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Fast homogenization without incipient melting is the key to designing solution heat treatment (SHT) process for single crystal superalloys. In this paper, a multicomponent phase-field model coupled with solidus temperature is developed for dynamically tracking incipient melting temperature, TIM, of alloy during SHT. The simulation process runs completely automatically only by inputting the composition information of as-cast specimen. Based on the obtained TIM-time profile, the holding temperature and the time of SHT are determined. Applying this approach to Co–30Ni–11Al–4W–1Ta–4Ti–5Cr single crystal specimen, a gradual increased TIM from 1247 °C to 1293 °C within 72,000 s is obtained, and thus a stepwise SHT process with a short time of less than 20 h is designed. The experimental verification shows that after SHT, the segregation coefficient of the slowest diffusing element W decreased from more than 2 to 1.065, the content of harmful secondary phase has decreased to below 0.1%, and no incipient melting occurs.

Within the Basis Light-Front Quantization framework, we systematically investigate the subleading twist (twist-3) transverse-momentum-dependent parton distribution functions (TMDs) of the proton beyond the Wandzura-Wilczek (WW) approximation. The subleading twist TMDs are not independent and can be decomposed into twist-2 and genuine twist-3 terms from the equations of motion. The latter involves quark-quark-gluon correlations and contains interferences between two light-front Fock sectors, |qqq〉 and |qqqg〉, which are usually neglected in the WW approximation. This work provides new nonperturbative input for future experiments at the EicC and EIC on high-twist effects, especially interference effects among multiple partons.

Gluon transverse-momentum dependent distributions (TMDs) are very important for revealing the internal structure of the proton. They correspond to a variety of experiments and are among the major tasks of the future electron-ion colliders. In this paper, we calculate the T-even gluon TMDs at the leading twist within the Basis Light-front Quantization framework. We employ the light-front wave functions of the proton obtained from a light-front quantized Hamiltonian with Quantum Chromodynamics input determined for its valence Fock-sector with three constituent quarks and an additional Fock-sector, encompassing three quarks and a dynamical gluon, with a three-dimensional confinement. After obtaining the numerical results we investigate the properties of gluon TMDs by checking whether they satisfy the Mulders-Rodrigues inequalities and investigate the correlations between transverse and longitudinal degrees of freedom. With their connection to unintegrated gluon distributions in mind, we further investigate the limiting behaviors of gluon TMDs in the small-x and large-x regions.

Benzene is a broadly used industrial chemicals which causes various hematologic abnormalities in human. Altered DNA methylation has been proposed as epigenetic biomarkers in health risk evaluation of benzene exposure, yet the role of methylation at specific CpG sites in predicting hematological effects remains unclear. In this study, we recruited 120 low-level benzene-exposed and 101 control male workers from a petrochemical factory in Maoming City, Guangdong Province, China. Urinary S-phenylmercapturic acid (SPMA) in benzene-exposed workers was 3.40-fold higher than that in control workers (P

The flowability and spreadability of powders are the important factors for additive manufacturing as these two factors directly impact the powder bed packing density, which further affect the quality and mechanical properties of the built components. The flowability and spreadability of powders are dramatically influenced by particle surface roughness as well as the surface energy. The present research attempt to demonstrate the effect of the particle surface roughness on the flowability and spreadability of Haynes 230 powder. The virgin atomized Haynes 230 powder and the atomized powder after ball milling treatment were employed in the present research. The results show that after ball milling, the surface roughness root mean square (rms) of the initial powder increased from 14.87 nm to 42.54 nm and the surface energy of powder increased from 41.19 mJ/m2 to 77.21 mJ/m2, the rest angle of powder increased 30% and the static cohesion index increased from 0.63 to 2.00. According to the calculated Bog coefficient of the two powders (from 2.85 to 15.56), the increase of particle surface roughness leading to the increase of contact force and non-contact force among particles, which were caused by the increased cohesion, leading to the decrease of powder flowability and spreadability as well as the powder bed packing density.

In this paper, the evolution of the γ′ and η phases of new Ni–Co-based superalloy with different Nb contents was investigated using a combination of thermodynamic calculations and high-throughput selective laser melting (SLM). Thermodynamic calculations show that the increase of Nb content lowered the solubility temperature of the γ′ phase and caused the precipitation of the η phase. The alloys with the Nb gradient content prepared by SLM during aging at 800 °C for 100h indicated that the maximum volume fraction and size of the γ′ phase reach the maximum at 3.0–3.5% Nb. The elongated η phases enrichment in Ni, Ti, and Nb atoms precipitate for the Nb content higher than 2.2% Nb and prefer to grow longitudinally at the expense of the γ′ precipitates. Combining the influence of the Al/(Nb + Ta + Ti) ratio on the η precipitates, the addition of Nb content in the Ni–Co-based superalloys is less than 2.2%, which increases the high-temperature yield strength and tensile strength.

ABSTRACTIn this work, by using multi-scale characterizations from electron channeling contrast imaging (ECCI) to atom probe tomography (APT), we directly evidenced that the massive cracking events in the selective-laser-melted (SLMed) Haynes 230 superalloy are due to the continuous decoration of an M23C6-type thin film at grain boundaries. The high-melting-point nature of the carbide rules out the possibility of liquidation cracking, while the long and straight film surface facilitates stress-induced solid-state cracking. Impurities, Si, Mn and Fe, greatly enhance the cracking susceptibility despite the interesting fact that they are strongly depleted from the carbide.

Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.

The deformation behavior of a new Ni-Co base superalloy GH4251 under hot compression tests within the deformation strain window of 0.36 to 1.2 was investigated in the temperature range of 1050 ∼ 1170 °C and strain rate range of 0.001 ∼ 1 s ^−1 . Based on the analysis of true stress-strain curves, constitutive equations were established to describe the rheological behavior during hot compression. Microstructure evolution was investigated by transmission electron microscope (TEM), scanning electron microscope (SEM) and optical metallography (OM). The results show that flow behavior of GH4251 alloy is combinedly determined by the effect of work hardening and dynamic recrystallization (DRX). The deformation activation energies at strain of 0.36 to 1.2 are calculated to be 311 ∼ 536 kJ mol ^−1 in the super-solvus temperature region, and 796 ∼ 1064 kJ mol ^−1 in the sub-solvus temperature region. The recrystallization nucleation mechanism of GH4251 alloy is strain induced grain boundary migration (SIBGM). The occurrence and expansion of recrystallization are strongly promoted by high deformation temperatures and high strain rates, while the DRX grain size increases with elevated deformation temperature. When the deformation temperature is below 1090°C, the recrystallized grain can be extremely small (

Objective: To evaluate the associations between childhood, parental, and grandparental asthma.Methods: We studied 59,484 children randomly selected from 94 kindergartens, elementary, and middle schools in seven Chinese cities from 2012 to 2013, using a cross-sectional survey-based study design. Information on their and their family members' (parents, paternal grandparents, and maternal grandparents) asthma status were reported by children's parents or guardians. Mixed effects logistic regressions were used to assess hereditary patterns of asthma and mediation analysis was performed to estimate the potential mediation effect of parents on the association between grandparental asthma and childhood asthma.Results: The magnitude of ORs for childhood asthma increased as the number of family members affected by asthma increased. Among children who had one family member with asthma, childhood asthma was associated with asthma in maternal grandmothers (OR: 2.08, 95% CI: 1.67–2.59), maternal grandfathers (OR: 2.08, 95% CI: 1.71–2.53), paternal grandmothers (OR: 2.40, 95% CI: 1.93–2.99), and paternal grandfathers (OR: 2.59, 95% CI: 2.14–3.13). Among children who had two family members with asthma, the highest asthma risk was found when both parents had asthma (OR: 15.92, 95% CI: 4.66–54.45). Parents had a small proportion of mediation effect (9–12%) on the association between grandparental asthma and childhood asthma.Conclusions: Grandparents with asthma were associated with childhood asthma and parents with asthma partially mediated the association.

Abstract Familial risk of ovarian cancer is well-established but whether ovarian cancer clusters with other cancers and the clusters differ by histology remains uncertain. Using data from the Swedish Family-Cancer Database, we explored familial associations of ovarian cancer with other cancers with a novel approach; relative risk for (histology-specific) ovarian cancer was estimated in families with patients affected by other cancers, and conversely, risks for other cancers in families with (histology-specific) ovarian cancer patients. Eight discordant cancers were associated with ovarian cancer risk, of which family history of breast cancer showed a dose-response (P-trend

Abstract Colorectal cancer (CRC) has a strong familial component which extends to discordant cancers (ie non-CRC tumors). This is best seen in cancer syndromes such as hereditary non-polyposis colorectal cancer (HNPCC) which predisposes to several tumor types. Population-based family studies have also found discordant associations for CRC but they have included cancers which manifest in HNPCC, and there is no convincing evidence of discordant associations beyond the known syndromes. We address familial associations of non-CRC tumors with CRC using the resources of the Swedish Family-Cancer Database and applying a powerful approach of assessing familial relative risks in families of increasing numbers of patients with discordant cancers. Among 1.8 million cancer patients and over 200,000 CRC cases consistent familial associations of CRC was observed for several HNPCC related cancers. However, for small intestinal, pancreatic and nervous system cancers RRs remained essentially unchanged when potential HNPCC families were excluded, suggesting involvement of genes not related to HNPCC. Two independent associations of CRC were found for melanoma, thyroid and eye cancers and these appeared not to be related to known syndromes. A number of other cancers associated with CRC in single analyses and independent studies are required to assess the relevance of such findings.

While treatment for testicular cancer (TC) has become standardized after the 1980s with an associated significant improvement in patient survival, this has been accompanied by an increased risk of second primary cancers (SPCs). Patients were identified from the Swedish Cancer Registry spanning the years from 1980 to 2015, including 8788 individuals with primary TC and their SPCs. Relative risks (RRs) for SPC were calculated using the generalized Poisson regression model. SPCs were diagnosed in 9.4% of patients with TC and half of them were late onset cancers not common in the population in their 40s. Overall RR of SPCs (excluding second TC) was 1.30 (95%CI: 1.20-1.40), including high risks for seven solid cancers, non-Hodgkin lymphoma and leukemia. Second TC was the most common SPC and the RR of 17.19 (95%CI: 14.89-19.85) was the highest recorded. Cancers known to be fatal as first primary cancers were also fatal as SPC in TC patients. Survival at 30 years of follow-up was approximately 80% for TC patients without SPC but it decreased to 40% for patients with SPC. The unexpected finding that half of the identified SPCs were typical late onset cancers in the middle-aged population raises concerns that therapy may facilitate premature aging. The risks of SPC are clinically important for the long-term management of TC patients and the high-mortality calls for a future management strategy.

Ovarian cancer is a heterogeneous disease. Data regarding familial risks for specific proband, age at diagnosis and histology are limited. Such data can assist genetic counseling and help elucidate etiologic differences among various histologic types of ovarian malignancies. By using the Swedish Family-Cancer Database, we calculated relative risks (RRs) for detailed family histories using a two-way comparison, which implied e.g. estimation of RRs for overall ovarian cancer when family history was histology-specific ovarian cancer, and conversely, RRs for histology-specific ovarian cancer when family history was overall ovarian cancer. In families of only mother, only sisters or both mother and sisters diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40, respectively; and were higher for cases diagnosed before the age of 50 years. All histological types showed a familial risk in two-way analyses, except mucinous and sex cord-stromal tumors. RRs for concordant histology were found for serous (2.47), endometrioid (3.59) and mucinous ovarian cancers (6.91). Concordant familial risks were highest for mucinous cancer; for others, some discordant associations, such as endometrioid-undifferentiated (9.27) and serous-undifferentiated (4.80), showed the highest RRs. Familial risks are high for early-onset patients and for those with multiple affected relatives. Sharing of different histological types of ovarian cancer is likely an indication of the complexity of the underlying mechanisms.

[This corrects the article DOI: 10.1371/journal.pone.0205000.].

Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

Induced pluripotent stem (iPS) cells have attracted enormous attention due to their vast potential in regenerative medicine, pharmaceutical screening and basic research. Most prior established iPS cell lines were derived and maintained on mouse embryonic fibroblast (MEF) cells supplemented with exogenous leukemia inhibitory factor (LIF). Drawbacks of MEF cells impede optimization as well as dissection of reprogramming events and limit the usage of iPS cell derivatives in therapeutic applications. In this study, we develop a reproducible protocol for efficient reprogramming mouse neural progenitor cells (NPCs) on human foreskin fibroblast (HFF) cells via retroviral transfer of human transcriptional factors OCT4/SOX2/KLF4/C-MYC. Two independent iPS cell lines are derived without exogenous LIF. They display typical undifferentiated morphology and express pluripotency markers Oct4 and Sox2. Transgenes are inactivated and the endogenous Oct4 promoter is completely demethylated in the established iPS cell lines, indicating a fully reprogrammed state. Moreover, the iPS cells can spontaneously differentiate or be induced into various cell types of three embryonic germ layers in vitro and in vivo when they are injected into immunodeficient mice for teratoma formation. Importantly, iPS cells extensively integrate with various host tissues and contribute to the germline when injected into the blastocysts. Interestingly, these two iPS cell lines, while both pluripotent, exhibit distinctive differentiation tendencies towards different lineages. Taken together, the data describe the first genuine mouse iPS cell lines generated on human feeder cells without exogenous LIF, providing a reliable tool for understanding the molecular mechanisms of nuclear reprogramming.