOSE: To evaluate the performance of conductivity imaging for reducing false-positive biopsy results related to breast US, as compared to diffusion-weighted imaging (DWI) and abbreviated MRI consisting of one pre- and one post-contrast T1-weighted imaging. STUDY TYPE: Prospective. SUBJECTS: Seventy-nine women (median age, 44 years) with 86 Breast Imaging Reporting and Data System (BI-RADS) category 4 masses as detected by breast US. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted turbo spin echo sequence, DWI, and abbreviated contrast-enhanced MRI (T1-weighted gradient echo sequence). ASSESSMENT: US-guided biopsy (reference standard) was obtained on the same day as MRI. The maximum and mean conductivity parameters from whole and single regions of interest (ROIs) were measured. Apparent diffusion coefficient (ADC) values were obtained from an area with the lowest signal within a lesion on the ADC map. The performance of conductivity, ADC, and abbreviated MRI for reducing false-positive biopsies was evaluated using the following criteria: lowest conductivity and highest ADC values among malignant breast lesions and BI-RADS categories 2 or 3 on abbreviated MRI. STATISTICAL TESTS: One conductivity parameter with the maximum area under the curve (AUC) from receiver operating characteristics was selected. A P-value <0.05 was considered statistically significant. RESULTS: US-guided biopsy revealed 65 benign lesions and 21 malignant lesions. The mean conductivity parameter of the single ROI method was selected (AUC = 0.74). Considering conductivity (≤0.10 S/m), ADC (≥1.60 × 10-3 mm2 /sec), and BI-RADS categories 2 or 3 reduced false-positive biopsies by 23% (15 of 65), 38% (25 of 65), and 43% (28 of 65), respectively, without missing malignant lesions. DATA CONCLUSION: Conductivity imaging may show lower performance than DWI and abbreviated MRI in reducing unnecessary biopsies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
Subject(s)
Breast Neoplasms , Contrast Media , Female , Humans , Adult , Prospective Studies , Retrospective Studies , Magnetic Resonance Imaging/methods , Diffusion Magnetic Resonance Imaging/methods , Biopsy , Image-Guided Biopsy , Diagnosis, Differential , Breast Neoplasms/diagnostic imaging , Sensitivity and SpecificityABSTRACT
Calibrating the phase in integrated optical phased arrays (OPAs) is a crucial procedure for addressing phase errors and achieving the desired beamforming results. In this paper, we introduce a novel phase calibration methodology based on a deep neural network (DNN) architecture to enhance beamforming in integrated OPAs. Our methodology focuses on precise phase control, individually tailored to each of the 64 OPA channels, incorporating electro-optic phase shifters. To effectively handle the inherent complexity arising from the numerous voltage set combinations required for phase control across the 64 channels, we employ a tandem network architecture, further optimizing it through selective data sorting and hyperparameter tuning. To validate the effectiveness of the trained DNN model, we compared its performance with 20 reference beams obtained through the hill climbing algorithm. Despite an average intensity reduction of 0.84 dB in the peak values of the beams compared to the reference beams, our experimental results demonstrate substantial agreements between the DNN-predicted beams and the reference beams, accompanied by a slight decrease of 0.06 dB in the side-mode-suppression-ratio. These results underscore the practical effectiveness of the DNN model in OPA beamforming, highlighting its potential in scenarios that necessitate the intelligent and time-efficient calibration of multiple beams.
ABSTRACT
Magnetic resonance electrical properties tomography (MR-EPT) is a non-invasive measurement technique that derives the electrical properties (EPs, e.g., conductivity or permittivity) of tissues in the radiofrequency range (64 MHz for 1.5 T and 128 MHz for 3 T MR systems). Clinical studies have shown the potential of tissue conductivity as a biomarker. To date, model-based conductivity reconstructions rely on numerical assumptions and approximations, leading to inaccuracies in the reconstructed maps. To address such limitations, we propose an artificial neural network (ANN)-based non-linear conductivity estimator trained on simulated data for conductivity brain imaging. Network training was performed on 201 synthesized T2-weighted spin-echo (SE) data obtained from the finite-difference time-domain (FDTD) electromagnetic (EM) simulation. The dataset was composed of an approximated T2-w SE magnitude and transceive phase information. The proposed method was tested three in-silico and in-vivo on two volunteers and three patients' data. For comparison purposes, various conventional phase-based EPT reconstruction methods were used that ignore B 1 + magnitude information, such as Savitzky-Golay kernel combined with Gaussian filter (S-G Kernel), phase-based convection-reaction EPT (cr-EPT), magnitude-weighted polynomial-fitting phase-based EPT (Poly-Fit), and integral-based phase-based EPT (Integral-based). From the in-silico experiments, quantitative analysis showed that the proposed method provides more accurate and improved quality (e.g., high structural preservation) conductivity maps compared to conventional reconstruction methods. Representatively, in the healthy brain in-silico phantom experiment, the proposed method yielded mean conductivity values of 1.97 ± 0.20 S/m for CSF, 0.33 ± 0.04 S/m for WM, and 0.52 ± 0.08 S/m for GM, which were closer to the ground-truth conductivity (2.00, 0.30, 0.50 S/m) than the integral-based method (2.56 ± 2.31, 0.39 ± 0.12, 0.68 ± 0.33 S/m). In-vivo ANN-based conductivity reconstructions were also of improved quality compared to conventional reconstructions and demonstrated network generalizability and robustness to in-vivo data and pathologies. The reported in-vivo brain conductivity values were in agreement with literatures. In addition, the proposed method was observed for various SNR levels (SNR levels = 10, 20, 40, and 58) and repeatability conditions (the eight acquisitions with the number of signal averages = 1). The preliminary investigations on brain tumor patient datasets suggest that the network trained on simulated dataset can generalize to unforeseen in-vivo pathologies, thus demonstrating its potential for clinical applications.
Subject(s)
Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Humans , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Electric Conductivity , Phantoms, Imaging , Neuroimaging , AlgorithmsABSTRACT
Extracellular vesicles (EVs) play an active role in regulating different physiological events, however, endocrine control of EVs cargo contents remain poorly understood. In this study, we aimed to isolate EVs from the porcine oviductal epithelial cells (POECs) that were primed with steroid hormones including estradiol (E2) and progesterone (P4), mimicking the in vivo conditions of the reproductive cycle and studied their effects on in vitro produced embryonic development. For this purpose, POECs were treated either with 0 concentration (control) or two different combinations of E2 and P4 including 50 pg/mL E2 + 0.5 ng/mL P4 (group H1), and 10 pg/mL E2 + 35 ng/mL P4 (group H2). Embryos were prepared after in vitro maturation either by parthenogenetic activation or somatic cell nuclear transfer (SCNT) technique. Treating parthenogenetic embryo with EVs, led a significantly higher rate of the blastocyst formation in the group supplemented with each EVs, compared to the control group. In addition, TUNEL assay and gene expression level analysis revealed that apoptosis was significantly reduced in the H2 EVs group. Furthermore, EVs from hormone-primed POECs improved the formation rate of porcine SCNT embryos compared to the control group. While in each EVs supplemented group (control EVs, H1 EVs, H2 EVs), the expression of cell reprogramming-related genes in cloned embryos showed a tendency of increase, the effect was stronger in H1 EVs and H2 EVs. In conclusion, EVs derived from POECs cultured in hormonal conditions simulating the in vivo environment had a positive effect on porcine blastocysts formation, which will likely facilitate in the production of cloned embryos.
Subject(s)
Embryonic Development , Extracellular Vesicles , Female , Pregnancy , Swine , Animals , Parthenogenesis , Nuclear Transfer Techniques/veterinary , Progesterone/pharmacology , Progesterone/metabolism , Epithelial Cells , Blastocyst/physiologyABSTRACT
We investigated the correlation between standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors' heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman's correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status.
Subject(s)
Breast Neoplasms , Fluorodeoxyglucose F18 , Humans , Female , Positron Emission Tomography Computed Tomography/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Radiopharmaceuticals/therapeutic use , Prognosis , Positron-Emission Tomography/methodsABSTRACT
Precise imaging in three-dimension (3D) is an essential technique for solid-state light detection and ranging (LiDAR). Among various solid-state LiDAR technologies, silicon (Si) optical phased array (OPA)-based LiDAR has the significant advantage of robust 3D imaging due to its high scanning speed, low power consumption, and compactness. Numerous techniques employing a Si OPA have utilized two-dimensional arrays or wavelength tuning for longitudinal scanning but the operation of those systems is restricted by additional requirements. Here, we demonstrate high-accuracy 3D imaging using a Si OPA with a tunable radiator. As we adapted a time-of-flight approach for distance measurement, we have developed an optical pulse modulator that allows a ranging accuracy of less than 2â cm. The implemented Si OPA is composed of an input grating coupler, multimode interferometers, electro-optic p-i-n phase shifters, and thermo-optic n-i-n tunable radiators. With this system, it is possible to attain a wide beam steering range of 45° in a transversal angle with a 0.7° divergence angle, and 10° in a longitudinal angle with a 0.6° divergence angle can be achieved using Si OPA. The character toy model was successfully imaged in three dimensions with a range resolution of 2â cm using the Si OPA. The further improvement of each component of the Si OPA will allow even more accurate 3D imaging over a longer distance.
ABSTRACT
Although T cell activation is known to involve the internalization of the T cell antigen receptor (TCR), much less is known regarding the release of TCRs following T cell interaction with cognate antigen-presenting cells. In this study, we examine the physiological mechanisms underlying TCR release following T cell activation. We show that T cell activation results in the shedding of TCRs in T cell microvilli, which involves a combined process of trogocytosis and enzymatic vesiculation, leading to the loss of membrane TCRs and microvilli-associated proteins and lipids. Surprisingly, unlike TCR internalization, this event results in the rapid upregulation of surface TCR expression and metabolic reprogramming of cholesterol and fatty acid synthesis to support cell division and survival. These results demonstrate that TCRs are lost through trogocytic 'molting' following T cell activation and highlight this mechanism as an important regulator of clonal expansion.
Subject(s)
Receptors, Antigen, T-Cell , T-Lymphocytes , Microvilli , Cell Membrane , AdipogenesisABSTRACT
The signaling pathways governing acetaminophen (APAP)-induced liver injury have been extensively studied. However, little is known about the ubiquitin-modifying enzymes needed for the regulation of APAP-induced liver injury. Here, we examined whether the Pellino3 protein, which has E3 ligase activity, is needed for APAP-induced liver injury and subsequently explored its molecular mechanism. Whole-body Peli3-/- knockout (KO) and adenovirus-mediated Peli3 knockdown (KD) mice showed reduced levels of centrilobular cell death, infiltration of immune cells, and biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), upon APAP treatment compared to wild-type (WT) mice. Peli3 deficiency in primary hepatocytes decreased mitochondrial and lysosomal damage and reduced the mitochondrial reactive oxygen species (ROS) levels. In addition, the levels of phosphorylation at serine 9 in the cytoplasm and mitochondrial translocation of GSK3ß were decreased in primary hepatocytes obtained from Peli3-/- KO mice, and these reductions were accompanied by decreases in JNK phosphorylation and mitochondrial translocation. Pellino3 bound more strongly to GSK3ß compared with JNK1 and JNK2 and induced the lysine 63 (K63)-mediated polyubiquitination of GSK3ß. In rescue experiments, the ectopic expression of wild-type Pellino3 in Peli3-/- KO hepatocytes restored the mitochondrial translocation of GSK3ß, but this restoration was not obtained with expression of a catalytically inactive mutant of Pellino3. These findings are the first to suggest a mechanistic link between Pellino3 and APAP-induced liver injury through the modulation of GSK3ß polyubiquitination.
Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury, Chronic , Animals , Mice , Acetaminophen/adverse effects , Phosphorylation , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Liver/metabolism , Hepatocytes/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Mice, Inbred C57BLABSTRACT
A cost-effective, simple to use, and automated technique that can provide real-time feedback control for droplet generation is required to obtain droplets with high-throughput, stability, and uniformity. This study introduces a disposable droplet generation microfluidic device (dDrop-Chip) that can simultaneously control both droplet size and production rate in real time. The dDrop-Chip consists of a reusable sensing substrate and a disposable microchannel that can be assembled using vacuum pressure. It also integrates a droplet detector and a flow sensor on-chip, enabling real-time measurement and feedback control of droplet size and sample flow rate. The dDrop-Chip has the additional advantage of being disposable, which can prevent chemical and biological contamination, due to low manufacturing cost by the film-chip technique. We demonstrate benefits of the dDrop-Chip by controlling droplet size at a fixed sample flow rate and the production rate at a fixed droplet size using real-time feedback control. The experimental results show that the dDrop-Chip consistently generates monodisperse droplets with a length of 219.36 ± 0.08 µm (CV 0.036%) at a production rate of 32.38 ± 0.48 Hz using the feedback control, while without feedback control, there is a significant deviation in droplet length (224.18 ± 6.69 µm, CV 2.98%) and production rate (33.94 ± 1.72 Hz) despite the use of identical devices. Therefore, the dDrop-Chip is a reliable, cost-effective, and automated technique for generating droplets of controlled size and production rate in real time, making it suitable for various droplet-based applications.
ABSTRACT
We employed the chemical potential equalization principle to demonstrate that fractional electrons are involved in the electro-inductive effect as well as the vibrational Stark effect. By the chemical potential model, we were able to deduce that the frontier molecular orbitals of immobilized molecules can provide valuable insight into these effects. To further understand and quantify these findings, we introduced fractional charge density functional theory (FC-DFT), a canonical ensemble approach for open systems. This method allows for the calculation of electronic energies, nuclear gradients, and the Hessian matrix of fractional electronic systems. To correct the spurious delocalization error commonly found in approximate density functionals for small systems, we imposed the Perdew-Parr-Levy-Balduz (PPLB) condition through linear interpolation of two adjacent integer points (LI-FC-DFT). Although this approach is relatively simple in terms of molecular modeling, the results obtained through LI-FC-DFT calculations predict the same trend seen in experimental reactivity and the frequency change of immobilized molecules.
ABSTRACT
We proposed inverse-designed nanophotonic waveguide devices which have the desired optical responses in the wide band of 1450-1650â nm. The proposed devices have an ultra-compact size of just 1.5â µm × 3.0â µm and are designed on a silicon-on-insulator (SOI) waveguide platform. Individual nano-pixels with dimensions of 150â nm × 150â nm were made of either silicon or silicon dioxide, and the materials for the 200 total cells were determined using a trained deep neural network. While training the two networks, the hyperparameter optimization method was applied to make the training process efficient. We then fabricated the proposed devices using a CMOS-compatible fabrication process, and experimentally verified the fabricated device performance.
ABSTRACT
BACKGROUND: Phase-based electrical property tomography (EPT) is a technique that allows conductivity reconstruction with only phase of the B1 field under the assumption that the magnitude of the B1 fields are homogeneous. The more this assumption is violated, the less accurate the reconstructed conductivity. Thus, a method that ensures homogeneity of | B 1 - | $| {{\rm{B}}_1^ - } |$ field is important for breast image using multi-receiver coil. PURPOSE: To develop a method for multi-receiver combination for phase-based EPT usable for breast EPT imaging in the clinic. METHODS: Theory of the proposed method is presented. To validate the proposed method, the phantom and in-vivo experiments were conducted. Conductivity images were reconstructed using the transceive phase of the combined image and results were compared with another combination method. RESULTS: The proposed method's conductivity results were more stable than those of the previous method when | B 1 + | $| {{\rm{B}}_1^ + } |$ was not homogeneous and when the homogeneous contrast region was small. The phantom and in-vivo results indicate that the proposed method produces improved conductivity images than the previous method. The proposed combination method also increased the conductivity contrast between benign and cancerous tissues. CONCLUSION: The proposed method produced more stable multi-receiver combination for phase-based EPT of the breast in a clinical environment.