273 research outputs found

    A bead sequence-driven deposition pattern evaluation criterion for lowering residual stresses in additive manufacturing

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    Deposition patterns can significantly influence the distribution and magnitude of residual stress in additively manufactured parts. Time-consuming thermal-mechanical simulations and costly experimental studies are often required to identify the optimal patterns. A simple and generic method to evaluate and optimize the deposition pattern for the purpose of minimizing residual stress is in urgent need. To overcome the shortcomings of the current practice, here we propose a novel pattern evaluation criterion. Starting from the discretization of the deposition pattern by a series of sequence numbers, we introduce two interconnected concepts. The first is called “equivalent bead sequence number” which can be physically interpreted as an index of the localized heat accumulation induced by the deposition process. Based on this point-wise “equivalent bead sequence number”, the second concept called “bead sequence number dispersion index” which can be considered as a representation of the global heat accumulation gradient, is proposed as a criterion for assessing the resulting residual stress. The temperature fields and residual stresses of a square part with six typical deposition patterns predicted by thermo-mechanical finite element simulations are used to develop and verify the proposed criterion. It is found that the “equivalent bead sequence number” of a given pattern is closely correlated to the distribution of the associated temperature and residual stress. More interestingly, both the highest equivalent and highest maximum principal residual stress of a pattern linearly increase with its corresponding value of “bead sequence number dispersion index”. Guided by this relation, two new patterns with lower residual stress are developed and evaluated. Among all the patterns considered, the so-called S pattern shows the lowest value of the “bead sequence number dispersion index” which corresponds to the lowest residual stress. The proposed sequence-driven approach provides a new candidate for real-time evaluation and optimization of the deposition pattern in additive manufacturing.publishedVersio

    Aspartyl protease in the secretome of honey bee trypanosomatid parasite contributes to infection of bees.

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    BackgroundThe exoproteome, which consists of both secreted proteins and those originating from cell surfaces and lysed cells, is a critical component of trypanosomatid parasites, facilitating interactions with host cells and gut microbiota. However, its specific roles in the insect hosts of these parasites remain poorly understood.MethodsWe conducted a comprehensive characterization of the exoproteome in Lotmaria passim, a trypanosomatid parasite infecting honey bees, under culture conditions. We further investigated the functions of two conventionally secreted proteins, aspartyl protease (LpAsp) and chitinase (LpCht), as representative models to elucidate the role of the secretome in L. passim infection of honey bees.ResultsApproximately 48% of L. passim exoproteome proteins were found to share homologs with those found in seven Leishmania spp., suggesting the existence of a core exoproteome with conserved functions in the Leishmaniinae lineage. Bioinformatics analyses suggested that the L. passim exoproteome may play a pivotal role in interactions with both the host and its microbiota. Notably, the deletion of genes encoding two secretome proteins revealed the important role of LpAsp, but not LpCht, in L. passim development under culture conditions and its efficiency in infecting the honey bee gut.ConclusionsOur results highlight the exoproteome as a valuable resource for unraveling the mechanisms employed by trypanosomatid parasites to infect insect hosts by interacting with the gut environment

    Variations in Stable Carbon Isotope Composition and Leaf Traits of Picea schrenkiana

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    To understand the morphological and physiological responses of leaves to changes in altitudinal gradients, we examined ten morphological and physiological characteristics in one-year-old needles of Picea schrenkiana var. tianschanica at ten points along an altitudinal gradient from 1420 to 2300 m a.s.l. on the northern slopes of the Tianshan Mountains in northwest China. Our results indicated that LA, SD, LPC, and LKC increased linearly with increasing elevation, whereas leaf δ13C, LNC, Chla + b, LDMC, LMA, and Narea varied nonlinearly with changes in altitude. With elevation below 2100 m, LNC, Narea, and Chla + b increased, while LDMC and LMA decreased with increasing altitude. When altitude was above 2100 m, these properties showed the opposite patterns. Leaf δ13C was positively correlated with Narea and LNC and negatively correlated with SD and LA, suggesting that leaf δ13C was indirectly controlled by physiological and morphological adjustments along altitudinal gradients. Based on the observed maximum values in LNC, Narea, Chla + b, and LA and the minimum values in LMA and LDMC at the elevation of 2100 m, suggesting higher photosynthetic capacity and greater potential for fast growth under superior optimum zone, we concluded that the best growing elevation for P. schrenkiana var. tianschanica in the Tianshan Mountains was approximately 2100 m

    Nonlinear optics and optical limiting properties of multifunctional fullerenol/polymer composite

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    The nonlinear optics and optical limiting properties of materials based on multifunctional fullerenol and poly(styrene-co-4-vinylpyridine) matrix were studied using 7 ns pulses of nanosecond laser operating at 532 nm wavelength. The observed imaginary and real parts of third order susceptibility of the fullerenol/polymer composite are found to be lower than that of its parent C60. The optical limiting performances of fullerenol and fullerenol incorporated with poly(styrene-co-4-vinylpyridine) have been proved to be poorer than that of C60 due to their higher limiting thresholds. Concentration dependence of poly(styrene-co-4-vinylpyridine) containing 32 mol% has been mainly contributed to the optical limiting performance of fullerenol.Comment: 23 pages, 9 figures, presented in ISMOA-2002, Bandung, Indonesia. Submitted to J. Nonlinear Opt. Phys. (December 2002

    MAPK-Mediated Transcription Factor GATAd Contributes to Cry1Ac Resistance in Diamondback Moth by Reducing \u3ci\u3ePxmALP\u3c/i\u3e Expression

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    The benefits of biopesticides and transgenic crops based on the insecticidal Cry-toxins from Bacillus thuringiensis (Bt) are considerably threatened by insect resistance evolution, thus, deciphering the molecular mechanisms underlying insect resistance to Bt products is of great significance to their sustainable utilization. Previously, we have demonstrated that the down-regulation of PxmALP in a strain of Plutella xylostella (L.) highly resistant to the Bt Cry1Ac toxin was due to a hormone-activated MAPK signaling pathway and contributed to the resistance phenotype. However, the underlying transcriptional regulatory mechanism remains enigmatic. Here, we report that the PxGATAd transcription factor (TF) is responsible for the differential expression of PxmALP observed between the Cry1Ac susceptible and resistant strains. We identified that PxGATAd directly activates PxmALP expression via interacting with a non-canonical but specific GATA-like cis-response element (CRE) located in the PxmALP promoter region. A six-nucleotide insertion mutation in this cis-acting element of the PxmALP promoter from the resistant strain resulted in repression of transcriptional activity, affecting the regulatory performance of PxGATAd. Furthermore, silencing of PxGATAd in susceptible larvae reduced the expression of PxmALP and susceptibility to Cry1Ac toxin. Suppressing PxMAP4K4 expression in the resistant larvae transiently recovered both the expression of PxGATAd and PxmALP, indicating that the PxGATAd is a positive responsive factor involved in the activation of PxmALP promoter and negatively regulated by the MAPK signaling pathway. Overall, this study deciphers an intricate regulatory mechanism of PxmALP gene expression and highlights the concurrent involvement of both trans-regulatory factors and cis-acting elements in Cry1Ac resistance development in lepidopteran insects

    Large-scale screening of clinical assessments to distinguish between states in the Integrated HD Progression Model (IHDPM)

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    BackgroundUnderstanding the sensitivity and utility of clinical assessments across different HD stages is important for study/trial endpoint selection and clinical assessment development. The Integrated HD Progression Model (IHDPM) characterizes the complex symptom progression of HD and separates the disease into nine ordered disease states.ObjectiveTo generate a temporal map of discriminatory clinical measures across the IHDPM states.MethodsWe applied the IHDPM to all HD individuals in an integrated longitudinal HD dataset derived from four observational studies, obtaining disease state assignment for each study visit. Using large-scale screening, we estimated Cohen’s effect sizes to rank the discriminative power of 2,472 clinical measures for separating observations in disease state pairs. Individual trajectories through IHDPM states were examined. Discriminative analyses were limited to individuals with observations in both states of the pairs compared (N = 3,790).ResultsDiscriminative clinical measures were heterogeneous across the HD life course. UHDRS items were frequently identified as the best state pair discriminators, with UHDRS Motor items – most notably TMS – showing the highest discriminatory power between the early-disease states and early post-transition period states. UHDRS functional items emerged as strong discriminators from the transition period and on. Cognitive assessments showed good discriminative power between all state pairs examined, excepting state 1 vs. 2. Several non-UHDRS assessments were also flagged as excellent state discriminators for specific disease phases (e.g., SF-12). For certain state pairs, single assessment items other than total/summary scores were highlighted as having excellent discriminative power.ConclusionBy providing ranked quantitative scores indicating discriminatory ability of thousands of clinical measures between specific pairs of IHDPM states, our results will aid clinical trial designers select the most effective outcome measures tailored to their study cohort. Our observations may also assist in the development of end points targeting specific phases in the disease life course, through providing specific conceptual foci

    Global acetylome profiling indicates EPA impedes but OA promotes prostate cancer motility through altered acetylation of PFN1 and FLNA.

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    Prostate cancer (PCa) is one of the leading causes of cancer morbidity and mortality in men. Metastasis is the main cause of PCa-associated death. Recent evidence indicated a significant reduction in PCa mortality associated with higher ω-3 polyunsaturated fatty acids (PUFAs) consumption. However, the underlying mechanisms remained elusive. In this study, we applied global acetylome profiling to study the effect of fatty acids treatment. Results indicated that oleic acid (OA, monounsaturated fatty acid, MUFA, 100 µM) elevates while EPA (eicosapentaenoic acid, 100 µM) reduces the acetyl-CoA level, which alters the global acetylome. After treatment, two crucial cell motility regulators, PFN1 and FLNA, were found with altered acetylation levels. OA increased the acetylation of PFN1 and FLNA, whereas EPA decreased PFN1 acetylation level. Furthermore, OA promotes while EPA inhibits PCa migration and invasion. Immunofluorescence assay indicated that EPA impedes the formation of lamellipodia or filopodia through reduced localization of PFN1 and FLNA to the leading edge of cells. Therefore, perturbed acetylome may be one critical step in fatty acid-affected cancer cell motility. This study provides some new insights into the response of ω-3 PUFAs treatment and a better understanding of cancer cell migration and invasion modulation

    Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

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    Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI
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