Search

Abstract Nominally anhydrous minerals (NAMs) composing Earth’s and planetary rocks incorporate microscopic amounts of volatiles. However, volatile distribution in NAMs and their effect on physical properties of rocks remain controversial. Thus, constraining trace volatile concentrations in NAMs is tantamount to our understanding of the evolution of rocky planets and planetesimals. Here, we present an approach of trace-element quantification using micro-scale Nuclear Magnetic Resonance (NMR) spectroscopy. This approach employs the principle of enhanced mass-sensitivity in NMR microcoils. We were able to demonstrate that this method is in excellent agreement with standard methods across their respective detection capabilities. We show that by simultaneous detection of internal reference nuclei, the quantification sensitivity can be substantially increased, leading to quantifiable trace volatile element amounts of about 50 ng/g measured in a micro-meter sized single anorthitic mineral grain, greatly enhancing detection capabilities of volatiles in geologically important systems.

Abstract Background Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems. Results In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals’ genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population. Conclusions The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs’ germplasm resources.

BackgroundLeukemia imposes a large healthcare burden both in China and the United States (US). The disease burden differs greatly between the two countries, but related research is limited. We explored the differences in leukemia incidence and mortality between China and the US.MethodsData on leukemia in China and the US from 1990 to 2021 were collected from the Global Burden of Disease 2021 database. Incidence and mortality were used to estimate the disease burden, and joinpoint regression was performed to compare their secular trends. We used an age-period-cohort model to analyze the effects of age, period, and birth cohort and project future trends in the next 15 years.ResultsIn 2021, the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) of leukemia were lower in China than in the US. However, the incidence and mortality of acute lymphoblastic leukemia (ALL) was considerably higher in China. In the past decades, the ASIR showed decreased tendency in the US, while ASIR showed stable in China. The ASDR tended to decrease in both countries from 1990 to 2021. Males have higher rates of incidence and mortality than females in two countries. The age effects showed that children and older individuals have higher RRs for incidence and mortality in China, while the RRs for incidence and mortality in the US particularly increased in the older population. The disease burden of leukemia in children is obviously greater in China. The ASIRs and ASDRs of leukemia will continue to decline in the next 15 years in China and the US, with the US experiencing a more obvious downtrend.ConclusionsOver the past decades, the ASDRs in two countries both tended to decrease. And compared to the US, China had lower leukemia incidence and mortality, However, the ASIRs in China tended toward stable, which it was showed downtrend in the US. Children have obviously greater RRs for incidence and mortality in China. The incidence and mortality will decrease continuously in two countries. Effective intervention measures are needed to reduce the burden of leukemia.

This study focuses on improving the application of the quadratic penalty smoothing technique for solving the fuel-optimal problem of low-thrust trajectory. Some practical techniques, including the Particle Swarm Optimization algorithm (PSO), the co-state normalization technique, and the single shooting method, are employed. These approaches can enhance convergence to the globally optimal solution. The application of PSO is improved through the introduction of the diversity termination term. Furthermore, a new parameter, the maximum thrust to initial mass ratio (CTm), is introduced and analyzed. The relationships among Lagrange multipliers for different CTm in the energy-optimal auxiliary problem are also derived. These relationships can be used in scenarios with high CTm to reduce the variable search space, leading to a significant decrease in computation time. Nonetheless, few researchers have proposed a well-defined strategy for the homotopic process. We propose a robust iteration strategy, involving the determination of the maximum step size and the distinction of sub-optimal solutions. This iterative strategy could ensure a robust convergence toward the optimal solutions. An interplanetary rendezvous example is provided to demonstrate the effectiveness of the presented techniques and strategy.

In order to encourage digital transformation in the traditional construction industry, the Chinese government has promoted 24 pilot cities to develop intelligent construction. The practices of intelligent construction are disparate in all 24 pilot cities. Given this context, it is important to effectively and comprehensively evaluate the level of intelligent construction in these pilot cities. This study thus evaluates the development of intelligent construction in different pilot cities. By conducting an in-depth analysis of the existing literature and policies, an evaluation system consisting of five dimensions and a total of 30 indicators is established. The entropy method and the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) are used to evaluate the development of intelligent construction in 23 pilot cities. The research findings indicate that the development of intelligent construction in different pilot cities is uneven, with clear gaps between first-tier cities and Western cities. The development of industries, the cultivation of talent, and economic growth are relatively satisfactory, while technological innovation and digital infrastructure are insufficient. Several suggestions are proposed to promote the development of intelligent construction, including expediting the construction of intelligent infrastructure, enhancing digital transformation, promoting technological innovation, and implementing talent cultivation strategies.

PURPOSEIncreased automation has been identified as one approach to improving global cancer care. The Radiation Planning Assistant (RPA) is a web-based tool offering automated radiotherapy (RT) contouring and planning to low-resource clinics. In this study, the RPA workflow and clinical acceptability were assessed by physicians around the world.METHODSThe RPA output for 75 cases was reviewed by at least three physicians; 31 radiation oncologists at 16 institutions in six countries on five continents reviewed RPA contours and plans for clinical acceptability using a 5-point Likert scale.RESULTSFor cervical cancer, RPA plans using bony landmarks were scored as usable as-is in 81% (with minor edits 93%); using soft tissue contours, plans were scored as usable as-is in 79% (with minor edits 96%). For postmastectomy breast cancer, RPA plans were scored as usable as-is in 44% (with minor edits 91%). For whole-brain treatment, RPA plans were scored as usable as-is in 67% (with minor edits 99%). For head/neck cancer, the normal tissue autocontours were acceptable as-is in 89% (with minor edits 97%). The clinical target volumes (CTVs) were acceptable as-is in 40% (with minor edits 93%). The volumetric-modulated arc therapy (VMAT) plans were acceptable as-is in 87% (with minor edits 96%). For cervical cancer, the normal tissue autocontours were acceptable as-is in 92% (with minor edits 99%). The CTVs for cervical cancer were scored as acceptable as-is in 83% (with minor edits 92%). The VMAT plans for cervical cancer were acceptable as-is in 99% (with minor edits 100%).CONCLUSIONThe RPA, a web-based tool designed to improve access to high-quality RT in low-resource settings, has high rates of clinical acceptability by practicing clinicians around the world. It has significant potential for successful implementation in low-resource clinics.

Abstract The significance of subducted organic carbon for the deep carbon cycle has been demonstrated by the presence of ultra-deep diamonds and arc emissions. However, there is no convincing evidence that organic carbon can be subducted to subarc depths. This study provides the evidence for deep subduction of sedimentary organic carbon to mantle depths through petrological observation, Raman and isotopic analyses of ultrahigh-pressure (UHP) coesite- and graphite-bearing pelitic schists. The analyzed graphite shows light δ13C values (−24.7 to −22.5‰), indicating a sedimentary organic carbon source. Petrological characteristics of graphite co-existing with coesite in garnet and P–T calculations suggest that organic graphite was subducted to the subarc depths exceeding 90 km. This research represents the petrological evidence for the deep subduction of organic carbon to mantle depths and may provide insight into the origin of diamonds with light δ13C values and contribute as key evidence for the Lomagundi event.

This study aimed to estimate the genetic and non-genetic factors that affect the nine early growth traits of Dumeng sheep, as well as to estimate the variance components and genetic parameters associated with these traits. A dataset containing detailed information on 17,896 preweaning trait records of 4474 lambs was collected. In addition, 5015 postweaning trait records of 1003 lambs were documented. The effects of recipient dam age, sex, year, season, and herd on the early growth traits were assessed using the general linear model procedure of the statistical analysis system, revealing different levels of significance across different traits. To determine the most suitable model for estimating the genetic parameters, the likelihood ratio (LR) test was employed, fitting six animal models that either excluded or included maternal genetic and maternal permanent environmental effects within the average information restricted maximum likelihood (AIREML) framework using WOMBAT software (Version: 23/11/23). The model incorporating direct additive genetic effects, maternal genetic effects, and maternal permanent environment effects as random effects (model 6) provided the best fit for birth weight (BW) estimation. In contrast, the model combining direct additive genetic effects and maternal permanent environment effects as random effects (model 2) demonstrated a superior fit for estimating the genetic parameters of weaning weight (WW), average daily gain weight from birth to weaning (ADG1), and Kleiber ratio from birth to weaning (KR1). With regard to the genetic parameters of body weight at 6 months of age (6MW), average daily gain weight from weaning to 6 months (ADG2), average daily gain weight from birth to 6 months (ADG3), Kleiber ratio from weaning to 6 months (KR2), and Kleiber ratio from birth to 6 months (KR3), model 1, which incorporates only direct additive genetic effects, was identified as the optimal choice. With the optimal model, the heritability estimates ranged from 0.010 ± 0.033 for 6MW to 0.1837 ± 0.096 for KR3. The bivariate analysis method was employed to estimate the correlation between various traits using the most suitable model. The absolute values of genetic correlation coefficients among the traits spanned a range from 0.1460 to 0.9998, highlighting both weak and strong relationships among the studied traits. Specifically, the estimated genetic correlations between WW and ADG1, ADG3, KR1, and KR3 were 0.9859, 0.9953, 0.9911, and 0.9951, respectively, while the corresponding phenotypic correlations were 0.9752, 0.7836, 0.8262, and 0.5767. These findings identified that WW could serve as an effective selection criterion for enhancing early growth traits.

AbstractAs the development of technology nodes proceeds to 7 nm node, chemical mechanical polishing (CMP) slurries for shallow trench isolation (STI) cannot fully meet the technical requirements. Higher goals are put forward for the polished surface qualities and the removal selectivity control. The polishing liquid exhibits issues such as easy agglomeration, removal rate of Si3N4 exceeding 50 Å/min, removal selectivity ratio of SiO2/Si3N4 below 20, increased surface scratches and roughness of SiO2 and Si3N4 after polishing exceeding 1 nm. Here, attention is given to studying the STI CMP process by introducing various ionic surfactants in ceria slurries, aiming to control removal rates, selectivity, as well as surface qualities. The findings of ball milling and settling tests were used as a starting point for choosing the effective surfactants, searching the minimal delamination phenomenon. Then the impact of surfactants on removal rates, selectivity and surface characteristics were next investigated in polishing trials at various pH levels. Depth of scratches on polished wafers and corresponding surface roughness, as well as morphology of ceria abrasive particles were characterized. Action mechanisms of selected ionic surfactants in ceria slurries have been revealed by solid-liquid interface adsorption characterization, thermogravimetric analysis and zeta potential tests. Through research finding the addition of piperazine and 2-methylpiperazine surfactant can reduce the number and depth of scratches on the surfaces of SiO2 and Si3N4 after polishing, and it exhibits better dispersibility in alkaline environment compared to acidic environment.

Technique: (1) A four-pointed star-shaped incision was made to separate the skin around the stoma intestine. (2) The stoma intestine was resected, and side-to-side or end-to-side anastomosis was performed to restore the continuity of the intestine. (3) The peritoneum and rectus sheath should be closed using continuous full-thickness sutures. (4) The subcutaneous fat layer and dermis layer should be sutured using purse-string sutures. Two holes should be made in the center of the sutured area. (5) The cross should be sutured intermittently on all four sides using 1–2 stitches. (6) A rubber strip should be placed in the center of the small hole. Results: The presence of a small hole in the center of the incision and the use of a rubber strip for drainage facilitate early fluid drainage. The design of a cross-stitched skin incision helps reduce local tension. Conclusion: The modified cross-suture technique may reduce postoperative incision infections and associated pain, which is a suitable incision treatment method for loop stoma reversal.

Polybrominated diphenyl ether (PBDE) contamination is common in aquatic environments and can severely damage aquatic organisms. However, there is a lack of information on the response and self-adaptation mechanisms of these organisms. Chlorella pyrenoidosa was treated with 2,2′,4,4′-tetrabromodiphenyl ether (BDE47), causing significant growth inhibition, pigment reduction, oxidative stress, and chloroplast atrophy. Photosynthetic damage contributed to inhibition, as indicated by Fv/Fm, Chl a fluorescence induction, photosynthetic oxygen evolution activity, and photosystem subunit stoichiometry. Here, Chl a fluorescence induction and quinone electron acceptor (QA−) reoxidation kinetics showed that the PSII donor and acceptor sides were insensitive to BDE47. Quantitative analyses of D1 and PsaD proteins illustrated that PSII and PSI complexes were the main primary targets of photosynthesis inhibition by BDE47. Significant modulation of PSII complex might have been caused by the potential binding of BDE47 on D1 protein, and molecular docking was performed to investigate this. Increased activation of antioxidant defense systems and photosystem repair as a function of exposure time indicated a positive resistance to BDE47. After a 5-day exposure, 23 % of BDE47 was metabolized. Our findings suggest that C. pyrenoidosa has potential as a bioremediator for wastewater-borne PBDEs and can improve our understanding of ecological risks to microalgae.

PURPOSEAutomation, including the use of artificial intelligence, has been identified as a possible opportunity to help reduce the gap in access and quality for radiotherapy and other aspects of cancer care. The Radiation Planning Assistant (RPA) project was conceived in 2015 (and funded in 2016) to use automated contouring and treatment planning algorithms to support the efforts of oncologists in low- and middle-income countries, allowing them to scale their efforts and treat more patients safely and efficiently (to increase access).DESIGNIn this review, we discuss the development of the RPA, with a particular focus on clinical acceptability and safety/risk across jurisdictions as these are important indicators for the successful future deployment of the RPA to increase radiotherapy availability and ameliorate global disparities in access to radiation oncology.RESULTSRPA tools will be offered through a webpage, where users can upload computed tomography data sets and download automatically generated contours and treatment plans. All interfaces have been designed to maximize ease of use and minimize risk. The current version of the RPA includes automated contouring and planning for head and neck cancer, cervical cancer, breast cancer, and metastases to the brain.CONCLUSIONThe RPA has been designed to bring high-quality treatment planning to more patients across the world, and it may encourage greater investment in treatment devices and other aspects of cancer treatment.

The mass imbalance of felsic crust in the India-Asia collision system can be explained by metamorphic densification of continental crust below 170 km depth, which would also help drive and maintain subduction, according to petrological-thermo-mechanical modeling.

Abstract The naturally occurring homo-polyamide biopolymer, ε-poly-L-lysine (ε-PL) consists of 25–35 L-lysine residues with amide linkages between α-carboxyl groups and ε-amino groups. ɛ-PL exhibits several useful properties because of its unusual structure, such as biodegradability, water solubility, no human toxicity, and broad-spectrum antibacterial activities; it is widely applied in the fields of food, medicine, clinical chemistry and electronics. However, current industrial production of ε-PL is only performed in a few countries. Based on an analysis of the physiological characteristics of ε-PL fermentation, current advances that enhance ε-PL fermentation, from strain improvement to product isolation are systematically reviewed, focusing on: (1) elucidating the metabolic pathway and regulatory mechanism of ε-PL synthesis; (2) enhancing biosynthetic performance through mutagenesis, fermentation optimization and metabolic engineering; and (3) understanding and improving the biological activity and functional properties of ε-PL. Finally, perspectives on engineering and exploiting ε-PL as a source material for the production of various advanced materials are also discussed, providing scientific guidelines for researchers to further improve the ε-PL fermentation process.

Although quartzo-feldspathic metasedimentary rocks are widespread in high pressure-ultrahigh pressure (HP-UHP) metamorphic belts worldwide, their petrogenesis and metamorphic evolution is poorly understood. We discovered an UHP eclogite-facies felsic schist in the Western Tianshan metamorphic belt, China. Petrological observations and phase equilibria modeling both indicate the felsic schist experienced UHP metamorphism in the coesite stability field. In particular, it experienced prograde metamorphism at 21–24 kbar, 445°C–470°C, a pressure peak at 25–28 kbar and 490°C–525°C, and eventually heating with decompression to 20 kbar and 560°C. The obtained clockwise P-T path was consistent with those of other lithologies (eclogite and pelitic schist) from the same belt, which provides new evidence for the coherent exhumation of the UHP unit of the Western Tianshan metamorphic belt. The final uplift of the Western Tianshan oceanic crust to the surface is attributed to fluid activity and late tectonic deformation.

Abstract Background Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. Methods In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. The in vivo hematopoietic reconstitution potential of c-kit+ cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. Results The c-kit+ cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. We interestingly found that our 3D+OP9 system enriched a higher percentage of CD201+c-kit+cells that showed more similar HSC-like features such as transcriptome level and CFU formation ability than CD201-c-kit+cells, which have not been reported in the field of mouse PSCs hematopoietic differentiation. Moreover, CD201+ hematopoietic cells remained in a relatively slow cycling state, consistent with high expression levels of P57 and Ccng2. Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201+ hematopoietic cell induction from mouse PSCs. Conclusions Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application.

The overlying weakly cemented, and poorly performing strata in Jurassic mines of western China have mechanical properties that are generally lower than those in the Carboniferous-Permian coal mines of central and east China. During coal mining, the overlying strata easily deform and fracture. These then formed water-conducting channels, triggering a series of eco-environmental issues, including ground fracturing, collapsed surfaces, declined underground water levels, deserted lands, and even severe water/sand burst accidents. To study the fracture characteristics of weakly cemented overlying strata and the evolution law of water-conducting fractures in Jurassic coal mines in western China, this study selected Tashidian Erjingtian Mine in Korla, Xinjiang, as the research object. Based on the simulation data obtained with physical analog model testing and field monitoring results, the authors investigated the development of water-conducting fractures in the weakly cemented overlying strata during the coal seam mining process. We simultaneously determined the location of key strata in the working face based on key stratum theory. According to the present research results, key strata controlled the development height of water-conducting fractures. When the primary key stratum or sub-key stratum was not fractured, the development of water-conducting fractures was stagnant; water-conducting fractures developed abruptly when the primary key stratum or sub-key stratum was cracked. The heights of water-conducting fractures in the weakly cemented overlying strata of western China exceeded that of similar stopes of central and east China. These research results provided theoretical and technical support for safety in production at Tashidian Coal Mine. In addition, they offered a reference for green and safe production in Jurassic coal mines of western China.

Abstract With the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

Circulating cell-free DNA (cfDNA) detection, a non-invasive method, appears promising for genetic analyses as well as quantitative assessment of tumor burden in patients with cancer. Although the analysis of cfDNA for clinical prognosis and monitoring disease burden in multiple myeloma (MM) has been recently studied, the results are unclear. In this meta-analysis, we explored the clinical significance of circulating cfDNA detection in patients with MM. We searched PubMed, Embase, and the Cochrane Library for eligible studies published up until July 25, 2021. Diagnostic accuracy variables were calculated and analyzed using Meta-Disc, and prognostic data were analyzed using Review Manager. Overall, seven studies comprising 235 myeloma patients met our inclusion criteria. The overall sensitivity and specificity of cfDNA to detect minimal residual disease (MRD) were 0.58 and 0.91, respectively. Moreover, higher levels of cfDNA were associated with worse progression-free survival as well as with poor overall survival. Our meta-analysis revealed that ctDNA detection has an obvious advantage in terms of MRD detection specificity, but it showed no superiority over bone marrow assessment in terms of MRD detection sensitivity, and higher levels of cfDNA were indicative of worse prognosis in patients with MM. cfDNA detection is a non-invasive method and thus shows promise as a good alternative to BM biopsies for monitoring clonal evolution and tumor burden so as to guide the treatment of patients with MM.

Ibrutinib, a bruton tyrosine kinase (BTK) inhibitor which suppresses B-cell receptor signaling, has remarkably improved the outcome of patients with mantle cell lymphoma (MCL). However, approximately 33% of MCL patients have primary Ibrutinib resistance, and acquired Ibrutinib resistance is nearly universal. Long intergenic non-coding RNA for kinase activation (LINK-A) exerts oncogenic role in different types of tumors, but the role of LINK-A in intrinsic ibrutinib resistance in MCL is still unclear. Here, LINK-A expression level was first assessed using quantitative Real-time PCR (qPCR) and immunofluorescence analysis in five MCL cell lines. The effect of LINK-A on regulating MCL cells viability and apoptosis was assayed using CCK-8 and TdT-mediated dUTP nick end labeling (TUNEL) assay, respectively. The association of LINK-A with AKT activation and B cell lymphoma 2 (Bcl2)expression was evaluated using qPCR and western blot analysis. We found that LINK-A level was elevated in Ibrutinib-resistant MCL cell lines (Mino, REC-1, MAVER-1, and Granta-519) compared to Ibrutinib-sensitive MCL cell lines (Jeko-1). Functionally, LINK-A overexpression in Jeko-1 cells enhanced cell viability and repressed Ibrutinib-induced cell apoptosis. LINK-A knockdown in MAVER-1 cells decreased cell viability and further accelerated Ibrutinib-induced cell apoptosis. LINK-A overexpression enhanced Bcl2 expression in Jeko-1 cells, and Bcl2 inhibition blocked the effect of LINK-A on increasing cell viability in the presence of Ibrutinib. On the contrary, LINK-A knockdown reduced Bcl2 expression in MAVER-1 cells, and Bcl2 overexpression damaged the role of LINK-A inhibition in regulating cell viability. Mechanistically, LINK-A positively regulated the activation of AKT signaling, and inhibition of AKT signaling destroyed LINK-A-induced increased of Bcl2 and resulted in a subsequent suppression of cell viability. Taken together, the current results demonstrate that LINK-A inhibition overcomes Ibrutinib resistance in MCL cells by regulating AKT/Bcl2 pathway.

Bacteria with carbapenem or tigecycline resistance have been spreading widely among humans, animals and the environment globally, being great threats to public health. However, bacteria co-carrying drug resistance genes of carbapenem and tigecycline in Shewanella and Acinetobacter species remain to be investigated. Here, we detected nine blaNDM-1-carrying Shewanella spp. isolates as well as three A. portensis isolates co-harboring tet(X3) and blaNDM-1 from seventy-two samples collected from a dairy farm in China. To explore their genomic characteristic and transmission mechanism, we utilized various methods, including PCR, antimicrobial susceptibility testing, conjugation experiment, whole-genome sequencing, circular intermediate identification and bioinformatics analysis. Clonal dissemination was found among three A. portensis, of which tet(X3) and blaNDM-1 were located on a novel non-conjugative plasmid pJNE5-X3_NDM-1 (333,311 bp), and the circular intermediate ΔISCR2-tet(X3)-blaNDM-1 was identified. Moreover, there was another copy of tet(X3) on the chromosome of A. portensis. It was verified that blaNDM-1 could be transferred to Escherichia coli C600 from Shewanella spp. by conjugation, and self-transmissible IncA/C2 plasmids mediated the transmission of blaNDM-1 in Shewanella spp. strains. Stringent surveillance was warranted to curb the transmission of such vital resistance genes.

Purpose: The purpose of this study was to validate a fully automatic treatment planning system for conventional radiotherapy of cervical cancer. This system was developed to mitigate staff shortages in low-resource clinics. Methods: In collaboration with hospitals in South Africa and the United States, we have developed the Radiation Planning Assistant (RPA), which includes algorithms for automating every step of planning: delineating the body contour, detecting the marked isocenter, designing the treatment-beam apertures, and optimizing the beam weights to minimize dose heterogeneity. First, we validated the RPA retrospectively on 150 planning computed tomography (CT) scans. We then tested it remotely on 14 planning CT scans at two South African hospitals. Finally, automatically planned treatment beams were clinically deployed at our institution. Results: The automatically and manually delineated body contours agreed well (median mean surface distance, 0.6 mm; range, 0.4 to 1.9 mm). The automatically and manually detected marked isocenters agreed well (mean difference, 1.1 mm; range, 0.1 to 2.9 mm). In validating the automatically designed beam apertures, two physicians, one from our institution and one from a South African partner institution, rated 91% and 88% of plans acceptable for treatment, respectively. The use of automatically optimized beam weights reduced the maximum dose significantly (median, −1.9%; P < .001). Of the 14 plans from South Africa, 100% were rated clinically acceptable. Automatically planned treatment beams have been used for 24 patients with cervical cancer by physicians at our institution, with edits as needed, and its use is ongoing. Conclusion: We found that fully automatic treatment planning is effective for cervical cancer radiotherapy and may provide a reliable option for low-resource clinics. Prospective studies are ongoing in the United States and are planned with partner clinics.

Impure dolomitic marble from the Great Himalayan Sequences (GHS) in Thongmön area, central Himalaya, is first systematically reported here concerning its petrographic features, textural relations, and fluid evolution. The Thongmön impure marble is characterized by the assemblage of calcite + dolomite + forsterite + spinel + phlogopite + clinohumite ± diopside ± retrograde serpentine. Three groups of calcite and dolomite occurring both as inclusions and in the matrix were identified: group I is represented by relatively magnesium-rich calcite (Cal) (CalI:XMg = 0.10–0.15) and almost pure dolomite (Dol) (DolI:XMg = 0.47–0.48), corresponding to the Cal-Dol solvus temperatures of 707–781 °C; group II is characterized by vermicular dolomite exsolutions (DolII:XMg = 0.45–0.46) in Mg-rich calcite and Mg-poor calcite (CalII:XMg = 0.05–0.08) adjacent to DolII, and the recorded solvus temperatures are 548–625 °C; group III is represented by nearly pure calcite (CalIII:XMg = 0.003–0.02) and Ca-rich dolomite in the matrix (DolIII:XMg = 0.33–0.44). Isobaric T-X(CO2) pseudosection at a peak pressure of 15 kbar in the system K2O-CaO-MgO-Al2O3-FeO-SiO2-H2O-CO2 suggests that the peak fluid composition of the Thongmön forsterite marble is restricted to X(CO2) < 0.04 at T > 780 °C due to a potential infiltration event of H2O-rich fluid. Alternatively, the forsterite marble is a retrograde product subordinated to the GHS exhumation process, and its fluid composition is relatively CO2-rich (0.6 < X(CO2) < 0.8 at 5 kbar, 750 °C) at a nearly isothermal decompression stage. In either case, we suggest that the carbon flux contributed by metacarbonate rocks in an orogen setting to the global carbon cycling must be considered.

To date, multiple myeloma remains an incurable disease. Immunotherapy is an encouraging option in the development of multiple myeloma (MM) therapy. CS1 is a specific myeloma antigen, which is highly expressed in myeloma cells. Calreticulin (CRT) is a key determinant of cell death, which can influence antigen presentation and promote cellular phagocytic uptake. In the current study, we constructed a DNA vaccine encoding both CS1 and CRT. Our results show that the PcDNA3.1-CS1/CRT vaccine was able to induce cytotoxic T cell responses against myeloma cells in vivo, and the tumor growth was significantly suppressed in mice immunized with this vaccine. Therefore, our findings indicate that the CS1/CRT fusion DNA vaccine may represent a promising novel myeloma therapy, and the potential for combining the CS1/CRT vaccine with other myeloma treatments.

The behavior of the bond between Engineering Cementitious Composites (ECC) and Glass Fiber Reinforced Polymer (GFRP) bar has a strong effect on the behavior of this composite structure. However, it is difficult to detect the failure mode and damage status of the interface using traditional testing methods. This is due to the strain-hardening mechanical behavior of ECC. An effective monitoring method using patch lead zirconate titanate (PZT) transducers and active sensing technology was used to detect the internal damage. In this active sensing technology, a PZT smart aggregate was bonded onto the middle surface of ECC, acting as a sensor. This study conducted a series of experimental studies on the bond behavior of GFRP-reinforced ECC based on pull-out tests. The test results are presented and discussed to investigate the bond-slip relationship and failure mechanism between FRP reinforcing bars and the ECC matrix. The status of interfacial damage between ECC and GFRP can be represented by the attenuation change of the stress wave. Finally, a damage index (DI) obtained using wavelet packet analysis is proposed to evaluate and quantify the level of FRP–ECC interaction damage. The analytical results reveal that the debonding and failure mechanism can be detected by using this DI index value, and the influence of the diameter of reinforcing bars should be considered, as should the Poisson's effect.

Purpose: We assessed automated contouring of normal structures for patients with head-and-neck cancer (HNC) using a multiatlas deformable-image-registration algorithm to better provide a fully automated radiation treatment planning solution for low- and middle-income countries, provide quantitative analysis, and determine acceptability worldwide. Methods: Autocontours of eight normal structures (brain, brainstem, cochleae, eyes, lungs, mandible, parotid glands, and spinal cord) from 128 patients with HNC were retrospectively scored by a dedicated HNC radiation oncologist. Contours from a 10-patient subset were evaluated by five additional radiation oncologists from international partner institutions, and interphysician variability was assessed. Quantitative agreement of autocontours with independently physician-drawn structures was assessed using the Dice similarity coefficient and mean surface and Hausdorff distances. Automated contouring was then implemented clinically and has been used for 166 patients, and contours were quantitatively compared with the physician-edited autocontours using the same metrics. Results: Retrospectively, 87% of normal structure contours were rated as acceptable for use in dose-volume-histogram–based planning without edit. Upon clinical implementation, 50% of contours were not edited for use in treatment planning. The mean (± standard deviation) Dice similarity coefficient of autocontours compared with physician-edited autocontours for parotid glands (0.92 ± 0.10), brainstem (0.95 ± 0.09), and spinal cord (0.92 ± 0.12) indicate that only minor edits were performed. The average mean surface and Hausdorff distances for all structures were less than 0.15 mm and 1.8 mm, respectively. Conclusion: Automated contouring of normal structures generates reliable contours that require only minimal editing, as judged by retrospective ratings from multiple international centers and clinical integration. Autocontours are acceptable for treatment planning with no or, at most, minor edits, suggesting that automated contouring is feasible for clinical use and in the ongoing development of automated radiation treatment planning algorithms.

The onset of modern-style plate tectonics remains under debate. Here, Xu et al. report a cold thermal-gradient recorded in an eclogite xenolith in Paleoproterozoic carbonatite from orogen, and propose that modern-style subduction has operated since at least the Paleoproterozoic.

Comparative analysis of the crustal evolution of the Early Precambrian Belomorian and Trans-North China orogens (Fig. 1) has shown [Slabunov et al., 2015] that: Both belts were formed by the superposition of two Precambrian orogenies. The earth crust of the Belomorian belt was produced during the Mesoarchaean to Neoarchaean Belomorian collisional orogeny [Slabunov, 2008; Slabunov et al., 2006] and then was reworked during the Palaeoproterozoic Lapland-Kola collisional orogeny [Daly at al., 2006; Balagansky et al., 2014]. The earth crust of the Trans-North China orogen was formed during a Neoarchean accretionary orogeny and then was reworked during a Paleoproterozoic collisional orogeny [Zhao et al., 2012; Guo et al., 2012, 2005]. The Lapland granulite belt is the core of the Lapland-Kola Palaeoproterozoic collisional orogen in the Fennoscandian shield and the Khondolite belt occupies the same tectonic position in a Palaeoproterozoic collisional orogen in the North China craton.

Purpose: Radiomics has shown great promise to use quantifiable imaging characteristics to predict the behavior and prognosis of neoplasms. This is the first study to evaluate whether radiomic texture analysis can predict outcomes in gastroesophageal junction adenocarcinoma (GEJAC) treated with neoadjuvant chemoradiotherapy (CRT). Materials and Methods: Pretreatment contrast-enhanced CT images of 146 patients with stage II-III GEJAC were reviewed (2009–2011), and randomly split into training and validation groups at a 1:1 ratio stratified with baseline clinical characteristics. Whole-tumor texture was assessed using quantitative image features based on intensity, shape, and gray-level co-occurrence matrix. The relevant pretreatment texture features, in addition to the significant baseline clinical features to predict survival, were identified using multivariate Cox proportional hazard regression model with stepwise variable selection in the training sample and verified in the validation sample, to facilitate the proposal of a multi-point index for standard patient pre-treatment risk classification. Results: Of the factors identified in the training cohort independently associated with OS, only shape compactness (p = 0.04) and pathologic grade differentiation (PDG) (p = 0.02) were confirmed in the validation sample. Using both parameters, we created a 3-point risk classification index: low-risk (well-moderate PDG and high compactness), medium-risk (poor PDG or low compactness), and high-risk (poor PDG and low compactness). The risk index showed a strong negative association with postoperative pathologic complete response (pCR) (p = 0.04). Median OS for the high-, medium-, and low-risk groups were 23, 51, and ≥72 months, respectively (p

Abstract Radiomics is the use of quantitative imaging features extracted from medical images to characterize tumor pathology or heterogeneity. Features measured at pretreatment have successfully predicted patient outcomes in numerous cancer sites. This project was designed to determine whether radiomics features measured from non–small cell lung cancer (NSCLC) change during therapy and whether those features (delta-radiomics features) can improve prognostic models. Features were calculated from pretreatment and weekly intra-treatment computed tomography images for 107 patients with stage III NSCLC. Pretreatment images were used to determine feature-specific image preprocessing. Linear mixed-effects models were used to identify features that changed significantly with dose-fraction. Multivariate models were built for overall survival, distant metastases, and local recurrence using only clinical factors, clinical factors and pretreatment radiomics features, and clinical factors, pretreatment radiomics features, and delta-radiomics features. All of the radiomics features changed significantly during radiation therapy. For overall survival and distant metastases, pretreatment compactness improved the c-index. For local recurrence, pretreatment imaging features were not prognostic, while texture-strength measured at the end of treatment significantly stratified high- and low-risk patients. These results suggest radiomics features change due to radiation therapy and their values at the end of treatment may be indicators of tumor response.

Previously, generative adversarial networks (GAN) have been widely applied on super resolution reconstruction (SRR) methods, which turn low-resolution (LR) images into high-resolution (HR) ones. However, as these methods recover high frequency information with what they observed from the other images, they tend to produce artifacts when processing unfamiliar images. Optical satellite remote sensing images are of a far more complicated scene than natural images. Therefore, applying the previous networks on remote sensing images, especially mid-resolution ones, leads to unstable convergence and thus unpleasing artifacts. In this paper, we propose Enlighten-GAN for SRR tasks on large-size optical mid-resolution remote sensing images. Specifically, we design the enlighten blocks to induce network converging to a reliable point, and bring the Self-Supervised Hierarchical Perceptual Loss to attain performance improvement overpassing the other loss functions. Furthermore, limited by memory, large-scale images need to be cropped into patches to get through the network separately. To merge the reconstructed patches into a whole, we employ the internal inconsistency loss and cropping-and-clipping strategy, to avoid the seam line. Experiment results certify that Enlighten-GAN outperforms the state-of-the-art methods in terms of gradient similarity metric (GSM) on mid-resolution Sentinel-2 remote sensing images.

In this paper, a low-cost small-sized strap-down inertial navigation system (SINS)—Gyrolab GL-VG 109—is studied. When the system is installed on an unmanned vehicle and works in autonomous mode, it is difficult to determine the navigation parameters of the unmanned vehicle. Correcting the SINS information from the Global Navigation Satellite System (GNSS) can significantly increase the determination accuracy of the navigation parameters. However, this is only available when the GNSS signals are stable. A new adaptive estimation algorithm that can automatically detect, evaluate, and process the abnormal measurements is proposed in the present work. The determination of the navigation parameters can reach the third accuracy class using the proposed method. The effectiveness of the algorithm is verified by the mathematical simulation and the experimental tests (with a real SINS GL-VG 109), which are conducted in urban environments with a GNSS signal containing 15% and 40% abnormal measurements. The results show that the proposed method can significantly reduce the impact of abnormal measurements and improve the estimation accuracy.

The isothermal bulk moduli of anhydrous Mg2SiO4-ringwoodite (Rw) and Fe2SiO4-Rw, and other 4–2 oxide spinels at ambient P-T condition have been evaluated, and empirically fitted to a model as KT0 = 270.8(300) + 0.343(59)*V0 + 23.04(269)*EN-total, where KT0 is the isothermal bulk modulus in GPa, V0 the unit-cell volume in Å3 and EN-total the electronegativity total of all cations in the chemical formula. This model well reproduces all data used in its calibration, and may be used to predict the KT0 of other 4–2 oxide spinels. Combined with the generally linear volume–composition relationship of the Rw solid solutions along the join Mg2SiO4–Fe2SiO4, this model leads to a much smaller composition effect on the KT0: KT0 = 185.0(1) + 7.0(1)*XFe, where XFe is the atomic ratio Fe/(Fe + Mg). Furthermore, a bulk composition-independent compositional variation with P has been disclosed for the Rw at the P-T conditions of the lower part of the mantle transition zone (MTZ): XFe = 0.222(41) – 0.0053(19)*P, with P in GPa. The nearly ideal mixing behavior, much smaller composition effect on the bulk modulus, and significant compositional variation of the Rw in the lower part of the MTZ substantially increase the gradients of the Vs-P and Vp-P profiles to generally match those constrained by the seismic reference models PREM and AK135. If there is any global low-T anomaly at the depth of 660 km, its required magnitude is most likely not larger than 200 K.

The control performance of a dynamic system can be checked by the degree of controllability. In this work, we present a new method for determining the degree of observability of state variables for the linear quadratic optimal estimation (LQE) problem. We carried out the calculation of the degree of controllability for the linear quadratic optimal control (LQR) problem using a duality theorem. Compared with the traditional measures of controllability such as determinant, trace, and maximal eigenvalue of the inverse controllability Gramian, the proposed degree of controllability was developed for each state variable and takes into account both the controllability Gramian and the cost function. The new method is convenient to apply to LQR problem. In the numerical simulation, we determined the influence of the model parameters on the degree of controllability. Besides that, we analyzed the degree of controllability, which gives an insight into the relationship between the system model design and the control performance.

[This corrects the article DOI: 10.1371/journal.pone.0178524.].

The purpose of this paper is to develop an approach to multiattribute group decision making under interval-valued hesitant fuzzy environment. To do this, this paper defines some new operations on interval-valued hesitant fuzzy elements, which eliminate the disadvantages of the existing operations. Considering the fact that elements in a set may be interdependent, two generalized interval-valued hesitant fuzzy operators based on the generalized Shapley function and the Choquet integral are defined. Then, some models for calculating the optimal fuzzy measures on the expert set and the ordered position set are established. Because fuzzy measures are defined on the power set, it makes the problem exponentially complex. To simplify the complexity of solving a fuzzy measure, models for the optimal 2-additive measures are constructed. Finally, an investment problem is offered to show the practicality and efficiency of the new method.

Consistent pixel sizes are of fundamental importance for assessing texture features that relate intensity and spatial information in radiomics studies. To correct for the effects of variable pixel sizes, we combined image resampling with Butterworth filtering in the frequency domain and tested the correction on computed tomography (CT) scans of lung cancer patients reconstructed 5 times with pixel sizes varying from 0.59 to 0.98 mm. One hundred fifty radiomics features were calculated for each preprocessing and field-of-view combination. Intra-patient agreement and inter-patient agreement were compared using the overall concordance correlation coefficient (OCCC). To further evaluate the corrections, hierarchical clustering was used to identify patient scans before and after correction. To assess the general applicability of the corrections, they were applied to 17 CT scans of a radiomics phantom. The reduction in the inter-scanner variability relative to non-small cell lung cancer patient scans was quantified. The variation in pixel sizes caused the intra-patient variability to be large (OCCC

Object detection on very-high-resolution (VHR) remote sensing imagery has attracted a lot of attention in the field of image automatic interpretation. Region-based convolutional neural networks (CNNs) have been vastly promoted in this domain, which first generate candidate regions and then accurately classify and locate the objects existing in these regions. However, the overlarge images, the complex image backgrounds and the uneven size and quantity distribution of training samples make the detection tasks more challenging, especially for small and dense objects. To solve these problems, an effective region-based VHR remote sensing imagery object detection framework named Double Multi-scale Feature Pyramid Network (DM-FPN) was proposed in this paper, which utilizes inherent multi-scale pyramidal features and combines the strong-semantic, low-resolution features and the weak-semantic, high-resolution features simultaneously. DM-FPN consists of a multi-scale region proposal network and a multi-scale object detection network, these two modules share convolutional layers and can be trained end-to-end. We proposed several multi-scale training strategies to increase the diversity of training data and overcome the size restrictions of the input images. We also proposed multi-scale inference and adaptive categorical non-maximum suppression (ACNMS) strategies to promote detection performance, especially for small and dense objects. Extensive experiments and comprehensive evaluations on large-scale DOTA dataset demonstrate the effectiveness of the proposed framework, which achieves mean average precision (mAP) value of 0.7927 on validation dataset and the best mAP value of 0.793 on testing dataset.

A natural chromian spinel with the composition (Mg0.48(3)Fe0.52(3))(Fe0.06(1)Al0.28(1)Cr0.66(2))2O4 was investigated up to 15 GPa via synchrotron X-ray diffraction with a diamond-anvil cell at room temperature. No phase transition was clearly observed up to the maximum experimental pressure. The pressure⁻volume data fitted to the third-order Birch⁻Murnaghan equation of state yielded an isothermal bulk modulus ( K T 0 ) of 207(5) GPa and its first pressure derivative ( K T 0 ′ ) of 3.2(7), or K T 0 = 202(2) GPa with K T 0 ′ fixed as 4. With this new experimental result and the results on some natural chromian spinels in the literature, a simple algorithm describing the relation between the K T 0 and the compositions of the natural chromian spinels was proposed. To examine this algorithm further, more compression experiments should be performed on natural chromian spinels with different chemical compositions.

Background Recently, several important polymorphisms have been identified in T-cell activation and effector pathway genes and have been reported to be associated with inter-patient variability in alloimmune responses. The present study was designed to assess the impact of these genetic variations on the outcomes of allogeneic hematopoietic stem cell transplantation.Design and Methods We first investigated ten single nucleotide polymorphisms in six genes, CD28, inducible co-stimulator, cytotoxic T-lymphocyte antigen 4, granzyme B, Fas and Fas ligand, in 138 pairs of patients and their unrelated donors and a second cohort of 102 pairs of patients and their HLA-identical sibling donors.Results We observed that patients receiving stem cells from a donor with the cytotoxic T-lymphocyte antigen 4 gene CT60 variant allele (AA genotype) had a reduced incidence of grades II–IV acute graft-versus-host disease; however, they experienced early cytomegalovirus infection and relapsed more frequently, which suggested an interaction between the donor cytotoxic T-lymphocyte antigen 4 gene CT60 AA genotype and reduced T-cell alloreactivity. Furthermore, an unrelated donor with the granzyme B +55 variant genotype (AA) was an independent risk factor for development of grades II–IV acute graft-versus-host disease (P=0.024, RR=1.811). Among patients with acute myelogenous leukemia, those with the Fas -670 TT genotype were at higher risk of relapse (P=0.003, RR=3.823). The presence of these susceptible alleles in the donor and/or patient resulted in worse overall survival (54.9% versus 69.5%, P=0.029).Conclusions Our data suggest that genotype analysis of T-cell activation and effector pathway genes can be used for risk assessment for patients with hematologic malignancies before hematopoietic stem cell transplantation.

The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P