Search Results (12)

Background/Objectives: The insula is a deep, functionally heterogeneous region involved in various pathological conditions. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic avenue for neuromodulation, yet very few studies have directly investigated its effects on insular activity. Moreover, empirical evidence of target engagement of this region remains scarce. This study aimed to stimulate the insula with rTMS and assess blood oxygen level-dependent (BOLD) signal modulation using concurrent functional magnetic resonance imaging (fMRI). Methods: Ten participants were recruited, six of whom underwent a single session of 5 Hz high-frequency rTMS over the right insular cortex inside the MRI scanner. Stimulation was delivered using a compatible MRI-B91 TMS coil. Stimulation consisted of 10 trains of 10 s each, with a 50 s interval between trains. Frameless stereotactic neuronavigation ensured precise targeting. Paired t-tests were used to compare the mean BOLD signal obtained between stimulation trains with resting-state fMRI acquired before the rTMS stimulation session. A significant cluster threshold of q < 0.01 (False Discovery Rate; FDR) with a minimum cluster size of 10 voxels was applied. Results: Concurrent rTMS-fMRI revealed the significant modulation of BOLD activity within insular subregions. Increased activity was observed in the anterior, middle, and middle-inferior insula, while decreased activity was identified in the ventral anterior and posterior insula. Additionally, two participants reported transient dysgeusia following stimulation, which provides further evidence of insular modulation. Conclusions: These findings provide preliminary evidence that rTMS can modulate distinct subregions of the insular cortex. The combination of region-specific BOLD responses and stimulation-induced dysgeusia supports the feasibility of using rTMS to modulate insular activity. Full article

This study presents a theoretical framework for a radiative thermal memristor (RTM), utilizing Tungsten-doped vanadium dioxide (WVO) as the phase-change material (PCM) and silicon carbide (SiC) in the far-field regime. The behavior of the RTM is depicted through a Lissajous curve, illustrating the relationship between net flux (Q) and a periodically modulated temperature difference $\Delta$T(t). It is established that temperature variations in the memristance (M) of the RTM form a closed loop, governed by PCM hysteresis. The analysis explores the impact of thermal conductivity contrast (r) and periodic thermal input amplitude ($\theta$) on the Q–$\Delta$T curve and the M–$\Delta$T curve and negative differential thermal resistance (NDTR), revealing notable effects on the curve shapes and the emergence of NDTR. An increasing r leads to changes in the Lissajous curve’s shape and enhances the NDTR influence, while variations in both r and ($\theta$) significantly affect the Q values and Lissajous curve amplitudes. In the M–$\Delta$T curve, the height is linked to thermal conductivity contrast (r), with increasing r resulting in higher curve heights. Full article

Acid in situ leaching (ISL) is a common approach to the recovery of uranium in the subsurface. In acid ISL, there are numerous of chemical reactions among the injected sulfuric acid, groundwater, and porous media containing ore layers. A substantial amount of radioactive elements including U, Ra, Rn, as well as conventional elements like K, Na, and Ca, and trace elements such as As, Cd, and Pb, are released into the groundwater. Thus, in acid ISL, understanding the transport and reactions of these substances and managing pollution control is crucial. In this study, a three-dimensional reactive transport modeling (RTM) using TOUGHREACT was built to investigate the dynamic reactive migration process of UO₂²⁺, H⁺, and SO₄²⁻ at a typical uranium mine of Bayan-Uul. The model considering the partial penetration through wellbore in confined aquifer and complex chemical reactions among main minerals like uranium, K-feldspar, calcite, dolomite, anhydrite, gypsum, iron minerals, clay minerals, and other secondary minerals. The results show that after mining for one year, from the injection well to the extraction well, the spatial distribution of uranium volume fraction does not consistently increase or decrease, but it decreases initially and then increases. After mining for one year, the concentration front of UO₂²⁺ is about 20 m outside the mining area, the high concentration zone is mainly inside the mining area. The concentration front of H⁺ is no more than 50 m. SO₄²⁻ is the index with the highest concentration among the three indexes, the concentration front of SO₄²⁻ is no more than 100 m. The concentration breakthrough curve of the observation well 10 m from the mining area indicates that the concentrations of the three indicators began to significantly rise approximately after mining 0.05 years, reached the maximum value after mining 0.08 to 0.1 years, and then stabilized. The parameter sensitivity of absolute permeability and specific surface area of minerals shows that the concentration of H⁺ and SO₄²⁻ is positively correlated with absolute permeability. The concentration of H⁺ is negatively correlated with the specific surface area of calcite, anhydrite, K-feldspar, gypsum, hematite, and dolomite. The concentration of SO₄²⁻ is positively correlated with the specific surface area of K-feldspar and Hematite, and negatively correlated with the specific surface area of calcite, anhydrite, gypsum, and dolomite. The influence analysis of pumping ratio and non-uniform injection ratio shows that the non-uniform injection scheme has a more significant impact on pollution control. The water table, streamline, capture envelope, and the concentration breakthrough curve of five schemes with different pumping ratios and non-uniform injection ratio were obtained. The water table characteristics of five schemes shown that increase in the pumping ratio and the non-uniform injection ratio, the water table convex near the outer injection well is weakened and the groundwater depression cone near the pumping well is strengthened. This characteristic of water table exerts a notable retarding influence on the migration of pollutants from the mining area to the outside. For the scheme with a pumping ratio is 0 (the total pumping flow rate is equal to the total injection flow rate) and a non-uniform injection ratio is 0 (the flow rate of inner injection well Q1,Q2,Q3 is equal to the flow rate of outer injection well Q4,Q5,Q6), the streamline characteristics shown that a segment of the streamline of is diverging from inner region to the outer region. For other schemes, the streamline exhibits a convergent feature. It is indicated that by increasing the pumping ratio and non-uniform injection ratio, a closure flow field can be established, confining the groundwater pollutants resulting from mining within the capture envelope. Hence, the best scheme for preventing pollution migration is the scheme with a pumping ratio is 0 (the total pumping flow rate is equal to the total injection flow rate) and a non-uniform injection ratio is 0.1 (the flow rate of inner injection well Q₁,Q₂,Q₃ is 10% more than the flow rate of outer injection well Q₄,Q₅,Q₆). In this scheme, the optimal stable concentration of UO₂²⁺, H⁺, and SO₄²⁻ at the observation well obtained by RTM is lower than other schemes, and the values are 0.00316 mol/kg, 2.792 (pH), and 0.0952 mol/kg. The inner well injection rate is 194.09 m³/d, the outer well injection rate is 158.89 m³/d, and the pumping rate is 264.00 m³/d. Numerical simulation analysis suggests that a scheme with a larger non-uniform injection ratio is more conducive to the formation of a strong hydraulic capture zone, thereby controlling the migration of pollutants in the acid ISL. A reasonable suggestion is to adopt non-uniform injection mining mode in acid ISL. Full article

Q-compensated reverse time migration (Q-RTM) is a crucial technique in seismic imaging. However, stability is a prominent concern due to the exponential increase in high-frequency ambient noise during seismic wavefield propagation. The two primary strategies for mitigating instability in Q-RTM are regularization and low-pass filtering. Q-RTM instability can be addressed through regularization. However, determining the appropriate regularization parameters is often an experimental process, leading to challenges in accurately recovering the wavefield. Another approach to control instability is low-pass filtering. Nevertheless, selecting the cutoff frequency for different Q values is a complex task. In situations with low signal-to-noise ratios (SNRs) in seismic data, using low-pass filtering can make Q-RTM highly unstable. The need for a small cutoff frequency for stability can result in a significant loss of high-frequency signals. In this study, we propose a multi-task learning (MTL) framework that leverages data-driven concepts to address the issue of amplitude attenuation in seismic records, particularly when dealing with instability during the Q-RTM (reverse time migration with Q-attenuation) process. Our innovative framework is executed using a convolutional neural network. This network has the capability to both predict and compensate for the missing high-frequency components caused by Q-effects while simultaneously reconstructing the low-frequency information present in seismograms. This approach helps mitigate overwhelming instability phenomena and enhances the overall generalization capacity of the model. Numerical examples demonstrate that our Q-RTM results closely align with the reference images, indicating the effectiveness of our proposed MTL frequency-extension method. This method effectively compensates for the attenuation of high-frequency signals and mitigates the instability issues associated with the traditional Q-RTM process. Full article

Traumatic brain injury (TBI) is a significant public health concern, often leading to long-lasting impairments in cognitive, motor and sensory functions. The rapid development of non-invasive systems has revolutionized the field of TBI rehabilitation by offering modern and effective interventions. This narrative review explores the application of non-invasive technologies, including electroencephalography (EEG), quantitative electroencephalography (qEEG), brain–computer interface (BCI), eye tracking, near-infrared spectroscopy (NIRS), functional near-infrared spectroscopy (fNIRS), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) in assessing TBI consequences, and repetitive transcranial magnetic stimulation (rTMS), low-level laser therapy (LLLT), neurofeedback, transcranial direct current stimulation (tDCS), transcranial alternative current stimulation (tACS) and virtual reality (VR) as therapeutic approaches for TBI rehabilitation. In pursuit of advancing TBI rehabilitation, this narrative review highlights the promising potential of non-invasive technologies. We emphasize the need for future research and clinical trials to elucidate their mechanisms of action, refine treatment protocols, and ensure their widespread adoption in TBI rehabilitation settings. Full article

Several nucleotide analogues have been approved for use in treating hepatitis B virus (HBV) infection. Long-term exposure to therapy leads to the emergence of mutations within the HBV DNA polymerase gene, resulting in drug resistance, a major factor contributing to therapy failure. Chronic HBV patients from the Khyber Pakhtunkhwa province, Pakistan, who had completed 6 months of therapy participated in this study. Samples were collected from 60 patients. In this study, the entire reverse transcriptase domain of the HBV polymerase gene was amplified using nested polymerase chain reaction and sequenced. Drug-resistant mutations were detected in nine (22.5%) patients. All of these patients had lamivudine-resistant mutations (rtM204V + L180M), while seven individuals (17.5%) had both lamivudine- plus entecavir-resistant mutations (L180M + M204V + S202G). N236T, a mutation that gives rise to tenofovir and adefovir resistance, was observed in two (5%) patients. T184A, a partial drug-resistant mutation to entecavir, was found in five (12.5%) patients. Furthermore, other genotypic variants (100%) and vaccine escape mutations (5%) were additionally observed. Moreover, pN459Y (35%), pN131D (20%), pL231S (20%), pP130Q (17.5%), pS189Q (12.5%), pP161S (5%), pH160P (2.5%), pT322S (2.5%), and pA223S (2.5%) mutations in the polymerase gene, as well as sA166V (17.5%), sQ181K (12.5%), sV184R (7.5%), sA17E (5%), sP153S/K (5%), sW156C (5%), sC76Y (2.5%), and S132F (2.5%) mutations in the small surface gene, were identified for the first time in this study. Phylogenetic analysis showed that genotype D was predominant amongst the HBV carriers. Subtype D1 was found in most patients, while two patients were subtype D9. These novel findings may contribute to the body of knowledge and have clinical significance for treating and curing HBV infections in Pakistan. Full article

Seismic attenuation occurs during seismic wave propagation in a viscous medium, which will result in a poor image of subsurface structures. The attenuation compensation by directly amplifying the extrapolated wavefields may suffer from numerical instability because of the exponential compensation for seismic wavefields. To alleviate this issue, we have developed a stabilized frequency-domain Q-compensated reverse time migration (FQ-RTM). In the algorithm, we use a stabilized attenuation compensation operator, which includes both the stabilized amplitude compensation operator and the dispersion correction operator, for the seismic wavefield extrapolation. The dispersion correction operator is calculated based on the frequency-domain dispersion-only viscoacoustic wave equation, while the amplitude compensation operator is derived via a stabilized division of two propagation wavefields (the dispersion-only wavefield and the viscoacoustic wavefield). Benefiting from the stabilization scheme in the amplitude compensation, the amplification of the seismic noises is suppressed. The frequency-domain cross-correlation imaging condition is exploited to obtain the compensated image. The layered model experiments demonstrate the effectiveness and great compensation performance of our method. The BP gas model examples further verify its feasibility and stability. The field data applications indicate the practicability of the proposed method. The comparison between the acoustic and compensated results confirms that the proposed method is able to compensate for the seismic attenuation while suppressing the amplification of the high-frequency seismic noise. Full article

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2 mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient. Full article

Recently, it has been reported that the rt269I type of hepatitis B virus (HBV) polymerase (Pol) versus the rt269L type is more significantly related to lower viral replication and HBeAg negative infections in chronic hepatitis B (CHB) patients of genotype C2. In this study, we compared mutation rates within HBV genomes between rt269L and rt269I using a total of 234 HBV genotype C2 full genome sequences randomly selected from the HBV database (115 of rt269L and 119 of rt269I type). When we applied the Benjamini and Hochberg procedure for multiple comparisons, two parameters, dN and d, at the amino acids level in the Pol region were significantly higher in the rt269I type than in the rt269L type. Although it could not reach statistical significance from the Benjamini and Hochberg procedure, nonsynonymous (NS) mutations in the major hydrophilic region (MHR) or “a” determinant in the surface antigens (HBsAg ORF) related to host immune escape or vaccine escape are more frequently generated in rt269I strains than in rt269L. We also found that there are a total of 19 signature single nucleotide polymorphisms (SNPs), of which 2 and 17 nonsynonymous mutation types were specific to rt269L and rt269I, respectively: Of these, most are HBeAg negative infections (preC-W28*, X-V5M and V131I), lowered HBV DNA or virion production (C-I97F/L, rtM204I/V) or preexisting nucleot(s)ide analog resistance (NAr) (rtN139K/H, rtM204I/V and rtI224V) or disease severity (preC-W28*, C-I97F/L, C-Q182K/*, preS2-F141L, S-L213I/S, V/L5M, T36P/S/A, V131I, rtN139K/H, rtM204I/V and rtI224V). In conclusion, our data showed that rt269I types versus rt269L types are more prone to overall genome mutations, particularly in the Pol region and in the MHR or “a” determinant in genotype C2 infections and are more prevalent in signature NS mutations related to lowered HBV DNA replication, HBsAg and HBeAg secretion and potential NAr variants and hepatocellular carcinoma (HCC), possibly via type I interferon (IFN-I)-mediated enhanced inflammation. Our data suggest that rt269L types could contribute to liver disease progression via the generation of immune escape or enhanced persistent infection in chronic patients of genotype C2. Full article

Inevitable long-term therapy with nucleos(t)ide analogs in patients with chronic hepatitis B virus (HBV) infection has selected reverse-transcriptase (rt) mutants in a substantial proportion of patients. Some of these mutants introduce premature stop codons in the overlapping surface (s) gene, including rtA181T/sW172*, which has been shown to enhance oncogenicity. The oncogenicity of another drug-resistant mutant, rtM204I/sW196*, has not been studied. We constructed plasmids harboring rtM204I/sW196* and assessed the in vitro cell transformation, endoplasmic reticulum (ER) stress response, and xenograft tumorigenesis of the transformants. Cellular gene expression was analyzed by cDNA microarray and was validated. The rtM204I/sW196* transformants, compared with the control or wild type, showed enhanced transactivation activities for c-fos, increased cell proliferation, decreased apoptosis, more anchorage-independent growth, and enhanced tumor growth in mouse xenografts. X box-binding protein-1 (XBP1) splicing analysis showed no ER stress response. Altered gene expressions, including up-regulated MGST2 and HIF1A, and downregulated transforming growth factor beta-induced (TGFbi), were unveiled by cDNA microarray and validated by RT-qPCR. The TGFbi alteration occurred in transformants with wild type or mutated HBV. The altered MGST2 and HIF1A were found only with mutated HBV. The rtM204I/sW196* preS/S truncation may endorse the cell transformation and tumorigenesis ability via altered host gene expressions, including MGST2, HIF1A, and TGFbi. Downregulated TGFbi may be a common mechanism for oncogenicity in HBV surface truncation mutants. Full article

Drought is one of the most important factors affecting plant growth and productivity. The previous results on drought tolerance (DT) genetic system in soybean indicated a complex of genes not only few ones were involved in the trait. This study is featured with a relatively thorough identification of QTL-allele/candidate-gene system using an efficient restricted two-stage multi-locus multi-allele genome-wide association study, on two comprehensive DT indicators, membership index values of relative plant weight (MPW) and height (MPH), instead of a single biological characteristic, in a large sample (564 accessions) of the Chinese cultivated soybean population (CCSP). Based on 24,694 multi-allele markers, 75 and 64 QTL with 261 and 207 alleles (2–12/locus) were detected for MPW and MPH, explaining 54.7% and 47.1% of phenotypic variance, respectively. The detected QTL-alleles were organized into a QTL-allele matrix for each indicator, indicating DT is a super-trait conferred by two (even more) QTL-allele systems of sub-traits. Each CCSP matrix was separated into landrace (LR) and released cultivar (RC) sub-matrices, which showed significant differentiation in QTL-allele constitutions, with 58 LR alleles excluded and 16 new ones emerged in RC. Using the matrices, optimal crosses with great DT transgressive recombinants were predicted. From the detected QTL, 177 candidate genes were annotated and validated with quantitative Real-time PCR, and grouped into nine categories, with ABA and stress responders as the major parts. The key point of the above results is the establishment of relatively full QTL-allele matrices composed of numerous gene functions jointly conferring DT, therefore, demonstrates the complexity of DT genetic system and potential of CCSP in DT breeding. Full article

Die-stacking technology is expanding the space diversity of on-chip communications by leveraging through-silicon-via (TSV) integration and wafer bonding. The 3D network-on-chip (NoC), a combination of die-stacking technology and systematic on-chip communication infrastructure, suffers from increased thermal density and unbalanced heat dissipation across multi-stacked layers, significantly affecting chip performance and reliability. Recent studies have focused on runtime thermal management (RTM) techniques for improving the heat distribution balance, but performance degradations, owing to RTM mechanisms and unbalanced inter-layer traffic distributions, remain unresolved. In this study, we present a Q-function-based traffic- and thermal-aware adaptive routing algorithm, utilizing a reinforcement machine learning technique that gradually incorporates updated information into an RTM-based 3D NoC routing path. The proposed algorithm initially collects deadlock-free directions, based on the RTM and topology information. Subsequently, Q-learning-based decision making (through the learning of regional traffic information) is deployed for performance improvement with more balanced inter-layer traffic. The simulation results show that the proposed routing algorithm can improve throughput by 14.0%–28.2%, with a 24.9% more balanced inter-layer traffic load and a 30.6% more distributed inter-layer thermal dissipation on average, compared with those obtained in previous studies of a 3D NoC with an 8 $\times$ 8 $\times$ 4 mesh topology. Full article