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Today, as deep learning (DL) is applied more often in daily life, dedicated processors such as CPUs and GPUs have become very important for accelerating model executions. With the growth of technology, people are becoming accustomed to using edge devices, such as mobile phones, smart watches, and VR devices in their daily lives. A variety of technologies using DL are gradually being applied to these edge devices. However, there is a large number of computations in DL. It faces a challenging problem how to provide solutions in the edge devices. In this article, the proposed method enables a flow with the RISC-V Packed extension (P extension) in TVM. TVM, an open deep learning compiler for neural network models, is growing as a key infrastructure for DL computing. RISC-V is an open instruction set architecture (ISA) with customized and flexible features. The Packed-SIMD extension is a RISC-V extension that enables subword single-instruction multiple-data (SIMD) computations in RISC-V architectures to support fallback engines in AI computing. In the proposed flow, a fixed-point type that is supported by an integer of 16-bit type and saturation instructions is added to replace the original 32-bit float type. In addition, an auto-tuning method is proposed to use a uniform selector mechanism (USM) to find the binary point position for fixed-point type use. The tensorization feature of TVM can be used to optimize specific hardware such as subword SIMD instructions with RISC-V P extension. With our experiment on the Spike simulator, the proposed method with the USM can improve performance by approximately 2.54 to 6.15× in terms of instruction counts with little accuracy loss.

Although multi-parent populations (MPPs) integrate the advantages of linkage and association mapping populations in the genetic dissection of complex traits and especially combine genetic analysis with crop breeding, it is difficult to detect small-effect quantitative trait loci (QTL) for complex traits in multiparent advanced generation intercross (MAGIC), nested association mapping (NAM), and random-open-parent association mapping (ROAM) populations. To address this issue, here we proposed a multi-locus linear mixed model method, namely mppQTL, to detect QTLs, especially small-effect QTLs, in these MPPs. The new method includes two steps. The first is genome-wide scanning based on a single-locus linear mixed model; the P-values are obtained from likelihood-ratio test, the peaks of negative logarithm P-value curve are selected by group-lasso, and all the selected peaks are regarded as potential QTLs. In the second step, all the potential QTLs are placed on a multi-locus linear mixed model, all the effects are estimated using expectation-maximization empirical Bayes algorithm, and all the non-zero effect vectors are further evaluated via likelihood-ratio test for significant QTLs. In Monte Carlo simulation studies, the new method has higher power in QTL detection, lower false positive rate, lower mean absolute deviation for QTL position estimate, and lower mean squared error for the estimate of QTL size (r(2)) than existing methods because the new method increases the power of detecting small-effect QTLs. In real dataset analysis, the new method (19) identified five more known genes than the existing three methods (14). This study provides an effective method for detecting small-effect QTLs in any MPPs.

Patients with small cell lung cancer (SCLC) are prone to developing refractoriness to standard treatment, and some patients are ineligible for systemic therapy owing to comorbidities or poor pulmonary function. The prognosis of patient with standard treatment-refractory/ineligible (STRI)-SCLC remains poor. This retrospective cohort study aimed to investigate the efficacy and safety of drug-eluting beads bronchial arterial chemoembolization (DEB-BACE) for the treatment of SRTI-SCLC and to identify the predictors of overall survival (OS).A total of 18 patients with STRI-SCLC who received DEB-BACE were included. Treatment response, adverse events, progression-free survival (PFS), and OS were evaluated. Further molecular targeted therapy or immunotherapy was administered as a second-line treatment or beyond for those patients who had not received these regimens previously. Univariate and multivariate Cox analyses were used to explore the predictors of OS for STRI-SCLC treated with DEB-BACE.The overall disease control rate at 3 months after DEB-BACE was 77.8% (14/18); of these patients who experienced disease control, partial response and stable disease were achieved in 2 patients (11.1%) and 12 patients (66.7%), respectively. There were 7 patients (38.9%) who received anlotinib after DEB-BACE. No severe DEB-BACE-related or anlotinib-related adverse events were observed. The median PFS was 5.0 months; the 6- and 12-month PFS rates were 55.6% (10/18) and 11.1% (2/18), respectively. The median OS was 9.0 months; the 6- and 12-month OS rates were 77.8% (14/18) and 33.3% (6/18), respectively. Postoperative anlotinib [hazard ratio: 0.302; 95% confidence interval (CI): 0.098-0.930; P=0.037] was identified as the predictor of OS in patients with STRI-SCLC treated with DEB-BACE.DEB-BACE is an effective and well-tolerated approach for patients with STRI-SCLC. Postoperative anlotinib is the predictor of OS and may indicate a better prognosis for patients with STRI-SCLC.

A benzothiadiazole-based chromophore using the molecular design strategy of engineering multipolar charge distributions was synthesized and obtained a large nonlinear response.

The purpose of this study is to investigate the effects of environmental and human factors on communication attenuation as well as to improve radio signal attenuation. In this study, a fire training containerized structure for firefighters and commercial rescue portable radios were used for a communication experiment in a fire scene. It was found that the firefighter’s relief communication posture reduced radio communication power. The prone posture had the greatest effect on radio communication attenuation. Also, smoke caused a decrease in communication power regardless of flame burning conditions or temperature effects. The results of the study showed that the communication power can be improved by changing the radio antenna orientation and operating the radio in a non-dense smoke layer. Finally, this study proposed that a new portable radio protection bag with thermal protection designed for firefighters wearing radios on oxygen cylinder straps could effectively improve the communication attenuation problem.

Observational evidence of two extratropical pathways to forcing tropical convective disturbances is documented through a statistical analysis of satellite-derived OLR and ERA5 reanalysis. The forcing mechanism and the resulting disturbances are found to strongly depend on the structure of the background zonal wind. Although Rossby wave propagation is prohibited in easterlies, modeling studies have shown that extratropical forcing can still excite equatorial waves through resonance between the tropics and extratropics. Here this “remote” forcing pathway is investigated for the first time in the context of convectively coupled Kelvin waves over the tropical Pacific during northern summer. The extratropical forcing is manifested by eddy momentum flux convergence that arises when extratropical eddies propagate into the subtropics and encounter their critical line. This nonlinear forcing has similar wavenumbers and frequencies with Kelvin waves and excites them by projecting onto their meridional eigenstructure in zonal wind, as a form of resonance. This resonance is also evidenced by a momentum budget analysis, which reveals the nonlinear forcing term is essential for maintenance of the waves, while the remaining linear terms are essential for propagation. In contrast, the “local” pathway of extratropical forcing entails the presence of a westerly duct during northern winter that permits Rossby waves to propagate into the equatorial east Pacific, while precluding any sort of resonance with Kelvin waves due to Doppler shifting effects. The intruding disturbances primarily excite tropical “cloud plumes” through quasigeostrophic forcing, while maintaining their extratropical nature. This study demonstrates the multiple roles of the extratropics in forcing in tropical circulations and illuminates how tropical–extratropical interactions and extratropical basic states can provide be a source of predictability at the S2S time scale. Significance Statement This study seeks to understand how circulations in the midlatitudes excite the weather systems in the tropics. Results show that the mechanisms, as well as the types of tropical weather systems excited, are strongly dependent on the mean large-scale wind structure. In particular, when the large-scale wind blows from east to west, a special type of eastward-moving tropical weather system, the Kelvin wave, is excited owing to its resonance with remote eastward-moving weather systems in the extratropics. On the contrary, when the average wind blows from west to east, midlatitude systems are observed to intrude into the lower latitudes and directly force tropical convection, the cloud plumes, while maintaining their extratropical nature. These results speak to how the midlatitudes can excite distinct types of tropical weather systems under different climatological wind regimes. Understanding these tropical weather systems and their interactions with the midlatitudes may ultimately help to improve predictions of weather beyond 2 weeks.

Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 13 (STAT1 and STAT3).We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored.We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3.Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.

Let $G$ be a graph with adjacency matrix $A(G)$ and let $D(G)$ be the diagonal matrix of vertex degrees of $G$. For any real $\alpha \in [0,1]$, Nikiforov defined the $A_\alpha$-matrix of a graph $G$ as $A_\alpha(G)=\alpha D(G)+(1-\alpha)A(G)$. The largest eigenvalue of $A_\alpha(G)$ is called the $\alpha$-index or the $A_\alpha$-spectral radius of $G$. A graph is minimally $k$-(edge)-connected if it is $k$-(edge)-connected and deleting any arbitrary chosen edge always leaves a graph which is not $k$-(edge)-connected. In this paper, we characterize the minimally 2-edge-connected graphs and minimally 3-connected graph with given order having the maximum $\alpha$-index for $\alpha \in [\frac{1}{2},1)$, respectively., Comment: arXiv admin note: text overlap with arXiv:2301.03389

The accurate analysis of chemical isomers plays an important role in the study of their different toxic effects and targeted detection of pollutant isomers in foods. The Alternaria mycotoxins tenuazonic acid (TeA) and iso-tenuazonic acid (ITeA) are two isomer mycotoxins with the lack of single analysis methods due to the similar structures. Antibody-based immunoassays exhibit high sensitivity and superior application in isomer-specific determination. Previously, various kinds of antibodies for TeA have been prepared in our group. Herein, high -ly specific nanobodies (Nbs) against ITeA mycotoxin were selected from immune nanobody phage display li-brary, and one of Nbs, namely Nb(B3G3) exhibited excellent affinity, thermal stability as well as organic solvent tolerance. By molecular simulation and docking technology, it was found that stronger interaction between Nb (B3G3) and ITeA lead to higher affinity than that for its isomer TeA. Furthermore, a sensitive indirect competitive enzyme-linked immunosorbent assay (icELISA) was established with a limit of detection (LOD) of 0.09 ng/mL for ITeA mycotoxin. The recovery rate of ITeA in spiked samples was analyzed with 84.8%-89.5% for rice, 78.3%- 96.3% for flour, and 79.5%-90.7% for bread. A conventional LC-MS/MS method was used to evaluate the ac-curacy of this proposed icELISA, which showed a satisfactory consistent correlation. Since the convenient strategy for nanobody generation by phage display technology, this study provide new biorecognition elements and sensitive immunoassay for analysis of ITeA in foods.

An efficient NaNO2-catalyzed synthesis of 2-methylene-3-cyclohexenones from easily accessible cyclohexenone-MBH acetates has been established for the first time. Target products were rapidly generated in moderate to high yields and with relatively high E/Z selectivity. Easy operation, good functional group tolerance, mild reaction conditions and the practicality of high efficiency of NaNO2 for the formation of 2-methylene-3-cyclohexenones constitute the attractive advantages of this reaction.

The study was designed to evaluate the efficiency of microwave ablation (MWA) in combination with anti-programmed death receptor 1 (anti-PD-1)/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in renal cell carcinoma (RCC) treatment. After tumors were established on C57/BL6 mice, MWA treatment and/or immune checkpoint inhibitor (ICI) treatment to the mice were performed. Tumor volume was recorded every 7 days. A rechallenge test was conducted on mice with tumors in the left kidney to explore the systemic establishment of antitumor immunity on day 7. In this study, during the 21-day observation period, tumors were continued to grow in all groups. However, compared with the tumor growth rate in MWA or control group, the rate in the ICI or MWA+ICI groups was decreased. Moreover, the population of CD8+T-cells was increased only in the MWA+ICI group, while that of regulatory T cells was decreased in the MWA, ICI, and MWA+ICI groups. Additionally, the MWA+ICI group had the highest interferon-γ level among all groups. Furthermore, histopathological examination revealed that CTLA-4 expression in distant tumors was reduced in the ICI and MWA + ICI groups. MWA treatment increased PD-L1/PD-1 expression; however, after the combination treatment with ICI, PD-L1/PD-1 expression was decreased. According to the rechallenge test, mice (16.7%) in the MWA group, ICI group (50%), and MWA+ICI group (66.7%) exhibited successful tumor rejection, whereas no mice in the control group exhibited the capability of tumor rejection. Overall, the systemic antitumor immunity induced by MWA was boosted when combined with anti-PD-1/CTLA-4 treatment in an RCC murine model.

Background Millions of people throughout the world suffer from parasite infections. Traditionally, technicians use manual eye inspection of microscopic specimens to perform a parasite examination. However, manual operations have limitations that hinder the ability to obtain precise egg counts and cause inefficient identification of infected parasites on co-infections. The technician requirements for handling a large number of microscopic examinations in countries that have limited medical resources are substantial. We developed the helminth egg analysis platform (HEAP) as a user-friendly microscopic helminth eggs identification and quantification platform to assist medical technicians during parasite infection examination. Methods Multiple deep learning strategies including SSD (Single Shot MultiBox Detector), U-net, and Faster R-CNN (Faster Region-based Convolutional Neural Network) are integrated to identify the same specimen allowing users to choose the best predictions. An image binning and egg-in-edge algorithm based on pixel density detection was developed to increase the performance. Computers with different operation systems can be gathered to lower the computation time using our easy-to-deploy software architecture. Results A user-friendly interface is provided to substantially increase the efficiency of manual validation. To adapt to low-cost computers, we architected a distributed computing structure with high flexibilities. Conclusions HEAP serves not only as a prediction service provider but also as a parasitic egg database of microscopic helminth egg image collection, labeling data and pretrained models. All images and labeling resources are free and accessible at http://heap.cgu.edu.tw . HEAP can also be an ideal education and training resource for helminth egg examination.

Background Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome. Methods FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out. Results From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT. Conclusions FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.

Purpose CPAP is the “gold standard” treatment for obstructive sleep apnea (OSA). Current CPAP models have developed additional functions including automatic CPAP and pressure relief. However, CPAP adherence has not improved over the last three decades. Many patients in low-income countries cannot afford these CPAP devices. A novel simple CPAP device with a fixed pressure without pressure controller was developed. Methods Manual CPAP pressure titration was performed in 127 patients with OSA. Six patients with a titration pressure higher than 11 cmH2O and 14 patients who could not tolerate CPAP were excluded, leaving 107 participating in the following 2 studies. In study one, 54 of 107 patients were treated by both conventional fixed CPAP and simple CPAP in random order. In the second study, another 53 patients were treated by both autoCPAP in automatic function and simple CPAP in random order. Simple CPAP was fixed at 10 cmH2O, 8 cmH2O, and 6 cmH2O for patients whose titration pressure was between 9–10, 7–8, and ≤ 6 cmH2O, respectively. Conventional fixed CPAP device was set exactly the same as manual titration pressure. Results All patients whose manual titration pressure ≤ 10 cmH2O were effectively treated by simple CPAP (AHI 40.7 ± 2.3 events/h before vs 2.5 ± 0.3 events/h after, p p > 0.05). Conclusions We conclude that a novel simple CPAP is an alternative treatment for most patients with OSA, which may widen access to CPAP therapy in the developing countries because of its low cost.

Mesoscale convective systems (MCSs) produce over 50% of tropical precipitation and account for the majority of extreme rainfall and flooding events. MCSs are considered the building blocks of larger-scale convectively coupled equatorial waves (CCEWs). While CCEWs can provide favorable environments for convection, how CCEWs can systematically impact organized convection and thereby MCS characteristics is less clear. We examine this question by analyzing a global MCS tracking dataset. During the active phase of CCEWs, MCS frequency increases and MCSs rain harder, produce more lifetime total rain, and grow larger in size. The probability of extreme MCSs also elevates. These changes are most pronounced when MCSs are associated with Kelvin waves and tropical depression-type waves while least so with the Madden-Julian Oscillation. These results can be benchmarks to improve model representation of MCS interactions with large-scale circulations and can be leveraged operationally for extended forecasts of high-impact MCSs.

Spatial symmetries can enrich the topological classification of interacting quantum matter and endow systems with non-trivial strong topological invariants (protected by internal symmetries) with additional "weak" topological indices. In this paper, we study the edge physics of systems with a non-trivial shift invariant, which is protected by either a continuous $\text{U}(1)_r$ or discrete $\text{C}_n$ rotation symmetry, along with internal $\text{U}(1)_c$ charge conservation. Specifically, we construct an interface between two systems which have the same Chern number but are distinguished by their Wen-Zee shift and, through analytic arguments supported by numerics, show that the interface hosts counter-propagating gapless edge modes which cannot be gapped by arbitrary local symmetry-preserving perturbations. Using the Chern-Simons field theory description of two-dimensional Abelian topological orders, we then prove sufficient conditions for continuous rotation symmetry protected gapless edge states using two complementary approaches. One relies on the algebraic Lagrangian sub-algebra framework for gapped boundaries while the other uses a more physical flux insertion argument. For the case of discrete rotation symmetries, we extend the field theory approach to show the presence of fractional corner charges for Abelian topological orders with gappable edges, and compute them in the case where the Abelian topological order is placed on the two-dimensional surface of a Platonic solid. Our work paves the way for studying the edge physics associated with spatial symmetries in symmetry enriched topological phases., 9 + 3 pages, 3 figures. v3: Edits to Sec IV and added App B; close to published version

Background Wild apple (Malus sieversii) is under second-class national protection in China and one of the lineal ancestors of cultivated apples worldwide. In recent decades, the natural habitation area of wild apple trees has been seriously declining, resulting in a lack of saplings and difficulty in population regeneration. Artificial near-natural breeding is crucial for protecting and restoring wild apple populations, and adding nitrogen (N) and phosphorous (P) is one of the important measures to improve the growth performance of saplings. In this study, field experiments using N (CK, N1, N2, and N3: 0, 10, 20, and 40 g m− 2 yr− 1, respectively), P (CK, P1, P2, and P3: 0, 2, 4, and 8 g m− 2 yr− 1, respectively), N20Px (CK, N2P1, N2P2, and N2P3: N20P2, N20P4 and N20P8 g m− 2 yr− 1, respectively), and NxP4 (CK, N1P2, N2P2, and N3P2: N10P4, N20P4, and N40P4 g m− 2 yr− 1, respectively) treatments (totaling 12 levels, including one CK) were conducted in four consecutive years. The twig traits (including four current-year stem, 10 leaf, and three ratio traits) and comprehensive growth performance of wild apple saplings were analyzed under different nutrient treatments. Results N addition had a significantly positive effect on stem length, basal diameter, leaf area, and leaf dry mass, whereas P addition had a significantly positive effect on stem length and basal diameter only. The combination of N and P (NxP4 and N20Px) treatments evidently promoted stem growth at moderate concentrations; however, the N20Px treatment showed a markedly negative effect at low concentrations and a positive effect at moderate and high concentrations. The ratio traits (leaf intensity, leaf area ratio, and leaf to stem mass ratio) decreased with the increase in nutrient concentration under each treatment. In the plant trait network, basal diameter, stem mass, and twig mass were tightly connected to other traits after nutrient treatments, indicating that stem traits play an important role in twig growth. The membership function revealed that the greatest comprehensive growth performance of saplings was achieved after N addition alone, followed by that under the NxP4 treatment (except for N40P4). Conclusions Consequently, artificial nutrient treatments for four years significantly but differentially altered the growth status of wild apple saplings, and the use of appropriate N fertilizer promoted sapling growth. These results can provide scientific basis for the conservation and management of wild apple populations.

The propagation of spin waves in magnetically ordered systems has emerged as a potential means to shuttle quantum information over large distances. Conventionally, the arrival time of a spin wavepacket at a distance, d , is assumed to be determined by its group velocity, v g . Here, we report time-resolved optical measurements of wavepacket propagation in the Kagome ferromagnet Fe 3 Sn 2 that demonstrate the arrival of spin information at times significantly less than d / v g . We show that this spin wave “precursor” originates from the interaction of light with the unusual spectrum of magnetostatic modes in Fe 3 Sn 2 . Related effects may have far-reaching consequences toward realizing long-range, ultrafast spin wave transport in both ferromagnetic and antiferromagnetic systems.

Abstract Metabolic dysregulations have emerged as a major mediator of cardiovascular disorders and fibrotic diseases. Metabolic reprogramming contributes a lot to cardiac fibroblast activation and cardiac fibrosis post-myocardial infarction (MI), yet the mechanism remains incompletely understood. Our work aimed to determine whether or not glycolytic reprogramming, regulated by phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), is a therapeutic target for alleviating post-MI cardiac fibrosis. Here, we showed that cardiac fibroblasts displayed cell energy phenotype toward augmented glycolysis in response to transforming growth factor-beta 1 (TGF-β1), evidenced by significant extracellular acidification rate (ECAR) increase and lactate accumulation. The expression of glycolytic enzyme PFKFB3, a master activator of glycolysis, was up-regulated in TGF-β1-treated cardiac fibroblasts and in cardiac fibroblasts of post-MI mice. Pharmacological inhibition of PFKFB3 by 3PO diminished TGF-β1-mediated profibrotic phenotypes, attenuated cardiac fibrosis, and preserved cardiac functions in post-MI mice. Meanwhile, the genetic inhibition of PFKFB3 decreased the cardiac fibroblast activation and reversed the differentiated phenotypes in vitro and in vivo. Mechanistically, we identified deubiquitinase OTUD4 as a new binding protein of PFKFB3, and their interaction blocked PFKFB3 degradation via OTUD4-mediated deubiquitylation. Taken together, this work characterized a key role for PFKFB3 in cardiac fibroblast activation and suggested that inhibiting PFKFB3-involved glycolysis is an alternative way to alleviate post-MI cardiac fibrosis. Key messages PFKFB3, a master activator of glycolysis, was highly expressed in ischemic cardiac fibroblasts to enhance cardiac fibrosis The deubiquitinase OTUD4 was identified as a new binding protein of PFKFB3 TGF-β1 blunted the ubiquitination-mediated degradation of PFKFB3 via OTUD4-mediated deubiquitylation Blockade of PFKFB3 contributed to ameliorating ischemia-induced cardiac fibrosis

We propose two single-wavelength notch filters and one dual-wavelength (480 and 620 nm) notch filter to enhance image contrast. The stack structure of the notch filters was designed as (Ta2O5/SiO2)4Ta2O5 in Essential Macleod thin film simulation software. Dual-electron-beam evaporation with ion beam-assisted deposition was used to prepare optical interference filters with different center wavelengths. A multilayer notch filter with a center wavelength of 620 nm was deposited on the front surface of the glass, and then a notch filter with a center wavelength of 480 nm was coated on the rear surface of the same glass. The proposed dual-wavelength (480 and 620 nm) notch filter is a combination of two single-wavelength notch filters coated on a double-sided glass substrate to compensate for residual stress. The transmittance, residual stress, and surface roughness of the proposed notch filter were evaluated using different measuring instruments. The experimental results show that the residual stress of the dual-wavelength notch filter could be reduced to 10.8 MPa by using a double-sided coating technique. The root-mean-square (RMS) surface roughness of the notch filters was measured by using a Linnik microscopic interferometer. The RMS surface roughness was 1.80 for the 620 nm notch filter and 2.09 for the 480 nm notch filter. The image contrast obtained with the three different notch filters was measured using an optical microscope and a CMOS camera. The contrast value could be increased from 0.328 (without a filter) to 0.696 (dual-wavelength notch filter).

Supplementary Table 1. Antibodies and Primer list Supplementary Table 2. IPA results for HNSCC upstream transcriptional regulators Supplementary Table 3. Clinical characteristics of RUNX2 in validation HNSCC cohort Supplementary Table 4. Lung colony formation abilities among HNSCC cells Supplementary Table 5. Relative expression and hazard ratio of RUNX2 target genes in GSE37991 HNSCC cohort and TCGA HNSCC cohort Supplementary Table 6. Clinical characteristics of RUNX2 and INHBA expression among TCGA HNSCC cohort Supplementary Table 7. Prediction binding affinity between 14q32.2 miRNAs and RUNX2 3'-UTR in HNSCC Supplement Table 8. Transcription factor 3'UTR miR-376c MRE analysis and binding prediction analysis of INHBA promoter. Supplementary Table 9. IPA Interaction analysis between RUNX2 and TFs and revealed differential expressed genes in GSE37991 HNSCC patients

Epigenetic correlates of the head and neck cancer may illuminate its pathogenic roots. Through a gene set enrichment analysis, we found that the oncogenic transcription factor RUNX2 is widely upregulated in the head and neck squamous cell carcinoma (HNSCC) with lymph node metastasis, where it also predicts poor prognosis in patients with HNSCC. Enforced expression of ectopic RUNX2 promoted the metastatic capabilities of HNSCC, whereas RUNX2 silencing inhibited these features. Mechanistic investigations showed that manipulating levels of activin A (INHBA) could rescue or compromise the RUNX2-mediated metastatic capabilities of HNSCC cells. Furthermore, we found that miR-376c-3p encoded within the 3′-untranslated region of RUNX2 played a pivotal role in regulating RUNX2 expression in highly metastatic HNSCC cells, where it was downregulated commonly. Restoring miR-376c expression in this setting suppressed expression of RUNX2/INHBA axis along with metastatic capability. Clinically, we observed an inverse relationship between miR-376c-3p expression and the RUNX2/INHBA axis in HNSCC specimens. In summary, our results defined a novel pathway in which dysregulation of the RUNX2/INHBA axis due to miR-376c downregulation fosters lymph node metastasis in HNSCC. Cancer Res; 76(24); 7140–50. ©2016 AACR.

Supplementary Figure 1. RUNX2 is nucleus location protein among HNSCC cells. Supplementary Figure 2. RUNX2 was a poor prognostic marker in HNSCC. Supplementary Figure 3. Lung colony formation ability of HNSCC cells. Supplementary Figure 4. RUNX2 and its regulation targets, INHBA, promoted HNSCC invasion and migration assay in HNSCC cells. Supplementary Figure 5. The TCGA-HNSCC dataset shows the positive correlation between RUNX2 and INHBA and their prognostic value. Supplementary Figure 6. Ectopic anti-miR-376c-3p increases RUNX2 3'-UTR reporter assay in Ca9-22 cells. Supplementary Figure 7Knockdown RUNX2 prevent anti-miR-376c-3p induced cell migration and invasion ablilties in Ca9-22 cells.

Supplementary Information. Include supplementary material, methods, table title and figure legends

Supplementary Tables S1-S4. Supplementary Table S1: Clinicopathological characteristics of 40 pairs of OSCC specimens and their corresponding non-tumorous epithelia. Supplementary Table S2: A list of deregulated miRNA in 40 pairs of OSCC specimens and their corresponding non-tumorous epithelia. Supplementary Table S3: Characteristics of 83 OSCC patients for Wnt-7b IHC study. Supplementary Table S4: Top ten of enriched transcriptional factors in miRNA overexpression.

Supplementary Figures S1-S7. Supplementary Figure S1: Genome-wide profiling of chromosome 14q32.2 miRNA on OSCC tissues. Supplementary Figure S2: Mi-RNA level in miR-PM overexpressed OEC-M1 and SCC-15 cells. Supplementary Figure S3: Effect of miR-329 and miR-410 on Wnt/β-catenin signaling pathway. Supplementary Figure S4: The effects of miR-329 and miR-410 on tumor cell proliferation. Supplementary Figure S5: Expression level of miRNA in xenograft tumor tissue. Supplementary Figure S6: Effects of miR-329 and -410 on tumorigenicity. Supplementary Figure S7: Effects of arecoline on Wnt/β-catenin signaling pathway.

Background: Trichomonas vaginalis is an anaerobic parasitic protozoan of the human urogenital tract. Infection can cause vaginitis in women and urethritis in men. Accumulated reports indicated that exosomes released by protozoan parasites play important roles in transmitting information and substances between cells and mediating communication during host-parasite interactions in several parasitic infections. However, current knowledge on the protein contents in T. vaginalis exosome is mainly generated from three previous studies which used different T. vaginalis isolates as an experimental model. Therefore, whether T. vaginalis exosomes comprise a common set of proteins (core exosome proteome) is still unclear. Methods: To explore the core exosome proteome in T. vaginalis, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the contents of sucrose ultracentrifugation-enriched exosome isolated from six isolates. Results: Transmission electron microscopy (TEM) revealed the presence of exosomes in the enriched fraction with the classical cup-shaped morphology and size around 150 nm. Proteomic analysis identified a total of 1870 proteins from exosomal extracts. There were 1207 exosomal-specific proteins after excluding 436 contaminant proteins. Among these, 72 common exosomal-specific proteins were expressed in all six isolates. Compared with three published T. vaginalis exosome proteome datasets, we identified 16 core exosomal-specific proteins. These core exosomal-specific proteins included tetraspanin (TvTSP1), the classical exosome marker, and proteins mainly involved in catalytic activity and binding such as ribosomal proteins, ras-associated binding (Rab) proteins, and heterotrimeric G proteins. Conclusions: Our study highlighted the importance of using supernatant fraction from exosomal extract as a control to remove contaminant proteins. In addition, we compiled a reference core exosome proteome of T. vaginalis, which is important for developing a fundamental understanding of exosome-mediated cell communication and host-parasite interaction.

BackgroundAlgorithm malfunction may occur when there is a performance mismatch between the dataset with which it was developed and the dataset on which it was deployed.MethodsA baseline segmentation algorithm and a baseline classification algorithm were developed using public dataset of Lung Image Database Consortium to detect benign and malignant nodules, and two additional external datasets (i.e., HB and XZ) including 542 cases and 486 cases were involved for the independent validation of these two algorithms. To explore the impact of localized fine tuning on the individual segmentation and classification process, the baseline algorithms were fine tuned with CT scans of HB and XZ datasets, respectively, and the performance of the fine tuned algorithms was tested to compare with the baseline algorithms.ResultsThe proposed baseline algorithms of both segmentation and classification experienced a drop when directly deployed in external HB and XZ datasets. Comparing with the baseline validation results in nodule segmentation, the fine tuned segmentation algorithm obtained better performance in Dice coefficient, Intersection over Union, and Average Surface Distance in HB dataset (0.593 vs. 0.444; 0.450 vs. 0.348; 0.283 vs. 0.304) and XZ dataset (0.601 vs. 0.486; 0.482 vs. 0.378; 0.225 vs. 0.358). Similarly, comparing with the baseline validation results in benign and malignant nodule classification, the fine tuned classification algorithm had improved area under the receiver operating characteristic curve value, accuracy, and F1 score in HB dataset (0.851 vs. 0.812; 0.813 vs. 0.769; 0.852 vs. 0.822) and XZ dataset (0.724 vs. 0.668; 0.696 vs. 0.617; 0.737 vs. 0.668).ConclusionsThe external validation performance of localized fine tuned algorithms outperformed the baseline algorithms in both segmentation process and classification process, which showed that localized fine tuning may be an effective way to enable a baseline algorithm generalize to site-specific use.

Background Iron is an essential element for cellular functions, such as energy metabolism. Trichomonas vaginalis, a human urogenital tract pathogen, is capable of surviving in the environment without sufficient iron supplementation. Pseudocysts (cyst-like structures) are an environmentally tolerated stage of this parasite while encountering undesired conditions, such as iron deficiency. We demonstrated that iron deficiency induces more active glycolysis but a drastic downregulation of hydrogenosomal energy metabolic enzymes. Therefore, the metabolic direction of pyruvate is still controversial. Methods In the present work, we conducted an LC‒MS-based metabolomics analysis to obtain accurate insights into the enzymatic events of T. vaginalis under iron-depleted (ID) conditions. Results First, we showed the possible digestion of glycogen, cellulose polymerization, and accumulation of raffinose family oligosaccharides (RFOs). Second, a medium-chain fatty acid (MCFA) capric acid was elevated, whereas most detected C18 fatty acids were reduced significantly. Third, amino acids were mostly reduced, especially alanine, glutamate, and serine. There were 33 dipeptides that showed significant accumulation in ID cells, which was probably associated with the decrease in amino acids. Our results indicated that glycogen was metabolized as the carbon source, and the structural component cellulose was synthesized at same time. The decrease in C18 fatty acids implied possible incorporation in the membranous compartment for pseudocyst formation. The decrease in amino acids accompanied by an increase in dipeptides implied incomplete proteolysis. These enzymatic reactions (alanine dehydrogenase, glutamate dehydrogenase, and threonine dehydratase) were likely to be involved in ammonia release. Conclusion These findings highlighted the possible glycogen utilization, cellulose biosynthesis, and fatty acid incorporation in pseudocyst formation, as well as NO precursor ammonia production induced by iron-depleted stress.

Navigation bronchoscopy is an emerging technique used to evaluate pulmonary lesions. Using Veran’s SPiN electromagnetic navigation bronchoscopy (ENB) and Archimedes virtual bronchoscopy navigation (VBN), this study aimed to compare the accuracy and safety of these procedures for lung lesions and to identify potentially relevant knowledge for the application of artificial intelligence in interventional pulmonology in a single institute. This single-center, retrospective study compared the ENB and VBN results in patients with pulmonary lesions unsuitable for biopsy via percutaneous transthoracic needle biopsy methods. A total of 35 patients who underwent navigation bronchoscopy for pulmonary lesion diagnosis were enrolled. Nineteen patients were stratified in the ENB group, and sixteen were in the VBN group. The mean age of this cohort was 67.6 ± 9.9 years. The mean distance of the lesion from the pleural surface was 16.1 ± 11.7 mm (range: 1.0–41.0 mm), and most lesions were a solid pattern (n = 33, 94.4%). There were 32 cases (91.4%) of pulmonary lesions with an air-bronchus sign. A statistically significant difference was found between pulmonary size and transparenchymal nodule access (p = 0.049 and 0.037, respectively). The navigation success rate was significantly higher in the VBN group (93.8% vs. 78.9%). Moreover, no procedure-related complications or mortality were noted. The radiographic characteristics, such as size or solid component, can affect the selection of the biopsy procedure, either ENB or VBN. Navigation bronchoscopy-guided biopsy demonstrated acceptable accuracy and a good safety profile in evaluating pulmonary lesions when the percutaneous approach was challenging or life threatening.

Soybean cyst nematode (SCN, Heterodera glycines, HG) is one of the severe pests in plant-parasitic nematodes, which impairs root development and causes severe losses in soybean production worldwide. Breeding SCN-resistant cultivars is an important measure for securing harvests without affecting the environment, as can be done with pesticides. The majority of genetic resources for plant pest resistances are found in wild or closely related species which are often difficult to use in breeding due to crossing barriers or close linkage with unfavorable agronomic traits. In this study, 12 soybean cultivars were evaluated for their marker haplotype at the rhg1 and Rhg4 SCN resistance loci and their SCN resistance tested against multiple races in environmentally controlled bioassays. The results showed that all 12 cultivars displayed Peking-type resistance marker haplotypes and all of them proved to be resistant to multiple SCN races. These cultivars provide potential for improving H. glycines resistance of soybean as donor parent in breeding and can contribute to reduce SCN field populations as part of a sustainable agriculture management.